Antibiotic resistance and production of extended-spectrum β-Mactamases amongst Klebsiella spp. from intensive care units in Europe

Consecutive klebsiellae were collected from ICU patients at 35 centres in Western and Southern Europe. Of 966 isolates obtained, 716 were Klebsiella pneumoniae, 248 were Klebsiella oxytoca and two were Klebsiella ozaenae. Most were from Belgium, France, Germany, Holland, Italy, Portugal, Spain, Turkey and a few from Greece and the UK. Production of extended-spectrum beta-lactamases (ESBLs) was inferred in 220 isolates on the basis of synergy between ceftazidime and clavulanate. Putative ESBL producers were received from 23 centres, including 20 of the 27 that contributed more than 10 klebsiellae. Over 88% of putative ESBL producers were resistant to ceftazidime 2 mg/L, ceftriaxone 1 mg/L and aztreonam 1 mg/L, whereas, amongst ESBL-negative isolates, more than 98% of K. pneumoniae and 87% of K. oxytoca were susceptible to these concentrations. Putative ESBL producers wre also more resistant to cefuroxime and cefoxitin than non-producers, but not to biapenem. MIC distributions of ciprofloxacin, piperacillin/tazobactam and aminoglycosides were bimodal for ESBL producers, with some isolates highly sensitive and others very resistant. For example, 70% of putative ESBL producers were susceptible to piperacillin/tazobactam 16 + 4 mg/L, but 30% were resistant, some highly so. Resistance to this combination, and to ciprofloxacin, was clustered in certain centres. Two other groups of cephalosporin-resistant isolates were identified besides ESBL producers, viz. (i) nine isolates, from three centres, with AmpC beta-lactamases and (ii) 20 K. oxytoca, from 15 centres, that hyperproduced K1 enzyme. Examination of the hospitals' own susceptibility data indicated that up to 33% of putative ESBL producers had been reported susceptible to third-generation cephalosporins or monobactams. This is disturbing, since ESBLs have been associated with clinical failure even when only low-level resistance was apparent in vitro.