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Wang L, Xu T, Wu S, Zhao C, Huang H. The efficacy and underlying mechanisms of berberine in the treatment of recurrent Clostridioides difficile infection. Int J Antimicrob Agents 2025; 65:107468. [PMID: 39986400 DOI: 10.1016/j.ijantimicag.2025.107468] [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: 10/14/2024] [Revised: 01/05/2025] [Accepted: 02/14/2025] [Indexed: 02/24/2025]
Abstract
Recurrent Clostridioides difficile infection (rCDI) is a global health threat that has received considerable attention. Berberine (BBR), a natural pentacyclic isoquinoline alkaloid, has been used as a cost-effective treatment for intestinal infections in Asia for many years. However, the effect of BBR on rCDI is not clear. The efficacy and underlying mechanisms of BBR were evaluated in a vancomycin-dependent rCDI mouse model and an intestinal organoids model. The study findings showed that BBR treatment alleviated the severity of infection and increased survival rate in rCDI mice. Mechanistically, BBR alleviated intestinal epithelial damage with higher Occludin expression, suppressed some inflammatory pathways and reduced the level of inflammatory factors in both the caecum and serum. Moreover, 16S rRNA sequencing analysis indicated that BBR reshaped the gut microbiota by increasing the abundance of Firmicutes and reducing the abundance of Proteobacteria. At genus level, BBR treatment increased levels of Blautia and Bilophila, and reduced levels of Proteus. In addition, acetic acid, one of the short-chain fatty acids (SCFAs), was also increased after BBR treatment in rCDI mice. Collectively, BBR exerted a protective effect in rCDI via multiple underlying mechanisms and is a potential drug candidate for alleviating rCDI, but further research is needed in this area.
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Affiliation(s)
- Li Wang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the PRC, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Teng Xu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the PRC, Shanghai, China
| | - Shi Wu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the PRC, Shanghai, China
| | - Chao Zhao
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
| | - Haihui Huang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the PRC, Shanghai, China.
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2
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Choi MH, Kim D, Lee KH, Kim HJ, Sul WJ, Jeong SH. Dysbiosis of the gut microbiota is associated with in-hospital mortality in patients with antibiotic-associated diarrhoea: A metagenomic analysis. Int J Antimicrob Agents 2024; 64:107330. [PMID: 39244165 DOI: 10.1016/j.ijantimicag.2024.107330] [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: 05/11/2024] [Revised: 07/12/2024] [Accepted: 08/29/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear. METHODS Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses. RESULTS Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20-4.99). CONCLUSION This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.
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Affiliation(s)
- Min Hyuk Choi
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Dokyun Kim
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyoung Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyeon Jin Kim
- Department of Systems Biotechnology, Chung-Ang University, Anseong, South Korea
| | - Woo Jun Sul
- Department of Systems Biotechnology, Chung-Ang University, Anseong, South Korea
| | - Seok Hoon Jeong
- Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
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3
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Mendo-Lopez R, Alonso CD, Villafuerte-Gálvez JA. Best Practices in the Management of Clostridioides difficile Infection in Developing Nations. Trop Med Infect Dis 2024; 9:185. [PMID: 39195623 PMCID: PMC11359346 DOI: 10.3390/tropicalmed9080185] [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: 06/14/2024] [Revised: 08/13/2024] [Accepted: 08/13/2024] [Indexed: 08/29/2024] Open
Abstract
Clostridioides difficile infection (CDI) is a well-known cause of hospital-acquired infectious diarrhea in developed countries, though it has not been a top priority in the healthcare policies of developing countries. In the last decade, several studies have reported a wide range of CDI rates between 1.3% and 96% in developing nations, raising the concern that this could represent a healthcare threat for these nations. This review defines developing countries as those with a human development index (HDI) below 0.8. We aim to report the available literature on CDI epidemiology, diagnostics, management, and prevention in developing countries. We identify limitations for CDI diagnosis and management, such as limited access to CDI tests and unavailable oral vancomycin formulation, and identify opportunities to enhance CDI care, such as increased molecular test capabilities and creative solutions for CDI. We also discuss infection prevention strategies, including antimicrobial stewardship programs and opportunities emerging from the COVID-19 pandemic, which could impact CDI care.
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Affiliation(s)
- Rafael Mendo-Lopez
- Division of Infectious Disease, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA
- School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
- Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, USA
| | - Carolyn D. Alonso
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA;
- Harvard Medical School, Harvard University, Boston, MA 02215, USA;
| | - Javier A. Villafuerte-Gálvez
- Harvard Medical School, Harvard University, Boston, MA 02215, USA;
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
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4
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Banawas SS. Systematic Review and Meta-Analysis on the Frequency of Antibiotic-Resistant Clostridium Species in Saudi Arabia. Antibiotics (Basel) 2022; 11:antibiotics11091165. [PMID: 36139945 PMCID: PMC9495114 DOI: 10.3390/antibiotics11091165] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/16/2022] Open
Abstract
Clostridium is a genus comprising Gram-positive, rod-shaped, spore-forming, anaerobic bacteria that cause a variety of diseases. However, there is a shortage of information regarding antibiotic resistance in the genus in Saudi Arabia. This comprehensive analysis of research results published up until December 2021 intends to highlight the incidence of antibiotic resistance in Clostridium species in Saudi Arabia. PubMed, Google Scholar, Web of Science, SDL, and ScienceDirect databases were searched using specific keywords, and ten publications on antibiotic resistance in Clostridium species in Saudi Arabia were identified. We found that the rates of resistance of Clostridium difficile to antibiotics were as follows: 42% for ciprofloxacin, 83% for gentamicin, 28% for clindamycin, 25% for penicillin, 100% for levofloxacin, 24% for tetracycline, 77% for nalidixic acid, 50% for erythromycin, 72% for ampicillin, and 28% for moxifloxacin; whereas those of C. perfringens were: 21% for metronidazole, 83% for ceftiofur, 39% for clindamycin, 59% for penicillin, 62% for erythromycin, 47% for oxytetracycline, and 47% for lincomycin. The current findings suggest that ceftiofur, erythromycin, lincomycin, and oxytetracycline should not be used in C. perfringens infection treatments in humans or animals in Saudi Arabia.
