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Taghaddos D, Saqib Z, Bai X, Bercik P, Collins SM. Post-infectious ibs following Clostridioides difficile infection; role of microbiota and implications for treatment. Dig Liver Dis 2024; 56:1805-1809. [PMID: 38653643 DOI: 10.1016/j.dld.2024.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/21/2024] [Accepted: 03/13/2024] [Indexed: 04/25/2024]
Abstract
Up to 25% of patients recovering from antibiotic-treated Clostridioides difficile infection (CDI) develop functional symptoms reminiscent of Post-Infectious Irritable Bowel Syndrome (PI-IBS). For patients with persistent symptoms following infection, a clinical dilemma arises as to whether to provide additional antibiotic treatment or to adopt a conservative symptom-based approach. Here, we review the literature on CDI-related PI-IBS and compare the findings with PI-IBS. We review proposed mechanisms, including the role of C. difficile toxins and the microbiota, and discuss implications for therapy. We suggest that gut dysfunction post-CDI may be initiated by toxin-induced damage to enteroglial cells and that a dysbiotic gut microbitota maintains the clinical phenotype over time, prompting consideration of microbiota-directed therapies. While Fecal Microbial Transplant (FMT) is currently reserved for recurrent CDI (rCDI), we propose that microbiota-directed therapies may have a role in primary CDI in order to avoid or mitigate futher antibiotic treatment that further disrupts the microbiota and thus prevent PI-IBS. We discuss novel microbial transfer therapies and as they emerge, we recommend clinical trials to determine whether microbial transfer therapy of the primary infection prevents both rCDI and CDI-related PI- IBS.
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Affiliation(s)
- Dana Taghaddos
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Zarwa Saqib
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Xiaopeng Bai
- Division of Gastroenterology, Kyushu University, Japan
| | - Premysl Bercik
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Stephen M Collins
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
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2
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Varma S, Trudeau SJ, Li J, Freedberg DE. Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series. Inflamm Bowel Dis 2024; 30:38-44. [PMID: 36917215 PMCID: PMC11491639 DOI: 10.1093/ibd/izad035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Indexed: 03/16/2023]
Abstract
BACKGROUND We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers. METHODS This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors. RESULTS Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn's disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years. CONCLUSIONS Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.
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Affiliation(s)
- Sanskriti Varma
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Stephen J Trudeau
- Columbia Vagelos College of Physicians and Surgeons, New York, NY, USA
| | - Jianhua Li
- Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA
| | - Daniel E Freedberg
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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3
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Miller AC, Arakkal AT, Sewell DK, Segre AM, Tholany J, Polgreen PM. Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study. Open Forum Infect Dis 2023; 10:ofad413. [PMID: 37622034 PMCID: PMC10444966 DOI: 10.1093/ofid/ofad413] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
Background Antibiotics are the greatest risk factor for Clostridioides difficile infection (CDI). Risk for CDI varies across antibiotic types and classes. Optimal prescribing and stewardship recommendations require comparisons of risk across antibiotics. However, many prior studies rely on aggregated antibiotic categories or are underpowered to detect significant differences across antibiotic types. Using a large database of real-world data, we evaluate community-associated CDI risk across individual antibiotic types. Methods We conducted a matched case-control study using a large database of insurance claims capturing longitudinal health care encounters and medications. Case patients with community-associated CDI were matched to 5 control patients by age, sex, and enrollment period. Antibiotics prescribed within 30 days before the CDI diagnosis along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression were considered. Conditional logistic regression and a Bayesian analysis were used to compare risk across individual antibiotics. A sensitivity analysis of antibiotic exposure windows between 30 and 180 days was conducted. Results We identified 159 404 cases and 797 020 controls. Antibiotics with the greatest risk for CDI included clindamycin and later-generation cephalosporins, and those with the lowest risk included minocycline and doxycycline. We were able to differentiate and order individual antibiotics in terms of their relative level of associated risk for CDI. Risk estimates varied considerably with different exposure windows considered. Conclusions We found wide variation in CDI risk within and between classes of antibiotics. These findings ordering the level of associated risk across antibiotics can help inform tradeoffs in antibiotic prescribing decisions and stewardship efforts.
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Affiliation(s)
- Aaron C Miller
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
| | - Alan T Arakkal
- University of Iowa, College of Public Health, Iowa City, Iowa, USA
| | - Daniel K Sewell
- University of Iowa, College of Public Health, Iowa City, Iowa, USA
| | - Alberto M Segre
- Department of Computer Science, University of Iowa, Iowa City, Iowa, USA
| | - Joseph Tholany
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
| | - Philip M Polgreen
- University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
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4
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Naz F, Petri WA. Host Immunity and Immunization Strategies for Clostridioides difficile Infection. Clin Microbiol Rev 2023; 36:e0015722. [PMID: 37162338 PMCID: PMC10283484 DOI: 10.1128/cmr.00157-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/11/2023] Open
Abstract
Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.
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Affiliation(s)
- Farha Naz
- Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - William A. Petri
- Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
- Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
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5
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Itoh N, Kawabata T, Akazawa N, Kawamura D, Murakami H, Ishibana Y, Kodama EN, Ohmagari N. Reduction strategies for inpatient oral third-generation cephalosporins at a cancer center: An interrupted time-series analysis. PLoS One 2023; 18:e0281518. [PMID: 36758108 PMCID: PMC9910666 DOI: 10.1371/journal.pone.0281518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 01/24/2023] [Indexed: 02/11/2023] Open
Abstract
Oral third-generation cephalosporins (3GCs) are not recommended for use owing to their low bioavailability and the risk of emergence of resistant microorganisms with overuse. A standardized and effective method for reducing their use is lacking. Here, in a 60-month, single-institution, interrupted time-series analysis, which was retrospectively conducted between April 1, 2017, and March 31, 2022, we evaluated the effectiveness of a four-phase intervention to reduce the use of 3GCs in patients at a cancer center: Phase 1 (pre-intervention), Phase 2 (review of clinical pathways), Phase 3 (establishment of infectious disease consultation service and implementation of antimicrobial stewardship program), and Phase 4 (educational lecture and pop-up displays for oral antimicrobials at the time of ordering). Although no significant changes were observed in Phases 3 and 4, the first intervention resulted in a significant decrease in the trend and level of days of therapy (DOT) for 3GCs. The level for cephalexin DOT and the trend for sulfamethoxazole-trimethoprim DOT increased in Phase 4, and the trend for amoxicillin and amoxicillin-clavulanate DOT increased in Phase 3. Macrolide DOT showed a decreasing trend in Phases 2 and 4 and decreasing and increased levels in Phases 3 and 4, respectively; no change was observed for quinolones. Actual and adjusted purchase costs of 3GCs decreased significantly during all study periods, while those for oral antimicrobials decreased in Phase 2, and actual purchase costs increased in Phases 3 and 4. No significant reduction in resistant organisms, length of hospital stay, or mortality was observed. This is the first study on the effects of oral 3GC reduction strategies in patients with cancer. We conclude that even facilities that substantially use antimicrobials can efficiently reduce the use of 3GCs.
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Affiliation(s)
- Naoya Itoh
- Collaborative Chairs Emerging and Reemerging Infectious Diseases, National Center for Global Health and Medicine, Graduate School of Medicine, Tohoku University, Miyagi, Japan
- Division of Infectious Diseases, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takanori Kawabata
- Department of Data Science, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Nana Akazawa
- Division of Infectious Diseases, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Daichi Kawamura
- Division of Infectious Diseases, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hiromi Murakami
- Division of Infectious Diseases, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yuichi Ishibana
- Division of Infectious Diseases, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Eiichi N. Kodama
- Division of Infectious Diseases, International Research Institute of Disaster Science, and Graduate School of Medicine, Tohoku University and Tohoku Medical Megabank Organization, Sendai, Japan
| | - Norio Ohmagari
- Collaborative Chairs Emerging and Reemerging Infectious Diseases, National Center for Global Health and Medicine, Graduate School of Medicine, Tohoku University, Miyagi, Japan
- AMR Clinical Reference Center, Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
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6
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Squire N, Lux C, Tolbert K, Lidbury J, Sun X, Suchodolski JS. Characterization of the Fecal Microbiome in Dogs Receiving Medical Management for Congenital Portosystemic Shunts. Front Vet Sci 2022; 9:897760. [PMID: 35968011 PMCID: PMC9366551 DOI: 10.3389/fvets.2022.897760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/20/2022] [Indexed: 12/02/2022] Open
Abstract
Background The GI microbiome has not been characterized in dogs being medically managed for congenital portosystemic shunts (CPSS). Objectives To characterize the fecal microbiome in a population of dogs being medically managed for CPSS. Animals 27 client-owned dogs. Methods Prospective cohort study enrollment of fecal samples was performed with follow-up data collected retrospectively. The overall fecal dysbiosis index (DI) and individual bacterial abundances were determined using real-time qPCR. Medical management, clinical findings, clinicopathologic, and outcome variables were collected, and logistic regression analyses were performed to evaluate associations between these variables and overall DI and bacterial abundances. Numerical variables were evaluated with general linear models for normality and equal variance using Shapiro-Wilk test and Levene's test, respectively. Results All dogs were administered a hepatic diet and lactulose, while antibiotics were used in 22 (81.5%) and acid suppressants in 7 (25.9%). Seventeen dogs (63.0%) had a DI >2. The median DI in this population was 3.02 (range 4.23–8.42), and the median DI in dogs receiving and not receiving antibiotics was 4.3 (range −4.23–8.42) and 1.52 (range −1.62–5.43), respectively. No significant association between any of the analyzed variables and the DI was identified. There was a significant association between the use of metronidazole and a larger abundance of E. coli (p = 0.024). Conclusions and Clinical Importance Dysbiosis appears to be common in dogs that are being medically managed for CPSS, though the clinical significance remains unclear.
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Affiliation(s)
- Nathan Squire
- Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN, United States
| | - Cassie Lux
- Department of Small Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN, United States
- *Correspondence: Cassie Lux
| | - Katie Tolbert
- Department of Veterinary Small Animal Clinical Sciences, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States
| | - Jonathan Lidbury
- Department of Veterinary Small Animal Clinical Sciences, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States
| | - Xiaocun Sun
- Office of Information and Technology, University of Tennessee Knoxville, Knoxville, TN, United States
| | - Jan S. Suchodolski
- Department of Veterinary Small Animal Clinical Sciences, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, United States
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Forrester JD, Cao S, Schaps D, Liou R, Patil A, Stave C, Sokolow SH, Leo GD. Influence of Socioeconomic and Environmental Determinants of Health on Human Infection and Colonization with Antibiotic-Resistant and Antibiotic-Associated Pathogens: A Scoping Review. Surg Infect (Larchmt) 2022; 23:209-225. [PMID: 35100052 DOI: 10.1089/sur.2021.348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: Antibiotic-resistant and antibiotic-associated pathogens are commonly encountered by surgeons. Pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Clostridioides difficile infection (CDI), and carbapenem-resistant Enterobacteriaceae (CRE) result in considerable human morbidity, mortality, and excess healthcare expenditure. Human colonization or infection can result from exposure to these pathogens across a range of domains both inside and outside of the built healthcare environment, exposure that may be influenced by socioeconomic and environmental determinants of health, the importance of which has not been investigated fully. Methods: We performed a scoping review of published literature describing potential socioeconomic and environmental variables that may increase the likelihood of human infection or colonization with common antibiotic-resistant or antibiotic-associated pathogens, using MRSA, CDI, and CRE as examples. Results: We identified 7,916 articles meeting initial search criteria. Of these, 101 provided supportive evidence of socioeconomic and environmental determinants of human infection or colonization and were included in the scoping review after abstract and full-text screening. Sixty-seven evaluated MRSA, nine evaluated CRE, and 29 evaluated CDI. Twenty-nine articles evaluated exposure to livestock or companion animals; 28, exposure to antibiotics; 20, impact of socioeconomic factors, education level, or race; 14, the influence of temperature, humidity, or season; 13, the effect of travel or human population migration; 11, exposure to built healthcare environments; and eight assessed impact of population density or urbanization. Conclusions: Although articles outlining socioeconomic and environmental drivers of antibiotic-resistant and antibiotic-associated infection are still disconcertedly few, evidence of such associations are overwhelming for MRSA and CDI and supportive for CRE. Additional research is needed to investigate the role and importance of different potential socioeconomic and environmental drivers of antibiotic-resistant and antibiotic-associated infections and colonization in humans.
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Affiliation(s)
- Joseph D Forrester
- Division of General Surgery, Department of Surgery, Stanford University, Stanford, California, USA
| | - Siqi Cao
- School of Medicine, Stanford University, Stanford, California, USA
| | - Diego Schaps
- School of Medicine, Duke University, Durham, North Carolina, USA
| | - Raymond Liou
- School of Medicine, Stanford University, Stanford, California, USA
| | | | - Christopher Stave
- School of Medicine, Stanford University, Stanford, California, USA
- Lane Medical Library, Stanford University, Stanford, California, USA
| | - Susanne H Sokolow
- Woods Institute for the Environment, Stanford University, Stanford, California, USA
- Marine Science Institute, University of California Santa Barbara, Santa Barbara, California, USA
| | - Giulio De Leo
- Woods Institute for the Environment, Stanford University, Stanford, California, USA
- Hopkins Marine Station, Stanford University, Stanford, California, USA
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8
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The feasibility of rifampicin Re-administration in patients with tuberculosis and Clostridioides difficile infection. J Infect Chemother 2022; 28:558-562. [DOI: 10.1016/j.jiac.2021.12.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/17/2021] [Accepted: 12/28/2021] [Indexed: 11/24/2022]
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9
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Butler AM, Durkin MJ, Keller MR, Ma Y, Powderly WG, Olsen MA. Association of Adverse Events with Antibiotic Treatment for Urinary Tract Infection. Clin Infect Dis 2021; 74:1408-1418. [PMID: 34279560 DOI: 10.1093/cid/ciab637] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Little is known about the relative harms of different antibiotic regimens prescribed to treat uncomplicated urinary tract infection (UTI). We sought to compare the risk of adverse events associated with commonly-used oral antibiotic regimens for the outpatient treatment of uncomplicated UTI. METHODS We identified 1,169,033 otherwise healthy, non-pregnant women aged 18-44 years with uncomplicated UTI who initiated an oral antibiotic with activity against common uropathogens from July 1, 2006 to September 30, 2015. We used propensity score-weighted Kaplan-Meier methods and Cox proportional hazards regression models to estimate the association between antibiotic agent and adverse events. RESULTS Of two first-line agents, TMP/SMX (versus nitrofurantoin) was associated with higher risk of several adverse drug events including hypersensitivity reaction (hazard ratio [HR] 2.62, 95% CI 2.30-2.98), acute renal failure (HR 2.56, 95% CI 1.55-4.25), skin rash (HR 2.42, 95% CI 2.13-2.75), urticaria (HR 1.37, 95% CI 1.19-1.57), abdominal pain (HR 1.14, 95% CI 1.09-1.19), and nausea / vomiting (HR 1.18, 95% CI 1.10-1.28), but similar risk of potential microbiome-related adverse events. Compared to nitrofurantoin, non-first-line agents were associated with higher risk of several adverse drug events and potential microbiome-related adverse events including non-C. difficile diarrhea, C. difficile infection, vaginitis / vulvovaginal candidiasis, and pneumonia. Treatment duration modified the risk of potential microbiome-related adverse events. CONCLUSIONS The risks of adverse drug events and potential microbiome-related events differ widely by antibiotic agent and duration. These findings underscore the utility of using real-world data to fill evidentiary gaps related to antibiotic safety.
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Affiliation(s)
- Anne M Butler
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.,Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA
| | - Michael J Durkin
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Matthew R Keller
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Yinjiao Ma
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - William G Powderly
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.,Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA
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10
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Inghammar M, Svanström H, Voldstedlund M, Melbye M, Hviid A, Mølbak K, Pasternak B. Proton-Pump Inhibitor Use and the Risk of Community-Associated Clostridium difficile Infection. Clin Infect Dis 2021; 72:e1084-e1089. [PMID: 33629099 PMCID: PMC8204777 DOI: 10.1093/cid/ciaa1857] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Indexed: 12/26/2022] Open
Abstract
Background Proton-pump inhibitors (PPIs) have been reported to increase the risk of community-associated Clostridium difficile infection (CDI), but the association remains disputed. Methods A nationwide cohort study among adults in Denmark, 2010–2013, linking register data on C. difficile testing, filled prescriptions, and patient characteristics. All incident episodes of community-associated CDI (ie, positive culture, molecular assay, or toxin test in individuals without previous hospitalization in the prior 12 weeks and without a positive test for C. difficile in the prior 8 weeks) were identified in the Danish National Microbiological Database. Self-controlled case-series analyses were used to estimate incidence rate ratios (IRRs) for community-associated CDI, comparing periods with and without exposure to PPIs. By design, models took fixed confounders such as chronic disease, genetics, and socioeconomic status into account; further, time-varying confounders, including hospital stay and antibiotic and corticosteroid use were adjusted for. Results 3583 episodes of community-associated CDI were identified, of which 964 occurred during current use of PPIs, 324 occurred 0–6 months after treatment cessation, 123 occurred 6–12 months after treatment cessation, and 2172 occurred during time periods without use of PPIs. The adjusted IRR was 2.03 (95% confidence interval, 1.74–2.36), comparing use of PPI with nonuse. The increased risk remained elevated in later time periods: 1.54 (1.31–1.80) for 0–6 months, 1.24 (1.00–1.53) for 6–12 months after current use. Conclusions Use of PPIs was associated with moderately increased risk of community-associated CDI. The risk remained elevated up to 1 year after PPI treatment had ended.
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Affiliation(s)
- Malin Inghammar
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Section for Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Henrik Svanström
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Marianne Voldstedlund
- Division of Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark
| | - Mads Melbye
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Anders Hviid
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
| | - Kåre Mølbak
- Division of Infectious Diseases Preparedness, Statens Serum Institut, Copenhagen, Denmark.,Department of Animal and Veterinary Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Björn Pasternak
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.,Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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11
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Li J, Zhang Y, Jilg AL, Wolk DM, Khara HS, Kolinovsky A, Rolston DDK, Hontecillas R, Bassaganya-Riera J, Williams MS, Abedi V, Lee MTM. Variants at the MHC Region Associate With Susceptibility to Clostridioides difficile Infection: A Genome-Wide Association Study Using Comprehensive Electronic Health Records. Front Immunol 2021; 12:638913. [PMID: 33841421 PMCID: PMC8026859 DOI: 10.3389/fimmu.2021.638913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 03/09/2021] [Indexed: 01/13/2023] Open
Abstract
Background Clostridioides difficile is a major cause of healthcare-associated and community-acquired diarrhea. Host genetic susceptibility to Clostridioides difficile infection has not been studied on a large-scale. Methods A total of 1,160 Clostridioides difficile infection cases and 15,304 controls were identified by applying the eMERGE Clostridioides difficile infection algorithm to electronic health record data. A genome-wide association study was performed using a linear mixed model, adjusted for significant covariates in the full dataset and the antibiotic subgroup. Colocalization and MetaXcan were performed to identify potential target genes in Clostridioides difficile infection - relevant tissue types. Results No significant genome-wide association was found in the meta-analyses of the full Clostridioides difficile infection dataset. One genome-wide significant variant, rs114751021, was identified (OR = 2.42; 95%CI = 1.84-3.11; p=4.50 x 10-8) at the major histocompatibility complex region associated with Clostridioides difficile infection in the antibiotic group. Colocalization and MetaXcan identified MICA, C4A/C4B, and NOTCH4 as potential target genes. Down-regulation of MICA, upregulation of C4A and NOTCH4 was associated with a higher risk for Clostridioides difficile infection. Conclusions Leveraging the EHR and genetic data, genome-wide association, and fine-mapping techniques, this study identified variants and genes associated with Clostridioides difficile infection, provided insights into host immune mechanisms, and described the potential for novel treatment strategies for Clostridioides difficile infection. Future replication and functional validation are needed.
