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Bacterial superinfection and associated lung immunopathology are major contributors to hospitalizations and mortality after influenza. However, the underlying mechanisms and effective intervention strategies remain poorly defined. By using a model of influenza and pneumococcal superinfection, we found that dual-infected animals experienced rapid weight loss and succumbed to infection. Bacterial outgrowth, dysregulated cytokines, including keratinocyte-derived chemokine and macrophage inflammatory protein 2, and severe lung neutrophilia and immunopathology were linked to the poor clinical outcome. In vivo neutralization of highly induced macrophage inflammatory protein 2 did not affect clinical outcome, bacterial loads, or lung immunopathology. On the other hand, in vivo neutrophil depletion did not alter the clinical outcome and bacterial burden, although it moderately improved lung immunopathology. Treatment with a bacteriostatic antibiotic, azithromycin, alone significantly improved clinical outcome and bacterial clearance, but failed to reduce lung immunopathology. In comparison, treatment with a global inflammation inhibitor, dexamethasone, alone failed to alter clinical outcome, bacterial infection, and immunopathology, despite its moderate reducing effects on neutrophilic and cytokine responses. In contrast, combined treatment with both azithromycin and dexamethasone best improved clinical outcome, bacterial clearance, lung cellular and cytokine responses, and immunopathology. Our study suggests that marked improvement of clinical outcome and lung immunopathology caused by bacterial superinfection requires the control of both bacterial infection and aberrant host immune responses. Our findings hold implications in clinical management for influenza-associated bacterial superinfections.
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Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31%) participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G), Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4%) were observed to ceftriaxone, tetracycline and cotrimoxazole.
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Parental consent was obtained for 2849 (86.9%) of the 3278 matriculated students in grades 7 through 12. Fifty-one parents (1.6%) returned consent forms refusing permission for their child to participate in this screening and treatment program. The remaining 378 (11.5%) could not be reached by mail or telephone. Among all students with consent, 1933 (67.8% of those consented and 59.0% of those matriculated) were tested. Girls were less likely to be tested than boys (861/1363 [63. 2%] vs 1072/1465 [73.2%]). The overall prevalence of C trachomatis was 6.5%, with rates among girls more than twice that of boys (9.7% vs 4.0%). Generally, rates of infection increased with age. The prevalence rates among boys were for 7th grade, 2/208 (1%); 8th grade, 2/196 (2%); 9th grade, 10/236 (4.2%); 10th grade, 12/185 (6. 5%); 11th grade, 8/146 (5.5%); and 12th grade, 9/101 (8.9%). For boys 15 to 19 year old, the prevalence of chlamydia was 5.7%. Among girls, the prevalence rates were 7th grade, 0/105 (0%); 8th grade, 11/166 (6.6%); 9th grade, 23/218 (10.6%); 10th grade 23/146 (15.8%); 11th grade, 13/118 (11%); and 12th grade, 13/107 (12.1%). Among girls 15 to 19 years old, 12.7% were infected. Of 126 infected students, treatment was provided to 111 (88%). For this project, the laboratory cost of LCR testing was $17.76 per test. Without considering clinical staff time to collect the specimens, the average laboratory cost per infected student identified was $272. For students 15 to 19 years of age, of whom 104 (8.9%) of 1170 were infected, the laboratory cost was $200 per case identified.
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Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-alpha (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics.
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This randomized controlled trial compared short-course therapy of once-daily azithromycin (500 mg before the wound repair followed by 250 mg/day for 5 days) with cephalexin (1000 mg before wound repair followed by 250 mg every 6 hours for 5 days) in the treatment of patients with simple traumatic wounds. A total of 366 patients were randomly selected for the study and 303 were evaluated for the final analysis.
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Ureaplasma spp. infection has been associated with bronchopulmonary dysplasia (BPD) in preterm infants. Macrolides have been used for the treatment of Ureaplasma spp. infection, with an intention to prevent BPD. The objective of this meta-analysis is to evaluate the use of macrolides in the prevention of BPD in preterm infants.
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A series of novel 11,12-cyclic carbonate azithromycin 4''-O-carbamate derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 7b and 7d were the most effective (0.5 and 0.5 microg ml(-1)) against two strains of erythromycin-resistant Streptococcus pneumoniae whose resistance was encoded by the erm gene and the erm and mef genes, respectively. Compounds 7a, 7e and 7g showed significantly potent activity against erythromycin-susceptible strains such as Staphylococcus aureus and S. pyogenes. These results suggest that the introduction of the prolonged arylalkylcarbamoyl group to the C-4'' position can dramatically enhance the activity against erythromycin-resistant bacteria encoded by the erm gene or the erm and mef genes.