Different types of pulmonary granuloma necrosis in immunocompetent vs. TNFRp55-gene-deficient mice aerogenically infected with highly virulent Mycobacterium avium

The immunopathogenesis of mycobacterial infections frequently involves the formation of caseating granulomas which cause tissue destruction and, in the case of tuberculosis (TB), may lead to cavity formation. Both intravenous and aerosol models of Mycobacterium tuberculosis infection in mice do not reflect the pulmonary lesions characteristic of TB patients. Using both low-dose (10² colony-forming units, cfu) and high-dose (10⁵ cfu) aerosol infection with a highly virulent strain of Mycobacterium avium (TMC724) in C57BL/6 mice, it is now shown that these mice are capable of developing centrally caseating necrosis in lung granulomas after approximately 4 months of infection. In contrast, mice infected intravenously with the high dose never developed this type of lesion, although bacterial counts in their lungs reached levels comparable to those attained by aerosol-infected mice (10¹⁰ cfu). To study the relevance of events signalled by tumour necrosis factor (TNF) in this model, TNFRp55 gene-deficient and syngeneic C57BL/6 immunocompetent mice were infected with 10⁵ cfu M. avium via aerosol. In gene-deficient mice, newly formed pulmonary granulomas acutely disintegrated, showing signs of apoptotic cell death and neutrophil influx, and TNFRp55 knock-out mice all succumbed to infection just beyond the stage of granuloma initiation. Aerogenic infection with M. avium in mice is a suitable model to study the immunopathogenesis of granuloma necrosis because it closely mimicks the histopathology of mycobacterial infections in humans, including TB. Furthermore, the use of TNFRp55 gene-deficient mice in this model establishes a role for TNF in maintaining the integrity of a developing pulmonary granuloma. Copyright © 1999 John Wiley & Sons, Ltd.     

Micobacterias no tuberculosas. ¿Una amenaza emergente?

Introduction and objective

Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates.

Port site infection in laparoscopic surgery: A review of its management

Laparoscopic surgery(LS), also termed minimal access surgery, has brought a paradigm shift in the approach to modern surgical care. Early postoperative recovery, less pain, improved aesthesis and early return to work have led to its popularity both amongst surgeons and patients. Its application has progressed from cholecystectomies and appendectomies to various other fields including gastrointestinal surgery, urology, gynecology and oncosurgery. However, LS has its own package of complications. Port site infection(PSI), although infrequent, is one of the bothersome complications which undermine the benefits of minimal invasive surgery. Not only does it add to the morbidity of the patient but also spoils the reputation of the surgeon. Despite the advances in the field of antimicrobial agents, sterilization techniques, surgical techniques, operating room ventilation, PSIs still prevail. The emergence of rapid growing atypical mycobacteria with multidrug resistance, which are the causative organism in most of the cases, has further compounded the problem. PSIs are preventable if appropriate measures are taken preoperatively, intraoperatively and postoperatively. PSIs can often be treated non-surgically, with early identification and appropriate management. Macrolides, quinolones and aminoglycosides antibiotics do show promising activity against the atypical mycobacteria. This review article highlights the clinical burden, presentations and management of PSIs in LS as shared by various authors in the literature. We have given emphasis to atypical mycobacteria, which are emerging as a common etiological agent for PSIs in LS. Although the existing literature lacks consensus regarding PSI management, the complication can be best avoided by strictly abiding by the commandments of sterilization techniques of the laparoscopic instruments with appropriate sterilizing agent.     

34株慢速生长非结核分枝杆菌针对一线和二线抗结核药物的敏感性试验研究

慢速生长分枝杆菌主要分布于土壤、污水等环境中,这类细菌可对人类致病,尤其是肺部疾病。 本研究中,通过分析一线和二线抗结核药物的药敏试验,为了找到治疗慢速生长分枝杆菌病的最佳药物。结果 表明,异烟肼(4/34)是敏感性最低的药物,只对Mycobacterium szulgai, Mycobacterium celatum, Mycobacterium duvalii和Mycobacterium elephantis敏感。 利福平 (13/34) 和乙胺丁醇 (14/34) 有相似的敏感性。链霉素 (27/34) 是一线抗结核药物中效果最好的,对绝大多数的试验菌株都有较好的活性。氧氟沙星 (23/34), 卡那霉素 (26/34) 和妥布霉素 (26/34) 具有强有力的抗菌活性。环丙沙星 (31/34), 左氧氟沙星 (31/34), 阿米卡星 (33/34) 和卷曲霉素 (33/34) 具有极好的抗慢速生长分枝杆菌活性。莫西沙星 (34/34) 的抗菌活性最强。在本试验的测试慢速生长分枝杆菌中, Mycobacterium simiae和Mycobacterium africanum对更多的药物耐药。Mycobacterium szulgai和Mycobacterium duvalii 对一线和二线抗结核药物都有较好的活性。总之,二线抗结核药物是治疗慢速生长分枝杆菌的良好药物,可被广泛用于慢速生长分枝杆菌病的治疗。     

The effects of Mycobacteria vaccae derivative on allergen-specific responses in children with atopic dermatitis

