Single Dose Of Ofloxacin Research Articles

Resistance of M. leprae to Quinolones: A Question of Relativity?

Multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (FQ), has been described in Mycobacterium leprae. However, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in DNA gyrase (GyrA2GyrB2), has not been precisely assessed. Our objective was to measure the impact of a DNA gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluoroquinolones: ofloxacin, moxifloxacin and garenoxacin.Methodology/Principal FindingsWe used the proportional bactericidal method. 210 four-week-old immunodeficient female Nude mice (NMRI-Foxn1nu/Foxn1nu) were inoculated in the left hind footpad with 0.03 ml of bacterial suspension containing 5×103, 5×102, 5×101, and 5×100 M. leprae AFB organisms of strain Hoshizuka-4 which is a multidrug resistant strain harboring a GyrA A91V substitution. An additional subgroup of 10 mice was inoculated with 5×10−1 bacilli in the untreated control group. The day after inoculation, subgroups of mice were treated with a single dose of ofloxacin, moxifloxacin, garenoxacin or clarithromycin at 150 mg/kg dosing. 12 months later mice were sacrificed and M. leprae bacilli were numbered in the footpad. The results from the untreated control group indicated that the infective inoculum contained 23% of viable M. leprae. The results from the moxifloxacin and garenoxacin groups indicated that a single dose of these drugs reduced the percentage of viable M. leprae by 90%, similarly to the reduction observed after a single dose of the positive control drug clarithromycin. Conversely, ofloxacin was less active than clarithromycin.Conclusion/SignificanceDNA gyrase mutation is not always synonymous of lack of in vivo fluoroquinolone activity in M. leprae. As for M. tuberculosis, in vivo studies allow to measure residual antibiotic activity in case of target mutations in M. leprae.

Pharmacokinetics of ofloxacin enantiomers after intravenous administration for antibiotic prophylaxis in biliary surgery.

The pharmacokinetics of S-(-)- and R-(+)-ofloxacin, enantiomers of the fluoroquinolone ofloxacin, were characterized after prophylactic administration in 15 patients undergoing elective biliary surgery. A single dose of ofloxacin 400 mg given intravenously as an infusion was administered 1 hour before surgery. Plasma levels of S-(-)- and R-(+)-ofloxacin showed very small differences between both enantiomers, although the ratio of S-(-)- to R-(+)-enantiomer concentration in plasma showed significant differences (p < 0.05) at 4 and 12 hours. Adequate S-(-)-ofloxacin (levofloxacin, the active enantiomer) plasma levels (> or = minimum inhibitory concentration [MIC90] for Escherichia coli) were found throughout the procedure. For pharmacokinetic parameters, the authors found small but statistically significant differences (p < 0.05) in the area under the concentration-time curve, AUC0-infinity (22.30 +/- 2.72 mg h/L for S-(-)-ofloxacin vs. 20.50 +/- 2.06 mg h/L for R-(+)-ofloxacin), and in the clearance (0.15 +/- 0.04 L/h/Kg for S-(-)-ofloxacin vs. 0.16 +/- 0.04 L/h/Kg for R-(+)-ofloxacin). To test the penetration of ofloxacin enantiomers into tissues, the authors measured levels in subcutaneous cell tissue and gall-bladder cell tissue. They did not observe statistical differences between the two isomers, which means that distribution is not an estereoselective process. Enantiomer levels in these two tissues decreased rapidly, but the highest concentrations were reached during the 4 first hours (i.e., when the surgical procedure was being performed). In conclusion, with the prophylactic treatment used, levofloxacin plasma and tissue levels are high enough to prevent surgical infections.

Identification of nasopharyngeal carriage of an outbreak strain of Neisseria meningitidis by pulsed-field gel electrophoresis versus phenotypic methods.

