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Donskey CJ, Dubberke ER, Klein NP, Liles EG, Szymkowiak K, Wilcox MH, Lawrence J, Bouguermouh S, Zhang H, Koury K, Bailey R, Smith HM, Lockhart S, Lamberth E, Kalina WV, Pride MW, Webber C, Anderson AS, Jansen KU, Gruber WC, Kitchin N. CLOVER (CLOstridium difficile Vaccine Efficacy tRial) Study: A Phase 3, Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection. Clin Infect Dis 2024; 79:1503-1511. [PMID: 39180325 PMCID: PMC11650871 DOI: 10.1093/cid/ciae410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 05/20/2024] [Accepted: 08/13/2024] [Indexed: 08/26/2024] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. METHODS This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed. RESULTS The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], -38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, -28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P = .02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups. CONCLUSIONS Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. CLINICAL TRIALS REGISTRATION NCT03090191.
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Affiliation(s)
- Curtis J Donskey
- Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
| | - Erik R Dubberke
- Division of Infectious Diseases, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Nicola P Klein
- Kaiser Permanente Vaccine Study Center, Oakland, California, USA
| | | | | | - Mark H Wilcox
- Leeds Teaching Hospitals NHS Trust and Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom
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Butler AM, Nickel KB, Olsen MA, Sahrmann JM, Colvin R, Neuner E, O'Neil CA, Fraser VJ, Durkin MJ. Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults. Clin Infect Dis 2024:ciae519. [PMID: 39442057 DOI: 10.1093/cid/ciae519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 09/05/2024] [Accepted: 10/21/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. METHODS We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. RESULTS Of 145 137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared with macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (eg, β-lactam: nausea/vomiting/abdominal pain [RD per 1000, 3.20; 95% CI, 0.99–5.73]; non–Clostridioides difficile diarrhea [RD per 1000, 4.61; 95% CI, 2.47–6.82]; vulvovaginal candidiasis/vaginitis [RD per 1000, 3.57; 95% CI, 0.87, 6.88]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. CONCLUSIONS Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.
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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
| | - Katelin B Nickel
- 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
| | - John M Sahrmann
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Ryan Colvin
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Elizabeth Neuner
- Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, MO, USA
| | - Caroline A O'Neil
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Victoria J Fraser
- Department of Medicine, Division of Infectious Diseases, 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
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Stămăteanu LO, Pleşca CE, Miftode IL, Bădescu AC, Manciuc DC, Hurmuzache ME, Roșu MF, Miftode RȘ, Obreja M, Miftode EG. " Primum, non nocere": The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era-Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe. Antibiotics (Basel) 2024; 13:461. [PMID: 38786189 PMCID: PMC11117487 DOI: 10.3390/antibiotics13050461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 05/25/2024] Open
Abstract
Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes.
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Affiliation(s)
- Lidia Oana Stămăteanu
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Claudia Elena Pleşca
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Ionela Larisa Miftode
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Aida Corina Bădescu
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
- Department of Preventive Medicine and Interdisciplinarity, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Doina Carmen Manciuc
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Mihnea Eudoxiu Hurmuzache
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Manuel Florin Roșu
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
- Surgical (Dentoalveolar and Maxillofacial Surgery) Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Radu Ștefan Miftode
- Department of Internal Medicine I (Cardiology), “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Maria Obreja
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
| | - Egidia Gabriela Miftode
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (L.O.S.); (D.C.M.); (M.E.H.); (M.O.); (E.G.M.)
- “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (A.C.B.); (M.F.R.)
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Nickel KB, Durkin MJ, Olsen MA, Sahrmann JM, Neuner E, O’Neil CA, Butler AM. Utilization of broad- versus narrow-spectrum antibiotics for the treatment of outpatient community-acquired pneumonia among adults in the United States. Pharmacoepidemiol Drug Saf 2024; 33:e5779. [PMID: 38511244 PMCID: PMC11016291 DOI: 10.1002/pds.5779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 02/22/2024] [Accepted: 03/04/2024] [Indexed: 03/22/2024]
Abstract
PURPOSE To characterize antibiotic utilization for outpatient community-acquired pneumonia (CAP) in the United States. METHODS We conducted a cohort study among adults 18-64 years diagnosed with outpatient CAP and a same-day guideline-recommended oral antibiotic fill in the MarketScan® Commercial Database (2008-2019). We excluded patients coded for chronic lung disease or immunosuppressive disease; recent hospitalization or frequent healthcare exposure (e.g., home wound care, patients with cancer); recent antibiotics; or recent infection. We characterized utilization of broad-spectrum antibiotics (respiratory fluoroquinolone, β-lactam + macrolide, β-lactam + doxycycline) versus narrow-spectrum antibiotics (macrolide, doxycycline) overall and by patient- and provider-level characteristics. Per 2007 IDSA/ATS guidelines, we stratified analyses by otherwise healthy patients and patients with comorbidities (coded for diabetes; chronic heart, liver, or renal disease; etc.). RESULTS Among 263 914 otherwise healthy CAP patients, 35% received broad-spectrum antibiotics (not recommended); among 37 161 CAP patients with comorbidities, 44% received broad-spectrum antibiotics (recommended). Ten-day antibiotic treatment durations were the most common for all antibiotic classes except macrolides. From 2008 to 2019, broad-spectrum antibiotic use substantially decreased from 45% to 19% in otherwise healthy patients (average annual percentage change [AAPC], -7.5% [95% CI -9.2%, -5.9%]), and from 55% to 29% in patients with comorbidities (AAPC, -5.8% [95% CI -8.8%, -2.6%]). In subgroup analyses, broad-spectrum antibiotic use varied by age, geographic region, provider specialty, and provider location. CONCLUSIONS Real-world use of broad-spectrum antibiotics for outpatient CAP declined over time but remained common, irrespective of comorbidity status. Prolonged duration of therapy was common. Antimicrobial stewardship is needed to aid selection according to comorbidity status and to promote shorter courses.
