Single β-lactams versus combinations as empiric therapy for infections with Pseudomonas aeruginosa: assessing the in vitro susceptibility

Background: While the value of combination versus monotherapy of infections with Pseudomonas aeruginosa infection is a subject of debate, increasing antimicrobial resistance of this pathogen makes it difficult to select appropriate empiric regimens. We evaluated the probability that P. aeruginosa would be susceptible to beta-lactams either as monotherapy or as part of a combination regimen. Methods: Contemporary non-duplicate isolates of P. aeruginosa derived from blood or the respiratory tract of patients hospitalized in the United States were investigated. Minimum inhibitory concentrations were determined using broth microdilution methods for amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), ceftolozane/tazobactam (C/T), ciprofloxacin (CIP), fosfomycin (FOF), meropenem (MEM), piperacillin/tazobactam (TZP) and tobramycin (TOB). Susceptibility to a regimen was derived from the minimum inhibitory concentrations value of the beta-lactam plus the minimum inhibitory concentrations value of the additional agent. Results: In 1209 P. aeruginosa, susceptibility to C/T exceeded 90%, while susceptibility to FEP, CAZ, MEM and TZP ranged from 73 to 78%. For antibiotic combinations, the addition of the 2nd agent AMK, TOB, CIP or FOF raised the susceptibility to FEP, CAZ, MEM and TZP, whereas very little added activity was noted for C/T due to the intrinsic potency of this compound alone. Conclusions: While the addition of AMK, TOB, CIP or FOF markedly increased the probability that an active regimen would be selected for empirical therapy with FEP, CAZ, MEM and TZP, C/T alone had higher activity than the combinations.