In vitro activity of ceftolozane/tazobactam in combination with other classes of antibacterial agents

Combination antibiotic therapy has been used successfully to treat some patients with bacterial infections. However, although certain combinations may result in beneficial synergistic activity, others may produce antagonistic effects resulting in poor treatment outcomes. Ceftolozane/tazobactam is an antibacterial agent with potent activity against Pseudomonas aeruginosa and many other Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. This study aimed to evaluate potential synergistic or antagonistic interactions between ceftolozane/tazobactam and a selection of antibacterial agents.

Chequerboard analyses were conducted with Escherichia coli, Klebsiella pneumoniae and P. aeruginosa isolates.

Combinations of ceftolozane/tazobactam with aztreonam, amikacin, tigecycline and meropenem resulted in synergistic effects in some of the bacterial strains tested. The potency of ceftolozane/tazobactam against common Gram-negative pathogens was not compromised in the presence of other commonly prescribed antibacterial agents, and ceftolozane/tazobactam did not antagonise the activity of these other antibacterials.

The synergy observed for some antibacterial combinations in this study supplements the currently available information for combination therapy and may suggest new directions for treating challenging cases. Some synergistic effects may be attributed, at least in part, to the ESBL-inhibitory activity of tazobactam, although this remains to be proven. The mechanisms of the other synergistic interactions observed also require further elucidation. Ceftolozane/tazobactam did not adversely affect the activity of, and was not affected by, other antibacterial agents given concurrently. In vivo studies will be needed to substantiate these results and to determine their clinical relevance.