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Affiliation(s)
- Katelin B. Nickel
- Department of Medicine, Division of Infectious Diseases, 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
| | - Margaret A. Olsen
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - John M. Sahrmann
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - Elizabeth Neuner
- Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, MO, USA
| | - Caroline A. O’Neil
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - 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
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Hamad Y, Nickel KB, Olsen MA, George IA. Outcomes of Ceftriaxone Compared With Cefazolin or Nafcillin/Oxacillin for Outpatient Therapy for Methicillin-Sensitive Staphylococcus aureus Bloodstream Infections: Results From a Large United States Claims Database. Open Forum Infect Dis 2024; 11:ofad662. [PMID: 38352150 PMCID: PMC10863560 DOI: 10.1093/ofid/ofad662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 12/22/2023] [Indexed: 02/16/2024] Open
Abstract
Background Ceftriaxone is a convenient option for methicillin-sensitive Staphylococcus aureus (MSSA) outpatient parenteral antimicrobial therapy (OPAT), but population-based studies for its effectiveness are lacking. Methods In this retrospective cohort, a large insurance claims database was queried from 2010 to 2018 for adults with MSSA bloodstream infection (BSI). Patients discharged on OPAT on cefazolin or oxacillin/nafcillin were compared with ceftriaxone with respect to 90-day hospital readmission with the same infection category and 90-day all-cause readmission using logistic regression models. Results Of 1895 patients with MSSA BSI, 1435 (75.7%) patients received cefazolin, oxacillin, or nafcillin and 460 (24.3%) ceftriaxone. Readmission due to the same infection category occurred in 366 (19.3%), and all-cause readmission occurred in 535 (28.3%) within 90 days. Risk factors significantly associated with readmission with the same infection category were the oldest sampled age group (61-64 years: adjusted odds ratio [aOR], 1.47 [95% confidence interval {CI}, 1.01-2.14]), intensive care unit stay during index admission (aOR, 2.33 [95% CI, 1.81-3.01]), prosthetic joint infection (aOR, 1.96 [95% CI, 1.18-2.23]), central line-associated BSI (aOR, 1.72 [95% CI, 1.33-2.94]), and endocarditis (aOR, 1.63 [95% CI, 1.18-2.23]). Ceftriaxone was not associated with increased risk of readmission with the same infection category (aOR, 0.89 [95% CI, .67-1.18]), or 90-day all-cause readmission (aOR, 0.86 [95% CI, .66-1.10]) when compared with oxacillin/nafcillin/cefazolin. Conclusions In this cohort of MSSA BSI patients discharged on OPAT, there were no differences in outcomes of readmission with the same infection and 90-day all-cause readmission in patients treated with ceftriaxone compared to oxacillin/nafcillin or cefazolin. Patients with complicated BSIs such as endocarditis and epidural abscess were more likely to be prescribed cefazolin or oxacillin/nafcillin.
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Affiliation(s)
- Yasir Hamad
- Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland, USA
| | - Katelin B Nickel
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA
| | - Margaret A Olsen
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri, USA
| | - Ige A George
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri, USA
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Eeuwijk J, Ferreira G, Yarzabal JP, Robert-Du Ry van Beest Holle M. A Systematic Literature Review on Risk Factors for and Timing of Clostridioides difficile Infection in the United States. Infect Dis Ther 2024; 13:273-298. [PMID: 38349594 PMCID: PMC10904710 DOI: 10.1007/s40121-024-00919-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 01/10/2024] [Indexed: 02/25/2024] Open
Abstract
INTRODUCTION Clostridioides difficile infection (CDI) is a major public health threat. Up to 40% of patients with CDI experience recurrent CDI (rCDI), which is associated with increased morbidity. This study aimed to define an at-risk population by obtaining a detailed understanding of the different factors leading to CDI, rCDI, and CDI-related morbidity and of time to CDI. METHODS We conducted a systematic literature review (SLR) of MEDLINE (using PubMed) and EMBASE for relevant articles published between January 1, 2016, and November 11, 2022, covering the US population. RESULTS Of the 1324 articles identified, 151 met prespecified inclusion criteria. Advanced patient age was a likely risk factor for primary CDI within a general population, with significant risk estimates identified in nine of 10 studies. Older age was less important in specific populations with comorbidities usually diagnosed at earlier age, such as bowel disease and cancer. In terms of comorbidities, the established factors of infection, kidney disease, liver disease, cardiovascular disease, and bowel disease along with several new factors (including anemia, fluid and electrolyte disorders, and coagulation disorders) were likely risk factors for primary CDI. Data on diabetes, cancer, and obesity were mixed. Other primary CDI risk factors were antibiotics, proton pump inhibitors, female sex, prior hospitalization, and the length of stay in hospital. Similar factors were identified for rCDI, but evidence was limited. Older age was a likely risk factor for mortality. Timing of primary CDI varied depending on the population: 2-3 weeks in patients receiving stem cell transplants, within 3 weeks for patients undergoing surgery, and generally more than 3 weeks following solid organ transplant. CONCLUSION This SLR uses recent evidence to define the most important factors associated with CDI, confirming those that are well established and highlighting new ones that could help to identify patient populations at high risk.
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Affiliation(s)
- Jennifer Eeuwijk
- Pallas Health Research and Consultancy, a P95 Company, Rotterdam, Netherlands
| | | | - Juan Pablo Yarzabal
- GSK, Wavre, Belgium.
- GSK, B43, Rue de l'Institut, 89, 1330, Rixensart, Belgium.
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Olsen MA, Stwalley D, Tipping AD, Keller MR, Yu H, Dubberke ER. Trends in the incidence of Clostridioides difficile infection in adults and the elderly insured by Medicaid compared to commercial insurance or Medicare only. Infect Control Hosp Epidemiol 2023; 44:1076-1084. [PMID: 36082779 PMCID: PMC9995604 DOI: 10.1017/ice.2022.208] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Few data are available to quantify the Clostridioides difficile infection (CDI) burden in US adults depending on Medicaid insurance status; thus, we sought to contribute to this body of information. METHODS Retrospective cohort study to identify adults with codes for CDI from 2011 to 2017 in MarketScan commercial and Medicaid databases (for those aged 25-64 years) and the CMS Medicare database (for those aged ≥65 years). CDI was categorized as healthcare-facility-associated (HCA-CDI) and community-associated CDI (CA-CDI). CDI incidence rates were compared by year, insurer, and age group. RESULTS The overall CDI incidence in the elderly was 3.1-fold higher in persons insured by Medicare plus Medicaid than in those insured by Medicare only (1,935 vs 618 per 100,000 person years (PY)), and the CDI incidence was 2.7-fold higher in younger adults with Medicaid compared to commercial insurance (195 vs 73 per 100,000 PY). From 2011 to 2017, HCA-CDI rates declined in the younger Medicaid population (124.0 to 95.2 per 100,000 PY; P < .001) but were stable in those commercially insured (25.9 to 24.8 per 100,000 PY; P = .33). In the elderly HCA-CDI rates declined from 2011 to 2017 in the Medicare-only population (403 to 318 per 100,000 PY; P < .001) and the Medicare plus Medicaid population (1,770 to 1,163 per 100,000 PY; P < .002). Persons with chronic medical conditions and those with immunocompromising conditions insured by Medicaid had 2.8- and 2.7-fold higher CDI incidence compared to the commercially insured population, respectively. The incidence of CDI was lowest in Medicaid and commercially insured younger adults without chronic medical or immunosuppressive conditions (67.5 and 45.6 per 100,000 PY, respectively). CONCLUSIONS Although HCA-CDI incidence decreased from 2011 to 2017 in elderly and younger adults insured by Medicaid, the burden of CDI remains much higher in low-income adults insured by Medicaid.
