rifampin and Mycobacterium-avium-intracellulare-Infection

A 52-year-old patient misdiagnosed with spinal tuberculosis was successfully diagnosed with Mycobacterium avium infection using metagenomic next-generation sequencing and cured with four-drug combination protocol chemotherapy (amikacin, rifampicin, clarithromycin, ethambutol) and spinal fixation.

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Humans; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

We report the clinical results and problems of combined administration of rifampicin, ethambutol, and clarithromycin (REC) for the treatment of Mycobacterium avium complex (MAC) infection of the hand (hand MAC).Participants included 7 patients with hand MAC. After resection of the infected lesion, REC was prescribed for 12 months. For these patients, the site of infection, clinical course after initiation of REC, adverse drug effects (ADEs), and incidence of recurrence were evaluated.Sites of infection were the flexor tenosynovium in 5 patients, extensor tenosynovium in 1 patient, and both flexor and extensor tenosynovium in 1 patient. ADEs of REC occurred in 5 patients, and included visual disturbance caused by ethambutol in 2 patients, liver function abnormality caused by rifampicin in 2 patients, and fever with diarrhea caused by rifampicin in 1 patient. For 2 of these 5 patients, desensitization therapy was applied and REC was able to be reinstated. In the remaining 3 patients, the causative drugs were discontinued and levofloxacin, a new quinolone, was administered. Complete healing was achieved in 5 patients, and recurrence was observed in 2 patients. These 2 patients with recurrence included 1 patient in whom REC was completed and 1 patient in whom REC therapy was modified due to ADE.REC provided relatively good clinical results as a treatment for hand MAC. However, recurrences were observed even after the completion of REC and the use of an alternative drug. Optimal duration of REC and appropriate alternative drugs need to be identified in the future.

Topics: Aged; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Hand; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Tenosynovitis

Mycobacterium Avium Complex (MAC) is an established microbiologic cause of pulmonary disease, lymphadenitis, and disseminated disease in cases of advanced immune suppression. However, MAC manifesting as vertebral osteomyelitis is less common, and is particularly rare in the absence of Acquired Immunodeficiency Syndrome (AIDS). Prompt diagnosis of MAC vertebral osteomyelitis is challenging, but necessary to prevent serious morbidity or mortality.. We report a case of MAC osteomyelitis of the lumbar spine in a 70-year-old woman on extended duration corticosteroid therapy for systemic lupus erythematosus who presented with progressive back pain. Upon presentation, imaging revealed osteomyelitis of the lumbar spine with associated paraspinal abscess. Cultures from the surgical evacuation of the paraspinal abscess yielded no pathogen growth and she was therefore treated with empiric antibacterial therapy. Two weeks after her initial hospital discharge she represented with severe back pain and radiologic evidence of progressive disease in her lumbar spine. Two additional vertebral biopsies were required during her first 2 weeks of admission. MAC eventually grew from culture 14 days after collection. She was treated with ethambutol and rifampin and her symptoms resolved in 2 weeks, though therapy was continued for 12 months.. MAC is an unusual cause of vertebral osteomyelitis in patients with AIDS, but is exceedingly rare in those without severe immune compromise. Despite its rarity, it must be considered in cases of vertebral osteomyelitis that do not respond to empiric antibiotic therapy. Multiple biopsies may be necessary to obtain a diagnosis and avoid destructive infectious complications of an untreated infection.

Topics: Abscess; Aged; Anti-Bacterial Agents; Drug Therapy, Combination; Ethambutol; Female; Humans; Lumbosacral Region; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin

We report the first Italian case of Mycobacterium chimaera disseminated infection in a patient with a history of cardiac surgery. The patient was initially diagnosed with sarcoidosis and started on immunosuppressive therapy. Ten months later she developed a vertebral osteomyelitis: M. chimaera was isolated from bone specimen. A review of the literature shows that M. chimaera infection occurs specifically in this population of patients, due to contamination of heater-cooler units used during cardiosurgery. Devices responsible for the transmission were produced by Sorin Group Deutschland. Mycobacterium chimaera infection should be included in the differential diagnosis for patients undergoing cardiac surgery.

Topics: Acinetobacter Infections; Aged; Bacteremia; Diagnostic Errors; Drug Therapy, Combination; Equipment Contamination; Female; Heart Valve Prosthesis Implantation; Heating; Humans; Linezolid; Lumbar Vertebrae; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Postoperative Complications; Prednisone; Rifampin; Sarcoidosis; Spondylitis; Vertebroplasty; Water Microbiology

MYCOBACTERIUM AVIUM complex (MAC) consists of nontuberculous mycobacteria that cause disease in immunocompromised and immunocompetent hosts. The organisms are ubiquitous in the environment, and acquisition occurs through ingestion or inhalation of aerosols from soil, water, or biofilms. Disease may manifest as disseminated infection, soft tissue infection, chronic pneumonia, or hypersensitivity pneumonitis. Nontuberculous mycobacteria are increasingly associated with pulmonary disease, with MAC being the most common nontuberculous mycobacteria to cause pulmonary disease in the United States. Pulmonary symptoms, nodular or cavitary opacities on a chest radiograph or high-resolution computed tomographic scan with multifocal bronchiectasis and multiple small nodules, plus positive culture results from two sputum specimens or one bronchoscopic specimen are consistent with MAC pulmonary disease. Treatment consists of a macrolide, rifamycin, and ethambutol given three times weekly for noncavitary disease and daily with or without an aminoglycoside for cavitary disease.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Clinical Trials as Topic; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

Chemotherapy of pulmonary MAC (Mycobacterium avium complex) infection has been almost universally agreed with the multidrugs regimen that contains Clarithromycin (CAM), Rifampin (RFP), Ethambtol (EB), and aminoglycoside in case of advanced stage. One of the reason for the multidrugs regimen which is similar to tuberculous chemotherapy is to inhibit the emersion of resistant MAC strain. The other reasons, enhancement of anti microbial activity and response to polyclonal infection are unique to the MAC chemotherapy. In the current MAC chemotherapy, both CAM and aminoglycoside are main axes because only they can suppress the growth of MAC alone respectively. Efficacy of CAM was revealed through the randomized controlled trials of disseminated MAC infection with HIV and that consequences applied to pulmonary MAC infection treatment. CAM is not effective unless exceed 2 microg/ml blood concentration. RFP decreases CAM blood concentration remarkably, but the regimens contained RFP and CAM are superior clinically to the regimens without RFP. There seemed to be unknown pharmacological mechanisms with RFP. Although the advantage of aminoglycosides is easily achieved high blood concentration, if aminoglycoside dosage is exceed 15 mg/kg, the possibility of auditory disturbance increase. About the duration of MAC chemotherapy, many guidelines recommended that one year continuation after the negative conversion of sputum culture. It is not the evidence but an expert opinion. We often experience recurrences several months later after the all drugs are ceased. The interval days to positive conversion of sputum culture from the day of completion of chemotherapy are randomly distributed with weibull's equation. It suggests that exogenous re-infection may cause the recurrence of pulmonary MAC infection as pointed out by Wallace Jr. Considering these issues, we have the conception of pulmonary MAC infection chemotherapy as follows. 1. Full dose induction chemotherapy (two years). 2. Maintenance chemotherapy (one year). 3. Preventive chemotherapy (one year). These conceptions have to be the problem validated. However, these current chemotherapies are not effective adequately, we need the combination treatment with surgical resection when indicated as a localized focus for example. Generally chemotherapy could not cured the destructed bronchial lesion due to MAC infection as like as local bronchiectasis or cavities. Consequently, the chemotherapy just after the surgical resec

Topics: Aminoglycosides; Antitubercular Agents; Clarithromycin; Combined Modality Therapy; Drug Therapy, Combination; Ethambutol; Evidence-Based Medicine; Humans; Mycobacterium avium-intracellulare Infection; Practice Guidelines as Topic; Rifampin; Secondary Prevention; Time Factors; Tuberculosis, Pulmonary

Several rifamycin derivatives have been developed during the last 15 years for the treatment of mycobacterial infections. For tuberculosis, rifabutin (RFB) showed strong activity and seemed to be suitable when tuberculosis patients were also treated for their AIDS infection. Rifapentine (RPT) was evaluated in patients with or without AIDS for its intermittent use. It displayed promising activity but must be strengthened in situations, such as AIDS or patients without AIDS but with cavities. Rifalazil (RLZ) has been evaluated in mice but the dosages used were much higher than those tolerated by patients. Regarding Mycobacterium avium infections, RFB showed significant prophylactic activity in humans, RPT displayed some activity in mice and RLZ showed modest activity in mice.

Topics: AIDS-Related Opportunistic Infections; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; France; Humans; Meta-Analysis as Topic; Mycobacterium avium-intracellulare Infection; Randomized Controlled Trials as Topic; Rifampin; Switzerland; Tuberculosis, Pulmonary

Topics: Clarithromycin; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Pneumonia, Bacterial; Prognosis; Rifampin; Streptomycin

Topics: Antibiotics, Antitubercular; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Changing incidence and nature of mycobacterial infections subsequent to the historical regression of tuberculosis and the acquired human immunodeficiency syndrome (AIDS) epidemic, as well as the development of new technical tools for molecular biology, have profoundly modified the methods used for the bacteriological diagnosis of mycobacteria infections. Although microscopic search for acid-fast bacilli, culture and antibiotic resistance tests on Löwenstein-Jensen medium remain the reference methods, more rapid and sophisticated methods are now available. Culture on radiolabeled media using the Bactec system has shortened the delay for positive culture and interpretable antibiotic sensitivity tests. Molecular techniques allow: 1) rapid identification of the most frequently isolated mycobacteria strains, including the most frequent laboratory contaminant M. gordonae, with genome probes; 2) genome typing of M. tuberculosis strains to trace interhuman transmission, detect recurrence or exogenous reinfection or demonstrate laboratory contamination; 3) rapid detection of rifampicin resistance; and 4) direct detection of M. tuberculosis and M. avium in pathological specimens. The role of mycobacteria in the environment causing opportunistic infections, atypical mycobacteria or non-tuberculosis mycobacteria (NTM), particularly the aviaire complex, has grown considerably. Isolation and identification relies on methods used to detect bacilli as well as blood cultures and analysis of fecal matter. NTM are naturally resistant to most of the antituberculosis antibiotics but are sometimes sensitive to aminoglycosides, fluoroquinolones or new macrolides.

Topics: AIDS-Related Opportunistic Infections; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Bacteriological Techniques; Culture Media; Drug Resistance, Microbial; Fluoroquinolones; Genome, Bacterial; Humans; Incidence; Macrolides; Microbial Sensitivity Tests; Molecular Biology; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Radiopharmaceuticals; Recurrence; Rifampin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Rifabutin is a derivative of rifamycin S with activity against mycobacteria including atypical organisms such as Mycobacterium avium and M. intracellulare, also referred to as Mycobacterium avium-intracellulare complex (MAC). To date, rifabutin is the only drug to have been studied in large prospective placebo-controlled trials that has been shown to significantly reduce the incidence of disseminated MAC infection when administered prophylactically as a single agent to patients with acquired immune deficiency syndrome (AIDS). Initial studies also indicate that rifabutin may be a useful component of multiple drug regimens for the treatment of MAC infection, although further studies combining rifabutin with other recently available antimycobacterial drugs are required to determine the most effective regimens. When rifabutin is combined with at least two other antimycobacterial drugs, the combination appears to be of similar efficacy to rifampicin (rifampin)-containing regimens in patients with newly diagnosed pulmonary tuberculosis. Since available therapy for MAC infection in patients with AIDS is still suboptimal, rifabutin, at present the only first-line agent for prophylaxis against disseminated MAC infection in patients with advanced human immunodeficiency virus (HIV) infection, has the potential to make a valuable contribution to the continuing attempts to preserve the quality of life of patients with AIDS.

Topics: AIDS-Related Opportunistic Infections; Animals; Bacteria; Biological Availability; Drug Interactions; Half-Life; Humans; Intestinal Absorption; Metabolic Clearance Rate; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tissue Distribution; Tuberculosis, Pulmonary

Ethambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.. This study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.. We retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.. Ethambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).. A lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Humans; Lung Diseases; Macrolides; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Toxic Optic Neuropathy

Standard treatment for nodular/bronchiectatic. A total of 140 patients diagnosed with NB MAC-LD in Japan will be randomly assigned, in a 1:1 ratio, to intermittent treatment group or daily treatment group, and three-drug combination therapy with clarithromycin, rifampicin and ethambutol will be continued for 1 year. The primary endpoint is the proportion of patients requiring modification of the initial treatment regimen. Secondary endpoints are adverse events, sputum culture conversion, time to sputum culture conversion, improvement of chest CT findings, change in health-related quality of life score and development of clarithromycin resistance.. This trial was approved by the National Hospital Organisation Review Board for Clinical Trials (Headquarters). The results of this study will be reported at a society meeting or published in a peer-review journal.

Topics: Adult; Aged; Antitubercular Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Japan; Male; Middle Aged; Multicenter Studies as Topic; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quality of Life; Randomized Controlled Trials as Topic; Rifampin; Treatment Outcome; Young Adult

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

Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen.. To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease.. In a preliminary open-label study, we randomly assigned newly diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data were analyzed using the intention-to-treat method.. Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two-drug regimens, respectively.. This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Sputum; Treatment Outcome; Tuberculosis, Pulmonary

Despite recent advances in chemotherapy, the treatment of pulmonary Mycobacterium avium complex (MAC) disease remains unsatisfactory. Judging from its MIC, fluoroquinolones including gatifloxacin (GFLX) are expected to demonstrate efficacy against MAC disease. However, there have been few clinical studies using fluoroquinolones. Therefore, a prospective study to evaluate the clinical efficacy and safety of a fluoroquinolone-containing regimen for the treatment of pulmonary MAC disease was conducted. In this trial, patients with pulmonary MAC disease received protocol-guided combined chemotherapy with rifampin (RFP) and ethambutol (EB) plus either GFLX or clarithromycin (CAM). Adult patients who fulfilled the criteria of the ATS definition of pulmonary MAC disease were enrolled in this study. The patients provided their informed consent, and treatments were administered for 1 year. Of 27 patients enrolled from three facilities, 14 patients were treated with the CAM-containing regimen and 13 patients were treated with the GFLX-containing regime. Four patients did not complete the 1-year treatment because of adverse events. Nine patients (64.3%) in the CAM group and 11 patients (84.6%) in the GFLX group achieved eradication of pathogens. Adverse events were observed more frequently in the GFLX group than in the CAM group. However, there were no severe adverse events in either group. The long-term results showed a similar relapse rate between the CAM and GFLX groups. The fluoroquinolone-containing regimen demonstrated both high efficacy and relative safety for pulmonary MAC disease that was similar to that of the CAM-containing regimen, which is considered to be the standard regimen.