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Affiliation(s)
- Jiang Li
- Department of Molecular and Functional Genomics, Geisinger, Danville, PA, United States
| | - Yanfei Zhang
- Genomic Medicine Institute, Geisinger, Danville, PA, United States
| | - Alexandria L Jilg
- Department of Internal Medicine, Geisinger, Danville, PA, United States
| | - Donna M Wolk
- Diagnostic Medicine Institute, Department of Laboratory Medicine, Geisinger, Danville, PA, United States
| | - Harshit S Khara
- Department of Gastroenterology and Hepatology, Geisinger, Danville, PA, United States
| | | | - David D K Rolston
- Department of Internal Medicine, Geisinger, Danville, PA, United States
| | | | | | - Marc S Williams
- Genomic Medicine Institute, Geisinger, Danville, PA, United States
| | - Vida Abedi
- Department of Molecular and Functional Genomics, Geisinger, Danville, PA, United States
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12
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Alsaleh NA, Al-Omar HA, Mayet AY, Mullen AB. Evaluating the appropriateness of carbapenem and piperacillin-tazobactam prescribing in a tertiary care hospital in Saudi Arabia. Saudi Pharm J 2020; 28:1492-1498. [PMID: 33250656 PMCID: PMC7679439 DOI: 10.1016/j.jsps.2020.09.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 09/17/2020] [Indexed: 01/14/2023] Open
Abstract
Background Antimicrobial resistance (AMR) is presently considered an emergent major global public health concern and excessive and/or inappropriate use of broad-spectrum antimicrobials contribute to the development of AMR. Objective To evaluate the appropriateness of carbapenems and piperacillin-tazobactam use in a tertiary care hospital. Methods A retrospective, observational, cross-sectional, drug-utilization study was conducted. The study included all adult hospitalized patients who had received at least one dose of the antimicrobials during their admission for the period between 1 January 2016 and 31 December 2017. The appropriateness of antimicrobial therapy was evaluated according to the Infectious Diseases Society of America (IDSA) guidelines with the consideration of the institutional antibiogram. Results Overall, 2731 patients received 5005 courses with one of the antimicrobials, for a total of 5045.9 defined daily doses (DDD) of imipenem-cilastatin, 6492.3 of meropenem and 15,595 of piperacillin-tazobactam (4.93, 6.34 and 15.24 DDD/100 bed days, respectively). The mean age of the patients who received either antimicrobial was 55.5 ± 20.3 years, with a 14-day average length of hospital stay. About half (52%) of the prescriptions were written for patients treated in the medical ward. Pneumonia (26.6%) and sepsis (24.9%) were the most common indication for the initiation of antimicrobial therapy. Of the assessed prescriptions, only 2787 (56.5%) were prescribed appropriately, with 2142 (43.5%) deemed inappropriate. The three most common reasons for inappropriate prescription were: the spectrum of activity was too broad (44.6%), followed by antimicrobial use without culture request (32.4%), and failure of suitable antimicrobial de-escalation (19.9%). Conclusions The study indicates that the overall rate of inappropriateness was high, emphasizing the need to develop initiatives to effectively improve broad-spectrum antimicrobial prescribing.
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Affiliation(s)
- Nada A Alsaleh
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
| | - Hussain A Al-Omar
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Ahmed Y Mayet
- Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- King Khalid University Hospital, Riyadh 11451, Saudi Arabia
| | - Alexander B Mullen
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom
- Corresponding author.
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13
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Muhsen K, Na'amnih W, Adler A, Carmeli Y, Cohen D. Clostridium difficile-associated disease and Helicobacter pylori seroprevalence: A case-control study. Helicobacter 2020; 25:e12668. [PMID: 31721371 DOI: 10.1111/hel.12668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 10/02/2019] [Accepted: 10/03/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Helicobacter pylori inhabits the stomach and causes persistent inflammation, with changes in gastric acidity. However, it is unclear whether the presence of H pylori plays a role in Clostridium difficile-associated disease (CDAD). The study's aim was to examine relationships of H pylori seroprevalence and serum pepsinogens (PGs), as markers of gastric inflammation, with CDAD. MATERIALS AND METHODS A case-control study was conducted among 49 CDAD cases and 54 controls (median age 82 years). Using enzyme-linked immunosorbent assays, sera were tested for H pylori IgG antibody, and PGI and PGII levels. Helicobacter pylori-positive samples were tested for IgG antibody to recombinant cytotoxin-associated gene A (CagA) virulent protein. Logistic regression models were fitted. RESULTS Cases and controls were comparable in age (P = .5) and sex distribution (females 62% vs 57%, P = .6). Helicobacter pylori IgG seroprevalence was 47%, of whom 23% were CagA seropositives. Among cases compared to controls, 43% vs 28% were H pylori seropositive but lacking CagA IgG antibody: adjusted odd ratio (OR) 3.43 (95% confidence intervals [CI] 1.29-9.10); 18% vs 4% were positive for CagA phenotype: adjusted OR 9.32 (95% CI 1.61-53.76). This association was not affected by PG levels. CONCLUSIONS Helicobacter pylori infection, especially with CagA virulent phenotype, might predispose to C difficile infection in elderly patients.
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Affiliation(s)
- Khitam Muhsen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Wasef Na'amnih
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Geriatric Rehabilitation, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
| | - Amos Adler
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.,Clinical Microbiology Laboratory, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
| | - Yehuda Carmeli
- Division of Epidemiology, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dani Cohen
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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14
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Karp J, Edman-Wallér J, Toepfer M, Lundqvist A, Jacobsson G. Clostridioides difficile incidence related to in-hospital cephalosporin use: a tale of two highly comparable hospitals. J Antimicrob Chemother 2020; 74:182-189. [PMID: 30358837 DOI: 10.1093/jac/dky408] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 09/07/2018] [Indexed: 11/14/2022] Open
Abstract
Background Antibiotic treatment is a well-known risk factor for healthcare facility-associated Clostridioides (Clostridium) difficile infection (HCF-CDI). Antibiotic stewardship programmes (ASPs) targeting high-risk antibiotics have been shown to decrease HCF-CDI incidence. HCF-CDI incidence is high in Nordic countries despite relatively low antibiotic use in hospital. Objectives To determine if HCF-CDI incidence was modified by a hospital ASP that restricted cephalosporin use. Methods The effects of an ASP on HCF-CDI incidence were evaluated in a two-centre setting using a retrospective design. We exploited a strategy of both individual case ascertainment based on chart reviews and aggregated data from the hospitals. Cases were attributed to the antibiotics given prior to disease onset, in proportion to the number of DDDs used. Three periods were studied: 2007 (before the ASP), 2012 and 2015. Results At the ASP hospital, cephalosporin use decreased by 87% and the number of HCF-CDI/1000 hospital admissions decreased significantly from 2.25 (2007) to 1.16 (2015) (P = 0.0014). The corresponding results at the non-ASP hospital showed a non-significant increase from 2.09 to 2.38. A high number of cases could be attributed to cephalosporins at both hospitals. The increased use of other broad-spectrum antibiotics, e.g. piperacillin/tazobactam, at the ASP hospital was not associated with offsetting increases in attributable HCF-CDI cases. Conclusions Decreased use of cephalosporins is an effective strategy to decrease HCF-CDI incidence over time in a setting with high incidence and low antibiotic use.
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Affiliation(s)
- Johan Karp
- Department of Infectious Diseases, Skaraborg Hospital, Lövängsvägen, Skövde, Sweden.,Center for Antibiotic Resistance Research (CARe), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
| | - Jon Edman-Wallér
- Center for Antibiotic Resistance Research (CARe), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.,Department of Hospital Infection Control, Södra Älvsborg Hospital, Brämhultsvägen, Borås, Sweden
| | - Michael Toepfer
- Clinical Microbiology, Unilabs AB, Rådhusgatan 6, Skövde, Sweden
| | - Anders Lundqvist
- Department of Infectious Diseases, Södra Älvsborg Hospital, Brämhultsvägen 53, Borås, Sweden
| | - Gunnar Jacobsson
- Department of Infectious Diseases, Skaraborg Hospital, Lövängsvägen, Skövde, Sweden.,Center for Antibiotic Resistance Research (CARe), Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
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15
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Bolukcu S, Hakyemez IN, Gultepe BS, Okay G, Durdu B, Koc MM, Aslan T. Clostridium difficile infection: Is there a change in the underlying factors? Inflammatory bowel disease and Clostridium difficile. Saudi J Gastroenterol 2019; 25:384-389. [PMID: 31793457 PMCID: PMC6941457 DOI: 10.4103/sjg.sjg_44_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND / AIMS Clostridium difficile is a Gram-positive, strict anaerobe, spore-forming bacterium. It can cause self-limiting mild diarrhea, severe diarrhea, pseudomembranous colitis, and fatal fulminant colitis. We aimed to investigate the changes in epidemiology and incidence of C. difficile infection in our hospital database. PATIENTS AND METHODS Episodes of C. difficile toxin were identified in hospital database, and data such as age, sex, community versus hospital acquisition, intensive care follow-up, current or previous treatments with antibiotics within the past 3 months, medication with proton pump inhibitors, or immunosuppressive therapies were collected. RESULTS Toxin-positive 78 individuals constituted the patient group. In univariate analyses, independent risk factors for toxin positivity were community versus hospital acquisition [odds ratio (OR), 5.49; 95% confidence interval (CI), 2.52-11.95; P = 0.0001], presence of inflammatory bowel diseases (IBDs) (OR, 21.5; 95% CI, 8.65-53.44; P = 0.0001), proton pump inhibitors' use (OR, 4.53; 95% CI, 1.97-10.43; P = 0.0001), immunosuppressive drug use (OR, 4.1; 95% CI, 2.01-8.3; P = 0.0001), and use of quinolone group of antibiotics (OR, 5.95; 95% CI, 1.92-18.46; P = 0.001). Antibiotic use was a protective risk factor (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01) and presence of IBDs was an independent risk factor (OR, 6.8; 95% CI, 1.5-30.08; P = 0.01) in community-acquired group (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01). CONCLUSION In recent studies, C. difficile infections were demonstrated to be more frequent in younger individuals who did not have a history of hospitalization but had an underlying disease such as IBD. In our study, we showed the change in the epidemiological data with prominence of underlying diseases such as IBDs.
