# Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

**Authors:** Mario Tumbarello, Francesca Raffaelli, Maddalena Giannella, Gennaro De Pascale, Antonio Cascio, Francesco Giuseppe De Rosa, Anna Maria Cattelan, Alessandra Oliva, Annalisa Saracino, Matteo Bassetti, Cristina Mussini, Roberto Luzzati, Alessandro Capone, Liana Signorini, Michele Bartoletti, Margherita Sambo, Loredana Sarmati, Spinello Antinori, Alessandra Mularoni, Carlo Tascini, Alberto Corona, Renato Pascale, Raffaella Rubino, Silvia Corcione, Maria Mazzitelli, Gabriele Giuliano, Antonio Lovecchio, Davide Fiore Bavaro, Marianna Meschiari, Francesca Montagnani, Massimiliano Fabbiani, Ilaria De Benedetto, Massimo Antonelli, Mario Venditti, Pierluigi Viale

PMC · DOI: 10.1093/ofid/ofae273 · 2024-05-08

## TL;DR

This study examines the effectiveness of meropenem-vaborbactam in treating KPC-Kp infections and identifies factors that predict patient mortality.

## Contribution

The study provides real-world evidence on the efficacy of meropenem-vaborbactam for KPC-Kp infections and identifies key mortality predictors.

## Key findings

- 30-day mortality rate was 31.6% among patients treated with meropenem-vaborbactam for KPC-Kp infections.
- Septic shock, high comorbidity index, dialysis, and concomitant COVID-19 were independently associated with higher mortality.
- Early administration of meropenem-vaborbactam within 48 hours was linked to lower mortality.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Chemicals:** meropenem-vaborbactam (PubChem CID 86298703), ceftazidime-avibactam (PubChem CID 90643431), fosfomycin (PubChem CID 441029), tigecycline (PubChem CID 54686904), gentamicin (PubChem CID 3467)
- **Diseases:** COVID-19 (MONDO:0100096)
- **Species:** Klebsiella pneumoniae (taxon 573)

## Full-text entities

- **Diseases:** respiratory tract infections (MESH:D012141), KPC-Kp Infections (MESH:D007710), Mortality (MESH:D003643), bloodstream infections (MESH:D018805), COVID-19 (MESH:D000086382), urinary tract infections (MESH:D014552), infection (MESH:D007239), septic shock (MESH:D012772)
- **Chemicals:** tigecycline (MESH:D000078304), gentamicin (MESH:D005839), fosfomycin (MESH:D005578), ceftazidime-avibactam (MESH:C000595613), Meropenem Vaborbactam (MESH:C000654127)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11161898/full.md

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Source: https://tomesphere.com/paper/PMC11161898