Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Zheng, Gang; Zhang, Jianxin; Wang, Bei; Cai, Jiaqi; Wang, Lili; Hou, Kaixuan; Zhang, Yan; Zhang, Liang; Yang, Zhitao; He, Juan; Bian, Xiaolan

doi:10.1007/s40121-021-00479-7

Cited by 32 publications

(46 citation statements)

References 53 publications

(67 reference statements)

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“…In a study of bloodstream infections caused by CRKP, 25 early initiation of appropriate antibiotic therapy was associated with lower 30-day mortality. A study by Zheng et al 26 found that CAZ-AVI combined with in vitro insensitive drugs significantly reduced the 30-day mortality in CRKP-infected patients compared with CAZ-AVI alone, which is consistent with our findings. In a model of Galleria Mellonella larvae infected with CRKP, CAZ-AVI combined with carbapenem significantly improved the survival rate and inhibited the development of drug resistance compared with CAZ-AVI alone.…”

Section: Discussionsupporting

confidence: 92%

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation

Zhang¹,

Zhong²,

Ding³

et al. 2021

IDR

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The clinical efficacy of ceftazidime-avibactam (CAZ-AVI) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP)-infected recipients after kidney transplantation (KT) has not been well evaluated. We aimed to assess its efficacy in a single-center cohort of KT recipients infected with CRKP. Materials and Methods: We retrospectively observed KT recipients diagnosed with CRKP infection from June 2019 to July 2021. The primary outcome was 30-day mortality and secondary outcomes were 14-day clinical cure and 14-day microbiological cure. Logistic regression analysis was used to evaluate the relationship between CAZ-AVI treatment and prognosis. Results: A total of 54 CRKP-infected KT recipients were recorded in this study. Twenty-two recipients received CAZ-AVI and 32 received other antibiotic regimens. Recipients in both groups had similar baseline characteristics, with the most common site of infection being surgical site infections (n=27; 50.0%) and bloodstream infections (n=23; 42.6%). Recipients treated with CAZ-AVI had significantly lower 30-day mortality (3/22 vs 14/32, P=0.019), significantly higher 14-day clinical cure (18/22 vs 17/32, P=0.030) and 14-day microbiological cure (19/22 vs 15/32, P=0.003) compared with recipients receiving other treatment regimens. Kaplan-Meier survival curves for 30-day mortality confirmed the findings (log-rank=0.014). In a multivariate logistic regression model, receiving CAZ-AVI was found to be an independent protective factor for 30-day mortality (odds ratio=0.148, 95% confidence interval, 0.027-0.800; P=0.026). No significant side effects were recorded. Conclusion: CAZ-AVI may be more valuable than other antibiotic regimens for the treatment of CRKP infection after kidney transplantation, and further large randomized controlled trials are needed to assess its efficacy.

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Section: Discussionsupporting

confidence: 92%

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation

Zhang¹,

Zhong²,

Ding³

et al. 2021

IDR

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“…Studies are conducted in vitro and vivo to compare CAZ/AVI monotherapy with combination therapy. Zheng and his colleagues suggested that CAZ/AVI combined with another in vitro non-susceptible antimicrobials could significantly decrease the 30-day mortality rate of critically ill patients with CRKP infections compared with CAZ/AVI monotherapy (Zheng et al, 2021). An in vitro study indicated that polymyxin B and CAZ/AVI combinations could improve the antimicrobial activity, delay or suppress the regrowth of CRKP resistant subpopulation (Ma et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…The worldwide outbreak of CRKP, especially in China, high mortality rate, and lack of effective therapies have brought new clinical practice challenges. Several retrospective observational studies showed that CAZ/AVIbased regimens had greater mortality benefits against CRE isolates, predominately KPC-producing Klebisella pneumonia, than best available regimens including tigecycline, aminoglycosides, and polymyxins (Shields et al, 2017a;van Duin et al, 2018;Tumbarello et al, 2019;Tsolaki et al, 2020;Zheng et al, 2021). Most studies with polymyxins have compared the clinical outcomes of colistinbased therapy with CAZ/AVI.…”

Section: Introductionmentioning

confidence: 99%

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

Fang

Zhang

et al. 2021

Front. Pharmacol.

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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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“…In a previous study, we found that using a combination treatment scheme of CAZ/AVI with carbapenems, fosfomycin, or tigecycline could significantly decrease the mortality of critically ill patients with CRKP infection [ 12 ]. However, PMB-based treatment regimen were not evaluated.…”

Section: Introductionmentioning

confidence: 99%

Ceftazidime/Avibactam-Based Versus Polymyxin B-Based Therapeutic Regimens for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in Critically Ill Patients: A Retrospective Cohort Study

et al. 2022

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Introduction: Considering the importance of ceftazidime/avibactam (CAZ/AVI) and polymyxin B (PMB) in treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, it is essential to evaluate the efficacy and safety of these agents and provide appropriate medical advice to clinical specialists. Methods: We conducted a retrospective cohort study in two Chinese tertiary hospitals for critically ill patients with CRKP infection who received at least 24-h CAZ/AVI-based or PMBbased treatment. A binary logistic model and a Cox proportional hazards regression model were constructed to analyze variables that could potentially affect 30-day microbiological eradication and all-cause mortality, respectively. Results: From January 2019 to December 2021, 164 eligible patients were divided into CAZ/AVI and PMB cohorts. A notably lower 30-day Guanhao Zheng and Jiaqi Cai contributed equally to this work and share first authorship.

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Ceftazidime-Avibactam in Combination with In Vitro Non-susceptible Antimicrobials Versus Ceftazidime-Avibactam in Monotherapy in Critically Ill Patients with Carbapenem-Resistant Klebsiella Pneumoniae Infection: A Retrospective Cohort Study

Cited by 32 publications

References 53 publications

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation

Efficacy of Ceftazidime-Avibactam in the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection After Kidney Transplantation

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

Ceftazidime/Avibactam-Based Versus Polymyxin B-Based Therapeutic Regimens for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infection in Critically Ill Patients: A Retrospective Cohort Study

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