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Affiliation(s)
- Sibel Bolukcu
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey,Address for correspondence: Dr. Sibel Bolukcu, Adnan Menderes Bulvarý Vatan Caddesi 34093 Fatih/İstanbul, Turkey. E-mail:
| | - Ismail Necati Hakyemez
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Bilge Sumbul Gultepe
- Department of Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Gulay Okay
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Bulent Durdu
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Meliha Meric Koc
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
| | - Turan Aslan
- Department of Infectious Diseases and Clinical Microbiology, Bezmialem Vakif University, Istanbul, Turkey
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16
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Tariq R, Cho J, Kapoor S, Orenstein R, Singh S, Pardi DS, Khanna S. Low Risk of Primary Clostridium difficile Infection With Tetracyclines: A Systematic Review and Metaanalysis. Clin Infect Dis 2019; 66:514-522. [PMID: 29401273 DOI: 10.1093/cid/cix833] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 09/15/2017] [Indexed: 11/13/2022] Open
Abstract
Background The choice of antibiotics for systemic infections in patients with a high risk of Clostridium difficile infection (CDI) remains a clinical practice dilemma. Although some studies suggest that tetracyclines may be associated with a lower risk of CDI than other antibiotics, other results are conflicting. We conducted a systematic review and metaanalysis of studies that assessed the risk of CDI with tetracyclines compared to other antibiotics. Methods We conducted a systematic search of Medline, Embase, and Web of Science from January 1978 through December 2016 to include studies that assessed the association between tetracycline use and risk of CDI. Weighted summary estimates were calculated using generalized inverse variance with a random-effects model using RevMan 5.3. Study quality was assessed using the Newcastle-Ottawa scale. Results Six studies (4 case control, 2 cohort) with patient recruitment between 1993 and 2012 were included. Metaanalysis using a random-effects model, demonstrated that tetracyclines were associated with a decreased risk of CDI (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.47-0.81; P < .001). There was significant heterogeneity, with an I2 of 53% with no publication bias. Subgroup analysis of studies that evaluated the risk of CDI with doxycycline alone also demonstrated a decreased risk of CDI (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Conclusions Metaanalyses of existing studies suggest that tetracyclines may be associated with a decreased risk of CDI compared with other antimicrobials. It may be reasonable to use tetracyclines whenever appropriate to decrease CDI associated with antibiotic use.
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Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.,Division of Internal Medicine, Rochester General Hospital, New York
| | - Janice Cho
- Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Saloni Kapoor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Robert Orenstein
- Division of Infectious Diseases, Mayo Clinic Hospital, Phoenix, Arizona
| | - Siddharth Singh
- Division of Gastroenterology and Hepatology, University of California San Diego, La Jolla
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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17
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Efficacy of educational intervention on reducing the inappropriate use of oral third-generation cephalosporins. Infection 2019; 47:1037-1045. [PMID: 31605309 DOI: 10.1007/s15010-019-01362-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 09/30/2019] [Indexed: 12/30/2022]
Abstract
PURPOSE This study aimed to evaluate the efficacy of an educational intervention on reducing the inappropriate use of oral third-generation cephalosporins, the prevalence of resistant bacteria, and clinical outcomes. METHODS A before-after study was conducted to compare the data for 1 year before and after intervention at a Japanese university hospital. Educational intervention included lectures for all medical staff on oral antibiotics and educational meetings with each medical department. The primary outcome was the use of oral third-generation cephalosporins in inpatients as measured by the monthly median days of therapy (DOTs) per 1000 patient days. Secondary outcomes included the use of each oral antibiotic in inpatients and outpatients, proportion of β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (BLNAR), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum β-lactamase producing Escherichia coli (ESBLEC), the incidence of hospital-acquired Clostridioides difficile infection (HA-CDI), and hospital mortality. RESULTS The use of oral third-generation cephalosporins in inpatients was significantly decreased after intervention [DOTs (interquartile range): 24.2 (23.5-25.1) vs. 3.7 (0.0-7.1), P < 0.001], and the value in outpatients was also decreased significantly. The use of fluoroquinolones and macrolides did not increase after intervention. The proportion of BLNAR, PRSP and ESBLEC did not change significantly during the study period. The incidence of HA-CDI was significantly decreased, and hospital mortality did not change after intervention. CONCLUSION Educational intervention was effective in reducing the use of oral third-generation cephalosporins without increasing the use of broad-spectrum antibiotics and worsening clinical outcome. The prevalence of resistant bacteria did not change during the study period.
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18
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Giau VV, Lee H, An SSA, Hulme J. Recent advances in the treatment of C. difficile using biotherapeutic agents. Infect Drug Resist 2019; 12:1597-1615. [PMID: 31354309 PMCID: PMC6579870 DOI: 10.2147/idr.s207572] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 05/03/2019] [Indexed: 12/12/2022] Open
Abstract
Clostridium difficile (C. difficile) is rapidly becoming one of the most prevalent health care–associated bacterial infections in the developed world. The emergence of new, more virulent strains has led to greater morbidity and resistance to standard therapies. The bacterium is readily transmitted between people where it can asymptomatically colonize the gut environment, and clinical manifestations ranging from frequent watery diarrhea to toxic megacolon can arise depending on the age of the individual or their state of gut dysbiosis. Several inexpensive approaches are shown to be effective against virulent C. difficile in research settings such as probiotics, fecal microbiota transfer and immunotherapies. This review aims to highlight the current advantages and limitations of the aforementioned approaches with an emphasis on recent studies.
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Affiliation(s)
- Vo Van Giau
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
| | - Hyon Lee
- Department of Neurology, Gachon University Gil Medical Center, Incheon, South Korea
| | - Seong Soo A An
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
| | - John Hulme
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
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19
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Pan J, Kavanagh K, Marwick C, Davey P, Wuiff C, Bryson S, Robertson C, Bennie M. Residual effect of community antimicrobial exposure on risk of hospital onset healthcare-associated Clostridioides difficile infection: a case-control study using national linked data. J Hosp Infect 2019; 103:259-267. [PMID: 31173780 DOI: 10.1016/j.jhin.2019.05.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 05/29/2019] [Indexed: 11/28/2022]
Abstract
BACKGROUND Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. METHODS A matched case-control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. RESULTS Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13-1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33-2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. CONCLUSIONS Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.
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Affiliation(s)
- J Pan
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UK.
| | - K Kavanagh
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UK; Information Services Division, NHS National Services Scotland, Edinburgh, Scotland, UK
| | - C Marwick
- Population Health Sciences, School of Medicine, University of Dundee, Dundee, Scotland, UK
| | - P Davey
- Population Health Sciences, School of Medicine, University of Dundee, Dundee, Scotland, UK
| | - C Wuiff
- Health Protection Scotland, NHS National Services Scotland, Glasgow, Scotland, UK
| | - S Bryson
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK
| | - C Robertson
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, Scotland, UK; Health Protection Scotland, NHS National Services Scotland, Glasgow, Scotland, UK; International Prevention Research Institute, Lyon, France
| | - M Bennie
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK; Information Services Division, NHS National Services Scotland, Edinburgh, Scotland, UK
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20
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Oguri N, Sakuraba A, Morikubo H, Kikuchi O, Sato T, Tokunaga S, Minowa S, Ikezaki O, Mitsui T, Miura M, Saito D, Hayashida M, Mori H, Osaki T, Kamiya S, Senoh M, Kato H, Hisamatsu T. Community-acquired fulminant colitis caused by binary toxin-producing Clostridium difficile in Japan. Clin J Gastroenterol 2019; 12:325-329. [PMID: 30767176 DOI: 10.1007/s12328-019-00949-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 01/31/2019] [Indexed: 01/05/2023]
Abstract
We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.
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Affiliation(s)
- Noriaki Oguri
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Akihito Sakuraba
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Hiromu Morikubo
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Oki Kikuchi
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Taro Sato
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Soutaro Tokunaga
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Shintaro Minowa
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Osamu Ikezaki
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Tatsuya Mitsui
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Miki Miura
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Daisuke Saito
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Mari Hayashida
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Hideaki Mori
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Mitsutoshi Senoh
- Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Haru Kato
- Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Tadakazu Hisamatsu
- Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
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21
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Primavilla S, Farneti S, Petruzzelli A, Drigo I, Scuota S. Contamination of hospital food with Clostridium difficile in Central Italy. Anaerobe 2019; 55:8-10. [DOI: 10.1016/j.anaerobe.2018.10.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/24/2018] [Accepted: 10/21/2018] [Indexed: 01/01/2023]
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22
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Bouza E, Cobo J, Almirante B. [Recommendations from a panel of experts on the usefulness of fidaxomicin for the treatment of infections caused by Clostridium difficile]. REVISTA ESPANOLA DE QUIMIOTERAPIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE QUIMIOTERAPIA 2019; 32:50-59. [PMID: 30547500 PMCID: PMC6372963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Clostridium difficile infections have a high recurrence rate, which can complicate the prognosis of affected patients. It is therefore important to establish an early detection and an appropriate therapeutic strategy. The objective of this manuscript was to gather the opinion of an expert group about the predictive factors of poor progression, as well as when to use fidaxomicin in different groups of high-risk patients. METHODS A scientific committee of three experts in infectious diseases reviewed the most recent literature on the management of C. difficile infections, and the use of fidaxomicin. They developed a questionnaire of 23 items for consensus by 15 specialists in this type of infection using a modified Delphi method. RESULTS The consensus reached by the panelists was 91.3% in terms of agreement. The most important agreements were: recurrence is a risk criterion per se; fidaxomicin is effective and safe for the treatment of infections caused by C. difficile in critical patients, immunosuppressed patients, or patients with chronic renal failure; fidaxomicin is recommended from the first episode of infection to ensure maximum efficacy in patients with well-contrasted recurrence risk factors. CONCLUSIONS The experts consulted showed a high degree of agreement on topics related to the selection of patients with poorer prognosis, as well as on the use of fidaxomicin in groups of high-risk patients, either in the first line or in situations of recurrence.