Topics: Aged; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Fluoroquinolones; Gatifloxacin; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Treatment Outcome

The treatment of fibrocavitatory pulmonary infection due to Mycobacterium avium complex and Mycobacterium malmoense poses a challenge. This study assessed microbial, inflammatory, radiographic, and clinical outcomes for a standardized 24-month triple-drug regime. Following treatment completion, all patients had fewer symptoms, experienced a reduction in systemic inflammation, and had negative sputum mycobacterial culture results.

Topics: Aged; Anti-Bacterial Agents; Blood Sedimentation; Ciprofloxacin; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Radiography; Rifampin; Sputum; Treatment Outcome; Tuberculosis, Pulmonary

Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate.. To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin.. A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed.. Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times.. TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.

Topics: Aged; Antitubercular Agents; Bronchiectasis; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Ethambutol; Female; Forced Expiratory Flow Rates; Forced Expiratory Volume; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Radiography; Rifampin; Sputum; Treatment Outcome; Tuberculosis, Pulmonary

To investigate whether the combined therapy according to the guideline proposed by American Thoracic Society (ATS) and Japanese Society for Tuberculosis (JST) is clinically appropriate for Mycobacterium avium complex (MAC) pulmonary disease.. Seventy-one patients in whom MAC pulmonary disease was diagnosed at Kawasaki Medical School and our associated ten hospitals were prospectively studied.. Seventy-one patients with Mycobacterium avium complex (MAC) pulmonary disease were 27 males and 44 females with a mean age of 64.4 +/- 10.2 years old. Patients received 400 mg/day or 600 mg/day of clarithromycin plus ethambutol, rifampicin, and initial streptomycin for 12 months. Among 71 patients who received more than 12 months of therapy, 41 patients (57.7%) converted their sputum to negative within six months after the initiation of this regimen, 16 of 41 patients (39.0%) relapsed, and 23 of 71 patients (32.4%) obtained clinical improvement on chest X-ray and/or clinical symptoms. The mortality rate had a comparatively good prognosis with a low incidence of 2.8%. Although the species of pathogen (M. avium or M. intracellulare) did not significantly affect the conversion rate or clinical improvement, the infectious form with or without respiratory underlying disease, the characteristics and extent of lesion on chest X-ray, and the dose of clarithromycin significantly influenced the conversion rate or clinical improvement. There were no problems concerning adverse reactions for this regimen.. This combined therapy, according to the guideline proposed by ATS and JST, was one of the effective treatments compared to the clinical effect of only antituberculous drugs through this study. However, this combined therapy was unsatisfactory compared to the clinical effect for pulmonary tuberculosis. The development of new companion drugs for MAC pulmonary diseases is needed.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Practice Guidelines as Topic; Prospective Studies; Rifampin; Streptomycin; Treatment Outcome

Previous reports on small numbers highlighted the need for a prospective study of the clinical features and response to treatment of pulmonary disease caused by Mycobacterium avium-intracellulare (MAC).. Patients with two positive cultures were randomised to 2 years of rifampicin and ethambutol or of rifampicin, ethambutol and isoniazid. Clinical, bacteriological and radiological progress was monitored for 5 years.. Seventy-five patients entered the study. They had a mean age of 64 years (range 29-87) and the sexes were balanced. Approximately two-thirds had previous/ co-existing lung disease(s). Sputum was positive on direct smear in 56%, and cavitation was observed in 61%, most having at least one large cavity. Just under half had bilateral disease and one-third extensive disease. Disease was confined to upper zone(s) in 25%. Twenty-seven (36%) died within 5 years, three because of MAC disease. There were 11 treatment failures and 10 relapses, with no correlation between those and in vitro resistance. Forty-five (60%) were alive at 5 years, of whom 23 were confirmed cured.. Pulmonary disease caused by MAC is associated with high morbidity and mortality. Standard susceptibility tests do not correlate with the response of the disease to chemotherapy. Rifampicin and ethambutol, with or without isoniazid, cured 31%, a result comparable with or better than that found previously with more toxic regimens, but mortality (36%) remains high. More effective regimens are needed, and management of coexisting illnesses and general health needs to be to maximised.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antitubercular Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Ethambutol; Female; HIV Seronegativity; Humans; Isoniazid; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Radiography, Thoracic; Rifampin; Sputum; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Roxithromycin; Treatment Outcome; Tuberculosis, Pulmonary

Our objective was to compare the effect of 2 regimens for treatment of Mycobacterium avium complex (MAC) bacteraemia in an HIV-positive population on symptoms and health status outcomes using a substudy of an open-label randomized controlled trial. The study was conducted in 24 hospital-based human immunodeficiency virus (HIV) clinics in 16 Canadian cities. Patients had HIV infection and MAC bacteraemia and were given either rifampin 600 mg, ethambutol 15 mg/kg daily, clofazimine 100 mg daily and ciprofloxacin 750 mg twice daily (4-drug arm) or rifabutin 600 mg daily (amended to 300 mg daily in mid-trial), ethambutol 15 mg/kg daily and clarithromycin 1000 mg twice daily (3-drug arm). The primary health status outcome was the change on the 8-item symptom subscale of the Medical Outcome Study (MOS)-HIV Health Survey adapted for MAC. Changes on other MOS-HIV subscales and on the Karnofsky score were also evaluated. Patients on the 3-drug arm had better outcomes on the MOS-HIV symptom subscale at 16 weeks (P=0.06), with statistically significant differences restricted to night sweats and fever and chills (P < 0.001). The proportion of patients improving on the symptom subscale relative to baseline was 55% on the 3-drug arm and 40% on the 4-drug arm. Patients on the 3-drug arm also had better Karnofsky score at 16 weeks (P < 0.001) and better outcomes on the social function, mental health, energy/fatigue, health distress and cognitive function subscales of the MOS-HIV. The 3-drug arm is superior to the 4-drug arm in terms of impact on MAC-associated symptoms, functional status and other aspects of health status.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Bacteremia; Canada; Ciprofloxacin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; Health Status; Humans; Mycobacterium avium-intracellulare Infection; Outcome and Process Assessment, Health Care; Rifabutin; Rifampin; Treatment Outcome

Annual incidence of Mycobacterium avium complex (MAC) pulmonary disease has been gradually increasing in the last 10 years in Japan, however, the optimal therapeutic regimen for the disease has not yet established. We investigated the effect of our new regimen in twenty seven cases of pulmonary MAC infection without HIV infection, diagnosed according to the American Thoracic Society criteria during the period from January 1996 to October 1997 at our hospital. These patients were treated with rifampicin (RFP), ethambutol (EB) and clarithromycin (CAM) for more than 12 months, together with streptomycin (SM) initially (first 2-3 months), except one patient who was treated for 11 months only. Twenty-four months after the therapy, sputum cultures converted from positive to negative in 13 patients and the amount of bacilli in sputum reduced in two patients. The radiological findings improved in 10 patients, showed no significant changes in 11 patients, while worsened in the remaining 6 patients. As to adverse reactions 1 case of liver damage, 3 cases of skin disorders, 4 cases of gastrointestinal malfunctions, and 1 case of optic neuritis were observed. This regimen was safe and tolerable even in the elderly outpatients, but not so effective against MAC pulmonary disease compared with the results of recent reports from the U.S. and Europe. Size of pulmonary lesions was closely associated with the effectiveness in this study. However, five bacteriologically converted cases did not show radiological improvement, and the reasons behind this fact remain to be investigated.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Streptomycin; Time Factors; Treatment Outcome

We have investigated the efficacy of a clarithromycin-containing four-drug regimen for Mycobacterium avium complex (MAC) pulmonary disease in 46 patients without acquired immunodeficiency syndrome (AIDS). The patients were 14 males and 32 females with a mean age of 60.9 +/- 11.5 yr. Patients received 10 mg/kg/d of clarithromycin plus ethambutol, rifampin, and initial kanamycin and subsequent quinolone for 24 mo. Seven patients (15.2%) were dropped in the first 6 mo. Among 39 patients who received more than 6 mo of therapy, 28 patients (71.8%) converted their sputa to negative: 26 of 31 patients (83.9%) infected with clarithromycin-susceptible strains and two of eight patients (25.0%) with resistant or intermediate strains. The timing of sputum conversion was 3.6 +/- 1.9 mo, with a range of 2 to 9 mo. The conversion rate was significantly lower in patients who were infected with clarithromycin-resistant or intermediate strains, who had had prior therapy (55.0% versus 89.5%), or who were acid-fast bacilli (AFB) smear-positive at entry (60.7% versus 100%). The age and sex of patients, the species of pathogen (M. avium or M. intracellulare), type and extent of the disease, and the use of kanamycin did not significantly affect the conversion rate. Although the regimen was efficacious for newly treated patients, frequent adverse reactions and a low conversion rate of sputum in retreated patients are problems that remain to be solved.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Clarithromycin; Drug Administration Schedule; Drug Resistance, Microbial; Drug Therapy, Combination; Enzyme Inhibitors; Ethambutol; Female; Fluoroquinolones; Humans; Kanamycin; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Survival Analysis; Treatment Outcome

To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients.. A randomized, open-labeled, comparative trial.. Outpatient clinics.. Seventy-four patients with HIV and symptomatic bacteremic M. avium infection.. Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks.. Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium.. No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups.. The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.

Topics: Adult; AIDS-Related Opportunistic Infections; Amikacin; Bacteremia; Ciprofloxacin; Clofazimine; Colony Count, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

The ability of various in vitro methods of antibiotic susceptibility testing to predict therapeutic outcome in patients infected with Mycobacterium avium complex (MAC) was evaluated. Pretreatment bloodstream MAC isolates from 38 patients with AIDS, previously treated in a randomized fashion with either ethambutol, rifampin, or clofazimine, were tested by three conventional methods using broth or agar, as well as by cocultivation with macrophages. The results obtained with each method were compared with the quantitatively determined bacteriologic response to the administration of the single agent in humans. None of the conventional in vitro susceptibility methods was predictive of therapeutic outcome, while the results of cocultivation with macrophages were of moderate predictive value. The positive predictive value of a response in humans based on a response in macrophages (defined by > or = to 1.0 log reduction in baseline colony counts after 5 days of treatment) was 74%. The negative predictive value was 82%.

Topics: AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antitubercular Agents; Bacteremia; Clofazimine; Ethambutol; Humans; In Vitro Techniques; Macrophages; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

To determine the predictive value of a standard murine model in the treatment of disseminated Myocardium avium complex (MAC) infection, beige mice were infected with MAC strains isolated from human immunodeficiency virus-infected patients and treated with the same antibiotic (ethambutol, clofazimine, or rifampin) that had been administered to the subject from whom that strain had been recovered. While ethambutol had the greatest bacteriologic efficacy in humans (mean decrease +/-SD, 1.0+/-0.5 log 10 cfu/mL of blood), clofazimine had the greatest bacteriostatic efficacy in mice (mean decrease +/- SD, 2.8 +/- 0.7 log(10) cfu/g of tissue). A linear correlation was not observed between bacteriostatic activity in mouse liver or spleen and the degree of bacteriologic response in humans (P > or = to .1). Odds ratios for a response in humans based on a bacteriologic response in mice were not significant for each agent (P > or = to .1, all cases).

Topics: AIDS-Related Opportunistic Infections; Animals; Antitubercular Agents; Clofazimine; Colony Count, Microbial; Disease Models, Animal; Ethambutol; Humans; Liver; Mice; Mycobacterium avium-intracellulare Infection; Rifampin; Species Specificity; Spleen

Intermediate results of the first 50 patients treated with clarithromycin (CLARI) regimens for Mycobacterium avium-intracellulare (MAI) lung disease were evaluated. Patients were HIV negative, and pretreatment isolates were susceptible to CLARI. Patients received CLARI 500 mg twice daily, ethambutol, rifampin (RMP), or rifabutin (RBT) and initial streptomycin, and they were treated until culture-negative 1 yr. Eleven of 50 patients (22%) were dropped in the first 3 mo. Of the remaining 39 patients, 36 (92%) converted their sputa to negative, and 32 (82%) remain culture negative to date. This includes 11 of 16 (69%) with prior drug therapy and 21 of 23 (91%) with no prior therapy. One or more companion drugs were discontinued in 16 of 39 (41%) of patients because of adverse events. Isolates from six of 39 patients (15%) became CLARI-resistant. Of 23 patients who are alive and were culture-negative a mean of 12.0 mo while receiving therapy, all remain culture-negative without therapy a mean of 19.1 mo. Despite reduced CLARI serum levels in patients also receiving RMP, 10 of 13 patients (77%) receiving this regimen were successfully treated. Although not directly compared with previous regimens, the success of this regimen strongly suggests it is superior to previous non-CLARI-containing regimens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Antitubercular Agents; Clarithromycin; Colony Count, Microbial; Drug Administration Schedule; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Protein Synthesis Inhibitors; Rifabutin; Rifampin; Streptomycin; Treatment Outcome

Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear.. We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis.. Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001).. In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antitubercular Agents; Bacteremia; Ciprofloxacin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Survival Analysis; Treatment Outcome; Uveitis

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Humans; Kanamycin; Mycobacterium avium-intracellulare Infection; Ofloxacin; Pilot Projects; Rifampin; Tuberculosis, Pulmonary

Studies have shown clarithromycin (Biaxin) and rifabutin to be effective against Mycobacterium avium complex (MAC), and to improve survivability. Abbott Laboratories is seeking approval from the Food and Drug Administration (FDA) for clarithromycin use in preventing MAC. Marion Merrell Dow, the manufacturer of rifabutin, is planning a prophylaxis trial with a close cousin of the drug, rifapentine. Rifapentine has a long half-life, and has the potential to lengthen intermittent treatment for tuberculosis. It is believed that this long half-life may mean it can maintain a higher blood level and thereby maintain better effectiveness than rifabutin against fast-growing MAC organisms.

