Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients

Vasiliki Tsolaki; Konstantinos Mantzarlis; Athanasios Mpakalis; Ergina Malli; Fotios Tsimpoukas; Athanasia Tsirogianni; Constantinos Papagiannitsis; Paris Zygoulis; Maria-Eirini Papadonta; Efthimia Petinaki; Demosthenes Makris; Epaminondas Zakynthinos

doi:10.1128/AAC.02320-19

Ceftazidime-Avibactam To Treat Life-Threatening Infections by Carbapenem-Resistant Pathogens in Critically Ill Mechanically Ventilated Patients

Antimicrob Agents Chemother. 2020 Feb 21;64(3):e02320-19. doi: 10.1128/AAC.02320-19. Print 2020 Feb 21.

Affiliations

¹ Department of Critical Care, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.
² Microbiology Department, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece.
³ Intensive Care Unit, General Hospital of Lamia, Lamia, Greece.
⁴ Department of Critical Care, University Hospital of Larissa, School of Medicine, University of Thessaly, Larissa, Greece ezakynth@yahoo.com.

Abstract

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general intensive care units (ICUs) in central Greece, compared critically ill, mechanically ventilated patients suffering from carbapenem-resistant Enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical and microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with bloodstream infections (BSIs) was conducted. Forty-one patients that received CAZ-AVI (the CAZ-AVI group) were compared to 36 patients that received antibiotics other than CAZ-AVI (the control group). There was a significant improvement in the Sequential Organ Failure Assessment (SOFA) score on days 4 and 10 in the CAZ-AVI group compared to that in the control group (P = 0.006, and P = 0.003, respectively). Microbiological eradication was accomplished in 33/35 (94.3%) patients in the CAZ-AVI group and 21/31 (67.7%) patients in the control group (P = 0.021), and clinical cure was observed in 33/41 (80.5%) versus 19/36 (52.8%) patients (P = 0.010), respectively. The results were similar in the BSI subgroups for both outcomes (P = 0.038 and P = 0.014, respectively). The 28-day survival was 85.4% in the CAZ-AVI group and 61.1% in the control group (log-rank test = 0.035), while there were 2 and 12 relapses in the CAZ-AVI and control groups, respectively (P = 0.042). A CAZ-AVI-containing regime was an independent predictor of survival and clinical cure (odds ratio [OR] = 5.575 and P = 0.012 and OR = 5.125 and P = 0.004, respectively), as was illness severity. No significant side effects were recorded. In conclusion, a CAZ-AVI-containing regime was more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically ventilated ICU population evaluated.

Keywords: ceftazidime-avibactam; critically ill; infections; mechanically ventilated; survival.

MeSH terms

Aged
Azabicyclo Compounds / therapeutic use*
Carbapenems / therapeutic use*
Ceftazidime / therapeutic use*
Critical Illness
Drug Combinations
Enterobacteriaceae / drug effects
Enterobacteriaceae / pathogenicity
Enterobacteriaceae Infections / drug therapy*
Enterobacteriaceae Infections / therapy
Female
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Respiration, Artificial*
Retrospective Studies

Substances

Azabicyclo Compounds
Carbapenems
Drug Combinations
avibactam, ceftazidime drug combination
Ceftazidime