Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial

Abstract

Background The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator‑associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP. Methods Patients with PA-VAP randomized in the iDIAPASON trial (short-duration—8 days vs. long-duration—15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan–Meier survival curves and compared between groups using a Log-rank test. Results A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission. Conclusions Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group. Trial registration: NCT02634411, Registered 15 December 2015.

Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study

“…Our data argue against this hypothesis. First, and in concordance with the available evidence [7,10,12,38], combination therapy was not associated with a greater likelihood of clinical cure, including in patients infected with non-fermenting Gram-negative pathogens or in those receiving second agents with substantial lung bioavailability (i.e., fluoroquinolones or cotrimoxazole). Conversely, there was a trend toward a higher clinical cure rate in the single-drug group; moreover, receiving combination therapy for 3 days or more was negatively linked with the likelihood of clinical cure in adjusted analyses.…”

“…Companion drugs, mostly aminoglycosides (72.5%) and fluoroquinolones (21.3%), were administered for a median duration of 3 (2-5) days. The total duration of antimicrobial therapy was longer in the combination group than in the singledrug group (8.5 [6][7][8][9][10][11][12][13] versus 7 [5][6][7][8][9][10] days, P = 0.04). Initial dosing schemes are exposed in Additional file 1: Table S2.…”

“…Beyond the enhanced probability of administering at least one adequate agent in patients at-risk for multidrug-resistant bacteria (MDRB), combination therapy (usually a β-lactam plus an aminoglycoside or a fluoroquinolone) could conceptually improve bacterial clearance when both drugs are active against the causative pathogen, thereby hastening infection resolution and preventing the emergence of resistant mutants [6]. Nevertheless, most of randomized trials and observational studies addressing this issue reported no improvement in survival, treatment success rate or others patient-centered outcomes with combination therapy [7][8][9], including in patients with pneumonia due to potentially difficult-totreat pathogens such as Pseudomonas aeruginosa [10][11][12]. In addition, combination therapy has been linked with an increased hazard of adverse events, especially acute kidney injury (AKI) when aminoglycosides are used as companion drugs [13,14].…”

Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapies

“…The prevalence of MDR P. aeruginosa VAP is reported to be generally high (33%) (Li et al, 2024). The crude mortality rate for P. aeruginosa VAP has been estimated at 42.1-87% even in patients receiving appropriate antimicrobial therapy (Foucrier et al, 2023). In addition to its impact on VAP, P. aeruginosa is among the top microorganisms responsible for healthcare respiratory infections.…”

Diagnosis and antibiotic therapy of nosocomial pneumonia in adults: from recommendations to real practice. A review

“…В недавно опубликованном исследовании A. Foucrier и соавт. при лечении пациентов с НПИВЛ, вызванной P. aeruginosa, различий в эффективности моно-и комбинированной АБТ не наблюдалось [34]. Комбинации АБ скорее могут рассматриваться как вынужденная мера и использоваться при невозможности в рамках монотерапии перекрыть весь спектр наиболее актуальных возбудителей НП, среди которых доля поли-и экстремально резистентных энтеробактерий, P. aeruginosa и Acinetobacter spp.…”