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Antibiotic prophylaxis in variceal hemorrhage: Timing, effectiveness and Clostridium difficile rates  [cached]
Matthew RL Brown, Graeme Jones, Kathryn L Nash, Mark Wright, Indra Neil Guha
World Journal of Gastroenterology , 2010,
Abstract: AIM: To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection (CDI).METHODS: A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken. The primary outcome measure was 28-d mortality. Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI. All patients were admitted to a tertiary liver unit with a consultant-led, 24-h endoscopy service. Patients received standard care including terlipressin therapy. Data collection included: primary and secondary outcome measures, timing of first administration of intravenous antibiotics, etiology of liver disease, demographics, endoscopy details and complications. A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration. Statistical analysis was undertaken using univariate, non-parametric tests and multivariate logistic regression analysis.RESULTS: There were 70 first presentations of variceal hemorrhage during the study period. Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease. In total, 64/70 (91.4%) patients received antibiotics as prophylaxis during their admission. Specifically, 53/70 (75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy (8 h) group], whereas 17/70 (24.3%) received antibiotics at > 8 h after endoscopy or not at all (non peri-endoscopy group). Overall mortality and rebleeding rates were 13/70 (18.6%) and 14/70 (20%), respectively. The peri-endoscopy (8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%, P = 0.04, odds ratio (OR) = 0.28 (0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%, P = 0.27, OR = 0.49 (0.14-1.74)]. On univariate analysis, the non peri-endoscopy group [P = 0.02, OR = 3.58 (1.00-12.81)], higher model for end-stage liver disease (MELD) score (P = 0.02), presence of hepatorenal syndrome [P < 0.01, OR = 11.25 (2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03, OR = 4.03 (1.11-14.58)] were significant predictors of death at 28 d. On multivariate logistic regression analysis, lower MELD score [P = 0.01, OR = 1.16 (1.04-1.28)] and peri-endoscopy (8 h) group [P = 0.01, OR = 0.15 (0.03-0.68)] were independent predictors of survival at 28 d. The CDI incidence (5.7%) was comparable to that in the general medical population (5%).CONCL
Molecular epidemiology of antibiotic-associated diarrhoea due to Clostridium difficile and clostridium perfringens in Ain Shams University Hospitals
MA Shaheen, SM Zaki, AA El-Sayed, NM Sayed, AA Abdel Aziz, SA Hamza
Egyptian Journal of Medical Human Genetics , 2007,
Abstract: Background: As we are living in the era of antibiotic overuse, antibiotic associated diarrhea (AAD) is considered now a distinct health problem with a need for more attention. Aim of the Study: was to perform a highly specific detection and definition of pathogenic Clostridium perfringens and Clostridium difficile related AAD in children compared to adults and geriatircs. Patients and Methods: One hundred and fifty patients diagnosed for AAD were included in this study (50 children, 50 adults and 50 geriatric patients). All of them were subjected to full medical history including complete therapeutic history of antibiotics and collection of stool sample during the attack for detection of Clostridium perfringenes enterotoxin (CPEnt) and Clostridium difficile cytotoxin by (EIA) kit. PCR detection of Clostridium perfringenes cpe gene (Coding gene for CPEnt) was performed as well. Results: Results showed that prevalence of Clostridium difficile cytotoxin was 24% while Clostridium perfringenes enterotoxin was 12% as detected by EIA in faecal specimens as a whole. Detection of cpe gene by PCR was positive in 16% of all cases. Children (OR: 4.2, 95% CI: 1.3-14.8, P_0.01) and geriatric patients (OR: 3.4, 95% CI: 1.2-13.5, P_0.02) were significantly more prone to Clostridium difficile AAD compared to adults. Also, childhood was a significant risk for Clostridium perfringens AAD (OR: 2.1, 95% CI: 0.54-7.4, P_0.04). In Conclusion: children and geriatric patients are more vulnerable to develop AAD with antibiotic abuse compared to adults. Abbreviations: AAD=Antibiotic associated diarrhea, CI=Confidence interval, ELISA=Enzyme-linked immunosorbent assay, OR=Odd ratio, PCR=Polymerase chain reaction.