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Affiliation(s)
- Margaret A. Olsen
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
- Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | - Dustin Stwalley
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Andrew D. Tipping
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | - Matthew R. Keller
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
| | | | - Erik R. Dubberke
- Department of Medicine, Washington University School of Medicine, St. Louis, MO
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Butler AM, Brown DS, Newland JG, Nickel KB, Sahrmann JM, O’Neil CA, Olsen MA, Zetts RM, Hyun DY, Durkin MJ. Comparative Safety and Attributable Healthcare Expenditures Following Inappropriate Versus Appropriate Outpatient Antibiotic Prescriptions Among Adults With Upper Respiratory Infections. Clin Infect Dis 2023; 76:986-995. [PMID: 36350187 PMCID: PMC10226742 DOI: 10.1093/cid/ciac879] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 10/28/2022] [Accepted: 11/03/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Little is known about the clinical and financial consequences of inappropriate antibiotics. We aimed to estimate the comparative risk of adverse drug events and attributable healthcare expenditures associated with inappropriate versus appropriate antibiotic prescriptions for common respiratory infections. METHODS We established a cohort of adults aged 18 to 64 years with an outpatient diagnosis of a bacterial (pharyngitis, sinusitis) or viral respiratory infection (influenza, viral upper respiratory infection, nonsuppurative otitis media, bronchitis) from 1 April 2016 to 30 September 2018 using Merative MarketScan Commercial Database. The exposure was an inappropriate versus appropriate oral antibiotic (ie, non-guideline-recommended vs guideline-recommended antibiotic for bacterial infections; any vs no antibiotic for viral infections). Propensity score-weighted Cox proportional hazards models were used to estimate the association between inappropriate antibiotics and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable healthcare expenditures by infection type. RESULTS Among 3 294 598 eligible adults, 43% to 56% received inappropriate antibiotics for bacterial and 7% to 66% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and nausea/vomiting/abdominal pain (hazard ratio, 2.90; 95% confidence interval, 1.31-6.41 and hazard ratio, 1.10; 95% confidence interval, 1.03-1.18, respectively, for pharyngitis). Thirty-day attributable healthcare expenditures were higher among adults who received inappropriate antibiotics for bacterial infections ($18-$67) and variable (-$53 to $49) for viral infections. CONCLUSIONS Inappropriate antibiotic prescriptions for respiratory infections were associated with increased risks of patient harm and higher healthcare expenditures, justifying a further call to action to implement outpatient antibiotic stewardship programs.
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Affiliation(s)
- Anne M Butler
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Derek S Brown
- Brown School, Washington University, St. Louis, Missouri, USA
| | - Jason G Newland
- Department of Pediatrics, Washington University School of Medicine, St. Louis, St. Louis, Missouri, USA
| | - Katelin B Nickel
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
| | - John M Sahrmann
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Caroline A O’Neil
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Margaret A Olsen
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
- Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, Missouri, USA
| | | | | | - Michael J Durkin
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
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Tran PT, Antonelli PJ, Winterstein AG. Quinolone Ear Drops and Achilles Tendon Rupture. Clin Infect Dis 2023; 76:e1360-e1368. [PMID: 36065683 DOI: 10.1093/cid/ciac709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/15/2022] [Accepted: 08/27/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Delayed eardrum healing has been observed in the ear opposite to the ear treated with otic quinolones (OQ) in rats. Case reports describe tendinopathies after OQ treatment, suggesting adverse systemic effects. METHODS We studied patients aged 19 to 64 years with diagnosis of otitis externa or media in private insurance between 2005 and 2015. We compared OQ treatment against otic neomycin, oral amoxicillin, or azithromycin. Outcomes included Achilles tendon rupture (ATR), Achilles tendinitis (AT), and all-type tendon rupture (ATTR). We applied an active comparator, new-user design with 1-year look-back and ceased follow-up at initiation of systemic steroids or oral quinolones, external injury, hospitalization, and after 35 days. We used trimmed stabilized inverse probability of treatment weights to balance comparison groups in a survival framework. Negative outcomes (clavicle fractures or sports injuries) were examined to rule out differences from varied physical activity (unmeasured confounding). RESULTS We examined 1 501 009 treated otitis episodes. Hazard ratios (HR) for OQ exposure associated with ATR were 4.49 (95% confidence interval [CI], 1.83-11.02), AT 1.04 (95% CI, 0.73-1.50), and ATTR 1.71 (95% CI, 1.21-2.41). Weighted risk differences (RD) per 100 000 episodes for OQ exposure were ATR 7.80 (95% CI, 0.72-14.89), AT 1.01 (95% CI, -12.80 to 14.81), and ATTR 18.57 (95% CI, 3.60-33.53). Corresponding HRs for clavicle fractures and sports injuries were HR,1.71 (95% CI, 0.55-5.27) and HR,1.45 (95% CI, 0.64-3.30), suggesting limited residual confounding. CONCLUSIONS OQ exposure may lead to systemic consequences. Clinicians should consider this potential risk and counsel patients accordingly. Risk factors and mechanisms for this rare, adverse effect deserve further evaluation. Mechanistic and other clinical studies are warranted to corroborate this finding.
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Affiliation(s)
- Phuong T Tran
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.,Faculty of Pharmacy, HUTECH University, Ho Chi Minh City, Vietnam
| | - Patrick J Antonelli
- College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, USA.,Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Almut G Winterstein
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.,College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, USA.,Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida, USA
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10
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Hess A, Byerly S, Lenart E, Evans C, Kerwin A, Filiberto D. Risk factors for clostridium difficile infection in general surgery patients. Am J Surg 2023; 225:118-121. [PMID: 36244834 DOI: 10.1016/j.amjsurg.2022.09.031] [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] [Received: 04/18/2022] [Revised: 07/19/2022] [Accepted: 09/18/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Clostridium Difficile Infection (CDI) is a significant cause of mortality. This study aims to identify predictors of CDI in general surgery patients. METHODS Patients who underwent general surgery operations in the 2019 National Surgical Quality Improvement Program database were identified with demographic, intervention, and outcome data abstracted. Patients with CDI and no CDI were compared by univariate analysis. Multivariable logistic regression (MLR) was performed to determine independent predictors of CDI. RESULTS Of 436,831 surgical patients, 1,840 patients were diagnosed with CDI (0.4%). Patients with CDI have a higher mortality (2.1% vs 0.76%,p < 0.0001), longer length of stay (7 days vs 1 day, p < 0.0001), and are less likely to undergo a laparoscopic procedure (29.9% vs 37.5%, p < 0.0001). MLR identified older age, emergent operation, increased time to operation, surgical site infection, deep organ space infection, steroid use, metastatic cancer, smoking, and decreased body mass index (BMI) as independent predictors of CDI. CONCLUSIONS CDI is rare following general surgery. Infections, delay to operation, and emergency operations are associated with CDI.
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Affiliation(s)
- Alexis Hess
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
| | - Saskya Byerly
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
| | - Emily Lenart
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
| | - Cory Evans
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
| | - Andrew Kerwin
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
| | - Dina Filiberto
- Department of General Surgery, University of Tennesse Health Science Center, 920 Madison Avenue, Memphis, TN, 38163, USA.
