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Abstract Background The new β-lactamase inhibitor, avibactam (AVI), has recently been combined with ceftazidime (CAZ) as CAZ-AVI. AVI is also in Phase 3 clinical trials combined with aztreonam as ATM-AVI.… Click to show full abstract
Abstract Background The new β-lactamase inhibitor, avibactam (AVI), has recently been combined with ceftazidime (CAZ) as CAZ-AVI. AVI is also in Phase 3 clinical trials combined with aztreonam as ATM-AVI. Both drug combinations have similar in vitro activity against some organisms, but ATM-AVI is more potent against metallo-β-lactamase (MBL) producing organisms. However, against P. aeruginosa (PA), CAZ-AVI is more potent. Since these compounds have similar pharmacokinetic (PK)/pharmacodynamic (PD) profiles, and there is a need for drugs for the treatment of resistant microorganisms, a Monte-Carlo analysis (MCA) was used to assess their potential efficacy against carbapenem-resistant pathogens. Methods MCA (n = 10,000) was performed for ATM-AVI and CAZ-AVI using PK parameters, CrCl vs. Cl regression, PD targets, and recent MICs from peer-reviewed literature against five carbapenem-resistant (CR) organisms: P. aeruginosa (CR-PA), E. cloacae (CR-EC), K. pneumoniae (CR-KP), Enterobacteriaceae (CR-ENT), and MBL producing Enterobacteriaceae (MBL-ENT). Only MIC studies that directly evaluated both combinations were utilized. Our institution’s inpatient CrCl distribution (range: 10–120 mL/minute) was used to assess drug clearance. The ATM-AVI regimen was 1.5 g q6h with a 3 hours infusion and adjusted for renal function) and the CAZ-AVI regimen was 2 g q8h with a 2-hour infusion and adjusted for renal function). PD targets (%fT>MIC) for ATM-AVI were 40 and 60% and for CAZ-AVI were 40 and 70%. Results Target attainment (TA%) for each regimen and organism was: Drug ATM-AVI CAZ-AVI Regimen 1.5 g q6h (3h infusion) 2 g q8h (2h infusion) fT>MIC (% of interval) 40 60 40 70 CR-PA 48 43 93 87 CR-EC 100 100 100 100 CR-KP 100 100 100 100 CR-ENT 100 100 96 96 MBL-ENT 100 99 2 2 Conclusion Both ATM-AVI and CAZ-AVI displayed very high TA% (>95%) for CR-EC, CR-KP, and CR-ENT at both PD targets. However, TA% for MBL-ENT was very low for CAZ-AVI and ≥99% for ATM-AVI. Against CR-PA, CAZ-AVI was had much higher TA% than ATM-AVI (87–93% vs. 43–48%). These differences suggest different roles for each drug combination in clinical practice. Disclosures All authors: No reported disclosures.