Real-World Effectiveness of Ceftazidime–Avibactam for Multidrug-Resistant Gram-Negative Pneumonia, Time-Stratified Risk Factors for Short- and Long-Term Mortality, and Inpatient Costs: A Multicenter Retrospective Cohort Study

Multidrug-resistant (MDR) Gram-negative pneumonia is associated with high mortality and substantial healthcare resource utilization. Ceftazidime–avibactam (CAZ-AVI) is an important option, yet real-world experience in Chinese pneumonia cohorts is limited and the associated inpatient costs are seldom reported. This study aimed to describe the clinical response to CAZ-AVI in routine practice, to identify the factors associated with 14-day and with 30-day all-cause mortality separately so as to examine how they differ over time, and to characterize inpatient costs. We retrospectively studied 693 adults with MDR pneumonia who received at least 3 days of CAZ-AVI at eight hospitals in Hubei, China, between August 2022 and August 2025. Factors associated with 14-day and 30-day all-cause mortality were examined by univariable and multivariable logistic regression, with LASSO-penalized regression and cross-validation as a sensitivity analysis. Acute kidney injury (AKI) was recorded as a safety observation, and pneumonia-related inpatient costs were summarized descriptively. The study is reported in line with Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Overall, 480 patients (69.3%) had a favorable response (cure, 356 [51.4%]; improvement, 124 [17.9%]). A higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score was independently associated with mortality at both 14 days (adjusted OR 1.20; 95% CI 1.14–1.26) and 30 days (1.27; 1.18–1.37). At 14 days, death was further associated with bacteremia (4.76; 2.39–9.66), carbapenem-resistant organisms (CRO; 5.93; 2.60–13.60), and septic shock (3.30; 1.32–8.39). At 30 days, the associated factors were Klebsiella pneumoniae (15.19; 3.25–78.94; the wide confidence interval warrants caution) and septic shock (5.74; 1.34–24.97), while a later rise in serum albumin accompanied lower mortality (0.89; 0.82–0.95). AKI occurred in 15 of 693 patients (2.2%). The median total inpatient cost was USD 14,982 (IQR 8462–25,136), of which CAZ-AVI accounted for a median of USD 3901 (IQR 2069–6159). In routine practice, CAZ-AVI for MDR pneumonia was associated with a favorable response, and the factors linked to early death differed from those linked to later death. These associations are hypothesis-generating; together with the cost description, they may help inform time-stratified management and the controlled studies needed to confirm these findings. Multidrug-resistant Gram-negative pneumonia carries significant morbidity and mortality, often requiring resource-intensive care. Ceftazidime–avibactam is an essential therapeutic option for these resistant infections. This retrospective, multicenter study evaluated the real-world clinical response to ceftazidime–avibactam in 693 adult patients across central China. Overall, 69.3% of patients achieved a favorable clinical response. Notably, the clinical factors associated with early mortality (within 14 days) differed from those linked to later mortality (up to 30 days). Early mortality was primarily associated with acute infectious dissemination, such as bacteremia and septic shock, whereas later mortality correlated with sustained inflammation, poor nutritional status, and specific pathogens such as Klebsiella pneumoniae. While lacking a comparator group to establish comparative efficacy, these findings highlight the necessity of time-stratified clinical management and provide real-world inpatient cost data to inform future controlled trials.