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Affiliation(s)
- Saeed S. Banawas
- Department of Medical Laboratories, College of Applied Medical Science, Majmaah University, Al-Majmaah 11952, Saudi Arabia; ; Tel.: +966-164041510
- Health and Basic Sciences Research Center, Majmaah University, Al-Majmaah 11952, Saudi Arabia
- Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA
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5
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Meng X, Huang X, Peng Z, Wang Y, Liu S, Zeng C, Duan J, Wen X, Fu C, Wu A, Li C. Antibiotic Resistances and Molecular Characteristics of Clostridioides difficile in ICUs in a Teaching Hospital From Central South China. Front Med (Lausanne) 2021; 8:745383. [PMID: 34938744 PMCID: PMC8685378 DOI: 10.3389/fmed.2021.745383] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/01/2021] [Indexed: 11/21/2022] Open
Abstract
Clostridioides (C.) difficile is a major healthcare-associated pathogen inducing infectious diarrhea. Approximately 25–33% of patients with antibiotic-associated diarrhea (AAD) and 90% of patients with pseudomembranous enteritis are caused by C. difficile infection (CDI). Stool samples were collected from hospitalized adults with presumptive AAD in four nonneonatal intensive care units (ICUs). Diagnosis of CDI was based on both clinical symptoms and laboratory results. The stool specimens were transferred onto CDIF (C. difficile agar), and C. difficile was finally confirmed by the latex agglutination test. Toxin-producing genes tcdA (A), tcdB (B), and cdt (CDT) were detected by PCR, and all isolates were performed multilocus sequence typing analysis. The antibiotic susceptibility of C. difficile isolates was assessed by the agar dilution method. A total of 184 C. difficile were isolated from 857 specimens in our study, the isolation rate of C. difficile was 21.5% (184/857). The 184 C. difficile were isolated from 179 patients, among these 115 patients were toxin-positive, giving the incidence of CDI being 58.0/10,000 patient days in the four ICUs. Among these 115 toxin-positive C. difficile isolates, 100 (87.0%) isolates produced two toxins (A+B+CDT-), three (2.6%) isolates were A+B+ with binary toxin-producing (A+B+CDT+), and 12 (10.4%) isolates only produced one toxin (A-B+CDT-). A total of 27 sequencing types (STs) were obtained. The most prevalent was ST3 (34 isolates), followed by ST39 (27 isolates), ST54 (19 isolates), ST26 (16 isolates), ST35 (15 isolates), and ST2 (13 isolates). All the ST26 isolates were nontoxigenic. Meanwhile, five STs were newly discovered. Although multidrug resistance was present in ≥50% of these C. difficile isolates, all of them were susceptible to tigecycline, fidaxomicin, metronidazole, and vancomycin. In conclusion, C. difficile isolates producing two toxins (A+B+CDT-) were dominant in our hospital. The most prevalent was ST3, and all ST26 isolates were NTCD. Although multidrug resistance was present in ≥50% of the C. difficile isolates, metronidazole, tigecycline, fidaxomicin, and vancomycin were still effective treatments for CDI in our hospital.
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Affiliation(s)
- Xiujuan Meng
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Xun Huang
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Zhong Peng
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Yaowang Wang
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Sidi Liu
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Cui Zeng
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Juping Duan
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Ximao Wen
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Chenchao Fu
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China
| | - Anhua Wu
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
| | - Chunhui Li
- Infection Control Center, Xiangya Hospital of Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, China
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6
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Lazebnik LB, Sarsenbaeva AS, Avalueva EB, Oreshko LS, Sitkin SI, Golovanova EV, Turkina SV, Khlynova OV, Sagalova OI, Mironchev OV. Clinical guidelines “Chronic diarrhea in adults”. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:7-67. [DOI: 10.31146/1682-8658-ecg-188-4-7-67] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Affiliation(s)
- L. B. Lazebnik
- Federal State Budgetary Educational Institution of Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russion Federation
| | | | - E. B. Avalueva
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - L. S. Oreshko
- North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - S. I. Sitkin
- North- Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation;
Federal State Budgetary Institution “Almazov National Medical Research Centre” of the Ministry of Health of the Russian Federation
| | - E. V. Golovanova
- Federal State Budgetary Educational Institution of Higher Education “A. I. Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russion Federation
| | - S. V. Turkina
- State-funded Educational Establishment of Higher Professional Education “Volgograd State Medical University of the Ministry of Public Health of the Russian Federation”
| | - O. V. Khlynova
- Perm State Medical University named after academician E. A. Vagner Ministry of Health care of Russia
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7
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Grinevich VB, Kravchuk YA, Ped VI, Sas EI, Salikova SP, Gubonina IV, Tkachenko EI, Sitkin SI, Lazebnik LB, Golovanova EV, Belousova EA, Makarchuk PA, Eremina EY, Sarsenbaeva AS, Abdulganieva DI, Tarasova LV, Gromova OA, Ratnikov VA, Kozlov KV, Ratnikova AK. Management of patients with digestive diseases during the COVID-19 pandemic. Clinical Practice Guidelines by the Russian scientific medical society of internal medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (2nd edition). EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:5-82. [DOI: 10.31146/1682-8658-ecg-187-3-5-82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
The presented clinical practice guidelines of the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The guidelines were approved by the XXIII Congress of the GSSR and the 22nd International Slavonic-Baltic Scientifi c Forum “St. Petersburg - Gastro-2020 ON-LINE” (St. Petersburg, June 11, 2020). The presented clinical practice guidelines of the Russian Scientific Medical Society of Internal Medicine (RSMSIM) and the Gastroenterological Scientific Society of Russia (GSSR), diagnostic, and therapeutic approaches for patients with digestive diseases during the COVID-19 pandemic. The recommendations were approved at the XV National Congress of Internal Medicine, XXIII Congress of NOGR on the basis of the 1st edition, adopted at the 22nd International Slavic- Baltic Scientific Forum “St. Petersburg - Gastro-2020 ON-LINE”.