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Affiliation(s)
- Emilio Bouza
- Hospital General Universitario Gregorio Marañón. Madrid
| | - Javier Cobo
- Servicio de Enfermedades infecciosas. Hospital Universitario Ramón y Cajal. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Madrid
| | - Benito Almirante
- Servicio de Enfermedades Infecciosas. Hospital Universitario Vall d’Hebron. Barcelona
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Balsells E, Shi T, Leese C, Lyell I, Burrows J, Wiuff C, Campbell H, Kyaw MH, Nair H. Global burden of Clostridium difficile infections: a systematic review and meta-analysis. J Glob Health 2019; 9:010407. [PMID: 30603078 PMCID: PMC6304170 DOI: 10.7189/jogh.09.010407] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Clostridium difficile is a leading cause of morbidity and mortality in several countries. However, there are limited evidence characterizing its role as a global public health problem. We conducted a systematic review to provide a comprehensive overview of C. difficile infections (CDI) rates. Methods Seven databases were searched (January 2016) to identify studies and surveillance reports published between 2005 and 2015 reporting CDI incidence rates. CDI incidence rates for health care facility-associated (HCF), hospital onset-health care facility-associated, medical or general intensive care unit (ICU), internal medicine (IM), long-term care facility (LTCF), and community-associated (CA) were extracted and standardized. Meta-analysis was conducted using a random effects model. Results 229 publications, with data from 41 countries, were included. The overall rate of HCF-CDI was 2.24 (95% confidence interval CI = 1.66-3.03) per 1000 admissions/y and 3.54 (95%CI = 3.19-3.92) per 10 000 patient-days/y. Estimated rates for CDI with onset in ICU or IM wards were 11.08 (95%CI = 7.19-17.08) and 10.80 (95%CI = 3.15-37.06) per 1000 admission/y, respectively. Rates for CA-CDI were lower: 0.55 (95%CI = 0.13-2.37) per 1000 admissions/y. CDI rates were generally higher in North America and among the elderly but similar rates were identified in other regions and age groups. Conclusions Our review highlights the widespread burden of disease of C. difficile, evidence gaps, and the need for sustainable surveillance of CDI in the health care setting and the community.
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Affiliation(s)
- Evelyn Balsells
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint first authorship
| | - Ting Shi
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint first authorship
| | - Callum Leese
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Iona Lyell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - John Burrows
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | | | - Harry Campbell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
| | - Moe H Kyaw
- Sanofi Pasteur, Swiftwater, Pennsylvania, USA.,Joint last authorship
| | - Harish Nair
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.,Joint last authorship
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DiDiodato G, Fruchter L. Antibiotic exposure and risk of community-associated Clostridium difficile infection: A self-controlled case series analysis. Am J Infect Control 2019; 47:9-12. [PMID: 30172612 DOI: 10.1016/j.ajic.2018.06.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/25/2018] [Accepted: 06/26/2018] [Indexed: 01/05/2023]
Abstract
BACKGROUND Community-associated Clostridium difficile infection is inconsistently associated with antibiotic exposure. This study uses a self-controlled case series (SCCS) design to estimate antibiotic exposure effect sizes and compare them with those estimated from previous case-control studies. METHODS We estimated the association between antibiotic exposure and community-associated Clostridium difficile infection among 139,000 patients registered to the Barrie Family Health Team from January 1, 2011, to May 1, 2017, using an SCCS design. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) between antibiotic exposure versus nonexposure periods within individuals. Antibiotic exposure was categorized as either high risk (fluoroquinolone, clindamycin, or cephalosporin) or low risk (all other antibiotic classes). RESULTS The final analysis included 189 cases. The pooled IRR for high-risk antibiotics was 2.26 (95% confidence interval [CI] 1.29, 3.98) and 2.03 (95% CI 1.19, 3.47) for lower-risk antibiotics. There was no difference between high-risk and lower-risk antibiotics (IRR 1.11, 95% CI 0.53, 2.36). INTERPRETATION The IRRs were smaller than the odds ratios reported in previous case-control studies, suggesting a less biased estimate because SCCS designs control for time-invariant confounders. Compared with case-control studies, SCCS designs are underused in infection prevention and control studies.
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Affiliation(s)
- Giulio DiDiodato
- Department of Pharmacy, Royal Victoria Regional Health Centre, Barrie, Ontario, Canada.
| | - Lauren Fruchter
- Family Medicine Teaching Unit, Royal Victoria Regional Health Centre, Barrie, Ontario, Canada
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Doell A, Walus A, To J, Bell A. Quantifying Candidacy for Deprescribing of Proton Pump Inhibitors among Long-Term Care Residents. Can J Hosp Pharm 2018; 71:302-307. [PMID: 30401996 PMCID: PMC6209507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a commonly prescribed drug class used to inhibit gastric acid secretion. They are prescribed for both treatment and prophylaxis of several gastrointestinal conditions. Although PPIs can be used safely in the short term, several serious adverse effects have been reported following long-term use, including increased risk of falls and fragility fractures. Long-term care home (LTCH) residents represent a population in which the long-term adverse effects of PPIs can be significant and PPI deprescribing should be considered when appropriate. OBJECTIVES To determine the proportion of LTCH residents with PPI prescriptions who were eligible for PPI deprescribing, and to examine vitamin B12 deficiencies and fall risk in the study population. METHODS This cross-sectional, multisite chart review involved LTCH residents who had an active PPI prescription during October 2016. A convenience sample of 150 charts was randomly selected, and the appropriateness of PPI deprescribing was determined using Canadian guidelines. Descriptive statistics were used to examine demographic characteristics, PPI dosing and indication, vitamin B12 supplementation, fall history, and fall risk. RESULTS Three of the selected charts were excluded because of missing information. Of the 147 residents included in the chart review, 93 (63%) were candidates for deprescribing. PPI use for gastroesophageal reflux disease for more than 8 weeks without a deprescribing attempt in the past year was the most frequently observed opportunity for deprescribing (49/93 [53%]). Twenty-nine residents (20%) had no documented indication for PPI use. Thirteen residents (9%) had had a fall within the past 30 days, and 53 (36%) had a prescription for vitamin B12 supplements and/or had low serum vitamin B12 levels. CONCLUSIONS A majority of the residents whose charts were reviewed were candidates for PPI deprescribing. This finding suggests an opportunity for clinicians who care for LTCH residents to increase their deprescribing efforts.
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Affiliation(s)
- Alanna Doell
- , BScPharm, ACPR, is a Staff Pharmacist with Seven Oaks General Hospital of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Ashley Walus
- , BScPharm, ACPR, is a Clinical Resource Pharmacist with the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Jaclyn To
- , BScPharm, ACPR, is a Staff Pharmacist with the Victoria General Hospital of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Allison Bell
- , BScPharm, is the Pharmacy Manager with the Long Term Care Program of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
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26
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Claeys KC, Hopkins TL, Vega AD, Heil EL. Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention. Curr Infect Dis Rep 2018; 20:7. [PMID: 29572691 DOI: 10.1007/s11908-018-0615-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE OF REVIEW Fluoroquinolones are a commonly prescribed antibiotic class that has come under scrutiny in recent years due to mounting evidence of association between adverse drug events, C. difficile infection and isolation of antibiotic-resistant bacteria. RECENT FINDINGS Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may "squeeze the antibiotic balloon" and will likely be insufficient if not implemented in conjunction with other AMS interventions. There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.
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Affiliation(s)
- Kimberly C Claeys
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA. .,Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA.
| | - Teri L Hopkins
- Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, TX, USA
| | - Ana D Vega
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA
| | - Emily L Heil
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, N423, Baltimore, MD, 21201, USA.,Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA
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The Impact of Clostridium difficile Infection on Future Outcomes of Solid Organ Transplant Recipients. Infect Control Hosp Epidemiol 2018; 39:563-570. [PMID: 29553007 DOI: 10.1017/ice.2018.48] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVEClostridium difficile infection (CDI) is common in solid organ transplant (SOT) recipients, but few studies have examined long-term outcomes. We studied the impact of CDI after SOT on mortality and transplant organ complication-related hospitalizations (TOH).METHODSSOT recipients ≥18 years of age with at least 1 year of posttransplant data were analyzed using the MarketScan database for 2007-2014. Patients who died within one year of transplant were followed until death. Patients were grouped as early CDI (ie, first occurrence ≤90 days posttransplant), late CDI (ie, first occurrence >90 days posttransplant) and controls (ie, no CDI occurrence during follow-up). The risk of mortality or TOH after CDI was evaluated using Cox and logistic regressions, respectively.RESULTSOverall, 96 patients had early CDI, 97 patients had late CDI, and 5,913 patients were used as controls. The risk for death was significantly higher in the early CDI group than the control group (hazard ratio [HR],1.92; 95% confidence interval [CI], 1.12-3.29; P=.018); there was no significant difference between the late CDI group and the control group (HR, 0.86; 95% CI, 0.38-1.94; P=.717). Both the early CDI group (odds ratio [OR], 2.19; 95% CI, 1.45-3.31; P90 days posttransplant, both the early CDI group (n=89) and the late CDI group (n=97) had increased risk for death or TOH during follow-up than the control group (n=5,734).CONCLUSIONThough our study could not prove causality, both early and late CDI occurrence in SOT recipients were associated with worse future outcomes than for SOT recipients without CDI.Infect Control Hosp Epidemiol 2018;39:563-570.
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Hopkins RJ, Wilson RB. Treatment of recurrent Clostridium difficile colitis: a narrative review. Gastroenterol Rep (Oxf) 2018; 6:21-28. [PMID: 29479439 PMCID: PMC5806400 DOI: 10.1093/gastro/gox041] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 10/17/2017] [Accepted: 10/31/2017] [Indexed: 12/11/2022] Open
Abstract
Clostridium difficile is a gram-positive, spore-forming, obligate anaerobic bacillus that was originally isolated from the stool of a healthy neonate in 1935. In high-income countries, C. difficile is the most common cause of infectious diarrhoea in hospitalized patients. The incidence of C. difficile infection in the USA has increased markedly since 2000, with hospitalizations for C. difficile infections in non-pregnant adults doubling between 2000 and 2010. Between 20% and 35% of patients with C. difficile infection will fail initial antibiotic treatment and, of these, 40-60% will have a second recurrence. Recurrence of C. difficile infection after initial treatment causes substantial morbidity and is a major burden on health care systems. In this article, current treatments for recurrent C. difficile infection are reviewed and future directions explored. These include the use of antibiotics, probiotics, donor faecal transplants, anion resins, secondary bile acids or anti-toxin antibodies.
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Affiliation(s)
- Roy J Hopkins
- Department of Upper GI Surgery, Liverpool Hospital, Sydney, New South Wales, Australia
| | - Robert B Wilson
- Department of Upper GI Surgery, Liverpool Hospital, Sydney, New South Wales, Australia
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29
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Trifan A, Stanciu C, Girleanu I, Stoica OC, Singeap AM, Maxim R, Chiriac SA, Ciobica A, Boiculese L. Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. World J Gastroenterol 2017; 23:6500-6515. [PMID: 29085200 PMCID: PMC5643276 DOI: 10.3748/wjg.v23.i35.6500] [Citation(s) in RCA: 169] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 08/11/2017] [Accepted: 08/25/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI).
