In Vitro Activities of Six Fluoroquinolones against 250 Clinical Isolates of Mycobacterium tuberculosis Susceptible or Resistant to First-Line Antituberculosis Drugs

Abstract

Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated for susceptibility to ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, and gemifloxacin (SB-265805). Levofloxacin, ciprofloxacin, and grepafloxacin showed the greatest activity (MIC for 90% of strains tested [MIC 90 ] 1 g/ml), although ofloxacin also showed good activity, with an MIC 90 of 2 g/ml. Trovafloxacin and gemifloxacin showed lower in vitro activity, with MIC 90 s of 64 and 8 g/ml, respectively.The increase in drug-resistant Mycobacterium tuberculosis isolates during recent years presents a therapeutic challenge to physicians selecting antimicrobial agents (2,3,4,10,12). Fluoroquinolones may have a useful role in the treatment of these infections not only because some of their derivatives, e.g., ofloxacin (11), have already been used for the treatment of pulmonary tuberculosis but also because newer derivatives are continually being developed. However, comparative in vitro susceptibility data for classic and new agents of this class against a representative number of M. tuberculosis isolates are scarce (5,13,14).In our study, we compared the activities of the fluoroquinolones ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, and the novel compound gemifloxacin (SB-265805) against 250 clinical isolates of M. tuberculosis with different levels of susceptibility to first-line antituberculosis drugs.(Part of this study was presented as a poster at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1999.) The active substances of the assayed antimycobacterial agents were kindly provided as reference powders by SmithKline Beecham (Worthing, United Kingdom). Ofloxacin was obtained from Sigma Chemical Co. (St. Louis, Mo.). Agent corrections were made for purity of antimicrobials. Stock solutions of all of the fluoroquinolones were prepared at 10,000 g/ml in distilled water by adding a 0.1 M NaOH solution for dilution when necessary. Aliquots of the antituberculosis agents were frozen at Ϫ70°C until use. Staphylococcus aureus strain ATCC 29213 was used for quality control to ensure the potency of the fluoroquinolones tested.Two hundred fifty clinical isolates of M. tuberculosis from 250 tuberculosis patients were selected from our laboratory collection (1988 to 1999). Of the samples tested, 197 were of respiratory origin and 53 were of nonrespiratory origin. Testing of susceptibility to first-line antituberculosis drugs (isoniazid, rifampin, ethambutol, and streptomycin) was performed by the agar proportion method in a reference laboratory. Of the strains tested, 44 (18%) were resistant to at least one first-line antituberculosis drug (R-MTB group; 24 monodrug-resistant and 20 multidrug-resistant strains) while the rest were fully susceptible (S-MTB group). The agar proportion method was performed as recommended by the National Committee for Clinical Laboratory Standards (9). Briefly, 7H10 agar medium (Difco) was prepared from a dehydrated base as recommended by the manufact...

Incidence of Moxifloxacin Resistance in Clinical Mycobacterium tuberculosis Isolates in Houston, Texas

“…Their tolerability and relative low to moderate cost have made them an attractive target for development as antituberculosis drugs. The newer quinolones, such as sparfloxacin, gatifloxacin, and moxifloxacin, have better in vitro activity against Mycobacterium tuberculosis clinical isolates than older quinolones, such as ofloxacin, levofloxacin and ciprofloxacin, as suggested by lower MICs, a higher ratio of the peak serum drug concentration to the MIC, and a higher ratio of the 24-h area under the curve to the MIC (11,22,(27)(28)(29)36). In vivo studies in animal models and humans have corroborated these findings (19,34).…”

A Study of the Effectiveness of Two Common Fluoroquinolones on Mycobacterial Strains Isolated From Patients

“…Of these drugs we can name ofloxacin (OFL) and ciprofloxacin (CIP) which are of fluoroquinolones. Totally these antibiotics act against DNA synthesis by preventing activity of DNA-gyrase, which has been explained completely in introduction part [7][8][9][10][11].…”

“…Fluoroquinolones cause inhibition of topoisomerase II or DNA gyrase and topoisomerase IV of bacterium. Topoisomerases are very important and necessary enzymes for copying, proliferation, restoring of bacterium DNA, and keeping bacterium DNA in super coiling state [7][8][9][10][11].…”

Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis

“…The anti-TB potential of gemifloxacin appears to be limited. Gemifloxacin showed a MIC90 value of 8mcg/ml, compared with 1mcg/ml for levofloxacin, trovafloxacin and grepafloxacin [61].…”

“…The principles of treatment for MDR-TB and XDR-TB are the same. The main difference is that XDR-TB is associated with a much higher mortality rate than MDR-TB, because of reduced number of effective treatment options [61][62][63]. Hence there is an urgent need for novel drugs that are active against Mtb in order to shorten the duration of TB therapy [55], [64].…”