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Affiliation(s)
| | | | - V. I. Ped
- Military Medical Academy named after S. M. Kirov
| | - E. I. Sas
- Military Medical Academy named after S. M. Kirov
| | | | | | | | - S. I. Sitkin
- State Research Institute of Highly Pure Biopreparations of FMBA of Russia; Almazov National Medical Research Centre; North-Western state medical University named after I. I. Mechnikov, Ministry of health of the Russian Federation
| | - L. B. Lazebnik
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. V. Golovanova
- Moscow state University of Medicine a. Densitry named after A. I. Yevdokimov of the Ministry of Health of Russia
| | - E. A. Belousova
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - P. A. Makarchuk
- State Budgetary Institution of Moscow Region “Moscow Regional Research Clinical Institute n.a. M. F. Vladimirsky”
| | - E. Yu. Eremina
- Federal State Budgetary Educational Institution of Higher Education “National Research Ogarev Mordovia State University”
| | - A. S. Sarsenbaeva
- FSBEI HE SUSMU MOH Russia, st. Vorovskogo, 64, Ural Federal District
| | | | - L. V. Tarasova
- FSBEI of HE “The Chuvash State University n.a. I. N. Ulyanov”; BI of HE “The Surgut State University”
| | - O. A. Gromova
- Federal Research Center “Informatics and Management” of the Russian Academy of Sciences; Federal State Educational Institution of Higher Education Lomonosov Moscow State University
| | - V. A. Ratnikov
- Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
| | - K. V. Kozlov
- Military Medical Academy named after S. M. Kirov
| | - A. K. Ratnikova
- Military Medical Academy named after S. M. Kirov; Federal state budgetary institution “North-West District Scientific and Clinical Center named after L. G. Sokolov Federal Medical and Biological Agency“
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8
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Zhou H, Xu Q, Liu Y, Guo LT. Risk factors, incidence, and morbidity associated with antibiotic-associated diarrhea in intensive care unit patients receiving antibiotic monotherapy. World J Clin Cases 2020; 8:1908-1915. [PMID: 32518780 PMCID: PMC7262719 DOI: 10.12998/wjcc.v8.i10.1908] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/09/2020] [Accepted: 04/28/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND This study aimed to identify factors associated with antibiotic-associated diarrhea (AAD) in patients in the department of intensive care medicine who received antibiotic monotherapy in order to reduce the incidence of AAD and improve rational use of antibiotics in these patients.
AIM To report the incidence of AAD and the factors associated with AAD in patients receiving antibiotic monotherapy.
METHODS The study used a single-center retrospective design. A total of 209 patients were enrolled. Patients were divided into two groups: No-AAD group (without AAD) and AAD group (with AAD). There were 45 cases in the AAD group and 164 cases in the no-AAD group. Clinical data of all patients were collected. Data were analyzed using SPSS (version 18.0), and statistical significance was set at P < 0.05.
RESULTS The overall incidence of AAD was 21.53%. Age [odds ratio (OR) 1.022, 95% confidence interval (CI): 1.001-1.044, P = 0.040], proton pump inhibitor usage time (OR 1.129, 95%CI: 1.020-1.249, P = 0.019), antibiotic usage time (OR 1.163, 95%CI: 1.024-1.320, P = 0.020), and intensive care unit (ICU) stay time (OR 1.133, 95%CI: 1.041-1.234, P = 0.004) were associated with AAD in ICU patients receiving antibiotic monotherapy. mean ± SD ICU stay time was lower in the no-AAD group (8.49 ± 6.31 vs 15.89 ± 10.69, P < 0.001). However, there was no significant difference in ICU-related mortality rates between the two groups (P = 0.729).
CONCLUSION Older age, longer ICU stay time, duration of use of proton pump inhibitors, and duration of antibiotic increase the incidence of AAD in ICU patients receiving antibiotic monotherapy.
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Affiliation(s)
- Hong Zhou
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Qiang Xu
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Yu Liu
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
| | - Li-Tao Guo
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
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9
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Gao Y, Li H, Yang H, Su J, Huang L. The current novel therapeutic regimens for Clostridium difficile infection (CDI) and the potentials of Traditional Chinese Medicine in treatment of CDI. Crit Rev Microbiol 2019; 45:729-742. [PMID: 31838936 DOI: 10.1080/1040841x.2019.1700905] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Clostridium difficile infection (CDI) is featured as the dysbiosis of gut microbiota and consequent mild diarrhoea or severe pseudomembranous colitis. However, the frequent recurrence of CDI following treatment course challenged the antibiotic therapy. Currently, to address the relapse of CDI, several novel therapeutic approaches have emerged, including Bezlotoxumab, SYN-004 (Ribaxamase), RBX2660, and faecal microbial transplant. Traditional Chinese Medicine (TCM) is an old medical system accumulated for thousands of years. Orientated by syndrome-based treatment, TCM functions in a multicomponent and multitarget mode. This old medical system showed superiority over conventional medical treatment, particularly in the treatment of complex disorders, including CDI. In the present review, we will elaborate the TCM intervention in the management of CDI and others disorders via restoring the gut microbiota dysbiosis. We hope that this review will deepen our understanding of TCM as an alternative to CDI treatment. However, more rigorously designed basic researches and randomised controlled trials need to conduct to appraise the function mechanisms and effects of TCM. Finally, it is concluded that the combined therapeutic potentials of TCM and western medicine could be harness to resolve the recurrence and improve the outcome of CDI.
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Affiliation(s)
- Yan Gao
- Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Li
- Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences, Beijing, China
| | - Hongjun Yang
- Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences, Beijing, China
| | - Jianrong Su
- Department of Clinical Laboratory Diagnostics, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Luqi Huang
- China Academy of Chinese Medical Sciences, Beijing, China
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10
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Ma H, Zhang L, Zhang Y, Liu Y, He Y, Guo L. Combined administration of antibiotics increases the incidence of antibiotic-associated diarrhea in critically ill patients. Infect Drug Resist 2019; 12:1047-1054. [PMID: 31118710 PMCID: PMC6503325 DOI: 10.2147/idr.s194715] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 03/25/2019] [Indexed: 01/12/2023] Open
Abstract
Background: The widespread use of antibiotics has resulted in a high incidence of antibiotic-associated diarrhea (AAD); moreover, the AAD-associated mortality rates have also increased. The effect of combined antibiotic administration on AAD in critically ill patients was analyzed to assist in antibiotic selection for AAD prevention. Methods: Clinical data of patients hospitalized were retrospectively analyzed. Patients were either assigned to the combined-use group (CG) or the monotherapy group (MG). Age, sex, albumin levels, proton pump inhibitors, the type antibiotics, occurrence of AAD were collected. All relevant data were analyzed using SPSS version 18.0 (IBM Inc., Armonk, NY, USA), and significance was set at P<0.05. Measurements and main results: Overall, 277 patients were enrolled (CG, n=143; MG, n=134). The incidence of AAD was significantly different between the groups (44.06% vs 17.16%, P<0.001). Combined use of three or more antibiotics, other antibiotics combined with antifungals antibiotics increases the incidence of AAD (P<0.05). Duration of proton pump inhibitor therapy (odds ratio [OR] 1.142, 95% confidence interval [CI] 1.048–1.244, P=0.002), antifungal antibiotic administration (OR 3.189, 95% CI 1.314–7.740, P=0.010), and beta-lactam plus enzyme inhibitor antibiotic administration (OR 3.072, 95% CI 1.309–7.205, P=0.010) were associated with AAD in critically ill patients receiving combined antibiotics therapy. The mean duration of intensive care unit admission was longer among patients with AAD compared with patients without AAD (19.70±12.16 vs 12.29±8.06 days, P<0.001), with no significant difference in intensive care unit-related mortality rates. Conclusion: Combined administration of antibiotics, especially beta-lactam plus enzyme inhibitors and antifungals, may increase the incidence of AAD in critically ill patients.
