1736. Xeruborbactam (QPX) Potentiates the Activity of Multiple β-Lactams Against Highly Resistant Pseudomonas aeruginosa to a Greater Degree than Other β-Lactamase Inhibitors

Abstract

Background. Pseudomonas aeruginosa (PA) is an important pathogen notorious for antibiotic resistance. Xeruborbactam (QPX) is a potent ultra-broad-spectrum boronic acid β-lactam inhibitor (BLI) that, in combination with selected BL antibiotics, has excellent in vitro activity against carbapenem-resistant Enterobacterales (CRE), and Acinetobacter baumanii or PA producing class A/B or D carbapenemases. We evaluated QPX in combination with anti-pseudomonal BLs against clinical PA isolates from tertiary care US hospitals. Methods. We tested PA clinical isolates resistant to ≥1 BL (imipenem (IMP), meropenem (MEM), cefepime (FEP), piperacillin-tazobactam (PIP-TAZ), aztreonam (ATM), ceftolozane-tazobactam (TOL-TZP), ceftazidime-avibactam (CZA), IMI-relebactam (IMI-REL), MEM-vaborbactam (MVB)) against QPX (in fixed concentration of 8 μg/mL) combined with anti-pseudomonal BLs. We performed wholegenome sequencing on isolates using the MiSeq platform (Illumina). Results. Antibiograms and resistance determinants of 77 isolates tested to date are summarized in Figs 1, 2. 91% of isolates were CR; 43%, 58% and 61% were resistant to CZA, IMI-REL and MVB, respectively. No isolates produced class A/B/D carbapemases. All except 2 isolates carried PDC variants. 92% either had oprD porin single nucleotide polymorphism (SNP) or deletions. mutS mutations (present in 23% of isolates) were associated with resistance to IPM/QPX (p=.04), but not TOL-QPX or PIP-QPX. Addition of QPX significantly reduced MIC50 of IPM (32-fold), PIP (16-fold), FEP and ATM (4-fold) (all p< .0001, Fig 3). Addition of QPX to MEM or TOL reduced MIC50 by 2-fold (p=.02, p< .0001). QPX reduced IMP and PIP MICs more than did REL (32 vs 8-fold,