The clustering of four cases of meningococcal disease during a 3-month period in a small community with 2233 inhabitants prompted an interventional carrier survey in persons < 19 years old and in family members of the patients. The aims of the survey were to identify the nasopharyngeal carriers and the carriage rate of the outbreak strain, to offer chemoprophylaxis to those carrying the outbreak strain, and to study the discriminatory power of phenotypic methods versus pulsed-field gel electrophoresis (PFGE) on carrier isolates during an outbreak. A high percentage of the population in the age group 0-19 years (73.7%) participated in the study. Among the 469 samples collected in this age group, meningococci were grown from 43 (9.2%). The highest carriage rates were in the age group 18-19 years (36.4%). With a provisional definition of the outbreak strain (group B or non-groupable Neisseria meningitidis with reduced sulphonamide sensitivity), six carriers were identified. All were treated with a single dose of ofloxacin. Four of these persons (0.76% of all tested) were later shown to have harboured the outbreak strain when analysed by PFGE. Three of them were epidemiologically closely related to one of the index cases. Serogrouping alone is not sufficient for the identification of an epidemic strain of N. meningitidis. Complete concordance of type and subtype antigens correctly identified the outbreak strain in this study. PFGE is well suited for the identification of an outbreak strain of N. meningitidis versus non-epidemic strains in tonsillo-pharyngeal specimens.

Pharmacokinetics and Tissue Distribution of Intravenous Ofloxacin for Antibiotic Prophylaxis in Biliary Surgery

The plasma levels and tissue penetration of ofloxacin were studied after prophylactic administration in 17 patients undergoing elective biliary surgery. A single dose of ofloxacin 400mg given intravenously as an infusion was administered 1 hour before surgery. Adequate drug plasma levels [>/= minimum inhibitory concentration (MIC(90)) for Escherichia coli] were found throughout the procedure. Mean peak (1 hour) and last-determined (36 hours) ofloxacin serum levels were 7.97 +/- 3.79 mg/L and 0.19 +/- 0.13 mg/L, respectively. The elimination half-life (t((1/2)lambda)) was 8.86 +/- 3.07 hours, and the clearance and steady-state volume of distribution were 0.17 +/- 0.05 L/h.kg and 112.90 +/- 37.09L, respectively. The area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 41.60 +/- 12.51 mg/L.h. In bile, ofloxacin levels were higher than in plasma and showed great variability. Adequate ofloxacin levels in subcutaneous cell tissue and gallbladder wall tissue were observed during the surgical procedure. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalisation stay and time of recuperation were normal for this type of surgery.

Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea.

Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature. The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea. Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days. The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool. Results: Ofloxacin and loperamide were well tolerated. Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001). Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001). Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours. Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.

No effect of single dose ofloxacin on postoperative infection rate after first‐trimester abortion

In a double-blind stratificated, placebo controlled study the efficacy and safety of a single oral dose of ofloxanin (Tarivid) (400 mg) in preventing postabortal pelvic inflammatory disease (P-PID) in women with induced first-trimester abortions were assessed. The tablets were given 1 1/2-2 h before the abortion, and the women were followed one month after the operation. Group I consisted of 308 with previous PID. Ofloxacin tablets were given to 149 women and 159 women received placebo tablets. In the ofloxacin group 20 women (13.4%) and in the placebo group 27 women (17%) developed P-PID, a non-significant difference (p = 0.39). Group II consisted of 765 women without a history of PID. Ofloxacin tablets were given to 376 women and 389 women received placebo tablets. Thirty-five women (9.3%) in the ofloxacin group and 46 women (11.9%) in the placebo group developed P-PID, a non-significant difference (p = 0.26). A single oral dose of ofloxacin (400 mg) did not reduce the incidence of P-PID either among women with previous PID or among women without previous PID.

Use of single-dose ofloxacin to eradicate tonsillopharyngeal carriage of Neisseria meningitidis

After an outbreak of three cases of serogroup B meningococcal disease at a Norwegian college, 84 of 392 (21%) subjects were tonsillopharyngeal carriers of Neisseria meningitidis. To eradicate meningococcal carriage, 80 volunteers received a single dose of 400 mg of ofloxacin. Three days after treatment, all 75 evaluable volunteers were culture negative for N. meningitidis, and after 7 days none carried the strain that they carried initially, as judged by DNA fingerprinting. A single dose of ofloxacin was found to be 97.2% effective in eradicating carriage of N. meningitidis for a period of 33 days. The carriage acquisition rate among treated students was four times higher than that among nontreated noncarriers (P = 0.02). After ofloxacin treatment, no case of meningococcal disease occurred for 6 months. Ofloxacin may thus prevent the outbreak and spread of meningococcal disease.

Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients.

