Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine against Mycobacterium avium infection in mice.

Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice.

Bacterial identification by 16S rRNA gene PCR-hybridization as a supplement to negative culture results.

PCR-hybridization was compared to culture methods for evaluating suspected blood infections. A total of 231 clinical samples from blood culture bottles that were flagged positive by the BacT/Alert system or were negative 1 week after inoculation were tested. When the PCR-hybridization and culture method results were compared, the positive and negative concordance rates were 99.

EDP-420, a bicyclolide (bridged bicyclic macrolide), is active against Mycobacterium avium.

Infection caused by Mycobacterium avium complex (MAC) is common in patients with immunosuppression, such as AIDS, and deficiencies of gamma interferon and interleukin-12, as well as patients with chronic lung diseases. Treatment of MAC disease is limited since few drugs show in vivo activity. We tested a new bridged bicyclic macrolide, EDP-420, against MAC in vitro and in beige mice.

Clinical, microbiological, and immunological characteristics in HIV-infected subjects at risk for disseminated Mycobacterium avium complex disease: an AACTG study.

The clinical, microbiologic, and immunologic parameters in HIV-infected subjects first presenting with disseminated Mycobacterium avium complex (DMAC) were determined. Four HIV-positive groups not yet on DMAC treatment were enrolled: 19 subjects with CD4 lymphocyte counts < or =50/microl thought to have DMAC on clinical grounds; 18 subjects newly found to have a positive blood culture for MAC; 25 asymptomatic controls (CD4 cell counts < or =50); and 25 asymptomatic controls (CD4 counts 100-250/microl). Outcome measures include comparisons between groups for clinical characteristics; results of cultures from blood, marrow, and gastrointestinal and respiratory tracts; immunological markers from staining of marrow and flow cytometry of circulating lymphocytes; and cytokine production of PBMCs.

Differential virulence of Mycobacterium avium strains isolated from HIV-infected patients with disseminated M. avium complex disease.

The role that colonization with Mycobacterium avium plays in the development of disseminated disease is unclear. In this study, we determined whether all M. avium strains isolated from the portals of M.

New 2,4-diamino-5-(2',5'-substituted benzyl)pyrimidines as potential drugs against opportunistic infections of AIDS and other immune disorders. Synthesis and species-dependent antifolate activity.

In a continuing effort to design small-molecule inhibitors of dihydrofolate reductase (DHFR) that combine the enzyme-binding selectivity of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP) with the potency of 2,4-diamino-5-methyl-6-(2',5'-dimethoxybenzyl)pyrido[2,3-d]pyrimidine (piritrexim, PTX), seven previously undescribed 2,4-diamino-5-[2'-methoxy-5'-(substituted benzyl)]pyrimidines were synthesized in which the substituent at the 5'-position was a carboxyphenyl group linked to the benzyl moiety by a bridge of two or four atoms in length. The new analogues were all obtained from 2,4-diamino-5-(5'-iodo-2'-methoxybenzyl)pyrimidine via a Sonogashira reaction, followed, where appropriate, by catalytic hydrogenation. The new analogues were tested as inhibitors of DHFR from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three life-threatening pathogens often found in AIDS patients and individuals whose immune system is impaired as a result of treatment with immunosuppressive chemotherapy or radiation.

A prospective, randomized trial examining the efficacy and safety of clarithromycin in combination with ethambutol, rifabutin, or both for the treatment of disseminated Mycobacterium avium complex disease in persons with acquired immunodeficiency syndrome.

This multicenter, randomized, open-label phase 3 clinical trial compared the safety and efficacy of 3 clarithromycin-containing combination regimens for the treatment of disseminated Mycobacterium avium complex (MAC) disease in persons with acquired immunodeficiency syndrome. A total of 160 eligible patients with bacteremic MAC disease were randomized to receive clarithromycin with either ethambutol (C+E), rifabutin (C+R), or both (C+E+R) for 48 weeks. After 12 weeks of treatment, the proportion of subjects with a complete microbiologic response was not statistically significantly different among treatment arms: the proportion was 40% in the C+E group, 42% in the C+R group, and 51% in the C+E+R group (P=.

Thiosemicarbazole (thiacetazone-like) compound with activity against Mycobacterium avium in mice.

In vitro screening of thiacetazone derivatives indicated that two derivatives, SRI-286 and SRI-224, inhibited a panel of 25 Mycobacterium avium complex (MAC) isolates at concentrations of 2 micro g/ml or lower. In mice, SRI-224 and thiacetazone had no significant activity against the MAC in livers and spleens, but treatment with SRI-286 resulted in significant reduction of bacterial loads in livers and spleens. A combination of SRI-286 and moxifloxacin was significantly more active than single drug regimens in liver and spleen.

Mefloquine, moxifloxacin, and ethambutol are a triple-drug alternative to macrolide-containing regimens for treatment of Mycobacterium avium disease.

Macrolides are the core of effective drug regimens for the treatment of Mycobacterium avium complex (MAC) disease. Mefloquine (MFQ), moxifloxacin (MXF), and ethambutol (EMB), in combination, were evaluated against both clarithromycin-resistant (CLR-R) and CLR-susceptible (CLR-S) MAC; MFQ (40 mg/kg), MXF (100 mg/kg), or EMB (100 mg/kg/day) was given to mice for 4 weeks. MFQ was bactericidal, whereas MXF and EMB were bacteriostatic against both MAC 101 CLR-S and CLR-R.

Multisite reproducibility of results obtained by two broth dilution methods for susceptibility testing of Mycobacterium avium complex.

A multicenter study was conducted to assess the interlaboratory reproducibility of susceptibility testing of Mycobacterium avium complex (MAC) by broth microdilution using two different media (cation-adjusted Mueller-Hinton broth with 5% oleic acid-albumin-dextrose-catalase and 7H9 broth with casein) and by macrodilution using the BACTEC 460TB and 12B media at pH 6.8 and 7.3 to 7.