Ceftazidime-Avibactam for Carbapenem-Resistant Gram-Negative Bacteria Infections: A Real-World Experience in the ICU

Abstract

Purpose

Ceftazidime-avibactam (C-A) is a treatment option for carbapenem-resistant gram-negative bacterial (CR-GNB) infections, but little is known regarding its suitability for the intensive care unit (ICU). The current study aimed to analyze use of C-A for critically ill patients, determine independent predictors of clinical outcome and mortality and explore routine dosages for patients in continuous renal replacement therapy (CRRT).

Patients and Methods

A single-center, retrospective and observational study was conducted in critically ill patients receiving different C-A-based therapies for CR-GNB infections in a tertiary teaching hospital in Beijing, China. Demographic data, severity of infection, clinical outcomes and mortality were assessed. The primary and secondary outcome of this study was 90-day all-cause mortality and 14-day clinical response, respectively.

Results

A total of 43 patients with CR-GNB infection were enrolled, including 14 (32.6%) patients received C-A monotherapy. C-A monotherapy and combination with other agents did not affect 14-day clinical response or 90-day survival. All-cause mortality at 90-days was 39.5% (17/43). Multivariate Cox analysis showed that concomitant with bloodstream infection was independent risk factors for 90-day mortality and that the time to initiation of C-A and Acute Physiology and Chronic Health Evaluation (APACHE) score was independent predictors of 14-day clinical response. Five CRRT patients who received high-dose C-A therapy (>3.75 g/d) had prolonged survival compared with 5 who received low-dose C-A (<3.75 g/d, p = 0.03).

Conclusion

C-A was an effective therapy for severe CR-GNB infections and clinical response correlated with the time of C-A initiation. A dosage >3.75g/d C-A was associated with prolonged survival of CRRT patients. Randomized controlled trials or multicenter studies are needed to confirm these findings.

Keywords:

• ceftazidime-avibactam
• renal replacement therapy
• infections
• intensive care unit
• carbapenem-resistant gram-negative bacteria

Abbreviations

C-A, Ceftazidime-avibactam; CR-GNB, carbapenem-resistant gram-negative bacterial; ICU, intensive care unit; CRRT, continuous renal replacement therapy; ECMO, extra-corporeal membrane oxygenation; APACHE, Acute Physiology and Chronic Health Evaluation; PMs, polymyxins; AGs, aminoglycosides; FDA, Food and Drug Administration; MALDI-TOF/MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; MIC, minimum inhibitory concentrations; CLSI Clinical and Laboratory Standards Institute; IQR, Interquartile range; BMI, Body mass index; GPB, Gram-positive bacteria; CrCL, creatinine clearance; HR, Hazard ratios; OR, odds ratios; CI, Confidence interval.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval

The research was conducted in accordance with the Declaration of Helsinki. All organs were donated voluntarily with written informed consent, and this was conducted in accordance with the Declaration of Istanbul. The study got approved by the Research Ethics Committee of Peking Union Medical College Hospital (I-22PJ203). The requirement of informed consent from patients including the review of their medical records was waived by the Committee, the reasons consisted of (1) the patients may suffer almost no risk from this study, and the risk less than a minimum, (2) the study had no negative influence on rights and interests of the patients, (3) the personal details of patients were anonymous and had no commercial interests.

Acknowledgments

We wish to thank the staff of the Medical Records Department at Peking Union Medical College for their support and cooperation in the follow-up of patients.

Author Contributions

All authors contributed significantly to the work reported, whether in terms of conception, study design, execution, acquisition of data, analysis and interpretation, or all of these; participated in the drafting, revision or critical review of the article; provided final approval of the version to be published; agreed on the journal to which the article was to be submitted; and agreed to take responsibility for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This study was supported by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-059).