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Meta-Analysis
. 2024 Nov 25;28(1):387.
doi: 10.1186/s13054-024-05159-9.

Inhaled antibiotics for treating pneumonia in invasively ventilated patients in intensive care unit: a meta-analysis of randomized clinical trials with trial sequential analysis

Nicolò Sella #  1 , Tommaso Pettenuzzo #  1 , Alessandro De Cassai  2 , Francesco Zarantonello  1 , Sabrina Congedi  2 , Andrea Bruni  3 , Eugenio Garofalo  3 , Honoria Ocagli  4 , Dario Gregori  4 , Federico Longhini  3 , Paolo Navalesi #  5   6 , Annalisa Boscolo #  1   2   7 ; PADOVA ICU Group
Collaborators, Affiliations
Meta-Analysis

Inhaled antibiotics for treating pneumonia in invasively ventilated patients in intensive care unit: a meta-analysis of randomized clinical trials with trial sequential analysis

Nicolò Sella et al. Crit Care. .

Abstract

Background: The use of inhaled antibiotics for treating pneumonia in invasively ventilated patients offers a direct approach, allowing for high local concentrations of the drug in the lower respiratory tract while simultaneously reducing systemic toxicity. However, the real efficacy and safety of nebulized antibiotics remain unclear. The aim of the present is to assess among critically adult patients with pneumonia and invasive ventilation, whether receiving adjuvant inhaled antibiotics improves the rate of microbiological eradication.

Methods: A comprehensive literature search of randomized clinical trials (RCTs) was conducted (from inception until September 20, 2024, PROSPERO-CRD592906) across Medline, Embase, and Scopus. Randomized controlled trials, enrolling intensive care units (ICU) patients with pneumonia and comparing nebulized antimicrobial therapy (inhaled group) with intravenous antimicrobial treatment or intravenous antimicrobial therapy plus inhaled placebo (control group), were included. The primary outcome was the rate of microbiological eradication after treatment. Secondary outcomes were the rate of clinical recovery, the incidence of drug-related adverse events, ICU and hospital mortality. A qualitative analysis was conducted according to the GRADE framework. Data were pooled using an odds-ratio analysis. The heterogeneity and reliability of our results were evaluated using the I2-statistic and trial sequential analysis (TSA), respectively.

Results: A total of 11 RCTs (1472 patients) met the inclusion criteria. Compared to controls, the use of adjuvant inhaled antibiotics determined a greater rate of microbiological eradication (OR 2.63, 95% CI 1.36-5.09; low certainty of evidence). The TSA confirmed the reliability of our primary outcome. Moreover, nebulized antibiotics increased the risk of bronchospasm (OR 3.15, 95% CI 1.33-7.47; high evidence), while nephrotoxicity, clinical recovery, ICU and hospital survival (either in the case of pneumonia caused by MDR bacteria or not) were not different between groups.

Conclusions: In conclusion, compared to the sole intravenous therapy, the use of adjuvant inhaled antibiotics for treatment of pneumonia in invasively ventilated critically ill patients was associated with a greater incidence of microbiological eradication (low GRADE and high risk of publication bias), but not with clinical recovery and survival.

Keywords: Antibiotics; Infection; Inhaled; Multi-drug resistant; Multi-drug resistant organism; Nebulized; Treatment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow-chart
Fig. 2
Fig. 2
Manuscript quality assessment using risk of bias (ROB)-2 tool
Fig. 3
Fig. 3
Primary outcome and TSA. Abbreviations: OR, odds ratio; CI, confidential interval; TSA, trial sequential analysis
Fig. 4
Fig. 4
Most relevant secondary outcomes. Abbreviations: OR, odds ratio; CI, confidential interval
See this image and copyright information in PMC

References

    1. Fernando SM, Tran A, Cheng W, Klompas M, Kyeremanteng K, Mehta S, et al. Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis. Intensive Care Med. 2020;46(6):1170–9. - PMC - PubMed
    1. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–9. - PubMed
    1. Zaragoza R, Vidal-Cortés P, Aguilar G, Borges M, Diaz E, Ferrer R, et al. Update of the treatment of nosocomial pneumonia in the ICU. Crit Care Lond Engl. 2020;24(1):383. - PMC - PubMed
    1. Dudeck MA, Weiner LM, Allen-Bridson K, Malpiedi PJ, Peterson KD, Pollock DA, et al. National healthcare safety network (NHSN) report, data summary for 2012 Device-associated module. Am J Infect Control. 2013;41(12):1148–66. - PMC - PubMed
    1. Mehta AB, Syeda SN, Wiener RS, Walkey AJ. Epidemiological trends in invasive mechanical ventilation in the United States: a population-based study. J Crit Care. 2015;30(6):1217–21. - PMC - PubMed

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