Topics: AIDS-Related Opportunistic Infections; Animals; Antitubercular Agents; CD4 Lymphocyte Count; Clarithromycin; Half-Life; Humans; Mycobacterium avium-intracellulare Infection; Placebos; Randomized Controlled Trials as Topic; Rifabutin; Rifampin

The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined. Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks. Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia. The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046). In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4). Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M. avium infection.

Topics: Adolescent; Adult; AIDS-Related Opportunistic Infections; Bacteremia; Clofazimine; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin

It is generally assumed that Mycobacterium avium complex (MAC) bacteremia, once it develops, is unremitting. On the basis of this presumption, changes in the level of mycobacteremia are used to gauge therapeutic response. In 7 (12%) of 60 patients enrolled in a prospective trial of MAC bacteremia and AIDS, bacteremia became undetectable before the initiation of antimycobacterial therapy. Patients with transient bacteremia reported fewer and shorter symptoms and survived longer than those with sustained bacteremia (59 vs. 31 weeks; P = .022). There was no difference in the duration of AIDS, CD4+ cell count, hematocrit, or body weight between groups. Two additional patients with transient bacteremia were identified outside this study setting. Despite disappearance of detectable mycobacteremia and subsequent administration of antimycobacterial agent(s), bacteremia once again became detectable in 6 patients 4-45 weeks after their negative pretreatment cultures. Patients with disseminated MAC may have fluctuating levels of mycobacteremia that become undetectable in the absence of antimycobacterial therapy.

Topics: Adult; AIDS-Related Opportunistic Infections; Bacteremia; Clofazimine; Drug Therapy, Combination; Ethambutol; Humans; Life Tables; Mycobacterium avium-intracellulare Infection; Prospective Studies; Recurrence; Rifampin; Risk Factors; Survival Analysis

Patients with AIDS and disseminated Mycobacterium avium complex (MAC) infection received rifampin (600 mg) plus ethambutol (25 mg/kg) plus ciprofloxacin (750 mg) or matching placebos daily for 8 weeks. Patients were monitored every 2 weeks clinically and by quantitating MAC colony-forming units (cfu) per milliliter of blood. Analysis of baseline characteristics revealed no significant differences between groups. After 8 weeks, MAC cfu had decreased by > or = 1 log/mL in 4 of 9 treated patients versus 0 of 10 placebo recipients while increasing by > or = 1 log/mL in 1 and 7, respectively (P = .006). While the average combined clinical response score declined in both groups, it tended to decrease less in treated patients (P = .36). On the other hand, dose-limiting toxicity (primarily nausea and adverse drug interactions) occurred in 9 of 12 treatment versus 1 of 12 placebo patients (P = .005). Combined rifampin [corrected]-ethambutol-ciprofloxacin therapy for disseminated MAC infection had significant microbiologic efficacy with some evidence of clinical efficacy but was associated with drug intolerance.

Topics: Adult; AIDS-Related Opportunistic Infections; Ciprofloxacin; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin

To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen.. A phase II, multicenter clinical trial.. Four university-affiliated medical centers.. Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen.. Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator.. Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined.. The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common.. A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Amikacin; Anti-Infective Agents; Bacteremia; Ciprofloxacin; Clofazimine; Colony Count, Microbial; Drug Evaluation; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifampin

Disseminated Mycobacterium avium infection is common in patients with acquired immune deficiency syndrome (AIDS), but no drug studies have been reported establishing antimicrobial activity against this organism in a controlled, randomized trial. Clarithromycin, a new macrolide, has activity against M. avium in vitro and in animals, but it has not been studied in humans. In this randomized, double-blind, placebo-controlled trial, we measured the ability of clarithromycin to reduce M. avium bacteremia in patients with AIDS and disseminated infection. Of 23 patients initially enrolled, 15 men with late-stage AIDS qualified for the study. One group received clarithromycin alone for 6 wk, then placebo plus rifampin, isoniazid, ethambutol, and clofazimine for 6 wk. The other group received placebo alone, then clarithromycin plus the other four drugs. Colony-forming units (CFU) of M. avium per milliliter of blood were determined by quantitative cultures taken at baseline and every 2 wk thereafter. Minimum inhibitory concentration of clarithromycin for 90% of the strains isolated from patients at baseline, as measured on 7H11 agar at pH 6.6, was 8 micrograms/ml. Eight eligible patients with initial positive cultures who were initially receiving clarithromycin alone had marked declines in blood M. avium CFU; in six cases, CFU decreased to zero. When seven patients were switched to placebo plus the other four drugs, CFU rose in four patients and remained undetectable in three. The five eligible patients initially treated with placebo had progressive CFU increases; when three were switched to clarithromycin plus the four drugs, their CFU declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Clarithromycin; Colony Count, Microbial; Double-Blind Method; Drug Therapy, Combination; Erythromycin; Humans; Isoniazid; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

Clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) combination therapy is used to treat pulmonary Mycobacterium avium complex (MAC) infection; however, serum CAM concentration decreases due to RFP-mediated induction of CYP3A activity. Therefore, we investigated the pharmacokinetics of CAM, 14-hydroxy clarithromycin (14-OH CAM), EB, and RFP in patients receiving this three-drug combination therapy.. CAM monotherapy was started, EB was added 2 weeks later, and RFP was added 2 weeks after that. Serum CAM, 14-OH CAM, EB, and RFP concentrations were measured before and at 2, 4, 6, and 12 or 24 h after administration on days 14, 28, and 42, and pharmacokinetic parameters were calculated.. Median area under the curve (AUC) of CAM decreased by 92.1% from 0 to 12 h after concomitant administration of RFP compared with CAM monotherapy [1.7 (interquartile range [IQR], 1.4-1.8) μg·h/mL vs. 21.5 (IQR, 17.7-32.3) μg·h/mL, respectively]. In contrast, median AUC of 14-OH CAM was not significantly different between concomitant administration of RFP [9.1 (IQR, 7.9-10.9) μg·h/mL] and CAM monotherapy [8.2 (IQR, 6.3-9.3) μg·h/mL]. AUCs of CAM and 14-OH CAM did not change in CAM+EB combination therapy.. When RFP is combined with CAM in the treatment of pulmonary MAC infection, the blood concentration of CAM significantly decreased and that of the active metabolite 14-OH CAM increased, but not significantly. Our results suggest that combination therapy with CAM and RFP needs to be reconsidered and may require dose modification in the treatment of pulmonary MAC infection.

Topics: Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

During the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD), ethambutol or rifampin is often discontinued because of adverse events. This study investigated the treatment outcomes when broader-spectrum fluoroquinolones replace ethambutol or rifampin in MAC-PD treatment based on the radiologic type. From 2006 to 2019, patients who initiated standard treatment and whose treatment duration was ≥1 year were retrospectively identified at a tertiary referral center in South Korea, including 178 patients with cavitary disease (fibrocavitary and cavitary nodular bronchiectatic types) and 256 patients with the noncavitary nodular bronchiectatic (NC-NB) type. We compared the microbiologic cure at 1 year between the patients who maintained the initial regimen and those who replaced ethambutol or rifampin with fluoroquinolones (moxifloxacin or levofloxacin). The overall microbiologic cure rate of the 178 patients with cavitary disease was 71.3%. Among these, the microbiologic cure rates of the 16 patients who substituted fluoroquinolones for ethambutol were lower than those of the 156 patients who maintained three-drug oral antibiotics with aminoglycoside (37.5% versus 74.4%, respectively;

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Ethambutol; Fluoroquinolones; Humans; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin

Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection.. Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed.. A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57).. Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.

Topics: Coinfection; Heterocyclic Compounds, 3-Ring; HIV; HIV Infections; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Oxazines; Piperazines; Pyridones; Rifabutin; Rifampin; Tuberculosis

Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes.. Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage.. Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07).. An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Topics: Anti-Bacterial Agents; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Optic Nerve Diseases; Retrospective Studies; Rifampin; Treatment Outcome

In Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database.. We included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.. The total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181-300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3-7.44), 2.61 (95% CI, 1.39-4.91), and 2.38 (95% CI, 1.04-5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62-351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35-14.77) and 6.99 (95% CI, 3.22-15.18). The β value of EB was 2.07 (95% CI, 1.48-2.76), which was classified as a wear-out failure type.. For MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.

Topics: Clarithromycin; Drug-Related Side Effects and Adverse Reactions; Ethambutol; Humans; Japan; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

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

Mycobacterium tuberculosis (MTB) is commonly diagnosed via the GeneXpert MTB/RIF assay. The cycle threshold (Ct) value of probe A from this assay produced a fluorescence signal upon Mycobacterium intracellulare detection. No other nontuberculous mycobacteria (NTM) exhibited positive probe signals. Using a confirmed mycobacterial culture as a standard, probe A of the assay exhibited 84% sensitivity (95% confidence interval [CI]: 71%-97%) and 50% specificity (95% CI: 37%-63%) for clinical samples. For M. intracellulare strains, probe A exhibited 90% sensitivity (95% CI: 80%-100%) and 50% specificity (95% CI: 37%-63%). The identity of the amino acid sequence and 81-bp core region of rpoB from MTB and NTM suggested that the highly conserved property might be associated with a mismatch between the probes and the chromosomal DNA target. Probe A yielded a positive signal upon M. intracellulare detection; thus, probe A may help diagnose M. intracellular infections.

Topics: Bacterial Proteins; Bacteriological Techniques; Drug Resistance, Bacterial; Humans; Molecular Diagnostic Techniques; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Rifampin; Sensitivity and Specificity; Sequence Analysis

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

Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates.. Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients.. Macrolide resistance was rare, 1.2% (95% CI 0.7-7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8-23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin.. pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Child; Child, Preschool; Cohort Studies; Drug Resistance, Bacterial; Genotype; Humans; Infant; Macrolides; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phenotype; Rifampin; Young Adult

Clinical management of macrolide-resistant Mycobacterium avium complex (MR-MAC) lung disease is difficult. To date, there only exist a limited number of reports on the treatment of clarithromycin-resistant MAC (CR-MAC) lung disease. This study aimed to evaluate prognostic factors and identify effective treatments in CR-MAC lung disease. We retrospectively collected clinical data of patients newly diagnosed with CR-MAC lung disease at the Kinki-Chuo Chest Medical Center between August 2010 and June 2018. Altogether, 37 patients with CR-MAC lung disease were enrolled. The median age was 69 years; 30, 22, and 21 patients received clarithromycin, ethambutol, and rifampicin, respectively, on their own or in drug combination. The observed sputum culture conversion rate was 29.7% (11/37 patients). In univariate analysis, ethambutol significantly increased the rate of sputum culture conversion (p = 0.027, odds ratio (OR) 10; 95% confidence interval (CI) 1.11-89.77). Multivariate analysis confirmed that ethambutol increased sputum culture conversion rate (p = 0.026; OR 21.8; 95% CI 1.45-329) while the existence of lung cavities decreased it (p = 0.04; OR 0.088; 95% CI 0.009-0.887). The combined use of ethambutol with other drugs may improve sputum culture conversion rate in CR-MAC lung disease.

Topics: Aged; Antitubercular Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Female; Humans; Japan; Lung; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prognosis; Respiratory Tract Infections; Retrospective Studies; Rifampin; Sputum; Tomography, X-Ray Computed; Treatment Outcome

Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear.. To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease.. We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test.. The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593).. These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

Topics: Aged; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Female; Humans; Incidence; Japan; Macrolides; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Negative Results; Pneumonia, Bacterial; Rifampin

A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD.. Patients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide.. Among the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67-88.92; 15.82, 2.38-105.33; and 17.12, 3.93-74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54-21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72-15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01-0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only.. Maintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop.

Topics: Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Radiography, Thoracic; Retrospective Studies; Rifampin; Time Factors; Treatment Outcome; Young Adult

Topics: Aged; Antitubercular Agents; Female; Glomerulonephritis, IGA; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prednisolone; Rifampin

The number of patients with non-tuberculous mycobacterial lung disease (NTM-LD) worldwide has been increasing.. To evaluate adverse reactions with long-term administration of drugs for MAC-LD.. We conducted a retrospective single-centre medical chart review of 364 patients administered two or more drugs between July 2010 and June 2015.. The prevalence and median time to onset of adverse reactions were as follows: hepatotoxicity 19.5%, 55 days; leucocytopaenia 20.0%, 41 days; thrombocytopaenia 28.6%, 61.5 days; cutaneous reactions 9.3%, 30 days; ocular toxicity 7.7%, 278 days; and increase in serum creatinine 12.4%, 430.5 days. Multivariate analysis showed that rifampicin use was independently associated with thrombocytopaenia, and ethambutol use was independently associated with increases in serum creatinine.. The main adverse reactions appeared within 3 months after start of treatment. Most patients were able to continue treatment with liver-supporting therapy, antihistamine agents or desensitisation therapy; however, ocular toxicity must be monitored for up to 1 year after start of treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Ethambutol; Female; Humans; Japan; Logistic Models; Lung Diseases; Male; Middle Aged; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Sputum; Time Factors; Young Adult

Lung transplantation remains an important potential therapeutic option for end-stage lung disease. It can improve quality of life and in some cases be a life-lengthening therapy. Despite the possible benefits, there are also many potential complications following transplantation. Here we describe a novel presentation of nontuberculous mycobacterium manifesting as an endobronchial mass developing 4 years after lung transplantation.. A 66-year-old African-American woman presented with progressive dyspnea, cough, and persistent wheezing of 2 months' duration. She had a distant history of breast cancer and received bilateral lung transplantation due to end-stage pulmonary fibrosis 4 years prior to her current presentation. She denied fevers, but did endorse night sweats. She had diffuse expiratory wheezing on auscultation. Chest computed tomography imaging showed an endobronchial soft tissue lesion nearly occluding the left mainstem bronchus, which was concerning for endobronchial carcinoma. Rigid bronchoscopy demonstrated a fibrinous mass protruding into the left mainstem proximal to the anastomosis. A pathology report noted fragments of partially necrotic granulation tissue in addition to scant fragments of focally ulcerated bronchial mucosa. Both the tissue culture and bronchial wash stained positively for acid-fast bacilli and grew Mycobacterium avium complex.. Nontuberculous mycobacterium pulmonary disease is common post lung transplant and risk factors are related to immunosuppression and history of structural lung disease. Mycobacterium avium complex presenting as an endobronchial lesion in a patient post lung transplant is a novel presentation.

