2186. Treatment-emergent resistance to ceftazidime-avibactam (CZA) is more common than ceftolozane-tazobactam (CT) among patients infected with multidrug-resistant (MDR) Pseudomonas aeruginosa

BACKGROUND: CZA and CT are front-line agents for treatment (tx) of MDR Pseudomonas aeruginosa; however, comparative data are lacking. The purpose of this study was to compare rates of tx-emergent resistance among patients (pts) with bacteremia or pneumonia at a single center. METHODS: Adult pts treated for >48 hours with CZA or CT were included. Pts with cystic fibrosis or colonization were excluded. Isolates were tested by broth microdilution (BMD) in triplicate and underwent whole-genome sequencing. RESULTS: 113 pts were included. Demographics, severity of illness, and durations of tx were similar for pts tx’d with CZA or CT (Table 1). CT-treated pts were less likely to receive prolonged infusions and monotherapy, but more likely to have empyema/endovascular infections. Baseline median (range) MICs were 4 (2–8mg/L) and 2 (0.25–8mg/L) for CZA and CT, respectively. Within 90-days from tx onset, rates of resistance defined as either ≥4-fold MIC increase or MIC >8mg/L were higher among CZA-treated pts (Table 1). Corresponding median MICs of resistant isolates were 16 (16–128mg/L) and 64 (32–512mg/L), respectively. Across 107 baseline isolates, 59 different sequence types (ST) were represented. The most common P. aeruginosa cephalosporinase (PDC) variants were PDC-3, PDC-5, and PDC-8, present in 10%, 21%, and 10% of isolates, respectively. Resistance evolved across varying STs. A subgroup of contemporary pts was well-balanced and supported overall findings (Table 2). From this subgroup, rates of tx-emergent resistance among pts receiving CZA or CT monotherapy were 50% (6/12) and 6% (1/17), respectively (P=0.01). Rates of CT-resistance were lower among pts who received prolonged (5%, 1/19) versus standard (20%, 5/25) infusions. Paired baseline and resistant isolates showing ≥4-fold MIC increase were compared (Table 3). CZA resistance was associated with sequence changes in ampD and/or efflux genes in 5 pts; 2 additional pairs showed mutations in ftsI (PBP3). CT resistance was associated with new ampC mutations in 83% of pairs. [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: In this non-matched, descriptive analysis, tx-emergent resistance occurred more commonly among pts treated with CZA compared to CT for MDR P. aeruginosa infections. Future multicenter studies evaluating comparative clinical outcomes are warranted. DISCLOSURES: Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support