METHODS
We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS).
RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002).
CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
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Affiliation(s)
- Anca Trifan
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Oana Cristina Stoica
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Ana Maria Singeap
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Roxana Maxim
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Stefan Andrei Chiriac
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, 700506 Iasi, Romania
| | - Lucian Boiculese
- Department of Preventive Medicine and Interdisciplinarity, “Grigore. T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
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Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection. J Hosp Infect 2017; 98:4-13. [PMID: 28842261 DOI: 10.1016/j.jhin.2017.08.017] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 08/18/2017] [Indexed: 12/18/2022]
Abstract
Attention has recently been directed toward a plausible link between Clostridium difficile infection (CDI) and proton-pump inhibitors (PPIs). However, the results of studies on the association between CDI and PPI remain controversial. We searched the literature databases from their inception to December 2016, without restriction of language, including all controlled observational studies examining the association between acid-suppressive therapy and CDI. Pooled analysis of 50 studies showed a significant association between PPI use and risk of developing CDI (odds ratio: 1.26; 95% confidence interval: 1.12-1.39) as compared with non-users. When stratified by study patients, the relative risk of hospital-acquired CDI and community-associated CDI were 1.29 (1.14-1.44) and 1.17 (0.74-1.59). After restricting the studies according to hospital department, the relative risks of hospital-acquired CDI in ICUs and general wards were 1.43 (0.74-2.11) and 1.29 (1.13-1.45). By implementing cumulative meta-analysis, it was clear that earlier trials of CDI conducted in the early 2000s demonstrated a high degree of heterogeneity and a high percentage of negative results. Since 2011, the overall association between PPI use and risk of developing CDI has remained relatively stable within an effect size between OR 1.20 and 1.26. Our findings indicate a significant associated risk of incident CDI among PPI users, especially in general ward patients. The totality of evidence, when using cumulative meta-analysis, showed that further trials are unlikely to overturn this positive result. Therefore establishing a guideline for the use of PPIs may help in future with the control of CDI.
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Healthcare-Associated Clostridium difficile Infections are Sustained by Disease from the Community. Bull Math Biol 2017; 79:2242-2257. [PMID: 28776206 DOI: 10.1007/s11538-017-0328-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 07/20/2017] [Indexed: 02/08/2023]
Abstract
Clostridium difficile infections (CDIs) are some of the most common hospital-associated infections worldwide. Approximately 5% of the general population is colonised with the pathogen, but most are protected from disease by normal intestinal flora or immune responses to toxins. We developed a stochastic compartmental model of CDI in hospitals that captures the condition of the host's gut flora and the role of adaptive immune responses. A novel, derivative-based method for sensitivity analysis of individual-level outcomes was developed and applied to the model. The model reproduced the observed incidence and recurrence rates for hospitals with high and moderate incidence of hospital-acquired CDI. In both scenarios, the reproduction number for within-hospital transmission was less than 1 (0.67 and 0.44, respectively), but the proportion colonised with C. difficile at discharge (7.3 and 6.1%, respectively) exceeded the proportion colonised at admission (5%). The transmission and prevalence of CDI were most sensitive to the average length of stay and the transmission rate of the pathogen. Recurrent infections were most strongly affected by the treatment success rate and the immune profile of patients. Transmission within hospitals is substantial and leads to a net export of colonised individuals to the broader community. However, within-hospital transmission alone is insufficient to sustain endemic conditions in hospitals without the constant importation of colonised individuals. Improved hygiene practices to reduce transmission from symptomatic and asymptomatic individuals and reduced length of stay are most likely to reduce within-hospital transmission and infections; however, these interventions are likely to have a smaller effect on the probability of recurrence. Immunising inpatients against the toxins produced by C. difficile will reduce the incidence of CDI but may increase transmission.
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Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection. Antimicrob Agents Chemother 2017; 61:AAC.00125-17. [PMID: 28348151 DOI: 10.1128/aac.00125-17] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 03/06/2017] [Indexed: 12/18/2022] Open
Abstract
Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.
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Kavanagh K, Pan J, Marwick C, Davey P, Wiuff C, Bryson S, Robertson C, Bennie M. Cumulative and temporal associations between antimicrobial prescribing and community-associated Clostridium difficile infection: population-based case-control study using administrative data. J Antimicrob Chemother 2017; 72:1193-1201. [PMID: 27999064 DOI: 10.1093/jac/dkw528] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Accepted: 11/10/2016] [Indexed: 12/11/2022] Open
Abstract
Background Community-associated Clostridium difficile infection (CA-CDI; defined as cases without prior hospitalization in the previous 12 weeks who were either tested outside of hospital or tested within 2 days of admission to hospital) is a major public health problem. This study estimates the magnitude of the association between temporal and cumulative prescribing of antimicrobials in primary care and CA-CDI. Methods Three national patient-level datasets, covering CDI cases, community prescriptions and hospitalizations, were linked by the NHS Scotland unique patient identifier, the Community Health Index (CHI). All validated cases of CDI from August 2010 to July 2013 were extracted and up to six population-based controls were matched to each case from the CHI register for Scotland. Statistical analysis used conditional logistic regression. Results The 1446 unique cases of CA-CDI were linked with 7964 age-, sex- and location-matched controls. Cumulative exposure to any antimicrobial in the previous 6 months has a monotonic dose-response association with CA-CDI. Individuals with more than 28 DDDs to any antimicrobial (19.9% of cases) had an OR of 4.4 (95% CI 3.4-5.6) compared with those unexposed. Individuals exposed to 29+ DDDs of high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR of 17.9 (95% CI 7.6-42.2). Elevated CA-CDI risk following high-risk antimicrobial exposure was greatest in the first month (OR = 12.5, 95% CI 8.9-17.4), but was still present 4-6 months later (OR = 2.6, 95% CI 1.7-3.9). Cases exposed to 29+ DDDs had prescription patterns more consistent with repeated therapeutic courses, using different antimicrobials, than long-term prophylactic use. Conclusions This analysis demonstrated temporal and dose-response associations between CA-CDI risk and antimicrobials, with an impact of exposure to high-risk antimicrobials remaining 4-6 months later.
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Affiliation(s)
- Kimberley Kavanagh
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
- Information Services Division, NHS National Services Scotland, Edinburgh, UK
| | - Jiafeng Pan
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
| | - Charis Marwick
- Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK
| | - Peter Davey
- Population Health Sciences, School of Medicine, University of Dundee, Dundee, UK
| | - Camilla Wiuff
- Health Protection Scotland, NHS National Services Scotland, Glasgow, UK
| | - Scott Bryson
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Chris Robertson
- Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK
- Health Protection Scotland, NHS National Services Scotland, Glasgow, UK
- International Prevention Research Institute, Lyon, France
| | - Marion Bennie
- Information Services Division, NHS National Services Scotland, Edinburgh, UK
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
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Cecal Perforation Associated with Clostridium difficile Infection: A Case Report. J Emerg Med 2017; 52:554-556. [PMID: 28161256 DOI: 10.1016/j.jemermed.2016.12.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 12/21/2016] [Accepted: 12/22/2016] [Indexed: 11/21/2022]
Abstract
BACKGROUND Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation. CASE REPORT A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI.
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Durham DP, Olsen MA, Dubberke ER, Galvani AP, Townsend JP. Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings. Emerg Infect Dis 2016; 22:608-16. [PMID: 26982504 PMCID: PMC4806959 DOI: 10.3201/eid2204.150455] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
To quantify the effect of hospital and community-based transmission and control measures on Clostridium difficile infection (CDI), we constructed a transmission model within and between hospital, community, and long-term care-facility settings. By parameterizing the model from national databases and calibrating it to C. difficile prevalence and CDI incidence, we found that hospitalized patients with CDI transmit C. difficile at a rate 15 (95% CI 7.2-32) times that of asymptomatic patients. Long-term care facility residents transmit at a rate of 27% (95% CI 13%-51%) that of hospitalized patients, and persons in the community at a rate of 0.1% (95% CI 0.062%-0.2%) that of hospitalized patients. Despite lower transmission rates for asymptomatic carriers and community sources, these transmission routes have a substantial effect on hospital-onset CDI because of the larger reservoir of hospitalized carriers and persons in the community. Asymptomatic carriers and community sources should be accounted for when designing and evaluating control interventions.
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Freedberg DE, Salmasian H, Cohen B, Abrams JA, Larson EL. Receipt of Antibiotics in Hospitalized Patients and Risk for Clostridium difficile Infection in Subsequent Patients Who Occupy the Same Bed. JAMA Intern Med 2016; 176:1801-1808. [PMID: 27723860 PMCID: PMC5138095 DOI: 10.1001/jamainternmed.2016.6193] [Citation(s) in RCA: 89] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To assess whether receipt of antibiotics by prior hospital bed occupants is associated with increased risk for CDI in subsequent patients who occupy the same bed. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective cohort study of adult patients hospitalized in any 1 of 4 facilities between 2010 and 2015. Patients were excluded if they had recent CDI, developed CDI within 48 hours of admission, had inadequate follow-up time, or if their prior bed occupant was in the bed for less than 24 hours. MAIN OUTCOMES AND MEASURES The primary exposure was receipt of non-CDI antibiotics by the prior bed occupant and the primary outcome was incident CDI in the subsequent patient to occupy the same bed. Incident CDI was defined as a positive result from a stool polymerase chain reaction for the C difficile toxin B gene followed by treatment for CDI. Demographics, comorbidities, laboratory data, and medication exposures are reported. RESULTS Among 100 615 pairs of patients who sequentially occupied a given hospital bed, there were 576 pairs (0.57%) in which subsequent patients developed CDI. Receipt of antibiotics in prior patients was significantly associated with incident CDI in subsequent patients (log-rank P < .01). This relationship remained unchanged after adjusting for factors known to influence risk for CDI including receipt of antibiotics by the subsequent patient (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.02-1.45) and also after excluding 1497 patient pairs among whom the prior patients developed CDI (aHR, 1.20; 95% CI, 1.01-1.43). Aside from antibiotics, no other factors related to the prior bed occupants were associated with increased risk for CDI in subsequent patients. CONCLUSIONS AND RELEVANCE Receipt of antibiotics by prior bed occupants was associated with increased risk for CDI in subsequent patients. Antibiotics can directly affect risk for CDI in patients who do not themselves receive antibiotics.
