In vitro activity of four fluoroquinolones against eighty-six isolates of mycobacteria

Texier-Maugein, J; Mormede, M.; Fourche, J.; Bébéar, C.

doi:10.1007/bf02014255

Cited by 28 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

Heifets

Lindholm-Levy

1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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...

show abstract

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.…”

mentioning

confidence: 89%

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

Heifets

Lindholm-Levy

1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…strain 7E1B1W and Mycobacterium sp. strain PYR100) and Mycobacterium smegmatis mc 2 155 were less susceptible to norfloxacin than most of the clinical isolates tested by TexierMaugein et al (36). Because norfloxacin enters mycobacterial cells quickly by simple diffusion (38), the abilities of these strains to transform norfloxacin may partly explain their resistance.…”

Section: Discussionmentioning

confidence: 96%

Transformation of the Antibacterial Agent Norfloxacin by Environmental Mycobacteria

Adjei

Heinze

Deck

et al. 2006

Appl Environ Microbiol

View full text Add to dashboard Cite

Because fluoroquinolone antimicrobial agents may be released into the environment, the potential for environmental bacteria to biotransform these drugs was investigated. Eight Mycobacterium sp. cultures in a sorbitol-yeast extract medium were dosed with 100 g ml ؊1 of norfloxacin and incubated for 7 days. The MICs of norfloxacin for these strains, tested by an agar dilution method, were 1.6 to 25 g ml ؊1 . Cultures were extracted with ethyl acetate, and potential metabolites in the extracts were purified by high-performance liquid chromatography. The metabolites were identified using mass spectrometry and nuclear magnetic resonance spectroscopy. N-Acetylnorfloxacin (5 to 50% of the total absorbance at 280 nm) was produced by the eight Mycobacterium strains. N-Nitrosonorfloxacin (5 to 30% of the total absorbance) was also produced by Mycobacterium sp. strain PYR100 and Mycobacterium gilvum PYR-GCK. The MICs of N-nitrosonorfloxacin and N-acetylnorfloxacin were 2-to 38-and 4-to 1,000-fold higher, respectively, than those of norfloxacin for several different bacteria, including the two strains that produced both metabolites. Although N-nitrosonorfloxacin had less antibacterial activity, nitrosamines are potentially carcinogenic. The biotransformation of fluoroquinolones by mycobacteria may serve as a resistance mechanism.Environmental residues of fluoroquinolone antibacterial agents, such as ciprofloxacin and norfloxacin (11), are of concern because they may select for resistant strains of potentially pathogenic bacteria (12). Because fluoroquinolones are excreted largely unchanged (30), they may be released into the environment (28). Several fluoroquinolones are metabolized by soil fungi, but the role of bacteria in fluoroquinolone metabolism has been less studied (8,25,37).Norfloxacin is a fluoroquinolone used in the treatment of several bacterial diseases, including urinary tract infections in humans (17), enteritis in dogs (2), and chronic respiratory disease in chickens (34). A dextran-linked prodrug has been developed from norfloxacin for treatment of Mycobacterium bovis infections (10). Metabolism of norfloxacin via N acetylation, oxidation, and breakdown of the piperazine ring has been reported for humans (26) and fungi (25).Several Mycobacterium spp. biotransform fluoroquinolones, polycyclic aromatic hydrocarbons (PAHs), and other ring compounds (8, 13). Chen et al. (8) demonstrated by chromatographic techniques and radiolabeling methods that several soil microorganisms, including two strains of mycobacteria, biotransform the fluoroquinolone danofloxacin to N-desmethyldanofloxacin, 1-cyclopropyl-6-fluoro-7-amino-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, and other metabolites that may also include CO 2 . However, nothing is known about the bacterial transformation of other fluoroquinolones that may persist in the environment (11, 28).Based on this existing knowledge and on the potential of mycobacteria to degrade high-priority pollutants, such as PAHs (5, 9, 13), we screened extracts from dosed cultures...

show abstract

“…Some discrepancies may be the result of differences in method. It is, however, shown that MICs vary little, regardless of whether agar or broth dilution was used (48 (2,9,13,16,22,25,37,52,66). However, since different comparison agents were used in these studies it is difficult to be certain about the activities of these compounds in relation to the parent compounds.…”

Section: Vitro Activitymentioning

confidence: 99%