624. Molecular Characterization of Baseline Enterobacteriaceae and Pseudomonas aeruginosa from a Phase 3 Nosocomial Pneumonia (ASPECT-NP) Clinical Trial

BACKGROUND: ASPECT-NP, a phase 3, randomized, double-blind, multicenter trial, evaluated ceftolozane/tazobactam (C/T) 3 g q8h vs. meropenem 1 g q8h for 8–14 days in adults for treatment of ventilated nosocomial pneumonia. Baseline Gram-negative (GN) isolates from patients were tested for mechanisms of resistance. METHODS: Lower respiratory tract (LRT) isolates were sent to a central laboratory for organism identification and susceptibility. Of 664 total Enterobacteriaceae (ENT) and Pseudomonas aeruginosa (PsA) isolates, 351 (53%) were nonsusceptible to broad-spectrum cephalosporins and/or carbapenems and underwent whole-genome sequencing, quantitative RT–PCR, and western blot analysis. ENT isolates were tested for the presence of acquired β-lactamase genes and AmpC levels (selected species). PsA isolates were tested for acquired β-lactamase genes, AmpC (PDC) levels, efflux pump expression, and OprD loss. RESULTS: Of 262 ENT isolates, 114 (44%) were susceptible to C/T (MIC ≤2 µg/mL). An extended-spectrum β-lactamase (ESBL) gene was carried by 89 (78%) of the C/T-susceptible isolates. Of 148 C/T-nonsusceptible (C/T-NS) isolates, 87 (59%) were carbapenemase negative, and the majority 135 (91%) also carried an ESBL gene. The most common ESBL was bla(CTX-M15) with bla(OXA-1) and bla(OXA-30). Klebsiella pneumoniae often displayed higher C/T MICs compared with other species carrying the same resistance genes. Among all C/T-NS isolates, 61 (41%) were carbapenemase positive, most commonly K. pneumoniae carrying bla(OXA-48), bla(NDM-1), and bla(NDM-5). Of 89 PsA isolates, 58 (65%) were susceptible to C/T (MIC ≤4 µg/mL), despite elevated AmpC expression, efflux pumps, or loss of OprD; only 5 isolates had an acquired β-lactamase. Of the 31 C/T-NS PsA isolates, only 12 (39%) were carbapenemase positive and carried bla(VIM) or bla(GES); isolates carrying bla(GES) had lower C/T MICs (8–32 µg/mL) compared with bla(VIM) (MIC > 128 µg/mL). PDC alleles were similar in isolates with high and low C/T MICs. CONCLUSION: In baseline GN LRT isolates from ASPECT-NP, the most common ESBL detected in ENT was bla(CTX-M15;) carbapenemases were uncommon. There was no correlation of ESBL phenotype to C/T susceptibility among ENT, nor of PDC allele to C/T susceptibility among PsA. DISCLOSURES: All authors: No reported disclosures.