In vitro and in vivo activities of clarithromycin against Mycobacterium avium

Fernandes, Prabhavathi; Hardy, Dwight J.; McDaniel, Dennis P.; Hanson, Charles W.; Swanson, R. N.

doi:10.1128/aac.33.9.1531

Cited by 159 publications

(93 citation statements)

References 9 publications

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“…This hypothesis presupposes that impermeability is the mechanism of resistance to clarithromycin in M. tuberculosis. This may not be the case, since clarithromycin apparently penetrates the cell envelope of other mycobacteria to a degree sufficient to cause inhibition (1,3,4,8,23).…”

Section: Discussionmentioning

confidence: 95%

“…Clarithromycin is a new macrolide antibiotic which achieves good concentrations in the respiratory tract, is orally administered, and has been shown to have antimycobacterial activity (1,3,4,8,11,23). These facts led us to Clarithromycin and its metabolite, either alone or in combination, had very little activity against multidrug-resistant M. tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

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The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at >8.0 g/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 g/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4-to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.In recent years there has been renewed interest in infections caused by Mycobacterium tuberculosis. This has been due in part to the resurgence of tuberculosis cases nationwide and an alarming increase in multidrug resistance in M. tuberculosis isolates from these infections (2,5,6,12,14,27,29). Multidrug resistance in M. tuberculosis is especially prevalent in certain geographic localities in the United States, including New York City and Florida (2,9,12,14,29). In addition, certain populations, including those infected with human immunodeficiency virus, recent immigrants to the United States, and patients with a history of treatment for tuberculosis (2,10,14,19,27), have an increased incidence. Most of these strains are resistant to the primary antituberculous drugs isoniazid and/or rifampin (2,10,12,29). Multidrug resistance complicates therapeutic options for the clinician. Indeed, patients infected with multidrug-resistant M. tuberculosis must be treated for a much longer period of time than are patients infected with susceptible strains and response rates are decreased (7,9,12,19).Clarithromycin is a new, acid-stable macrolide antibiotic which has good bioavailability after oral dosing (11,15,25). Peak serum and lung clarithromycin concentrations are 2 to 4 g/ml and 17.5 g/g, respectively (11, 15). Clarithromycin is metabolized to 14-hydroxyclarithromycin, which also has antibacterial activity and may act synergistically with the parent compound (18, 25). Clarithromycin has broad-spectr...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

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“…Therapy resorts to a combination of several drugs and, as in tuberculosis, is very lengthy. Long-term treatment with macrolides such as clarithromycin, which is highly effective in the treatment of MAC infections (4,5), leads to the emergence of resistant forms (6 -8), which can be prevented by combining at least two or three drugs (9,10). However, this in turn can lead to severe side effects (11,12).…”

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confidence: 99%

Blocking the Receptor for IL-10 Improves Antimycobacterial Chemotherapy and Vaccination

Silva

Pais

Appelberg

2001

The Journal of Immunology

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Novel approaches are required for the prevention and therapy of mycobacterial infections since the only vaccine in use, bacillus Calmette-Guérin, is poorly effective and chemotherapy is long and often ineffective in sterilizing the infection. We used a mouse model of Mycobacterium avium infection to address the usefulness of a mAb able to block IL-10R both in treatment of primary infections and in conventional multidrug therapy and subunit vaccination. Treatment of infected mice with this mAb during the entire period of experimental infection had little impact on the course of M. avium infection, with a slight improvement in the resistance of infected mice observed in the liver and spleen at day 30 of infection, which was associated with increased macrophage activation and priming of CD4+ T cells for IFN-γ production. Administration of this mAb later in infection had no effect on its course, but improved the effectiveness of chemotherapy when the latter was started in a chronic phase of infection. Also, the anti-IL-10R mAb acted as an adjuvant in the induction of protective immunity upon vaccination with a mycobacterial subunit preparation.

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“…There could be scope further improve survival by better management of comorbid conditions and by improving the general health of the patient. It may be that macrolides and/or quinolones, which, during the period of this study, were found to have in vitro activity against opportunist mycobacteria [14][15][16][17][18], will result in better cure rates when added to rifampicin and ethambutol. The British Thoracic Society9s ongoing multicentre trial should answer this question by the end of 2004.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary disease caused byM. malmoensein HIV negative patients: 5‐yr follow-up of patients receiving standardised treatment

2003

Eur Respir J

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Pulmonary disease caused by M. malmoense in HIV negative patients:5-yr follow-up of patients receiving standardised treatment When two positive cultures were confirmed by the Mycobacterium Reference Units for England, Wales, Scotland or Scandinavia, the coordinating physician invited the patient9s physician to enrol the patient, who was then treated on a random basis with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid for 2 yrs. Clinical, bacteriological and radiological progress were monitored at set intervals for 5 yrs.In over 5 yrs a total of 106 patients were recruited to the study. The mean age was 58 yrs, range 24-89 yrs. A total of 58% were male and just over half previously or at the time of the study had other lung diseases. Sputum was positive on direct smear in 58%. Cavitation was seen on the chest radiographs of 74%, the majority having cavities of o2 cm in diameter. Less than half of the patients showed bilateral disease, 26% having involvement of more than three lung zones. Disease was confined to the upper zone(s) in 30%. Other lung diseases were evident in 52%. Although clinical response was judged satisfactory at most reviews (90%), one in three patients died within 5 yrs andv5% were thought to have died primarily because of M. malmoense. There were three failures of treatment and eight relapses after the end of treatment. There was no correlation between failure of treatment/relapse and in vitro resistance. A total of 63 (59%) of patients were alive at 5 yrs, of whom 44 (42% of the total entry) were known to be cured.Pulmonary disease caused by Mycobacterium malmoense is a serious condition that is associated with high morbidity and mortality. The results of standard susceptibility tests do not correlate with the bacteriological response of the disease to chemotherapy. Rifampicin and ethambutol, with or without isoniazid, cured only 42% of patients but were better tolerated than previously described, more complex regimens of equal or lesser efficacy. There is a need for more effective regimens that will reduce mortality and failure of treatment/relapse rates, but, in addition, attention should be directed at improving management of comorbid conditions and improving the general health of the patient.

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In vitro and in vivo activities of clarithromycin against Mycobacterium avium

Cited by 159 publications

References 9 publications

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Blocking the Receptor for IL-10 Improves Antimycobacterial Chemotherapy and Vaccination

Pulmonary disease caused byM. malmoensein HIV negative patients: 5‐yr follow-up of patients receiving standardised treatment

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