2667. Does Ceftazidime–Avibactam (CAZ-AVI) Improve Short- and Long-Term Outcomes Among Solid-Organ Transplant (SOT) Recipients with Carbapenem-Resistant Enterobacteriaceae (CRE) Infections?

Abstract

BackgroundSOT recipients are an ideal population in which to study the impact of new antibiotics, since they are particularly dependent upon drug activity to clear infections. In 3/15, FDA approved CAZ-AVI, the first new anti-CRE agent to arrive in the clinic. Our objective was to determine whether CAZ-AVI improves short- and long-term outcomes of CRE-infected SOT recipients.MethodsWe performed a retrospective study of SOT recipients infected with CRE since 2012, who were treated with CAZ-AVI or salvage agents for ≥ 3 days.Results35 CRE-infected SOT recipients (14 liver, 11 lung, 6 kidney, 3 intestine, 1 heart) with bacteremia (20), pneumonia (11), intra-abdominal abscess (3) and soft-tissue infection/osteomyelitis (1) were enrolled. 16 and 19 patients (pts) were treated with CAZ-AVI and salvage agents, respectively. Types of infection or SOT, APACHE II and McCabe scores did not differ significantly between patients treated with CAZ-AVI or salvage agents. 30- and 90-d mortality rates were significantly lower among SOT recipients treated with CAZ-AVI (0% and 6%, respectively) compared with salvage agents (26% and 37%; P = 0.049 and 0.047). Among patients who survived 90 days, recurrent CRE infections were diagnosed in 53% and 17% of those treated with CAZ-AVI and a salvage regimen, respectively (P = 0.10). Median time from end of therapy for the 1st CRE infection to recurrent infection was 116 days (max 1,242) and 361 days (max 799) for CAZ-AVI and salvage regimens, respectively. Survival and recurrence-free survival were greater for treatment with CAZ-AVI and salvage agents, respectively, as measured by Kaplan–Meier (Figures). CAZ-AVI resistance developed in 37% (n = 3) of patients with recurrent infections. Recurrent isolates were genetically indistinguishable from parent isolates by core genome SNP phylogeny (< 15 SNP).ConclusionCAZ-AVI significantly reduced short-term mortality among SOT recipients with CRE infections compared with salvage regimens, but was limited by recurrent infections and emergence of resistance. The same strains caused recurrent and initial infections, suggesting that CAZ-AVI did not eliminate CRE from GI sites that serve as sources of recurrence. Optimizing outcomes in SOT recipients with CRE infections will require new agents like CAZ-AVI, and strategies to eliminate long-term colonization. Disclosures All authors: No reported disclosures.