1601. Evaluation of Synergy with β-Lactams Plus Aztreonam Against Pseudomonas aeruginosa (PSA)

Abstract

BackgroundCombination therapy is often employed in the treatment of PSA infections. Agents commonly used in combination with β-lactams include aminoglycosides, polymyxins, and fluoroquinolones but are limited by resistance and toxicity concerns. The use of dual β-lactam therapy is an emerging area of interest for the treatment of patients with resistant Gram-negative pathogens. This study evaluated synergy between β-lactam agents and aztreonam (ATM) against PSA isolates with varying degrees of susceptibility.Methods4 PSA clinical isolates were collected from Albany Medical Center; 1 ATCC isolate was used (Table 1). Synergy with cefepime (FEP), meropenem (MER), and ceftazidime (CAZ), each in combination with ATM, was assessed using fractional inhibitory concentration index determined by checkerboard method. Synergistic combinations were tested in 24-hour time-kill, utilizing minimum and steady-state physiological concentrations (Cmin and Css). Tested bacteria were grown to late log phase, diluted to 1 × 106 cfu/mL and incubated at 37°C for 24 hours. Samples were drawn at 0, 2, 4, 6 and 24 hours. Synergy in time-kill was defined as ≥ 2 log10 cfu/mL kill greater than the most active individual agent at 24 hours.ResultsIn checkerboard studies, combinations with ATM resulted in 80% synergy with FEP and 60% synergy with MER or CAZ combinations. ATM/MER and ATM/CAZ time-kill experiments resulted in indifference for most organisms and concentrations tested. For both single and combination regimens, initial killing was observed but varying degrees of regrowth occurred by 24 hours. The only strain with no regrowth at 24 hours was AMC-PSA2 (bactericidal activity and no regrowth at 24 hours observed for MER Cmin MER Css, and MER+ATM Css). Against AMC-PSA2, CAZ+ATM at Cmin was synergistic with limited regrowth observed.ConclusionAgainst PSA, tested β-lactam combinations with ATM resulted in lack of synergy in time-kill experiments, despite checkerboard results. Due to the extent of regrowth observed with nearly all single agent and combination regimens, testing of alternative combinations, including those that evade common resistance mechanisms such as efflux pumps or β-lactamases, and studies of dynamic concentrations are warranted. Disclosures All authors: No reported disclosures.