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Affiliation(s)
- Hongye Ma
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Lei Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yanshu Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yu Liu
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Yingli He
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
| | - Litao Guo
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China
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11
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Jingjing S, Yanshu Z, Yu L, Qindong S, Xue W, Lei Z, Yingli H, Litao G. Factors related to antibiotic-associated diarrhea in patients in the intensive care unit receiving antifungals: a single-center retrospective study. J Int Med Res 2019; 47:2067-2076. [PMID: 30898003 PMCID: PMC6567793 DOI: 10.1177/0300060519836305] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Objective To analyze factors related to antibiotic-associated diarrhea (AAD) in patients in the intensive care unit (ICU) receiving antifungals with the aim of informing rational antibiotic use. Methods Sex, age, medical history, use of proton pump inhibitors, administration of parenteral nutrition, albumin level, occurrence of AAD, type of antibiotics, duration of ICU admission, and prognosis were retrospectively analyzed. The associations of age, sex, medical history, and other factors with AAD were associated by logistic regression. Results In total, 284 patients were enrolled (antifungals, n = 110; no antifungals, n = 174). The total incidence of AAD was 32.39%. The incidence of AAD was significantly different between the groups (52.73% vs. 19.54%). The duration of proton pump inhibitor therapy, duration of antifungal therapy, enzyme inhibitor antibiotic use, and azithromycin use were associated with AAD in ICU patients receiving antifungal therapy. The mean duration of ICU admission was higher in patients receiving antifungal therapy (20.14 ± 11.50 vs. 14.48 ± 8.54 days). There was no significant difference in ICU mortality rates. Conclusion The duration of proton pump inhibitor therapy, duration of antifungal therapy, use of enzyme inhibitor antibiotics, and use of azithromycins were associated with AAD in ICU patients receiving antifungal therapy.
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Affiliation(s)
- Sun Jingjing
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhang Yanshu
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Liu Yu
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shi Qindong
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Wang Xue
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhang Lei
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - He Yingli
- 2 Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Guo Litao
- 1 Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Clostridium difficile in Asia: Opportunities for One Health Management. Trop Med Infect Dis 2018; 4:tropicalmed4010007. [PMID: 30597880 PMCID: PMC6473466 DOI: 10.3390/tropicalmed4010007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 12/22/2018] [Accepted: 12/23/2018] [Indexed: 01/05/2023] Open
Abstract
Clostridium difficile is a ubiquitous spore-forming bacterium which causes toxin-mediated diarrhoea and colitis in people whose gut microflora has been depleted by antimicrobial use, so it is a predominantly healthcare-associated disease. However, there are many One Health implications to C. difficile, given high colonisation rates in food production animals, contamination of outdoor environments by use of contaminated animal manure, increasing incidence of community-associated C. difficile infection (CDI), and demonstration of clonal groups of C. difficile shared between human clinical cases and food animals. In Asia, the epidemiology of CDI is not well understood given poor testing practices in many countries. The growing middle-class populations of Asia are presenting increasing demands for meat, thus production farming, particularly of pigs, chicken and cattle, is rapidly expanding in Asian countries. Few reports on C. difficile colonisation among production animals in Asia exist, but those that do show high prevalence rates, and possible importation of European strains of C. difficile like ribotype 078. This review summarises our current understanding of the One Health aspects of the epidemiology of CDI in Asia.
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Zhang Y, Sun J, Zhang J, Liu Y, Guo L. Enzyme Inhibitor Antibiotics and Antibiotic-Associated Diarrhea in Critically Ill Patients. Med Sci Monit 2018; 24:8781-8788. [PMID: 30512009 PMCID: PMC6289033 DOI: 10.12659/msm.913739] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND This study aimed to analyze the factors associated with the development of antibiotic-associated diarrhea (AAD) in critically ill patients receiving enzyme inhibitor antibiotics. MATERIAL AND METHODS A retrospective study of patients with and without AAD admitted to the intensive care unit (ICU) of the First Teaching Hospital of Xi'an Jiaotong University from February 1, 2014, to January 31, 2016, was undertaken. Relevant clinical data underwent univariate or multivariate regression analysis. RESULTS Of 184 patients who received enzyme inhibitor antibiotic therapy, 70 patients (38.04%) developed AAD, with a mean duration of onset of 6.97±3.64 days. AAD was associated with the use of enzyme inhibitor antibiotic therapy alone (OR, 1.142; 95% CI, 1.038-1.256; P=0.007), and in combination with antifungal agents (OR, 2.449; 95% CI, 1.116-5.372; P=0.025), quinolones (OR, 5.219; 95% CI, 1.746-15.601; P=0.003), and oxazolidinones (OR 2.895; 95% CI, 1.183-7.083; P=0.020). The mean duration of ICU stay was significantly increased in patients with AAD (19.00±11.49 days vs. 9.60±6.76 days) (P<0.001). Mean duration of antibiotic therapy (14.09±8.82 days vs. 8.10±4.91 days) (P<0.001) and duration of enzyme inhibitor antibiotic therapy (9.26±5.06 days vs. 6.61±3.24 days) (P<0.001) were significantly increased in patients with AAD. CONCLUSIONS Duration of use of enzyme inhibitor antibiotic therapy and the combined use of antifungals, quinolones, and oxazolidinones increased the incidence and duration of AAD and increased the length of stay in ICU.
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Affiliation(s)
- Yanshu Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Jingjing Sun
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Jing Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Yu Liu
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Litao Guo
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
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Litao G, Jingjing S, Yu L, Lei Z, Xiaona H, Zhijing Z. Risk Factors for Antibiotic-Associated Diarrhea in Critically Ill Patients. Med Sci Monit 2018; 24:5000-5007. [PMID: 30020891 PMCID: PMC6067053 DOI: 10.12659/msm.911308] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 07/06/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND We analyzed the factors related to AAD to inform the rational use of antibiotics in critically ill patients and to reduce the incidence of AAD by providing a reference for antibiotic use in the clinical setting. MATERIAL AND METHODS This study was a retrospective analysis of the clinical data of patients who were hospitalized in the ICU of the First Teaching Hospital of Xi'an Jiaotong University from January 1, 2015 to December 31, 2016. Patients with AAD were assigned to the case group, and all others were assigned to the control group. Basic data were collected for all the selected patients. All the relevant data were analyzed with univariate or multivariate regression analyses, and P<0.05 was considered statistical significance. RESULTS A total of 293 patients were enrolled. Statistical analyses showed that gender (OR 1.915; 95% [CI] 1.061-3.455; P=0.031), parenteral nutrition (OR 1.877; 95% [CI] 1.043-3.377; P=0.036), preventive use of probiotics (OR 0.497; 95% [CI] 0.285-0.866; P=0.014), APACHE II score upon admission to the ICU (OR 0.961; 95% [CI] 0.927-0.998; P=0.037) and use of enzyme-inhibitor antibiotics (OR 1.899; 95% [CI] 1.044-3.420; P=0.016) were associated with AAD. Further subgroup analysis by gender showed that parenteral nutrition (OR 2.144; 95% [CI] 1.064-4.322; P=0.033), preventive use of probiotics (OR 0.367; 95% [CI] 0.186-0.722; P=0.004), and APACHE II score upon admission to the ICU (OR 1.055; 95% [CI] 1.011-1.101; P=0.014) were associated with AAD in critically ill male patients. Age (OR 0.975; 95% [CI] 0.951-0.999; P=0.041) and use of carbapenem antibiotics (OR 4.826; 95% [CI] 1.011-23.030; P=0.048) were associated with AAD in critically ill female patients. CONCLUSIONS Parenteral nutrition, prophylactic use of probiotics, use of enzyme-inhibitor antibiotics, and use of combinations of antibiotics were associated with AAD in critically ill patients. The prophylactic use of probiotics may be a protective factor in AAD.
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Wang B, Lv Z, Zhang P, Su J. Molecular epidemiology and antimicrobial susceptibility of human Clostridium difficile isolates from a single institution in Northern China. Medicine (Baltimore) 2018; 97:e11219. [PMID: 29924052 PMCID: PMC6023650 DOI: 10.1097/md.0000000000011219] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Because the epidemiology of Clostridium difficile infection (CDI) is region-specific, the present study was undertaken to examine the epidemiology of C difficile outbreaks in Beijing, China.Eighty nonduplicate isolates were collected from March, 2016 to December, 2016. The molecular type and phylogenetic analysis were evaluated by multilocus sequence typing (MLST). The minimum inhibitory concentrations (MICs) for 11 antibiotics and the resistance mechanisms were investigated.Sixty-five toxigenic strains (81.25%), including 22 tcdABCDT strains (27.5%) and 43 tcdABCDT strains (53.75%), and also 15 nontoxigenic strains (tcdABCDT; 18.75%) were detected. MLST identified 21 different sequence types (STs), including 2 novel types (ST409 and ST416). All isolates were susceptible to metronidazole, vancomycin, fidaxomicin, piperacillin/tazobactam, and meropenem, and all were effectively inhibited by emodin (MICs 4-8 μg/mL). The resistance rates to rifaximin, ceftriaxone, clindamycin, erythromycin, and ciprofloxacin were 8.75%, 51.25%, 96.25%, 81.25%, and 96.25%, respectively; 81.25% (65/80) of isolates were multidrug-resistant. Amino acid mutations in GyrA and/or GyrB conferred quinolone resistance. One novel amino acid substitution, F86Y in GyrA, was found in 1 CIP-intermediate strain. The erm(B) gene played a key role in mediating macrolide-lincosamide-streptogramin B (MLSB) resistance. Erm(G) was also found in erm(B)-negative strains that were resistant to both erythromycin and clindamycin. RpoB mutations were associated with rifampin resistance, and 2 new amino mutations were identified in 1 intermediate strain (E573A and E603N).Regional diversity and gene heterogeneity exist in both the ST type and resistant patterns of clinical C difficile isolates in Northern China.
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Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8414257. [PMID: 29682562 PMCID: PMC5841113 DOI: 10.1155/2018/8414257] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 01/28/2018] [Indexed: 12/11/2022]
Abstract
Clostridium difficile (C. difficile) is the most prevalent causative pathogen of healthcare-associated diarrhea. Notably, over the past 10 years, the number of Clostridium difficile outbreaks has increased with the rate of morbidity and mortality. The occurrence and spread of C. difficile strains that are resistant to multiple antimicrobial drugs complicate prevention as well as potential treatment options. Most C. difficile isolates are still susceptible to metronidazole and vancomycin. Incidences of C. difficile resistance to other antimicrobial drugs have also been reported. Most of the antibiotics correlated with C. difficile infection (CDI), such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones, continue to be associated with the highest risk for CDI. Still, the detailed mechanism of resistance to metronidazole or vancomycin is not clear. Alternation in the target sites of the antibiotics is the main mechanism of erythromycin, fluoroquinolone, and rifamycin resistance in C. difficile. In this review, different antimicrobial agents are discussed and C. difficile resistance patterns and their mechanism of survival are summarized.
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Borren NZ, Ghadermarzi S, Hutfless S, Ananthakrishnan AN. The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact. PLoS One 2017; 12:e0176797. [PMID: 28463987 PMCID: PMC5413003 DOI: 10.1371/journal.pone.0176797] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 04/17/2017] [Indexed: 12/18/2022] Open
Abstract
Background Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. Methods We systematically searched PubMed/Medline and Embase for publications from Asia between 2000–16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Results Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. Conclusions In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.
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Affiliation(s)
- Nienke Z. Borren
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- University of Groningen, Groningen, The Netherlands
| | - Shadi Ghadermarzi
- Division of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Susan Hutfless
- Division of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, Maryland, United States of America
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
| | - Ashwin N. Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
- Harvard Medical School, Boston, Massachusetts, United States of America
- * E-mail:
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18
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Chen Y, Zhao JY, Shan X, Han XL, Tian SG, Chen FY, Su XT, Sun YS, Huang LY, Han L. A point-prevalence survey of healthcare-associated infection in fifty-two Chinese hospitals. J Hosp Infect 2016; 95:105-111. [PMID: 28007308 DOI: 10.1016/j.jhin.2016.08.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 08/10/2016] [Indexed: 11/29/2022]
Abstract
BACKGROUND Healthcare-associated infection (HCAI) represents a major problem for patient safety worldwide. AIM To demonstrate the prevalence, causative agents, and risk factors for HCAI in Chinese hospitals. METHODS A one-day point-prevalence survey was conducted in 52 Chinese hospitals between October 2014 and March 2015. A web-based software system was developed for data entry and management. FINDINGS Among 53,939 patients surveyed, the prevalence of patients with at least one HCAI was 3.7%. Of 2182 HCAI episodes, the most frequently occurring types were lower respiratory tract infections (47.2%), followed by urinary tract infection (12.3%), upper respiratory tract infection (11.0%), and surgical site infection (6.2%). The prevalence of patients with at least one HCAI in critical care units was highest (17.1%). Device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central catheter-associated bloodstream infection, accounted for only 7.9% of all HCAIs. The most frequently isolated micro-organisms were Pseudomonas aeruginosa [206 infections (9.4%)], Acinetobacter baumannii [172 infections (7.9%)], Klebsiella pneumoniae [160 infections (7.3%)], and Escherichia coli [145 infections (6.6%)]. Of the survey patients (18,206/53,939), 33.8% were receiving at least one antimicrobial agent at the time of the survey. Risk factors for HCAI included older age (≥80 years), male gender, days of hospital admission, admission into a critical care unit, and device utilization. CONCLUSION Our study suggests that the overall prevalence of HCAI in surveyed Chinese hospitals was lower than that reported from most European countries and the USA. More attention should be given to the surveillance and prevention of non-device-associated HCAI in China.
