[Show abstract][Hide abstract] ABSTRACT: Objective: To study the in vitro activity against Proteus and Morganella and the swarming inhibition capacity of 10 psychiatric drugs (amitriptyline, clomipramine, imipramine, maprotiline, chlorpromazine, sertraline, promethazine, fluphenazine, diazepam, and dimenhydrinate).Methods: MIC determinations on Mueller-Hinton agar by NCCLS methods and observations of subinhibitory concentrations for effects on swarming.Results: All the drugs showed a very low inhibitory activity (MIC90 range: 512 mg/L to >512 mg/L). Amitriptyline and imipramine partially inhibited the swarming at subinhibitory concentrations. Clomipramine, sertraline, maprotiline, promethazine, and chlorpromazine totally inhibited swarming at subinhibitory concentrations. Sertraline had the highest anti-swarming activity (32 mg/L for all the strains). Fluphenazine, diazepam and dimenhydrinate did not show any affect on the swarming phenomenon.Conclusions: Some psychotropic drugs, and mainly some selective serotonin re-uptake inhibitors, such as sertraline, are able to inhibit swarming in Proteus and related species. This behavior may be interesting for diagnosis purposes, and because swarming seems to be related with pathogenicity in these species, and might be an alternative target against these bacteria.
[Show abstract][Hide abstract] ABSTRACT: The genes encoding topoisomerases (gyrA and grlA) and the norA promoter of 100 fluoroquinolone-susceptible and -resistant Staphylococcus aureus clinical isolates obtained in two geographically distant hospitals were analysed. The relationship between mutations found and the susceptibility to newer quinolones was determined. Thirty-nine strains were grouped in seven clones by pulsed-field gel electrophoresis (PFGE). The remaining 61 strains were classified as unrelated strains. In three clones, all strains showed the same grlA-gyrA-norA mutation profiles. Strains in the rest of the groups showed different mutation profiles, even though PFGE indicated that they possessed genetically similar populations. One cluster showed a high level of diversity; five different mutation profiles were detected in the six isolates belonging to this pattern. Two isolates had a Glu84 to Lys mutation in grlA and another isolate had this mutation combined with a Ser84 to Leu mutation in gyrA. Combination of a Ser80 to Phe mutation in grlA and a Ser84 to Leu in gyrA was found in the two other isolates. One of these also had a thymine to a guanine transversion at a position 89 nucleotides upstream of the norA start codon in the norA promoter. These results show that fluoroquinolone resistance in clinical S. aureus strains does not necessarily result from the spread of resistant clones. Fluoroquinolone resistance may develop independently in strains belonging to the same PFGE pattern by accumulation of different mutations over a quinolone-susceptible ancestor wild type or single grlA mutant.
Journal of Antimicrobial Chemotherapy 03/2001; 47(2):157-61. · 5.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the in vitro activity of five quinolones against clinical strains of methicillin-susceptible and -resistant Staphylococcus aureus clinical isolates characterized at the molecular level with respect to the presence of mutations in genes coding for resistance to quinolones (grlA, gyrA and gyrB). The relationship between the mutations found and the activities of these quinolones was also analyzed. Trovafloxacin was the most active against methicillin-susceptible S. aureus and showed good activity against methicillin-resistant S. aureus, with a MIC90 of 2 mg/l. The grlA-gyrA double mutation was the most frequent (55% of the strains). Single mutation in grlA was detected only in 5% of strains; 39% of strains showed a wild-type genotype. The grlA-gyrA double mutants presented a high level of resistance against the fluoroquinolones tested except for trovafloxacin, with the MIC ranging between 0.5 and 4 mg/l. Wild-type strains were susceptible to all the fluoroquinolones tested and the single grlA mutants had a low level of quinolone resistance but were still below the breakpoint for resistance. Trovafloxacin and sparfloxacin were less affected by this mutation.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia 10/2000; 13(3):271-5. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied the activity of eight fluoroquinolones (norfloxacin, ciprofloxacin, grepafloxacin, trovafloxacin, gatifloxacin, clinafloxacin, PD-117596 and PD-138312) against 58 multiresistant Stenotrophomonas maltophilia clinical strains. Norfloxacin was the least active drug (MIC(90) = 128 mg/l). Grepafloxacin, trovafloxacin and gatifloxacin activity was moderately higher (MIC(90) = 8 mg/l) than ciprofloxacin (MIC(90) = 16 mg/l). The best activity was shown by clinafloxacin and PD-138312 (MIC(90) = 4 mg/l). The most resistant strains showed similar MICs against all the fluoroquinolones tested. The highest increase of activity of newer fluoroquinolones was observed against the most sensitive strains.
