Systemic Expression of Cytokine Production in Patients with Severe Pneumococcal Pneumonia: Effects of Treatment with a β-Lactam versus a Fluoroquinolone

Abstract

Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1␤, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-␣, for which lower concentrations were obtained at 120 h in the levofloxacin group (P ‫؍‬ 0.014). Basal oxygen saturation (P ‫؍‬ 0.034) and heart rate (P ‫؍‬ 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro-and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a ␤-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia

“…Previous studies have reported that an excess of proinflammatory cytokines is associated with poor prognosis of CAP [7][8][9][10][11][12][13][14]. Our results showed a similar relationship between high levels of cytokines and poor outcomes in the specific population with PP.…”

“…The possible beneficial effects of fluoroquinolones on the systemic expression of cytokine response when combined with -lactam therapy in patients with PP have not been previously explored, but our results suggest that their potential anti-inflammatory and immunomodulatory effects persist when combined with -lactam. A previous study [8] explored the effects of fluoroquinolone monotherapy in modulating the cytokine response in patients with PP, finding that it achieved a faster decrease in serum TNF- production at 120 hours postadmission than -lactam monotherapy.…”

“…Excessive cytokine response in patients with severe CAP has been linked with deleterious effects and poor prognosis [7][8][9][10][11][12][13][14].…”

Of mice and men: innate immunity in pneumococcal pneumonia

“…Only a few studies have been conducted in a homogeneous group of patients with documented pneumococcal pneumonia [59,67,68]. The observation period ranged from 0-12 h to 10 days from inclusion, with a variable period of daily determination of cytokine levels.…”

Time to Blood Culture Positivity as a Predictor of Clinical Outcomes and Severity in Adults with Bacteremic Pneumococcal Pneumonia

“…A higher bacterial load could lead to a higher inflammatory response when a β-lactam antibiotic is used [5]; this effect was observed in meningitis and sepsis [28] and was proposed as the key for benefits of corticosteroids, macrolides or fluoroquinoles in adjuvant treatment of pneumonia [29][30][31][32][33].…”