Susceptibility of the Bacteroides fragilis group to newer quinolones and other standard anti-anaerobic agents.

The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to four quinolones (moxifloxacin, clinafloxacin, trovafloxacin and ciprofloxacin) were determined, as well as to cefoxitin, clindamycin, metronidazole, imipenem and ticarcillin-clavulanic acid. The results for the latter five agents were compared with those of a study on 200 isolates done 6 years previously. Clinafloxacin and trovafloxacin were the most active agents tested with MIC90s lower than all other antimicrobials except imipenem. Susceptibility rates for imipenem, ticarcillin- clavulanic and metronidazole continue to be high, although resistant strains are emerging. For ticarcillin-clavulanic acid and metronidazole, MIC90s increased four- to eight-fold for the B. fragilis species between the two study periods.     

Comparative in vitro activities of clinafloxacin and trovafloxacin against 1,000 isolates of bacteroides fragilis group: effect of the medium on test results

The in vitro antibacterial activities of clinafloxacin, trovafloxacin, ciprofloxacin, and cefoxitin against 1,000 clinical isolates of Bacteroides fragilis group were compared by agar dilution in brucella blood agar (BBA) and Wilkins Chalgren agar (WCA). Significantly higher geometric mean MICs for the three quinolones and cefoxitin (P<0.001) were obtained in BBA than in WCA. Regardless of medium, clinafloxacin was slightly more active than trovafloxacin. The activity of clinafloxacin and trovafloxacin was greater than that of cefoxitin against B. distasonis, B. ovatus, and B. thetaiotaomicron but lower against B. vulgatus. High cross resistance between trovafloxacin and clinafloxacin was observed.     

Changing patterns of fluoroquinolone resistance among Bacteroides fragilis group organisms over a 6-year period (1997-2002)

The evolution of susceptibility to the newer fluoroquinolones, moxifloxacin and trovafloxacin, of Bacteroides fragilis group organisms isolated in our hospital from 1997 to 2002 was studied. A total of 927 strains were included in the study. Trovafloxacin was more active than moxifloxacin against the various species of the group. During the study period, an increase in resistance to both quinolones was observed. Rates of resistance to moxifloxacin at a breakpoint of 8 microg/mL remained stable at around 6% during the period 1997-1998 and increased to 11.4% in 2000 and to 16.5% in 2001-2002 (P<0.005). Resistance to trovafloxacin rose significantly from 0.6% in 1998 to 6.8% in 1999 (P<0.05) and did not change appreciably over the last 3 years studied. This study confirms the increasing resistance of B. fragilis group organisms to trovafloxacin and moxifloxacin and emphasizes the need to perform periodic antimicrobial susceptibility tests to guide the selection of appropriate antimicrobial therapy.     

Comparative in vitro activity of gemifloxacin

Gemifloxacin is a new quinolone and, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, is more potent in vitro than ciprofloxacin or ofloxacin against Gram-positive aerobes. Gemifloxacin was the most potent of the quinolones tested against streptococci and most ciprofloxacin-resistant pneumococci were susceptible to gemifloxacin. Gemifloxacin, like moxifloxacin, trovafloxacin, grepafloxacin and clinafloxacin, was more potent than ciprofloxacin or ofloxacin against all staphylococci and many ciprofloxacin-resistant isolates were susceptible to these quinolones. Against Gram-negative aerobes gemifloxacin was as potent as or slightly less potent than ciprofloxacin, and isolates resistant to ciprofloxacin were also resistant to gemifloxacin and to moxifloxacin, trovafloxacin and grepafloxacin. Gemifloxacin was also the most potent quinolone against Gram-positive anaerobes and fusobacteria but trovafloxacin was the most potent agent tested against other Gram-negative anaerobes.     

