Introduction
Cefiderocol is the only FDA-approved treatment for MetalloBeta Lactamase (MBL) bacteria but remains inaccessible in many low- and middle-income countries. Ceftazidime-avibactam plus Aztreonam (CAZAVI+ATM) presents a promising alternative, though clinical data are limited. This study aims to assess the efficacy and safety of CAZAVI+ATM compared to other active antibiotics (OAA) for MBL-CPE bacteremia.
Method
This study emulated a target trial using observational data from adults with MBL-CPE bacteremia across 15 hospitals in Argentina from July 2019 to June 2024. The inclusion time (T0) was the identification of MBL-CPE, and patients were categorized based on the treatment received within 24 hours: either CAZAVI+ATM or other active antibiotics (OAA). To mitigate selection bias, propensity score inverse probability weighting was applied. Patients were followed for 30 days, with the primary outcome being 14-day mortality and clinical failure, defined as bacteremia relapse, antibiotic treatment restart, or suppurative complications.
Results
Among the 206 patients with MBL-type CPE bacteremia, the mean age was 58.2 years (SD 17.7), and 62% were male. More than half (55%) required ICU admission. The most common primary infection sites were the respiratory tract (27%) and the urinary tract (25.5%). Klebsiella pneumoniae was the predominant pathogen, accounting for 85.9% of cases, with NDM-producing strains identified in 31% of patients. Regarding treatment distribution, 27% (61/206) of patients received CAZAVI+ATM, while 73% (145/206) were treated with OAA.
|
Outcome |
Adjusted OR |
95% CI |
p-value |
|
14-day Mortality |
0.38 |
0.19-0.72 |
<0.01 |
|
30-day Mortality |
0.74 |
0.47-1.16 |
0.1 |
|
Clinical Failure |
0.4 |
0.2-0.76 |
<0.01 |
No significant differences were observed between the two treatment groups regarding adverse events, including Clostridium difficile infection, neutropenia, leukopenia, renal failure, hepatic failure, or skin rash.
Conclusion
This multicentre study represents the largest cohort of patients with MBL-type CPE bacteremia assessing the effectiveness of CAZAVI+ATM. Our findings indicate that this combination therapy lowers 14-day mortality and clinical failure rates compared to OAA. However, no significant difference was observed in 30-day mortality, possibly due to limited statistical power.
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