Abstract
BackgroundIn community-acquired pneumonia host inflammatory response against the causative microorganism is necessary for infection resolution. However an excessive response can have deleterious effects. In addition to antimicrobial effects, macrolide antibiotics are known to possess immunomodulatory properties.We aimed to evaluate inflammatory cytokine profiles – both locally (bronchoalveolar lavage) and systemically (blood) – in community-acquired pneumonia admitted patients after at least 72 hours of antibiotic treatment (with and without macrolide containing regimens) and requiring bronchoscopic examination for inadequate response due to infection progression and/or lack of clinical stability.MethodsA prospective study was performed on 52 admitted patients who developed an inadequate response after 72 hours of antibiotic treatment - non-responders community-acquired pneumonia - (blood and bronchoalveolar lavage), and two control groups: 1) community-acquired pneumonia control (blood) and 2) non-infection control (blood and bronchoalveolar lavage). Cytokine profiles (interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor α and clinical outcomes were assessed.ResultsNon–responders patients treated with macrolide containing regimens showed significantly lower levels of IL-6 and TNF-α in bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those patients treated with non-macrolide regimens. Clinical outcomes showed that patients treated with macrolide regimens required fewer days to reach clinical stability (p < 0.01) and shorter hospitalization periods (p < 0.01).ConclusionsAfter 72 hours of antibiotic effect, patients who received macrolide containing regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic compartments along with faster stabilization of infectious parameters.
Highlights
The majority of hospitalized community-acquired pneumonia (CAP) patients respond favorably to antibiotic treatment but around 10% develop an inadequate response to treatment that leads to a poorer prognosis [1]
The aims of the present study were to investigate 1) lung and systemic inflammatory cytokine profiles in hospitalized CAP patients after at least 72 hours of antibiotic treatment and who required bronchoscopic examination owing to an inadequate response consequent upon infection progression and/or lack of clinical stability; and 2) the impact of macrolide containing regimens treatment on clinical resolution parameters
The most important findings of our study are: 1) Levels of IL-6 and tumour necrosis factor α (TNF-α) in Bronchoalveolar lavage (BAL) and of IL-8 and IL-10 in blood were significantly lower in Non-responders CAP (NCAP) patients who received macrolide containing regimens than in those treated with non-macrolide regimens; and 2) there were improved clinical outcomes, such as earlier clinical stability and shorter length of hospital stay (LOS), in patients who received macrolide containing regimens
Summary
The majority of hospitalized community-acquired pneumonia (CAP) patients respond favorably to antibiotic treatment but around 10% develop an inadequate response to treatment that leads to a poorer prognosis [1]. The immunomodulatory effects of macrolides benefit the host due to their capacity to temper the production of inflammatory cytokines [5,6,7]. Some recent observational studies have reported better outcomes in severe CAP cases [8,9,10,11,12], when antibiotics regimens contained macrolides. In community-acquired pneumonia host inflammatory response against the causative microorganism is necessary for infection resolution. We aimed to evaluate inflammatory cytokine profiles – both locally (bronchoalveolar lavage) and systemically (blood) – in community-acquired pneumonia admitted patients after at least 72 hours of antibiotic treatment (with and without macrolide containing regimens) and requiring bronchoscopic examination for inadequate response due to infection progression and/or lack of clinical stability
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