zithromax and Mycobacterium-avium-intracellulare-Infection

We report a case of liver transplant patient who presented with lung masses, found to be Mycobacterium spindle cell pseudotumors. The masses demonstrated hypermetabolic activities on positron emission tomography. Core biopsy revealed sheets of spindle histiocytic cells with abundant acid-fast bacilli identified as Mycobacterium avium-intracellulare complex. This finding is a rare presentation of Mycobacterium infection, mainly nontuberculous Mycobaterium. It is characterized by a benign, spindle cell mass-forming reaction. Most of the reported cases had acquired immune deficiency syndrome or organ transplant. Histopathology illustrating the proliferation of spindle cell shaped histiocytes containing numerous acid-fast bacilli is the gold standard for diagnosis. The standard treatment has not been well established; previously reported cases followed the standard treatment for Mycobacterium based on organ involvement. Our case is the first case to our knowledge that reports pulmonary Mycobacterium spindle cell pseudotumors in a liver transplant recipient.

Topics: Aged; Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Ethambutol; Female; Humans; Liver Transplantation; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Plasma Cell Granuloma, Pulmonary

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 trials: There 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. monotherapy: Patients 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 deaths. Combination therapy versus monotherapy: There 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.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Child; Clarithromycin; Clofazimine; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Randomized Controlled Trials as Topic; Rifabutin

Recently, the clinical importance of nontuberculous mycobacteria (especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, essence of this official statement will be introduced. In MAC respiratory infection, (i) primarily fibrocavitary disease, (ii) nodular/bronchiectatic disease, and (iii) hypersensitivity-like disease are identified, and (i) and (ii) are clinically important. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, disseminated MAC disease in patients with acquired immunodeficiency syndrome should be considered. Further studies concerning transmission route as well as mechanism of MAC disease should be performed.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Female; Humans; Immunocompromised Host; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Tuberculosis, Pulmonary

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Therapeutic and prophylactic regimens directed specifically against Mycobacterium avium complex (MAC) are increasingly being used in patients infected with the human immunodeficiency virus (HIV). Several of the drugs used in the management of MAC have been associated with significant drug interactions involving the cytochrome P450 (CYP) enzyme system. This enzyme system is also highly influenced by other drugs used in the management of patients with HIV, particularly the protease inhibitors, non-nucleoside reverse transcriptase inhibitors (NNRTIs) and azole antifungals. This article reviews the published concentrations or subtherapeutic concentrations of other drugs have been described. In particular, concurrent use of rifabutin with clarithromycin or fluconazole has resulted in increased concentrations of rifabutin and an accompanying increase in the incidence of rifabutin toxicities, including uveitis and leucopenia. Similar results have been seen when rifabutin is combined with protease inhibitors or delavirdine. The macrolides, clarithromycin and azithromycin, have also been associated with significant drug interactions. Clarithromycin has a higher affinity for CYP than azithromycin and, thus, is more frequently associated with clinically significant drug interactions. Clarithromycin is an inhibitor of CYP and may result in toxic concentrations of other drugs metabolised by this enzyme system. Such interactions have been described with rifabutin and the statin lipid-lowering agents. In addition, nevirapine and efavirenz have been shown to significantly reduce clarithromycin concentrations, whereas the protease inhibitors and delavirdine may increase clarithromycin concentrations. Other drugs used in the management of patients with MAC are not metabolised by CYP and thus have a lower incidence of interactions, although the absorption of ciprofloxacin may be impaired when it is given with products containing multivalent cations, such as didanosine. However, clinicians must remain vigilant for drug interactions when reviewing a patient's medication profile, keeping in mind both interactions that have been described in the literature and those that may be predicted based upon known pharmacokinetic profiles.

Topics: Azithromycin; Clarithromycin; Drug Interactions; HIV Protease Inhibitors; Humans; Mycobacterium avium-intracellulare Infection; Reverse Transcriptase Inhibitors; Rifabutin

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clarithromycin; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Disseminated Mycobacterium avium-intracellulare complex (DMAC) infection is a common complication of AIDS. The cumulative incidence is 40% in patient surviving 2 years after diagnosis of AIDS. AIDS patients with DMAC reduced life expectancy compared with those without. Antimycobacterial therapy with Clarithromycin (CAM) can significantly reduce bacteremia and improve symptoms, quality of life, and survival of patients with DMAC. Prophylactic therapy with Rifabutin, CAM and Azithromycin is effective and Synergic effect can be expected as Rifabutin and Azithromycin are administered together. But it is serious problem to get resistance to CAM when prophylactic therapy with CAM failed because we lose one of the most effective medicines against DMAC. It is recommended to start prophylactic therapy when CD4 Lymphocyte count falls below 50-75/microliters in patients who had opportunistic infection. In Japan, 32 cases of AIDS with NTM are reported. All of them are male and mean count of CD4+lymphocyte was 11/microliters. Twenty three out of 32 were MAC and 6 were M. kansasii. Cases of NTM bacteremia were 9 (69.2%) and cases of those without bacteremia were 4 (30.8%). Three out of 4 were cases of M. kansasii.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Clarithromycin; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifabutin

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clarithromycin; Community-Acquired Infections; Helicobacter Infections; Humans; Malaria; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial

We treated 39 elderly human immunodeficiency virus-noninfected patients with Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with azithromycin (600 mg daily), given initially as monotherapy. Adverse events occurred in 33 of 39 patients (85%) receiving azithromycin alone, most commonly gastrointestinal (GI) symptoms (32 of 39, or 82%) and hearing impairment (10 of 39, or 26%). Twenty-four of 39 patients (62%) required a lower dose or withdrawal of the drug. The mean serum level in patients who required a dose reduction because of hearing impairment was 0.8 +/- 0.4 microg/mL, and that in patients whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 microg/mL; in comparison, the mean serum level was 0.3 +/- 0.16 microg/mL in patients with no adverse events (P = .004 and .003, respectively). Decreasing the daily dose to 300 mg resulted in resolution of most adverse events. Serum levels with monotherapy were comparable to levels after the addition of other antituberculous drugs that included rifampin or rifabutin. Thus, a 300-mg rather than 600-mg daily dose of azithromycin is better tolerated by elderly patients, and serum levels appear unaffected by other antituberculous agents, including rifampin.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Dizziness; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Hearing Disorders; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Treatment Outcome

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Fluconazole; Humans; Immunocompromised Host; Mycobacterium avium-intracellulare Infection; Rifabutin

The survival rate in patients with AIDS who have CD4+ cell counts < 75 cells/microliter is increasing because of improved preventive and treatment strategies for opportunistic infections and also because of the efficacy of antiretroviral drug treatment. These patients are at high risk of developing disseminated Mycobacterium avium-intracellulare (MAC) disease, which decreases both quality of life and life expectancy. Measures aimed at preventing MAC contamination are largely ineffective in decreasing the incidence of disseminated MAC disease in patients with AIDS, because of the large natural reservoir of MAC. Chemoprophylaxis is superior to early bacteriological diagnosis as a preventive strategy, and it is preferable to wait for the appearance of symptoms of disseminated MAC disease before a curative treatment is initiated. Well-conducted studies of clarithromycin or rifabutin monotherapy as chemoprophylaxis have demonstrated a decrease in the incidence of disseminated MAC disease, as well as an increase in quality of life and survival. Clarithromycin, azithromycin and rifabutin have all been shown to be effective as prophylaxis against disseminated MAC disease. Although some combinations of drugs have been shown to be more effective than monotherapy in preventing disseminated MAC disease, these regimens are more costly and have less favourable tolerability profiles than single-agent treatment. In conclusion, chemoprophylaxis is the most effective preventive strategy against disseminated MAC disease and has been shown to improve quality of life and to decrease the risk of death associated with this disease in AIDS patients.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; HIV Infections; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin

In patients with AIDS, disseminated Mycobacterium avium-intracellulare complex (MAC) infection is a common bacterial infection and is associated with considerable morbidity and mortality. In placebo-controlled studies, rifabutin, clarithromycin and azithromycin (administered as single agents) have been shown to prevent the development of MAC bacteraemia in patients with advanced HIV disease. Clarithromycin also conferred a survival benefit over placebo, but this was not initially observed with either rifabutin or azithromycin. Subsequently, the efficacy of single agent therapy was compared with that of combination treatment as prophylaxis against the development of disseminated MAC. In the AIDS Clinical Trials Group (ACTG) 196/Community Programs for Clinical Research on AIDS (CPCRA) 009 study, clarithromycin monotherapy and clarithromycin and rifabutin combination therapy regimens were both more effective than rifabutin monotherapy in reducing the incidence of MAC bacteraemia. However, the combination regimen was generally not well tolerated. In the California Consortium Treatment Group (CCTG)/Multiple Opportunistic Prevention Prophylactic Strategy (MOPPS) study, azithromycin plus rifabutin was significantly more effective than either agent administered alone, and azithromycin was more effective than rifabutin. However, azithromycin (alone or in combination with rifabutin) caused frequent gastrointestinal adverse events. Emergence of resistance in those failing prophylaxis appeared to be higher with clarithromycin than with azithromycin or rifabutin. The use of the combination regimen of clarithromycin plus rifabutin did not reduce the selection of clarithromycin-resistant isolates. Several issues need to be considered in the choice of MAC prophylaxis for the individual patient. On the basis of efficacy and potential drug interactions with protease inhibitors, clarithromycin or azithromycin is preferred to rifabutin. However, rifabutin is less likely to result in the emergence of resistance than the macrolides, and is likely to prevent tuberculosis, whereas azithromycin and clarithromycin will prevent some bacterial infections. Combination therapy for prophylaxis is not indicated in most situations.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Controlled Clinical Trials as Topic; Drug Therapy, Combination; HIV Infections; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin

The most common pathogens involved in disseminated bacterial infection in people with acquired immunodeficiency syndrome (AIDS) are organisms of the Mycobacterium avium-intracellulare complex (MAC). Azithromycin and clarithromycin, a new azalide and macrolide, respectively, are among the most potent monotherapies for MAC bacteraemia, Although many bloodstream isolates demonstrate increased minimum inhibitory concentrations after 4 months of treatment. Current recommended prophylaxis, based on the results of two randomized, double-blind, prospective studies, is rifabutin 300 mg daily for people with AIDS with < 100 CD4 lymphocytes/mm3. In the beige mouse model, we have shown that both azithromycin and clarithromycin prevent MAC bacteraemia following repetitive oral challenge. Clinical trails are now underway to confirm these effects in man; comparative treatments include placebo, rifabutin and an azalide/macrolide plus rifabutin. While combinations might be more effective and reduce the emergence of resistance, the spectre of cytochrome P-450 drug interactions necessitates careful study before combination prophylactic approaches are accepted. Such interactions are associated with rifabutin and some macrolides, although azithromycin may be less problematic in this respect as it appears to have little potential to interact with other antimicrobial agents.

