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Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.
Antimicrob Agents Chemother. 2019 10; 63(10)AA

Abstract

In this article, we report a case series of patients with infections caused by Enterobacteriales 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 (MIC90, 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%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Authors+Show Affiliations

Instituto Central, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil tguimaraes@terra.com.br.School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.Laboratório de Bacteriologia LIM-49, Universidade de São Paulo, São Paulo, Brazil.Laboratório de Bacteriologia LIM-49, Universidade de São Paulo, São Paulo, Brazil.Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Laboratório Diagnósticos da América, DASA, Rio de Janeiro, Brazil.Laboratório de Bacteriologia LIM-49, Universidade de São Paulo, São Paulo, Brazil.Division of Infectious Diseases, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31358592

Citation

Guimarães, Thaís, et al. "Ceftazidime-Avibactam as Salvage Therapy for Infections Caused By Enterobacteriales Coresistant to Carbapenems and Polymyxins." Antimicrobial Agents and Chemotherapy, vol. 63, no. 10, 2019.
Guimarães T, Nouér SA, Martins RCR, et al. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins. Antimicrob Agents Chemother. 2019;63(10).
Guimarães, T., Nouér, S. A., Martins, R. C. R., Perdigão Neto, L. V., Martins, W. M. B. S., Narciso Barbosa, A. C., Ferreira, A. L. P., Costa, S. F., & Gales, A. C. (2019). Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins. Antimicrobial Agents and Chemotherapy, 63(10). https://doi.org/10.1128/AAC.00528-19
Guimarães T, et al. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused By Enterobacteriales Coresistant to Carbapenems and Polymyxins. Antimicrob Agents Chemother. 2019;63(10) PubMed PMID: 31358592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins. AU - Guimarães,Thaís, AU - Nouér,Simone A, AU - Martins,Roberta C R, AU - Perdigão Neto,Lauro V, AU - Martins,Willames M B S, AU - Narciso Barbosa,Ana Clara, AU - Ferreira,Adriana L P, AU - Costa,Silvia F, AU - Gales,Ana C, Y1 - 2019/09/23/ PY - 2019/03/12/received PY - 2019/07/17/accepted PY - 2019/7/31/pubmed PY - 2020/8/4/medline PY - 2019/7/31/entrez KW - CRE KW - Enterobacteriales KW - KPC-Kp KW - extensively drug resistant JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 63 IS - 10 N2 - In this article, we report a case series of patients with infections caused by Enterobacteriales 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 (MIC90, 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%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/31358592/Ceftazidime_Avibactam_as_Salvage_Therapy_for_Infections_Caused_by_Enterobacteriales_Coresistant_to_Carbapenems_and_Polymyxins_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=31358592 DB - PRIME DP - Unbound Medicine ER -