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Affiliation(s)
- Y Chen
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - J Y Zhao
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - X Shan
- School of Public Health, Peking University, Beijing, China
| | - X L Han
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - S G Tian
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - F Y Chen
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - X T Su
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - Y S Sun
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - L Y Huang
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China
| | - L Han
- Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
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Li Y, Huang Y, Li Y, Nie Y. Clinical characteristics of Clostridium difficile-associated diarrhea among patients in a tertiary care center in China. Pak J Med Sci 2016; 32:736-41. [PMID: 27375724 PMCID: PMC4928433 DOI: 10.12669/pjms.323.9400] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Objective: This study investigated the incidence, risk factors, and clinical characteristics of Clostridium difficile-associated diarrhea (CDAD) in Chinese patients. Methods: Fecal specimens of patients with antibiotic-associated diarrhea (AAD) were collected to test C. difficile toxin A and B using enzyme-linked fluorescent assay to identify CDAD. By adopting a nested case-control design, the matched people (ratio 1:3) without AAD were included as controls. Results: Out of 56,172 inpatients, 39,882 (71.0%) used antibiotics, 470 suffered from AAD, and 93 were diagnosed with CDAD. The incidence of nosocomial CDAD was 166 per 100,000. The proportion of CDAD in AAD was 19.8%. CDAD patients presented with more severe clinical manifestations and exhibited more concurrent illness. Logistic regression analysis showed the risk factors of CDAD: advanced age, nasogastric tube-feeding, high APACHE II scores, high level of serum C-reaction protein, low level of serum albumin, severe underlining disease or comorbidity, and number of antibiotic intake. Twenty-nine patients (31.2%) were cured with vancomycin, 54 (58.1%) were cured after dual therapy of vancomycin plus metronidazole, 7 (7.5%) died of underlying diseases aggravated with CDAD, and 3 (3.2%) were transferred to other hospitals for personal reasons. Conclusion: The incidence of nosocomial CDAD in China was high. Some risk factors could predispose CDAD.
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Affiliation(s)
- Yongqiang Li
- Yongqiang Li, Department of Gastroenterology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangdong, China
| | - Yi Huang
- Yi Huang, Department of Gastroenterology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangdong, China
| | - Yuyuan Li
- Yuyuan Li, Department of Gastroenterology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangdong, China
| | - Yuqiang Nie
- Yuqiang Nie, Department of Gastroenterology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangdong, China
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Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland. Epidemiol Infect 2015; 143:3235-43. [DOI: 10.1017/s0950268815000552] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
SUMMARYOver the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.
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Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai, China. Anaerobe 2014; 30:65-9. [PMID: 25219941 DOI: 10.1016/j.anaerobe.2014.08.015] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Revised: 08/26/2014] [Accepted: 08/29/2014] [Indexed: 01/03/2023]
Abstract
Clostridium difficile infection (CDI) is an increasing concern in China. However, the risk factors of CDI are rarely reported in the Chinese population. A prospective observational study was therefore conducted among patients with hospital-acquired C. difficile diarrhoea and the risk factors of CDI in a retrospective case-control study. The CDI patients were compared with the non-CDI diarrhoeal patients and those without diarrhoea, respectively. The recurrent CDI patients were compared with the corresponding non-recurrent CDI patients and those without diarrhoea, respectively. Overall, of the 240 patients with hospital-acquired diarrhoea 90 (37.5%) were diagnosed as CDI, and 12 (13.3%) of the 90 CDI patients experienced recurrence. Multivariate analysis indicated that renal disease, malignancy, hypoalbuminemia, prior antibiotic treatment, chemotherapy, nasogastric tube use, length of stay>14 days and intra-abdominal surgery, defined daily dose of antimicrobial agents≥19, prior use of more than three antimicrobial agents, and use of carbapenems were independent risk factors for the first episode of CDI. Use of laxatives, the first- and second-generation narrow-spectrum cephalosporins or metronidazole was identified as protective factors. It is necessary to make testing of C. difficile available as a routine practice and control these risk factors in Chinese hospitals to avoid CDI outbreaks.
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Zhou FF, Wu S, Klena JD, Huang HH. Clinical characteristics of Clostridium difficile infection in hospitalized patients with antibiotic-associated diarrhea in a university hospital in China. Eur J Clin Microbiol Infect Dis 2014; 33:1773-9. [PMID: 24820293 DOI: 10.1007/s10096-014-2132-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 04/21/2014] [Indexed: 12/12/2022]
Abstract
The purpose of this study was to identify clinical characteristics of Clostridium difficile infection (CDI) in patients with antibiotic-associated diarrhea (AAD). A prospective study was conducted among patients hospitalized in Fudan University Hospital Huashan from August 1, 2012 to July 31, 2013. Toxigenic C. difficile isolates were characterized by PCR ribotyping and multilocus sequence typing. AAD developed in 1.0 % (206/20437) of the antibiotic-treated hospitalized patients and toxigenic C. difficile was isolated from 30.6 % (63/206) of patients with AAD. The frequency of AAD was highest in the intensive care unit (10.7 %); however the proportion of CDI in AAD was highest in the Geriatric Unit (38 %). AAD ranged in severity from mild to moderate. One case with pseudomembranous colitis was identified. Use of carbapenems was found to significantly increase the risk of CDI (OR, 2.31; 95 % CI, 1.22-4.38; p = 0.011). Patient demographics, presumed risk factors, clinical manifestations and laboratory findings revealed no significant difference between patients with CDI and non-C. difficile AAD. Over 90 % of the patients with CDI or non-C. difficile AAD were cured. Two patients had CDI recurrence. Ribotype H was the dominant (18.8 %) genotype, followed by ribotype 012 and ribotype 017. C. difficile plays a significant role in AAD in our setting in China. Because the severity of diarrhea ranges from mild to moderate, it is difficult for Chinese clinicians to identify CDI from AAD patients, therefore CDI should be included in the routine differential diagnoses for hospitalized patients presenting with AAD.
