Interventions for the prevention of mycobacterium avium complex in adults and children with HIV
ABSTRACT Mycobacterium avium complex (MAC) infection is a common complication of advanced acquired immunodeficiency syndrome (AIDS) disease and is an independent predictor of mortality and shortened survival.
To determine the effectiveness and safety of interventions aimed at preventing MAC infection in adults and children with HIV infection.
We searched MEDLINE, EMBASE, and The Cochrane Library (search date December 2012).
Randomised controlled trials comparing different strategies for preventing MAC infection in HIV-infected individuals.
Two reviewers independently assessed trial eligibility and quality, and extracted data. Where data were incomplete or unclear, a third reviewer resolved conflicts and/or trial authors were contacted for further details. Development of MAC infection and survival were compared using risk ratios (RR) and 95% confidence intervals (CI). The quality of evidence has been assessed using the GRADE methodology.
Eight studies met the inclusion criteria.Placebo-controlled trialsThere was no statistically significant difference between clofazimine and no treatment groups in the number of patients that developed MAC infection (RR 1.01; 95% CI 0.37 to 2.80). Rifabutin (one study; RR 0.48; 95% CI 0.35 to 0.67), azithromycin (three studies; RR 0.37; 95% CI 0.19 to 0.74) and clarithromycin (one study; RR 0.35; 95% CI 0.21 to 0.58) were more effective than placebo in preventing the development of MAC infection. There was no statistically significant difference between those treated with clofazimine (one study; RR 0.98; 95% CI 0.41 to 2.32), rifabutin (one study RR 0.91; 95% CI 0.78 to 1.05), azithromycin (three studies, pooled RR 0.96; 95% CI 0.69 to 1.32) and placebo in number of reported deaths. One study found that the risk of death was reduced by 22% in patients treated with clarithromycin compared to those treated with placebo (RR 0.78; 95% CI 0.64 to 0.96). Monotherapy vs. monotherapyPatients treated with clarithromycin (RR 0.60; 95% CI 0.41 to 0.89) and azithromycin (RR 0.60; 95% CI 0.40 to 0.89) were 40% less likely to develop MAC infection than those treated with rifabutin. There was no statistically significant difference between those treated with clarithromycin (RR 0.98; 95% CI 0.83 to 1.15), azithromycin (RR 0.98; 95% CI 0.77 to 1.24) and rifabutin in the number of reported deathsCombination therapy versus monotherapyThere was no statistically significant difference between patients treated with a combination of rifabutin and clarithromycin and those treated with clarithromycin alone (RR 0.74; 95% CI 0.46 to 1.20); and those treated with combination of rifabutin and azithromycin and those treated with azithromycin alone (RR 0.59; 95% CI 1.03). Patients treated with a combination of rifabutin plus clarithromycin were 56% less likely to develop MAC infection than those treated with rifabutin alone (RR 0.44; 95% CI 0.29 to 0.69). Patients treated with a combination of rifabutin plus azithromycin were 65% less likely to develop MAC infection than those treated with rifabutin alone (RR 0.35; 95% CI 0.21 to 0.59). There was no statistically significant difference in the number of reported deaths in all the four different comparisons of prophylactic agents.
Based on limited data, azithromycin or clarithromycin appeared to be a prophylactic agent of choice for MAC infection. Further studies are needed, especially direct comparison of clarithromycin and azithromycin. In additions, studies that will compare different doses and regimens are needed.
- 5th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC); 11/2014
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ABSTRACT: Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the activation of CD4+ T-cells. Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal antibodies in the presence of 0.6 mg/L, 2.5 mg/L, 10 mg/L or 40 mg/L AZM or CLM. Cell proliferation, cytokine level in supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated using reporter cell lines, FACS analysis, immunoblotting and in vitro kinase assays. AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent manner. Similarly, high concentrations of CLM (40 mg/L) also suppressed these T-cell functions. Analysis of molecular signaling pathways revealed that exposure to AZM reduced the phosphorylation of the S6 ribosomal protein, a downstream target of mTOR. This effect was also observed at 40 mg/L CLM. In vitro kinase studies using recombinant mTOR showed that AZM inhibited mTOR activity. In contrast to rapamycin, this inhibition was independent of FKBP12. We show for the first time that AZM and to a lesser extent CLM act as immunosuppressive agents on CD4+ T-cells by inhibiting mTOR activity. Our results might have implications for the clinical use of macrolides.Scientific Reports 12/2014; 4:7438. DOI:10.1038/srep07438 · 5.58 Impact Factor
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ABSTRACT: Complete DiGeorge syndrome (cDGS) describes a subset of patients with DiGeorge syndrome that have thymic aplasia, and thus are at risk for severe opportunistic infections. Patients with cDGS and mycobacterial infection have not previously been described. We present this case to illustrate that patients with cDGS are at risk for nontuberculous mycobacterial infections and to discuss further antimicrobial prophylaxis prior to thymic transplantation. A 13-month old male was identified as T cell deficient by the T cell receptor excision circle (TREC) assay on newborn screening, and was subsequently confirmed to have cDGS. He presented with fever and cough, and was treated for chronic aspiration pneumonia as well as Pneumocystis jirovecii infection without significant improvement. It was only after biopsy of mediastinal lymph nodes seen on CT that the diagnosis of disseminated Mycobacterium kansasii was made. We reviewed the literature regarding atypical mycobacterial infections and prophylaxis used in other immunocompromised patients, as well as the current data regarding cDGS detection through TREC newborn screening. Multiple cases of cDGS have been diagnosed via TREC newborn screening, however this is the first patient with cDGS and disseminated mycobacterial infection to be reported in literature. Thymic transplantation is the definitive treatment of choice for cDGS. Prophylaxis with either clarithromycin or azithromycin has been shown to reduce mycobacterial infections in children with advanced human immunodeficiency virus infection. Children with cDGS should receive thymic transplantion as soon as possible, but prior to this are at risk for nontuberculous mycobacterial infections. Severe, opportunistic infections may require invasive testing for diagnosis in patients with cDGS. Antimicrobial prophylaxis should be considered to prevent disseminated mycobacterial infection in these patients.Journal of Clinical Immunology 06/2015; DOI:10.1007/s10875-015-0171-3 · 2.65 Impact Factor