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Humans; Mice; Mycobacterium avium-intracellulare Infection

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Survival Analysis; Treatment Outcome

Mycobacterium avium infection is a frequent complication during the late stage of AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are bactericidal against M. avium, and their use has dramatically improved the prognosis of this infection. In vitro, azithromycin has MICs against M. avium ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low concentrations in serum, close to 0.4 mg/l, very high intracellular concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is active in vitro in the model of macrophage infection. Furthermore, azithromycin is active against murine experimental infection with M. avium. Clinical studies conducted among patients with AIDS have shown that azithromycin was active against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies are designed to better determine the ideal dose, to compare its activity with that of clarithromycin and to determine the antibiotics that could be combined to prevent the selection of resistant mutants. Other ongoing studies are evaluating the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Humans; In Vitro Techniques; Macrophages; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rats; Tuberculosis

Perhaps the most important recent advance in the field of infections due to the Mycobacterium avium complex (MAC) is the identification and development of more effective agents for the treatment and prevention of disseminated disease. These agents include clarithromycin, azithromycin, rifabutin and other rifamycins, ethambutol, clofazimine, fluoroquinolones, amikacin, and liposome-encapsulated gentamicin. Most clinicians currently use multidrug therapy to maximize efficacy and to minimize the emergence of resistance. Prospective clinical trials of multidrug regimens suggest that MAC colony counts in blood decline during therapy, usually with alleviation of clinical symptoms. The small size and short duration of these trials have not permitted an evaluation of survival or quality of life. Because the contribution of any single agent to multidrug trials is difficult to assess, short-term trials of monotherapy have been conducted recently; clarithromycin, azithromycin, ethambutol, and liposome-encapsulated gentamicin have been most active. Rifabutin and rifampin, clofazimine, amikacin, and ciprofloxacin may contribute to the efficacy of multidrug regimens. Current recommendations include the following: (1) disseminated MAC disease should be treated in patients with AIDS; (2) initial treatment should consist of at least two agents; (3) oral clarithromycin or azithromycin is the preferred first agent; (4) ethambutol is the most rational choice for the second agent; and (5) in appropriate cases, additional agents (rifampin or rifabutin, clofazimine, ciprofloxacin, or parenteral amikacin) may be added. Therapy should continue for life.

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Colony Count, Microbial; Drug Therapy, Combination; Ethambutol; Gentamicins; Humans; Mycobacterium avium-intracellulare Infection; Prospective Studies; Randomized Controlled Trials as Topic

Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.).

Topics: Aged; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Drug Administration Schedule; Ethambutol; Female; Humans; Lung; Male; Middle Aged; Models, Statistical; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Sputum

Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited.. To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for nodular bronchiectatic MAC lung disease.. A retrospective cohort study of 217 patients with treatment-naive noncavitary nodular bronchiectatic MAC lung disease. All patients received either daily (n = 99) or intermittent therapy (n = 118) that included clarithromycin or azithromycin, rifampin, and ethambutol.. Modification of the initial antibiotic therapy occurred more frequently in the daily therapy group than in the intermittent therapy group (46 vs. 21%; P < 0.001); in particular, ethambutol was more frequently discontinued in the daily therapy group than in the intermittent therapy group (24 vs. 1%; P ≤ 0.001). However, the rates of symptomatic improvement, radiographic improvement, and sputum culture conversion were not different between the two groups (daily therapy vs. intermittent therapy: 75 vs. 82%, P = 0.181; 68 vs. 73%, P = 0.402; 76 vs. 67%, P = 0.154, respectively). In addition, the adjusted proportion of sputum culture conversion was similar between the daily therapy (71.3%; 95% confidence interval, 59.1-81.1%) and the intermittent therapy groups (73.6%; 95% confidence interval, 62.9-82.2%; P = 0.785).. These results suggest that intermittent three-times-weekly therapy with a macrolide, rifampin, and ethambutol is a reasonable initial treatment regimen for patients with noncavitary nodular bronchiectatic MAC lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00970801).

Topics: Aged; Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Clarithromycin; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Logistic Models; Macrolides; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Outcome and Process Assessment, Health Care; Practice Guidelines as Topic; Republic of Korea; Retrospective Studies; Rifampin; Sputum

Immune function was observed for 144 weeks in 643 human immunodeficiency virus (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3, followed by a sustained increase to > or =100 cells/mm3 after the initiation of HAART, and (2) were enrolled in a randomized trial of continued azithromycin prophylaxis versus withdrawal for prevention of Mycobacterium avium complex disease. The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3 at week 144. Anergy (80.2% of patients) and lack of lymphoproliferative response to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be evidence of impaired immune reconstitution. Receipt of azithromycin did not have an effect on CD4+ cell count but was associated with higher rates of delayed-type hypersensitivity responses to TT (25% of subjects who received azithromycin vs. 15% of those who did not; P=.009) and mumps skin test antigen (29% vs. 17%; P=.001). Although the subjects had only partial responses to immune function testing, the rate of opportunistic infections was very low, and none of the tests was predictive of risk.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Antiretroviral Therapy, Highly Active; Antiviral Agents; Azithromycin; Biomarkers; CD4 Lymphocyte Count; Female; Hepatitis A Antibodies; Hepatitis A Vaccines; HIV Infections; HIV-1; Humans; Longitudinal Studies; Male; Mumps virus; Mycobacterium avium-intracellulare Infection; RNA, Viral; Tetanus Toxoid

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Female; Humans; Male; Mycobacterium avium-intracellulare Infection; Placebos; Viral Load

Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy.. We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia.. A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002).. Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; CD4 Lymphocyte Count; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; HIV; HIV Infections; Humans; Male; Mycobacterium avium-intracellulare Infection; RNA, Viral

Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain.. To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo.. Randomized, double-blind, placebo-controlled trial.. 29 university-based clinical centers in the United States.. 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy.. Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322).. Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals.. During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]).. Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Azithromycin; CD4 Lymphocyte Count; Disease Progression; Double-Blind Method; Female; HIV Infections; HIV-1; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Placebos; Proportional Hazards Models; RNA, Viral; Viral Load

Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Gastrointestinal Diseases; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Survival Analysis; Treatment Outcome

The intracellular dispositions of clarithromycin and azithromycin in AIDS patients requiring Mycobacterium avium complex (MAC) prophylaxis were studied. The dispositions of both drugs in mononuclear and polymorphonuclear leukocytes were markedly different. Our data support the proven efficacy of these agents for MAC prophylaxis since clarithromycin and azithromycin displayed sustained intracellular concentrations which exceeded their MICs for MAC throughout the dosing periods.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Clarithromycin; Cross-Over Studies; Female; Half-Life; Humans; Leukocytes, Mononuclear; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Neutrophils

This multicenter, randomized, dose-ranging study was performed to determine the safety and efficacy of two different doses of azithromycin for treating disseminated Mycobacterium avium complex (MAC) in patients with AIDS. Eighty-eight AIDS patients with symptoms and blood cultures consistent with disseminated MAC were treated with 600 or 1,200 mg of azithromycin daily for 6 weeks; 62 patients completed the entire 6 weeks of study. Of note, this study was done prior to the time when combination antiretroviral or anti-MAC regimens were the standard of care. Over the 6-week study period, symptomatic improvement was noted in both dose groups. Microbiological responses were comparable, with mean decreases of 1. 5 and 2.0 log CFU/ml in the high- and low-dose groups, respectively. Sterilization of blood cultures occurred in 54% of samples; patients with lower baseline colony counts were more likely to achieve culture negativity. Resistance developed in one patient. Gastrointestinal symptoms were the most common side effects and were more frequent in patients receiving 1,200 mg. Azithromycin is a useful alternative treatment for disseminated MAC infection in AIDS patients. Symptomatic improvement correlates with measurable decreases in mycobacterial load.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Middle Aged; Mycobacterium avium; Mycobacterium avium-intracellulare Infection

We conducted a cost-effectiveness analysis to determine the clinical and economic consequences of Mycobacterium avium complex (MAC) prophylaxis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in a health care system with access unrestricted by financial barriers. The analysis was performed from a health care perspective and compared azithromycin (1200 mg/week) with no prophylaxis over a period of 10 years based on data from the Swiss HIV Cohort Study (SHCS) and randomized controlled trials. The main outcome measures were: expected survival; average health care costs; and cost-effectiveness in 1997 Swiss francs ( pound1 corresponds to about 2.3 CHF) per life-year saved. In patients with an initial CD4 count <50 cells/mm(3) and no AIDS, azithromycin increased expected survival by 4 months. In patients with AIDS, HAART durability had a major impact on expected survival and costs. Incremental survival increased from 2 to 4 months if we assumed a 10 year, instead of a 3 year, HAART effect. The cost-effectiveness of azithromycin relative to no prophylaxis in patients without AIDS was between 47,000 CHF (3-year HAART effect) and 60,000 CHF (10-year HAART effect) per life-year saved. The cost-effectiveness ratio increased to 118,000 CHF per life-year saved in patients with symptomatic AIDS. In conclusion, in the era of HAART, MAC prophylaxis with azithromycin increases expected survival and reduces health care costs substantially. Starting MAC prophylaxis in patients without AIDS is more effective and cost-effective than in patients with AIDS.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antibiotic Prophylaxis; Azithromycin; Bayes Theorem; Cohort Studies; Cost-Benefit Analysis; Health Care Costs; HIV Infections; Humans; Mycobacterium avium-intracellulare Infection

