Breakthrough Bacteremia with Meropenem-resistant Pseudomonas aeruginosa in Hematologic Malignancy Patients Receiving Levofloxacin Prophylaxis

BACKGROUND: Fluoroquinolone (FQ) exposure has been reported to induce Pseudomonas aeruginosa cross-resistance specifically to carbapenems (CP) in vitro but in vivo data are lacking. The purpose of this study was to determine the impact of FQ prophylaxis for high-risk neutropenia on the emergence of CP-resistant P. aeruginosa infections. METHODS: We conducted a retrospective review of P. aeruginosa bacteremia in adult patients with hematologic malignancies at Oregon Health and Science University (OHSU) between January 01, 2015 and May 01, 2017. Levofloxacin was administered as prophylaxis during neutropenia (absolute neutrophil count (ANC) <500 cells/mL) except when contraindicated due to allergy, severe intolerance, or other reasons. When levofloxacin could not be used, another agent or no prophylaxis was used at the discretion of the medical team. Categorical variables were analyzed using the Fisher exact two-tailed test. The study was approved by the OHSU institutional review board. RESULTS: Twenty-seven episodes of P. aeruginosa bacteremia occurred in 25 patients. Eleven (40.7%) episodes of bacteremia occurred in patients receiving levofloxacin; the remainder of patients were receiving no antibiotics (N = 9) or non-FQ antibiotics (N = 7). Isolates from patients receiving FQ prophylaxis were less likely to be CP- sensitive than from patients receiving non-FQ or no prophylaxis (27% vs. 81%, P = 0.01). Susceptibility to anti-pseudomonal β-lactams was not affected and FQ prophylaxis did not affect CP susceptibility among E. coli isolates from the same patient population. FQ prophylaxis at the time of bacteremia (P = 0.01) and any FQ exposure within 90 days of bacteremia (P = 0.02) were the only host factors associated with CP non-susceptibility in univariate analysis. CONCLUSION: FQ exposure in vivo results in P. aeruginosa cross-resistance specific to CPs. Limitations of our study include its retrospective, single-center design and relatively small number of isolates. CPs are recommended as a first-line option for the empiric management of febrile neutropenia based on studies performed prior to the routine use of FQ prophylaxis. Confirmation of our results in larger studies should prompt re-assessment of this recommendation in patients receiving FQ prophylaxis. DISCLOSURES: J. S. Lewis II, Merck & Co.: Consultant, Consulting fee