rifampin and sparfloxacin

Catheter-associated urinary tract infection (CAUTI) is the commonest hospital-acquired infection, accounting for over 100,000 hospital admissions within the USA annually. Biomaterials and processes intended to reduce the risk of bacterial colonization of the catheters for long-term users have not been successful, mainly because of the need for long duration of activity in flow conditions. Here we report the results of impregnation of urinary catheters with a combination of rifampicin, sparfloxacin and triclosan. In flow experiments, the antimicrobial catheters were able to prevent colonization by common uropathogens Proteus mirabilis, Staphylococcus aureus and Escherichia coli for 7 to 12weeks in vitro compared with 1-3days for other, commercially available antimicrobial catheters currently used clinically. Resistance development was minimized by careful choice of antimicrobial combinations. Drug release profiles and distribution in the polymer, and surface analysis were also carried out and the process had no deleterious effect on the mechanical performance of the catheter or its balloon. The antimicrobial catheter therefore offers for the first time a means of reducing infection and its complications in long-term urinary catheter users.

Topics: Anti-Infective Agents; Bacteria; Biofilms; Drug Liberation; Fluoroquinolones; Rifampin; Triclosan; Urinary Catheters

Moxifloxacin(MFLX) and garenoxacin(GRNX), new synthetic antibacterial agents, were assessed for in vitro anti-M. leprae activities. The anti-bacterial activities of these two drugs were compared to those of sparfloxacin (SPFX), gatifloxacin(GFLX), levofloxacin(LVFX) and rifampicin (RFP). The anti-M leprae activity obtained by Buddemeyer system was stronger in order of RFP, MFLX, SPFX, GFLX and GRNX and LVFX. The anti-M. leprae activity of MFLX or GRNX was also examined by the nude mouse footpad method. MFLX completely inhibited the growth of M. leprae inoculated into nude mouse footpads, when given orally at a daily dose of 10 mg/kg , while GRNX completely inhibited at a daily dose of 60 mg/kg. Both in vitro and in vivo tests indicated that MFLX was equal or superior to SPFX, but GRNX was equipotent to LVFX, in terms of anti-M. leprae activities.

Topics: Animals; Anti-Infective Agents; Aza Compounds; Drug Resistance, Bacterial; Female; Fluoroquinolones; Gatifloxacin; Leprostatic Agents; Levofloxacin; Mice; Mice, Inbred BALB C; Mice, Nude; Moxifloxacin; Mycobacterium leprae; Ofloxacin; Quinolines; Rifampin

We determined antimicrobial susceptibilities and analyzed molecular epidemiology of 26 strains of Bordetella pertussis clinically isolated and then performed pulsed-field gel electrophoresis (PFGE) in Japan (Japanese Pertussis Surveillance Group Participants), from 2001 to 2002. The MICs of erythromycin, clindamycin, tetracyclines, fluoroquinorones, trimethoprim-sulfamethoxazole and rifampicin of all isolates against these showed 1 microgram/ml or less. Sparfloxacin is the most potent agent, of which the MICs showed 0.008-0.016 microgram/ml. Results of DNA fingerprinting by pulsed-field gel electrophoresis (PFGE) differentiated three types (Type I; 11 strains (42%), type II; 14 strains (54%) and type III; 1 strains (4%)). However, no relation between regions and identical PFGE patterns was found in this study. Further, surveillance of the antimicrobial susceptibilities and molecular epidemiology of B. pertussis will be required.

Topics: Anti-Bacterial Agents; Bordetella pertussis; Child, Preschool; DNA, Bacterial; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Erythromycin; Female; Fluoroquinolones; Humans; Infant; Male; Microbial Sensitivity Tests; Molecular Epidemiology; Rifampin; Tetracyclines; Whooping Cough