We conducted a randomized, double-blind, placebo-controlled multicenter trial of azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3. In an intent-to-treat analysis through the end of therapy plus 30 days, nine (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients developed MAC infection (hazard ratio, 0.34; P = .004). There was no difference in the ranges of minimal inhibitory concentrations of either clarithromycin or azithromycin for the five breakthrough (first) MAC isolates from the azithromycin group and the 18 breakthrough MAC isolates from the placebo group. Of the 76 patients who died during the study, four (10.5%) of 38 azithromycin recipients and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P = .025). For deaths due to all causes, there was no difference in time to death or number of deaths between the two groups. Episodes of non-MAC bacterial infection per 100 patient years occurred in 43 azithromycin recipients and 88 placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73). The most common toxic effect noted during the study was gastrointestinal, reported by 78.9% of azithromycin recipients and 27.5% of placebo recipients. Azithromycin given once weekly is safe and effective in preventing disseminated MAC infection, death due to MAC infection, and respiratory tract infections in patients with AIDS and CD4 cell counts of < 100/mm3.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium-intracellulare Infection; Survivors

Eight AIDS patients with Mycobacterium avium complex (MAC) bacteremia were randomized to receive azithromycin with or without granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 weeks to examine the effect of GM-CSF administration on clearance of mycobacteremia and on monocyte function. Superoxide anion production was significantly increased ex vivo in monocytes from patients receiving GM-CSF but not in those from patients receiving azithromycin alone. Relative to monocytes obtained from untreated healthy controls, median differences in viable intracellular MAC at 2, 4, and 6 weeks were -0.76, -0.94, and -0.47 log10 cfu/mL of lysate for cells from patients receiving GM-CSF versus -0.15, -0.11, and -0.19 log10 cfu/mL for cells from patients receiving azithromycin alone. Although no effect on mycobacteremia was detected, the administration of GM-CSF to AIDS patients with MAC bacteremia resulted in activation of their blood monocytes, as evidenced by increased superoxide anion production and enhanced mycobactericidal activity. GM-CSF deserves further investigation in the treatment of mycobacterial infections.

Topics: Adjuvants, Immunologic; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Bacteremia; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Microbial Sensitivity Tests; Monocytes; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Superoxides

Two consecutive, open, prospective trials of intermittent azithromycin (600 mg), usually given Monday, Wednesday, and Friday (TIW) for Mycobacterium avium complex (MAC) lung disease were initiated in human immunodeficiency virus-negative patients. Regimen A consisted of TIW azithromycin and daily ethambutol (15 mg/kg/day), daily rifabutin (300 mg/day), and initial twice weekly (BIW) streptomycin. Regimen B consisted of TIW azithromycin, TIW ethambutol (25 mg/kg/dose), TIW rifabutin (600 mg/dose), and initial BIW streptomycin. Of 19 patients enrolled in regimen A who completed at least 6 months of therapy, 14 (74%) had sputum samples become culture-negative. Of 39 patients enrolled in regimen B who completed at least 6 months of therapy, 24 (62%) had sputum conversion. These sputum conversion rates are comparable to previous rates at 6 months in patients receiving daily clarithromycin- or azithromycin-containing regimens. No resistance to azithromycin emerged with either regimen. This is the first study to demonstrate the efficacy of intermittent administration of medication for MAC lung disease.

Topics: Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifabutin; Streptomycin; Treatment Outcome

Disseminated Mycobacterium avium complex (MAC) infection continues to be a common opportunistic infection in patients infected with human immunodeficiency virus (HIV). The optimal therapy for disseminated MAC infection is unclear. We compared azithromycin plus ethambutol with clarithromycin plus ethambutol in the treatment of disseminated MAC infection in HIV type 1-infected patients, examining the frequency of bacteremia clearance, time to clearance, and study drug tolerance after 16 weeks of therapy. Fifty-nine patients for whom blood cultures were positive for MAC were enrolled in the study from 10 university-affiliated Veterans Affairs Medical Centers. Thirty-seven patients were evaluable for determination of quantitative bacteremia and clinical outcomes. Clearance of bacteremia was seen at the final visit in 37.5% of azithromycin-treated patients and in 85.7% of clarithromycin-treated patients (P = .007). The estimated median time to clearance of bacteremia was also significantly different between the two treatment arms: 4.38 weeks for clarithromycin recipients vs. > 16 weeks for azithromycin recipients (P = .0018). Only one isolate developed macrolide resistance during therapy. Abatement of symptoms, other laboratory-evident abnormalities, and adverse effects were similar in the two groups. At the doses used in this study, clarithromycin/ethambutol produced a more rapid resolution of bacteremia than did azithromycin/ethambutol, and clarithromycin/ethambutol was more effective at sterilization of blood cultures after 16 weeks of therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Bacteremia; Clarithromycin; Drug Therapy, Combination; Ethambutol; HIV-1; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Time Factors; Treatment Outcome

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Anti-Infective Agents; Atovaquone; Azithromycin; Clarithromycin; Dapsone; Ethnicity; Female; HIV Infections; Humans; Longitudinal Studies; Male; Medical Records; Mycobacterium avium-intracellulare Infection; Naphthoquinones; New York City; Pentamidine; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Regression Analysis; Rifabutin; Risk-Taking; Time Factors; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; United States; United States Public Health Service

We treated 39 elderly human immunodeficiency virus-noninfected patients with Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with azithromycin (600 mg daily), given initially as monotherapy. Adverse events occurred in 33 of 39 patients (85%) receiving azithromycin alone, most commonly gastrointestinal (GI) symptoms (32 of 39, or 82%) and hearing impairment (10 of 39, or 26%). Twenty-four of 39 patients (62%) required a lower dose or withdrawal of the drug. The mean serum level in patients who required a dose reduction because of hearing impairment was 0.8 +/- 0.4 microg/mL, and that in patients whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 microg/mL; in comparison, the mean serum level was 0.3 +/- 0.16 microg/mL in patients with no adverse events (P = .004 and .003, respectively). Decreasing the daily dose to 300 mg resulted in resolution of most adverse events. Serum levels with monotherapy were comparable to levels after the addition of other antituberculous drugs that included rifampin or rifabutin. Thus, a 300-mg rather than 600-mg daily dose of azithromycin is better tolerated by elderly patients, and serum levels appear unaffected by other antituberculous agents, including rifampin.

Topics: Adult; Aged; Anti-Bacterial Agents; Azithromycin; Dizziness; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Hearing Disorders; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Treatment Outcome

Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing.. We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex.. In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups.. 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.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Humans; Mycobacterium avium-intracellulare Infection

Prophylaxis for Mycobacterium avium complex (MAC) should be considered standard treatment for all patients with advanced HIV disease. MAC is the most common bacterial infection that affects AIDS patients. There are three effective agents that significantly reduce the risk of MAC--rifabutin, clarithromycin, and azithromycin. MAC prophylaxis is cost-effective, improves the quality of a patient's life, and improves overall survival by 25 to 32 percent.

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Azithromycin; Clarithromycin; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Randomized Controlled Trials as Topic; Rifabutin

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Erythromycin; Humans; Mycobacterium avium-intracellulare Infection

Mycobacterium avium complex infection is common in patients with AIDS. Experimentally infected mice have been treated successfully with azithromycin, a macrolide antibiotic. We report an uncontrolled phase I study in which male homosexuals with AIDS and M avium complex disease were given 500 mg azithromycin per day orally for 10, 20, or 30 days. Quantitative blood cultures showed a mean reduction in mycobacteraemia from 118 colony forming units (cfu)/ml to 43 cfu/ml in 3 patients treated for 10 days, and from 2028 cfu/ml to 136 cfu/ml in 21 patients treated for 20 or 30 days. Of the patients treated for 20 or 30 days, 15 of 21 with fever pretreatment and 12 of 18 with night sweats pretreatment reported resolution of these symptoms. The principal side-effects were loose stools or diarrhoea, but these did not result in cessation of therapy. Azithromycin, as a single oral agent, safely reduced M avium complex bacteraemia and associated symptoms in almost 75% of patients treated for at least 20 days. Further studies are needed to assess emergence of resistance.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Azithromycin; Bacteremia; Drug Administration Schedule; Drug Evaluation; Erythromycin; Follow-Up Studies; Homosexuality; Humans; Male; Mycobacterium avium-intracellulare Infection; Opportunistic Infections

Mycobacterium avium complex (MAC) thrives in various environments and mainly causes lung disease in humans. Because macrolide antibiotics such as clarithromycin or azithromycin are key drugs for MAC lung disease, the emergence of macrolide-resistant strains prevents the treatment of MAC. More than 95% of macrolide-resistant MAC strains are reported to have a point mutation in 23S rRNA domain V. This study successfully developed a melting curve assay using nonfluorescent labeled probes to detect the MAC mutation at positions 2058 to 2059 of the 23S rRNA gene (AA genotype, clarithromycin susceptible; TA, GA, AG, CA, AC, and AT genotypes, clarithromycin resistant). In the AA-specific probe assay, the melting peak of the DNA fragment of the AA genotype was higher than that of DNA fragments of other genotypes. Melting temperature (

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Leprostatic Agents; Lung Diseases; Macrolides; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis

Topics: Aged; Amikacin; Antitubercular Agents; Azithromycin; Biomarkers; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Stem Cells

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Cystic Fibrosis; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies

Antibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM.. We performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated.. Antibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364-4615) days. During follow-up, 13 patients had a negative conversion of sputum culture.. AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Retrospective Studies; Treatment Outcome

Anti-interferon-gamma (IFN-γ) autoantibodies has been recognised as an adult-onset immunodeficiency in the past decade in people who originate from Southeast Asia. These patients are susceptible to particular opportunistic infections, especially non-tuberculous mycobacteria (NTM). We present the case of a woman whom originally came from Thailand with disseminated

Topics: Adult; Anti-Bacterial Agents; Asian People; Autoantibodies; Azithromycin; Bacteremia; Disease Progression; Ethambutol; Female; Humans; Immunologic Deficiency Syndromes; Immunologic Factors; Interferon-gamma; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pericarditis; Pleurisy; Pneumonia, Bacterial; Recurrence; Rifampin; Rituximab; Thailand

