Carbapenem antibiotics for serious infections

An 81 year old woman with a long term, indwelling urinary catheter is admitted with fever and hypotension thought to be due to septicaemia secondary to urinary tract infection. She is treated empirically with intravenous cefotaxime and gentamicin, but her condition deteriorates over 24 hours, with increasing hypotension and continuing fever. For broader spectrum coverage, her empirical antibiotic treatment is changed to intravenous meropenem. The next day, urine and blood cultures grow an Escherichia coli producing an extended spectrum β lactamase (ESBL), conferring resistance to cefotaxime and gentamicin but not to meropenem. The meropenem is continued for seven days, with clinical and bacteriological resolution of the patient’s infection. Carbapenems are β lactam antibiotics, as are penicillins and cephalosporins, but differ from these other classes in their exact chemical structure. Carbapenem use has increased as a result of the rising resistance to cephalosporin antibiotics in Enterobacteriaceae ( Escherichia coli , Klebsiella , Enterobacter , and related genera). This cephalosporin resistance is largely due to the spread of extended spectrum β lactamases (ESBLs), which hydrolyse cephalosporins.1 ESBL producers are associated with poor clinical outcomes in severe infections: a meta-analysis found that bacteraemias caused by bacteria with these enzymes had 1.85-fold increased mortality (95% confidence interval 1.39 to 2.47, P<0.001), reflecting extended delays before effective therapy was initiated.2 ESBLs now occur in 10–12% of E coli from bacteraemias in the UK3 and in 50–80% of those in India and China, with many ESBL producing strains also resistant to quinolones and aminoglycosides.4 Carbapenems are the sole β lactam antibiotics with proven efficacy in severe infections due to ESBL producing bacteria: most Enterobacteriaceae strains with ESBLs in the UK are resistant to the β lactamase inhibitor combinations of amoxicillin-clavulanate and piperacillin-tazobactam—not because the ESBLs evade inhibition but because ESBL producers often also …