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Macrolides for the therapy of nosocomial infections
Maria Mouktaroudi1, Evangelos J Giamarellos-Bourboulis
14th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
Purpose Of Review:
Nosocomial infections are an emerging threat. Available solutions are limited due to the multidrug-resistance pattern of the pathogens. Macrolides modulate the immune function of the host and may be active in this setting.
Recent Findings:
Findings of in-vitro and experimental animal studies are presented. Clinical studies of community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP) are described.
Summary:
Macrolides decrease production of proinflammatory cytokines by circulating monocytes and by alveolar macrophages and decrease apoptosis of circulating lymphocytes in animal models of acute infections. They also inhibit gene expression of proteins participating in quorum sensing of Pseudomonas aeruginosa. Retrospective cohort studies indicate that addition of a macrolide significantly improves outcome in severe CAP. One randomized, double-blind, clinical study is available. This involves patients with VAP allocated to placebo or intravenous clarithromycin 1 g once daily for 3 days. Clarithromycin treatment significantly decreased time to resolution of VAP and time until weaning from mechanical ventilation. The described findings are promising for the use of macrolides in nosocomial infections.
Insights
Macrolides show promise in combating nosocomial infections by modulating host immunity and inhibiting bacterial virulence. Clinical studies suggest macrolide use improves outcomes in severe community-acquired pneumonia and ventilator-associated pneumonia.
Area of Science:
- Infectious Diseases
- Immunology
- Pharmacology
Background:
- Nosocomial infections pose a significant and growing threat.
- Multidrug-resistant pathogens limit current treatment options.
- Macrolides possess immunomodulatory properties with potential therapeutic applications.
Purpose of the Study:
- To review the role of macrolides in treating nosocomial infections.
- To explore macrolide mechanisms against multidrug-resistant pathogens.
- To evaluate clinical evidence for macrolide efficacy in hospital-acquired infections.
Main Methods:
- Review of in-vitro and experimental animal studies.
- Analysis of clinical studies on community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP).
- Examination of a randomized, double-blind trial of clarithromycin for VAP.
Main Results:
- Macrolides reduce proinflammatory cytokine production and lymphocyte apoptosis in animal models.
- Macrolides inhibit quorum sensing in Pseudomonas aeruginosa.
- Retrospective studies and a randomized trial show improved outcomes with macrolides in severe CAP and VAP, including reduced resolution time and faster mechanical ventilation weaning.
Conclusions:
- Macrolides demonstrate immunomodulatory and anti-virulence effects relevant to nosocomial infections.
- Clinical evidence supports the beneficial use of macrolides in severe CAP and VAP.
- Macrolides represent a promising therapeutic strategy for managing hospital-acquired infections.
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