Treatment failure of Mycobacterium avium complex (MAC) pulmonary disease occurs in about 30% of people with cystic fibrosis (CF) and may be a result of abnormal drug concentrations.. Prospective, cross-over, single-dose PK study of 20 pancreatic insufficient individuals with CF and 10 healthy controls (HC). CF subjects received simultaneous doses of oral azithromycin, ethambutol, and rifampin in the fasting state and with food and pancreatic enzymes, separated by two weeks. HC received fasting doses only. A non-compartmental model was used to estimate PK parameters of drugs and metabolites.. Azithromycin maximum concentration (C. PK profiles of azithromycin and ethambutol were similar between CF and HC, except azithromycin C. ClinicalTrials.gov Identifier: NCT02372383 Prior abstract publication: 1. Martiniano S, Wagner B, Brennan L, Wempe M, Anderson P, Nick J, Sagel S. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. Am J Resp Crit Care Med A4842-A4842, 2017. 2. Martiniano SL, Wagner BD, Brennan L, Wempe MF, Anderson PL, Nick JA, Sagel SD. Pharmacokinetics of oral MAC antibiotics in cystic fibrosis. J Cyst Fibros 16: S52-53, 2017.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Azithromycin; Cross-Over Studies; Cystic Fibrosis; Ethambutol; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifampin

This study aimed to compare the discontinuation rates attributed to adverse events and treatment outcomes between clarithromycin (CLR) and azithromycin (AZM) in patients with Mycobacterium avium complex lung disease (MAC-LD).. Among patients diagnosed with MAC-LD during 2001-2013, 560 for whom treatment was initiated as a guideline-based therapy until May 2018 were selected for adverse event analysis. Of them, 316 who underwent treatment for ≥12 months were selected for outcome analysis. Their medical records were retrospectively reviewed. The discontinuation and treatment success rates were analysed after adjustments using the inverse probability of treatment weighted (IPTW) method.. Among the 560 patients, 466 (83.2%) and 94 (16.8%) started CLR-containing and AZM-containing regimens, respectively. The IPTW method using propensity scoring revealed that the discontinuation rate attributed to adverse events was significantly higher with CLR than AZM use (24.6% vs. 9.6%; P=0.001). The overall treatment success rate of the 316 patients who received guideline-based therapy for ≥12 months was 83.2%. Analysis adjusted by the IPTW method showed no significant difference in the treatment success rate between the use of CLR and AZM. Furthermore, 1-year and 3-year recurrence rates were similar with the two drugs (6.8% vs. 6.0%; P>0.999 and 31.0% vs. 37.5%; P=0.482, respectively).. These findings suggest that an AZM-containing regimen may be the better initial treatment choice for MAC-LD as it resulted in lesser discontinuation rates attributed to adverse events while offering similar patient outcomes when compared with CLR.

Topics: Anti-Bacterial Agents; Azithromycin; Clarithromycin; Humans; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Propensity Score; Retrospective Studies; Treatment Outcome

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary

Topics: Antitubercular Agents; Azithromycin; Body Mass Index; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Odds Ratio; Treatment Outcome

Mycobacterium avium causes atypical infection in both immunocompetent and immunocompromised individuals. Conventional chemotherapy for M. avium infection is not efficient due to lengthy course of treatment and drug-associated toxic side effects. The present study was aimed at reducing dosing frequency of antimicrobial regimen consisting of azithromycin (AZM), rifabutin (RBT) and ethambutol (EMB) by encapsulation of drugs in nanoparticles (NPs) in experimental M. avium infection in mice.. Poly (DL-lactide-co-glycolide) NPs containing anti-M. avium drugs were prepared, characterized and studied for their pharmacokinetics and pharmacodynamics parameters. Drug-loaded NPs were further analyzed for their therapeutic efficacy against experimental M. avium infection in mice.. Drug-loaded NPs were of size 227.3±16.4 for RBT, 334.35±11.7 for AZM and 509.85±20.5 for EMB with smooth surface morphology and negative zeta potential. AZM, EMB and RBT from NPs were detectable for 6, 4 and 5 days, respectively, in the mice plasma, whereas free drugs were cleared from mice circulation within 24 h. Chemotherapeutic effects of weekly administered drug-loaded NPs were equivalent to daily administered free drugs.. Our findings showed that NPs gave sustained release of drugs inside plasma and organs, thus decreasing dosage frequency, and their weekly dosage had therapeutic efficacy equivalent to daily dosage of free drugs.

Topics: Animals; Antibiotics, Antitubercular; Azithromycin; China; Drug Therapy, Combination; Ethambutol; Mice; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Nanocapsules; Rifabutin

To investigate the performance of the two backbone drugs in the standard combination therapy regimen in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) infection.. Six HFS were inoculated with human-derived monocytes infected with MAC, and treated with 15 mg/kg of ethambutol and 500 mg of azithromycin daily for 28 days to recapitulate the concentration-time profiles seen in the lungs of humans treated with these drugs and doses. The concentration-time profiles achieved were validated by sampling the central compartment at seven timepoints over 24 h. The total MAC burden, as well as the subpopulation resistant to 3 × MIC of each drug, was identified based on sampling the peripheral compartment of each system on days 0, 3, 7, 14, 21 and 28 of therapy. The experiment was performed twice.. In non-treated control HFS, MAC grew from 5.0 to 8.53 log10 cfu/mL in 28 days. The dual therapy killed a maximum of 1.52 ± 0.43 log10 cfu/mL during the first 7 days, after which it failed. By day 28 there was no difference in MAC burden between the combination-therapy-treated and non-treated systems. Failure arose in parallel with the emergence of acquired ethambutol resistance. By day 28, 100% of the bacterial population was ethambutol resistant in the combination-therapy-treated HFS replicates.. The backbone combination of macrolide and ethambutol has poor MAC kill rates and is ineffective. Microbial kill is rapidly abrogated by acquired drug resistance. This backbone should be replaced.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; Drug Resistance, Multiple, Bacterial; Ethambutol; Humans; Models, Biological; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; THP-1 Cells

Mycobacterium aviumcomplex is now the leading mycobacterial cause of chronic pneumonia in the United States. Macrolides and ethambutol form the backbone of the regimen used in the treatment of pulmonary disease. However, therapy outcomes remain poor, with microbial cure rates of 4% in cavitary disease. The treatment dose of azithromycin has mostly been borrowed from that used to treat other bacterial pneumonias; there are no formal dose-response studies in pulmonaryM. aviumdisease and the optimal dose is unclear. We utilized population pharmacokinetics and pharmacokinetics/pharmacodynamics-derived azithromycin exposures associated with optimal microbial kill or resistance suppression to perform 10,000 patient Monte Carlo simulations of dose effect studies for daily azithromycin doses of 0.5 to 10 g. The currently recommended dose of 500 mg per day achieved the target exposures in 0% of patients. Exposures associated with optimal kill and resistance suppression were achieved in 87 and 54% of patients, respectively, only by the very high dose of 8 g per day. The azithromycin susceptibility breakpoint above which patients failed therapy on the very high doses of 8 g per day was an MIC of 16 mg/liter, suggesting a critical concentration of 32 mg/liter, which is 8-fold lower than the currently used susceptibility breakpoint of 256 mg/liter. If the standard dose of 500 mg a day were used, then the critical concentration would fall to 2 mg/liter, 128-fold lower than 256 mg/liter. The misclassification of resistant isolates as susceptible could explain the high failure rates of current doses.

Topics: Anti-Bacterial Agents; Area Under Curve; Azithromycin; Computer Simulation; Drug Dosage Calculations; Drug Resistance, Bacterial; Female; Humans; Male; Microbial Sensitivity Tests; Models, Statistical; Monte Carlo Method; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.. Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 μg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings.. Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found.. Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; C-Reactive Protein; Clarithromycin; Drug Resistance, Bacterial; Female; Humans; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Risk Factors; Serum Albumin; Sputum; Tomography, X-Ray Computed; Treatment Outcome

Long-term outcomes in non-HIV immunocompromised patients with disseminated Mycobacterium avium complex (dMAC) infections are unknown and the need for post-treatment secondary prophylaxis against MAC is uncertain in this setting. The objective of this study was to determine the need of continuing secondary anti-MAC prophylaxis in non-HIV patients after completing treatment of the primary dMAC episode.. We conducted a ten-year multi-center analysis of non-HIV immunosuppressed patients with dMAC infections in Hong Kong.. We observed sixteen patients with dMAC during the study period of which five (31 %) were non-HIV immunosuppressed patients. In the non-HIV immunosuppressed group, three patients completed a treatment course without secondary prophylaxis, one patient received azithromycin-based secondary prophylaxis and one patient was still receiving therapy for the first dMAC episode. All the three patients who completed treatment without being given secondary prophylaxis developed recurrent dMAC infection requiring retreatment.. In view of the high rate of dMAC infection recurrence in non-HIV immunocompromised patients following treatment completion, our data support long-term anti-MAC suppression therapy after treatment of the first dMAC infection episode in immunocompromised non-HIV patients, as is recommended for patients with advanced HIV. Tests of cell mediated immune function need to be evaluated to guide prophylaxis discontinuation in non-HIV patients.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; Female; HIV Infections; Hong Kong; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Recurrence

Topics: Abscess; Anti-Bacterial Agents; Azithromycin; Ethambutol; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Leg; Lung Diseases, Interstitial; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycophenolic Acid; Polymyositis; Prednisone; Rifabutin; Skin Diseases, Bacterial

Mycobacterial spindle cell pseudotumor (MSP) represents a rare, non-malignant, mass-forming reaction to various mycobacterial infections, typically occurring in immunocompromised patients. It is characterized by the proliferation of spindle-shaped fibrohistiocytic cells without the formation of epithelioid granulomas. Without staining for acid-fast bacilli, histological distinction from other spindle cell lesions, including malignancy, can be difficult. Most of the MSP cases reported in the literature have involved lymph nodes, skin, spleen, or bone marrow, but rarely involve the lung. MSP predominately occurs in patients who are immunosuppressed. We present a patient with MSP of the transplanted lung caused by non-tuberculous mycobacteria, in whom both the natural course of the untreated pseudotumor as well as the response to antimycobacterial treatments were observed.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Disease Progression; Ethambutol; Female; Fluoroquinolones; Humans; Immunocompromised Host; Lung; Lung Transplantation; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Treatment Outcome

Topics: Anti-Bacterial Agents; Azithromycin; Bronchial Fistula; Cysts; Ethambutol; Humans; Hydropneumothorax; Immunocompromised Host; Liver Diseases; Lung; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pleura; Rifampin; Tomography, X-Ray Computed

There is no large study validating the appropriateness of current treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is a retrospective single-center review evaluating the efficacy of macrolide/azalide-containing regimens for nodular/bronchiectatic (NB) MAC lung disease.. Patients were treated according to contemporary guidelines with evaluation of microbiologic responses. Macrolide susceptibility of MAC isolates was done at initiation of therapy, 6 to 12 months during therapy, and on the first microbiologic recurrence isolate. Microbiologic recurrence isolates also underwent genotyping for comparison with the original isolates.. One hundred eighty patients completed > 12 months of macrolide/azalide multidrug therapy. Sputum conversion to culture negative occurred in 154 of 180 patients (86%). There were no differences in response between clarithromycin or azithromycin regimens. Treatment regimen modification occurred more frequently with daily (24 of 30 [80%]) vs intermittent (2 of 180 [1%]) therapy (P = .0001). No patient developed macrolide resistance during treatment. Microbiologic recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC isolates, 27% with true relapse isolates (P = .03). Overall, treatment success (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after completion of therapy: 75% reinfection isolates, 25% true relapse isolates.. Current guidelines for macrolide/azalide-based therapies for NB MAC lung disease result in favorable microbiologic outcomes for most patients without promotion of macrolide resistance. Intermittent therapy is effective and significantly better tolerated than daily therapy. Microbiologic recurrences during or after therapy are common and most often due to reinfection MAC genotypes.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electrophoresis, Gel, Pulsed-Field; Female; Follow-Up Studies; Genotype; Humans; Lung Diseases; Macrolides; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Practice Guidelines as Topic; Recurrence; Retrospective Studies; Sputum; Treatment Outcome

We analyzed 369 patients with no prior Mycobacterium avium complex (MAC) infection and CD4 <50 cells/μL (baseline), while on combination antiretroviral therapy(cART), for incidence rates of primary MAC infection during the 6 months after baseline, by prophylaxis status. Of participants (median age, 40 years old), most were male (81%) and about half were non-white; at baseline, 81% of participants were on cART >60 days and 19% had HIV RNA <1000 copies/mL, whereas 65% had HIV RNA >10,000 copies/mL. Eleven patients had MAC infection within 6 months baseline (rate=0.6/100 person months): 4/175 on MAC prophylaxis vs. 7/194, no MAC prophylaxis (p=0.64). Of the 11 patients, seven had HIV RNA >10,000, and three >1000-9999 copies/mL at baseline (one missing). Median time to MAC infection was 62 days (IQR 43-126, maximum 139 days). No MAC infection occurred among 71 (19%) patients virologically suppressed (HIV RNA <1000 copies/mL) at baseline, including 41 patients with no MAC prophylaxis during follow-up. A small number of eligible virologically suppressed participants and the lack of data on cART/MAC prophylaxis adherence limited our observational nonrandomized study. Primary MAC prophylaxis may not be required for cART-virologically suppressed patients with CD4 <50 cells/mL.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifabutin; RNA, Viral; United States; Viral Load

Topics: Azithromycin; Bronchiectasis; Clarithromycin; Female; Humans; Lung Diseases; Macrolides; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Existing literature is inconclusive regarding how the nodular bronchiectatic form of Mycobacterium avium complex (MAC) disease will progress without treatment and when treatment initiation should be considered.. To assess the natural course of MAC pulmonary disease by serial thin-section computed tomography (CT).. Of 339 patients with nodular bronchiectatic form of MAC disease, we selected 265 untreated patients who had serial CTs (mean observation period, 32 ± 21 mo). Two independent chest radiologists reviewed retrospectively all CT scans for the presence and extent of lung abnormalities (maximal total score, 30).. Of 265 patients, 126 patients (48%) had disease that had progressed and that needed treatment owing to radiologic deterioration or worsening symptoms, and the remaining 139 patients (52%) did not. On multivariate analysis, the presence of cavity (adjusted hazard ratio, 2.06; P = 0.004) and consolidation (adjusted hazard ratio, 1.55; P = 0.019) at initial CT remained as independent factors associated with disease progression and treatment requirement. The presence of cavitary lesions demonstrated the highest positive predictive value (61%) and significant correlation (P = 0.005) with smear positivity. Differences in the extent of each pattern and total CT score in the serial studies were significantly larger (P < 0.05) in patients requiring treatment. The total CT score increased by 2.41 in the treatment-requiring group compared with 0.25 in the group that did not receive treatment.. Without treatment, about half of patients demonstrate progressive disease on serial CT over a mean follow-up period of 32 months and, thus, required treatment. Patients showing cavities or consolidation on initial CT are more likely to have progressive disease and thus to require treatment eventually.

Topics: Aged; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; Disease Progression; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung; Male; Middle Aged; Multiple Pulmonary Nodules; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Proportional Hazards Models; Retrospective Studies; Rifampin; Tomography, X-Ray Computed

We reported a case of Mycobacterium avium infection in which disease activity appeared to have been suppressed after fungal infection. After the increase in β-D-glucan, her symptoms of fever and chest pain disappeared. We think this phenomenon may be microbial substitution and mild fungal infection may improve the activity due to M avium.

Topics: Aged; Anti-Bacterial Agents; Antitubercular Agents; Azithromycin; beta-Glucans; C-Reactive Protein; Drug Therapy, Combination; Female; Humans; Lung Diseases, Fungal; Mycobacterium avium-intracellulare Infection; Recurrence; Tomography, X-Ray Computed

Topics: Aged, 80 and over; Anti-Bacterial Agents; Arthritis, Rheumatoid; Azithromycin; Drug Therapy, Combination; Ethambutol; Female; Glucocorticoids; Humans; Immunocompromised Host; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prednisone; Rifampin; Skin Diseases, Bacterial

Lung disease due to mycobacterium avium complex (MAC) is being increasingly recognized. The clinical and radiological manifestations are varied and treatment is complex. We present two cases of MAC-induced lung disease to illustrate this disease.

Topics: Aged; Azithromycin; Bronchoalveolar Lavage Fluid; Drug Therapy, Combination; Ethambutol; Female; Humans; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Rifampin; Tomography, X-Ray Computed; Treatment Outcome

Because most HIV-infected patients die of diseases caused by opportunistic pathogens, the prevention of these infections is an important clinical issue. Cost-containment in the healthcare system is a subject of high priority in public debate. Methods to determine cost-effectiveness of different therapeutic strategies are therefore needed to obtain valid data as the basis for decisions on cost reduction without a decrease in the quality of care. A disease state transition model based on a Markov process was developed to simulate the natural history of HIV infection and the acquired immunodeficiency syndrome (AIDS). Using this model survival time and treatment costs for every patient can be estimated and the results of alternative medications compared. We determined the cost-effectiveness (per life-year saved, LYS) of different strategies for prevention of Mycobacterium avium complex infections in AIDS patients whose treatment regimens include protease inhibitors. The cost-effectiveness ratios for treatment strategies vary from 13,510 euro to 46,152 euro per LYS without protease inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors. When azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the most cost-effective medication for preventing M. avium complex. The results were stable against a wide range of parameter variations concerning costs and incidence rates.

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Cost-Benefit Analysis; Drug Therapy, Combination; Health Care Costs; Humans; Models, Economic; Mycobacterium avium-intracellulare Infection; Protease Inhibitors; Quality-Adjusted Life Years; Rifabutin

Mycobacterium avium causes disseminated infection in immunosuppressed individuals and lung infection in patients with chronic lung diseases. M. avium forms biofilm in the environment and possibly in human airways. Antibiotics with activity against the bacterium could inhibit biofilm formation. Clarithromycin inhibits biofilm formation but has no activity against established biofilm.

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Aza Compounds; Azithromycin; Biofilms; Clarithromycin; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolines

The genomic DNA patterns (genotypes) of 55 episodes of late positive sputum isolates, collected after >or=4 consecutive months of negative sputum cultures, in prospective macrolide treatment trials of Mycobacterium avium complex (MAC) lung disease were assessed by pulsed-field gel electrophoresis (PFGE). Having >or=2 cultures positive for MAC after completion of therapy was documented 23 times; of 20 episodes studied by PFGE, 17 (85%) represented new genotypes (i.e., new infections), and 87% occurred in patients with nodular bronchiectasis. With >or=2 positive cultures after therapy was stopped prematurely, 6 (86%) of 7 episodes were relapses. Single positive cultures after completion of therapy occurred 16 times; only 1 (6%) was predictive of a subsequent relapse. No late isolates were macrolide resistant. Thus, relapses of MAC lung disease with these macrolide regimens are unusual, and most infections after completing therapy resulted from new strains in patients with nodular bronchiectasis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Clarithromycin; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Polymerase Chain Reaction; Prospective Studies; Sputum

Mycobacterium avium complex (MAC) disease was evaluated in a provincial program of azithromycin prophylaxis. Highly active antiretroviral therapy (HAART) was prescribed to 383 (65%) of 587 patients eligible for MAC prophylaxis (CD4 <75 cells/mm3). By use of an intent-to-treat analysis, MAC disease was observed in 21 of 271 patients who did not receive prophylaxis (incidence rate, 8 events per 100 person-years). MAC events occurred in 10 of 316 patients who received azithromycin (2.37 events per 100 person-years). Localized lymphadenitis compatible with immune reconstitution disease accounted for 23% of all MAC events, in contrast to studies in the pre-HAART era, where almost all cases were disseminated. None of the MAC isolates from the 10 prophylaxis failures were resistant to azithromycin. Azithromycin appeared to be protective against disseminated MAC in patients who were either unresponsive or nonadherent to HAART, but it did not prevent the development of immune reconstitution disease due to MAC.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antiretroviral Therapy, Highly Active; Azithromycin; HIV Infections; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Colonic Diseases; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Fatal Outcome; Granular Cell Tumor; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Nucleic Acid Amplification Techniques; Rifabutin; RNA, Bacterial; Whipple Disease

Moxifloxacin activity against Mycobacterium avium complex (MAC) was evaluated in vitro against 25 strains. The MIC was determined to range from 0.125 to 2.0 microg/ml. In addition, U937 macrophage monolayers infected with MAC strain 101 (serovar 1) were treated with moxifloxacin (0.25 to 8 microg/ml) daily, and the number of intracellular bacteria was quantitated after 4 days. Moxifloxacin showed inhibitory activity at 0.5 microg/ml and higher. To assess the activity of moxifloxacin containing regimens in vivo, we infected C57BL bg(+)/bg(+) mice with 3 x 10(7) MAC strain 101 bacteria intravenously. One week later treatment was begun with the following: (i) moxifloxacin (50 mg/kg/day or 100 mg/kg/day), ethambutol (100 mg/kg/day), or a combination of moxifloxacin and ethambutol; or (ii) moxifloxacin (100 mg/kg/day), azithromycin (200 mg/kg/day), or rifabutin (40 mg/kg/day) as oral monotherapy; or (iii) all permutations of two-drug therapy or all three drugs in combination. All groups contained at least 14 animals, and the control group received the drug vehicle. After 4 weeks, quantitative blood cultures were obtained and the number of bacteria in liver and spleen was quantitated. Moxifloxacin, ethambutol, and azithromycin were active as single agents in liver, spleen, and blood. Rifabutin showed inhibitory activity only in the blood. Two-drug combinations containing azithromycin were no more active than azithromycin alone. Similarly, the three-drug combination was not more active than azithromycin alone in the spleen. Rifabutin did not add to the activity of any other single agent or two-drug combination. Moxifloxacin at both concentrations in combination with ethambutol was significantly more active than each drug alone.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Aza Compounds; Azithromycin; Drug Interactions; Drug Therapy, Combination; Ethambutol; Female; Fluoroquinolones; Macrophages; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolines; Rifabutin

Ninety-two patients were assessable in 3 consecutive, open, noncomparative, prospective, controlled, single-center trials of the use of multidrug regimens that contain azithromycin for treating pulmonary Mycobacterium avium complex (MAC) disease. Azithromycin was provided at a dose of 300-600 mg per day with oral companion drugs administered daily (regimen A, 29 patients); 600 mg 3 times weekly (t.i.w.), with oral companion drugs administered daily (regimen B, 20 patients); and 600 mg (t.i.w.), with oral companion drugs administered t.i.w. (regimen C, 43 patients). All regimens included rifabutin (or rifampin) and ethambutol as companion drugs as well as initial streptomycin. Treatment success was defined as 12 months of negative cultures while on therapy. Treatment failure was defined as sputum culture positivity after at least 6 months of therapy. Of the patients in each regimen who reached study end points, 17 of 29 (59%) were in regimen A, 11 of 20 (55%) were in regimen B, and 28 of 43 (65%) were in regimen C met the treatment success criterion. There were no statistically significant differences in outcome between the 3 regimens. These studies demonstrate the effectiveness of daily and t.i.w. regimens containing azithromycin for treatment of MAC lung disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Drug Therapy, Combination; Drug Tolerance; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifabutin; Rifampin; Streptomycin; Treatment Outcome

Topics: Adult; Azithromycin; Chemoprevention; Female; HIV Infections; HIV Seropositivity; Humans; Mycobacterium avium-intracellulare Infection; Sexual Behavior; Sexually Transmitted Diseases

Azithromycin, has been proved to be effective in the treatment and prophylaxis of a wide variety of infections. While the penetration of azithromycin into a number of types of mammalian cells has been well characterized, the influence of HIV infection on the intracellular disposition of this agent has not been studied. We therefore studied the disposition of azithromycin in polymorphonuclear (PMN) and mononuclear (MONO) leukocytes from six healthy volunteers and six volunteers with AIDS. After oral administration of a single 1200-mg dose of azithromycin (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin concentrations in MONOs and PMNs were measured. Analysis of the intracellular pharmacokinetics revealed an apparent difference in the MONO and PMN profile; this profile was similar for both groups. Intracellular concentrations of azithromycin remained high throughout the study period. Furthermore, no statistically significant differences in the intracellular area under the curve (11309+/-2543 vs. 16650+/-6254 for PMN; 14180+/-3802 vs. 21211+/-10001 for MONO) were observed between the healthy and AIDS populations, respectively. Our data confirm the extensive uptake of azithromycin by white blood cells both in healthy volunteers and in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Female; Humans; Leukocytes; Leukocytes, Mononuclear; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Neutrophils

Pharmacoeconomic evaluations are often based on computer models which simulate the course of disease with and without medical interventions. The purpose of this study is to propose and illustrate a rigorous approach for validating such disease models. For illustrative purposes, we applied this approach to a computer-based model we developed to mimic the history of HIV-infected subjects at the greatest risk for Mycobacterium avium complex (MAC) infection in Switzerland. The drugs included as a prophylactic intervention against MAC infection were azithromycin and clarithromycin. We used a homogenous Markov chain to describe the progression of an HIV-infected patient through six MAC-free states, one MAC state, and death. Probability estimates were extracted from the Swiss HIV Cohort Study database (1993-95) and randomized controlled trials. The model was validated testing for (1) technical validity (2) predictive validity (3) face validity and (4) modelling process validity. Sensitivity analysis and independent model implementation in DATA (PPS) and self-written Fortran 90 code (BAC) assured technical validity. Agreement between modelled and observed MAC incidence confirmed predictive validity. Modelled MAC prophylaxis at different starting conditions affirmed face validity. Published articles by other authors supported modelling process validity. The proposed validation procedure is a useful approach to improve the validity of the model.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Computer Simulation; Disease Progression; Economics, Pharmaceutical; HIV Infections; Humans; Markov Chains; Mycobacterium avium-intracellulare Infection; Probability; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Factors; Switzerland

To develop a simulation model to project costs, life expectancy, and cost-effectiveness in discounted dollars per quality-adjusted life-year (QALY) saved for clinical strategies to prevent Mycobacterium avium complex (MAC) in patients with AIDS.. We used natural history data from the Multicenter AIDS Cohort Study, efficacy and toxicity data from randomized clinical trials, and cost data from the AIDS Cost and Services Utilization Survey. The model permits timing of prophylaxis to be stratified by CD4 count (201-300, 101-200, 51-100, and < or = 50/mm3), and allows combinations of prophylaxis, crossover to second- and third-line agents for toxicity, and consideration of adherence, resistance, and quality of life.. The model projects that the average HIV-infected patient with a beginning CD4 count between 201 and 300/mm3 has total lifetime costs of approximately $43,150 and a quality-adjusted life expectancy of 42.35 months. If azithromycin prophylaxis for M. avium complex is begun after the CD4 declines to 50/mm3, costs and quality-adjusted survival increase to approximately $44,040 and 42.78 months, respectively, for an incremental cost-effectiveness ratio of $25,000/QALY compared with no M. avium complex prophylaxis. Other prophylaxis options (i.e., rifabutin, clarithromycin, and combination therapies) either cost more but offer shorter survival, or have cost-effectiveness ratios above $260,000/QALY. Sensitivity analysis reveals that, for reasonable assumptions about quality of life, risk of infection, prophylaxis cost, adherence, and resistance, azithromycin remains the most cost-effective prophylaxis option.. Azithromycin prophylaxis, begun after the CD4 count has declined to 50/mm3, is the most cost-effective M. avium complex prophylaxis strategy. Consistent with new United States Public Health Service guidelines, it should be the first-line prophylaxis option.

Topics: AIDS-Related Opportunistic Infections; Azithromycin; Clarithromycin; Cost-Benefit Analysis; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Quality-Adjusted Life Years; Rifabutin

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC > or = 32 microg/ml) and azithromycin (azithromycin resistance was defined as MIC > or = 128 microg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 microg/ml or azithromycin at 128 microg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 x 10(-3) at week 8 and 1.1 x 10(-2) at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was approximately 3.5 x 10(-5) (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Clarithromycin; Disease Models, Animal; Drug Resistance, Microbial; Female; Mice; Mice, Inbred C57BL; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Spleen

Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors.. To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors.. Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin.. Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios.. Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l.. MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibiotics, Antitubercular; Azithromycin; Clarithromycin; Cost-Benefit Analysis; Drug Therapy, Combination; Health Care Costs; HIV Infections; HIV Protease Inhibitors; Humans; Male; Markov Chains; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quality of Life; Rifabutin; United States

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotic Prophylaxis; Azithromycin; HIV-1; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Recurrence; Retrospective Studies

Computer-aided simulations suggest that the doses and schedules of administration of azithromycin proposed in treatment and prophylaxis of Mycobacterium avium complex (MAC) in AIDS patients will result in drug concentrations in serum and extracellular fluids remaining for sustained periods of time in the 0.03-0.1 mg/L range. We exposed cultured rat embryo fibroblasts to these concentrations (and multiples up to 20 mg/L) for up to 16 days. Electron microscopy showed that after 7 days' incubation in 0.03 mg/L azithromycin, there was conspicuous accumulation of osmiophilic, lamellar structures (myeloid bodies) in lysosomes, suggesting the onset of a phospholipidosis. Assay of total cell phospholipids and cholesterol showed significant increases in cells exposed to > or = 1 to 5 mg/L of azithromycin in association with hyperactivity of the lysosomal enzyme cathepsin B. The data suggest that azithromycin, at extracellular concentrations pertinent to its use for MAC treatment, and perhaps also prophylaxis, causes limited morphological alterations of the lysosomes in cultured cells which are of the same nature as those developing rapidly and extensively at higher concentrations.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Cells, Cultured; Computer Simulation; Female; Fibroblasts; Lysosomes; Microscopy, Electron; Models, Biological; Mycobacterium avium-intracellulare Infection; Rats; Rats, Wistar

Azithromycin (Zithromax) has been used to treat a number of infections, including mycobacterium avium complex (MAC). A study using Azithromycin to prevent MAC shows the drug's effectiveness in reducing the outbreak of MAC and also protecting from other infections, including PCP. This study involved 180 HIV-positive subjects, of which 89 received 1200 mg of Azithromycin once a week, and 91 received a placebo once a week. Fifteen percent of the treated subjects developed MAC infections compared to 30 percent of the placebo group. In addition, more subjects taking the placebo developed PCP than subjects taking the Azithromycin. Diarrhea, nausea, and abdominal pain were the most common side effects from Azithromycin.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Female; Humans; Male; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis