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11
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Hamad Y, Nickel KB, Burnett YJ, Hamad T, George IA, Olsen MA. Prevalence and risk factors associated with readmission with acute kidney injury in patients receiving vancomycin outpatient parenteral antimicrobial therapy. J Clin Pharm Ther 2022; 47:2188-2195. [PMID: 36257600 PMCID: PMC10336722 DOI: 10.1111/jcpt.13790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/30/2022] [Accepted: 09/24/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Vancomycin is commonly used during outpatient parenteral antimicrobial therapy (OPAT). Therapeutic drug monitoring (TDM) of vancomycin is recommended to ensure effective and safe therapy, as use has been associated with acute kidney injury (AKI). METHODS The MarketScan® Commercial Database was queried from 2010 to 2016 to identify patients aged 18-64 years discharged from an inpatient hospitalization on vancomycin OPAT. The primary endpoint was hospital readmission with AKI within 6 weeks of index hospital discharge. TDM was defined as at least one vancomycin level obtained during outpatient therapy. Bivariate analysis was used to examine associations with outcomes; significant factors were incorporated into a multivariable logistic regression model. RESULTS A total of 14,196 patients were included in the study; median age was 54 years and 53.8% were male. Readmission with AKI occurred in 385 (2.7%) and was independently associated with chronic kidney disease (aOR 2.63 [95%CI 1.96-3.52]), congestive heart failure (1.81 [1.34-2.44]), chronic liver disease (1.74 [1.17-2.59]), hypertension (1.73 [1.39-2.17]), septicemia (1.61 [1.30-2.00]), and concomitant OPAT with IV penicillins (1.73 [1.21-2.49]) while skin and soft tissue infection (0.67 [0.54-0.83]) and surgical site infection (0.74 [0.59-0.93]) were associated with lower risk of readmission with AKI. TDM was not associated with lower risk of readmission with AKI. CONCLUSION Chronic kidney disease, congestive heart failure, hypertension, chronic liver disease, septicemia, and concomitant OPAT with IV penicillins were significantly associated with higher risk of readmission with AKI during vancomycin OPAT.
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Affiliation(s)
- Yasir Hamad
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
- Department of Critical Care Medicine, National Institute of Health Clinical Center, Bethesda, MD
| | - Katelin B Nickel
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Yvonne J Burnett
- University of Health Sciences and Pharmacy in St. Louis, St. Louis, Missouri
| | - Tarig Hamad
- Università della Calabria, Department of Pharmacy and Health and Nutrition Sciences, Rende, Italy
| | - Ige A George
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
| | - Margaret A Olsen
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri
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12
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Butler AM, Brown DS, Durkin MJ, Sahrmann JM, Nickel KB, O’Neil CA, Olsen MA, Hyun DY, Zetts RM, Newland JG. Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events and Health Care Expenditures. JAMA Netw Open 2022; 5:e2214153. [PMID: 35616940 PMCID: PMC9136626 DOI: 10.1001/jamanetworkopen.2022.14153] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
IMPORTANCE Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described. OBJECTIVE To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections. DESIGN, SETTING, AND PARTICIPANTS This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. Data were analyzed from August to November 2021. EXPOSURES Inappropriate (ie, non-guideline-recommended) vs appropriate (ie, guideline-recommended) oral antibiotic agents dispensed from an outpatient pharmacy on the date of infection. MAIN OUTCOMES AND MEASURES Propensity score-weighted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for the association between inappropriate antibiotic prescriptions and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable health care expenditures by infection type. National-level annual attributable expenditures were calculated by scaling attributable expenditures in the study cohort to the national employer-sponsored insurance population. RESULTS The cohort included 2 804 245 eligible children (52% male; median [IQR] age, 8 [4-12] years). Overall, 31% to 36% received inappropriate antibiotics for bacterial infections and 4% to 70% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and severe allergic reaction among children treated with a nonrecommended antibiotic agent for a bacterial infection (among patients with suppurative OM, C. difficile infection: HR, 6.23; 95% CI, 2.24-17.32; allergic reaction: HR, 4.14; 95% CI, 2.48-6.92). Thirty-day attributable health care expenditures were generally higher among children who received inappropriate antibiotics, ranging from $21 to $56 for bacterial infections and from -$96 to $97 for viral infections. National annual attributable expenditure estimates were highest for suppurative OM ($25.3 million), pharyngitis ($21.3 million), and viral URI ($19.1 million). CONCLUSIONS AND RELEVANCE In this cohort study of children with common infections treated in an outpatient setting, inappropriate antibiotic prescriptions were common and associated with increased risks of adverse drug events and higher attributable health care expenditures. These findings highlight the individual- and national-level consequences of inappropriate antibiotic prescribing and further support implementation of outpatient antibiotic stewardship programs.
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Affiliation(s)
- Anne M. Butler
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | | | - Michael J. Durkin
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
| | - John M. Sahrmann
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
| | - Katelin B. Nickel
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
| | - Caroline A. O’Neil
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
| | - Margaret A. Olsen
- Division of Infectious Diseases, John T. Milliken Department of Medicine, Washington University School of Medicine, St Louis, Missouri
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
| | | | | | - Jason G. Newland
- Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri
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13
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Clostridioides difficile Infection. Dis Colon Rectum 2021; 64:650-668. [PMID: 33769319 DOI: 10.1097/dcr.0000000000002047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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14
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Tran PT, Antonelli PJ, Hincapie-Castillo JM, Winterstein AG. Association of US Food and Drug Administration Removal of Indications for Use of Oral Quinolones With Prescribing Trends. JAMA Intern Med 2021; 181:808-816. [PMID: 33871571 PMCID: PMC8056313 DOI: 10.1001/jamainternmed.2021.1154] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
IMPORTANCE In May 2016, due to concerns of the risks outweighing the benefits, the US Food and Drug Administration (FDA) removed systemic quinolones' indications for acute, uncomplicated urinary tract infection (uUTI), acute sinusitis (AS), and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). How the change influenced oral quinolone use is unknown. OBJECTIVE To assess the association of oral quinolone safety warnings and indication restrictions with use. DESIGN, SETTING, AND PARTICIPANTS This interrupted time series (January 2015-November 2018) analysis of the monthly prevalence of oral quinolone-treated infection episodes used a national sample of privately insured patients in outpatient care from the IBM MarketScan Database and included adults with antibiotic treatment of new uUTI, AS, or AE-COPD episodes, excluding patients with conditions that complicate infections, previous hospitalization, or other infections. EXPOSURES Time before and after May 2016 when the FDA mandated label changes. MAIN OUTCOMES AND MEASURES Monthly oral quinolone use prevalence by each condition before and after the label changes, overall and stratified by prescriber specialty. RESULTS In January 2015, quinolone prevalence among antibiotic-treated uUTI episodes (n = 652 235) was 41.6% (95% CI, 40.6%-42.5%); AS (n = 1 742 248) was 8.3% (95% CI, 7.9%-8.6%), and AE-COPD (n = 22 817) was 31.9% (95% CI, 30.3%-33.4%). Before the label changes, trends in monthly quinolone prevalence were nearly flat. The month of the label changes we noted an immediate reduction for uUTI (-7.2%; 95% CI, -8.6% to -5.8%); and to a lesser extent for AS (-1.2%; 95% CI, -1.5% to -0.9%) and AE-COPD (-2.6%; 95% CI, -4.1% to -1.1%), and continued monthly declines thereafter. Falsification tests confirmed an immediate decrease after the label change of quinolone use for uUTI but more obscured effects for AS and AE-COPD. Treatment shifted mostly to first-line (eg, nitrofurantoin in uUTI, amoxicillin in AS, macrolides in AE-COPD) and other second-line agents but use of not recommended antibiotics also increased (eg, tetracyclines in AE-COPD). Prescribing preferences varied, but significant reductions were seen across all prescriber specialties. At the end of the study period, quinolone was used for 19.2% of treated uUTIs, 2.9% of treated AS, and 14.6% of treated AE-COPD episodes. CONCLUSIONS AND RELEVANCE Label changes and their announcements was associated with an immediate reduction in oral quinolone use for uUTI and to a lesser extent for AS and AE-COPD. Quinolones continued to contribute a considerable proportion of treatments for uUTI and AE-COPD episodes at the end of the study period, pointing to opportunities for further improvement.