Topics: Aged; Antitubercular Agents; Ethambutol; Female; Fluoroquinolones; Graft Rejection; Humans; Immunosuppressive Agents; Lung; Lung Transplantation; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prednisone; Pulmonary Fibrosis; Rifampin; Tacrolimus; Tomography, X-Ray Computed; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Bronchiectasis; Chest Pain; Clarithromycin; Cough; Drug Therapy, Combination; Dyspnea; Ethambutol; Humans; Leukocytosis; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Tracheobronchomegaly; Veterans

The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse.

Topics: Aged; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Marketing; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Sputum; Treatment Outcome

Mycobacterium avium complex (MAC) lung disease requires prolonged treatment with multiple antibiotics. Drug intolerances and interactions are common with the current recommended treatment. There is limited information on outcomes with alternative medications.. Retrospective review including adult patients with MAC lung disease who were treated and monitored for at least 6 months posttreatment. The aim was to evaluate the clinical and microbiologic outcomes in patients treated with regimens including clofazimine and/or rifampin.. One hundred and seven patients were included (79% were female; mean age, 67 years). Sputum samples were smear positive in 54% of patients. The majority (84%) were treated with clofazimine in combination with a macrolide and ethambutol. Fourteen patients (13%) were treated with rifampin, macrolide, and ethambutol. Most patients (95%) converted from positive to negative sputum culture results in an average of 4.5 ± 4.2 months (range, 0-30 months). A significantly greater proportion of patients treated with clofazimine converted to negative culture results compared with those treated with rifampin (100% vs 71%; P = .0002). Microbiologic relapse occurred in 52 of 107 patients (49%). Thirty-six percent of patients required retreatment. There was no difference in microbiologic relapse or re-treatment rates between the two treatment groups.. The majority of patients with MAC lung disease achieve negative sputum culture results. Re-treatment is needed in approximately one-third of patients. In this cohort, both initial outcomes and re-treatment rates were at least as good in patients treated with clofazimine-containing regimens as in patients receiving rifampin-containing regimens. Clofazimine should be considered as an alternative drug for the treatment of MAC lung disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clofazimine; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Macrolides; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia; Retrospective Studies; Rifampin

Topics: Aged; Antitubercular Agents; Biopsy; C-Reactive Protein; Erythema Induratum; Female; Humans; Mycobacterium avium-intracellulare Infection; Polymerase Chain Reaction; Rifampin

Macrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due to Mycobacterium avium complex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form. M. intracellulare was the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.

Topics: Aged; Anti-Bacterial Agents; Drug Combinations; Drug Resistance, Bacterial; Ethambutol; Female; Gene Expression; Genes, Bacterial; Humans; Lung; Macrolides; Male; Middle Aged; Mutation; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; RNA, Ribosomal, 23S; Survival Analysis; Treatment Outcome

Mycobacterium avium complex (MAC) is a ubiquitous pathogen, widely distributed in the environment including water, soil and animals. It is an uncommonly encountered clinical pathogen; primarily causing pulmonary infections in patients with underlying lung disease or disseminated disease in immunocompromised hosts. Sporadically, extra-pulmonary infections have been documented including involvement of the liver, spleen, skin, soft tissue and lymph nodes. Central nervous system (CNS) infections due to MAC are exceedingly rare and carry a poor prognosis. Additionally, such infections are largely reported in patients infected with HIV. Herein we report the first case of intracranial abscess due to MAC in an immunocompetent man with a normal CD4 count and negative HIV status.. A previously healthy 40-year-old male presented to us with progressively worsening CNS symptoms. The patient's presentation was uncharacteristic of MAC infection in immunocompetent hosts, as he developed subacute, progressive symptoms that included severe frontal headaches, left eyelid swelling, blurry vision, and diplopia, without any pulmonary or systemic manifestations. Neuroimaging revealed multiple ring-enhancing lesions, which required neurosurgical intervention. MAC was the only pathogen that grew from intraoperative tissue cultures. The patient was subsequently treated with a 12-month regimen consisting of Clarithromycin, Ethambutol, and Rifampin, with successful clinical resolution.. Our findings indicate that it is important to consider rare infections such as MAC in immunocompetent patients, regardless of atypical symptoms. Despite the severity of this infection, with timely diagnosis effective treatment is available.

Topics: Adult; Anti-Bacterial Agents; Brain Abscess; Clarithromycin; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

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

Biological agents inhibiting TNF-α and other molecules involved in inflammatory cascade have been increasingly used to treat rheumatoid arthritis (RA). However, it remains controversial whether biological agents can be used safely in a patient with an underlying chronic infectious disease.. A 63-year-old woman who had been treated with tocilizumab (TCZ), anti-interleukin-6 receptor antibody, for RA presented to our outpatient clinic due to hemoptysis. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection, and high-resolution computed tomography (HRCT) showed a single cavitary lesion in the right upper lobe. After diagnosis of pulmonary MAC disease, TCZ was discontinued and combination chemotherapy with clarithromycin, rifampicin, ethambutol and amikacin was started for MAC pulmonary disease. Since the lesion was limited in the right upper lobe as a single cavity formation, she underwent right upper lobectomy. As her RA symptoms were deteriorated around the operation, TCZ was resumed. After resumption of TCZ, her RA symptoms improved and a recurrence of pulmonary MAC infection has not been observed for more than 1 year.. This case suggested that TCZ could be safely reintroduced after the resection of a pulmonary MAC lesion. Although the use of biological agents is generally contraindicated in patients with pulmonary MAC disease, especially in those with a fibrocavitary lesion, a multimodality intervention for MAC including both medical and surgical approaches may enable introduction or resumption of biological agents.

Topics: Amikacin; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Clarithromycin; Ethambutol; Female; Humans; Immunocompromised Host; Lung; Middle Aged; Mycobacterium avium-intracellulare Infection; Pneumonectomy; Rifampin; Tomography, X-Ray Computed

Little information is available regarding changes in immune status for patients with Mycobacterium avium complex (MAC) lung disease during antibiotic therapy. Serum immunomolecules from 42 patients with MAC lung disease were assayed comparatively using an array-based system according to (i) patients with MAC lung disease at the time of diagnosis versus healthy controls and (ii) alterations after 12 months of antibiotic therapy in the MAC lung disease group. In addition, cytokine analyses were performed to determine whether cytokine responses were associated specifically with the disease phenotype, treatment outcome and aetiological agent. Notably, the serum concentrations of type 1 cytokine-associated molecules, such as CD40L, interferon (IFN)-γ, interleukin (IL)-8 and IL-23, were decreased significantly in patients at the time of diagnosis, suggesting that these molecules may serve as indicators of host susceptibility to MAC disease. Although the overall serum level of T helper type 1 (Th1)-related molecules, such as CD40L and IFN-γ, was restored after treatment, Th17-related cytokines, such as IL-17 and IL-23, were down-regulated significantly at 12 months post-treatment compared to pretreatment. Furthermore, these cytokine patterns differed among patient subgroups. Decreased serum concentrations of IL-17 and/or IL-23 were associated with failure of sputum conversion, the fibrocavitary disease phenotype and M. intracellulare lung disease. Thus, the reciprocal balance between Th1 and Th17 immunity during antibiotic therapy for MAC lung disease is critical for dictating the treatment response. In conclusion, a low level of Th1-related immunomolecules may perpetuate MAC lung disease, and the serum concentrations of Th17-related cytokines can reflect the treatment outcome, disease phenotype and aetiological agent.

Topics: Aged; Anti-Bacterial Agents; Clarithromycin; Cytokines; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifampin; Th1 Cells; Th17 Cells; Th2 Cells

Environmental exposure is a likely risk factor for the development of pulmonary Mycobacterium avium complex (MAC) disease. The influence of environmental exposure on the response to antimicrobial treatment and relapse is unknown.. We recruited 72 patients with pulmonary MAC disease (male [female], 18 [54]; age, 61.7 ± 10.3 years) who initiated and completed standard three-drug regimens for more than 12 months between January 2007 and December 2011. The factors associated with sputum conversion, relapse and treatment success without relapse were retrospectively evaluated after adjustments for confounding predictors.. Fifty-two patients (72.2%) demonstrated sputum conversion, and 15 patients (28.8%) relapsed. A total of 37 patients (51.4%) demonstrated treatment success. Sputum conversion was associated with negative smears (odds ratio [OR], 3.89; 95% confidence interval [CI], 1.27-12.60; P = 0.02). A relapse occurred in patients with low soil exposure after the start of treatment less frequently than in patients with high soil exposure (7/42 [16.7%] vs. 8/10 [80.0%], P = 0.0003). Treatment success was associated with low soil exposure after the beginning of treatment (OR, 13.46; 95% CI, 3.24-93.43; P = 0.0001) and a negative smear (OR, 2.97; 95% CI, 1.02-9.13; P = 0.047).. Low soil exposure was independently associated with better microbiological outcomes in patients with pulmonary MAC disease after adjusting for confounding clinical, microbiological and radiographic findings.

Topics: Aged; Antitubercular Agents; Clarithromycin; Environmental Exposure; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Recurrence; Retrospective Studies; Rifampin; Soil Microbiology; Sputum; Treatment Outcome; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Biopsy; Combined Modality Therapy; Deglutition Disorders; Drainage; Ethambutol; Goiter; Hormone Replacement Therapy; Humans; Hypothyroidism; Isoniazid; Lymphatic Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pyrazinamide; Rifampin; Thyroiditis; Thyroxine; Tuberculosis, Endocrine

Moxifloxacin (MXF) has in vitro and in vivo activity against Mycobacterium avium complex (MAC) in experimental models. However, no data are available concerning its treatment effect in patients with MAC lung disease. The aim of this study was to evaluate the clinical efficacy of an MXF-containing regimen for the treatment of refractory MAC lung disease. Patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified from our hospital database. We identified 41 patients who received MXF for ≥ 4 weeks for the treatment of refractory MAC lung disease. A total of 41 patients were treated with an MXF-containing regimen because of a persistent positive culture after at least 6 months of clarithromycin-based standardized antibiotic therapy. The median duration of antibiotic therapy before MXF administration was 410 days (interquartile range [IQR], 324 to 683 days). All patients had culture-positive sputum when MXF treatment was initiated. The median duration of MXF administration was 332 days (IQR, 146 to 547 days). The overall treatment success rate was 29% (12/41), and the median time to sputum conversion was 91 days (IQR, 45 to 190 days). A positive sputum acid-fast-bacillus smear at the start of treatment with MXF-containing regimens was an independent predictor of an unfavorable microbiological response. Our results indicate that MXF may improve treatment outcomes in about one-third of patients with persistently culture-positive MAC lung disease who fail to respond to clarithromycin-based standardized antibiotic treatment. Prospective studies are required to assess the clinical efficacy of MXF treatment for refractory MAC lung disease.

Topics: Aged; Anti-Bacterial Agents; Aza Compounds; Clarithromycin; Drug Resistance, Bacterial; Ethambutol; Female; Fluoroquinolones; Humans; Lung; Male; Microbial Sensitivity Tests; Middle Aged; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolines; Rifampin; Sputum

Mycobacterium intracellulare-caused pulmonary infections have mostly been reported in immunocompromised hosts, while cutaneous M. intracellulare infections are rare. We describe here an immunocompetent patient with cutaneous lesions due to M. intracellulare, which was diagnosed by acid-fast staining, in vitro culture, histopathology, and PCR-restriction fragment length polymorphism analysis and gene sequencing of heat-shock protein (hsp) 65 and 16S rDNA genes. In vitro susceptibility testing was also carried out and the patient was successfully treated with clarithromycin, rifampicin, and ethambutol.

Topics: Adult; Antitubercular Agents; Bacterial Proteins; Chaperonin 60; Clarithromycin; DNA, Bacterial; Drug Therapy, Combination; Ethambutol; Humans; Immunocompetence; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Polymerase Chain Reaction; Ribotyping; Rifampin; RNA, Ribosomal, 16S; Skin; Skin Diseases, Bacterial

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

There are a few recent reports about the relationship between the clinical effect and drug-sensitivity test. We investigated the relationship between the clinical efficacy of treatment for pulmonary Mycobacterium avium complex (MAC) and drug-sensitivity test for isolated MAC by comparison between data from 2005 to 2007 and from 2008 to 2010. We studied 60 patients who satisfied diagnostic criteria of nontuberculous mycobacterial infection established by the American Thoracic Society in 2007 and who received combination therapy using rifampicin (RFP), ethambutol (EB), streptomycin (SM), and clarithromycin (CAM). Average CAM dosage was increased from the early (517 mg/day) to the later (800 mg/day) period. Sputum conversion rate increased from 63% in the early period to 83% in the later period. Clinical improvement also increased from 38% in the early period to 53% in the later period. The causative microorganisms isolated were M. avium in 35 patients and M. intracellulare in 25. In both periods, isolated MAC strains showed excellent minimum inhibitory concentration (MIC) for CAM. Regarding the relationship between clinical efficacy and MICs of RFP, EB, CAM, and SM, most patients with good clinical effects showed low MIC for CAM in both periods. Good clinical efficacy, including the sputum conversion rate, was obtained with an increased dose of CAM in the later period. We speculate that the increased dose of CAM influenced the good clinical effect in both periods.

Topics: Aged; Antitubercular Agents; Clarithromycin; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Streptomycin; Treatment Outcome; Tuberculosis, Pulmonary

Currently recommended multidrug treatment regimens for Mycobacterium avium complex (MAC) lung disease yield limited cure rates. This results, in part, from incomplete understanding of the pharmacokinetics and pharmacodynamics of the drugs.. To study pharmacokinetics, pharmacodynamics, and drug interactions of multidrug treatment regimens in a large cohort of patients with MAC lung disease.. We retrospectively collected pharmacokinetic data of all patients treated for MAC lung disease in the Adult Care Unit at National Jewish Health, Denver, Colorado, in the January 2006 to January 2010 period; we retrospectively calculated areas under the time-concentration curve (AUC). Minimum inhibitory concentrations (MIC) of their MAC isolates were retrieved for pharmacodynamic calculations.. We included 531 pharmacokinetic analyses, performed for 481 patients (84% females; mean age, 63 yr; mean body mass index, 21.6). Peak serum concentrations (C(max)) below target range were frequent for ethambutol (48% of patients); clarithromycin (56%); and azithromycin (35%). Concurrent administration of rifampicin led to 68%, 23%, and 10% decreases in C(max) of clarithromycin, azithromycin, and moxifloxacin. C(max)/MIC or AUC/MIC ratios associated with bactericidal activity were seldom met; 57% of patients achieved target ratios for ethambutol, versus 42% for clarithromycin, 19% for amikacin, 18% for rifampicin, and 11% for moxifloxacin.. Currently recommended regimens for MAC lung disease yield important pharmacologic interactions and low concentrations of key drugs including macrolides. Pharmacodynamic indices for rifampicin, clarithromycin, amikacin, and moxifloxacin are seldom met. This may partly explain the poor outcomes of currently recommended treatment regimens. Trials of new drugs and new dosing strategies are needed.

Topics: Adult; Aged; Amikacin; Antibiotics, Antitubercular; Area Under Curve; Clarithromycin; Cohort Studies; Colorado; Drug Interactions; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial; Retrospective Studies; Rifabutin; Rifampin

Little is known regarding the application of therapeutic drug monitoring for treatment of Mycobacterium avium complex (MAC) lung disease.. To evaluate drug interactions of multidrug regimens and clinical usefulness of therapeutic drug monitoring in the management of MAC lung disease.. A total of 130 patients with MAC lung disease and 60 patients with Mycobacterium abscessus complex lung disease were enrolled in this study. All of the MAC patients were treated with multidrug regimens that included clarithromycin (CLR), rifampin (RIF) or rifabutin (RFB), and ethambutol (EMB), and the plasma drug concentrations of CLR, RIF, and EMB were measured.. Peak plasma CLR concentrations were lower in patients with MAC lung disease who received daily (median, 0.3 μg/ml) or intermittent (median, 0.2 μg/ml) therapy with CLR in conjunction with RIF in both groups, compared with those diagnosed with M. abscessus complex lung disease who received CLR without RIF (median, 3.8 μg/ml; P < 0.05). The proportion of patients with MAC lung disease who received daily therapy and whose plasma CLR levels were below the target range of 2 μg/ml was 97% (96 of 99), and this rate was 100% (21 of 21) among patients with MAC lung disease who received intermittent therapy. The peak plasma drug concentrations and the peak plasma drug concentration/minimal inhibitory concentration ratios of CLR, RIF, and EMB did not differ between patients with unfavorable treatment outcomes and those with favorable outcomes.. Low plasma CLR concentrations were common in patients treated for MAC lung disease. However, there was no association between low plasma CLR concentrations and treatment outcomes. Therefore, therapeutic drug monitoring may not be beneficial in managing the therapy of patients with MAC lung disease.

Topics: Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Clarithromycin; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Ethambutol; Female; Humans; Logistic Models; Lung Diseases; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Republic of Korea; Retrospective Studies; Rifabutin; Rifampin

Adverse drug reactions interfere with the standard treatment of pulmonary Mycobacterium avium complex (MAC) disease; however, few studies have investigated this issue. We studied adverse drug reactions in the treatment of pulmonary MAC disease.. We retrospectively examined 74 patients who underwent treatment for pulmonary MAC disease in our hospital between January 2001 and December 2009. These patients had received treatment with rifampicin, ethambutol (EB), and clarithromycin. We analyzed the adverse drug reactions seen in these patients.. Twenty-two patients developed one or more adverse drug reactions that led to treatment discontinuation or change in medication, whereas 52 patients did not experience any adverse reactions. The incidence rate of adverse reactions was 29.7%. The adverse drug reactions included visual impairment in 9 patients, liver function disorder in 2, skin eruption in 5, and fever in 5. In most of the cases, the standard treatment could not be continued.. Visual impairment associated with EB was the most common adverse drug reaction, and it led to the discontinuation of EB, and thus the standard treatment. Additionally, in case of other adverse drug reactions, it was difficult to find appropriate replacements for the causative drugs. Further investigations are required to establish a standard policy for the management of adverse drug reactions that can lead to the discontinuation of chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antitubercular; Antitubercular Agents; Clarithromycin; Ethambutol; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Tuberculosis, Pulmonary

A female patient with rheumatoid arthritis (RA) suffered from Mycobacterium avium (M. avium) infection during tocilizumab treatment. Tocilizumab was discontinued and she was treated with a recommended chemotherapy, resulting in improvement of M. avium. Tocilizumab retreatment did not aggravate M. avium infection, and radiographic abnormalities improved over 1 year after cessation of the recommended therapy. Tocilizumab may be one candidate for intractable RA patients with M. avium if any biologic is required.

Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Antitubercular Agents; Arthritis, Rheumatoid; Clarithromycin; Ethambutol; Female; Humans; Middle Aged; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Rifampin; Treatment Outcome

Topics: Abscess; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Axilla; Clarithromycin; Darunavir; Dideoxynucleosides; Enfuvirtide; Ethambutol; HIV Envelope Protein gp41; HIV-1; Humans; Immune Reconstitution Inflammatory Syndrome; Isoniazid; Lamivudine; Lymph Node Excision; Lymphadenitis; Male; Mycobacterium avium-intracellulare Infection; Peptide Fragments; Pyrazinamide; Rifampin; Ritonavir; Streptomycin; Sulfonamides

Non-tuberculous mycobacteria (NTM) are an unusual cause of osteomyelitis in immunocompetent children. Diagnosis is often difficult due to the paucity of clinical symptoms and a subtle course of the disease. NTM comprise a group of about 91 identified species of environmental mycobacteria that cause infections most frequently in immunocompromised individuals or in patients with predisposing factors. Cervical lymphadenitis is the most common presentation of NTM infection in children. Invasive and recurrent infections with these organisms have been associated with a genetic defect of the interferon gamma-receptor. We report a 3-year-old immunocompetent girl who presented a NTM osteomyelitis of the left femur. Four months before she had been treated with medical and surgical therapy for a mycobacterium avium complex cervical lymphadenitis. Polymerase chain reaction assay on bone aspirate specimens confirmed the diagnosis of mycobacterium avium osteomyelitis. The patient was treated successfully with clarithromycin and rifampicin for 6 months.

Topics: Anti-Bacterial Agents; Arthralgia; Child, Preschool; Clarithromycin; Drug Therapy, Combination; Female; Humans; Immunocompetence; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin; Treatment Outcome

Mycobacterium avium complex (MAC), the most frequent cause of opportunistic nontuberculous pulmonary infection, is made up of a group of intracellular pathogens that are able to survive and multiply inside lung alveolar macrophages. As nebulized liposomes are reported to be effective to target antibacterial agents to macrophages, in this work we have prepared and characterized re-dispersible freeze-dried rifampicin (RFP)-loaded vesicles by using soy lecithin (SL) and a commercial, enriched mixture of soy phosphatidylcholine (Phospholipon 90, P90) with or without cholesterol. The obtained results showed that RFP could be loaded stably in SL vesicles only when cholesterol was not present in the film preparation, whereas with P90 vesicles, the highest stability was obtained with formulations prepared with P90/cholesterol 7:1 or 4:1 molar ratios. RFP-liposome aerosols were generated using an efficient high-output continuous-flow nebulizer, driven by a compressor. After the experiments, nebulization efficiency (NE%) and nebulization efficiency of the encapsulated drug (NEED%) were evaluated. The results of our study indicated that nebulization properties and viscosity of formulations prepared with the low-transition-temperature phospholipids, SL and P90, are affected by vesicle composition. However, all formulations showed a good stability during nebulization and they were able to retain more than 65% of the incorporated drug. The effect of liposome encapsulation on lung levels of RFP following aerosol inhalation was determined in rats. The in vitro intracellular activity of RFP-loaded liposomes against MAC residing in macrophage-like J774 cells was also evaluated. Results indicated that liposomes are able to inhibit the growth of MAC in infected macrophages and to reach the lower airways in rats.

Topics: Animals; Antibiotics, Antitubercular; Cell Line; Cholesterol; Humans; Liposomes; Macrophages, Alveolar; Male; Mice; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phosphatidylcholines; Rats; Rats, Wistar; Rifampin

The objective of this study was to find an optimal initial combination chemotherapy that includes clarithromycin (CAM) for treatment-naive patients with Mycobacterium avium complex (MAC) pulmonary disease, as assessed by microbiological conversion using a Mycobacterium growth indicator tube (MGIT).. Thirty-four patients with treatment-naive MAC pulmonary disease (determined using 1997 American Thoracic Society criteria) were evaluated retrospectively. They demonstrated a nodular and bronchiectatic pattern without cavity on high-resolution CT (HRCT) scans. The following three regimens were administered: regimen A (n = 9) consisted of CAM (400 mg/d), ethambutol (EB) [750 mg/d], and rifampicin (RFP) [450 mg/d]; regimen B (n = 12) consisted of CAM (800 mg/d), EB (750 mg/d), and RFP (450 mg/d); and regimen C (n = 13) consisted of CAM (800 mg/d), EB (1,000 mg/d), and RFP (600 mg/d) during the first 2 months followed by a reduction of the dosage of EB from 1,000 to 750 mg/d. Gender, age, BMI, and HRCT scan finding scores were not significantly different among the three groups. Chemotherapy was continued for 18 months. Sputum culture was periodically assessed by MGIT.. Culture conversion at 18 months in regimen A (55.6%), which included a daily dosage of 400 mg of CAM (9.5 mg/kg), was significantly inferior to that in regimen B (91.7%), which included daily 800 mg of CAM (17.6 mg/kg; p < 0.05), but regimen B and C (92.3%) showed no between-group difference after > 18 months of chemotherapy.. The higher dose of CAM allowed for better culture conversion. Daily combination chemotherapy that includes CAM (800 mg) seems appropriate as an initial treatment against treatment-naive patients with nodular and bronchiectatic MAC pulmonary disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bronchiectasis; Clarithromycin; Dose-Response Relationship, Drug; Ethambutol; Female; Humans; Lung; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Tomography, X-Ray Computed; Treatment Outcome

Non-tuberculous mycobacterias (NTMs) have many clinical manifestations in humans, depending on the underlying immunological status. We present a patient with Mycobacterium avium intracellulare pulmonary infection and co-existing, biopsy proven non-granulomatous organising pneumonia in distinct regions within the lungs. Treatment consisting of anti-mycobacterial therapy and corticosteroids led to clinico-radiological resolution. This case represents a potential broader clinico-pathological manifestation of Mycobacterium avium intracellulare.

Topics: Bronchoscopy; Emphysema; Ethambutol; Female; Glucocorticoids; Humans; Lung; Middle Aged; Mycobacterium avium-intracellulare Infection; Pneumonia; Prednisolone; Rifampin; 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

We performed a long-term retrospective investigation of pulmonary Mycobacterium avium complex (MAC) disease treated with combined chemotherapy following the ATS guideline or the Japanese Society for Tuberculosis guideline. We also studied when to terminate the combined chemotherapy.. The subjects of this study consisted of 90 patients who underwent combined chemotherapy according to these guidelines for minimum one-year period and followed up for at least one year since April, 1998.. The mean patients' age was 64.8 years old and the gender distribution consisted of 34 males and 56 females. While the sputum negative conversion was observed in 54 of 90 patients (60%), clinical improvement was recognized in 35 patients (39%) following combined chemotherapy administered according to the guidelines. Out of 54 patients with sputum conversion, 30 cases were followed up after the discontinuation of treatment, and sputum relapse later was seen in 18 patients. Out of 24 patients who continued the same treatment, sputum relapse was seen in 10 patients. Out of 35 patients with clinical improvement, 17 cases have been followed up after the discontinuation of treatment, clinical worsening was later recognized in 9 patients. Out of 18 patients who continued the same treatment, clinical worsening was recognized in 6 patients.. As the probability of sputum relapse after discontinuation of treatment was high even among patients whose sputum converted to negative by combined treatment according to the guidelines, we think that it is better to continue treatment according to the guidelines as long as possible.

Topics: Aged; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Practice Guidelines as Topic; Recurrence; Rifampin; Sputum; Streptomycin; Time Factors; Tuberculosis, Pulmonary

No previous reports have compared clarithromycin (CAM), rifampicin (RFP) and ethambutol (EB) containing regimens with and without an aminoglycoside antibiotic kanamycin (KM) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. We conducted a retrospective study to investigate the clinical efficacy of KM using data from 40 patients who received combined chemotherapy for MAC disease with or without KM in the National Hospital Organization Tokyo Hospital from July, 1999 to December, 2005. All patients were administered CAM, RFP and EB for 6 to 12 months, and 20 of the 40 simultaneously received combined chemotherapy with KM. The difference in the backgrounds of the groups was not statistically significant. The improvement rates of clinical symptoms and radiological findings were significantly higher in the KM-treated group than in the KM-untreated group (75% versus 35% and 80% versus 25%). Moreover, the sputum relapse rate was significantly lower in the KM-treated group (18% versus 75%). However, there were no significant differences in the sputum conversion rate (55% with KM versus 40% without KM). As for adverse reactions, there were no significant differences between the groups. Furthermore, we examined time-kill kinetics of KM and streptomycin (SM) against a clinical isolate of M. avium. Most M. avium was killed by KM and SM at concentrations higher than MIC (8 microg/ml), and concentration- and time-dependent killing by KM and SM were almost identical. These observations indicate that KM is effective for treatment of patients with MAC disease.

Topics: Aged; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Kanamycin; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin

We report the case of a 58-year-old female who presented with productive cough, weight loss, pulmonary nodular infiltrates and cavitations. She had a positive anti-neutrophil cytoplasmic antibodies (ANCA) test. A diagnosis of vasculitis was considered and a video-assisted thoracoscopic biopsy of the lung nodules was organised. However, prior to the biopsy, the sputum results revealed the presence of acid-fast bacilli, which were identified as Mycobacterium avium complex. A repeat ANCA assay was positive for atypical ANCA with negative proteinase-3 and myeloperoxidase titres. The patient was treated with rifampicin, ethambutol and clarithromycin with clinical and radiological improvement. The objective of this report is to highlight a rare association between positive ANCA titres and a non-tuberculous mycobacterial infection as a misdiagnosis and treatment of this patient with immunosuppressive therapy might have led to serious consequences.

Topics: Antibiotics, Antitubercular; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Clarithromycin; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Sputum; Thoracic Surgery, Video-Assisted; Tuberculosis, Pulmonary; Vasculitis

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

Topics: Antitubercular Agents; Child, Preschool; Erythema Nodosum; Female; Humans; Lymphadenitis; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Tuberculin Test

We reviewed the interaction between rifampicin (RFP) and clarithromycin (CAM) during treatment of pulmonary Mycobacterium avium complex infection.. The subjects were patients with pulmonary non-tuberculous acid-fast bacillus infection during the period from September 2004 to January 2006 who consented to this study. Drug blood concentrations were compared with the minimum inhibitory concentrations for M. avium isolated from sputum and blood levels of CAM were assessed when the time of administration was changed for RFP.. The blood concentration of CAM showed a marked decrease in all cases (n = 6) when administered together with RFP, but there was no significant difference in the blood concentration of 14-R-hydroxy-clarithromycin (M-5), the active metabolite of CAM. However, the total blood concentration of CAM and M-5 showed a significant fall, similar to the blood concentration of CAM alone. When the blood concentration and bacterial MIC were compared for RFP, the blood concentration exceeded five MIC(s) in six samples as did the CAM+M-5 level in four out of six samples. There was no significant difference in the blood concentration of CAM (n = 5) when the time of RFP administration was altered. CONCLUSION; Because the total blood concentration of CAM+M-5 fell markedly by co-administration of RFP, this might have an influence on the antibacterial effect of CAM. In addition, examination of the administration of RFP and CAM at different times showed that the blood concentration of CAM did not increase and the influence of induction of hepatic drug-metabolizing enzymes by RFP could not be avoided.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Clarithromycin; Drug Interactions; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Tuberculosis, Pulmonary

Topics: Combined Modality Therapy; Debridement; Ethambutol; Forearm; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Postoperative Care; Rifampin; Skin Diseases, Bacterial; Skin Ulcer; Surgical Flaps

A 83-year-old man had been treated for pulmonary infiltration was referred to a nearby hospital because of slight fever and cough. His chest radiograph and CT showed right chronic empyema, and in which pleural aspirate was smear positive for acid-fast bacilli and positive for PCR-Mycobacterium intracellulare. He was diagnosed as chronic empyema caused by M. intracellulare. A month later exacerbation of bronchopleural fistula was observed and M. intracellulare infection expanded into the lung. He was treated with combined use of ethambutol, rifampicin, clarithromycin, and streptomycin for six months, and his chest radiograph showed improvement, however, finally he died as he was in advanced age and emaciation due to chronic lung infection.

Topics: Aged, 80 and over; Chronic Disease; Clarithromycin; Drug Therapy, Combination; Empyema; Ethambutol; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Radiography, Thoracic; Rifampin; Streptomycin; Tomography, X-Ray Computed

Nontuberculous mycobacteria (NTM) are increasingly recognized as important pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most lung infections due to NTM. Patients with preexisting lung disease or immunodeficiency are at greatest risk for developing MAC infection. The majority of MAC pulmonary cases, however, occur in immunocompetent elderly women in association with nodular infiltrates and bronchiectasis. More recently, pulmonary disease has also been described in immunocompetent patients after exposure to MAC-contaminated hot tubs. We describe a case of aggressive MAC lung disease in a young immunocompetent female patient without preexisting lung disease whose clinical and pathologic characteristics do not fit into any of these categories and may represent a unique manifestation of MAC lung disease.

Topics: Adult; Amikacin; Biopsy; Clarithromycin; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Female; Granuloma; Humans; Lung; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Necrosis; Pneumonia, Bacterial; Prednisone; Rifampin; Sputum; Tomography, X-Ray Computed

Forms of mutation never before described in the rpoB gene are reported for a sample of 20 rifampicin-resistant Mycobacterium avium Complex (MAC) strains isolated from AIDS patients in Thailand. All strains were analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and polymerase chain reaction-DNA sequencing (PCR-DNA sequencing). Sequence analysis of these strains revealed that only one strain (5%) has missense mutation at Lys-626 (Thr) and the rest of the strains had 15 different silent mutations within a 542 bp region of the rpoB gene. Five strains (25%) had a silent mutation at only one position, 7 (35%) at 2 positions, 7 (35%) at 3 positions, and 1 (5%) at 7 positions. The silent mutation at the Ala-630 codon occurred in the largest proportion of the strains (15 strains, 75%), followed by the Val-581 in 8 strains (40%), Tyr-578 and Thr-600 in 4 strains (20%), and Gly-597 in 3 strains (15%). This investigation demonstrates that mutation in the rpoB gene of MAC strains from Thailand are more varied than previously reported for RIF MAC strains. PCR-SSCP screening clearly separated RIFr strains from rifampicin-susceptible (RIFs) strains.

Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA Primers; DNA-Directed RNA Polymerases; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Polyacrylamide Gel; Genes, Bacterial; Humans; Mutation; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Thailand

A case was 56 years old woman, and she did not have any subjective symptom. She received multiphasic health screening, and abnormal shadow was detected on her chest radiograph. Chest radiography revealed infiltrations in the middle lobe. Computed tomography (CT) of the thorax showed clusters of small nodules in the middle lobe. The bronchial washing specimen showed acid-fast bacilli identified as Mycobacterium intracellulare by DNA-DNA hybridization (DDH) method. This case was diagnosed as Mycobacterium intracellulare lung disease. The patient received combination therapy with rifampicin, ethambutol, and clarithromycin for one year with radiological improvement. CT findings were characteristic and useful for the early diagnosis of MAC infection, which led to cure of the disease by chemotherapy.

Topics: Antitubercular Agents; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Ethambutol; Female; Humans; Lung Diseases; Magnetic Resonance Imaging; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Tomography, X-Ray Computed

We aimed to investigate the transitional pattern of the clinical features of pulmonary Mycobacterium-avium complex (MAC) disease, especially with regard to the clinical effect of treatment, in patients treated before and after the implementation of the 1998 guidelines of the Japanese Society for Tuberculosis for combined chemotherapy for pulmonary MAC disease. The clinical findings and treatments of 220 patients with pulmonary MAC disease during the past 10 years were compared by dividing the patients into two groups, each encompassing a 5-year period. During the past 5 years, we have carried out combined chemotherapy with rifampicin, ethambutol, an aminoglycoside (streptomycin or kanamycin), and clarithromycin (CAM) following the guidelines for the treatment of pulmonary MAC disease proposed in 1998, and we have achieved positive results; both the sputum conversion rate and clinical improvement of the outcome in patients with primary infectious type rose significantly. Although there were no significant differences in the background or in microbiological and radiological findings in the two groups, significant improvement was seen in the sputum conversion rate and in improvement of the clinical effect of treatment. The results of this combined chemotherapy were unsatisfactory, however, when compared with its clinical effect on pulmonary tuberculosis. Therefore, we anticipate the development of new companion drugs for pulmonary MAC disease that are as active as CAM.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Antitubercular Agents; Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Japan; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Outcome Assessment, Health Care; Practice Guidelines as Topic; Rifampin; Saliva; Sex Distribution; Streptomycin

Clarithromycin (CAM) and rifampicin (RFP) have both been recognized to be effective antibiotic agents against Mycobacterium avium complex (MAC) infection. Rifamycin derivatives including RFP and rifabutin modulate the CAM metabolism by inducing the hepatic cytochrome p-450 3A4. To clarify the effect of RFP on the CAM metabolism, we measured the plasma concentration of CAM and 14-R-hydroxyclarithromycin (M-5), the major metabolite of CAM, in 9 patients suffering from MAC infection before and after the addition of RFP. After the addition of RFP, the mean plasma concentration of CAM significantly decreased, while that of M-5 did not. In addition, the amount of CAM + M-5 concentration also significantly decreased. As M-5 is less effective against MAC infection than CAM, more attention should thus be paid to the plasma CAM concentration in patients administered CAM and RFP concomitantly.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotics, Antitubercular; Clarithromycin; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Female; Humans; Liver; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Time Factors

This report describes a patient with small-cell lung cancer who was infected with both Mycobacterium tuberculosis and non-tuberculous mycobacterium. He received irinotecan plus cisplatin, with and without rifampin. Rifampin slightly reduced the conversion of irinotecan to 7-ethyl-10-hydroxycamptothecin (SN-38), as determined by pharmacokinetic analysis. Rifampin may influence the metabolism and toxicity of irinotecan to some extent. However, there are possibilities to control M. tuberculosis and Mycobacterium avium complex infections in patients with small-cell lung cancer by using rifampin in combination with irinotecan plus cisplatin.

Topics: Antibiotics, Antitubercular; Antineoplastic Agents, Phytogenic; Camptothecin; Carcinoma, Small Cell; Drug Interactions; Glucuronates; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Tuberculosis, Pulmonary

To evaluate the response rate to antimycobacterial drug therapy in patients with cystic fibrosis (CF) suffering from infection by non-tuberculous mycobacteria (NTM).. Ten patients, aged 10-34 y, out of 180 CF patients, were diagnosed with NTM disease. They had been regularly checked and examined for pulmonary symptoms, and had had chest X-rays and sputum cultures (including for mycobacteria) performed. One additional 36-y-old female received her CF diagnosis soon after the NTM diagnosis.. Mycobacterium avium-intracellulare complex (MAC) was found in 10 out of 11 patients and M. kansasii in 1 patient. Treatment with antimycobacterial drugs resulted in clinical improvement (weight gain or stabilization of weight and/or improved or stabilized lung function in 8 out of 11 patients) and mycobacterial culture turned negative in 10 out of 1.. Promising results may be associated with early intervention with antimycobacterial therapy in CF patients.

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Antitubercular Agents; Child; Clarithromycin; Cohort Studies; Cystic Fibrosis; Ethambutol; Female; Humans; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii; Retrospective Studies; Rifampin; Streptomycin

Disseminated Mycobacterium avium intercellulare (MAI) infection is rare in non-AIDS patients. We report a 60-year-old woman with chronic lung disease who developed vertebral osteomyelitis due to MAI. She was treated successfully with combined therapy consisting of rifampin, ethambutol, and clarithromycin.

Topics: Clarithromycin; Drug Therapy, Combination; Ethambutol; Female; Humans; Middle Aged; Mycobacterium avium-intracellulare Infection; Osteomyelitis; Rifampin; Thoracic Vertebrae

We report on 3 children undergoing treatment for acute lymphoblastic leukemia (ALL), who developed systemic nontuberculous mycobacterial (NTM) infections. All 3 patients were treated successfully with 5 months or less of antimicrobial therapy and completed their chemotherapy with no further recurrence of their NTM infection. NTM infections in some children with ALL may be successfully treated with antimicrobial agents without necessarily compromising the ALL treatment. The optimal duration of therapy for NTM remains unclear, but may be shorter than previously reported.

Topics: Child, Preschool; Clarithromycin; Female; Humans; Male; Mycobacterium avium-intracellulare Infection; Mycobacterium chelonae; Mycobacterium Infections, Nontuberculous; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rifampin

Mycobacterium avium undergoes reversible morphotypic switching between the virulent transparent colony type and the less virulent opaque colony type. A new morphotypic switch in M. avium, termed red-white, that becomes visible when opaque colonies of clinical isolates are grown on agar media containing Congo red, was recently described. White opaque (WO) variants were found to be more resistant to multiple antibiotics than were red opaque (RO) variants. The present paper reports that transparent derivatives of RO and WO clones retain the differential Congo red binding properties of their opaque parents, indicating that the opaque-transparent switch operates independently of the red-white switch. White transparent variants were more resistant to clarithromycin and rifampin in vitro, and better able to survive within human macrophages, than their red transparent counterparts. Neither red nor white variants were markedly favoured during growth in vitro; however, red variants were better able to spread on soft agar (sliding motility), a potential selective advantage under some environmental circumstances. White-to-red switching was frequently observed in vitro and was accompanied by decreased antibiotic resistance and increased motility. Red-to-white switching has yet to be observed in vitro, indicating that the red morphotype is very stable. Significantly, some widely studied laboratory reference strains of M. avium, including strain 2151 and the genome sequence strain 104, are stable red clones. These strains are intrinsically antibiotic resistant and virulent in animal models, but they may not express genes encoding the elevated levels of antibiotic resistance and intracellular survival observed in white variants.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Clarithromycin; Congo Red; Drug Resistance, Microbial; Humans; Macrophages; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Phenotype; Pigments, Biological; Rifampin; Virulence

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

The clinical significance of rifampin's induction of warfarin metabolism is well documented, but no published studies or case reports have quantified this interaction with respect to the international normalized ratio (INR). A patient receiving concomitant rifampin and warfarin to treat a mycobacterial infection and intraventricular thrombus, respectively, underwent routine INR testing at a pharmacist-managed anticoagulation clinic to assess his anticoagulation regimen. A 233% increase in warfarin dosage over 4 months proved insufficient to attain a therapeutic INR during long-term rifampin therapy More aggressive titration of the warfarin dosage was needed. In addition, a gradual 70% reduction in warfarin dosage over 4-5 weeks was necessary to maintain a therapeutic INR after rifampin discontinuation, demonstrating the clinically significant offset of this drug interaction. Extensive changes in warfarin dosage are required to attain and maintain a therapeutic INR during the initiation, maintenance, and discontinuation of rifampin.

