Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system

Brown, Barbara A.; Wallace, Richard J.; Onyi, Grace O.

doi:10.1128/aac.36.9.1987

Cited by 122 publications

(53 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

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

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 99%

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

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Broth Microdilution-For the estimation of the minimum inhibitory concentrations (MICs) of each antibiotic, we used the broth microdilution method as previously described (22). Briefly, serial 2-fold dilutions of compounds were added to LB broth (for M. smegmatis) or 7H9-ADC-Tween (for BCG) to achieve final concentrations ranging from 128 -0.125 g/ml.…”

Section: Methodsmentioning

confidence: 99%

A Novel Mechanism of Growth Phase-dependent Tolerance to Isoniazid in Mycobacteria

Niki

Tateishi

Ozeki

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The mechanism underlying mycobacterial phenotypic tolerance to isoniazid is unknown. Results: MDP1, a mycobacterial histone-like protein, down-regulates KatG expression. Conclusion: Down-regulation of KatG by MDP1 causes growth phase-dependent phenotypic tolerance to isoniazid in mycobacteria. Significance: Understanding the mechanism by which mycobacteria acquire tolerance to isoniazid is important for developing novel therapies.

show abstract

“…Broth microdilution testing was performed with clarithromycin only. Testing was performed within 30 min following final inoculum preparation as described by Brown et al (1). Final inoculum suspensions were poured into sterile disposable reagent reservoirs (Matrix Technologies Corporation, Hudson, N.H.), and 100-l aliquots were transferred to each well of the MIC tray with a multichannel pipettor.…”

Section: Susceptibility Test Methods (I) Bactec 460tb Methodmentioning

confidence: 99%

Multisite Reproducibility of Results Obtained by Two Broth Dilution Methods for Susceptibility Testing of Mycobacterium avium Complex

et al. 2003

View full text Add to dashboard Cite

A multicenter study was conducted to assess the interlaboratory reproducibility of susceptibility testing of Mycobacterium avium complex (MAC) by broth microdilution using two different media (cation-adjusted Mueller-Hinton broth with 5% oleic acid-albumin-dextrose-catalase and 7H9 broth with casein) and by macrodilution using the BACTEC 460TB and 12B media at pH 6.8 and 7.3 to 7.4. Ten well-characterized strains of MAC (four macrolide susceptible, six macrolide resistant) were tested against clarithromycin and azithromycin (the latter only by BACTEC 460TB, pH 6.8). At each site, strains were tested against clarithromycin three times on each of three separate days (nine testing events per isolate) by using a common lot of microdilution trays and BACTEC 12B medium, pH 6.8; strains were tested once on three separate days against clarithromycin in 12B medium at pH 7.3 to 7.4 and against azithromycin. Agreement among MICs (i.e., mode ؎ 1 twofold dilution) was 100% for all strains and both drugs when BACTEC 460TB was used, regardless of the pH of the medium, but varied when microdilution with either medium was used, particularly with susceptible strains. Agreement based on interpretive category, with NCCLS-recommended breakpoints, was 100% for all strains with the BACTEC 460TB method (both drugs and both pH values) and with microdilution using 7H9 broth. With microdilution and Mueller-Hinton broth, agreement by interpretive category was 100% for eight isolates and >90% for two; errors occurred only in laboratories where personnel had minimal experience with this technique. MAC susceptibility testing may be performed by broth macrodilution or microdilution at either pH, with NCCLS-recommended interpretive breakpoints. However, because visual interpretation of broth microdilution end points is subjective, it is more prone to reader error; therefore, this method requires greater expertise than the BACTEC 460TB. Both techniques require appropriate validation and continued documentation of proficiency.

show abstract

Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system

Cited by 122 publications

References 27 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

A Novel Mechanism of Growth Phase-dependent Tolerance to Isoniazid in Mycobacteria

Multisite Reproducibility of Results Obtained by Two Broth Dilution Methods for Susceptibility Testing of Mycobacterium avium Complex

Contact Info

Product

Resources

About