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Affiliation(s)
- Phuong T Tran
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville.,Faculty of Pharmacy, Ho Chi Minh City University of Technology (HUTECH), Ho Chi Minh City, Vietnam
| | - Patrick J Antonelli
- Center for Drug Evaluation and Safety, University of Florida, Gainesville.,Department of Otolaryngology, College of Medicine, University of Florida, Gainesville
| | - Juan M Hincapie-Castillo
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville.,Center for Drug Evaluation and Safety, University of Florida, Gainesville
| | - Almut G Winterstein
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville.,Center for Drug Evaluation and Safety, University of Florida, Gainesville.,Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville
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15
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Clostridioides difficile infection in US hospitals: a national inpatient sample study. Int J Colorectal Dis 2020; 35:1929-1935. [PMID: 32556651 DOI: 10.1007/s00384-020-03646-3] [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] [Accepted: 05/20/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Hypervirulent strains of Clostridioides difficile have altered the landscape of hospital and community outbreaks. We aim to examine and compare spatiotemporal trends, incidence, hospital teaching status, mortality, and cost associated with hospital-acquired Clostridioides difficile infection (HCDI) and community-acquired Clostridioides difficile infection (CCDI). METHODS Retrospective cohorts were studied using data from the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) from 2006 to 2015. RESULTS A total of 76,124 cases of HCDI and 190,641 cases of CCDI were identified within the study period. The incidence of HCDI decreased from 8555 in 2006 to 7191 in 2015. Mortality also decreased during the same period (5.9% in 2006 to 1.4% 2015, p < 0.0001). Conversely, CCDI cases increased from 13,823 in 2006 to 20,637 in 2015. CCDI mortality decreased during the same period (4.3% in 2006 to 1.9% 2015, p < 0.0001). Rural hospital centers experienced the sharpest decline in HCDI mortality compared to urban and urban teaching centers (3.8%, p < 0.0001 vs 2.8%, p < 0.0001 vs 2.1%, p < 0.0001). Multivariate logistic regression indicated that increasing age (p = 0.0001), increasing hospital length of stay (p = 0.0001), and Medicare insurance (p = 0.002) were significant predictors of mortality for CDI mortality. Geospatial mapping of CCDI and HCDI revealed that the Eastern and Southern US experienced the largest incidence of CDI over 10 years. CONCLUSION The incidence of HCDI has decreased in the past decade while the incidence of CCDI hospitalization is sharply on the rise. While hospital length of stay and mortality has decreased over time, the cost of treating CDI remains high.
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16
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Kokai-Kun JF, Le C, Trout K, Cope JL, Ajami NJ, Degar AJ, Connelly S. Ribaxamase, an Orally Administered β-Lactamase, Diminishes Changes to Acquired Antimicrobial Resistance of the Gut Resistome in Patients Treated with Ceftriaxone. Infect Drug Resist 2020; 13:2521-2535. [PMID: 32801790 PMCID: PMC7383106 DOI: 10.2147/idr.s260258] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/05/2020] [Indexed: 12/16/2022] Open
Abstract
Introduction Intravenous (IV) β-lactam antibiotics, excreted through bile into the gastrointestinal (GI) tract, may disrupt the gut microbiome by eliminating the colonization resistance from beneficial bacteria. This increases the risk for Clostridium difficile infection (CDI) and can promote antimicrobial resistance by selecting resistant organisms and eliminating competition by non-resistant organisms. Ribaxamase is an orally administered β-lactamase for use with IV β-lactam antibiotics (penicillins and cephalosporins) and is intended to degrade excess antibiotics in the upper GI before they can disrupt the gut microbiome and alter the resistome. Methods Longitudinal fecal samples (349) were collected from patients who participated in a previous Phase 2b clinical study with ribaxamase for prevention of CDI. In that previous study, patients were treated with ceftriaxone for a lower respiratory tract infection and received concurrent ribaxamase or placebo. Extracted fecal DNA from the samples was subjected to whole-genome shotgun sequencing and analyzed for the presence of antimicrobial resistance (AMR) genes by alignment of sequences against the Comprehensive Antibiotic Resistance Database. A qPCR assay was also used to confirm some of the results. Results Database alignment identified ~1300 acquired AMR genes and gene variants, including those encoding β-lactamases and vancomycin resistance which were significantly increased in placebo vs ribaxamase-treated patients following antibiotic exposure. qPCR corroborated the presence of these genes and supported both new acquisition and expansion of existing gene pools based on no detectable copy number or a low copy number in pre-antibiotic samples which increased post-antibiotics. Additional statistical analyses demonstrated significant correlations between changes in the gut resistome and clinical study parameters including study drug assignment and β-lactamase and vancomycin resistance gene frequency. Discussion These findings demonstrated that ribaxamase reduced changes to the gut resistome subsequent to ceftriaxone administration and may help limit the emergence of AMR.
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17
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Rauseo AM, Olsen MA, Reske KA, Dubberke ER. Strategies to prevent adverse outcomes following Clostridioides difficile infection in the elderly. Expert Rev Anti Infect Ther 2020; 18:203-217. [PMID: 31976779 DOI: 10.1080/14787210.2020.1717950] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Introduction: Clostridioides difficile remains the most common cause of healthcare-associated infections in the US, and it disproportionately affects the elderly. Older patients are more susceptible and have a greater risk of adverse outcomes from C. difficile infection (CDI), despite advances in treatment and prevention.Areas covered: The epidemiology and pathogenesis of CDI, as well as risk factors in the aging host, will be reviewed. The importance of antimicrobial stewardship and infection prevention in order to avoid acquisition and transmission will be discussed, as well as strategies to prevent adverse outcomes and recurrent CDI, through optimization of CDI treatment s,election.Expert opinion: Appropriate CDI-prevention strategies to avoid adverse outcomes in this susceptible population involve antimicrobial stewardship and methods to prevent C. difficile transmission in healthcare settings. Management strategies to prevent adverse outcomes include initiation of supportive therapy and proper selection of CDI specific treatments. Many patients may also benefit from adjunctive therapies or additional procedures.