To identify the most active curative treatment of Buruli ulcer, two regimens incorporating the use of rifampin (RIF) were compared with the use of RIF alone in a mouse footpad model of Mycobacterium ulcerans infection. Treatments began after footpad swelling from infection and continued for 12 weeks with five doses weekly of one of the following regimens: (i) 10 mg of RIF/kg alone; (ii) 10 mg of RIF/kg and 100 mg of amikacin (AMK)/kg; and (iii) 10 mg of RIF/kg, 100 mg of clarithromycin (CLR)/kg, and 50 mg of sparfloxacin (SPX)/kg. The activity of each regimen was assessed in terms of the reduction of the average lesion index and acid-fast bacillus (AFB) and CFU counts. All three regimens displayed various degrees of bactericidal activity against M. ulcerans. The ranking of bactericidal activity was found to be as follows: RIF-AMK > RIF-CLR-SPX > RIF. RIF-AMK was able to cure M. ulcerans-infected mice and prevent relapse 26 weeks after completion of treatment. To determine the impact of different rhythms of administration of RIF-AMK on the suppression of M.ulcerans growth, mice were given the RIF-AMK combination for 4 weeks but doses were administered either 5 days a week or twice or once weekly. After completion of treatment, the mice were kept under supervision for 30 additional weeks. M. ulcerans was considered to have grown in the footpad if swelling was visually observed and harvests contained more than 5 x 10(5) AFB per footpad. The proportion of mice in which growth of M. ulcerans occurred, irrespective of drug dosage, was compared with the control mice to determine the proportion of M. ulcerans killed. Each dosage of RIF-AMK was bactericidal for M. ulcerans (P < 0.001), but the effect was significantly stronger in mice treated 5 days per week. The promising results of RIF-AMK treatment in M. ulcerans-infected mice support the clinical trial that is currently in progress under World Health Organization auspices in Ghana.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Clarithromycin; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Female; Fluoroquinolones; Foot; Mice; Mice, Inbred BALB C; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Rifampin; Skin Ulcer

Treatment of cerebral tuberculomas demands the combination of rifampicin, isoniazid, pyrazinamide and ethambutol. The place of fluoroquinolones remains to be defined.. A 36-year-old woman presented with a cerebral tuberculoma. Treatment with an antituberculous quadritherapy regimen was begun, but because of serious side effects, isoniazid and rifampicin weren't withdrawn during the fourth month. Sparfloxacin and ethambutol biotherapy was then started and continued for 12 months, which led to the disappearance of the cerebral lesion.. Our observation proves that sparfloxacin is an alternative for cerebral tuberculoma treatment in case of intolerance or resistance to first-line antituberculosis drugs.

Topics: Adult; Anti-Infective Agents; Antitubercular Agents; Ethambutol; Female; Fluoroquinolones; Humans; Isoniazid; Rifampin; Tuberculosis, Central Nervous System

The slow growth and highly infectious nature of Mycobacterium tuberculosis is a limiting factor in its use as test organism in high throughput screening for inhibitory compounds. To overcome these problems, use of surrogate strains and reporter genes have been considered. In this study, we have investigated the application of a fast growing nonpathogenic M. aurum expressing firefly luciferase in rapid screening of antituberculosis compounds in vitro and in infected macrophages using bioluminescence assay. The assay is based on luminescence determination using luciferin as substrate. Inhibition of bioluminescence was obtained with frontline antimycobacterial drugs like streptomycin, rifampicin, isoniazid, ethambutol, ofloxacin, and sparfloxacin at their reported MICs. Inhibition could be observed as early as 2 h in vitro and within 24 h in infected macrophages. The system can reliably be used in high throughput screening.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antitubercular Agents; Cell Line; Coleoptera; Fluoroquinolones; Genes, Reporter; Luciferases; Luminescent Measurements; Macrophages; Mice; Microbial Sensitivity Tests; Mycobacterium; Ofloxacin; Recombinant Proteins; Rifampin; Streptomycin; Transfection

Mycobacterium leprae were isolated from a Japanese patient, and susceptibility to antileprosy drugs was examined by the mouse foot pad method. The isolate was susceptible to clofazimine and clarithromycin, and resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Mutations were identified in the genes associated with resistance to these drugs. The risk of the emergence of leprosy with multidrug resistance is emphasized.

