Extended spectrum β-lactamases in Escherichia coli & Klebsiella pneumoniae & associated risk factors

Background & objectives: Extended spectrum beta-lactamases (ESBLs) have emerged as a major threat worldwide with limited treatment options. The genotypes of ESBL producing strains largely remain unknown in India; hence the present study was aimed to determine the occurrence of ESBLs in Escherichia coli and Klebsiella pneumoniae, their molecular types and associated risk factors in a tertiary care hospital. Methods: Total 200 consecutive clinical isolates of E. coli (n=143) and K. pneumoniae (n=57) collected between February and July 2006 at Sanjay Gandhi Postgraduate Institute of Medical Sciences, a tertiary care hospital in north India, were examined phenotypically for ESBL production. ESBL strains were further typed for the bla(TEM/SHV/CTX-M) genes by PCR using specific primers. The bla(CTX-M) cluster was identified by restriction analysis and genotype by sequencing of PCR product. Resistance to other antimicrobial agents was also studied. Various risk factors associated with ESBL infections were analyzed by logistic regressions. Results: ESBLs were found in 63.6 per cent E. coli and 66.7 per cent K. pneumoniae isolates. Majority of the typeable isolates harboured two or more ESBL genes (57.3%). Overall bla(CTX-M) was the commonest genotype (85.4%) followed by bla(TEM) (54.9%) and bla(SHV) (32.9%) either alone or in combination. All CTX-M enzymes in E. coli and 87.5 per cent in K. pneumoniae belonged to the CTX-M-1 cluster. Sequencing was done for randomly selected 20 bla(CTX-M) PCR products and all were identified as CTX-M-3. Resistance of ESBL isolates to other antibiotics was amikacin 14.7 per cent, gentamicin 66.7 per cent, trimethoprim/sulphamethoxazole 79.1 per cent and ciprofloxacin 93.8 per cent. Prior antibiotic exposure, use of intravenous device and urinary catheter, renal insufficiency and ICU admission were associated with ESBL infection on univariate analysis. On multivariate, antibiotic exposure (P=0.001) and use of urinary catheter (P<0.001) were identified as risk for ESBL infection. Interpretation & conclusions: Our study showed high ESBL occurrence with CTX-M as the emerging type in our hospital and CTX-M-3 being reported for the first time in India. High co-resistance to other non-p-lactam antibiotics is a major challenge for management of ESBL infections.