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Affiliation(s)
- Adriana M Rauseo
- Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
| | - Margaret A Olsen
- Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
| | - Kimberly A Reske
- Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
| | - Erik R Dubberke
- Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA
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18
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Marra AR, Perencevich EN, Nelson RE, Samore M, Khader K, Chiang HY, Chorazy ML, Herwaldt LA, Diekema DJ, Kuxhausen MF, Blevins A, Ward MA, McDanel JS, Nair R, Balkenende E, Schweizer ML. Incidence and Outcomes Associated With Clostridium difficile Infections: A Systematic Review and Meta-analysis. JAMA Netw Open 2020; 3:e1917597. [PMID: 31913488 PMCID: PMC6991241 DOI: 10.1001/jamanetworkopen.2019.17597] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE An understanding of the incidence and outcomes of Clostridium difficile infection (CDI) in the United States can inform investments in prevention and treatment interventions. OBJECTIVE To quantify the incidence of CDI and its associated hospital length of stay (LOS) in the United States using a systematic literature review and meta-analysis. DATA SOURCES MEDLINE via Ovid, Cochrane Library Databases via Wiley, Cumulative Index of Nursing and Allied Health Complete via EBSCO Information Services, Scopus, and Web of Science were searched for studies published in the United States between 2000 and 2019 that evaluated CDI and its associated LOS. STUDY SELECTION Incidence data were collected only from multicenter studies that had at least 5 sites. The LOS studies were included only if they assessed postinfection LOS or used methods accounting for time to infection using a multistate model or compared propensity score-matched patients with CDI with control patients without CDI. Long-term-care facility studies were excluded. Of the 119 full-text articles, 86 studies (72.3%) met the selection criteria. DATA EXTRACTION AND SYNTHESIS Two independent reviewers performed the data abstraction and quality assessment. Incidence data were pooled only when the denominators used the same units (eg, patient-days). These data were pooled by summing the number of hospital-onset CDI incident cases and the denominators across studies. Random-effects models were used to obtain pooled mean differences. Heterogeneity was assessed using the I2 value. Data analysis was performed in February 2019. MAIN OUTCOMES AND MEASURES Incidence of CDI and CDI-associated hospital LOS in the United States. RESULTS When the 13 studies that evaluated incidence data in patient-days due to hospital-onset CDI were pooled, the CDI incidence rate was 8.3 cases per 10 000 patient-days. Among propensity score-matched studies (16 of 20 studies), the CDI-associated mean difference in LOS (in days) between patients with and without CDI varied from 3.0 days (95% CI, 1.44-4.63 days) to 21.6 days (95% CI, 19.29-23.90 days). CONCLUSIONS AND RELEVANCE Pooled estimates from currently available literature suggest that CDI is associated with a large burden on the health care system. However, these estimates should be interpreted with caution because higher-quality studies should be completed to guide future evaluations of CDI prevention and treatment interventions.
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Affiliation(s)
- Alexandre R. Marra
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
- Division of Medical Practice, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Center for Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, Iowa
| | - Eli N. Perencevich
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
- Center for Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, Iowa
| | - Richard E. Nelson
- Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah
- Department of Internal Medicine, University of Utah, Salt Lake City
| | - Matthew Samore
- Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah
- Department of Internal Medicine, University of Utah, Salt Lake City
| | - Karim Khader
- Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah
- Department of Internal Medicine, University of Utah, Salt Lake City
| | - Hsiu-Yin Chiang
- Big Data Center, China Medical University Hospital, Taichung City, Taiwan
| | - Margaret L. Chorazy
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | - Loreen A. Herwaldt
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | - Daniel J. Diekema
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | | | - Amy Blevins
- Ruth Lilly Medical Library, Indiana University School of Medicine, Indianapolis
| | - Melissa A. Ward
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | - Jennifer S. McDanel
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | - Rajeshwari Nair
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
- Center for Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, Iowa
| | - Erin Balkenende
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
| | - Marin L. Schweizer
- Carver College of Medicine, Department of Internal Medicine, University of Iowa, Iowa City
- Center for Access and Delivery Research and Evaluation, Iowa City VA Health Care System, Iowa City, Iowa
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19
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Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study. J Gastroenterol 2019; 54:1052-1060. [PMID: 31187275 DOI: 10.1007/s00535-019-01598-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 06/04/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk. METHODS A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission. RESULTS PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5-2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4-2.2) and 2.0-fold with pantoprazole (95% CI 1.5-2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days. CONCLUSIONS Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.
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Incidence of Clostridioides difficile infections among young and middle-aged adults: Veterans Health Administration. Infect Control Hosp Epidemiol 2019; 40:997-1005. [DOI: 10.1017/ice.2019.160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
AbstractObjective:Clostridioides difficile infection (CDI) remains a significant public health concern, resulting in excess morbidity, mortality, and costs. Additional insight into the burden of CDI in adults aged <65 years is needed.Design/Setting:A 6-year retrospective cohort study was conducted using data extracted from United States Veterans Health Administration electronic medical records.Patients/Methods:Patients aged 18–64 years on January 1, 2011, were followed until incident CDI, death, loss-to-follow-up, or December 31, 2016. CDI was identified by a diagnosis code accompanied by metronidazole, vancomycin, or fidaxomicin therapy, or positive laboratory test. The clinical setting of CDI onset was defined according to 2017 SHEA-IDSA guidelines.Results:Of 1,073,900 patients, 10,534 had a CDI during follow-up. The overall incidence rate was 177 CDIs per 100,000 person years, rising steadily from 164 per 100,000 person years in 2011 to 189 per 100,000 person years in 2016. Those with a CDI were slightly older (55 vs 51 years) and sicker, with a higher baseline Charlson comorbidity index score (1.4 vs 0.5) than those without an infection. Nearly half (48%) of all incident CDIs were community associated, and this proportion rose from 41% in 2011 to 56% in 2016.Conclusions:The findings from this large retrospective study indicate that CDI incidence, driven primarily by increasing community-associated infection, is rising among young and middle-aged adult Veterans with high service-related disability. The increasing burden of community associated CDI in this vulnerable population warrants attention. Future studies quantifying the economic and societal burden of CDI will inform decisions surrounding prevention strategies.
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Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial. THE LANCET. INFECTIOUS DISEASES 2019; 19:487-496. [DOI: 10.1016/s1473-3099(18)30731-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 10/18/2018] [Accepted: 11/20/2018] [Indexed: 12/15/2022]
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Marley C, El Hahi Y, Ferreira G, Woods L, Ramirez Villaescusa A. Evaluation of a risk score to predict future Clostridium difficile disease using UK primary care and hospital data in Clinical Practice Research Datalink. Hum Vaccin Immunother 2019; 15:2475-2481. [PMID: 30945972 PMCID: PMC6816380 DOI: 10.1080/21645515.2019.1589288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
We evaluated the applicability of a Clostridium difficile infection (CDI) risk index developed for patients at hospital discharge to identify persons at high-risk of CDI in a primary care population. This retrospective observational study used data from the UK Clinical Practice Research Datalink, linked with Hospital Episodes Statistics. The risk index was based on the following patient characteristics: age, previous hospitalizations, days in hospital, and prior antibiotics use. Individual risk scores were calculated by summing points assigned to pre-defined categories for each characteristic. We assessed the association of risk factors with CDI by multivariate logistic regression. The estimated CDI incidence rate was 4/10,000 and 2/10,000 person-years in 2008 and 2012, respectively. On an index with a maximal risk of 19, a cut-off for high risk of ≥7 had sensitivity, specificity and positive predictive values of 80%, 87% and 12%, respectively. A high-risk person had a ~ 35% higher risk of CDI than a low-risk person. Multivariate risk factor analysis indicated a need to reconsider the relative risk scores. The CDI risk index can be applied to the UK primary care population and help identify study populations for vaccine development studies. Reassessing the relative weights assigned to risk factors could improve the index performance in this setting.
