Ceftazidime-avibactam in the treatment of infections caused by KPC-producing Klebsiella pneumoniae: factors associated with clinical efficacy in a single-center cohort.


Journal

International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860

Informations de publication

Date de publication:
Sep 2020
Historique:
received: 04 09 2019
revised: 09 01 2020
accepted: 28 06 2020
pubmed: 7 7 2020
medline: 20 5 2021
entrez: 7 7 2020
Statut: ppublish

Résumé

Infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are not well represented in pivotal trials with ceftazidime-avibactam (CAZ-AVI). This study aimed to investigate its efficacy in a single-centre cohort of patients infected with KPC-Kp. A retrospective observational study was conducted of consecutive patients treated for > 72 hours with CAZ-AVI for KPC-Kp infections. Fourteen-day clinical response was considered when none of these criteria were present: i) the patient died before day 14, ii) treatment with CAZ-AVI at day 14 for persistence of symptoms or signs of infection, iii) recurrence. A multivariate logistic regression model was used to identify factors predictive of 14-day clinical failure. A propensity score to receive targeted initial treatment with CAZ-AVI was used as a covariate of the analysis. Forty-seven patients were included. The median age was 70 years and the median Charlson index was 4. The most frequent sources of infection were intraabdominal (n = 18; 38.3%) followed by pneumonia (n = 14; 29.8%). Twenty-five patients (53.2%) had septic shock. CAZ-AVI was used as monotherapy in 34 (72.3%) of the cases. CAZ-AVI resistance was detected after CAZ-AVI therapy in six of 47 (12.7%) patients. Thirty-day crude mortality was 23.4% (n = 11). The 14-day clinical response rate was 59.6% (n = 28). Pneumonia (OR 7.57; 95% CI 1.45-39.43; P = 0.01), and INCREMENT-CPE score > 7 points (OR 6.73; 95% CI 1.39-34.94; P = 0.02) were associated with 14-day clinical failure. CAZ-AVI offers an advance for the treatment of KPC-Kp infections. In patients with pneumonia or an INCREMENT-CPE score > 7 points it may be reasonable to use CAZ-AVI in combination.

Sections du résumé

BACKGROUND BACKGROUND
Infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are not well represented in pivotal trials with ceftazidime-avibactam (CAZ-AVI). This study aimed to investigate its efficacy in a single-centre cohort of patients infected with KPC-Kp.
METHODS METHODS
A retrospective observational study was conducted of consecutive patients treated for > 72 hours with CAZ-AVI for KPC-Kp infections. Fourteen-day clinical response was considered when none of these criteria were present: i) the patient died before day 14, ii) treatment with CAZ-AVI at day 14 for persistence of symptoms or signs of infection, iii) recurrence. A multivariate logistic regression model was used to identify factors predictive of 14-day clinical failure. A propensity score to receive targeted initial treatment with CAZ-AVI was used as a covariate of the analysis.
RESULTS RESULTS
Forty-seven patients were included. The median age was 70 years and the median Charlson index was 4. The most frequent sources of infection were intraabdominal (n = 18; 38.3%) followed by pneumonia (n = 14; 29.8%). Twenty-five patients (53.2%) had septic shock. CAZ-AVI was used as monotherapy in 34 (72.3%) of the cases. CAZ-AVI resistance was detected after CAZ-AVI therapy in six of 47 (12.7%) patients. Thirty-day crude mortality was 23.4% (n = 11). The 14-day clinical response rate was 59.6% (n = 28). Pneumonia (OR 7.57; 95% CI 1.45-39.43; P = 0.01), and INCREMENT-CPE score > 7 points (OR 6.73; 95% CI 1.39-34.94; P = 0.02) were associated with 14-day clinical failure.
CONCLUSIONS CONCLUSIONS
CAZ-AVI offers an advance for the treatment of KPC-Kp infections. In patients with pneumonia or an INCREMENT-CPE score > 7 points it may be reasonable to use CAZ-AVI in combination.

Identifiants

pubmed: 32629116
pii: S0924-8579(20)30245-4
doi: 10.1016/j.ijantimicag.2020.106075
pii:
doi:

Substances chimiques

Azabicyclo Compounds 0
Bacterial Proteins 0
Drug Combinations 0
avibactam, ceftazidime drug combination 0
Ceftazidime 9M416Z9QNR
beta-lactamase KPC-1 EC 3.5.2.-
beta-Lactamases EC 3.5.2.6
carbapenemase EC 3.5.2.6

Types de publication

Journal Article Observational Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

106075

Informations de copyright

Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Auteurs

Juan José Castón (JJ)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain. Electronic address: juanj.caston.sspa@juntadeandalucia.es.

Marina Gallo (M)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Manuel García (M)

Department of Infectious Diseases, Microbiology and Preventive Medicine, Hospital Virgen del Rocío, Seville, Spain.

Angela Cano (A)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Antonio Escribano (A)

Service of Internal Medicine, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.

Isabel Machuca (I)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Irene Gracia-Aufinger (I)

Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Julia Guzman-Puche (J)

Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Elena Pérez-Nadales (E)

Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.

M Recio (M)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Monserrat Muñoz (M)

Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.

Luis Martínez-Martínez (L)

Unit of Microbiology, Reina Sofia University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain; Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.

Julian Torre-Cisneros (J)

Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain; Spanish Network of Research in Infectious Diseases (REIPI RD16/0016/0008), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.

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Classifications MeSH