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Affiliation(s)
- Daniel E Freedberg
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York
| | - Hojjat Salmasian
- Department of Biomedical Informatics, New York-Presbyterian Hospital, New York, New York
| | - Bevin Cohen
- Department of Epidemiology, Mailman School of Public Health, School of Nursing, Columbia University, New York, New York
| | - Julian A Abrams
- Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York
| | - Elaine L Larson
- Department of Epidemiology, Mailman School of Public Health, School of Nursing, Columbia University, New York, New York
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Balsells E, Filipescu T, Kyaw MH, Wiuff C, Campbell H, Nair H. Infection prevention and control of Clostridium difficile: a global review of guidelines, strategies, and recommendations. J Glob Health 2016; 6:020410. [PMID: 28028434 PMCID: PMC5140074 DOI: 10.7189/jogh.06.020410] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Clostridium difficile is the leading cause of health care-associated infections. Given the high incidence of C. difficile infection (CDI) and the lack of primary prevention through immunization, health care professionals should be aware of the most current guidance, as well as strengths and limitations of the evidence base underpinning this guidance. METHODS We identified publicly available national or organizational guidelines related to CDI infection and prevention control (IPC) published between 2000 and 2015 and for any health care setting through an internet search using the Google search engine. We reviewed CDI-targeted IPC recommendations and describe the assessment of evidence in available guidelines. RESULTS We identified documents from 28 countries/territories, mainly from acute care hospitals in North America, the Western Pacific, and Europe (18 countries). We identified only a few specific recommendations for long-term care facilities (LTCFs) and from countries in South America (Uruguay and Chile), South East Asia (Thailand), and none for Africa or Eastern Mediterranean. Of 10 IPC areas, antimicrobial stewardship was universally recognized as essential and supported by high quality evidence. Five other widely reported "strong" recommendations were: effective environment cleaning (including medical equipment), case isolation, use of personal protective equipment, surveillance, and education. Several unresolved and emerging issues were documented and currently available evidence was classified mainly as of mixed quality. CONCLUSION Our review underlines the need for targeted CDI IPC guidelines in several countries and for LTCFs. International harmonisation on the assessment of the evidence for best practices is needed as well as more robust evidence to support targeted recommendations.
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Affiliation(s)
- Evelyn Balsells
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland (UK)
| | - Teodora Filipescu
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland (UK)
| | | | | | - Harry Campbell
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland (UK); Joint last authorship
| | - Harish Nair
- Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland (UK); Public Health Foundation of India, New Delhi, India; Joint last authorship
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Maxson T, Mitchell DA. Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics. Tetrahedron 2016; 72:3609-3624. [PMID: 27429480 PMCID: PMC4941824 DOI: 10.1016/j.tet.2015.09.069] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Antibiotics are a cornerstone of modern medicine and have significantly reduced the burden of infectious diseases. However, commonly used broad-spectrum antibiotics can cause major collateral damage to the human microbiome, causing complications ranging from antibiotic-associated colitis to the rapid spread of resistance. Employing narrower spectrum antibiotics targeting specific pathogens may alleviate this predicament as well as provide additional tools to expand an antibiotic repertoire threatened by the inevitability of resistance. Improvements in clinical diagnosis will be required to effectively utilize pathogen-specific antibiotics and new molecular diagnostics are poised to fulfill this need. Here we review recent trends and the future prospects of deploying narrower spectrum antibiotics coupled with rapid diagnostics. Further, we discuss the theoretical advantages and limitations of this emerging approach to controlling bacterial infectious diseases.
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Affiliation(s)
- Tucker Maxson
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
| | - Douglas A. Mitchell
- Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Carle R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
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Vardakas KZ, Trigkidis KK, Boukouvala E, Falagas ME. Clostridium difficile infection following systemic antibiotic administration in randomised controlled trials: a systematic review and meta-analysis. Int J Antimicrob Agents 2016; 48:1-10. [PMID: 27216385 DOI: 10.1016/j.ijantimicag.2016.03.008] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 03/11/2016] [Accepted: 03/19/2016] [Indexed: 12/17/2022]
Abstract
Antibiotics have been the most important risk factor for Clostridium difficile infection (CDI). However, only data from non-randomised studies have been reviewed. We sought to evaluate the risk for development of CDI associated with the major antibiotic classes by analysing data from randomised controlled trials (RCTs). The PubMed, Cochrane and Scopus databases were searched and the references of selected RCTs were also hand-searched. Eligible studies should have compared only one antibiotic versus another administered systemically. Inclusion of studies comparing combinations of antibiotics was allowed only if the second antibiotic was the same or from the same class or if it was administered in a subset of the enrolled patients who were equally distributed in the two arms. Only a minority of the selected RCTs (79/1332; 5.9%) reported CDI episodes. Carbapenems were associated with more CDI episodes than fluoroquinolones [risk ratio (RR) = 2.44, 95% confidence interval (CI) 1.32-4.49] and cephalosporins (RR = 2.24, 95% CI 1.46-3.42), but not penicillins (RR = 2.53, 95% CI 0.87-7.41). Cephalosporins were associated with more CDIs than penicillins (RR = 2.36, 95% CI 1.32-4.23) and fluoroquinolones (RR = 2.84, 95% CI 1.60-5.06). There was no difference in CDI frequency between fluoroquinolones and penicillins (RR = 1.34, 95% CI 0.55-3.25). Finally, clindamycin was associated with more CDI episodes than cephalosporins and penicillins (RR = 3.92, 95% CI 1.15-13.43). In conclusion, data from RCTs showed that clindamycin and carbapenems were associated with more CDIs than other antibiotics.
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Affiliation(s)
- Konstantinos Z Vardakas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Internal Medicine-Infectious Diseases, IASO General Hospital, IASO Group, Athens, Greece.
| | | | - Eleni Boukouvala
- Department of Applied Mathematics and Physics, National Technical University of Athens, Athens, Greece
| | - Matthew E Falagas
- Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Internal Medicine-Infectious Diseases, IASO General Hospital, IASO Group, Athens, Greece; Department of Medicine, Tufts University School of Medicine, Boston, MA, USA
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Jose S, Madan R. Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections. Anaerobe 2016; 41:85-90. [PMID: 27063896 DOI: 10.1016/j.anaerobe.2016.04.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 04/04/2016] [Indexed: 12/19/2022]
Abstract
Clostridium difficile is the most important cause of nosocomial infectious diarrhea in the western world. C. difficile infections are a major healthcare burden with approximately 500,000 new cases every year and an estimated annual cost of nearly $1 billion in the U.S. Furthermore, the infections are no longer restricted to health care facilities, and recent studies indicate spread of C. difficile infection to the community as well. The clinical spectrum of C. difficile infection ranges from asymptomatic colonization to severe diarrhea, fulminant colitis and death. This spectrum results from a complex interplay between bacterial virulence factors, the colonic microbiome and the host inflammatory response. The overall vigor of host inflammatory response is believed to be an important determinant of C. difficile disease severity, and a more robust immune response is associated with worse outcomes. Neutrophils are the primary cells that respond to C. difficile invasion and neutrophilic inflammation is the hallmark of C. difficile-associated disease. In this review, we will focus on the role of neutrophils (infiltration to infected tissue, pathogen clearance and resolution of inflammation) in the immuno-pathogenesis of C. difficile-associated disease (CDAD).
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Affiliation(s)
- Shinsmon Jose
- Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, OH 45267, USA
| | - Rajat Madan
- Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati, OH 45267, USA.
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Penit A, Bemer P, Besson J, Cazet L, Bourigault C, Juvin ME, Fix MH, Bruley des Varannes S, Boutoille D, Batard E, Lepelletier D. Community-acquired Clostridium difficile infections. Med Mal Infect 2016; 46:131-9. [PMID: 27039068 DOI: 10.1016/j.medmal.2016.01.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2015] [Revised: 11/25/2015] [Accepted: 01/19/2016] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To describe the management and treatment of community-acquired C. difficile infections (CDI) and to evaluate family physicians' (FP) knowledge and practice. PATIENTS AND METHODS Observational study from December 2013 to June 2014. All community-acquired CDI case patients diagnosed in the community or at the University Hospital of Nantes were prospectively included. A questionnaire was mailed to 150 FPs of the area of Nantes. RESULTS A total of 27 community-acquired CDI case patients were included (incidence: 7.7 case patients/100,000 inhabitants). Mean age was higher among case patients diagnosed at hospital (69years) compared with those diagnosed in the community (44years). Fifteen patients were treated at home (55%) and 22 received a first-line treatment with metronidazole. Only one patient did not receive any prior antibiotic treatment. Amoxicillin-clavulanic acid was mainly prescribed (68%) for respiratory and ENT infections (40%). Twenty-three patients were cured on Day 7 and three had complications (two deaths). Thirty-one of 47 FPs reported to have already managed CDI patients. Twenty-two FPs reported to usually treat patients with uncomplicated CDI at home, 21 to refer patients to a specialist, and three to hospital. Forty-one FPs reported to prescribe a CD toxin test only after recent antibiotic exposure and 30 when patients are at risk of CDI. CONCLUSION The incidence and impact of community-acquired CDIs may be underestimated and the unjustified use of antibiotics may promote their emergence. FPs are not used to treat CDIs as more than 50% prefer referring patients to hospital or to a specialist.
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Affiliation(s)
- A Penit
- Pôle de gérontologie clinique, CHU de Nantes, 44093 Nantes, France
| | - P Bemer
- Service de bactériologie-hygiène hospitalière, CHU de Nantes, 44093 Nantes, France
| | - J Besson
- Laboratoire d'analyses médicales Biolance, 44000 Nantes, France
| | - L Cazet
- Service de bactériologie-hygiène hospitalière, CHU de Nantes, 44093 Nantes, France
| | - C Bourigault
- Service de bactériologie-hygiène hospitalière, CHU de Nantes, 44093 Nantes, France
| | - M-E Juvin
- Service de bactériologie-hygiène hospitalière, CHU de Nantes, 44093 Nantes, France
| | - M-H Fix
- Pôle de gérontologie clinique, CHU de Nantes, 44093 Nantes, France
| | | | - D Boutoille
- Service des maladies infectieuses et tropicales, CHU de Nantes, 44093 Nantes, France; UPRES EA 3826, UFR médecine, université de Nantes, 44035 Nantes, France
| | - E Batard
- Service d'accueil des urgences, CHU de Nantes, 44093 Nantes, France; UPRES EA 3826, UFR médecine, université de Nantes, 44035 Nantes, France
| | - D Lepelletier
- Service de bactériologie-hygiène hospitalière, CHU de Nantes, 44093 Nantes, France; UPRES EA 3826, UFR médecine, université de Nantes, 44035 Nantes, France.
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Morrill HJ, Caffrey AR, Gaitanis MM, LaPlante KL. Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment. PLoS One 2016; 11:e0150795. [PMID: 26978263 PMCID: PMC4792438 DOI: 10.1371/journal.pone.0150795] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 02/19/2016] [Indexed: 11/28/2022] Open
Abstract
Background Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. Methods Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10–10/11) and post-ASP (9/12–10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. Results Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3–8 vs. 4, IQR 2–7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1–3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). Conclusions Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events.
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Affiliation(s)
- Haley J. Morrill
- Veterans Affairs Medical Center, Infectious Diseases Research Program, Providence, Rhode Island, United States of America
- University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, Rhode Island, United States of America
- Veterans Affairs Medical Center, Center of Innovation in Long Term Services and Supports, Providence, Rhode Island, United States of America
| | - Aisling R. Caffrey
- Veterans Affairs Medical Center, Infectious Diseases Research Program, Providence, Rhode Island, United States of America
- University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, Rhode Island, United States of America
- Veterans Affairs Medical Center, Center of Innovation in Long Term Services and Supports, Providence, Rhode Island, United States of America
| | - Melissa M. Gaitanis
- Veterans Affairs Medical Center, Infectious Diseases Research Program, Providence, Rhode Island, United States of America
- Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, Rhode Island, United States of America
| | - Kerry L. LaPlante
- Veterans Affairs Medical Center, Infectious Diseases Research Program, Providence, Rhode Island, United States of America
- University of Rhode Island, Department of Pharmacy Practice, College of Pharmacy, Kingston, Rhode Island, United States of America
- Veterans Affairs Medical Center, Center of Innovation in Long Term Services and Supports, Providence, Rhode Island, United States of America
- Warren Alpert Medical School of Brown University, Division of Infectious Diseases, Providence, Rhode Island, United States of America
- * E-mail:
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Jamal W, Pauline E, Rotimi V. A prospective study of community-associated Clostridium difficile infection in Kuwait: Epidemiology and ribotypes. Anaerobe 2015; 35:28-32. [DOI: 10.1016/j.anaerobe.2015.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 06/24/2015] [Accepted: 06/26/2015] [Indexed: 12/16/2022]
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Shields K, Araujo-Castillo RV, Theethira TG, Alonso CD, Kelly CP. Recurrent Clostridium difficile infection: From colonization to cure. Anaerobe 2015; 34:59-73. [PMID: 25930686 PMCID: PMC4492812 DOI: 10.1016/j.anaerobe.2015.04.012] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 04/22/2015] [Accepted: 04/23/2015] [Indexed: 12/16/2022]
Abstract
Clostridium difficile infection (CDI) is increasingly prevalent, dangerous and challenging to prevent and manage. Despite intense national and international attention the incidence of primary and of recurrent CDI (PCDI and RCDI, respectively) have risen rapidly throughout the past decade. Of major concern is the increase in cases of RCDI resulting in substantial morbidity, morality and economic burden. RCDI management remains challenging as there is no uniformly effective therapy, no firm consensus on optimal treatment, and reliable data regarding RCDI-specific treatment options is scant. Novel therapeutic strategies are critically needed to rapidly, accurately, and effectively identify and treat patients with, or at-risk for, RCDI. In this review we consider the factors implicated in the epidemiology, pathogenesis and clinical presentation of RCDI, evaluate current management options for RCDI and explore novel and emerging therapies.
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Affiliation(s)
- Kelsey Shields
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, United States.
| | - Roger V Araujo-Castillo
- Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Lowry Medical Office Building, Suite GB 110 Francis Street, Boston, MA 02215, United States.
| | - Thimmaiah G Theethira
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, United States.
| | - Carolyn D Alonso
- Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Lowry Medical Office Building, Suite GB 110 Francis Street, Boston, MA 02215, United States.
| | - Ciaran P Kelly
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, United States.
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Peng JC, Shen J, Zhu Q, Ran ZH. The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis. Saudi J Gastroenterol 2015; 21:208-12. [PMID: 26228363 PMCID: PMC4542418 DOI: 10.4103/1319-3767.161644] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 11/20/2014] [Indexed: 12/14/2022] Open
Abstract
There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.
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Affiliation(s)
- Jiang-Chen Peng
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Avenue, 200127 Shanghai, China
| | - Jun Shen
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Avenue, 200127 Shanghai, China
| | - Qi Zhu
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Avenue, 200127 Shanghai, China
| | - Zhi-Hua Ran
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Inflammatory Bowel Disease Research Center, 160# Pu Jian Avenue, 200127 Shanghai, China
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The Magnitude of Time-Dependent Bias in the Estimation of Excess Length of Stay Attributable to Healthcare-Associated Infections. Infect Control Hosp Epidemiol 2015; 36:1089-94. [DOI: 10.1017/ice.2015.129] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUNDEstimates of the excess length of stay (LOS) attributable to healthcare-associated infections (HAIs) in which total LOS of patients with and without HAIs are biased because of failure to account for the timing of infection. Alternate methods that appropriately treat HAI as a time-varying exposure are multistate models and cohort studies, which match regarding the time of infection. We examined the magnitude of this time-dependent bias in published studies that compared different methodological approaches.METHODSWe conducted a systematic review of the published literature to identify studies that report attributable LOS estimates using both total LOS (time-fixed) methods and either multistate models or matching patients with and without HAIs using the timing of infection.RESULTSOf the 7 studies that compared time-fixed methods to multistate models, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 9.4 days longer or 238% greater than those generated using multistate models. Of the 5 studies that compared time-fixed methods to matching on timing of infection, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 12.6 days longer or 139% greater than those generated by matching on timing of infection.CONCLUSIONOur results suggest that estimates of the attributable LOS due to HAIs depend heavily on the methods used to generate those estimates. Overestimation of this effect can lead to incorrect assumptions of the likely cost savings from HAI prevention measures.Infect. Control Hosp. Epidemiol. 2015;36(9):1089–1094
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Wozniak TM, Rubin G, Raina MacIntyre C. The emergence of community-acquired Clostridium difficile in an Australian hospital. ACTA ACUST UNITED AC 2015. [DOI: 10.1071/hi15003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Furuya-Kanamori L, Stone JC, Clark J, McKenzie SJ, Yakob L, Paterson DL, Riley TV, Doi SAR, Clements AC. Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2015; 36:132-41. [PMID: 25632995 DOI: 10.1017/ice.2014.39] [Citation(s) in RCA: 123] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI. METHODS A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted. RESULTS Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80-10.04) and corticosteroid (1.81; 1.15-2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52-9.12), renal failure (2.64; 1.23-5.68), hematologic cancer (1.75; 1.02-5.68), and diabetes mellitus (1.15; 1.05-1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years. CONCLUSIONS Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.
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Affiliation(s)
- Luis Furuya-Kanamori
- 1Research School of Population Health,Australian National University,Canberra,Australia
| | - Jennifer C Stone
- 2School of Population Health,University of Queensland,Herston,Australia
| | | | | | - Laith Yakob
- 4Department of Disease Control,London School of Hygiene & Tropical Medicine,London,UK
| | - David L Paterson
- 5University of Queensland,UQ Centre for Clinical Research,Herston,Australia
| | - Thomas V Riley
- 6Microbiology & Immunology,University of Western Australia, andDepartment of Microbiology PathWest Laboratory Medicine,Queen Elizabeth II Medical Centre,Nedlands,Australia
| | - Suhail A R Doi
- 2School of Population Health,University of Queensland,Herston,Australia
| | - Archie C Clements
- 1Research School of Population Health,Australian National University,Canberra,Australia
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Predictors and outcomes of readmission for Clostridium difficile in a national sample of medicare beneficiaries. J Gastrointest Surg 2015; 19:88-99; discussion 99. [PMID: 25408315 PMCID: PMC4462125 DOI: 10.1007/s11605-014-2638-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2014] [Accepted: 08/21/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND Rates of Clostridium difficile (CD) infections are increasing. Elderly patients may be at particular risk of recurrent CD infection. Little is known about the risk for CD readmission specifically in this age group. METHODS A 5% random sample of Medicare data (2009-2011) was queried for patients surviving a hospitalization for CD by ICD-9 code. Demographic (age, sex, gender), clinical (Elixhauser index, gastrointestinal comorbidities), and hospitalization (length of stay, ICU admission) characteristics as well as exposure to antibiotics and interim non-CD hospitalization were compared for those with and without a readmission for CD. A multivariable survival analysis was used to determine predictors of readmission. RESULTS Of 7,564 patients surviving a CD hospitalization, 8.5% were readmitted with CD in a median of 25 days (interquartile range (IQR) 14-57). In multivariable survival analyses, interim non-CD hospital exposure was the strongest predictor of CD readmission (hazard ration (HR) 3.75 95%, confidence interval (CI) 3.2-4.42). Oral and intravenous/intramuscular (IV/IM) antibiotic use, Elixhauser index, and CD as the primary diagnosis also increased the risk of CD readmission. Discharge to hospice, long-term care or a skilled nursing facility decreased the odds of CD readmission. CONCLUSION Hospital exposure and antibiotic use put elderly patients at risk of CD readmission. Exposure to these factors should be minimized in the immediate post discharge period.
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Taniguchi LU, Correia MDT, Zampieri FG. Overwhelming Post-Splenectomy Infection: Narrative Review of the Literature. Surg Infect (Larchmt) 2014; 15:686-93. [DOI: 10.1089/sur.2013.051] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Affiliation(s)
- Leandro Utino Taniguchi
- Discipline of Emergency Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Education and Research Institute, Hospital Sírio Libanês, São Paulo, Brazil
| | - Mário Diego Teles Correia
- Discipline of Emergency Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Fernando Godinho Zampieri
- Discipline of Emergency Medicine, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
- Intensive Care Unit, Hospital Alemão Oswaldo Cruz, São Paulo, Brazil
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