Microbiologic and Immunologic Evaluation of a Single High Dose of Azithromycin for Treatment of Experimental Mycoplasma pneumoniae Pneumonia

Abstract

We evaluated the efficacy of azithromycin therapy given as a single high dose or divided over 5 days for the treatment of mild experimental Mycoplasma pneumoniae pneumonia. Although both azithromycin regimens significantly reduced quantitative cultures, lung histopathology, and pulmonary cytokines and chemokines, there were no significant differences between the two regimens.It is unknown if antimycoplasmal therapy can be optimized utilizing high-dose azithromycin therapy. The purpose of the present study was to evaluate the microbiologic and immunologic efficacy of azithromycin therapy given as a single highdose compared with divided doses over 5 days in our murine Mycoplasma pneumoniae pneumonia model (6,7,10). We compared the activities of these two regimens on the clearance of M. pneumoniae from the respiratory tract and assessed their impact on the pulmonary immune response as measured by bronchoalveolar lavage cytokines and chemokines and by histologic inflammation.As previously described in full detail, 2-month-old female BALB/c mice (Charles River) were intranasally inoculated once (day 0) with 10 7 to 10 8 CFU of M. pneumoniae (ATCC 29342) in 50 l SP4 broth (4, 7, 10). Methoxyflurane, an inhaled anesthetic, was used for inoculum sedation. Animal guidelines were followed in accordance with the Institutional Animal Care and Research Advisory Committee. Azithromycin (Pfizer) for injection was dissolved in sterile water as per container instructions. Azithromycin was given 24 h after M. pneumoniae inoculation and administered subcutaneously at 50 mg/kg of body weight for only 1 day (dosage, 1 mg in 0.1 ml per mouse) or 10 mg/kg once daily for 5 days (dosage, 0.2 mg in 0.1 ml per mouse). The placebo group received sterile water for 5 days starting at 24 h after inoculation. We used 10 mg/kg as the conventional azithromycin dosage in this study as it has been used in other mouse studies and has been shown to be

Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia

“…To our knowledge, this is the first report that investigates the effect of tigecycline on cytokines and chemokines. The significantly reduced concentrations of IL-12 (p40/p70), IFN-␥, TNF-␣, IL-1␤, MIG, MIP-1␣, and IP-10 with tigecycline therapy is similar to what our laboratory has observed with therapy with other antimicrobial classes (macrolides, ketolides, and peptide deformylase inhibitors) in the treatment of M. pneumoniae experimental infection (10,15,31,32). The ability of antimicrobials to reduce pulmonary cytokines and chemokines in M. pneumoniae infection does not appear to be specific to a particular protein synthesis inhibitor class of antimicrobials.…”

“…Clinical studies have shown that therapy with macrolides or tetracyclines, which are considered the drugs of choice for M. pneumoniae (11), is able to reduce the morbidity of pneumonia, shorten the duration of symptoms, and decrease the recurrence of wheezing (5,7,8,12,25,26). However, even though treatment with macrolide, ketolide, and peptide deformylase inhibitor antimicrobials significantly improves pulmonary inflammation in animal M. pneumoniae pneumonia investigations, M. pneumoniae is not eradicated from the lungs in these in vivo investigations (10,15,31,32). Of note, in these experimental investigations examining the effects of antimicrobials for M. pneumoniae pneumonia, a disassociation is often found between the microbiologic response and the significant improvement observed in other markers of disease severity.…”

Treatment of experimental chronic pulmonary mycoplasmosis

“…In contrast to the current chronic investigation, for acute murine M. pneumoniae infection we have demonstrated significant microbiological, histological, immunological and pulmonary function improvement with antimicrobial therapy [9,[20][21][22]. However, it is unknown whether the pathogenic mechanisms of M. pneumoniae leading to chronic sequelae are the same as those mechanisms involved in acute disease.…”

The Impact of Steroids Given with Macrolide Therapy on ExperimentalMycoplasma pneumoniaeRespiratory Infection

“…Treating M. pneumoniae pneumonia with appropriate antibiotics, such as macrolides, has been found to significantly improve the course of disease in both animal models and human investigations [5] [6] [7] [8] [9] [10] [11] [12]. Observational data in both children and adults indicate that the addition of systemic steroids to antimicrobial therapy may improve the outcome of severe M. pneumoniae pneumonia.…”