Comparative in vitro activity of piperacillin-tazobactam and temocillin against third-generation cephalosporin-resistant, carbapenem-susceptible Escherichia coli and Klebsiella pneumoniae

Carbapenems are considered the drugs of choice for first-line treatment of severe infections caused by carbapenem-susceptible, extended-spectrum β-lactamases (ESBL)-producing Enterobacterales, while piperacillin-tazobactam has been recommended as an alternative for treatment of non-severe infections. Temocillin is stable to ESBL and AmpC enzymes and may thus represent another treatment option. This study assessed the in vitro activity of piperacillin-tazobactam and temocillin against third-generation cephalosporin (3GC)-resistant Escherichia coli and Klebsiella pneumoniae, as compared to 3GC-susceptible isolates of either species. One hundred and nine isolates from hospitalized patients with bloodstream and urinary tract infections were tested. All isolates were collected during the resistance surveillance study of the Paul-Ehrlich-Society for Chemotherapy in 2016/17. Minimum inhibitory concentrations (MICs) were determined by broth microdilution according to the standard ISO 20776-1 and interpreted using EUCAST clinical breakpoints (version 11.0). Seventy-nine isolates (E. coli, n=58; K. pneumoniae, n=21) were 3GC-resistant and 30 (E. coli, n=15; K. pneumoniae, n=15) were 3GC-susceptible. Susceptibility to piperacillin-tazobactam was detected in 93.3% of 3GC-susceptible isolates (for both E. coli and K. pneumoniae) and in 79.3% and 57.1% of the 3GC-resistant E. coli and K. pneumoniae, respectively. In contrast, 3GC-susceptible isolates were 100% susceptible to temocillin as were 94.8% and 90.5% of the 3GC-resistant E. coli and K. pneumoniae, respectively. In conclusion, temocillin demonstrated potent in vitro activity against carbapenem-susceptible, 3GC-resistant E. coli and K. pneumoniae from bloodstream and urinary tract infection samples, with susceptibility rates exceeding those of piperacillin-tazobactam.