Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins

• Published in: Antimicrobial agents and chemotherapy Vol. 63; no. 10
• Main Authors: Guimarães, Thaís, Nouér, Simone A, Martins, Roberta C R, Perdigão Neto, Lauro V, Martins, Willames M B S, Narciso Barbosa, Ana Clara, Ferreira, Adriana L P, Costa, Silvia F, Gales, Ana C
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.10.2019
• Subjects: Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Ceftazidime; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Mechanisms of Resistance; Pneumonia, Bacterial; Salvage Therapy; extensively drug resistant; Enterobacteriales; KPC-Kp; CRE
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.00528-19

In this article, we report a case series of patients with infections caused by coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC , 1 μg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant .