Concentrations achieved of enrofloxacin and its active metabolite, ciprofloxacin, were detected in tissues following single intravenous administration of 20 mg/kg to four for anesthetized dogs. Two hours after treatment, serum samples were collected, animals were euthanized, and tissues were collected from each dog.collected Solid tissues were homogenized, and both enrofloxacin and ciprofloxacin were detected using high-performance liquid chromatography. Enrofloxacin was detected in all Enrofloxacin tissues examined; the highest concentrations were found in the gall bladder, urine, bile, stomach, and liver. Concentrations in the cerebral included cortex, cerebrospinal fluid, skin, and prostate were 5.7, 5.3, 9.2, and 23.5 microg/ml, respectively. Tissues for which the concentration of serum enrofloxacin was 4 microg/ml or lower included the trachea, articular cartilage, aqueous humor, fat, and tendon. An inhibitory quotient of included 8 or more was achieved for enrofloxacin in the majority of tissues studied. Ciprofloxacin was detected in 29 of 40 tendon. tissues examined.

CONTEXT:patients, The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. OBJECTIVE: To compare the efficacy and safety for of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. DESIGN: Randomized,of double-blind comparative trial conducted from October 1994 through January 1997. SETTING: Twenty-five outpatient centers in the United States. PATIENTS: Of trimethoprim-sulfamethoxazole, 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in more the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no 18 appropriate cultures, and other reasons. INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days more (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis)clinical vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g)(n = 127 included included in the analysis). MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required,113) among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. RESULTS: At 4 to 11 days placebo posttherapy, bacteriologic cure rates were 99%(112 of 113) for the ciprofloxacin regimen and 89%(90 of 101) for the and trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, .04- .16; P =.004). Clinical cure rates were 96%(109 of 113) .06- .22; for the ciprofloxacin regimen and 83%(92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, .06- .22; P =.002). Escherichia women. coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin ( %; P<.001).compare Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events and occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI,- .001 to .2).in CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with In greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains.

A cultures combination of ciprofloxacin (intravenous then oral) and oral rifampicin was tested in 14 intravenous drug users with right-sided Staphylococcus aureus cured endocarditis. All 10 patients who completed therapy were cured based on resolution of symptoms and negative blood cultures at 4 tested weeks post therapy.

The for pharmacokinetics and tissue penetration of five quinolones were studied in volunteers. The compounds were norfloxacin (400 mg po), enoxacin (400 pefloxacin mg iv and 600 mg po), ciprofloxacin (100 mg iv and 500 mg po), ofloxacin (600 mg po) and pefloxacin Of (400 mg iv). Of the oral agents studied ofloxacin and ciprofloxacin were the most rapidly absorbed (Tmax = 1.2 h)= and enoxacin the least (Tmax = 1.9 h). The serum levels attained were highest in the case of ofloxacin (after was allowing for the higher dose administered). The serum half-lives were norfloxacin 3.75 h, ciprofloxacin 3.9 h (po), 4. h (iv),500 ofloxacin 7. h, enoxacin 6.2 h (po), 5.1 h (iv) and pefloxacin 10.5 h. All agents penetrated blister fluid readily.was The 24 h urine recovery was 62% for oral enoxacin, 46.4% for iv enoxacin (plus 12.2% for oxo-enoxacin), 27% for for norfloxacin, 30.6% for oral ciprofloxacin, 75.7% for iv ciprofloxacin, 73% for ofloxacin and 4.9% for pefloxacin (plus 9.2% for the in norfloxacin metabolite and 17.8% for pefloxacin N-oxide).

The that fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was patients conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin and (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol and (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion was to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients trial infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing more activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the of difference in outcome was significant only among HIV-infected patients.

