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

Abstract

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.

Use of Ceftazidime-Avibactam in the Treatment of Clinical Syndromes With Limited Treatment Options: A Retrospective Study

“…The study did not reveal any significant difference in mortality or clinical cure among patients with or without combination therapy with other antibiotics, which included minocycline, polymyxins, metronidazole, levofloxacin, and fosfomycin. This is in concordance with other studies where there was no reduction in mortality with combination therapy whereas, a study on critically ill patients with CRE infections showed a lower 30-day mortality rate [4,27,28].…”

“…Septic shock is associated with high mortality and the pharmacokinetics of most drugs cannot be relied upon in this situation. Other studies depicted good efficacy with varying percentages of patients with sepsis or septic shock and a study by Vena et al demonstrated good clinical efficacy even when the majority of the study patients had septic shock [4,21,22].…”

“…Other studies depicted good efficacy with varying percentages of patients with sepsis or septic shock and a study by Vena et al. demonstrated good clinical efficacy even when the majority of the study patients had septic shock [ 4 , 21 , 22 ].…”

“…CEF-AVI was approved in India for use in CRE infections while polymyxins are the preferred agents for empiric therapy in the critically ill. Polymyxins have limited use in the renally impaired and polymyxin B cannot be used in urinary tract infections [3]. CEF-AVI has shown superior efficacy over polymyxins in studies over varying sites of infection [4][5][6]. This study retrospectively evaluated the clinical outcomes of CEF-AVI use in the Indian population on various clinical syndromes with a high risk of Carbapenem-Resistant Organism (CRO) infection and LTO.…”

Population Pharmacokinetic Modeling for Ceftazidime‐Avibactam Renal Dose Adjustments in Pediatric Patients 3 months and Older

“…However, analysis of post hoc predicted exposures for adults from the phase III program showed that in multiple subgroups of patients with markers of severe/critical illness, including APACHE II score > 10, systemic inflammatory response syndrome, bacteremia, fever, and augmented renal CL, approved adult doses achieved joint target attainment > 90% 5 . In addition, several real‐world studies have reported positive outcomes for the recommended ceftazidime‐avibactam doses in critically ill adult patients 33–35 . Our modeling approach and the resulting dose recommendations based on matching exposures for pediatric patients (including renal impairment) with adults suggests that the recommended pediatric doses will also be suitable for critically ill children.…”