Emergence of fluoroquinolone resistance among Bacteroides species

BACKGROUND: Several newer generation fluoroquinolones have demonstrated good in vitro activity against Bacteroides species; particularly when first introduced. However, resistance of Bacteroides to quinolones appears to be increasing. MATERIALS AND METHODS: From 1994 to 2001, consecutive non-duplicated Bacteroides isolates from clinical specimens in 12 US hospitals were sent to the Tufts anaerobe laboratory for identification and susceptibility testing. NCCLS recommended methodology for testing was employed. Breakpoints of 8 mg/l for trovafloxacin and 4 mg/l for moxifloxacin were used to examine susceptibility trends. RESULTS: In total, 4434 isolates were analysed. The geometric mean MIC increased significantly for clinafloxacin, trovafloxacin and moxifloxacin. Resistance to trovafloxacin (breakpoint of 8 mg/l) and moxifloxacin (breakpoint of 4 mg/l) increased from 8% to 25% and from 30% to 43%, respectively. Increased resistance was observed for all Bacteroides species, for all sites of isolation, and in 11 of 12 participating hospitals. Bacteroides vulgatus and isolates from decubitus ulcers were associated with increased resistance. During 2001, trovafloxacin and moxifloxacin resistance among blood isolates was 27% and 52%, respectively. The association between increased resistance and year of isolation remained significant after adjustment for hospital, species and site of isolation. CONCLUSIONS: Fluoroquinolone resistance among Bacteroides isolated in the US has markedly increased during the years 1994 to 2001. High rates of resistance among blood isolates are of particular concern.     

Comparative bactericidal activities of ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Streptococcus pneumoniae in a dynamic in vitro model

Several new quinolones that exhibit enhanced in vitro activity against Streptococcus pneumoniae have been developed. Using a dynamic in vitro model, we generated time-kill data for ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin against three isolates of quinolone-susceptible S. pneumoniae. Three pharmacokinetic profiles were simulated for each of the study agents (0.1, 1, and 10 times the area under the concentration-time curve [AUC]). Target 24-h AUCs were based upon human pharmacokinetic data resulting from the maximal daily doses of each agent. Ciprofloxacin was the least active agent against all three isolates. With regimens that simulated the human 24-h AUC, ciprofloxacin resulted in an initial, modest decline in the numbers of CFU per milliliter; however, by 48 h the numbers of CFU per milliliter returned to or exceeded the starting inoculum. At the AUC, levofloxacin resulted in variable bacteriostatic and bactericidal activities against the isolates. The remaining agents yielded bactericidal (99.9% reduction) activity by 48 h with regimens that simulated the AUC. At 0.1 time the AUC ciprofloxacin and levofloxacin produced no inhibitory effect, grepafloxacin exhibited bacteriostatic activity, trovafloxacin had mixed static and cidal activities, and clinafloxacin and moxifloxacin caused significant reductions in the numbers of CFU per milliliter by 48 h. All six agents produced cidal activity at 10 times the AUC. In this dynamic in vitro model of infection, the quinolones demonstrated various degrees of activity against S. pneumoniae. The rank order of activity, with respect to bactericidal effect, was ciprofloxacin (least active) < levofloxacin < grepafloxacin, trovafloxacin < clinafloxacin and moxifloxacin (most active). The rank order of the agents with respect to the selection of resistance was ciprofloxacin (most likely) > grepafloxacin, moxifloxacin, and trovafloxacin > levofloxacin > clinafloxacin.     

Comparative activities of eight quinolones against members of the Bacteroides fragilis group.

The in vitro activities of five new quinolones (clinafloxacin [CI-960 or PD-127391], BAY Y 3118, E-4868, E-5065, and E-5068) against 100 Bacteroides fragilis group bacterial isolates were compared with those of ciprofloxacin, ofloxacin, and sparfloxacin. Overall, E-5068 was the most active in vitro (MIC for 90% of isolates tested [MIC90], 0.25 microgram/ml); this was followed by clinafloxacin and BAY Y 3118 (MIC90, 0.5 microgram/ml). Ciprofloxacin, sparfloxacin, and ofloxacin were the least active (MIC90s, 64, 16, and 16 micrograms/ml, respectively). B. fragilis and Bacteroides caccae were more susceptible than the other members of the B. fragilis group to all of the quinolones tested.     

gyrA Mutations Associated with Quinolone Resistance in Bacteroides fragilis Group Strains