7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg.l-1) and trough levels (1.6 mg.l-1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2 beta) and during the haemodialysis session (t1/2 HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml.min-1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2 beta of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.

Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women

We compared the safety and efficacy of a single 400-mg dose of ofloxacin, ofloxacin (200 mg) once daily for 3 days, and trimethoprim-sulfamethoxazole (160:800 mg) twice daily for 7 days for the treatment of acute uncomplicated cystitis (urinary tract infection [UTI]) in women. At 5 weeks posttreatment, 35 (81%) of 43 patients treated with single-dose ofloxacin, 40 (89%) of 45 treated with 3 days of ofloxacin, and 41 (98%) of 42 treated with trimethoprim-sulfamethoxazole were cured (P = 0.03, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). Retreatment for symptomatic recurrent UTI was given to 7 (16%) of 43 patients initially treated with single-dose ofloxacin, 3 (7%) of 45 patients treated with 3 days of ofloxacin, and 0 of 42 patients treated with trimethoprim-sulfamethoxazole (P = 0.01, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). There was a trend in each of the three treatment groups toward an association between persistent or recurrent episodes of significant bacteriuria and a history of UTI in the past year and with diaphragm use. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during or soon after therapy, but there were no differences at later follow-up visits. Adverse effects were equally common among the three treatment groups. We conclude that single-dose ofloxacin was less effective than 7 days of trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women, while the 3-day ofloxacin regimen and the trimethoprim-sulfamethoxazole regimen were not significantly different in efficacy.

Single-dose ofloxacin shows promise in uncomplicated gonorrhoea

Single-dose ofloxacin shows promise in uncomplicated gonorrhoea

Randomized Comparison of Ofloxacin and Doxycycline for Chlamydia and Ureaplasma Urethritis and Cervicitis

Fifty-eight males and 34 females with nongonococcal urethritis and/or cervicitis were treated to compare the efficacy and safety of 7-day regimens of oral ofloxacin 300 mg twice daily and doxycycline hyclate 100 mg twice daily. Forty-seven patients were randomized to receive ofloxacin and 45 patients to receive doxycycline. The microbiologic response rate was 97% (32/33) for both ofloxacin and doxycycline; the combined microbiologic and clinical cure rates were 98% for both treatment groups (ofloxacin 46/47, doxycycline 44/45). Ofloxacin was as effective as doxycycline in the treatment of chlamydial infections (96% vs. 100%). In patients with Ureaplasma urealyticum, the initial response was complete with either drug, but recurrence of infection was observed with both treatment groups (1 of 4 patients in the ofloxacin group and 2 of 11 patients in the doxycycline group). In the treatment of mixed Chlamydia trachomatis and U. urealyticum infections, all 5 patients treated with ofloxacin and 3 of 4 patients treated with doxycycline were cured. In symptomatic patients whose initial cultures were negative, clinical cures were complete with both drugs, but Ureaplasma was isolated at 3 or more weeks post-treatment in 2 patients treated with ofloxacin. In a study of single-dose ofloxacin treatment of uncomplicated gonorrhea, Neisseria gonorrhoeae was eradicated in all subjects, but C. trachomatis was not reliably eradicated. Both drugs were well tolerated with only minimal adverse effects reported in either treatment group. A multiple-dose regimen of ofloxacin appears to be a highly effective and well-tolerated alternative to doxycycline in nongonococcal sexually transmitted disease.

Pharmacokinetics of a single dose of ofloxacin in healthy elderly subjects using noncompartmental and compartmental models

The pharmacokinetics of ofloxacin following a single 200 mg oral dose were studied in twelve healthy elderly volunteers. Relevant pharmacokinetic parameters were analysed by both noncompartmental and compartmental models. In compartmental analysis, the data on plasma concentrations was best described by an open two-compartment model. A zero-order absorption behaviour was found in some volunteers. The terminal half-lives were slightly prolonged and ranged from 6.2-11.6 h. A linear relationship was found between the renal clearance of the drug and the estimated creatinine clearance. Computer predictions of a multiple 200 mg dose regimen showed no important accumulation of ofloxacin. The recommendation of some authors that, in general, ofloxacin dosage may be halved in the elderly could not be confirmed. This has to be determined through further clinical experience in elderly ill subjects.