Topics: Antibiotics, Antitubercular; Anticoagulants; Blood Coagulation; Drug Interactions; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Ventricular Dysfunction, Left; Warfarin

We report two patients treated with the combination of itraconazole plus rifampin for more than 4 months. While on itraconazole plus rifampin, patient 1 lost weight at a rate of 30 g/d. After stopping rifampin, he gained 14 g/d. While on itraconazole plus rifampin, patient 2 lost 41 grams/day. After stopping rifampin, he gained 33 g/d. Weight loss while taking the combination of itraconazole plus rifampin, followed by weight gain after stopping rifampin, suggests the possibility of a clinically significant drug interaction between itraconazole and rifampin.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antifungal Agents; Drug Interactions; Drug Therapy, Combination; Histoplasmosis; Humans; Itraconazole; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Weight Loss

The postantibiotic effects (PAEs) of rifampin, amikacin, clarithromycin, and ethambutol were determined radiometrically against five AIDS-associated isolates of Mycobacterium avium. and were found to be 20.8+/-3.4. 18.4+/-2.5, 11.8+/-1.7. and 2.4+/-0.9 h, respectively. Various two-, three- or four-drug combinations were also screened: the PAEs for a two-drug combination were generally longer than individual drugs (mean PAE of 13.8+/-1.5 to 29.2+/-7.4 h instead of 2.4+/-0.9 to 18.4+/-2.5 h for single drugs). The addition of a third drug further increased the mean PAE to a range of 21.0+/-2.6 to 32.4+/-6.1 h. Both rifampin+clarithromycin and rifampin+amikacin were the most potent two-drug combinations resulting in longer PAEs than individual drugs, whereas rifampin+amikacin+clarithromycin was the most potent three-drug combination. Parallel viable count determinations showed a good correlation between the PAE results obtained by the radiometric method or by bacterial viability assessment. These results are useful in planning future clinical investigations to clarify the possible implication of PAE in drug schedule and dosage, a line of information that is urgently needed to guide the drug administration in M. avium-infected AIDS patients, who are presently over-burdened with the administration of too many drugs for HIV-treatment and opportunistic infections.

Topics: AIDS-Related Opportunistic Infections; Amikacin; Anti-Bacterial Agents; Antitubercular Agents; Clarithromycin; Colony Count, Microbial; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Radiometry; Rifampin

Cystic fibrosis (CF) patients require higher dosages of many antibiotics. The relapse of tuberculosis in one CF patient, and the repeated growth of Mycobacterium avium-intracellulare in another, despite conventional therapy, raised the question of whether the serum levels of the antimycobacterial drugs were adequate. Antimycobacterial drug serum concentrations were assayed in 10 CF patients with pulmonary mycobacterial disease. Serum levels below the proposed target range were seen 2 h after drug intake in the initial four patients treated: for rifampicin in 2/3, ethambutol in 3/4 and for clarithromycin in 2/3 patients, despite standard dosages. Reassays after dose adjustment and assays in six other patients showed that adequate levels were not achieved 4 h after clarithromycin in 3/5, ethambutol in 1/5, ciproflaxacin in 1/2 and ofloxacin in 2/2 patients. The patient with relapse of tuberculosis and the patient with continuous growth of M. avium-intracellulare improved and became culture negative after dose adjustment. Low drug serum levels is one reason for therapy failure in cystic fibrosis patients with mycobacterial disease. Therapeutic drug monitoring is recommended.

Topics: Adolescent; Adult; Antitubercular Agents; Biological Availability; Clarithromycin; Cystic Fibrosis; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Ethambutol; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Mycobacterium avium-intracellulare Infection; Pregnancy; Rifampin; Tuberculosis, Pulmonary

Topics: AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antitubercular Agents; Clinical Trials as Topic; Drug Approval; Drug Industry; Fluoroquinolones; Humans; Mycobacterium avium-intracellulare Infection; Rifampin; Technology, Pharmaceutical; Tuberculosis, Multidrug-Resistant; United States

Urban county medical center.. To compare clinical outcomes associated with two treatment regimens for AIDS-associated disseminated Mycobacterium avium complex (DMAC). From 1989 to mid-1992, patients were treated with rifampin, ethambutol, and clofazimine; in mid-1992 clarithromycin replaced rifampin.. A retrospective review of patients with DMAC; the main outcome measures assessed were toxicity associated with DMAC treatment, transfusions after the diagnosis of DMAC, and survival.. 88 patients received the rifampin-based regimen and 86 were treated with the clarithromycin-based regimen. Drug-related adverse events were recorded less frequently with clarithromycin treatment (21% vs. 42%, P = 0.005), and additional antimycobacterial agents were used less often (28% vs. 44%, P = 0.04). In a multivariate logistic regression model, severe anemia at the time of DMAC diagnosis was associated with transfusion-dependence (relative risk [RR] 5.6, 95% confidence interval [CI] 2.2, 13.8, P < 0.001) and clarithromycin treatment was inversely associated with transfusion dependence (RR 0.4, 95% CI 0.1, 0.98, P = 0.04). In a multivariate Cox regression model including other factors affecting survival, clarithromycin treatment did not confer a survival advantage (P = 0.74).. The clarithromycin-containing regimen was better tolerated and was associated with substantially lower transfusion requirements than the rifampin-based regimen; survival was not affected.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacteremia; Blood Transfusion; Clarithromycin; Colorado; Community Health Centers; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Retrospective Studies; Rifampin; Survival Rate; Treatment Outcome

In the past, Mycobacterium avium complex (MAC) was considered a colonizing microbe in the immunocompetent host. Today it should be considered a potential pathogen. We present a case of MAC necrotizing pneumonia in a 27-year-old man who tested negatively for the human immunodeficiency virus, had no typical granulomas, and responded rapidly to antimicrobial therapy.

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Ciprofloxacin; Clarithromycin; Drug Therapy, Combination; Ethambutol; HIV Seronegativity; Humans; Male; Mycobacterium avium-intracellulare Infection; Necrosis; Pneumonia, Bacterial; Pulmonary Atelectasis; Rifampin

We present five cases of mycobacterial tenosynovitis of the flexor tendons of the fingers. These cases were observed during the last 12 years and treated by the same surgeon. This pathology is uncommon now, but it is becoming more frequent, especially in patients with diminished immunity. The diagnosis was most commonly made after synovectomy in patients presenting with carpal tunnel syndrome associated with slightly painful swelling at the wrist. Histological and bacteriological examinations are very important and revealed tuberculosis in four of our patients and mycobacterium in one, and the treatment consists of synovectomy and appropriate antibiotics. The functional result is usually good, but recurrence is not uncommon. Long-term follow-up is necessary. Local corticosteroid therapy could have a part in the causation of this condition.

Topics: Adult; Aged; Antibiotics, Antitubercular; Antitubercular Agents; Carpal Tunnel Syndrome; Combined Modality Therapy; Ethambutol; Female; Hand; Humans; Isoniazid; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Tenosynovitis; Tuberculosis

Topics: Adrenal Cortex Hormones; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Antitubercular Agents; Ciprofloxacin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; HIV Infections; Humans; Isoniazid; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Nontuberculous Mycobacteria; Practice Guidelines as Topic; Pyrazinamide; Pyridoxine; Radiography; Rifabutin; Rifampin; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

The Community Programs for Clinical Research on AIDS (CPCRA) presented several recent findings from clinical trials at the International Conference on AIDS. Weekly doses of fluconazole can safely prevent persistent yeast infections in HIV-infected women who frequently develop yeast infections of the mouth, vagina and throat. Combination antibiotic therapy given intermittently is an effective initial treatment for persons with HIV-related tuberculosis. High dosages of clarithromycin should not be given to patients with Mycobacterium avium complex (MAC); doses above 500 mg are associated with higher mortality levels. Researchers have also determined the genetic sequence of the virus that causes molluscum contagiosum, a skin disease affecting up to 18 percent of AIDS patients.

Topics: Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antitubercular Agents; Candidiasis; Child; Clarithromycin; Clinical Trials as Topic; DNA, Viral; Drug Therapy, Combination; Ethambutol; Female; Fluconazole; Humans; Isoniazid; Molluscum Contagiosum; Molluscum contagiosum virus; Multicenter Studies as Topic; Mycobacterium avium-intracellulare Infection; Ofloxacin; Patient Compliance; Pyrazinamide; Rifampin; Sequence Analysis, DNA; Tuberculosis

Results from recent studies are shedding light on ways to prevent and treat Mycobacterium avium Complex (MAC) disease, a leading cause of death for people with AIDS. A two-drug combination treatment appears to be best. The Food and Drug Administration (FDA) has approved three drugs for the treatment of MAC disease: rifabutin (Mycobutin), clarithromycin (Biaxin), and azithromycin (Zithromax). Two studies using clarithromycin show promising results and indicate that clarithromycin is superior to rifabutin. Another study comparing azithromycin to rifabutin and then to a combination of the two showed azithromycin to be comparable to rifabutin, and the combination was significantly better than either drug alone. Other data show both rifabutin and clarithromycin have drug interactions with some, if not all, of the available protease inhibitors. Azithromycin has no known drug interactions with protease inhibitors and may be attractive for those taking a protease inhibitor. Many drug interactions are appearing so patients need to use caution when using rifabutin. Studies have shown that the optimum treatment for MAC disease is clarithromycin and ethambutol; the addition of clofazimine does not result in any additional benefit. Higher doses of clarithromycin (1000 mg twice a day) over the approved dose levels have proven to be life-threatening. Although the MAC treatment recommendations are to use either azithromycin or clarithromycin with ethambutol, azithromycin is not approved by the FDA for this use, despite many physicians' beliefs that azithromycin is as effective as clarithromycin for treating MAC.

Topics: Acquired Immunodeficiency Syndrome; Amikacin; Antitubercular Agents; Ciprofloxacin; Clarithromycin; Clofazimine; Drug Interactions; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Tuberculin Test; Zidovudine

Topics: Animals; Antibiotics, Antitubercular; Drug Resistance, Microbial; Humans; Mice; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis; Rifabutin; Rifampin; Tuberculosis

Topics: Adult; Drug Resistance, Microbial; HIV Seropositivity; Humans; Male; Mycobacterium avium-intracellulare Infection; Mycobacterium tuberculosis; Rifabutin; Rifampin; Tuberculosis, Pulmonary

The newer macrolides and rifamycins (rifabutin) are major advances for treatment or prophylaxis of disease due to Mycobacterium avium complex. Although rifampin and rifabutin are known to induce the hepatic cytochrome P-450 system, their impact on the metabolism of clarithromycin is unknown. Clarithromycin and its major metabolite, 14-OH clarithromycin, were measured in the sera of patients receiving 500 mg twice a day before and after the addition of antituberculous drugs, including 600 mg/day of rifampin or rifabutin. Mean serum levels of clarithromycin given as a single agent were 5.4 +/- 2.1 micrograms/mL. These decreased to 0.7 +/- 0.6 micrograms/mL in patients receiving rifampin and 2.0 +/- 1.5 micrograms/mL in those receiving rifabutin. Mean serum levels of 14-OH clarithromycin were similar in the 3 groups (1.8-1.9 micrograms/mL). Rifampin and (to a lesser degree) rifabutin appear to induce the metabolism of clarithromycin.

Topics: Clarithromycin; Drug Interactions; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin

Two case reports of deep hand infections with Mycobacterium avium-intracellulare are presented. Both occurred in elderly men. Aggressive surgical débridement combined with antitubercular chemotherapy resulted in an excellent outcome in both cases. Atypical mycobacterial infections should be considered in the differential diagnosis of any patient with prolonged and progressive tenosynovitis. A complete history, including temporally remote inoculation injuries or immunocompromised host status, should be elicited. Acid-fast staining and mycobacterial cultures, including reduced-temperature cultures, must be included in the diagnostic evaluation. Therapy should include immediate and aggressive surgical débridement, as well as appropriate chemotherapy.

Topics: Aged; Antibiotics, Antitubercular; Debridement; Drug Therapy, Combination; Hand; Humans; Male; Mycobacterium avium-intracellulare Infection; Rifampin; Soft Tissue Infections; Tenosynovitis

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

The incidence of disease caused by Mycobacterium tuberculosis (including drug-resistant strains) and M. avium complex (MAC) is increasing. Hypersensitivity reactions to antimycobacterial agents are relatively uncommon, but when they occur they may result in cessation of therapeutic medications. We report our experience with rapid oral desensitization to ethambutol and rifampin in a group of 10 patients with mycobacterial disease who had experienced cutaneous hypersensitivity reactions to these drugs. An adaptation of the rapid oral desensitization protocol for penicillin was used, with the dosing intervals increased to account for the different kinetics of these drugs. Adverse reactions were few and easily treated without necessitating cessation of therapy. We conclude that oral desensitization to rifampin and ethambutol by our protocol is safe and effective, allowing these patients to proceed with an optimal antimycobacterial regimen.

Topics: Administration, Oral; Aged; Clinical Protocols; Desensitization, Immunologic; Drug Administration Schedule; Drug Eruptions; Ethambutol; Humans; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Rifampin

Isolates of Mycobacterium avium complex from five patients on longterm (3-5 yrs) anti-mycobacterial drug treatment were collected during the early and late phase of disease, and studied in vitro for their susceptibility to anti-mycobacterial drugs and drug-combinations. All isolates were resistant or moderately resistant to ethambutol, rifampicin and streptomycin when given singly; however, all strains isolated early in the disease were susceptible to the combination of ethambutol with either rifampicin or streptomycin. All late isolates had developed resistance to one or both of these combinations. Three of the patients died within a year after the last isolation of M. avium complex, and the two remaining patients still have severe chronic disease. It is concluded that the susceptibility of M. avium strains to combinations of drugs should be monitored during the course of treatment, in order to guide the selection of effective drug-combinations throughout the infection.

