Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study
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Mario Tumbarello1,2, Francesca Raffaelli3, Maddalena Giannella4
1Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Background:
Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.
Methods:
We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.
Results:
The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.
Conclusions:
Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.
Insights
Meropenem-vaborbactam effectively treats KPC-producing Klebsiella pneumoniae infections, including those resistant to other drugs. Early administration within 48 hours improves survival rates in severe cases.
Area of Science:
- Infectious Diseases
- Antimicrobial Resistance
- Clinical Pharmacology
Background:
- Meropenem-vaborbactam offers a new treatment for KPC-producing Klebsiella pneumoniae (KPC-Kp) infections.
- This includes KPC-Kp strains resistant to ceftazidime-avibactam.
Purpose of the Study:
- To analyze the real-world use and outcomes of meropenem-vaborbactam in KPC-Kp infections.
- To identify factors associated with 30-day mortality in patients treated with meropenem-vaborbactam.
Main Methods:
- Retrospective analysis of observational data from 19 Italian hospitals.
- Included 342 adult patients with KPC-Kp infections treated with meropenem-vaborbactam for ≥24 hours.
- Used crude and propensity-weighted Cox regression models to assess mortality risk factors.
Main Results:
- The 30-day mortality rate was 31.6%.
- Independent predictors of mortality included septic shock, high Charlson comorbidity index, dialysis, and COVID-19.
- Early meropenem-vaborbactam administration (within 48 hours) was associated with lower mortality.
Conclusions:
- Meropenem-vaborbactam demonstrates efficacy in severe KPC-Kp infections.
- The drug is effective even when used as monotherapy.
- Early treatment initiation is crucial for improving patient outcomes.
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