# Treatment Options for Critically Ill Patients with Infections Caused by Metallo-Beta-Lactamase-Producing Klebsiella pneumoniae

## TL;DR

The study compares treatment options for critically ill patients infected with drug-resistant Klebsiella pneumoniae and finds no significant difference in outcomes between combination therapies and standard treatment.

## Contribution

The study evaluates the efficacy of CAZ-AVI + ATM and DCT therapies for MBL-producing K. pneumoniae infections in ICU patients.

## Key findings

- No significant differences in SOFA scores, ventilation duration, ICU length of stay, or mortality between treatment groups.
- SOFA score at day 1 and medical cause of admission were independent risk factors for mortality.
- CAZ-AVI + ATM and DCT showed similar efficacy to other appropriate antibiotic therapies.

## Abstract

Background/Objectives: Antimicrobial resistance (AMR) has increased significantly over the years, contributing to a real challenge in the intensive care unit (ICU). The emergence of metallo-beta-lactamases (MBLs) has contributed to the protection of pathogens against all current beta-lactam/beta-lactamase inhibitors (BL/BLIs), including the newer ceftazidime–avibactam (CAZ-AVI), meropenem–vaborbactam, and imipenem–relebactam. Treatment of such infections is challenging. In vitro and clinical data suggest that combinations of CAZ-AVI with aztreonam (ATM) and the use of two different carbapenems (double carbapenem therapy, DCT) may be an option for MBL-producing pathogens. The aim of our study was to evaluate the effectiveness of the combination CAZ-AVI + ATM and the effectiveness of DCT against MBL-producing K. pneumoniae infections in the critically ill, mechanically ventilated patients. Methods: This is a retrospective study conducted in the two ICUs of hospitals in central Greece. Mechanically ventilated patients admitted to the ICU were included in the study if they developed an infection by MBL-producing K. pneumoniae. Patients were divided into three groups: the first one consisted of patients who were treated with CAZ-AVI plus ATM (CAZ-AVI + ATM group), and the second group consisted of patients who received DCT (DCT group). The third group included patients who received appropriate antibiotic therapy other than CAZ-AVI + ATM and DCT (control group). The primary outcome of the study was the evolution of the sequential organ failure assessment (SOFA) score, and secondary outcomes were duration of mechanical ventilation (MV), ICU length of stay (LOS), and, finally, ICU mortality. Results: 108 patients were included in the study. 35 (32%) in the CAZ-AVI + ATM group, 31 (29%) in the DCT group, and the remaining 42 (39%) patients in the control group. The SOFA score was not statistically different on day 1, day 4, and day 7 of the infection among the three groups (p > 0.05). Duration of MV and ICU LOS were also similar. Finally, mortality did not differ between the groups [20 patients (57.1%) vs. 18 (58.1%) vs. 25 (59.5%) for CAZ-AVI + ATM, DCT and control group, respectively, p = 0.98]. Comparison between survivors and non-survivors revealed that independent risk factors for mortality were SOFA score at day 1 of infection and medical cause of admission (p < 0.05). Conclusions: Treatment with CAZ-AVI + ATM or DCT presented similar efficacy with appropriate antibiotic therapy for infections caused by MBL-producing K. pneumoniae strains. Larger studies are required to confirm the findings.