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Affiliation(s)
| | | | | | - Laura Woods
- Department of Non communicable disease epidemiology, London School of Hygiene & Tropical medicine , London , UK
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Kubota K, Kamijima Y, Kao Yang YH, Kimura S, Chia-Cheng Lai E, Man KKC, Ryan P, Schuemie M, Stang P, Su CC, Wong ICK, Zhang Y, Setoguchi S. Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study. PLoS One 2018; 13:e0208796. [PMID: 30540837 PMCID: PMC6291148 DOI: 10.1371/journal.pone.0208796] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 11/26/2018] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The number of patients with diabetes is increasing particularly in Asia-Pacific region. Many of them are treated with antidiabetics. As the basis of the studies on the benefit and harm of antidiabetic drugs in the region, the information on patterns of market penetration of new classes of antidiabetic medications is important in providing context for subsequent research and analyzing and interpreting results. METHODS We compared penetration patterns of dipeptidyl peptidase-4 (DPP-4) inhibitors in Taiwan, Hong Kong, Japan, and the United States. We used the Taiwan National Health Insurance Research Database, a random sample of the Hong Kong Clinical Data Analysis and Reporting System, the Japan Medical Data Center database, and a 5% random sample of the US Medicare database converted to the Observational Medical Outcomes Partnership's Common Data Model to identify new users of oral antidiabetic medications. We standardized prevalence and incidence rates of medication use by age and sex to those in the 2010 Taiwanese population. We compared age, sex, comorbid conditions, and concurrent medications between new users of DPP-4 inhibitors and biguanides. RESULTS Use of DPP-4 inhibitors 1 year after market entry was highest in Japan and lowest in Hong Kong. New users had more heart failure, hyperlipidemia, and renal failure than biguanide users in Taiwan, Hong Kong, and the United States while the proportions were similar in Japan. In a country with low penetration of DPP-4 inhibitors (eg, Hong Kong), users had diabetes with multiple comorbid conditions compared with biguanidine users. In a country with high penetration (eg, Japan), the proportion of users with comorbid conditions was similar to that of biguanide users. CONCLUSIONS We observed a marked difference of the penetration patterns of newly marketed antidiabetics in different countries in Asia. Those results will provide the basic information useful in the future studies.
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Affiliation(s)
- Kiyoshi Kubota
- NPO Drug Safety Research Unit Japan, Tokyo, Japan
- * E-mail:
| | | | - Yea-Huei Kao Yang
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | | | - Edward Chia-Cheng Lai
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
| | - Kenneth K. C. Man
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
- Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
| | - Patrick Ryan
- Janssen Research & Development, LLC, Titusville, New Jersey, United States of America
| | - Martijn Schuemie
- Janssen Research & Development, LLC, Titusville, New Jersey, United States of America
| | - Paul Stang
- Janssen Research & Development, LLC, Titusville, New Jersey, United States of America
| | - Chien-Chou Su
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ian C. K. Wong
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China
- Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
| | - Yinghong Zhang
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
| | - Soko Setoguchi
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
- Department of Epidemiology, Rutgers School of Public Health, New Brunswick, United States of America
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Clostridium difficile infection increases acute and chronic morbidity and mortality. Infect Control Hosp Epidemiol 2018; 40:65-71. [PMID: 30409240 DOI: 10.1017/ice.2018.280] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE In this study, we aimed to quantify short- and long-term outcomes of Clostridium difficile infection (CDI) in the elderly, including all-cause mortality, transfer to a facility, and hospitalizations. DESIGN Retrospective study using 2011 Medicare claims data, including all elderly persons coded for CDI and a sample of uninfected persons. Analysis of propensity score-matched pairs and the entire population stratified by the propensity score was used to determine the risk of all-cause mortality, new transfer to a long-term care facility (LTCF), and short-term skilled nursing facility (SNF), and subsequent hospitalizations within 30, 90, and 365 days. RESULTS The claims records of 174,903 patients coded for CDI were compared with those of 1,318,538 control patients. CDI was associated with increased risk of death (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.74-1.81; attributable mortality, 10.9%), new LTCF transfer (OR, 1.74; 95% CI, 1.67-1.82), and new SNF transfer (OR, 2.52; 95% CI, 2.46-2.58) within 30 days in matched-pairs analyses. In a stratified analysis, CDI was associated with greatest risk of 30-day all-cause mortality in persons with lowest baseline probability of CDI (hazard ratio [HR], 3.04; 95% CI, 2.83-3.26); the risk progressively decreased as the baseline probability of CDI increased. CDI was also associated with increased risk of subsequent 30-day, 90-day, and 1-year hospitalization. CONCLUSIONS CDI was associated with increased risk of short- and long-term adverse outcomes, including transfer to short- and long-term care facilities, hospitalization, and all-cause mortality. The magnitude of mortality risk varied depending on baseline probability of CDI, suggesting that even lower-risk patients may benefit from interventions to prevent CDI.
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Mejia-Chew C, Dubberke ER. Clostridium difficile control measures: current and future methods for prevention. Expert Rev Anti Infect Ther 2018; 16:121-131. [PMID: 29353504 DOI: 10.1080/14787210.2018.1429911] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Clostridium difficile is the most common cause of healthcare associated infection, and C. difficile infection (CDI) is associated with significant costs, morbidity, and mortality. One obstacle to preventing CDI is lack of high quality data on interventions to prevent CDI. This has led some to focus on areas, such as method of hand hygiene, unlikely to impact CDI incidence as much as others, such as contact precautions. In addition, existing strategies, although effective, do have limitations. Another challenge is the ability to rapidly, and accurately, diagnose CDI. Given these obstacles, new strategies to effectively prevent CDI are imperative to improve patient outcomes. Areas covered: Evidence of the interventions recommended by international scientific societies will be reviewed, as well as ongoing research on new strategies, such as screening for asymptomatic C. difficile carriage, microbiota sparing agents, bacteriocins and vaccines. Expert commentary: Current measures to prevent CDI are effective, but have significant limitations. Contact precautions and antimicrobial stewardship are likely the most effective of current prevention recommendations. Diagnostic assay utilization plays a role as well. New strategies to prevent CDI are needed, and, fortunately, several are being studied. Most likely a combination of approaches will be necessary to optimize CDI prevention.