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Affiliation(s)
- F F Zhou
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, China
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Abstract
The incidence and severity of Clostridium difficile infection (CDI) have dramatically increased in the Western world in recent years. In contrast, CDI is rarely reported in China, possibly due to under-diagnosis. This article briefly summarizes CDI incidence, management and preventive strategies. The authors intend to raise awareness of this disease among Chinese physicians and health workers, in order to minimize the medical and economic burden of a potential epidemic in the future.
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Affiliation(s)
- Xinhua Chen
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Concurrent infections of Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile in children during a cryptosporidiosis outbreak in a pediatric hospital in China. PLoS Negl Trop Dis 2013; 7:e2437. [PMID: 24069491 PMCID: PMC3772047 DOI: 10.1371/journal.pntd.0002437] [Citation(s) in RCA: 167] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 08/09/2013] [Indexed: 11/23/2022] Open
Abstract
Background Over 200 cryptosporidiosis outbreaks have been reported, but little is known if other enteric pathogens were also involved in some of these outbreaks. Recently, an outbreak of cryptosporidiosis linked to poor hygiene by two Cryptosporidium hominis subtypes occurred in a pediatric hospital ward (Ward A) in China, lasting for more than 14 months. In this study, the concurrence during the outbreak of three other enteric pathogens with a similar transmission route, Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile, was assessed. Methods/Principal Findings The occurrence of G. duodenalis, E. bieneusi, and C. difficile in 78 inpatients from Ward A and 283 and 216 inpatients from two control wards (Wards C and D) in the same hospital was examined using molecular diagnostic tools. Significantly higher infection rates were found in children in Ward A for all study pathogens than in Wards C and D (P<0.01): 9.5% versus 1.4% and 0% for G. duodenalis, 10.8% versus 2.8% and 3.7% for E. bieneusi, and 60.8% versus 37.8% and 27.8% for C. difficile, respectively. These differences were mostly seen in children ≤12 months. Enteric pathogen-positive children in Ward A (31/58 or 53.4%) were more likely to have mixed infections than those in Ward C (4/119 or 3.4%) or D (5/68, 7.4%; P<0.01). Having cryptosporidiosis was a risk factor for G. duodenalis (OR = 4.3; P = 0.08), E. bieneusi (OR = 3.1; P = 0.04), and C. difficile (OR = 4.7; P<0.01) infection. In addition, a lower diversity of G. duodenalis, E. bieneusi, and C. difficile genotypes/subtypes was observed in Ward A. Conclusions/Significance Data from this study suggest that multiple pathogens were concurrently present during the previous cryptosporidiosis outbreak. Examination of multiple enteric pathogens should be conducted when poor hygiene is the likely cause of outbreaks of diarrhea. The transmission of Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile is poorly understood in developing countries despite their wide occurrence. Because they are transmitted by the same fecal-oral route as Cryptosporidium, in this study, we have examined the occurrence of these enteric pathogens in children during a cryptosporidiosis outbreak in a pediatric hospital in China. Using molecular diagnostic tools, we have detected significantly higher infection rates of these enteric pathogens in the outbreak ward than in two control wards in the same hospital. We have also shown a much higher occurrence of these pathogens in children having cryptosporidiosis than those having no cryptosporidiosis. We have demonstrated that the genetic diversity of enteric pathogens is much lower in the outbreak ward than in control wards. Therefore, other enteric pathogens are concurrently present during the cryptosporidiosis outbreak, and examinations for multiple enteric pathogens should be conducted when poor hygiene is considered the likely cause of outbreaks of diarrhea.
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Molecular epidemiology of Clostridium difficile infection in a major chinese hospital: an underrecognized problem in Asia? J Clin Microbiol 2013; 51:3308-13. [PMID: 23903542 DOI: 10.1128/jcm.00587-13] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Clostridium difficile infection is almost unrecognized in mainland China. We have undertaken a study in a large Chinese teaching hospital in Changsha, Hunan, China, to identify cases of C. difficile, record patient characteristics, and define the molecular epidemiology with respect to ribotype distribution and cross-infection. Between April 2009 and February 2010, we examined fecal samples from 70 hospitalized patients with diarrhea who were receiving or had received antibiotics within the previous 6 weeks. Clinical information was collected and the samples were cultured for C. difficile retrospectively. Isolates were ribotyped, and multiple-locus variable-number tandem-repeat assay (MLVA) subtyping was performed on clusters of the same ribotype. The mean age of patients from whom C. difficile was cultured was 58 years, with only 4/21 patients aged >65 years. All patients, with a single exception, had received a third-generation cephalosporin and/or a quinolone antibiotic. Twenty-one isolates of C. difficile were recovered, and seven different ribotypes were identified, the dominant types being 017 (48%), 046 (14%), and 012 (14%). We identified two clusters of cross-infection with indistinguishable isolates of ribotype 017, with evidence of spread both within and between wards. We have identified C. difficile as a possibly significant problem, with cross-infection and a distinct ribotype distribution, in a large Chinese hospital. C. difficile may be underrecognized in China, and further epidemiological studies across the country together with the introduction of routine diagnostic testing are needed to ascertain the size of this potentially significant problem.
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Collins DA, Hawkey PM, Riley TV. Epidemiology of Clostridium difficile infection in Asia. Antimicrob Resist Infect Control 2013; 2:21. [PMID: 23816346 PMCID: PMC3718645 DOI: 10.1186/2047-2994-2-21] [Citation(s) in RCA: 178] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Accepted: 06/07/2013] [Indexed: 01/05/2023] Open
Abstract
While Clostridium difficile infection (CDI) has come to prominence as major epidemics have occurred in North America and Europe over the recent decade, awareness and surveillance of CDI in Asia have remained poor. Limited studies performed throughout Asia indicate that CDI is also a significant nosocomial pathogen in this region, but the true prevalence of CDI remains unknown. A lack of regulated antibiotic use in many Asian countries suggests that the prevalence of CDI may be comparatively high. Molecular studies indicate that ribotypes 027 and 078, which have caused significant outbreaks in other regions of the world, are rare in Asia. However, variant toxin A-negative/toxin B-positive strains of ribotype 017 have caused epidemics across several Asian countries. Ribotype smz/018 has caused widespread disease across Japan over the last decade and more recently emerged in Korea. This review summarises current knowledge on CDI in Asian countries.
