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Title: Epidemiological study of hospital-acquired Clostridium difficile infection in Kuwait teaching hospitals and investigation of their virulence characteristics
Author: Jamal, Wafaa
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2009
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Abstract:
Clostridium difficile infection (CDI) is the most common type of infectious nosocomial diarrhoea. Overwhelming evidence indicate that the most important risk factors are prior antibiotic use and elderly patients. The severity of the disease varies from asymptomatic carrier to mild diarrhoea to colitis (AAC) and life threatening pseudomembranous colitis (PMC). Because little is known about C. difficile and CDI in Kuwait, this study was undertaken to determine the nosocomial acquisition of C. difficile by new patients admitted to the intensive care units (ICU) of 4 teaching hospitals in Kuwait between February 2001 and January 2002 (first part) and January 2003 to December 2005 (second part) and evaluate cytotoxin (toxin B) production by clinical isolates upon exposure to minimum inhibitory concentrations (MICs) and sub-MICs of certain antibiotics. The first part of the study was accomplished by serially culturing the stool specimens of 922 newly admitted patients to the ICUs screening their stools for toxins A/B and screening their immediate environment for C. difficile. The isolates were typed by the PCR ribotyping technique developed in the Anaerobe Reference Unit, Cardiff. The effects of various concentrations of antibiotics that could predispose to CDI and those used for its therapy on the production of cell-bound and cell-free toxin B produced by C difficile was investigated by experiments using cell cultures of the Vero cell line. Prevalence, epidemiology and risk factors of CDI in Kuwait hospitals was investigated during second part of the study by culturing patients' stool specimens, ribotyping the isolates and detection of toxin A/B in stool samples. The susceptibility of all isolates was assessed by MIC determination to 16 antibiotics using the E test method. During the first part of the study, 95 (10.3%) out of 922 patients with negative cultures initially on the day of admission acquired C difficile during their hospitalisation at various time intervals. Of these, 65 (68%) remained symptom-free while 30 (32%) were symptomatic 2 patients had PMC, 4 AAC and 24 AAD. C. difficile toxin A/B was present in 28 (93%) of 30 symptomatic patients but in only 7 (10.8%) of 65 symptom-free patients. The hospital environments occupied by symptomatic patients as well as those occupied by asymptomatic patients were contaminated by C. difficile. The 95 isolates from patients belonged to a total of 32 different ribotypes. Ribotypes 097 and 078 were responsible for >40% of C. difficile infections in Kuwait ICUs. There was a heterogeneous relationship between antibiotic exposure and intra- and extra cellular toxin production by the toxigenic strains. Clinical strains of C. difficile when exposed to MIC and sub-inhibitory concentrations of certain antibiotics produced high level of cytotoxin. Ampicillin and clindamycin were the most potent inducers of cytotoxin followed by metronidazole and vancomycin. Cefotaxime induced the least amount of the cytotoxin activity. During the second part of the study, 73 (10.5%) out of 697 met the diagnosis of CDI. Out of these 73, 56 (76.7%) were hospital-acquired and 17 (23.3%) were from outpatient clinics. Thus, the prevalence of hospital-acquired CDI was 8% over the study period. The prevalence of hospital-acquired CDI in 2003, 2004 and 2005 were, 9.7%, 7.8% and 7.2%, respectively. Our data showed that 42.9% of the CDI patients were above 60 years out of which over 79% were aged 71 years and above. Patients with CDI were more likely than the controls to have been exposed to immunosuppressive drugs and feeding via naso-gastric tube. The most common ribotypes isolated during the second part of the study were 002 and 001. The later was isolated only from one environmental sample in the first part of the study. PCR-ribotype 027 was not isolated during 2003-2005 study. None of our 151 C. difficile isolates were resistant to amoxicillin-clavulanic acid, ampicillin, linezolid, metronidazole, piperacillin-tazobactam, teicoplanin or vancomycin. Resistance to penicillin and meropenem among the clinical isolates increased from 2.4 to 16.4% and 4.8 to 21.4%, respectively while resistance to imipenem (another carbapenem) was extremely high in both studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.584718  DOI: Not available
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