Prophylaxis against Disseminated<i>Mycobacterium avium</i>Complex with Weekly Azithromycin, Daily Rifabutin, or Both

Havlir, Diane V.; Dubé, Michael P.; Sattler, Fred R.; Forthal, Donald N.; Kemper, Carol A.; Dunne, Michael; Parenti, David M.; Lavelle, James J.; White, A. Clinton; Witt, Mallory D.; Bozzette, Samuel A.; McCutchan, J. Allen

doi:10.1056/nejm199608083350604

Cited by 319 publications

(126 citation statements)

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“…Longterm azithromycin therapy has been well tolerated except for minor, mostly gastrointestinal side effects (eg, nausea and diarrhea). 27 Azithromycin prevented the acceleration of atherosclerosis induced by C pneumoniae in rabbits. 26 In a pilot clinical study, Gupta et al 28,29 treated survivors of myocardial infarction (MI) (nϭ60) with 1 to 2 brief courses of azithromycin or placebo; selected markers of inflammation and anti-chlamydial antibody titers fell over a 3-to 6-month period, and there was an apparent reduction in clinical events.…”

Section: See P 1538mentioning

confidence: 99%

Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease and Serological Evidence for Chlamydia pneumoniae Infection

et al. 1999

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Background-Chlamydia pneumoniae commonly causes respiratory infection, is vasotropic, causes atherosclerosis in animal models, and has been found in human atheromas. Whether it plays a causal role in clinical coronary artery disease (CAD) and is amenable to antibiotic therapy is uncertain. Methods and Results-CAD patients (nϭ302) who had a seropositive reaction to C pneumoniae (IgG titers Ն1:16) were randomized to receive placebo or azithromycin, 500 mg/d for 3 days, then 500 mg/wk for 3 months. Circulating markers of inflammation (C-reactive protein [CRP], interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-␣), C pneumoniae antibody titers, and cardiovascular events were assessed at 3 and 6 months. Treatment groups were balanced, with age averaging 64 (SDϭ10) years; 89% of the patients were male. Azithromycin reduced a global rank sum score of the 4 inflammatory markers at 6 (but not 3) months (Pϭ0.011) as well as the mean global rank sum change score: 531 (SDϭ201) for active drug and 587 (SDϭ190) for placebo (Pϭ0.027). Specifically, change-score ranks were significantly lower for CRP (Pϭ0.011) and IL-6 (Pϭ0.043). Antibody titers were unchanged, and number of clinical cardiovascular events at 6 months did not differ by therapy (9 for active drug, 7 for placebo). Azithromycin decreased infections requiring antibiotics (1 versus 12 at 3 months, Pϭ0.002) but caused more mild, primarily gastrointestinal, adverse effects (36 versus 17, Pϭ0.003). Conclusions-In CAD patients positive for C pneumoniae antibodies, global tests of 4 markers of inflammation improved at 6 months with azithromycin. However, unlike another smaller study, no differences in antibody titers and clinical events were observed. Longer-term and larger studies of antichlamydial therapy are indicated. (Circulation. 1999;99:1540-1547.)

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Section: See P 1538mentioning

confidence: 99%

Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease and Serological Evidence for Chlamydia pneumoniae Infection

et al. 1999

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“…Furthermore, the effect of antibiotic treatment of disseminated MAC on these same serum cytokine levels was determined. These studies used stored serum samples obtained from patients in a randomized trial of drug regimens for the prevention of disseminated MAC infection, and serial samples from a second set of patients before and during treatment for disseminated MAC were used (11). IL-1␣, IL-6, IL-10, TNF-␣, sTNF-RII, and TGF-␤ were chosen for these studies because of their role(s) in immune responses to MAC and HIV-1 and because elevated levels of these molecules in serum can be measured readily.…”

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confidence: 99%

Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals withMycobacterium aviumComplex Disease

et al. 2001

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To characterize changes in serum cytokine levels in human immunodeficiency virus type 1 (HIV-1)-infected persons with Mycobacterium avium complex (MAC) bacteremia, the levels of IL-1␣ (interleukin-1␣), IL-6, IL-10, tumor necrosis factor alpha (TNF-␣), soluble type II TNF receptor (sTNF-RII), and transforming growth factor ␤ (TGF-␤) in serum were measured in two cohorts of HIV-1-infected persons with MAC bacteremia. The first cohort was part of a MAC prophylaxis study. Patients with bacteremia were matched with controls without bacteremia. Elevated IL-6, IL-10, TNF-␣, sTNF-RII, and TGF-␤ levels were noted at baseline for all subjects, a result consistent with advanced HIV-1 disease. IL-1␣ was not detected. No differences in cytokine levels in serum were noted at baseline and at the time of bacteremia between patients with MAC and controls. In the second cohort, subjects had serum samples collected at the time of MAC bacteremia and thereafter while on macrolide therapy. Serum samples at time of bacteremia were collected from HIV-1-infected persons at a time when neither highly active antiretroviral therapy (HAART) nor MAC prophylaxis was used routinely. MAC treatment resulted in decreased levels of IL-6 and TNF-␣ in serum, which were evident for IL-6 by 4 to 6 weeks and for TNF-␣ by 8 to 16 weeks. Thus, antibiotic treatment for MAC results in decreased levels of IL-6 and TNF-␣ in serum in HIV-1-infected persons who are not on HAART.

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“…There were no controlled studies of the use of azithromycin for treatment of NTM in HIV-negative patients or uncontrolled studies of azithromycin used in HIV-positive patients. As seen in figure 2a [28,38,39,52,53,64,77], there was significant heterogeneity between the controlled studies of toxicity of use of azithromycin for NTM in HIV-infected subjects, although only moderate heterogeneity between studies of SAEs attributed to azithromycin ( fig. 2b [21, 41, 47-49]) in the uncontrolled studies of NTM treatment in HIV-uninfected patients.…”

Section: Serious Adverse Eventsmentioning

confidence: 99%

Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment

2015

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The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated.We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5).We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) −0.13, 95% CI −0.40-0.14) and amoxicillin-clavulanate had no efficacy in two other studies (RD 0.07, 95% CI −0.21-0.35). The largest number of studies described prolonged use for treatment of nontuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI −0.02-0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs ( proportion 0.20, 95% CI 0.12-0.27).For most group 5 drugs we found inadequate evidence of safety for prolonged use or for efficacy for MDR-TB, although macrolides appeared to be safe in prolonged use. @ERSpublications Weak evidence for the efficacy and safety of group 5 drugs for MDR-TB suggests they should be evaluated using RCTs

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Prophylaxis against DisseminatedMycobacterium aviumComplex with Weekly Azithromycin, Daily Rifabutin, or Both

Abstract: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

Cited by 319 publications

References 20 publications

Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease and Serological Evidence for Chlamydia pneumoniae Infection

Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease and Serological Evidence for Chlamydia pneumoniae Infection

Serum Interleukin-6 (IL-6), IL-10, Tumor Necrosis Factor (TNF) Alpha, Soluble Type II TNF Receptor, and Transforming Growth Factor Beta Levels in Human Immunodeficiency Virus Type 1-Infected Individuals withMycobacterium aviumComplex Disease

Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment

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