Epidemiology of ‘Extended Spectrum Beta Lactamae’ producing isolates of Escherichia coli and Klebsiella spp among bacteremic adults admitted to a tertiary care teaching hospita

Paul Prabhakar Abliash, K (2008) Epidemiology of ‘Extended Spectrum Beta Lactamae’ producing isolates of Escherichia coli and Klebsiella spp among bacteremic adults admitted to a tertiary care teaching hospita. Masters thesis, Christian Medical College, Vellore.


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INTRODUCTION : The advent of plasmid mediated ESBL production by Klebsiella and E. coli in the early 1980s signaled an emerging and evolving global problem with antibiotic resistance among Enterobacteriaceae. These organisms were susceptible to β-lactam antibiotics, but, with widespread use, have developed resistance through production of β- lactamases, which are the major defense mechanism of gram-negative bacteria against β- lactam antibiotics, and were first reported in the early 1980s.1 The presence of ESBLs carries tremendous clinical significance. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides), thus limiting the antibiotic options available for treatment of resistant strains .2 Thus, it becomes imperative to quantify the problem, and reinforce guidelines promoting appropriate antibiotic use. Since -lactam antibiotics came into clinical use, -lactamases have coevolved with them. As and when agents like cephamycins, cephalosporins with an oxyimino side chain, carbapenems, and aztreonam, that could break through the antimicrobial resistance were introduced, bacteria responded with a plethora of "new" - lactamases —including extended-spectrum -lactamases (ESBLs), plasmid-mediated AmpC enzymes, and carbapenem-hydrolyzing -lactamases (carbapenemases) — that, with variable success, can confer resistance to the latest -lactam antibiotics.3 Presumably the selective pressure by the use and overuse of these new introductions periodically for the treatment of patients, has allowed the proliferation and survival of new variants of β-lactamase. Thus, ESBLs represent an impressive example of the ability of gramnegative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents. Antimicrobial resistance development is a function of bacterial genetic variability, such as the replication or generation rate in response to environmental stress (physical, nutrient availability etc), and selection pressure due to the use of similar antibiotics (class). The spreading antimicrobial resistance may be due to dispersion of resistant clones, or the genomes rapidly expanding its reservoirs or massive consumption of antimicrobials due to worldwide usage. OBJECTIVES : To determine 1. The prevalence of ESBL producing isolates of E.coli and Klebsiella among bacteremic adult hospitalized patients, 2. The rates of ESBL production among community acquired and nosocomial infections, 3. The risk factors for bacteremia due to ESBL producing E. coli and Klebsiella species. 4. The outcome of antibiotic treatment in bacteremia caused by E. coli and Klebsiella species in hospitalized adults. MATERIALS AND METHODS : Study Setting: The study was conducted in Christian Medical College Hospital, Vellore, a 2500 bedded academic medical center in South India with an average of 1815 inpatients and approximately 3500 out- patient visits every day. Study design: This was a prospective cohort study. Subjects: The study recruited all sequentially encountered patients older than 16 years with Klebsiella or E. coli bacteremia who were admitted in various wards and Intensive care units of this hospital during the study period. We recruited a total of 131 patients over a 4 month period. INCLUSION CRITERIA: 1. Isolation of E. coli or Klebsiella from blood culture samples and 2. Willingness to participate in the study. EXCLUSION CRITERIA: 1. Patients aged less than 16 years, 2. Outpatients , 3. Bacteremias of polymicrobial etiology, 4. Patients unwilling for inclusion in the study. METHODOLOGY : A written informed consent was taken from either the patient, or from the legal guardian in those with altered mental status, prior to enrollment. All patients with E coli and Klebsiella bacteremia were evaluated within 48 hours of detection of a positive blood culture. Bacteremias of polymicrobial etiology were not included. Blood culture was taken at the onset of fever by venupuncture from a peripheral vein after adequate preparation of the skin with povidone iodine (Betadine). A minimum of 5 ml of blood was inoculated into a blood culture bottle (BacT/ALERT) which is used with the BacT/ALERT microbial detection system in qualitative procedures for enhanced recovery and detection of aerobic and facultative anaerobic micro organisms. The blood culture bottles were then transported to the department of Microbiology where culture and sensitivity tests were done. In all patients only the first episode of bacteremia was included for further analysis. A study form was completed which included the patients demographic details, co-morbidities and the possible source of infection (community acquired or nosocomial). The history of prior antibiotic use and the details of antibiotics used for the current episode of bacteremia were noted. The antibiotics were prescribed by the treating physician and the choice was not influenced by the study. RESULTS : One hundred and thirty one episodes of bacteremia were included in the study during the period of 4 months from Feb 2007 to May 2007, the baseline characteristics are shown in table 5. Seventy eight (59.54%) of the subjects were males. CONCLUSIONS One hundred and thirty one sequentially encountered adult patients with E coli or Klebsiella bacteremia were studied and followed up prospectively over a period of 2 weeks to assess clinical outcome. 1. ESBL production was observed in 73.28% of the isolates with 53.06 % of the community acquired infection and 85.36% of nosocomial infections caused by ESBL producing strains. 2. Prior use of antibiotics, especially 3rd and 4th generation cephalosporins were associated with an increased risk of infection by ESBL producing isolates of E coli and Klebsiella 3. A very high rate (50.4% -81.7%) of resistance to other major classes of antibiotics (e.g. fluoroquinolones, aminoglycosides, β-lactams and β-lactamase inhibitors) was observed, with carbapenems being the only class of drug with a good activity against ESBL producing Enterobacteriaceae. That, resistance to carbapenems was also noted among the isolates, is a cause of concern for the future. 4. Initial antibiotics were inappropriate in 53% (based on antibiotic susceptibility profile). 5. The mortality following the episode of bacteremia was not influenced by the initial choice of the antibiotic. However, carbapenems should be the choice of initial empiric therapy for serious life threatening infections caused by ESBL producing Enterobacteriaceae (with de-escalation when culture and sensitivity reports are available).

Item Type: Thesis (Masters)
Uncontrolled Keywords: Epidemiology ; Extended Spectrum Beta Lactamae ; producing isolates ; Escherichia coli ; Klebsiella spp ; bacteremic adults ; tertiary care
Subjects: MEDICAL > General Medicine
Depositing User: Subramani R
Date Deposited: 15 Feb 2018 18:31
Last Modified: 15 Feb 2018 18:31
URI: http://repository-tnmgrmu.ac.in/id/eprint/5732

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