Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis

Abstract

Introduction Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. Methods Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). Results 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of − 0.069. Conclusion Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Antiinfektive Therapie in der Intensivmedizin

“…kos des Langzeitversterbens um ein Drittel gezeigt werden [18]. Über die letzten Jahre konnte mithilfe klinischer Studien gezeigt werden, dass eine kürzere Behandlungsdauer nicht von Nachteil für Patienten und Umfeld ist.…”

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP)

“…Even when Gram-positive sensitive pathogens usually cause CAP, guidelines suggest a broad-spectrum antibiotic empiric management in patients who require ICU 8 . In addition, dual therapy usually ensures coverage against atypical germs, improves the likelihood of initial adequate treatment, shortens the length of stay, and improves survival 20 , 32 – 34 . It is essential to point out that the prevalence of Pseudomonas aeruginosa as a causing pathogen of CAP in this cohort is 4.3% (88/2026) in all included patients and 18.2% (88/482) in those who had some identified micro-organisms which are comparable to the data generated in a multinational point prevalence study by Restrepo et alwhere they found a prevalence of 4.2% (133/3193) in the whole cohort and 11.3% (133/1173) among the culture-positive patients 14 .…”

“…The definition of CAP was based on the diagnostic criteria proposed by the ATS/IDSA guidelines 8 . The inclusion criteria were patients older than 18 years, requiring admission to the ICU with an ICD-9/ICD-10 code of pneumonia within the top ten diagnoses in the discharge note, as published previously 20 . Moreover, patients must have received cefepime or piperacillin/tazobactam, which started during the first 24 h of ICU admission and must be continued for at least 72 h. Patients with infectious diagnoses other than pneumonia and those with ventilator-associated pneumonia were excluded.…”

Antibacterial activity of cinnamon essential oil and its main component of cinnamaldehyde and the underlying mechanism

“…Frontiers in Pharmacology frontiersin.org Infection with P. aeruginosa is linked to various infectious diseases, including sepsis, endocarditis, pneumonia, urinary tract infections, peritonitis, and other health hazards (Jacobs et al, 2020;Reyes et al, 2023). Recognized as one of the most formidable nosocomial pathogens, the treatment of P. aeruginosa infection poses a challenge due to the restricted array of available antibiotics (Bassetti et al, 2018).…”

“…Pseudomonas aeruginosa ( P. aeruginosa ), a Gram-negative rod-shaped bacterium affiliated with the Pseudomonadaceae family, is distinguished for its pathogenicity, especially in individuals with compromised immune function, thus establishing it as a notable opportunistic human pathogen ( Stover et al, 2000 ; Sathe et al, 2023 ). It has been reported that P. aeruginosa may cause various serious infections, including sepsis, endocarditis, pneumonia, urinary tract infections, peritonitis, and other health hazards ( Reyes et al, 2023 ). In studies focused on the innate immunity of C. elegans , P. aeruginosa is commonly used as a representative pathogen to investigate host-pathogen interactions, infection, and anti-infection mechanisms ( Yu et al, 2018 ; Martineau et al, 2021 ).…”