Succession in the Gut Microbiome following Antibiotic and Antibody Therapies for Clostridium difficile  [PDF]
Gregory L. Peterfreund, Lee E. Vandivier, Rohini Sinha, Andre J. Marozsan, William C. Olson, Jun Zhu, Frederic D. Bushman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046966
Abstract: Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb) to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.
Surveillance of Infection Severity: A Registry Study of Laboratory Diagnosed Clostridium difficile  [PDF]
Iryna Schlackow,A. Sarah Walker,Kate Dingle,David Griffiths,Sarah Oakley,John Finney,Ali Vaughan,Martin J. Gill,Derrick W. Crook,Tim E. A. Peto,David H. Wyllie
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001279
Abstract: Background Changing clinical impact, as virulent clones replace less virulent ones, is a feature of many pathogenic bacterial species and can be difficult to detect. Consequently, innovative techniques monitoring infection severity are of potential clinical value. Methods and Findings We studied 5,551 toxin-positive and 20,098 persistently toxin-negative patients tested for Clostridium difficile infection between February 1998 and July 2009 in a group of hospitals based in Oxford, UK, and investigated 28-day mortality and biomarkers of inflammation (blood neutrophil count, urea, and creatinine concentrations) collected at diagnosis using iterative sequential regression (ISR), a novel joinpoint-based regression technique suitable for serial monitoring of continuous or dichotomous outcomes. Among C. difficile toxin-positive patients in the Oxford hospitals, mean neutrophil counts on diagnosis increased from 2003, peaked in 2006–2007, and then declined; 28-day mortality increased from early 2006, peaked in late 2006–2007, and then declined. Molecular typing confirmed these changes were likely due to the ingress of the globally distributed severe C. difficile strain, ST1. We assessed the generalizability of ISR-based severity monitoring in three ways. First, we assessed and found strong (p<0.0001) associations between isolation of the ST1 severe strain and higher neutrophil counts at diagnosis in two unrelated large multi-centre studies, suggesting the technique described might be useful elsewhere. Second, we assessed and found similar trends in a second group of hospitals in Birmingham, UK, from which 5,399 cases were analysed. Third, we used simulation to assess the performance of this surveillance system given the ingress of future severe strains under a variety of assumptions. ISR-based severity monitoring allowed the detection of the severity change years earlier than mortality monitoring. Conclusions Automated electronic systems providing early warning of the changing severity of infectious conditions can be established using routinely collected laboratory hospital data. In the settings studied here these systems have higher performance than those monitoring mortality, at least in C. difficile infection. Such systems could have wider applicability for monitoring infections presenting in hospital.
Surveillance for Clostridium difficile Infection: ICD-9 Coding Has Poor Sensitivity Compared to Laboratory Diagnosis in Hospital Patients, Singapore  [PDF]
Monica Chan,Poh Lian Lim,Angela Chow,Mar Kyaw Win,Timothy M. Barkham
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015603
Abstract: Clostridium difficile infection (CDI) is an increasingly recognized nosocomial infection in Singapore. Surveillance methods include laboratory reporting of Clostridium difficile toxin assays (CDTA) or use of International Classification of Diseases, 9th Revision (ICD-9) discharge code 008.45. Previous US studies showed good correlation between CDTA and ICD-9 codes. However, the use of ICD-9 codes for CDI surveillance has not been validated in other healthcare settings.
