Purpose: To review clinical outcomes in organ transplant recipients (OTRs) treated with Ceftazidime/avibactam (C/A) and ceftolozane/tazobactam (C/T) for infections caused by Multidrug resistant Pseudomonas aeruginosa (MDR PsAr) and carbapenem-resistant Enterobacteriaceae (CRE).

Methods: We conducted a retrospective single center study of all adult OTRs between 1/1/2015–10/31/2016 with ≥1 culture positive for MDR PsAr or CRE who received C/A or C/T. Data were obtained from pharmacy and manual review of electronic medical records. The primary outcome was clinical improvement, defined as survival to resolution of signs and symptoms in patients receiving ≥72 hours of C/A or C/T. Microbiologic cure was defined as clearance of bacteria from infection site cultures within 7 days of treatment initiation.

Results: We identified 32 OTRs who received ≥72 hours of C/A or C/T. Distribution of organ type was as follows:11 (34%) liver, 9 (28%) lung, 6 (19%) intestinal, 4 (13%) kidney, 1 (3%) kidney-pancreas, 1 (3%) heart-lung. 21 (66%) patients had infections with MDR PsAr and 11 (34%) with CRE. Approximately 60% required admission to the intensive care unit. All 9 lung transplant recipients, including 4 with cystic fibrosis, had MDR PsAr pneumonia. CRE infections were observed mostly in liver, intestinal and renal transplant patients in whom the source was often intra-abdominal or genitourinary. 9/21 (28%) had bloodstream infection. C/T was administered to 17 (53%) patients, all for MDR PsAr. C/A was given to 15 (47%) patients: 11 treated for CRE and 4 for MDR PsAr. Clinical improvement was seen in 24/32 (75%) patients. Microbiological cure was documented in 15/19 (79%) evaluable cases. Overall, 30-day mortality and 90-day mortality was 19% and 34%, respectively. 6/9 (67%) evaluable patients developed resistance to C/A or C/T during treatment or following completion.

Conclusion: The majority of OTRs with infections caused by MDR PsAr and CRE showed clinical improvement on C/T or C/A although 90-day mortality remains high. These results compare favorably to outcomes of therapy with greater toxicity. The role of these agents appears promising; however, further studies are required to validate clinical outcomes and to identify risks for the emergence of resistance.

CITATION INFORMATION: Nambiar P, Brizendine K, Athans V, Cober E. Clinical Experience with Novel Cephalosporin/Beta-Lactamase Inhibitor Combinations in the Treatment of Multidrug Resistant Pseudomonas aeruginosa and Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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