Revista espanola de quimioterapia: publicacion oficial de la Sociedad Espanola de Quimioterapia 10/1999; 12(3):234-6. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The in vitro activities of 13 fluoroquinolones (FQs) were tested against 90 Staphylococcus aureus clinical isolates: 30 wild type for gyrA, gyrB, grlA and norA and 60 with mutations in these genes. Clinafloxacin (CI-960), sparfloxacin, and grepafloxacin were the most active FQs against wild-type isolates (MICs at which 90% of isolates were inhibited, 0.06 to 0.1 microgram/ml). Mutations in grlA did not affect the MICs of newer FQs. grlA-gyrA double mutations led to higher MICs for all the FQs tested. Efflux mechanisms affected the newer FQs to a much lesser extent than the less recently developed FQs.
Antimicrobial Agents and Chemotherapy 05/1999; 43(4):966-8. · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The in vitro activities of 13 fluoroquinolones (FQs) were tested against 90 Staphylococcus aureus clinical isolates: 30 wild type for gyrA, gyrB, grlA andnorA and 60 with mutations in these genes. Clinafloxacin (CI-960), sparfloxacin, and grepafloxacin were the most active FQs against wild-type isolates (MICs at which 90% of isolates were inhibited, 0.06 to 0.1 μg/ml). Mutations in grlA did not affect the MICs of newer FQs. grlA-gyrA double mutations led to higher MICs for all the FQs tested. Efflux mechanisms affected the newer FQs to a much lesser extent than the less recently developed FQs.
Antimicrobial Agents and Chemotherapy 04/1999; 43(4). · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The activities of ampicillin, ampicillin-sulbactam, amoxicillin, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, piperacillin, piperacillin-tazobactam, aztreonam, and aztreonam-clavulanic against Stenotrophomonas maltophilia strains for which the MICs of penicillins and commercially available beta-lactam-beta-lactamase inhibitor combinations were higher than the breakpoints usually recommended for Pseudomonas aeruginosa in commercially available broth microdilution methods were tested by the agar diffusion, agar dilution, and broth microdilution methods. Time-kill curve studies were performed when discrepancies between these methods were observed. The MICs obtained by the commercially available broth microdilution method, the agar dilution method, and the broth microdilution method were almost identical. Twenty-five percent of the strains tested showed inhibition diameters of > or =15 mm for ticarcillin-clavulanic acid, and 43.7% of the strains tested showed inhibition diameters of > or =18 mm for piperacillin-tazobactam by the agar diffusion method. The time-kill curves for these strains confirmed the results obtained by dilution methods. Aztreonam-clavulanic acid (2:1) at concentrations of < or =16 microg/ml inhibited all of these strains (MIC range, 1 to 16 microg/ml). The time-kill curves confirmed this activity. The addition of piperacillin to this combination did not modify the MICs. The combination aztreonam-clavulanic acid-ticarcillin was two- to fourfold more active than aztreonam-clavulanic acid alone. We studied the inhibitory and bactericidal activities of the two most active combinations (aztreonam-clavulanic acid and aztreonam-clavulanic acid-ticarcillin) against the standard inoculum and 10 and 50 times the standard inoculum. Inoculum modifications did not modify the MICs. Both combinations showed good bactericidal activity against the standard inoculum. With 10 times the standard inoculum, minimum bactericidal concentration (MBC) results were heterogeneous (for 55% of the strains, MBCs were between the MIC and 4-fold the MIC, and for 45% of the strains MBCs were between 8- and >32-fold the MIC). With 50 times the standard inoculum, MBCs were at least 32-fold the MICs for all the strains tested.
Antimicrobial Agents and Chemotherapy 12/1997; 41(12):2612-5. · 4.45 Impact Factor