The Incidence of Nosocomial Toxigenic Clostridium difficile Associated Diarrhea in Tehran Tertiary Medical Centers
Norakhoda Sadeghifard,Mohammad Hossein Salari,Mohammad Raza Ghassemi,Saeed Eshraghi
Acta Medica Iranica , 2010,
Abstract: "nClostridium difficile is the most common cause of nosocomial diarrhea. It is usually a consequence of antibiotic treatment, But sporadic cases can occur. This study was aimed to determine the frequency of the nosocomial Clostridium difficile (C. difficile) associated diarrhea in Tehran University of Medical Sciences hospitals and study of antibacterial susceptibility of isolates. In this study a total of 942 stool samples from patients with nosocomial diarrhea that were hospitalized in Imam Khomeini hospital, Shariati hospital and Children clinical center were collected. The samples were cultured on a selective cycloserine cefoxitin fructose agar (CCFA) and incubated in anaerobic conditions, at 37°C for 5 days. Isolates were characterized to species level by conventional biochemical tests. Bacterial cytotoxicity was assayed on tissue culture (vero). Antimicrobial sensitivity of isolated toxigenic C. difficile were investigated by kirby Beuer method (disk diffusion). Our findings show that, of the total patients, 57 toxigenic C. difficile (6.1%) were isolated. Results of statistical analysis show significant differences between the rate of isolated toxigenic C. difficile and age group of patients (P<0.05). Among the wards of selected hospitals, in gastroenterology of Children clinical center, Toxigenic C. difficile was isolated from patients most frequently. The sensitivity of isolates to vancomycin, Chloramphenicol and ceftriaxone were higher than other antibiotics. Toxigenic C. difficile is a common hospital-acquired infection. The organism was found in 6.1% hospitalized patients. Further studies to evaluate the rate and role of toxigenic C. difficile in nosocomial diarrheal processes, ecological and pathogenic terms are suggested.
Emerging Insights into Antibiotic-Associated Diarrhea and Clostridium difficile Infection through the Lens of Microbial Ecology  [PDF]
Seth T. Walk,Vincent B. Young
Interdisciplinary Perspectives on Infectious Diseases , 2008, DOI: 10.1155/2008/125081
Abstract: Antibiotics are the main, and often only, clinical intervention for prophylactic and active treatment of bacterial infections in humans. Perhaps it is not surprising that these drugs also shift the composition of commensal bacteria inside our bodies, especially those within the gut microbial community (microbiota). How these dynamics ultimately affect the function of the gut microbiota, however, is not fully appreciated. Likewise, how antibiotic induced changes facilitate the outgrowth and pathogenicity of certain bacterial strains remains largely enigmatic. Here, we discuss the merits of a microbial ecology approach toward understanding a common side effect of antibiotic use, antibiotic-associated diarrhea (AAD), and the opportunistic bacterial infections that sometimes underlie it. As an example, we discuss how this approach is being used to address complex disease dynamics during Clostridium difficile infection.
Association of Clostridium difficile with Antibiotic Associated Diarrhea among Hospitalized Children in Diyala-Iraq  [PDF]
Abdulrazak S. H. Hasan, Rana S. M. Al-Zubaidi, Abbas A. Al-Duliami
Journal of Biosciences and Medicines (JBM) , 2019, DOI: 10.4236/jbm.2019.72006
Abstract: Background: Clostridium difficile infection (CDI) is an increasingly important cause of morbidity in hospitalized children. Absence of clinical suspicion and suboptimum laboratory diagnostic methods are behind the misdiagnosed infections. Objectives: To determine the association of Cl. difficle infection among hospitalized children suspected of having antibiotic associated diarrhea (AAD) plus detection of the bacterium’s toxins A and B and the enzyme glutamate dehydrogenase (GDH). Patients and methods: This cross-sectional study was conducted in Al-Batool Hospital for Maternity and Children in Baquba City for the period from March 2017 to April 2018. Sixty stool samples were collected from children inpatients. The age range was 15 days up to one year. 41 (68.3%) and 19 (31.7%) were males and females respectively. Additionally, 20 healthy children were enrolled as control group. The age range was 50 days up to one year, 12 (60%) and 8 (40%) were males and females respectively. Special questionnaire