Introduction

Clinical studies have shown that ceftazidime-avibactam (CAZ-AVI) is a valuable treatment option in infections caused by multidrug-resistant gram-negative bacteria. However, the role of CAZ-AVI in treating bacteremia caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) in hematological patients is not well studied.

Aim

To evaluate the efficacy of CAZ-AVI in the treatment of bacteremia due to carbapenem-resistant gram-negative bacteria in hematological patients and to explore the predictors of survival

Patient Profile

• 56 hematological patients (aged ≥14 years) who had a confirmed diagnosis of carbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) and from whom 57 strains were isolated

Method

Study Design

• Single-center, retrospective, observational study
• CAZ 2 g and AVI 0.5 g was administered via a 2-h intravenous infusion every 8 h in patients with normal kidney function
• CAZ-AVI dose was adjusted according to the creatinine clearance in patients with renal impairment
• Aztreonam (AZT) was administered at a dosage of 2 g every 8 h, also with an infusion time of 2 h in patients with metallo-beta-lactamase-CRE (MBL-CRE) bacteremia

Endpoints

• Primary outcome: survival at 30 days after the onset of CRGNB BSI
• Secondary outcomes: clinical success (survival at 30 days, the disappearance of clinical signs and symptoms of infection and the absence of infection recurrence) and microbiological eradication (negative blood culture after 7 days of treatment, without any recurrence of infections or colonization within 30 days)

Results

Efficacy

• The primary outcome of survival rate at 30 days with CAZ-AVI was achieved in 85% patients in the CRE group and 81.3% patients in the CRPA group
• In patients with MBL-CRE bacteremia, the 30-day survival was as high as 91.7% due to combination of CAZ-AVI with AZT therapy as compared to 70% in patients with bacteremia caused by serine-beta-lactamase-CRE
• Ceftazidime did not influence the activity of aztreonam-avibactam against MBL-CRE in-vitro
• The secondary outcome of clinical success with CAZ-AVI was achieved in 76.8% patients and microbiological eradication was achieved in 83.9% patients
• Neutropenia >14 days (P = 0.002, HR 34.483) and a higher Pitt bacteremia score (P = 0.005, HR 2.074) significantly predicted 30-day survival
• Although the susceptibility rates to CAZ-AVI were only 26.8 % in CRE and 80% in CRPA, CAZ-AVI-based regimens were frequently effective against BSI caused by these organisms
• Further, the susceptibility rates to CAZ-AVI were 60% in serine-beta-lactamase-CRE and 83.3% in CRE without carbapenemase bacteremia
• A median duration of CAZ-AVI treatment was 11 days; median time from reporting blood culture to initiating CAZ-AVI treatment was 1 day
• No significant difference in survival between the patients who received CAZ-AVI as empiric therapy and those who received definitive therapy (P = 0.390)

Figure 1: Effect of CAZ-AVI treatment on the primary outcome of survival at 30 days

Safety 

• No one discontinued this drug due to severe adverse effect

  Conclusion

• CAZ-AVI was highly effective in treating bacteremia due to CRE and CRPA
• The combination of avibactam (not ceftazidime) with AZT was highly effective in treating bacteremia due to AZT-resistant MBL producers
• This was a relatively larger study, till date, describing the outcome of CAZ-AVI for BSI due to CRGNB among hematological patients

J Infect Chemother 2024; 30(7): 608-615