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.

Autor: Barbier F; Médecine Intensive Réanimation, Centre Hospitalier Universitaire d'Orléans, Orléans, France. francois.barbier@chu-orleans.fr.; Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire d'Orléans, 14, Avenue de L'Hôpital, 45000, Orléans, France. francois.barbier@chu-orleans.fr., Dupuis C; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Gabriel Montpied, Clermont-Ferrand, France., Buetti N; Infection Control Programme, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.; IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France., Schwebel C; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Grenoble - Alpes, La Tronche, France., Azoulay É; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris, France., Argaud L; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Edouard Herriot, Hospices Civils de Lyon, Lyon, France., Cohen Y; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Avicenne, Assistance Publique - Hôpitaux de Paris, Bobigny, France., Hong Tuan Ha V; Réanimation Médicale, Grand Hôpital de L'Est Parisien, Meaux, France., Gainnier M; Réanimation des Urgences, Centre Hospitalier Universitaire La Timone, Assistance Publique - Hôpitaux de Marseille, Marseille, France., Siami S; Réanimation Polyvalente, Centre Hospitalier Sud-Essonne, Étampes, France., Forel JM; Médecine Intensive Réanimation, Centre Hospitalier Universitaire Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France., Adrie C; Réanimation Polyvalente, Centre Hospitalier Delafontaine, Saint-Denis, France., de Montmollin É; Service de Médecine Intensive et Réanimation Infectieuse, Centre Hospitalier Universitaire Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris, Paris, France., Reignier J; Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France., Ruckly S; Département de Biostatistiques, OutcomeRéa, Paris, France., Zahar JR; IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France.; Département de Microbiologie Clinique, Centre Hospitalier Universitaire Avicenne, Assistance Publique - Hôpitaux de Paris, Bobigny, France., Timsit JF; IAME UMR 1137, INSERM, Université Paris-Cité, Paris, France.; Service de Médecine Intensive et Réanimation Infectieuse, Centre Hospitalier Universitaire Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris, Paris, France.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2024 Jan 03; Vol. 28 (1), pp. 10. Date of Electronic Publication: 2024 Jan 03.
DOI: 10.1186/s13054-023-04792-0
Abstrakt: Key Messages: In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy.
Background: The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria.
Methods: We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock.
Results: Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results.
Conclusions: Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.
(© 2024. The Author(s).)
Databáze: MEDLINE
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