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Treatment Options for Critically Ill Patients with Infections Caused by Metallo-Beta-Lactamase-Producing Klebsiella
Konstantinos Mantzarlis1, Vassilios Vazgiourakis1, Dimitrios Papadopoulos2
1Department of Critical Care, University Hospital of Larissa, School of Medicine, University of Thessaly, 41110 Larissa, Thessaly, Greece.
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.
Insights
Ceftazidime-avibactam plus aztreonam (CAZ-AVI + ATM) and double carbapenem therapy (DCT) showed similar effectiveness to other antibiotics for treating metallo-beta-lactamase (MBL) producing Klebsiella pneumoniae infections in ICUs.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Antimicrobial Resistance
Background:
- Antimicrobial resistance (AMR) poses a significant challenge in intensive care units (ICUs).
- Metallo-beta-lactamases (MBLs) confer resistance to nearly all beta-lactam antibiotics, including newer agents like ceftazidime-avibactam (CAZ-AVI).
- Treating infections caused by MBL-producing pathogens is difficult, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the effectiveness of CAZ-AVI combined with aztreonam (ATM) against MBL-producing Klebsiella pneumoniae infections.
- To assess the efficacy of double carbapenem therapy (DCT) in critically ill, mechanically ventilated patients with MBL-producing K. pneumoniae infections.
- To compare these novel treatment strategies against standard appropriate antibiotic therapy.
Main Methods:
- Retrospective study in two ICUs in Greece involving mechanically ventilated patients with MBL-producing K. pneumoniae infections.
- Patients were categorized into three groups: CAZ-AVI + ATM, DCT, and a control group receiving other appropriate antibiotics.
- Primary outcome: Sequential Organ Failure Assessment (SOFA) score evolution. Secondary outcomes: duration of mechanical ventilation, ICU length of stay, and ICU mortality.
Main Results:
- No statistically significant differences were observed in SOFA scores, duration of mechanical ventilation, or ICU length of stay among the three groups.
- ICU mortality rates were similar across all groups: 57.1% for CAZ-AVI + ATM, 58.1% for DCT, and 59.5% for the control group (p = 0.98).
- Independent risk factors for mortality included SOFA score at day 1 of infection and medical cause of admission.
Conclusions:
- Combination therapy with CAZ-AVI + ATM and DCT demonstrated comparable efficacy to appropriate antibiotic therapy for MBL-producing K. pneumoniae infections in critically ill patients.
- These findings suggest that CAZ-AVI + ATM and DCT are viable treatment options for challenging MBL-producing infections.
- Larger prospective studies are warranted to confirm these results and further elucidate optimal treatment strategies.
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