was preconstructed for collection of demographic information. Isolation of Cl. difficile was carried out on Colombia blood agar and tryptose sulfite cycloserine agar. Enzyme linked immunosorband assays were used for the detection of toxin A and B (CerTest-Biotec, Spain), and for the detection of glutamate dehydrogenase enzyme (CerTest-Biotec, Spain). Human privacy was respected by obtaining the parents’ oral consent. Statistical analyses were done using SPSS Version 18 and P values less than 0.05 were considered significant. Results: The isolation rate of Cl. difficile form patients and healthy children was 11.7% and 5% respectively. The toxins detection rate among patients was 23.3%, of these 35.7% for toxin A, and 64.3% for toxin A and B together. Neither of the patients’ specimens was positive for toxin B alone, nor was healthy control positive for all toxins. The overall detection rate of GDH enzyme in study groups was 32.5%, with a significantly higher among patients as compared to control (28.8% vs. 3.8% , P = 0.045). The isolation and detection rate of Cl. difficile were increased as the time of the onset of diarrhea was increased. Other factors: age, sex, residence, and type of feeding were insignificantly affecting the isolation and detection rate of Cl. difficile by different techniques. The third generation cephalosporines either singly or in combinations with each other or with another antibiotic were mostly associated with the higher rates of diarrhea. Conclusion:
The Clostridium difficile problem: A South African tertiary institution’s prospective perspective
N Rajabally, M Pentecost, G Pretorius, A Whitelaw, M Mendelson, G Watermeyer
South African Medical Journal , 2013,
Abstract: Background and objectives. The aim of this study is to report the incidence of Clostridium difficile-associated disease (CDAD) in a tertiarycare hospital in South Africa and to identify risk factors, assess patient outcomes and determine the impact of the hypervirulent strain of the organism referred to as North American pulsed-field type 1 (NAP1). Methods. Adults who presented with diarrhoea over a period of 15 months were prospectively evaluated for CDAD using stool toxin enzyme immunoassay (EIA). Positive specimens were evaluated by PCR. Patient demographics, laboratory parameters and outcomes were analysed. Results. CDAD was diagnosed in 59 (9.2%) of 643 patients (median age 39 years, IQR 30 - 55). Thirty-four (58%) were female. Recent antibiotic exposure was reported in 39 (66%), 27 (46%) had been hospitalised within 3 months, and 14 (24%) had concomitant inflammatory bowel disease (IBD). Nineteen (32%) had community-acquired CDAD (CA-CDAD). The annual incidence of hospital-acquired CDAD (HA-CDAD) was 8.7 cases/10 000 hospitalisations. Two cases of the hypervirulent strain NAP1 were identified. Seven (12%) patients underwent colectomy (OR 6.83; 95% CI 2.41 - 19.3). On logistic regression, only antibiotic exposure independently predicted for CDAD (OR 2.9; 95% CI 1.6 - 5.1). Three (16%) cases of CA-CDAD reported antibiotic exposure (v. 90% of HA-CDAD, p<0.0001). Twelve (86%) patients had concomitant IBD (p<0.0001 v. HA-CDAD). CA-CDAD was significantly associated with antibiotic exposure (OR 0.04, 95% CI 0.01 - 0.24) and IBD (OR 9.6, 95% CI 1.15 - 79.8). Conclusion. The incidence of HA-CDAD in the South African setting is far lower than that reported in the West. While antibiotic use was a major risk factor for HA-CDAD, CA-CDAD was not associated with antibiotic therapy. Concurrent IBD was a predictor of CA-CDAD.
Recent changes in Clostridium difficile infection
Silva Júnior, Moacyr;
Einstein (S?o Paulo) , 2012, DOI: 10.1590/S1679-45082012000100023
Abstract: clostridium difficile is the main cause of nosocomial diarrhea. diarrhea associated with c. difficile has increased incidence, morbidity, and mortality in the last few years. the major related risk factors include use of antibiotics, elderly patients and prolonged hospital stay. many patients receive combinations of antibiotics or multiple antibiotics, which represents the main risk to develop diarrhea associated to c. difficile or its recurrence. therefore, interventions to improve antibiotic prescribing, as well as compliance with infection control measures can reduce hospital-acquired c. difficile infections. this review addresses the epidemiological changes in c. difficile disease and its treatment.
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