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Affiliation(s)
- Carlos Mejia-Chew
- a Division of Infectious Disease , Washington University School of Medicine , St Louis , MO , USA
| | - Erik R Dubberke
- a Division of Infectious Disease , Washington University School of Medicine , St Louis , MO , USA
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Durkin MJ, Keller M, Butler AM, Kwon JH, Dubberke ER, Miller AC, Polgreen PM, Olsen MA. An Assessment of Inappropriate Antibiotic Use and Guideline Adherence for Uncomplicated Urinary Tract Infections. Open Forum Infect Dis 2018; 5:ofy198. [PMID: 30191156 PMCID: PMC6121225 DOI: 10.1093/ofid/ofy198] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 08/08/2018] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND In 2011, The Infectious Diseases Society of America released a clinical practice guideline (CPG) that recommended short-course antibiotic therapy and avoidance of fluoroquinolones for uncomplicated urinary tract infections (UTIs). Recommendations from this CPG were rapidly disseminated to clinicians via review articles, UpToDate, and the Centers for Disease Control and Prevention website; however, it is unclear if this CPG had an impact on national antibiotic prescribing practices. METHODS We performed a retrospective cohort study of outpatient and emergency department visits within a commercial insurance database between January 1, 2009, and December 31, 2013. We included nonpregnant women aged 18-44 years who had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a UTI with a concurrent antibiotic prescription. We performed interrupted time series analyses to determine the impact of the CPG on the appropriateness of the antibiotic agent and duration. RESULTS We identified 654 432 women diagnosed with UTI. The patient population was young (mean age, 31 years) and had few comorbidities. Fluoroquinolones, nonfirstline agents, were the most commonly prescribed antibiotic class both before and after release of the guidelines (45% vs 42%). Wide variation was observed in the duration of treatment, with >75% of prescriptions written for nonrecommended treatment durations. The CPG had minimal impact on antibiotic prescribing behavior by providers. CONCLUSIONS Inappropriate antibiotic prescribing is common for the treatment of UTIs. The CPG was not associated with a clinically meaningful change in national antibiotic prescribing practices for UTIs. Further interventions are necessary to improve outpatient antibiotic prescribing for UTIs.
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Affiliation(s)
- Michael J Durkin
- Division of Infectious Diseases, Department of Internal Medicine
| | - Matthew Keller
- Division of Infectious Diseases, Department of Internal Medicine
| | - Anne M Butler
- Division of Infectious Diseases, Department of Internal Medicine
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri
| | - Jennie H Kwon
- Division of Infectious Diseases, Department of Internal Medicine
| | - Erik R Dubberke
- Division of Infectious Diseases, Department of Internal Medicine
| | | | - Phillip M Polgreen
- Department of Epidemiology, College of Public Health
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa
| | - Margaret A Olsen
- Division of Infectious Diseases, Department of Internal Medicine
- Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis, St. Louis, Missouri
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Olsen MA, Stwalley D, Demont C, Dubberke ER. Increasing Age Has Limited Impact on Risk of Clostridium difficile Infection in an Elderly Population. Open Forum Infect Dis 2018; 5:ofy160. [PMID: 30046643 PMCID: PMC6054265 DOI: 10.1093/ofid/ofy160] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Accepted: 07/11/2018] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Numerous studies have found increased risk of Clostridium difficile infection (CDI) with increasing age. We hypothesized that increased CDI risk in an elderly population is due to poorer overall health status with older age. METHODS A total of 174 903 persons aged 66 years and older coded for CDI in 2011 were identified using Medicare claims data. The comparison population consisted of 1 453 867 uninfected persons. Potential risk factors for CDI were identified in the prior 12 months and organized into categories, including infections, acute noninfectious conditions, chronic comorbidities, frailty indicators, and health care utilization. Multivariable logistic regression models with CDI as the dependent variable were used to determine the categories with the biggest impact on model performance. RESULTS Increasing age was associated with progressively increasing risk of CDI in univariate analysis, with 5-fold increased risk of CDI in 94-95-year-old persons compared with those aged 66-67 years. Independent risk factors for CDI with the highest effect sizes included septicemia (odds ratio [OR], 4.1), emergency hospitalization(s) (OR, 3.9), short-term skilled nursing facility stay(s) (OR, 2.7), diverticulitis (OR, 2.2), and pneumonia (OR, 2.1). Exclusion of age from the full model had no impact on model performance. Exclusion of acute noninfectious conditions followed by frailty indicators resulted in lower c-statistics and poor model fit. Further exclusion of health care utilization variables resulted in a large drop in the c-statistic. CONCLUSIONS Age did not improve CDI risk prediction after controlling for a wide variety of infections, other acute conditions, frailty indicators, and prior health care utilization.
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Affiliation(s)
- Margaret A Olsen
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Dustin Stwalley
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
| | | | - Erik R Dubberke
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
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Azab M, Doo L, Doo DH, Elmofti Y, Ahmed M, Cadavona JJ, Liu XB, Shafi A, Joo MK, Yoo JW. Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis. Gut Liver 2018; 11:781-788. [PMID: 28506028 PMCID: PMC5669593 DOI: 10.5009/gnl16568] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 12/21/2016] [Accepted: 12/21/2016] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Although proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs. Methods A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I², and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence. Results A total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I²=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low. Conclusions The use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.
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Affiliation(s)
- Mohamed Azab
- Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA
| | - Loomee Doo
- Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA
| | - Daniel H Doo
- Department of Global Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Yousif Elmofti
- Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA
| | - Muazer Ahmed
- Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA
| | - John Jay Cadavona
- Department of Graduate Education, University of Nevada School of Medicine, Reno, NV, USA
| | - Xibei B Liu
- Department of Graduate Education, University of Nevada School of Medicine, Reno, NV, USA
| | - Amaan Shafi
- Department of Graduate Education, University of Nevada School of Medicine, Reno, NV, USA
| | - Moon Kyung Joo
- Institute of Gastroenterology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Won Yoo
- Department of Internal Medicine, University of Nevada School of Medicine, Las Vegas, NV, USA
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Dubberke ER, Reske KA, Olsen MA, Bommarito K, Cleveland AA, Silveira FP, Schuster MG, Kauffman CA, Avery RK, Pappas PG, Chiller TM. Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients. Transpl Infect Dis 2018; 20:e12855. [PMID: 29427356 DOI: 10.1111/tid.12855] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 09/29/2017] [Accepted: 11/07/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. METHODS We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. RESULTS Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). CONCLUSIONS The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.
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Affiliation(s)
- E R Dubberke
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - K A Reske
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - M A Olsen
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - K Bommarito
- Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA
| | - A A Cleveland
- Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - F P Silveira
- Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA, USA
| | - M G Schuster
- University of Pennsylvania, Philadelphia, PA, USA
| | - C A Kauffman
- VA Ann Arbor Healthcare System, University of Michigan Medical School, Ann Arbor, MI, USA
| | - R K Avery
- Johns Hopkins University, Baltimore, MD, USA
| | - P G Pappas
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - T M Chiller
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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Oh SH, Kang HY. Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach. Int J Infect Dis 2017; 66:107-112. [PMID: 29162405 DOI: 10.1016/j.ijid.2017.11.021] [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: 09/23/2017] [Revised: 11/03/2017] [Accepted: 11/08/2017] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. METHODS We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. RESULTS Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). CONCLUSIONS The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship.
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Affiliation(s)
- Sung-Hee Oh
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea
| | - Hye-Young Kang
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
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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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32
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Khanna S, Shin A, Kelly CP. Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute. Clin Gastroenterol Hepatol 2017; 15:166-174. [PMID: 28093134 DOI: 10.1016/j.cgh.2016.10.024] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Revised: 10/02/2016] [Accepted: 10/13/2016] [Indexed: 02/07/2023]
Abstract
The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.
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Affiliation(s)
- Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Andrea Shin
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana
| | - Ciarán P Kelly
- Gastroenterology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
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