Impact of an Extended Infusion Β-lactam Strategy on Outcomes in Critically Ill Patients with Pseudomonas Infections

BACKGROUND: Pseudomonas aeruginosa (PSA) is frequently associated with nosocomial infections resulting in significant morbidity and mortality. High MICs in MDR strains highlights the need to maximize antibiotic exposure with the goal of improving patient outcomes. For β-lactams, optimal efficacy is achieved when free drug concentrations are above the MIC for ~ 40–60% of the dosing interval. Unfortunately, due to significant pharmacokinetic variability in the critically ill, achieving this target with standard intermittent infusions (II) is challenging, resulting in preference for extended (EI) or continuous infusion strategies. Additional data in patients with PSA infections are needed to understand the association between infusion strategy and clinical outcome. METHODS: A single-center, retrospective chart review. Adult patients with positive respiratory or blood cultures for PSA treated with cefepime or piperacillin/tazobactam managed in an ICU from January 2012 to May 2016 were included. Primary endpoint was clinical cure (CC) at end of therapy (EOT) between patients receiving EI or II. Secondary endpoints included microbiologic eradication (ME), 28-day mortality, length of ICU and hospital stay, and effect of baseline kidney function on clinical cure. RESULTS: Eighty-three patients were included in the analysis. Patient characteristics were well matched except for a higher frequency of malignancy in the EI arm (P = 0.02). CC was achieved in an overwhelming majority of EI patients compared with II (89.2% vs. 69.6%, P = 0.031). Further, patients with normal renal function (CrCL ≥ 60; P = 0.02) or APACHE II ≥ 17 (P = 0.04) receiving II experienced higher failure rates. In multivariate analysis, use of II associated with 4-fold higher incidence of clinical failure (OR 4.5 [1.3–16.3]). For other secondary endpoints, ME was observed in 73% of EI vs. 65% of II (P = 0.44) and 28-day mortality was observed in 13% of patients in both arms (P = 0.94). No significant differences were observed with other secondary variables. CONCLUSION: Use of an EI strategy in critically ill patients with PSA infections improves CC. Further, EI benefitted those patients with normal to augmented renal clearance suggesting that improved exposure may play a role in clinical outcomes. DISCLOSURES: K. Klinker, The Medicines Company: Scientific Advisor, Consulting fee.