Mutations in the gyrA gene contribute considerably to quinolone resistance in Escherichia coli. Mechanisms for quinolone resistance in anaerobic bacteria are less well studied. The Bacteroides fragilis group are the anaerobic organisms most frequently isolated from patients with bacteremia and intraabdominal infections. Forty-four clinafloxacin-resistant and-susceptible fecal and clinical isolates of the B. fragilis group (eight Bacteroides fragilis, three Bacteroides ovatus, five Bacteroides thetaiotaomicron, six Bacteroides uniformis, and 22 Bacteroides vulgatus) and six ATCC strains of the B. fragilis group were analyzed as follows: (i) determination of susceptibility to ciprofloxacin, levofloxacin, moxifloxacin, and clinafloxacin by the agar dilution method and (ii) sequencing of the gyrA quinolone resistance-determining region (QRDR) located between amino acid residues equivalent to Ala-67 through Gln-106 in E. coli. Amino acid substitutions were found at hotspots at positions 82 (n = 15) and 86 (n = 8). Strains with Ser82Leu substitutions (n = 13) were highly resistant to all quinolones tested. Mutations in other positions of gyrA were also frequently found in quinolone-resistant and -susceptible isolates. Eight clinical strains that lacked mutations in their QRDR were susceptible to at least two of the quinolones tested. Although newer quinolones have good antimicrobial activity against the B. fragilis group, quinolone resistance in B. fragilis strains can be readily selected in vivo. Mutational events in the QRDR of gyrA seem to contribute to quinolone resistance in Bacteroides species.     

Activity of clinafloxacin, compared with six other quinolones, against Acinetobacter baumannii clinical isolates

The in vitro activity of clinafloxacin was studied in comparison with ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, sparfloxacin and trovafloxacin against Acinetobacter baumannii clinical isolates. Clinafloxacin showed a MIC(90) of 4 mg/L, whereas the remaining quinolones showed a MIC(90) equal to or higher than 16 mg/L. MIC(50) determination in the presence of reserpine resulted in a two-fold decrease, except for trovafloxacin, which decreased four-fold, and for moxifloxacin and nalidixic acid, which did not change. The effect of reserpine was most pronounced among strains with a low level of resistance to quinolones. The MIC of clinafloxacin for strains with no mutation in either gyrA or parC genes ranged from 0.008 to 0.25 mg/L. In strains with a single mutation at amino acid codon Ser83 of the gyrA gene, the MIC of clinafloxacin ranged from 0.12 to 1 mg/L, whereas strains with a double mutation, one in the gyrA gene and another in the parC gene, showed a range of MIC of clinafloxacin from 1 to 8 mg/L. Therefore, clinafloxacin shows good activity against strains carrying a single mutation in the gyrA gene, and hence a second mutation is required for the microorganism to express resistance.     

Quinolones: clinical use and formulary considerations.

Quinolones are broad-spectrum antibiotics active primarily against aerobic gram-negative organisms. All quinolones have activity against oral anaerobes, but only trovafloxacin provides coverage against Bacteroides fragilis, the primary anaerobe of the abdomen/pelvis. In addition, quinolones are very active against atypical pulmonary pathogens, e.g., Legionella, but trovafloxacin is the least active against Chlamydia. As with other antibiotics, the selection of quinolones depends not simply on the degree of microbiologic activity but also on safety profile and cost. Ciprofloxacin and trovafloxacin are associated with central nervous system side effects. Photosensitivity reactions may occur with sparfloxacin. Trovafloxacin is associated with more adverse reactions than any other quinolone, and its gastrointestinal side effects are most frequent among the quinolones. Resistance potential is highest with ciprofloxacin and lowest with levofloxacin. Sparfloxacin and grepafloxacin are available only as oral formulations. Among the parenteral quinolones, ciprofloxacin and trovafloxacin are the most expensive, levofloxacin, the least expensive. Levofloxacin is preferred for general use alone or in combination because it has virtually no side effects, induces no resistance, and is the least expensive and most versatile quinolone currently available.     

Development and mechanism of fluoroquinolone resistance in Legionella pneumophila

The potential for selection in vitro of Legionella pneumophila mutants resistant to fluoroquinolones was investigated. Six distinct clinical isolates of L. pneumophila were subcultured in subinhibitory concentrations of ciprofloxacin, levofloxacin, clinafloxacin, trovafloxacin and moxifloxacin until MICs increased at least eight-fold. The numbers of serial passages required in microbroth dilution series were determined. The gyrA gene of the six parental strains, and 12 selected mutant strains, was sequenced. The five quinolones differed markedly in their ability to select mutants with decreased susceptibility. The average number of serial passages required was low in the cases of clinafloxacin (n = 10.6), ciprofloxacin and levofloxacin (both n = 13), but notably higher for trovafloxacin (n = 26.6) and moxifloxacin (n = 22.5). Five mutants treated with ciprofloxacin and three treated with moxifloxacin showed Thr83-->Lys or Thr83-->Ile amino acid changes in the gyrA gene. In conclusion, different quinolones lose their antimicrobial effect after a varying number of passages. This study demonstrated, for the first time to our knowledge, that gyrA in L. pneumophila is a possible target of fluoroquinolones.     

Fluoroquinolone Resistance in Bacteroides fragilis following Sparfloxacin Exposure

In vitro pharmacodynamic studies investigating the antimicrobial properties of five fluoroquinolones, (trovafloxacin, sparfloxacin, clinafloxacin, levofloxacin, and ciprofloxacin) against Bacteroides fragilis ATCC 23745 were conducted. The times required to reduce the viable counts by 3 log units were as follows: clinafloxacin, 2.9 h; levofloxacin, 4.6 h; trovafloxacin, 6 h; and sparfloxacin, 10 h. Exposure to ciprofloxacin did not achieve a 3-log decrease in viable counts. The susceptibility of B. fragilis was determined both prior to exposure and following 24 h of exposure to each of the five fluoroquinolones tested. The MICs of clinafloxacin, levofloxacin, trovafloxacin, sparfloxacin, ciprofloxacin, metronidazole, cefoxitin, chloramphenicol, and clindamycin were determined by the broth microdilution method. The MICs for B. fragilis preexposure were as follows: clinafloxacin, 0.25 microg/ml; trovafloxacin, 0.5 microg/ml; sparfloxacin, 2 microg /ml; levofloxacin, 2 microg/ml; and ciprofloxacin, 8 microg/ml. Similar pre- and postexposure MICs were obtained for cultures exposed to trovafloxacin, clinafloxacin, levofloxacin, and ciprofloxacin. However, following 24 h of exposure to sparfloxacin, a fluoroquinolone-resistant strain emerged. The MICs for this strain were as follows: clinafloxacin, 1 microg/ml; trovafloxacin, 4 microg/ml; sparfloxacin, 16 microg/ml; levofloxacin, 16 microg/ml; and ciprofloxacin, 32 microg/ml. No changes in the susceptibility of B. fragilis pre- and postexposure to sparfloxacin were noted for metronidazole (MIC, 1 microg/ml), cefoxitin (MIC, 4 microg /ml), chloramphenicol (MIC, 4 microg/ml), and clindamycin (MIC, 0.06 microg/ml). Resistance remained stable as the organism was passaged on antibiotic-free agar for 10 consecutive days. Mutant B. fragilis strains with decreased susceptibility to clinafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were selected on brucella blood agar containing 8x the MIC of levofloxacin at a frequencies of 6.4 x 10(-9), 4x the MICs of trovafloxacin and sparfloxacin at frequencies of 2.2 x 10(-9) and 3. 3 x 10(-10), respectively, and 2x the MIC of clinafloxacin at a frequency of 5.5 x 10(-11); no mutants were selected with ciprofloxacin. The susceptibilities of strains to trovafloxacin, levofloxacin, clinafloxacin, sparfloxacin, and ciprofloxacin before and after exposure to sparfloxacin were modestly affected by the presence of reserpine (20 microg/ml), an inhibitor of antibiotic efflux. The mechanism of fluoroquinolone resistance is being explored, but it is unlikely to be efflux due to a lack of cross-resistance to unrelated antimicrobial agents and to the fact that the MICs for strains before and after exposure to sparfloxacin are minimally affected by reserpine.     

