Efficacy of Ceftazidime-Avibactam Versus Polymyxin B and Risk Factors Affecting Clinical Outcomes in Patients With Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Infections a Retrospective Study

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Abstract

Background: The worldwide outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become an urgent public health problem. High mortality and lack of effective treatments further pose new challenges to control this infection. However, studies about the evaluation of available antibiotics for CRKP infection are limited. The present study aimed to compare the efficacy of polymyxin B versus ceftazidime-avibactam (CAZ/AVI) in Chinese patients with CRKP infections and to identify risk factors affecting 7-day bacterial eradication and 28-day all-cause mortality.

Methods: From January 8, 2018, to July 6, 2020, a total of 115 adult CRKP infected patients from two tertiary teaching hospitals in Shanghai, China were enrolled based on the inclusion and exclusion criteria. By reviewing electronic medical records of these patients, demographic and clinical data were extracted. The selected patients were divided into polymyxin B and CAZ/AVI groups according to primary antibiotic exposure to compare therapeutic effects. Binary logistic and cox’s regression analysis were performed to identify risk factors for 7-day bacterial eradication and all-cause mortality.

Results: One hundred and five patients were treated with polymyxin B (67.8%) or CAZ/AVI (32.2%). Patients in the CAZ/AVI group had significantly lower rates of 28-day mortality (8.1 vs 29.5%, p = 0.013), higher microbiological eradication and 28-day clinical success. Multivariate analysis showed that Charlson comorbidity index (≥3) and prior antibiotic use within 90 days were independent risk factors for poor microbiological eradication. Cox’s regression analysis indicated that the length of hospitalization after CRKP infection and baseline creatinine clearance negatively affected 28-day mortality.

Conclusion: CAZ/AVI was more effective than polymyxin B and appeared to be a promising drug for CRKP infection, especially for critically ill patients.

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Most cited references 46

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Hypervirulent Klebsiella pneumoniae

Thomas Russo, Candace Marr (2019)

Hypervirulent K. pneumoniae (hvKp) is an evolving pathotype that is more virulent than classical K. pneumoniae (cKp). hvKp usually infects individuals from the community, who are often healthy. Infections are more common in the Asian Pacific Rim but are occurring globally. hvKp infection frequently presents at multiple sites or subsequently metastatically spreads, often requiring source control. hvKp has an increased ability to cause central nervous system infection and endophthalmitis, which require rapid recognition and site-specific treatment. The genetic factors that confer hvKp’s hypervirulent phenotype are present on a large virulence plasmid and perhaps integrative conjugal elements. Increased capsule production and aerobactin production are established hvKp-specific virulence factors. Similar to cKp, hvKp strains are becoming increasingly resistant to antimicrobials via acquisition of mobile elements carrying resistance determinants, and new hvKp strains emerge when extensively drug-resistant cKp strains acquire hvKp-specific virulence determinants, resulting in nosocomial infection. Presently, clinical laboratories are unable to differentiate cKp from hvKp, but recently, several biomarkers and quantitative siderophore production have been shown to accurately predict hvKp strains, which could lead to the development of a diagnostic test for use by clinical laboratories for optimal patient care and for use in epidemiologic surveillance and research studies.

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Jie Fang: URI : https://loop.frontiersin.org/people/1086758/overview

Hui Li: URI : https://loop.frontiersin.org/people/966843/overview

Min Zhang: URI : https://loop.frontiersin.org/people/1129101/overview

Guochao Shi: URI : https://loop.frontiersin.org/people/45130/overview

Yujie Wang: URI : https://loop.frontiersin.org/people/1528039/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 10 December 2021

Publication date Collection: 2021

Volume: 12

Electronic Location Identifier: 780940

Affiliations

[ ¹ ]Department of Pharmacy, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

[ ² ]Department of Pharmacy Services, Boston Medical Center, Boston, MA, United States

[ ³ ]Department of Respiration and Critical Care Disease, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China

[ ⁴ ]Institute of Respiratory Diseases, School of Medicine, Shanghai Jiaotong University, Shanghai, China

[ ⁵ ]Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China

[ ⁶ ]Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Author notes

*Correspondence: Mengying Liu, nobodyxyy@ 123456126.com ; Yujie Wang, iwangyj@ 123456163.com ; Xiaolan Bian, bxl70029@ 123456hotmail.com

This article was submitted to Pharmacology of Infectious Diseases, a section of the journal Frontiers in Pharmacology

[ † ]

These authors have contributed equally to this work and share first authorship

Edited by: Younes Smani, Institute of Biomedicine of Seville (IBIS), Spain

Reviewed by: Fupin Hu, Fudan University, China

Hasan Ejaz, Al Jouf University, Saudi Arabia

Article

Publisher ID: 780940

DOI: 10.3389/fphar.2021.780940

PMC ID: 8703033

PubMed ID: 34955849

SO-VID: e7be3427-e2ca-40be-a716-3322b733d4de

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Efficacy of Ceftazidime-Avibactam Versus Polymyxin B and Risk Factors Affecting Clinical Outcomes in Patients With Carbapenem-Resistant Klebsiella pneumoniae Infections a Retrospective Study

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Most cited references 46

APACHE II: a severity of disease classification system.

Validation of a combined comorbidity index

Hypervirulent Klebsiella pneumoniae

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