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. 2024 May 8;11(6):ofae273.
doi: 10.1093/ofid/ofae273. eCollection 2024 Jun.

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

Mario Tumbarello  1   2 , Francesca Raffaelli  3 , Maddalena Giannella  4 , Gennaro De Pascale  5   6 , Antonio Cascio  7   8 , Francesco Giuseppe De Rosa  9 , Anna Maria Cattelan  10   11 , Alessandra Oliva  12 , Annalisa Saracino  13 , Matteo Bassetti  14   15 , Cristina Mussini  16 , Roberto Luzzati  17 , Alessandro Capone  18 , Liana Signorini  19 , Michele Bartoletti  20   21 , Margherita Sambo  1   2 , Loredana Sarmati  22 , Spinello Antinori  23 , Alessandra Mularoni  24 , Carlo Tascini  25 , Alberto Corona  26 , Renato Pascale  4 , Raffaella Rubino  8 , Silvia Corcione  9 , Maria Mazzitelli  10 , Gabriele Giuliano  2 , Antonio Lovecchio  17 , Davide Fiore Bavaro  13 , Marianna Meschiari  16 , Francesca Montagnani  1   2 , Massimiliano Fabbiani  1   2 , Ilaria De Benedetto  9 , Massimo Antonelli  5   6 , Mario Venditti  12 , Pierluigi Viale  4
Affiliations

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

Mario Tumbarello et al. Open Forum Infect Dis. .

Abstract

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.

Keywords: KPC-producing Klebsiella pneumoniae; bloodstream infection; carbapenemases; ceftazidime-avibactam resistance; meropenem-vaborbactam.

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Conflict of interest statement

Potential conflicts of interest. No reported conflicts of interest

Figures

Figure 1.
Figure 1.
Flow chart showing cohort enrollment.
Figure 2.
Figure 2.
Thirty-day mortality rates in patients receiving meropenem-vaborbactam alone, or in combination with other active antimicrobials, started as empiric therapy, or within 48 h from index culture or as second-line therapy. Results are shown for (A) patients with BSIs (n = 170) and LRTI (n = 104); (B) patients with complicated urinary tract infections (cUTIs, n = 25), and infections at other sites (n = 33).
Figure 3.
Figure 3.
Thirty-day mortality rates in patients receiving meropenem-vaborbactam for different infections depending on whether there is an underlying COVID-19 or not. BSI, bloodstream infection; LRTI, lower respiratory tract infection; cUTI, complicated urinary tract infection; Other, infections involving other sites.
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