In vitro activities of sitafloxacin (DU-6859a) and six other fluoroquinolones against 8,796 clinical bacterial isolates

The in vitro activities of sitafloxacin, ciprofloxacin, trovafloxacin, levofloxacin, clinafloxacin, gatifloxacin, and moxifloxacin against 5,046 gram-negative bacteria, 3,344 gram-positive cocci, and 406 anaerobes were determined. Sitafloxacin was the most active agent against gram-positive cocci and anaerobes. Against Enterobacteriaceae and nonfermenters, its activity was either equivalent to or better than that of clinafloxacin.     

Comparative activity of clinafloxacin and nine other compounds tested against 2000 contemporary clinical isolates from patients in United States hospitals.

The in vitro activity of clinafloxacin (formerly CI-960, AM-1091, PD-127391) was compared with other fluoroquinolones, cephalosporins, gentamicin, vancomycin, imipenem, piperacillin/tazobactam, clindamycin, and metronidazole against 2000 recent clinical strains from a large number of hospitals in the United States. Overall, clinafloxacin was the most active compound tested. Against Pseudomonas aeruginosa, clinafloxacin and ciprofloxacin demonstrated comparable activity (88% and 80% susceptible, respectively), and were four- to 16-fold more potent than levofloxacin (MIC90, 16 micrograms/ml) or trovafloxacin (MIC90, 32 micrograms/ml). Among anaerobic bacteria, clinafloxacin (MIC50s, 0.25-0.5 microgram/ml) and trovafloxacin (MIC50s, 0.5-2.0 micrograms/ml) were the most active quinolones, whereas metronidazole, imipenem and piperacillin/tazobactam were the most potent comparators. Clinafloxacin demonstrated sustained activity when compared to several available peer drugs against contemporary clinical isolates. The clinafloxacin spectrum against the 15 important pathogens monitored ranged from nil or 4.0% (vancomycin-resistant enterococci) to 100.0% (four different species) susceptible with an average percent susceptibility of 94.0%. This degree of potency and spectrum for clinafloxacin provides a wide potential for use against many species with established resistance to other anti-microbial classes.     

Activities of garenoxacin (BMS-284756) and other agents against anaerobic clinical isolates

A total of 590 clinical isolates consisting of 33 species of both gram-positive and gram-negative anaerobes were collected from nine centers in the Chicago area in 1998-1999. The largest number of isolates (330 isolates, 56%) belonged to the Bacteroides group. Isolates were tested by agar dilution against garenoxacin (BMS-284756, T-3811 ME), trovafloxacin, moxifloxacin, clindamycin, imipenem, piperacillin-tazobactam, and cefoxitin. All but one species (2% of Bacteroides vulgatus isolates) were fully susceptible to piperacillin-tazobactam and imipenem. A number of species were resistant to clindamycin. Among the fluoroquinolones, garenoxacin and trovafloxacin had an MIC at which 90% of the isolates tested were inhibited of <4 micro g/ml for all but two species (Fusobacterium mortiferum/varium and Peptostreptococcus anaerobius).     

Comparative activity of new quinolones against 326 clinical isolates of Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is an important emerging pathogen causing a variety of infections in severely ill patients. This microorganism is inherently resistant to many antibiotics, and only a few therapeutic options are available. The principal aim of this study was to assess the in vitro activity of new quinolones against this pathogen. Three hundred and twenty-six single clinical isolates were tested in this study. The MIC(90) was 16 mg/L for ciprofloxacin, 8 mg/L for levofloxacin and gatifloxacin, 4 mg/L for trovafloxacin, moxifloxacin and sparfloxacin and 2 mg/L for clinafloxacin. At a 2 mg/L concentration, a C(max) lung:MIC ratio of >/=10 can be reached for 95%, 84.3%, 83.1% and 81.5% of isolates, respectively, for clinafloxacin, trovafloxacin, moxifloxacin and sparfloxacin (P < 0. 001 compared with levofloxacin and ciprofloxacin). In spite of the rare but serious adverse events associated with the new-generation quinolones, these agents may become very useful in the treatment of certain severe or life-threatening infectious conditions due to S. maltophilia, notably lower respiratory tract infections.     