Prevention of opportunistic infections contributes to improved quality of life and survival in individuals with acquired immunodeficiency syndrome (AIDS). Agents which are more effective and convenient, less costly, and better tolerated are needed for multiple organism primary prophylaxis. Azithromycin, azalide with high and prolonged intracellular levels, promise to provide to protection against Mycobacterium avium complex (MAC) disease in those with advanced AIDS when given weekly. A large trail comparing rifabutin (300 mg daily), a currently approved primary prophylactic agent for MAC, with azithromycin (1200 mg weekly) has been completed and is under analysis. If weekly azithromycin provides equivalent or better protection from disseminated MAC, the cost effectiveness and convenience of MAC prophylaxis may be improved.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Clarithromycin; Clinical Trials as Topic; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin

Topics: Azithromycin; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; HIV Infections; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Uveitis

We initiated a prospective trial of an azithromycin-containing regimen for the treatment of human immunodeficiency virus-negative patients with Mycobacterium avium complex (MAC) lung disease; the initial 4 months of therapy were with azithromycin (600 mg/d) alone. The primary study endpoint was microbiological response measured at 4 and 6 months of therapy. Of 29 patients enrolled in the study, 23 completed therapy. Fifty-two percent of these 23 patients were male, and 65% were smokers. All 23 patients were older than 45 years of age; 83% had bilateral disease, and 48% had fibrocavitary disease. Macrolide (clarithromycin)-susceptible MAC isolates were recovered from these 23 patients before treatment. Cultures of sputum from 38% of these patients became negative, and the positivity of cultures of sputum from 76% of these patients was significantly reduced. Sixty-eight percent of sputum cultures were strongly positive (> 200 colonies) before therapy, while only 27% were strongly positive after therapy. Although most patients continued to receive 600 mg of azithromycin/d, the high incidence of gastrointestinal side effects (76%) and altered hearing (41%) suggests the need for lower or less frequent dosing. Macrolide (clarithromycin) resistance did not develop in any MAC isolates during monotherapy. These results, which demonstrate that azithromycin is active against MAC pulmonary disease, provide a rationale to include this drug in the initial multidrug regimens recommended for the treatment of this disease.

Topics: Aged; Aged, 80 and over; Azithromycin; Consumer Product Safety; Drug Tolerance; Female; Follow-Up Studies; HIV Infections; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Neutropenia; Rifabutin

Topics: Azithromycin; Clarithromycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; HIV; Humans; Leukocyte Count; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Platelet Count; Rifabutin

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Drug Approval; Humans; Mycobacterium avium-intracellulare Infection

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotics, Antitubercular; Azithromycin; Drug Approval; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; United States; United States Food and Drug Administration

The Third International Conference on the Macrolides, Azalides, and Streptogramins was held in Lisbon, Portugal. Conferees were given news on the latest advances in the development of innovative antibiotics belonging to these increasingly important groups of drugs, and learned of their expanding clinical indications. The following areas were emphasized at the conference: multiresistant gram-positive bacteremias in patients with serious underlying infections, azithromycin's effectiveness against acute community-acquired pneumonia, results of clarithromycin plus ethambutol in HIV-infected patients with MAC bacteremia, duodenal ulcers associated with Helicobacter pylori infections, and use of roxithromycin against AIDS-related cryptosporidium diarrhea.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Bacteremia; Bacterial Infections; Clarithromycin; Clofazimine; Cryptosporidiosis; Drug Therapy, Combination; Duodenal Ulcer; Ethambutol; Humans; Microbial Sensitivity Tests; Mycobacterium avium-intracellulare Infection; Pneumonia; Smoking; Virginiamycin

Study efforts are showing progress in the prevention and therapy of Mycobacterium avium complex (MAC) infection. A review of recent study developments highlights clinical findings on prophylactic use of rifabutin, clarithromycin, and azithromycin, used both as monotherapies and as combination therapies. Three tables highlight study results from MAC prophylaxis studies, MAC treatment studies, and candidate regimens for MAC prophylaxis in AIDS. Treatment of disseminated MAC is also addressed. The combination of clarithromycin and clofazimine should not be used as initial therapy. Clofazimine's role in initial therapy is uncertain, and combinations of clarithromycin and ethambutol, with or without rifabutin, appear to be the best current treatment options.

Topics: Acquired Immunodeficiency Syndrome; Antitubercular Agents; Azithromycin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin

The Food and Drug Administration (FDA) approved the broad-spectrum antibiotic azithromycin for prevention of Mycobacterium avium complex (MAC) in people with advanced HIV disease. The treatment offers flexibility in that it can be taken once a week. Clinical trials show that 1200 mg of azithromycin taken weekly reduced the risk of developing MAC bacteria in the bloodstream. In a large double-blind study, the drug was more effective than rifabutin in preventing MAC. A combination of azithromycin and rifabutin also was shown to be more effective than rifabutin alone. Common side effects for the drug include diarrhea, nausea, and abdominal pain.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Drug Approval; Humans; Mycobacterium avium-intracellulare Infection; United States; United States Food and Drug Administration

Mycobacterium avium complex (MAC) infection occurs in 18 to 40 percent of people with AIDS, and most commonly in those with CD4 counts under 50. MAC is a difficult infection to diagnose, as its symptoms mimic many other infections and tumors. MAC infections can occur in the respiratory system or gastrointestinal tract, and the infection may spread through the bloodstream. Clinical trials for MAC prophylaxis include clarithromycin, rifabutin, or a combination of both. The individual drugs and the combination both may cause side effects that would require discontinuation of treatment. Azithromycin administered weekly, compared to rifabutin, or a combination of both, also had some significant adverse effects. The azithromycin/rifabutin combination resulted in the lowest rate of MAC breakthrough. Drug resistance and cross resistance to these drugs exist.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin

Participants at the XI International Conference on AIDS in Vancouver appeared impressed by the improvements being made in the diagnosis, treatment, and prophylaxis of AIDS-related opportunistic infections. Improvements in the following areas are discussed: cytomegalovirus infection prophylaxis and maintenance with oral ganciclovir, prophylactic effects of azithromycin against Mycobacterium avium complex infection and its potential for preventing Pneumocystis carinii pneumonia, and the use of doxil versus bleomycin plus vincristine in treating Kaposi's sarcoma. Developments in the use of cyclodextrin (itraconazole) for treating oral candidiasis showed it may be a more suitable option than fluconazole given fluconazole's high price, drug interactions, and potential to cause resistance.

Topics: AIDS-Related Opportunistic Infections; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Azithromycin; Bleomycin; Candidiasis; Cytomegalovirus Infections; Doxorubicin; Drug Carriers; Ganciclovir; Humans; Liposomes; Mycobacterium avium-intracellulare Infection; Pneumonia, Pneumocystis; Sarcoma, Kaposi; Vincristine

A study concluded that for the prevention of disseminated Mycobacterium avium complex in patients with advanced HIV infection once-weekly dosing of azithromycin is a simpler and more effective regimen than daily rifabutin. The California Collaborative Treatment Group researchers found that azithromycin alone or in combination with rifabutin is more effective than rifabutin alone. Azithromycin does not interact with other commonly-prescribed medicines for AIDS patients. Azithromycin achieves high levels at the site of infection.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Drug Administration Schedule; Humans; Mycobacterium avium-intracellulare Infection

Disseminated Mycobacterium avium complex (DMAC) is the third most common opportunistic infection in people with AIDS, infecting up to 50 percent of them. Symptoms include high fever, weight loss, fatigue, diarrhea, poor appetite, night sweats, and anemia. Diagnosis is by blood culture. Results of two recent studies are presented, as well as treatment guidelines issued by a national panel.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibiotics, Antitubercular; Antifungal Agents; Azithromycin; Clarithromycin; Clinical Trials as Topic; Dexamethasone; Drug Interactions; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Fluconazole; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Risk Factors; Uveitis

To determine the impact of the introduction of clarithromycin and azithromycin on the treatment and survival of patients with AIDS and disseminated Mycobacterium avium complex (DMAC).. Retrospective review over a 3.5-year interval.. Tertiary-care, university teaching hospital.. Charts of all patients with cultures of blood or bone-marrow positive for acid-fast bacilli (n = 103) were reviewed. Data on laboratory results at the time of DMAC diagnosis, antimycobacterial therapy, antiretroviral therapy, and survival was collected.. Prior to the availability of clarithromycin and azithromycin 61.5% of patients received antimycobacterial treatment compared with 92% afterwards (P = 0.0014). Median survival of treated patients was 255 versus 145 days for untreated patients (P < 0.001). Median survival of macrolide-treated patients was 284 versus 168 days for patients receiving treatment without a macrolide (P = 0.09). Univariate predictors of survival were antimycobacterial treatment, use of antiretrovirals, and year of diagnosis. In a multivariate model, no antimycobacterial treatment (hazard ratio, 3.83; P = 0.003) was associated with shorter survival, and treatment without a macrolide (hazard ratio, 2.29; P = 0.075) showed a trend towards shorter survival versus treatment with macrolide-containing regimens.. The introduction of clarithromycin and azithromycin has been associated with an increase in the proportion of patients with DMAC receiving treatment and with increased survival of these patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Azithromycin; Clarithromycin; Cohort Studies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multivariate Analysis; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Survival Rate

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Cryptosporidiosis; Humans; Injections, Intravenous; Malaria, Falciparum; Mycobacterium avium-intracellulare Infection; Plasmodium falciparum; Pneumonia; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

We investigated the potential of the azalide, azithromycin, and rifabutin in preventing disseminated infection due to Mycobacterium avium complex (MAC) in beige mice. Azithromycin 200 mg/kg, rifabutin (30 mg/kg or 60 mg/kg) were administered by gavage 6 days before mice were challenged orally with 10(8) cfu MAC and daily for 10 days thereafter during which time the mice were again challenged with the same inoculum on alternate days (days +1, +3, +5, +7, and +9). Sixty-four days later, the presence of bacteria in the blood and the number of viable bacteria in liver, spleen and appendix were estimated. Treatment with azithromycin and 60 mg/kg/day rifabutin but not 30 mg/kg/day, significantly decreased the incidence of bacteraemia and the number of bacteria in the appendix. The administration of azithromycin resulted in significantly fewer MAC in the liver and spleen but not in the appendix whereas the converse was true of 60 mg/kg rifabutin. Our results indicate that both azithromycin and rifabutin can prevent MAC disseminated infection, but that the azalide is more effective than the rifamycin in reducing the burden of infection.

