2176. Single β-Lactams v. Combination Regimens: Assessing the Probability that an Active Agent Would be Selected When Considering Empiric Therapy for P. aeruginosa

Abstract

BackgroundWhile the value of a combination vs. monotherapy in the management of P. aeruginosa (PSA) infection continues to be a topic of debate, the rising antimicrobial resistance observed for this pathogen has made it increasingly difficult to select appropriate (i.e., susceptible) empiric regimens. Herein, we evaluated the probability of the β-lactams to provide a susceptible result for PSA when using the agents as either monotherapy or as part of a combination regimen.MethodsContemporary nonduplicate PSA isolates derived from blood or the respiratory tract of patients hospitalized in the United States were utilized. MICs 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). Overall susceptibility (%S) of the regimen was derived from the monotherapy value plus the cumulative susceptibility of the additional agent for each isolate.ResultsTotal of 560 unique PSA were studied. When assessing β-lactam monotherapy, only ceftolozane/tazobactam exceeded 90% susceptibility, while cefepime, ceftazidime, meropenem and piperacillin/tazobactam ranged from 72 ro 76% (table). When considering combination therapy, the addition of the second agent amikacin > tobramycin > ciprofloxacin > fosfomycin enhanced the achievable %S for cefepime, ceftazidime, meropenem and piperacillin/tazobactam, whereas very little change was noted for ceftolozane/tazobactam due to the intrinsic potency of this compound as a single agent (table).AMKC/TFEPCAZCIPFOFMEMTZPTOB%S939575767646727391%S + AMK-989696--9697-%S + CIP-978890--8889-%S + FOF-978687--8589-%S + TOB-979494--9495-ConclusionWhile the addition of amikacin, tobramycin, ciprofloxacin or fosfomycin increased the probability that an active agent would be selected when considering empirical with cefepime, ceftazidime, meropenem and piperacillin/tazobactam, ceftolozane/tazobactam achieves a similar activity profile using a monotherapy approach.Disclosures D. P. Nicolau, Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium.