Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis

Abstract

Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens.Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment.Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79–1.34), microbiologically negative (OR = 0.99, 95% CI 0.54–1.81), and clinical success (OR =0.95, 95% CI 0.64–1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34–1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04–0.78).Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

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

“…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). However, results of meta-analysis indicated that there were no siginifaicant difference in mortality rate, microbiologically negative and clinical success between CAZ/ AVI-based combination tehrapy and CAZ/AVI monotherapy (Li et al, 2021). Therefore, the actual effect of combination therapy on CRKP infection in humans is unknown.…”

Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-K. pneumoniae in Febrile Neutropenic Patients with Acute Leukemia Who are Colonized with KPC-K. pneumoniae. A 7-Years Retrospective Observational Cohort Study

“…CAZAVI represents a valuable option for treating patients with KPC -K.pneumoniae infections. 21 , 28 , 29 Associated with lower mortality rates respect historical non-CAZAVI-based regimens. 22–25 In our experience, the empirical use of CAZAVI, both combination therapy and monotherapy, for the treatment of FNE in AL patients who are KPC -K pneumoniae carriers resulted in better activity, lower toxicity, and a higher rate of successful outcome without EAT modification than colistin-based EAT, and independently associated with a significantly higher rate of overall successful response.…”

“…CAZAVI proved active against our KPC -K. pneumoniae blood isolates. CAZAVI resistance in KPC- K. pneumoniae is described, more likely in CAZAVI monotherapy than in combination, 28 , 29 but no decreased susceptibility or CAZAVI resistance emerged in prospective studies. 23 Our prevalent use of CAZAVI in combination might have limited the selection of CAZAVI-resistant subpopulations.…”

Risk Factors for Carbapenem-Resistant Enterobacterales Clinical Treatment Failure

“…Additional prespecified variables were entered into stepwise selection regardless of the P value cutoff as random effect variables, due to their basis in literature to affect CRE outcomes and/or their biological plausibility. These variables included respiratory source of infection, immunocompromised status, ID consult, and meropenem MICs ( 14 – 18 , 28 , 29 ). Time (function of admission date) was also entered as a variable in stepwise selection to account for the possibility that treatments and the care of patients have naturally improved over time ( 4 ).…”