Mupirocin resistance in methicillin-resistant Staphylococcus aureus clinical isolates in a Spanish hospital. Co-application of multiplex PCR assay and conventional microbiology methods

A total of 33 Stenotrophomonas maltophilia clinical isolates were tested for their susceptibility to clinafloxacin in comparison with ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, norfloxacin, sparfloxacin and trovafloxacin. The MIC(50) and MIC(90) were as follows: ciprofloxacin 4 and 64 microg/mL; clinafoxacin 0.5 and 4 microg/mL; levofloxacin 2 and 32 microg/mL; moxifloxacin 1 and 8 microg/mL; nalidixic acid 8 and 128 microg/mL; norfloxacin 64 and 256 microg/mL; sparfloxacin 1 and 16 microg/mL; and trovafloxacin 1 and 8 microg/mL. Clinafloxacin was the most active quinolone, with only a 15.1% of strains showing resistance. When the MICs were determined in the presence of 25 microg/ml of reserpine, the MIC(90) of trovafloxacin and moxifloxacin did not change, whereas decreased 2-fold for clinafloxacin, levofloxacin, sparfloxacin and nalidixic acid, and 4- and 8-fold for ciprofloxacin and norfloxacin respectively. No clinafloxacin-resistant strains were observed when the MIC was performed in the presence of reserpine. Therefore, clinafloxacin shows the better "in vitro"activity against these 33 strains of S.maltophilia.     

Activities of New Antimicrobial Agents (Trovafloxacin, Moxifloxacin, Sanfetrinem, and Quinupristin-Dalfopristin) against Bacteroides fragilis Group: Comparison with the Activities of 14 Other Agents

The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were determined. A group of 10 imipenem-resistant strains were also tested. Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the beta-lactams. Quinupristin-dalfopristin inhibited all of the strains at 2 microg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90% of the strains tested were 1 and 2 microg/ml, respectively.     

Activities of 13 quinolones by three susceptibility testing methods against a collection of Haemophilus influenzae isolates with different levels of susceptibility to ciprofloxacin: evidence for cross-resistance

The activities of nalidixic acid, ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, flerofloxacin, sparfloxacin, grepafloxacin, gatifloxacin, moxifloxacin, trovafloxacin, levofloxacin and clinafloxacin against a panel of Haemophilus influenzae strains were assessed by three susceptibility testing methods: Etest, agar dilution and the reference broth microdilution method using Haemophilus test medium (HTM) in all cases. The panel included 62 clinical and two reference H. influenzae strains; 32 had decreased susceptibility to ciprofloxacin (MIC > or = 0.12 mg/L) and 30 were susceptible to this antibiotic (MIC < or = 0.06 mg/L). Both Etest and HTM agar dilution results (r = 0.96; 86.61% and 82.1% of MICs within + one log(2), respectively) correlated well with the reference microdilution method. The MIC(90) of ciprofloxacin was 4.0 mg/L (range 0.007-32.0 mg/L). Trovafloxacin activity was similar to that of ciprofloxacin but sparfloxacin, grepafloxacin, ofloxacin, pefloxacin and flerofloxacin activities were higher (with MIC values one log(2) dilution lower than ciprofloxacin). The least active were norfloxacin (MIC(90) 16 mg/L) and nalidixic acid (MIC(90) 128 mg/L). Levofloxacin and moxifloxacin were more active than ciprofloxacin (MIC(90) 2 mg/L); clinafloxacin and gatifloxacin were the most active with an MIC(90) of 0.25 mg/L. Cross-susceptibility among all quinolones was observed (r > 0.9). Resistance to ciprofloxacin was associated with a similar magnitude of activity loss to other new and old quinolones. Ciprofloxacin MIC determination should be sufficient to detect the decreased susceptibility to the whole group of quinolones.     

Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia

The antibacterial activities of seven fluoroquinolones (ciprofloxacin, BAYy3118, clinafloxacin, gemifloxacin, moxifloxacin, sparfloxacin and trovafloxacin) against isogenic efflux-mediated multidrug-resistant strains of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia, were compared. The results indicate that these fluoroquinolones are all substrates for the multidrug efflux systems of these organisms. Clinafloxacin was found generally to be the most active agent against multidrug-resistant strains.