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. 2025 Jul 19:ciaf398.
doi: 10.1093/cid/ciaf398. Online ahead of print.

The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of Patients With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens

Mariya Huralska  1 , Jason M Pogue  2 , Michael Rybak  3 , Jacinda C Abdul-Mutakabbir  4 , Kyle Stamper  3 , Dror Marchaim  5 , Visanu Thamlikitkul  6 , Yehuda Carmeli  7 , Cheng-Hsun Chiu  8 , George Daikos  9 , Sorabh Dhar  10 , Emanuele Durante-Mangoni  11 , Achilles Gikas  12 , Anastasia Kotanidou  13 , Mical Paul  14 , Emmanuel Roilides  15 , Michael Samarkos  16 , Matthew Sims  17 , Dora Tancheva  18 , Sotirios Tsiodras  19 , Daniel H Kett  20 , Gopi Patel  21 , David P Calfee  22 , Leonard Leibovici  23 , Laura Power  24 , Silvia Munoz-Price  25 , Hamadullah Shaikh  1 , Laura Susick  26 , Katie Latack  26 , Christine Chiou  27 , George Divine  26 , Varduhi Ghazyaran  27 , Keith S Kaye  1
Affiliations

The Impact of Synergistic Therapy Between Colistin and Meropenem on Outcomes of Patients With Pneumonia or Bloodstream Infection Due to Carbapenem-Resistant Gram-Negative Pathogens

Mariya Huralska et al. Clin Infect Dis. .

Abstract

Background: Colistin, a last-line treatment for carbapenem-resistant Gram-negative bacilli (CRGNB), is frequently used in combination with meropenem because these agents often demonstrate in vitro synergy. Using data from the OVERCOME trial comparing colistin + meropenem to colistin + placebo for treatment of pneumonia or bloodstream infection due to CRGNB, we evaluated the impact of synergistic therapy on outcomes.

Methods: In vitro synergy testing between colistin and meropenem was conducted using 24-hour time-kill analysis; synergy was defined as >2-log reduction in colony-forming units/ml compared to the most active single agent. Patients receiving synergistic combination therapy were compared to patients receiving functional colistin monotherapy (colistin alone or combination therapy without synergy). Outcomes included mortality, clinical failure and microbiologic cure. Adjusted analyses controlled for variables on which randomization was stratified and confounders.

Results: 146 subjects receiving synergistic combination therapy and 261 subjects receiving functional monotherapy were included. Most had pneumonia (70%), CR Acinetobacter baumannii infection (79%) and were in intensive care (69%). A. baumannii was more common in those receiving synergistic combination therapy than functional monotherapy (p<0.001). Mortality rates were similar (38.3%, 41.4%, respectively). In adjusted analyses, synergistic combination therapy was associated with significantly lower clinical failure rates (55.3%, 64.3%, adjusted odds ratio [aOR] 0.62, p=0.049), with consistent findings in pneumonia (62.6%, 71.8%, aOR 0.55, p=0.04) and A. baumannii subgroups (57.4%, 69.4%, aOR 0.60, p=0.06). Microbiologic cure rates were similar.

Conclusions: Colistin-based, synergistic combination treatment with meropenem (compared to non-synergistic colistin-based therapy), was associated with decreased clinical failure, particularly in patients with pneumonia and A. baumannii.

Keywords: Acinetobacter baumannii; Colistin; OVERCOME; clinical failure; meropenem; mortality; synergy.

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