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Affiliation(s)
- Deirdre A Collins
- Microbiology and Immunology, School of Pathology and Laboratory Medicine, the University of Western Australia, Perth, Australia.
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Han XH, Du CX, Zhang CL, Zheng CL, Wang L, Li D, Feng Y, DuPont HL, Jiang ZD, Shi YK. Clostridium difficile infection in hospitalized cancer patients in Beijing, China is facilitated by receipt of cancer chemotherapy. Anaerobe 2013; 24:82-4. [PMID: 23770543 DOI: 10.1016/j.anaerobe.2013.05.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Revised: 03/29/2013] [Accepted: 05/11/2013] [Indexed: 02/04/2023]
Abstract
The purpose of this study was to determine the presence of Clostridium difficile infection (CDI) and risk factors for infection in hospitalized patients with diarrhea in a cancer hospital in Beijing, China. A total of 277 patients with hospital-associated diarrhea (HAD) were studied of which 41 (15%) were positive for fecal C. difficile toxin A/B. For each CDI case identified, a control with HAD but negative C. difficile specimen was enrolled to look for CDI risk factors. Receipt of cancer chemotherapy occurred in 20 (49%) patients with CDI and 9 (22.0%) patients with non-CDI HAD (OR3.39, 95%CI 1.78-10.05). Median length of chemotherapy before HAD developed was 39 days for those with CDI and 22 days for patients with CDI-negative HAD (P = 0.0391). The study found that CDI is commonly seen in cancer patients in China with increasing risk for patients who receive chemotherapy.
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Affiliation(s)
- X H Han
- Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China
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Jin K, Wang S, Huang Z, Lu S. Clostridium difficile infections in China. J Biomed Res 2013; 24:411-6. [PMID: 23554657 PMCID: PMC3596688 DOI: 10.1016/s1674-8301(10)60055-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2010] [Revised: 10/25/2010] [Accepted: 11/03/2010] [Indexed: 01/05/2023] Open
Abstract
Clostridium difficile (C. difficile) infection has become one of the major hospital-associated infections in Western countries in the last two decades. However, there is limited information on the status of C. difficile infection in Chinese healthcare settings. Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China, it is critical to understand the epidemiology and potential risk factors that may contribute to C. difficile infection in China. A literature review of available published studies, including those in Chinese language-based journals, was conducted. A review of the currently available literature suggested the presence of C. difficile infections in China, but also suggested that these infections were not particularly endemic. This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C. difficile infection in China, including the identification of any associated risk factors. Such information is ultimately valuable to develop appropriate strategies to prevent C. difficile infection and the vast negative impact of such infections in China and other developing countries.
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Affiliation(s)
- Ke Jin
- Department of Infectious Diseases, ; Jiangsu Province Key Laboratory in Infectious Diseases, ; China-US Vaccine Research Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China
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Chen Y, Chen X, Zheng S, Yu F, Kong H, Yang Q, Cui D, Chen N, Lou B, Li X, Tian L, Yang X, Xie G, Dong Y, Qin Z, Han D, Wang Y, Zhang W, Tang YW, Li L. Serotypes, genotypes and antimicrobial resistance patterns of human diarrhoeagenic Escherichia coli isolates circulating in southeastern China. Clin Microbiol Infect 2013; 20:52-8. [PMID: 23521436 DOI: 10.1111/1469-0691.12188] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 02/03/2013] [Accepted: 02/03/2013] [Indexed: 11/30/2022]
Abstract
Diarrhoeagenic Escherichia coli (DEC) infection is a major health problem in developing countries. The prevalence and characteristics of DEC have not been thoroughly investigated in China. Consecutive faecal specimens from outpatients with acute diarrhoea in nine sentinel hospitals in southeastern China were collected from July 2009 to June 2011. Bacterial and viral pathogens were detected by culture and RT-PCR, respectively. DEC isolates were further classified into five pathotypes using multiplex PCR. The O/H serotypes, sequence types (STs) and antimicrobial susceptibility profiles of the DEC isolates were determined. A total of 2466 faecal specimens were collected, from which 347 (14.1%) DEC isolates were isolated. DEC was the dominant bacterial pathogen detected. The DEC isolates included 217 EAEC, 62 ETEC, 52 EPEC, 14 STEC, one EIEC and one EAEC/ETEC. O45 (6.6%) was the predominant serotype. Genotypic analysis revealed that the major genotype was ST complex 10 (87, 25.6%). Isolates belonging to the serogroups or genotypes of O6, O25, O159, ST48, ST218, ST94 and ST1491 were highly susceptible to the majority of antimicrobials. In contrast, isolates belonging to O45, O15, O1, O169, ST38, ST226, ST69, ST31, ST93, ST394 and ST648 were highly resistant to the majority of antimicrobials. DEC accounted for the majority of bacterial pathogens causing acute diarrhoea in southeastern China, and it is therefore necessary to test for all DEC, not only the EHEC O157:H7. Some serogroups or genotypes of DEC were highly resistant to the majority of antimicrobials. DEC surveillance should be emphasized.
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Affiliation(s)
- Y Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Center of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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Clostridium difficile in foods and animals: history and measures to reduce exposure. Anim Health Res Rev 2013; 14:11-29. [PMID: 23324529 DOI: 10.1017/s1466252312000229] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Many articles have summarized the changing epidemiology of Clostridium difficile infections (CDI) in humans, but the emerging presence of C. difficile in foods and animals and possible measures to reduce human exposure to this important pathogen have been infrequently addressed. CDIs have traditionally been assumed to be restricted to health-care settings. However, recent molecular studies indicate that this is no longer the case; animals and foods might be involved in the changing epidemiology of CDIs in humans; and genome sequencing is disproving person-to-person transmission in hospitals. Although zoonotic and foodborne transmission have not been confirmed, it is evident that susceptible people can be inadvertently exposed to C. difficile from foods, animals, or their environment. Strains of epidemic clones present in humans are common in companion and food animals, raw meats, poultry products, vegetables, and ready-to-eat foods, including salads. In order to develop science-based prevention strategies, it is critical to understand how C. difficile reaches foods and humans. This review contextualizes the current understanding of CDIs in humans, animals, and foods. Based on available information, we propose a list of educational measures that could reduce the exposure of susceptible people to C. difficile. Enhanced educational efforts and behavior change targeting medical and non-medical personnel are needed.
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