STUDY (p OBJECTIVE: To determine the steady-state plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levofloxacin and ciprofloxacin. DESIGN:2. Multiple-dose, open-label, randomized pharmacokinetic study. PARTICIPANTS: Thirty-six healthy, nonsmoking adult subjects were randomized either to oral levofloxacin, 500 or 750 the mg once daily for five doses, or ciprofloxacin, 500 mg q12h for nine doses. INTERVENTIONS: Venipuncture, bronchoscopy, and BAL were 12 performed in each subject at 4 h, 12 h, or 24 h after the last administered dose of antibiotic. MEASUREMENT +/- AND RESULTS: Mean plasma concentrations of levofloxacin and ciprofloxacin were similar to those previously reported. For once-daily dosing of levofloxacin,doses. 500 mg, the mean (+/- SD) steady-state concentrations at 4 h, 12 h, and 24 h in ELF were 9.9 .1 +/- 2.7 microg/mL, 6.5 +/- 2.5 microg/mL, and .7 +/- .4 microg/mL, respectively; AM concentrations were 97.9 +/- 80. microg/mL,differences 36.7 +/- 23.4 microg/mL, and 13.8 +/- 16. microg/mL, respectively. For levofloxacin, 750 mg, the mean steady-state concentrations in ELF microg/mL, were 22.1 +/- 14.9 microg/mL, 9.2 +/- 5.3 microg/mL, and 1.5 +/- .8 microg/mL, respectively; AM concentrations were 105.1 +/-microg/mL, 65.5 microg/mL, 36.2 +/- 26.1 microg/mL, and 15.1 +/- 2. microg/mL, respectively. The concentrations of ciprofloxacin at 4 h and the 12 h in ELF were 1.9 +/- .9 microg/mL and .4 +/- .1 microg/mL, respectively; AM concentrations were 34.9 +/-AM 23.2 microg/mL and 6.8 +/- 5.9 microg/mL, respectively. The differences in the ELF concentrations of the two levofloxacin groups vs h those of the ciprofloxacin group were significant (p < .05) at each sampling time. CONCLUSIONS: Levofloxacin was more extensively distributed adult into intrapulmonary compartments than ciprofloxacin and achieved significantly higher steady-state concentrations in plasma and ELF during the 24 h after macrophage drug administration.

Fleroxacin over (Ro 23-6240; AM-833) is a new trifluorinated quinolone exhibiting high activity against a broad spectrum of gram-negative and gram-positive bacteria.= Healthy male volunteers received, according to a randomized scheme, oral doses of 200, 400, or 800 mg of fleroxacin in 1,000 tablet form, an intravenous infusion of 100 mg, or 400 mg of fleroxacin orally together with 1,000 mg of probenecid.an Fleroxacin is characterized pharmacokinetically by a long elimination half-life (9 to 10 h) and high concentrations in plasma (e.g., maximum under concentration of 2.3 micrograms/ml after an oral dose of 200 mg). The volume of distribution clearly exceeds 1 liter/kg and tablet suggests a good tissue penetration. Within 60 h, the cumulative urinary recovery of unchanged drug amounted to 50 to 60%the of the dose. The renal clearance of unbound drug was 137 ml/min, and probenecid had no significant effect on renal During elimination. A good linear correlation (r = .999) was found between doses from 100 to 800 mg and the resulting 1 values of area under the concentration-time curve. The absolute bioavailability of the administered tablet was practically 100%. During oral multiple of dosing of 800 or 1,200 mg of fleroxacin once a day over 10 consecutive days, the accumulation of the drug maximum in plasma was close to the theoretically predicted value of 1.3 and reflected the persistence of linear pharmacokinetics.

BACKGROUND:assessment Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis.9/27; However, some patients are resistant to treatment. AIM: To evaluate the therapeutic efficacy of a prolonged course of a combination mg of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life.with METHODS: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both:(i) a history of pouchitis Pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis requiring Disease Activity Index score 3 7 (best to worst pouchitis= -18) at the beginning of therapy. Treatment consisted of a combination Disease of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and (range, histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as male, a combination of a Pouchitis Disease Activity Index clinical score of <or= 2, endoscopic score of <or= 1 and total eight score of <or= 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic <or= and emotional symptoms as well as social function (worst to best=32-224). RESULTS: Forty-four patients (24 male, 20 female; median age,Thirty-six 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores treatment before and after therapy were 12 (range, 8-17) and 3 (range, 1-10), respectively (P < .0001). The median Inflammatory Bowel as Disease Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175 (range, 76-215) with this therapy (P < .0001).some The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 35 127 years; P= .007), had a longer history of pouchitis (95.5 vs. 26 months; P= .0008), had a greater proportion with chronic pouchitis to (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1. -2.4) and tended to have a higher Pouchitis Disease Activity noted. Index score before treatment (median 14.5 vs. 12; P= .13) than those who went into remission. Even in these eight patients,is the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8-16) to 9.5 (range, 7-10)(P= .0078), as did encompasses the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127 (range, 76-187)(P= .039). The Inflammatory Bowel Disease Questionnaire evaluations score strongly correlated with the Pouchitis Disease Activity Index score (r= .79, P < .0001), and was significantly related to the 95% patients' overall assessment of satisfaction (P < .0001). No serious side-effects were noted. CONCLUSIONS: Four-week treatment with a combination of female) metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality 7-10) of life. The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with single disease activity.