Topics: Animals; Anti-Infective Agents; Antitubercular Agents; Clarithromycin; Clofazimine; Colony Count, Microbial; Dapsone; Drug Resistance, Microbial; Drug Resistance, Multiple; Fluoroquinolones; Humans; Leprostatic Agents; Leprosy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Mycobacterium leprae; Ofloxacin; Rifampin

We studied the activities of the new fluoroquinolones clinafloxacin, levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the intracellular growth of Listeria monocytogenes. Against intracellular growth of the four strains tested, a similar reduction of the bacterial count was obtained with clinafloxacin at the dose of 10 x MIC (delta log10 CFU/ml = -2.19 +/- 0.24), with levofloxacin at 8 x MIC (delta log10 CFU/ml = -2.28 +/- 0.25), and with sparfloxacin at 4 x MIC (delta log10 CFU/ml = -2.16 +/- 0.21) after 24 h of incubation. The combination of the quinolones with trimethoprim-sulfamethoxazole or amoxicillin did not show a substantial increase in activity compared to the fluoroquinolone alone. Antagonism with rifampin was strongly suggested. No modification of the MIC was observed after 20 successive infections of HeLa cells and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and sparfloxacin for 24 h. We conclude that clinafloxacin, levofloxacin, or sparfloxacin could represent a therapeutic alternative to amoxicillin for the treatment of Listeria infections in adults, especially clinafloxacin, whose MIC is low (0.06 to 0.12 micrograms/ml), and whose best activity against intracellular L. monocytogenes was obtained at a concentration of 1.2 micrograms/ml, which is similar to clinically achievable levels. The results must be confirmed in an experimental model.

Topics: Amoxicillin; Anti-Infective Agents; Colony Count, Microbial; Dose-Response Relationship, Drug; Fluoroquinolones; HeLa Cells; Humans; Levofloxacin; Listeria monocytogenes; Ofloxacin; Quinolones; Rifampin; Sulfamethoxazole; Trimethoprim

Antimycobacterial drugs acting efficiently against Mycobacterium avium complex have in common low MICs and MBC/MIC ratios. The recently reported clinical efficacy of some of the newer drugs is also clearly linked to their pharmacokinetic properties such as higher serum level and/or intracellular concentrations and half-life. In the present investigation, comparative postantibiotic effects (PAEs) of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin were investigated. Bacteria were exposed to MIC, MIC x 4 and MIC x 8 concentrations of each drug for 2 h, the drug was removed by centrifugation and cells were thoroughly washed and resuspended in drug-free medium. Growth was compared to control organisms which underwent a similar treatment (but without drugs) and PAEs were assessed using the equation "T-C", where T equals the time required for colony counts to increase by 1 log10 in test samples after antibiotic exposure and C equals the time for 1 log10 growth in control. Our results underlined two distinct patterns concerning PAE: pattern I included drugs for which PAE (in hours) was dose-dependent and varied (for MIC, MIC x 4 and MIC x 8 concentrations) for amikacin (10.3 +/- 1.7, 14.7 +/- 1.9 and 17.7 +/- 4.1), rifampin (28.0 +/- 7.6, 62.0 +/- 18.5 and 71.0 +/- 3.2) and clarithromycin (2.6 +/- 1.0, 15.0 +/- 4.0 and 22.0 +/- 4.0), whereas pattern II included drugs with a stable PAE, relatively independent of the drug concentrations: sparfloxacin (11.0 +/- 2.5, 12.3 +/- 6.4 and 13.0 +/- 2.1) and clofazimine (26.0 +/- 2.8, 28.8 +/- 2.5 and 27.3 +/- 1.3). These results may be useful for guidance in scheduling of drug administration in M. avium-infected AIDS patients overburdened with too many drugs given for various opportunistic infections.

Topics: Amikacin; Anti-Bacterial Agents; Bacteriological Techniques; Clarithromycin; Clofazimine; Colony Count, Microbial; Fluoroquinolones; Humans; Mycobacterium avium Complex; Quinolones; Rifampin; Serum Bactericidal Test

In these studies we evaluated the activity of low levels of five antimicrobials against Mycobacterium leprae-infected mice when administered singly and in all possible two- and three-drug combinations. Antibiotics studied were: dapsone (D) 0.0001% in the diet, rifampin (R) 20 mg/kg by gavage once monthly, minocycline (M) 0.004% in the diet, clarithromycin (C) 0.001% in the diet, and sparfloxacin (S) 5 mg/kg by gavage five times weekly. Singly each agent was found bacteriostatic (D + R) or partially bactericidal (M, C, and S) but not fully bactericidal. All 10 two-drug regimens were found at least bacteriostatic, 2 being "partially bactericidal" and 4 being "fully bactericidal." Of the 10 three-drug regimens, 9 were found "fully bactericidal" and the other "partially bactericidal." We conclude that combinations of antibiotics active against M. leprae are generally additive in combination.