Single Doses of Ofloxacin in Uncomplicated Gonorrhoea

The clinical efficacies of 2 different single-dose oral treatments of ofloxacin were evaluated in a double-blind, randomised study of 60 males with gonococcal urethritis. 30 patients received a single dose of ofloxacin 100mg and 30 received a single dose of ofloxacin 200mg. The minimal inhibitory concentrations of ofloxacin against all isolates were less than or equal to 0.25 mg/L. Neisseria gonorrhoeae was eradicated from all 50 patients evaluated and clinical cure was achieved in 84%. In total, 8 patients developed post-gonococcal urethritis, although there was a significantly (p less than 0.05) lower rate of post-gonococcal urethritis in the group treated with ofloxacin 200mg. In conclusion, a single oral dose of ofloxacin 100mg could be an alternative treatment for uncomplicated gonorrhoea.

Single low-dose ofloxacin for the treatment of uncomplicated urinary tract infection in young women.

Fifty premenopausal women with uncomplicated urinary tract infection (UTI) were treated with a single dose of 100 mg of ofloxacin. Duration of symptoms before the treatment, number of episodes of UTI during the last year, association with sexual activity, and the use of contraceptives were evaluated in relation to the clinical and microbiological response. Forty-seven women (94%) were cured clinically and microbiologically three days after treatment. Follow up at 28 days disclosed that 43 (86%) were free of symptoms and in 40 (80%) the urinary cultures were negative. Significantly higher rates of microbiological failure or reinfection were found among women with three or more episodes of UTI during the last year. This study shows that a single dose of ofloxacin is effective for therapy of uncomplicated UTI in young women.

Single Doses of Ofloxacin in Uncomplicated Gonorrhoea

The clinical efficacies of 2 different single-dose oral treatments of ofloxacin were evaluated in a double-blind, randomised study of 60 males with gonococcal urethritis. 30 patients received a single dose of ofloxacin 100mg and 30 received a single dose of ofloxacin 200mg. The minimal inhibitory concentrations of ofloxacin against all isolates were less than or equal to 0.25 mg/L. Neisseria gonorrhoeae was eradicated from all 50 patients evaluated and clinical cure was achieved in 84%. In total, 8 patients developed post-gonococcal urethritis, although there was a significantly (p less than 0.05) lower rate of post-gonococcal urethritis in the group treated with ofloxacin 200mg. In conclusion, a single oral dose of ofloxacin 100mg could be an alternative treatment for uncomplicated gonorrhoea.

Assessment of immunomodulating activity of ofloxacin and three other quinolones in human plasma.

A time-dependent degree of immunosuppression or immunostimulation which may be correlated to pharmacokinetic variables was obtained by administering a single dose of ofloxacin, norfloxacin, pipemidic and piromidic acid to healthy volunteers. The plasma samples collected before drug administration and then at various time intervals were tested for their immunomodifying activity by employing a modified 2-way mixed lymphocyte reaction and a PMN chemotactic assay. Our results show that some of the quinolones tested--norfloxacin, pipemidic acid, piromidic acid--have an immunosuppressive activity.

The effect of food on the pharmacokinetics of ofloxacin

After oral administration of a single dose of ofloxacin (300 mg), with and without a standard breakfast, to 12 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using high pressure liquid chromatography (HPLC): parallel determinations using a microbiological assay were in close agreement. Maximum serum concentrations (Cmax) of ofloxacin, after fasting and with breakfast, respectively, were 3.7 and 3.1 micrograms/ml (HPLC, median values). The corresponding areas under the serum concentration-time curves (AUC0-28) were 29.9 and 24.5 micrograms/ml. The lower values of Cmax and AUC0-28 found after food intake were statistically significant (p less than 0.05) but not clinically relevant when compared to the fasting values. Time to reach Cmax and terminal elimination half-life (t1/2 beta) were not significantly affected by food intake: t1/2 beta was calculated as 5.3 and 5.9 hours (HPLC, median values), fasting and with breakfast, respectively. Urinary recovery (after 48 hours: 72% and 74%, respectively) was also not significantly affected by food intake, and urinary concentrations of ofloxacin remained far above 1 microgram/ml, i.e. above the minimum inhibitory concentration (MIC90) for most bacterial strains, for at least 48 hours after drug administration. General tolerability was good; no side-effects were reported.