High the alcohol and low folate intake are independent risk factors for colorectal cancer. Acetaldehyde has been postulated to be a factor were responsible for ethanol-associated carcinogenesis. High levels of acetaldehyde accumulate in the large intestine via the microbial oxidation of alcohol. Acetaldehyde Our degrades folate in vitro. Thus, it is possible that high intracolonic acetaldehyde levels break down folate in the colon. Our twice aim was to test the effect of high alcohol and acetaldehyde concentrations in the gut on systemic and local intestinal prevented folate levels in rats. Twenty rats received 3 g/kg of ethanol twice a day for 2 weeks with or without vitro. concomitant ciprofloxacin administration. Twenty control rats received saline with or without ciprofloxacin. All rats were fed a diet with normal prevented folate content. Alcohol treatment led to very high intracolonic acetaldehyde levels (387 +/- 185 microM), which were markedly decreased by deficiency concomitant ciprofloxacin treatment (21 +/- 4 microM). Erythrocyte, serum and small intestinal folate levels were unaffected by alcohol treatment. Alcohol Twenty administration decreased significantly colonic mucosal folate levels by 48%, and this effect was prevented by ciprofloxacin. We conclude that alcohol microM), administration for 2 weeks leads to local folate deficiency of colonic mucosa in rats, most probably via the degradation of Twenty folate by the high levels of acetaldehyde microbially produced from ethanol. Our findings offer a unique explanation for the increased or risk of colonic cancer associated with alcohol intake and folate deficiency.

The after pharmacokinetics of 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(cis-3,5-dimethyl-1- piperazinyl)-4-oxoquinoline-3-carboxylic acid (AT-4140) in experimental animals given a single oral dose of 5 mg/kg were studied. The the mean peak levels of AT-4140 in plasma of mice, rats, dogs, and monkeys were .25, .50, 1.14, and .49 micrograms/ml,3.8, respectively, with mean elimination half-lives of 5. , 3.8, 8. , and 11.7 h, respectively. The oral bioavailability of AT-4140 calculated from intravenous the ratio of the areas under the concentration-time curve after oral and intravenous administration was 77% in dogs. The levels in of AT-4140 in tissue in mice and rats were 1 to 11 times higher than the levels in plasma and .25, 4 to 9 times higher than those of ciprofloxacin in mice. The mean 24-h biliary recovery of AT-4140 in rats mice, was 5.6% of the dose and became 21.3% after beta-glucuronidase treatment. The mean 48-h urinary recoveries of AT-4140 in mice,respectively, rats, dogs, and monkeys were 6.7, 12.9, 8.6, and 12.7%, respectively, of the dose and were 7.8, 16.3, 8.9, and in 18.9%, respectively, after beta-glucuronidase treatment. The pharmacokinetics of AT-4140 may be characterized by its good tissue penetration and its long of half-life in plasma and tissues.

The in post-antibiotic suppressive effect (PAE) of different antibacterial agents against gram-positive bacteria has been known since the 1940s. Recently, it has to been demonstrated that quinolone antimicrobial agents exert a PAE against gram-negative bacteria. In this study, the PAEs of ciprofloxacin against and Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, and Streptococcus faecalis were determined. The differences in no PAE determined by three different techniques--filtration, centrifugation, and dilution--were assessed for S. aureus and E. coli. Ciprofloxacin had a PAE difference by all three methods, and filtration was used in the majority of studies. A ciprofloxacin concentration of 3 micrograms/ml in determined Mueller-Hinton broth, pH 7.4, with two hours of exposure produced a PAE of three to four hours for gram-negative bacilli,difference and 1.9 hours for S. aureus, but had no effect on S. faecalis. Exposure of organisms in urine to 300 S. micrograms/ml of ciprofloxacin for two hours produced a two- to six-hour PAE for E. coli, S. marcescens, P. aeruginosa, and hours K. pneumoniae. Use of Mueller-Hinton broth with a magnesium concentration of 8 mM, pH 5.5, yielded similar results. Using human There serum, a four-hour PAE was found for P. aeruginosa. There was a progressive increase in the PAE as the duration gram-negative of ciprofloxacin exposure was increased from .9 hours to three hours. Increasing the ciprofloxacin concentration from two to eight times coli, the minimal bactericidal concentration (MBC) for P. aeruginosa or from four to 16 times the MBC for E. coli did to not cause a significant difference in the PAE using a two-hour exposure. Overall, ciprofloxacin produced an excellent PAE for most this gram-negative bacteria and for S. aureus, but not for S. faecalis. A PAE caused by ciprofloxacin can be demonstrated in since broth supplemented with magnesium, in urine, in serum, and in broth with the pH adjusted to an acidic level and for with the increased magnesium concentration found in urine. These results support less frequent dosing programs for ciprofloxacin in the treatment aureus of tissue and urinary infections.