The capacity of microbial products to inhibit allergic inflammation make them logical candidates for novel therapies in allergic diseases such as atopic dermatitis. To assess the effects of intradermal Mycobacterium vaccae derivative on allergen‐specific immune responses in children with moderate to severe atopic dermatitis. Peripheral blood mononuclear cells were isolated from children aged 5–16 years who received intradermal injections of M. vaccae derivative AVAC^TM (n = 26) or placebo (n = 34) three times at 2‐weekly intervals, weeks 0, 2 and 4. Cytokine [interleukin (IL)‐13, interferon (IFN)‐γ and IL‐10] responses to allergen [house dust mite (HDM)], mitogen [phytohaemagglutinin (PHA)], Staphylococcal enterotoxin B (SEB) and Toll‐like receptor (TLR) ligands were assessed. At week 8 (1 month after all injections given) children in the AVAC group showed a significant increase in IL‐10 (P = 0·009), T helper type 1 (Th1) IFN‐γ (P = 0·017) and Th2 IL‐13 (P = 0·004) responses to HDM compared with baseline (week 0). There were no significant changes in any cytokine production in the placebo. HDM‐specific IL‐10 responses remained significantly higher (P = 0·014) than at baseline in the AVAC group by week 12; however, the HDM‐specific IL‐13 and IFN‐γ responses were no longer significantly different from baseline. IL‐13 (r = 0·46, P < 0·001) and IL‐10 (r = 0·27, P = 0·044) responses to HDM were correlated with total immunoglobulin E but not with disease severity. There were no effects of AVAC on mitogen, SEB, TLR‐2‐ or TLR‐4‐mediated responses. This M. vaccae derivative appeared to modulate responses to HDM selectively, suggesting the capacity for in vivo effects on allergen‐specific immune responses.     

145株非结核分枝杆菌对10种药物的耐药性分析

目的了解我院非结核病患者分离的非结核分枝杆菌对10种药物的耐药状况。方法用MB/Bact 240分枝杆菌培养仪和改良罗氏管对患者的多种标本进行分枝杆菌分离培养鉴定,对分离到的分枝杆菌采用绝对浓度法对10种抗结核药物,利福平、异烟肼、乙胺丁醇、链霉素,利福喷丁、丙硫异烟肼、氧氟沙星、卷曲霉素、卡那霉素和对氨基水扬酸进行药物敏感性试验。结果 1722例患者的标本非结核分枝杆菌培养阳性145株,对10种药总耐药率97.2%（141/145）,单耐药率最高为异烟肼、链霉素和对氨基水扬酸,最低为氧氟沙星。结论非结核分枝杆菌耐药情况十分严重,应加强抗结核药物的耐药性监测;根据药敏试验选择科学有效的化疗方案。     

Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature

J.S. Doggett, L. Strasfeld. Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature.
Transpl Infect Dis 2011: 13: 38–43. All rights reserved Abstract: We report a case of disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient and review the associated literature. Disease caused by M. genavense has been recognized in acquired immunodeficiency syndrome (AIDS) patients since 1990, with subsequent case reports in other immunocompromised host populations. In AIDS patients, pulmonary lesions are an uncommon finding. This is the first report to our knowledge of a human immunodeficiency virus (HIV)‐negative patient with pulmonary nodules as a feature of disseminated M. genavense. Diagnosis of M. genavense is often challenging and frequently requires nucleic acid‐based identification techniques. Because of limitations in culture and drug susceptibility testing, treatment regimens rely on reported clinical experience. This case report and literature review illustrates a successful approach to the diagnosis and treatment of disseminated M. genavense and summarizes the reports of M. genavense infection in HIV‐negative patients.     

Immunological markers of lung disease due to non-tuberculous mycobacteria

Lung disease due to non-tuberculous mycobacteria (NTM) is a poorly understood condition that is difficult to treat. Treatment remains problematic as few tools are available to help clinicians monitor disease progression or predict treatment outcome. In this study, plasma levels of several inflammatory molecules and the frequency of circulating T cell subsets were measured in patients with NTM lung disease and known treatment status, and compared with their adult offspring and with unrelated healthy controls. Plasma levels of the chemokine CXCL10 and IL-18 were assessed for associations with treatment efficacy. CXCL10 was higher in patients than adult offspring (p< 0.001) and unrelated controls (p< 0.001). Plasma CXCL10 was also lower in patients who responded well to therapy or who controlled their infection without requiring therapy, when compared to patients who did not respond to therapy (p=0.03). Frequencies of activated (HLA-DR(+)) CD4(+) T cells were higher in patients than adult offspring (p<0.001) and unrelated controls (p<0.05), with the highest frequencies in individuals who had completed at least 6 months of treatment. Frequencies of activated (CD38(+)) CD8(+) T cells in most treatment responders were similar to unrelated controls. Low plasma levels of CXCL10 may reflect successful control of NTM lung disease with or without therapy. Compared with responders, patients who responded poorly to treatment generally had higher plasma levels of CXCL10 and IL-18, and higher frequencies of activated CD8(+) T cells.     

Standardized combination antibiotic treatment of Mycobacterium avium complex lung disease

Purpose

The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease.

Materials and Methods

This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006.

Results

All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response.

Conclusion

Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.