Minimal Inhibitory Concentrations of Rifabutin, Ciprofloxacin, and Ofloxacin against<i>Mycobacterium tuberculosis</i>Isolated before Treatment of Patients in Taiwan

Chen, Chung-Hua; Shih, Jen‐Fu; Lindholm-Levy, Pamela J.; Heifets, Leonid

doi:10.1164/ajrccm/140.4.987

Cited by 31 publications

(11 citation statements)

References 7 publications

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“…Despite these aggravating circumstances, the five remaining patients did convert to negative, which fact was considered by the authors of the paper as evidence that A. pH 6. (1,3,5,7,8,9,14,22,23,26,28). The 29.1% for ciprofloxacin, and 85.5% for Win 57273.…”

Section: Resultsmentioning

confidence: 99%

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MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis

Heifets

Lindholm-Levy

1990

Antimicrob Agents Chemother

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A new quinolone, Win 57273 [1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolonecarboxylic acid], synthesized by Sterling Research Group, was tested in vitro against Mycobacterium tuberculosis and Mycobacterium avium strains. The broth-determined MICs of this agent ranged from 1.0 to 4.0 ,ug/ml for M. tuberculosis strains and from 0.25 to 8.0 ,ug/ml for M. avium strains. A distinctive feature of this agent, in comparison with ofloxacin and ciprofloxacin, is its substantially greater activity at the low pHs. For M. avium strains, the MICs of Win 57273 were 2.0 ,ug/ml or less for 54.5% of strains at pH 6.8 and 85.5% of strains at pH 5.0. Win 57273 was more active than ciprofloxacin against M. avium strains, and this difference was very substantial for all M. avium strains at pH 5.0. Taking into account that the predominant locations of these organisms in vivo are within the phagosomes and phagolysosomes of macrophages, i.e., in acidic environments at pH 5.0 or lower, the greater activity of Win 57273 at low pH makes this quinolone especially promising for M. avium infection. The bactericidal activity of Win 57273 for M. avium strains was the same as that of ciprofloxacin, with MBCs from 4.0 to 16.0 ,ug/ml.Evaluation of the in vitro activity of various quinolones led to the identification of the two, ofloxacin and ciprofloxacin, having the most potential against mycobacteria. The MICs of these two drugs were found to be within the same range when tested against Mycobacterium tuberculosis in liquid media (3,14,26), in agar plates (1,5,7,14,22,23), and in Lowenstein-Jensen medium (27; R. D. Urbanczik, Abstr. XXVI Int. Union against Tuberculosis World Conf., A012, p. 13, 1986), but because of the differences in pharmacokinetics, the preference was given to ofloxacin. At the same time, ciprofloxacin was found to be more active than ofloxacin and other quinolones in experiments in vitro with Mycobacterium avium complex (4, 7-9, 14, 23, 25). The MICs of ofloxacin and ciprofloxacin were quite consistent in different studies, regardless of the type of media, solid or liquid, used in the test.In our previous study (14), the MICs of ofloxacin found for 46 M. avium strains were over a wide range and were all greater than 2.0 Fxg/ml. The MICs of ciprofloxacin for these strains were also over a wide range, but for 13 of 46 strains (28%), they were 2.0 gig/ml or less. The same distribution of M. avium complex strains was found in another study (15), in which 30% of the cultures were susceptible to s2.0 ,ug of ciprofloxacin per ml. Ofloxacin and ciprofloxacin have been reported as having high bactericidal activities in vitro against M. tuberculosis, with MBC/MIC ratios of 2 and 4 (4, 9). We confirmed this in our previous study and also reported that these drugs are highly bactericidal for M. avium strains as well, with MBC/MIC ratios between 1 and 8 (14). The available information about MICs and MBCs of ofloxacin and ciprofloxacin for M. tuberculosis and M. avium and the fact that some quinolones are...

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Section: Resultsmentioning

confidence: 99%

“…The MICs of these two drugs were found to be within the same range when tested against Mycobacterium tuberculosis in liquid media (3,14,26), in agar plates (1,5,7,14,22,23), and in Lowenstein-Jensen medium (27; R. D. Urbanczik, Abstr. XXVI Int.…”

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confidence: 89%

MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis

Heifets

Lindholm-Levy

1990

Antimicrob Agents Chemother

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“…Some data from AST of second-line drugs with BACTEC 12B medium were presented quite early (11) but have never been published. Allen et al (1) defined the MICs on Middlebrook agar of aminoglycosides while Heifets' group undertook several investigations into AST with the BACTEC 12B medium, e.g., with aminoglycosides (13), ethionamide (16,22), and quinolones (15), the last group of compounds having also been studied by others (4,5,8,9). The MICs of rifabutin, generated either with the radiometric BACTEC 12B medium (17) or with Middlebrook 7H9 broth (7), are also available.…”

