Lung inflammatory pattern and antibiotic treatment in pneumonia

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.

Pneumolysin as a potential therapeutic target in severe pneumococcal disease

“…For purposes of comparison, the patients were categorised according to the inclusion or exclusion of a macrolide in their therapeutic regimens (n=23 vs 29, and n=9 vs 6 for the clinically unstable and stable groups, respectively) and cytokine concentrations in blood and BAL were measured at 72 hours following initiation of therapy. In the clinically unstable group, treatment with macrolide-containing antibiotic regimens was associated with substantial reductions in the concentrations of all 4 of the measured cytokines in both blood and BAL in comparison with patients receiving non-macrolide regimens 144. These differences achieved statistical significance in the case of IL-8 and IL-10 in blood and IL-6 and TNF-α in BAL.…”

“…141 In this context, it is noteworthy that excessive levels of type I interferons and IFN-γ, as may occur in the airways during influenza virus infection, have been reported to inhibit the phagocytic activities of alveolar macrophages, predisposing to secondary pneumococcal infection. 142,143 One of the very few clinical studies addressing the effects of macrolide therapy of acute lung infection on systemic and pulmonary indices of inflammation has recently been reported by Lorenzo et al 144 These authors, using a prospective, longitudinal study design, compared the effects of varying types of antimicrobial therapy on the concentrations of IL-6, IL-8, IL-10, and TNF-α in the circulation and lungs of older CAP patients (n=52) who had failed to respond satisfactorily, with those who had achieved clinical stability (n=15) following 72 hours of antimicrobial therapy. 144 however, that several mechanisms may underpin statin-mediated protection of eukaryotic cells against Ply, 145,146 such as interference with G-protein receptormediated intracellular signalling via inhibition of synthesis of other isoprenoids.…”

“…142,143 One of the very few clinical studies addressing the effects of macrolide therapy of acute lung infection on systemic and pulmonary indices of inflammation has recently been reported by Lorenzo et al 144 These authors, using a prospective, longitudinal study design, compared the effects of varying types of antimicrobial therapy on the concentrations of IL-6, IL-8, IL-10, and TNF-α in the circulation and lungs of older CAP patients (n=52) who had failed to respond satisfactorily, with those who had achieved clinical stability (n=15) following 72 hours of antimicrobial therapy. 144 however, that several mechanisms may underpin statin-mediated protection of eukaryotic cells against Ply, 145,146 such as interference with G-protein receptormediated intracellular signalling via inhibition of synthesis of other isoprenoids. 147 In addition to these in vitro studies, the protective potential of statins has also been demonstrated in a murine model of sickle cell disease in which significantly improved survival was observed in simvastatin-treated animals experimentally infected with the pneumococcus.…”

“…Pathogen identification was made in <50% of patients, with the pneumococcus identified as the causative pathogen in 21.7% and 27.6% of the former and latter groups respectively. Patients in the clinically unstable group were treated with fluoroquinolone (levofloxacin) monotherapy (n=6), or combination therapy with either a beta-lactam (ceftriaxone/cefotaxime) or co-amoxicillin/clavulanic acid azithromycin (n=23) or a beta-lactam + fluoroquinolone (n=8), while the remainder (n=15) received other types of therapy 144. For purposes of comparison, the patients were categorised according to the inclusion or exclusion of a macrolide in their therapeutic regimens (n=23 vs 29, and n=9 vs 6 for the clinically unstable and stable groups, respectively) and cytokine concentrations in blood and BAL were measured at 72 hours following initiation of therapy.…”

Initial Inflammatory Profile in Community-acquired Pneumonia Depends on Time since Onset of Symptoms

“…The interest in knowing the different patterns of inflammation and their related factors has led to a better understanding of the immunopathogenic process that occurs in CAP (15)(16)(17). The natural course of the infection and its systemic inflammatory pattern prior to diagnosis is rather unknown, although presumably it can differ depending on the duration of the infection and the distinct kinetics of inflammatory cytokine and biomarkers.…”