Topics: Aged; Antitubercular Agents; Child; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Streptomycin; Time Factors

Twenty-seven human immunodeficiency virus-infected patients with disseminated Mycobacterium avium complex disease who were treated with oral antimycobacterial agents (clofazimine, ciprofloxacin, ethambutol, and rifampin) were studied to evaluate the usefulness of monitoring serum drug concentrations and testing in vitro susceptibility of M. avium complex (MAC) isolates. Twenty patients tolerated treatment with three or four antimycobacterial agents for at least 8 weeks; mycobacteremia was eradicated in 7 (35%). The in vitro susceptibilities of MAC isolates to antimycobacterial agents were similar for these 7 and for the 13 who did not respond to antimycobacterial treatment. Serum drug levels were below the expected range in 6 of the 7 whose mycobacteremia was cleared and in 9 of the 13 nonresponders (P = .41). These low serum concentrations of antimycobacterial drugs may be due to impaired drug absorption in patients with AIDS and disseminated MAC disease.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Ciprofloxacin; Clofazimine; Drug Monitoring; Ethambutol; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Prospective Studies; Rifampin

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

Clinical characteristics are analysed in patients with primary infection of Mycobacterium avium complex (MAC). The definition of primary infection of MAC are determined as follows; 1) MAC is found several times since the beginning of the disease, 2) clinical symptoms or abnormal shadows on chest roentgenogram corresponding to MAC infection, 3) no old tuberculous lesions nor other abnormal shadows like bronchectasis, 4) no abnormal serological results suggesting other bacterial or viral infections. According to this definition, 17 out of 84 MAC patients are diagnosed as primary MAC infection, and clinical features are analyzed in these 17 patients. Average age of patients is 61.1 +/- 12.9 year old. This age is significantly higher than that of inpatients with pulmonary tuberculosis in our hospital, and lower than that of all MAC patients including primary and secondary infection. Five (29.4%) are male and 12 (70.6%) are female, the ratio of male to female is 1 to 2.4. This value is significantly different with that of inpatients with pulmonary tuberculosis in our hospital which revealed about 3 to 1. Most of the patients complained of cough with sputum, especially of hemosputum. Eleven patients (64.7%) out of 17 patients complained of repeated hemosputum. The frequency of hemosputum is very high compared with that of the patients with pulmonary tuberculosis (about 20%). No compromised condition was present except for a patient with Behcet's disease who was taking steroid hormone. Roentgenographic features of primary infection of MAC are those of scattered small nodular lesions in the peripheral part of the lung, thin wall cavity formation, no contraction of the diseased lung nor dislocation of the trachea.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Tuberculosis, Pulmonary

A patient with AIDS developed a purplish, necrotic skin lesion followed by fevers, constitutional symptoms, and watery diarrhea. Stains of samples from the skin lesion and of stool and bone marrow revealed acid-fast bacilli, and Mycobacterium avium was isolated from cultures of these specimens and blood. With the initiation of multiagent oral antimycobacterial therapy, the patient's symptoms abated and the cutaneous lesion reepithelialized. We believe this lesion to be a manifestation of disseminated infection due to Mycobacterium avium complex (MAC). As the population of patients with AIDS who have CD4 cell counts of < 100/mm3 increases, new and unusual manifestations of disseminated MAC infection can be expected. New oral agents with increased activity against MAC may make early recognition and treatment of MAC infections more rewarding.

Topics: Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Ciprofloxacin; Clarithromycin; Drug Therapy, Combination; Ethambutol; Humans; Male; Mycobacterium avium; Mycobacterium avium-intracellulare Infection; Rifampin; Skin Diseases, Bacterial

In vitro and animal investigations have demonstrated the antimycobacterial activity of some fluoroquinolones, including ciprofloxacin, but information regarding their clinical usefulness in mycobacterial infections is sparse. This article presents treatment results of 11 patients with tuberculosis and 4 with atypical mycobacterial infections. They were treated with combinations of ciprofloxacin and one or two other antituberculosis agents. Susceptibility of the infecting organisms to ciprofloxacin was determined in 14 of the 15 patients: in 12 of them, minimum inhibitory concentrations ranged between 0.31 and 1.25 micrograms/mL, suggesting a good level of activity. Serum concentrations of ciprofloxacin, sampled one hour after dosing and measured by a specific HPLC assay, revealed considerable variability (range 0.22-8.41 micrograms/mL). Serial plasma samples taken under controlled conditions suggested that a decreased rate of absorption was responsible for low one-hour concentrations in one of the subjects. Adverse reactions to ciprofloxacin were few and included nausea in four patients, crystalluria in one, and febrile reaction in another. A satisfactory response in terms of clinical and radiologic improvement, bacteriologic conversion, and absence of relapse was seen in 13 of the 14 patients who completed an adequate course of therapy. A controlled clinical trial of this promising antimycobacterial agent is needed.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Child; Ciprofloxacin; Drug Therapy, Combination; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Rifabutin; Rifampin; Rifamycins; Tuberculosis, Pulmonary

The comparative activities of newer rifamycin analogs and the activity of rifabutin or rifapentine in combination with other antimycobacterial agents was evaluated in the beige (C57BL/6J; bgj/bgj) mouse model of disseminated Mycobacterium avium infection. Rifabutin and rifapentine at 20 mg/kg of body weight had comparable activities. P/DEA and CGP 7040 at 20 mg/kg were less active. The combination of ethambutol at 125 mg/kg and rifabutin at 20 mg/kg resulted in a slight increase in activity beyond that seen with rifabutin alone against organisms in the spleens. The combination of ethambutol and rifapentine at 20 mg/kg resulted in a modest increase in activity beyond that seen with rifapentine alone against organisms in the lungs. The combination of ethionamide at 125 mg/kg and rifapentine resulted in a decrease in activity compared with that for rifapentine alone. The combination of clofazimine at 20 mg/kg and rifapentine resulted in increased activity in the mouse model. The combination of clofazimine and rifapentine (or rifabutin) appears to be an attractive regimen that should be evaluated for the treatment of human infections due to M. avium complex.

Topics: Animals; Culture Media; Drug Therapy, Combination; Female; Male; Mice; Mice, Inbred C57BL; Mycobacterium avium-intracellulare Infection; Rifabutin; Rifampin; Rifamycins

During the period of 24 years from 1965 to 1988, we treated a total of 181 patients who had pulmonary infection caused by Mycobacterium avium--Mycobacterium intracellulare complex (MAI complex). Of these 181, 34 (19%) were cured showing sputum conversion and disappearance of cavity or marked reduction of cavity in the size to 1/2 or less or change of the cavity to thin-walled one. In these patients, negative culture continued at least for one year by monthly sputum examination. The most frequently used regimen in these patients was RFP + INH + SM, and the secondly RFP + INH + EVM, and thereafter multiple drug regimens including RFP + INH. The most frequently used drugs were RFP, INH, EVM, SM and EB. Based on the above results, we recommend the regimen RFP + INH + EVM + EB or RFP + INH + SM + EB, to which, if possible, were added a combination of MC + SX + KT. (As to abbreviations, refer to Table 3).

Topics: Adult; Aged; Drug Therapy, Combination; Enviomycin; Ethambutol; Female; Humans; Isoniazid; Kanamycin; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin; Streptomycin; Tuberculosis, Pulmonary

Disease due to Mycobacterium avium complex (MAC) in patients with the acquired immunodeficiency syndrome (AIDS) typically occurs late in the course of AIDS and is usually disseminated with evidence of multiorgan involvement. Most patients are persistently bacteremic. Previously published studies have noted a poor response to antimycobacterial chemotherapy. We describe successful treatment of MAC disease in an AIDS patient with a multiple drug regimen, including amikacin, clofazimine, rifampin, ethambutol, and ciprofloxacin. This patient, whose presentation and MAC disease course distinctly differ from most published experience, remains clinically and microbiologically MAC-disease free 25 months after initiation of therapy. We describe four additional AIDS patients with MAC disease who had a favorable clinical and microbiological response to this regimen without developing serious adverse effects after periods ranging from 4 to 12 months. We suggest a prospective, controlled clinical trial using this regimen for treatment of MAC disease in patients with AIDS may be warranted.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amikacin; Antitubercular Agents; Ciprofloxacin; Clofazimine; Drug Therapy, Combination; Ethambutol; Humans; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Rifampin

Topics: Antibiotics, Antitubercular; Drug Therapy, Combination; Ethambutol; Humans; Isoniazid; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections, Nontuberculous; Rifampin; Streptomycin; Tuberculosis

We tested the activity of the new fluoroquinolone sparfloxacin (CI-978; AT 4140) against 30 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome. MICs of sparfloxacin (range, less than or equal to 0.06 to 4 micrograms/ml) were lower than MICs of ciprofloxacin for all 30 strains, and MBCs for acid-fast bacteria were lower for 28 of the 30 strains. In synergism experiments using 10 strains of MAC, fractional inhibitory concentration indices revealed that the combination of sparfloxacin plus ethambutol was synergistic against 9 strains, and the three-drug combination of sparfloxacin plus ethambutol plus rifampin was synergistic against all strains. In the absence of ethambutol, the combination of sparfloxacin plus rifampin appeared to be antagonistic against three of the MAC strains.

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Ciprofloxacin; Drug Synergism; Ethambutol; Fluoroquinolones; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Humans; Male; Methadone; Mycobacterium avium-intracellulare Infection; Opioid-Related Disorders; Rifampin; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

To determine the efficacy of combination drug therapy for disseminated Mycobacterium avium complex infection in patients with the acquired immunodeficiency syndrome (AIDS).. Prospective, nonrandomized, before-after comparison.. Outpatient clinics at three university medical centers.. Seventeen patients with at least two consecutive blood cultures positive for M. avium complex who had not been previously treated with antituberculous medications. Fifteen of the seventeen patients completed at least 4 weeks of treatment.. Patients received daily intravenous amikacin (7.5 mg/kg body weight) for the first 4 weeks plus the following oral medications for at least 12 weeks: ciprofloxacin, 750 mg twice daily; ethambutol, 1000 mg daily; and rifampin, 600 mg daily.. The baseline geometric mean colony count from blood cultures decreased from 537/mL to 14/mL (P less than 0.001) after 4 weeks of therapy. The microbiologic suppression was sustained while on treatment and was associated with a decrease in systemic symptoms related to M. avium complex infection. Premature withdrawal from treatment (less than 12 weeks) occurred in 7 of 17 patients. The commonest reasons for early withdrawal were gastrointestinal intolerance and hepatic toxicity.. Mycobacterial load and systemic symptoms in patients with AIDS and disseminated M. avium complex infection can be effectively reduced by a regimen containing amikacin, ethambutol, rifampin, and ciprofloxacin.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Amikacin; Chemical and Drug Induced Liver Injury; Ciprofloxacin; Drug Therapy, Combination; Ethambutol; Female; Humans; Infusions, Intravenous; Male; Mycobacterium avium-intracellulare Infection; Rifampin; Vomiting

The rate of sputum conversion (continuously negative cultures for six months or more) was compared among four regimens given to 83 patients with moderately advanced, cavitary lung disease caused by Mycobacterium avium complex untreated previously. The regimens of rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin appeared to be superior to the regimen of rifampin + isoniazid + ethambutol. No statistically significant difference was observed between the regimens rifampin + isoniazid + enviomycin and rifampin + isoniazid + streptomycin.

Topics: Clinical Protocols; Drug Combinations; Enviomycin; Ethambutol; Female; Humans; Isoniazid; Lung Diseases; Male; Middle Aged; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin; Sputum; Streptomycin; Viomycin

Three treatment protocols using rifabutine for mycobacterial infections resistant to rifampicin were prepared by a study group (GETIM) and were accepted by the ethical committee concerned. A prospective study has been carried out since April 1986. Thirty-five cases of tuberculosis with bacilli resistant to rifampicin received daily treatment with 5 to 7 mg/kg of rifabutine combined with several other drugs which were still active in vitro. Sixteen cases of M. xenopi infection occurred in individuals without apparent immune deficiency and they were treated with a daily combination of 5 to 7 mg/kg of rifabutine, 20 mg/kg of ethambutol, 3 to 5 mg/kg of isoniazid and 400 mg of ofloxacin (or 800 mg of pefloxacin). Twenty-one cases of M. avium-intracellulare infection, also in patients without any evident immune deficiency, and fifty-nine cases in patients suffering from the acquired immunodeficiency syndrome (AIDS), were treated with a similar combination in which the fluoroquinolone was replaced with 100 mg of clofazimine. During the first three months of treatment there were few major problems of toxicity or acceptability in the different combinations of drugs with the exception of three cases of leukopenia with thrombocytopenia. The proportion of negative cultures on the third month was 8 out of 24 (33%) for the cases of pulmonary tuberculosis and 10 out of 13 (77%) for the cases of M. xenopi infection, and 6 out of 11 (55%) and 9 out of 13 (69%), respectively, for infections by M. avium-intracellulare in subjects without immune deficiency and in subjects suffering from AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Ofloxacin; Rifabutin; Rifampin; Rifamycins; Tuberculosis, Pulmonary

Liposome-entrapped rifampin (RFP) was examined for therapeutic efficacy against experimental infection induced in mice by the Mycobacterium avium complex. Intraperitoneal injections (once daily, six times weekly) of liposome-entrapped RFP led to a greater reduction in bacterial growth in the lungs and spleen of infected mice than did free RFP alone. Liposome-entrapped RFP given to mice via the intramuscular or subcutaneous route failed to show such an increased therapeutic efficacy. RFP entrapped in the lipid layer of liposomal vesicles exhibited a level of therapeutic activity similar to that seen with RFP encapsulated in the inner solute of the vesicles. Entrapment of RFP in liposomal vesicles increased incorporation of the drug into host peritoneal macrophages and increased the activity of the agent against M. avium complex phagocytosed into the macrophages.

Topics: Animals; Female; In Vitro Techniques; Liposomes; Lung; Macrophages; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Mycobacterium avium-intracellulare Infection; Organ Size; Rifampin; Tissue Distribution