Topics: Animals; Anti-Bacterial Agents; Appendix; Azithromycin; Bacteremia; Female; Liver; Mice; Mice, Inbred C57BL; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin; Spleen

Clarithromycin (CLM) and azithromycin (AZM) are important agents in the treatment of disseminated Mycobacterium avium complex disease; however, monotherapy with these macrolides often leads to clinically significant resistance. The underlying resistance mechanism was investigated by comparing 23S rRNA gene sequences in the domain V region of 10 CLM-susceptible strains included in this study. The only differences in the domain V sequences associated with CLM resistance were at position 2274 of the complete M. avium 23S rRNA gene (GenBank accession no. X74494). All the CLM-susceptible strains had an A residue at this site, whereas seven of the eight CLM-resistant strains had either a C, G, or T. Four of these seven CLM-resistant strains emerged during monotherapy with CLM and two emerged during AZM monotherapy, showing that resistance selected by either macrolide was associated with mutation of the 23S rRNA gene. Thermodynamic analysis of secondary rRNA structure suggests that the observed mutations cause an alteration in free energy associated with rRNA folding, which may result in a localized conformation change in assembled ribosomes. Such a shift may be important in the resistance of ribosomes to the effects of macrolides. This study therefore establishes a link between mutations within the 23S rRNA gene and clinically significant macrolide resistance in M. avium and also identifies a possible molecular mechanism of resistance at the level of the ribosome.

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Base Sequence; Clarithromycin; DNA, Bacterial; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Nucleic Acid Conformation; Operon; Polymerase Chain Reaction; RNA, Bacterial; RNA, Messenger; RNA, Ribosomal, 23S

Several new studies are attempting to optimize prevention and treatment of Mycobacterium avium complex infection. Studies from California, France, and Canada are creating new data showing that a three-drug combination using clarithromycin is superior to two-drug or four-drug combinations. It is also suggested that a three-drug combination which includes clarithromycin may also delay the emergence of clarithromycin-resistant organisms.

Topics: AIDS-Related Opportunistic Infections; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Clinical Trials as Topic; Clofazimine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin

We report the successful treatment of disseminated Mycobacterium intracellulare osteomyelitis, without evidence of other visceral involvement, in a previously healthy, HIV-negative, 2-year-old female using a 23-month regimen of antimicrobial agents that included 18 months of oral therapy with azithromycin, rifabutin, trimethoprim-sulfamethoxazole (TMP/SMX), and ethambutol.

Topics: Azithromycin; Child, Preschool; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; HIV Seronegativity; Humans; Immunocompetence; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteolysis; Osteomyelitis; Rifabutin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: AIDS-Related Opportunistic Infections; Azithromycin; Drug Labeling; Hearing Loss, Sensorineural; Humans; Mycobacterium avium-intracellulare Infection

The comparative activities of azithromycin (AZI) and clarithromycin (CLA) against eight Mycobacterium avium complex (MAC) isolates were evaluated in the beige mouse model of disseminated infection. Mice were infected intravenously with approximately 10(7) viable MAC isolate. AZI at 100 or 200 mg/kg of body weight or CLA at 200 mg/kg of body weight was given by gavage daily for 10 days starting at 7 days postinfection. In each study, groups of treated mice were compared with untreated control animals. A dose-related reduction in organism cell counts in the spleens between the groups receiving AZI at 100 and 200 mg/kg was observed. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against six of eight MAC isolates in the spleens. CLA at 200 mg/kg was more active than AZI at 200 mg/kg against three of eight MAC isolates in the lungs. The difference between AZI at 200 mg/kg and CLA at 200 mg/kg against organisms in the lungs was not significant for the remaining five isolates. Clinical trials comparing the activities of AZI and CLA in combination with other agents in patients with disseminated MAC infection are necessary to ascertain any clinically significant differences in the efficacies of these agents.

Topics: Animals; Azithromycin; Clarithromycin; Culture Media; Disease Models, Animal; Female; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Spleen

Topics: Adult; AIDS-Related Opportunistic Infections; Azithromycin; Ciprofloxacin; Clofazimine; Drug Therapy, Combination; Humans; Male; Mycobacterium avium-intracellulare Infection; Prednisolone

Topics: AIDS-Related Opportunistic Infections; Azithromycin; Clarithromycin; Drug Resistance, Microbial; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Organisms of the Mycobacterium avium complex (MAC) cause disseminated disease in patients with AIDS, and evidence points to the gastrointestinal tract as the major route of infection. Since MAC can bind to and invade intestinal mucosal cells, we examined whether subinhibitory concentrations of antibiotics which have anti-MAC activity in vitro affect the interaction between MAC and HT-29 intestinal mucosal cells. MAC isolates were exposed to subinhibitory concentrations of rifabutin (MIC, 2.6 micrograms/ml), sparfloxacin (MIC, 8.4 micrograms/ml), or azithromycin (MIC, 32 micrograms/ml) for 30 to 120 min, washed, and incubated with HT-29 cell monolayers for 2 h at 4 degrees C. HT-29 cell monolayers were then washed to remove unbound bacteria and were subsequently lysed. The number of MAC isolates that bound to the HT-29 cells was determined by plating the cell lysate onto 7H10 agar. Preincubation of the MAC isolates with rifabutin at concentrations of 1 and 2 micrograms/ml reduced MAC binding to HT-29 cells by 80 to 90%, while MAC exposed to sparfloxacin at 1 and 7 micrograms/ml inhibited binding by 77 to 93%. Azithromycin at concentrations of 2, 10, and 30 micrograms/ml had no effect on MAC binding to HT-29 cells. Inhibition of MAC binding to the gastrointestinal mucosa may be one underlying mechanism for the prophylactic effects of rifabutin and quinolones.

Topics: Anti-Infective Agents; Azithromycin; Bacterial Adhesion; Fluoroquinolones; Humans; Intestinal Mucosa; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolones; Rifabutin; Tumor Cells, Cultured

Previous studies have shown that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates human and murine macrophages to inhibit growth and kill intracellularly. This study shows the effect of GM-CSF on Mycobacterium avium complex (MAC) infection in vivo using a C57BL/6 beige mouse model of disseminated MAC infection. Furthermore, it examined the activity of the combination of GM-CSF and amikacin or azithromycin, two antimicrobials active against MAC, on the survival of MAC within macrophages in vitro and in the mouse model of disseminated infection. Although GM-CSF (25 mg/kg) induced mycobactericidal and mycobacteriostatic activity in macrophages in vitro and in vivo, the combination of GM-CSF and amikacin (50 mg/kg) or azithromycin (250 mg/kg) was associated with a significant increase in killing of MAC both within cultured macrophages and in the beige mouse model. Therefore, a significant reduction in the number of viable bacteria was observed in blood, liver, and spleen of mice treated with a combination of GM-CSF and azithromycin or amikacin compared with control mice and those treated with GM-CSF or antimicrobials alone.

Topics: Amikacin; Animals; Azithromycin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Macrophages; Mice; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Recombinant Proteins

Topics: AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Bacteremia; Bone Marrow; Clarithromycin; Drug Therapy, Combination; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin

Mycobacterium avium strains susceptible to clarithromycin and azithromycin contain mutants resistant to these macrolides with a frequency of 1.1 x 10(-10) to 1.2 x 10(-6). Cross-resistance between clarithromycin and azithromycin was demonstrated with mutants selected in the laboratory as well as with resistant strains isolated from patients. The susceptibility-resistance patterns of the macrolide-resistant strains with drugs other than macrolides were the same as those of the original susceptible strains. The emergence of clarithromycin resistance in patients was a result of multiplication of the preexisting resistant mutants that survived the elimination of bacteria during the initial period of treatment and was an exclusive cause of the relapse of bacteremia.

Topics: Azithromycin; Clarithromycin; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

Azithromycin, rifabutin, and rifapentine were used to treat or prevent disseminated Mycobacterium avium complex (MAC) infections produced in rats immunosuppressed with cyclosporine. Animals with bacteremic infections were treated 1 week after intravenous inoculation with 10(7) CFU of MAC with azithromycin, 100 mg/kg of body weight administered subcutaneously for 5 days and then 75 mg/kg on Monday, Wednesday, and Friday, or with rifabutin or rifapentine, 20 mg/kg administered intraperitoneally on Monday through Friday. All three drugs showed efficacy after 1 and 2 months. Rifabutin cleared the organisms from tissues more rapidly than azithromycin or rifapentine. To approximate prophylaxis, treatment was started 2 weeks before intravenous inoculation with 10(4) organisms. MAC infections were undetectable in treated animals after 4 months, while control animals had disseminated infections. These findings support the rationale for clinical trials of treatment and prophylaxis with these agents. The cyclosporine-treated rat appears to be a useful model in which to evaluate compounds for the treatment and prophylaxis of disseminated MAC infections.

Topics: Animals; Antitubercular Agents; Azithromycin; Cyclosporine; Erythromycin; Male; Mycobacterium avium-intracellulare Infection; Rats; Rats, Sprague-Dawley; Rifabutin; Rifampin; Rifamycins; Tissue Distribution

An effective intracellular concentration of an antimicrobial agent is essential for therapy of infections caused by organisms of the Mycobacterium avium complex. We previously reported on the effect of the combination of azithromycin and tumor necrosis factor (TNF) against M. avium infection in macrophages. We now report that stimulation of macrophages either with recombinant human gamma interferon (IFN-gamma, 10(2) U/ml) or with recombinant human TNF-alpha (10(2) U/ml) resulted in an increase in the intracellular concentration of azithromycin by approximately 200% within 3 h, compared with the concentration in unstimulated macrophages. Infection of macrophages with M. avium complex led to a decrease in the uptake of [14C]azithromycin by infected cells, compared with that by uninfected controls. Stimulation of infected macrophages with recombinant IFN-gamma or TNF-alpha overcame the inhibitory effect associated with infection. These results suggest that the increased bactericidal activity of the TNF-alpha-azithromycin or IFN-gamma-azithromycin combination against M. avium is related to enhanced uptake of the antibiotic by the stimulated phagocyte.

Topics: Azithromycin; Erythromycin; Humans; Interferon-gamma; Macrophages; Mycobacterium avium-intracellulare Infection; Recombinant Proteins; Tumor Necrosis Factor-alpha

Topics: Animals; Azithromycin; Disease Models, Animal; Erythromycin; Female; Hepatomegaly; Mice; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Specific Pathogen-Free Organisms; Splenomegaly