This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.

Incision and drainage without adjunctive antibiotic therapy was effective management of CA-MRSA skin and soft tissue abscesses with a diameter of <5 cm in immunocompetent children.

Mycoplasma pneumoniae produces an ADP-ribosylating and vacuolating toxin known as the CARDS (Community Acquired Respiratory Distress Syndrome) toxin that has been shown to be cytotoxic to mammalian cells in tissue and organ culture. In this study we tested the ability of recombinant CARDS (rCARDS) toxin to elicit changes within the pulmonary compartment in both mice and baboons. Animals responded to a respiratory exposure to rCARDS toxin in a dose and activity-dependent manner by increasing the expression of the pro-inflammatory cytokines IL-1α, 1β, 6, 12, 17, TNF-α and IFN-γ. There was also a dose-dependent increase in several growth factors and chemokines following toxin exposure including KC, IL-8, RANTES, and G-CSF. Increased expression of IFN-γ was observed only in the baboon; otherwise, mice and baboons responded to CARDS toxin in a very similar manner. Introduction of rCARDS toxin to the airways of mice or baboons resulted in a cellular inflammatory response characterized by a dose-dependent early vacuolization and cytotoxicity of the bronchiolar epithelium followed by a robust peribronchial and perivascular lymphocytic infiltration. In mice, rCARDS toxin caused airway hyper-reactivity two days after toxin exposure as well as prolonged airway obstruction. The changes in airway function, cytokine expression, and cellular inflammation correlate temporally and are consistent with what has been reported for M. pneumoniae infection. Altogether, these data suggest that the CARDS toxin interacts extensively with the pulmonary compartment and that the CARDS toxin is sufficient to cause prolonged inflammatory responses and airway dysfunction.

Burkholderia thailandensis is closely related to Burkholderia pseudomallei , the causative agent of melioidosis. It is generally considered avirulent and previously has been reported to occur only in Southeast Asia. We report the first case of pneumonia and septicemia caused by B. thailandensis in the United States.

Because chronic Mycoplasma pneumoniae respiratory infection is hypothesized to play a role in asthma, the potential of M. pneumoniae to establish chronic respiratory infection with associated pulmonary disease was investigated in a murine model. BALB/c mice were intranasally inoculated once with M. pneumoniae and examined at 109, 150, 245, 368, and 530 days postinoculation. M. pneumoniae was detected in bronchoalveolar lavage fluid by culture or PCR in 70 and 22% of mice at 109 and 530 days postinoculation, respectively. Lung histopathology was normal up to 368 days postinoculation. At 530 days, however, 78% of the mice inoculated with M. pneumoniae demonstrated abnormal histopathology characterized by peribronchial and perivascular mononuclear infiltrates. A mean histopathologic score (HPS) at 530 days of 5.1 was significantly greater (P < 0.01) than that for controls (HPS score of 0). Serum anti-M. pneumoniae immunoglobulin G was detectable in all of the mice inoculated with M. pneumoniae and was inversely correlated with HPS (r ‫؍‬ ؊0.95, P ‫؍‬ 0.01) at 530 days postinoculation. Unrestrained whole-body plethysmography measurement of enhanced pause revealed significantly elevated airway methacholine reactivity in M. pneumoniae-inoculated mice compared with that in controls at 245 days (P ‫؍‬ 0.03) and increased airway obstruction at 530 days (P ‫؍‬ 0.01). Murine M. pneumoniae respiratory infection can lead to chronic pulmonary disease characterized by airway hyperreactivity, airway obstruction, and histologic inflammation.While Mycoplasma pneumoniae is known to be a significant cause of acute respiratory illness in children and adults, the significance of chronic infection is undetermined. In humans, M. pneumoniae is reported to commonly be detectable by culture of the respiratory tract for up to several months after clinical recovery from acute pneumonia (5). Even after therapy with effective antibiotics, such as erythromycin or tetracycline, M. pneumoniae can still be cultured from respiratory secretions (6, 18). After receiving macrolides for 14 days, children have been found to have pulmonary structural abnormalities, by high-resolution computed tomography, suggestive of small airway obstruction 1 to 2 years after M. pneumoniae pneumonia with significantly increased frequency compared with that of controls. In these children, a greater antimycoplasma antibody titer was a significant risk factor for the development of abnormal pulmonary sequelae, suggesting that the host immune response may play a pathogenic role in this condition (10). The duration of M. pneumoniae infection in the human lower respiratory tract after acute pneumonia as determined by a method more sensitive than culture, such as PCR, has not been investigated in a controlled fashion.Of potentially greater relevance, chronic M. pneumoniae respiratory infection has been hypothesized to play a role in asthma. By PCR, M. pneumoniae has been detected in the lower airways of chronic, stable asthmatics with significantly greater frequency than in ...

Because Mycoplasma pneumoniae is hypothesized to play an important role in reactive airway disease/asthma, a comprehensive murine model of M. pneumoniae lower respiratory infection was established. BALB/c mice were intranasally inoculated once with M. pneumoniae and sacrificed at 0 to 42 days postinoculation. All mice became infected and developed histologic evidence of acute pulmonary inflammation, which cleared by 28 days postinoculation. By contrast, M. pneumoniae persisted in the respiratory tract for the entire 42 days studied. Tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), KC (functional IL-8), MIP-1␣, and MCP-1/JE concentrations were significantly elevated in bronchoalveolar lavage samples, whereas IL-4 and IL-10 concentrations were not significantly elevated. Pulmonary airflow resistance, as measured by plethysmography, was detected 1 day postinoculation and persisted even after pulmonary inflammation had resolved at day 28. Serum anti-M. pneumoniae immunoglobulin G titers were positive in all mice by 35 days. This mouse model provides a means to investigate the immunopathogenesis of M. pneumoniae infection and its possible role in reactive airway disease/asthma.

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.

Background Systemic steroids have been advocated in addition to antimicrobial therapy for severe Mycoplasma pneumoniae pneumonia. We evaluated the efficacy of clarithromycin, dexamethasone, or combination therapy for M. pneumoniae respiratory infection. Methods Mice infected with M. pneumoniae were treated with clarithromycin, dexamethasone, combined clarithromycin/dexamethasone, or placebo daily; mice were evaluated at baseline and after 1, 3, and 6 days of therapy. Outcome variables included M. pneumoniae culture; lung histopathologic score (HPS); bronchoalveolar lavage cytokine, chemokine and growth factor concentrations. Results Clarithromycin monotherapy resulted in the greatest reductions in M. pneumoniae concentrations. After 3 days of treatment, combination therapy significantly reduced lung HPS compared with placebo, clarithromycin, and dexamethasone alone; while after 6 days of therapy, clarithromycin alone and combination therapy significantly reduced lung HPS compared with placebo. IL-12 p40, RANTES, MCP-1, and KC were significantly lower in mice treated with clarithromycin alone and/or combination therapy compared with dexamethasone alone and/or placebo; combination therapy resulted in a significantly greater reduction than clarithromycin alone for IL-12 p40 and RANTES. Conclusions While monotherapy with clarithromycin had the greatest effect on reducing concentrations of M. pneumoniae, combination therapy had the greatest effect on decreasing cytokines and chemokines, as well as pulmonary histologic inflammation.