Capsaicin Protects Mice from Community-Associated Methicillin-Resistant Staphylococcus aureus Pneumonia

BACKGROUND: α-toxin is one of the major virulence factors secreted by most Staphylococcus aureus strains, which played a central role in the pathogenesis of S. aureus pneumonia. The aim of this study was to investigate the impact of capsaicin on the production of α-toxin by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA 300 and to further assess its performance in the treatment of CA-MRSA pneumonia in a mouse model. METHODOLOGY/PRINCIPAL FINDINGS: The in vitro effects of capsaicin on α-toxin production by S. aureus USA 300 were determined using hemolysis, western blot, and real-time RT-PCR assays. The influence of capsaicin on the α-toxin-mediated injury of human alveolar epithelial cells was determined using viability and cytotoxicity assays. Mice were infected intranasally with S. aureus USA300; the in vivo protective effects of capsaicin against S. aureus pneumonia were assessed by monitoring the mortality, histopathological changes and cytokine levels. Low concentrations of capsaicin substantially decreased the production of α-toxin by S. aureus USA 300 without affecting the bacterial viability. The addition of capsaicin prevented α-toxin-mediated human alveolar cell (A549) injury in co-culture with S. aureus. Furthermore, the in vivo experiments indicated that capsaicin protected mice from CA-MRSA pneumonia caused by strain USA 300. CONCLUSIONS/SIGNIFICANCE: Capsaicin inhibits the production of α-toxin by CA-MRSA strain USA 300 in vitro and protects mice from CA-MRSA pneumonia in vivo. However, the results need further confirmation with other CA-MRSA lineages. This study supports the views of anti-virulence as a new antibacterial approach for chemotherapy

Tuberculosis and malignancy

Background: Tuberculosis (TB) and malignancy represent global threats claiming millions of lives and inflicting formidable suffering worldwide. Surprisingly, the pathophysiological and practical implications of their co-existence have received little attention. Methods: Therefore, we sought to review the available literature on the field and identify data regarding the association between TB and malignancy in order to highlight the neglected aspects of this association and probably derive clinically useful information. We searched PubMed up to June 2008 for case reports, case series, non-comparative and comparative studies that were written in English and reported data on the occurrence of both TB infection and a neoplastic disorder in the same patient(s). The development of mycobacterial infections in patients with immunocompromized conditions is well known and was considered outside the scope of this review. Evidence synthesis: The synthesis of the available evidence enabled us to establish three different types of association between malignancy and TB: (i) the development of cancer on the background of a previous tuberculous infection; (ii) the concurrent existence of TB and malignancy in the same patient(s) or clinical specimen(s); and (iii) the diagnostic challenges arising from the multi-faceted presentations of these two disorders. Conclusions: We conclude that clinicians need to be aware of the protean manifestations of TB and cancer and maintain a high index of suspicion for simultaneous and/or misleading presentations. In addition, further research is required to determine if a tuberculous infection, being similar to other chronic infections and inflammatory conditions, may facilitate carcinogenesis

Short- versus long-course antibacterial therapy for community-acquired pneumonia: A meta-analysis

Background: The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established. Objectives: We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP. Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing short- (≤7 days) versus long- (≥2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages. Results: Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2-59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3-7 days; children 3 days) and long- (adults 7-10 days; children 5 days) course regimens (adults - amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children - amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens. Conclusion: No difference was found in the effectiveness and safety of short- versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity. © 2008 Adis Data Information BV. All rights reserved