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Multicenter Laboratory Validation of Susceptibility Testing of Mycobacterium tuberculosis against Classical Second-Line and Newer Antimicrobial Drugs by Using the Radiometric BACTEC 460 Technique and the Proportion Method with Solid Media

Bonato²,

et al. 1999

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In a large multicenter study involving six major study sites in the United States, Canada, and Europe, the susceptibilities of 272Mycobacterium tuberculosis strains to classical second-line antituberculosis (anti-TB) drugs (capreomycin, cycloserine, ethionamide, and kanamycin) and newer compounds (amikacin, clofazimine, ofloxacin, and rifabutin) were determined by the radiometric BACTEC 460 procedure and the conventional proportion method on Middlebrook 7H10 agar. Previously established critical concentrations for classical second-line anti-TB drugs were compared with several concentrations in liquid medium to establish equivalence. MICs of newer compounds determined in liquid medium were either the same or up to four times lower than those determined in agar medium. After establishing critical concentrations (breakpoints) in the extended testing of clinical isolates, we obtained an excellent overall correlation between the two systems, with no errors with amikacin, kanamycin, and ofloxacin and very few major or very major errors with the other drugs; however, for cycloserine, no breakpoint concentration could be recommended due to repeatedly inconsistent results by both methods. Based on these data we conclude that the BACTEC 460 procedure is a simple and rapid method requiring 4 to 8 days on average to generate accurate antimicrobial susceptibility testing (AST) results for eight anti-TB drugs other than those considered primary ones. These data not only fill a major gap of knowledge regarding the critical test concentrations of secondary anti-TB drugs but also provide a baseline for future evaluations ofM. tuberculosis AST with the more recently developed, nonradiometric broth-based culture systems.

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“…New drugs are needed for the control of tuberculosis because resistance to classical antituberculosis drugs has dramatically increased (39). Fluoroquinolone antibiotics are active in vitro against Mycobacterium tuberculosis isolates (7,20) and are increasingly being used in combination with other agents to treat tuberculosis. As with all antituberculosis agents, M. tuberculosis strains can develop resistance to fluoroquinolones (42).…”

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Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra

Kocagoz

Hackbarth

Ünsal

et al. 1996

Antimicrob Agents Chemother

110

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To characterize mechanisms of resistance to fluoroquinolones by Mycobacterium tuberculosis, mutants of strain H37Ra were selected in vitro with ofloxacin. Their quinolone resistance-determining regions for gyrA and gyrB were amplified and sequenced to identify mutations in gyrase A or B. Three types of mutants were obtained: (i) one mutant (TKp1) had no mutations in gyrA or gyrB; (ii) mutants that had single missense mutations in gyrA, and (iii) mutants that had two missense mutations resulting in either two altered gyrase A residues or an altered residue in both gyrases A and B. The TKp1 mutant had slightly reduced levels of uptake of [14C]norfloxacin, which was associated with two- to fourfold increases in the MICs of ofloxacin, ciprofloxacin, and sparfloxacin. Gyrase mutations caused a much greater increase in the MICs of fluoroquinolones. For mutants with single gyrA mutations, the increases in the MICs were 4- to 16-fold, and for mutants with double gyrase mutations, the MICs were increased 32-fold or more compared with those for the parent. A gyrA mutation in TKp1 secondary mutants was associated with 32- to 128-fold increases in the MICs of ofloxacin and ciprofloxacin compared with the MICs for H37Ra and an eight-fold increase in the MIC of sparfloxacin. Sparfloxacin was the most active fluoroquinolone tested. No sparfloxacin-resistant single-step mutants were selected at concentrations of > 2.5 micrograms/ml, and high-level resistance (i.e., MIC, > and = 5 micrograms/ml) was associated with two gyrase mutations. Mutations in gyrB and possibly altered levels of intracellular accumulation of drug are two additional mechanisms that may be used by M. tuberculosis in the development of fluoroquinolone resistance. Because sparfloxacin is more active in vitro and selection of resistance appears to be less likely to occur, it may have important advantage over ofloxacin or ciprofloxacin for the treatment of tuberculosis.

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Minimal Inhibitory Concentrations of Rifabutin, Ciprofloxacin, and Ofloxacin againstMycobacterium tuberculosisIsolated before Treatment of Patients in Taiwan

Cited by 31 publications

References 7 publications

MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis

MICs and MBCs of Win 57273 against Mycobacterium avium and M. tuberculosis

Multicenter Laboratory Validation of Susceptibility Testing of Mycobacterium tuberculosis against Classical Second-Line and Newer Antimicrobial Drugs by Using the Radiometric BACTEC 460 Technique and the Proportion Method with Solid Media

Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra

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