Topics: Animals; Anti-Infective Agents; Clarithromycin; Dapsone; Drug Therapy, Combination; Female; Fluoroquinolones; Leprosy; Mice; Mice, Inbred BALB C; Minocycline; Quinolones; Rifampin

The activity of sparfloxacin on Staphylococcus epidermidis biofilms on different plastic catheters was evaluated. Sparfloxacin showed high bactericidal activity against S. epidermidis biofilms on Vialon and polyvinylchloride catheters. The combination of sparfloxacin with amikacin or rifampicin significantly increased its activity against bacterial biofilms on polyurethane and Teflon catheters.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular; Biocompatible Materials; Biofilms; Catheterization; Drug Therapy, Combination; Fluoroquinolones; Microbial Sensitivity Tests; Plastics; Polytetrafluoroethylene; Polyurethanes; Quinolones; Rifampin; Staphylococcus epidermidis

The bactericidal activities against Mycobacterium leprae of single or multiple doses of various combinations of new antileprosy drugs [minocycline (MINO), clarithromycin (CLARI), ofloxacin (OFLO), and sparfloxacin (SPFX)] and/or rifampin (RMP) were titrated in immunocompetent mice by the proportional bactericidal method. Drugs were administered by gavage at the following dosages (mg/kg) per dose: RMP 10, MINO 25, CLARI 100, OFLO 150, and SPFX 50. All 15 regimens exerted significant bactericidal activities, at least 96% of viables were killed. The activity of a single dose MINO + CLARI was only slightly inferior to that of RMP, and the activities of a single dose OFLO/SPFX + MINO + CLARI were similar to that of RMP. This suggests that either MINO + CLARI or OFLO/SPFX + MINO + CLARI may be administered once monthly together with RMP 600 mg for the treatment of multibacillary (MB) leprosy, and monthly administration of MINO + CLARI or OFLO/SPFX + MINO + CLARI may also be employed for the treatment of RMP-resistant MB leprosy. Because the killing effects of multiple doses of the combinations were so powerful, comparison of the bactericidal activities of these regimens was beyond the sensitivity of the immunocompetent mouse model, and are being tested in the nude mouse model. Although SPFX is more active against M. leprae than OFLO on a weight-to-weight basis, when both drugs were administered in mice at dosages equivalent to clinically tolerated dosages in humans, SPFX did not show more superiority than OFLO, and its real advantage over OFLO in the treatment of leprosy remains unclear.

Topics: Animals; Clarithromycin; Disease Models, Animal; Female; Fluoroquinolones; Foot; Hindlimb; Immunocompetence; Leprostatic Agents; Leprosy; Mice; Microbial Sensitivity Tests; Minocycline; Mycobacterium leprae; Ofloxacin; Quinolones; Rifampin

We tested the activity of the new fluoroquinolone sparfloxacin (CI-978; AT 4140) against 30 strains of Mycobacterium avium complex (MAC) isolated from patients with acquired immune deficiency syndrome. MICs of sparfloxacin (range, less than or equal to 0.06 to 4 micrograms/ml) were lower than MICs of ciprofloxacin for all 30 strains, and MBCs for acid-fast bacteria were lower for 28 of the 30 strains. In synergism experiments using 10 strains of MAC, fractional inhibitory concentration indices revealed that the combination of sparfloxacin plus ethambutol was synergistic against 9 strains, and the three-drug combination of sparfloxacin plus ethambutol plus rifampin was synergistic against all strains. In the absence of ethambutol, the combination of sparfloxacin plus rifampin appeared to be antagonistic against three of the MAC strains.

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Ciprofloxacin; Drug Synergism; Ethambutol; Fluoroquinolones; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rifampin