Introduction

Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are a global public health problem. Avibactam, a novel non-β-lactam β-lactamase inhibitor, inhibits OXA-48 carbapenemases. However, there is paucity of clinical efficacy studies of ceftazidime-avibactam (CAZ-AVI) in CRKP-BSIs, especially in oxacillinase-48 (OXA-48) predominant regions.

Aim

To evaluate the factors affecting the treatment outcomes with CAZ-AVI in CRKP-BSIs patients with OXA-48-producing and endemic carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

Patient Profile

• 106 adult patients with CAZ-AVI-sensitive CRKP-BSIs and received CAZ-AVI monotherapy within the first 7 days of blood culture positivity

Method

Study Design

• Multicenter retrospective observational study
• Patients received CAZ-AVI intravenously (2/0.5 g every 8 h as a 2-hour infusion) for at least 72 h
• CAZ-AVI was used either as the initial treatment or as salvage therapy during the infection course

Endpoints

• 30-day mortality
• Relapse in CRKP-BSIs (recurrence of infection within 30 days after treatment)
• Clinical success (survival and absence of recurrence 30 days after the onset of infection)

Results

Efficacy

• Initial first-line therapy with CAZ-AVI lowered mortality rates as compared to patients who switched treatment to CAZ-AVI (14.3% vs. 37.7%, p = 0.04; Figure 1)
• Initiating CAZ-AVI on the day of blood culture was obtained was significantly more common among the survived cases than the fatal cases (32.3% vs. 8.5%, p = 0.007)
• No development of resistance or relapse was observed in any of the cases
• Initiating CAZ-AVI, on the day blood culture was obtained, significantly reduced fatality compared to switching treatment from colistin-based-regimen to CAZ-AVI (hazard ratio 0.25, p = 0.025)
• Older age and severe neutropenia were also linked to significantly higher fatality rates
• The mean initiation time of CAZ-AVI, after blood culture collection, among the survived cases was 2.1 days versus 2.9 days among the fatal cases (p = 0.035)

Figure 1: Effect of CAZ-AVI therapy on 30-day mortality rates

Conclusion

• Ceftazidime-avibactam monotherapy was an important treatment option for CRKP-BSIs in OXA-48 endemic areas
• Early initiation of CAZ-AVI was a convenient and preferred option rather than switching to CAZ-AVI from a last-resort regimen, in terms of survival benefits

Sci Rep 2024; 14: 26337