Establishment of an immunological detection method of fleroxacin by fluorescence-linked immunosorbent assay.

The direct and indirect competitive fluorescence-linked immunosorbent assay (FLISA and icFLISA) incorporating quantum dots (QDs) for the detection of fleroxacin (FLE) was established for the first time in this study. The monoclonal antibody specific for FLE was successfully conjugated with QDs after purification by the caprylic acid-ammonium sulphate method. The limits of detection of FLISA and icFLISA were 0.012 ng/mL and 0.006 ng/mL, respectively; IC50 were 0.32 ng/mL and 0.19 ng/mL; and the detection ranges were 0.012-24.490 ng/mL and 0.006-16.210 ng/mL. The recovery was 93.8%-112.4% and the coefficient of variation was below 11.75%. The fabricated FLISA and icFLISA are cost-effective, high sensitive and can be an alternative method in the detection of FLE residues.

First population pharmacokinetic analysis showing increased quinolone metabolite formation and clearance in patients with cystic fibrosis compared to healthy volunteers.

Understanding the pharmacokinetics in patients with cystic fibrosis (CF) is important for dosing. For antibiotics with extensive metabolism, however, a comparison of metabolite formation and elimination between patients with CF and healthy volunteers has never been performed via population modeling. We aimed to compare the population pharmacokinetics of fleroxacin and its N­oxide and demethyl metabolites between patients with CF and healthy volunteers. Our analysis included eleven adult patients with CF and twelve healthy volunteers who received 800 mg fleroxacin as a single oral dose followed by five doses every 24 h from a previously published study. All plasma concentrations and amounts in urine for fleroxacin and its metabolites were simultaneously modelled. The estimates below accounted for differences in body size and body composition via allometric scaling by lean body mass. Oral absorption was slower in patients with CF than in healthy volunteers. For fleroxacin, the population mean in patients with CF divided by that in healthy volunteers was 1.12 for renal clearance, 1.01 for linear nonrenal clearance, 0.83 for saturable exsorption clearance into intestine, and 0.81 for volume of distribution. The formation clearances of N­oxide fleroxacin and N­demethylfleroxacin were 0.520 L/h and 0.496 L/h in patients with CF; these formation clearances were 0.378 L/h and 0.353 L/h in healthy volunteers. Renal clearance in patients with CF divided by that in healthy volunteers was 1.53 for N­oxide fleroxacin and 1.70 for N­demethyl fleroxacin. Allometric scaling by lean body mass best explained the variability. While fleroxacin pharmacokinetics was comparable, both formation and elimination clearances of its two metabolites were substantially larger in patients with CF compared to those in healthy volunteers.

Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.

BACKGROUND: Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted. HYPOTHESIS: Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls. STUDY DESIGN: Controlled laboratory study. METHODS: Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant. RESULTS: Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups. CONCLUSION: In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing. CLINICAL RELEVANCE: These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery.

Photodegradation of fleroxacin injection: II. Kinetics and toxicological evaluation.

Photodegradation kinetics of fleroxacin were investigated in different injections. Five commercial formulations were analyzed before and after irradiation by determining residual volumes of fleroxacin with high-pressure liquid chromatography (HPLC), and different decomposition functions and models were obtained. Concentration levels of fleroxacin in injections caused the differences in photodegradation kinetics instead of ingredients. Influences of different pH values and presence of NaCl on photodegradation of fleroxacin were observed. Low pH value decreased the efficacy of photolysis and enhanced photostability of fleroxacin injections. Tentative structure of a new degradation product afforded was proposed. An acute toxicity assay using the bioluminescent bacterium Q67 was performed for fleroxacin injections after exposure to light. The research proved that fleroxacin was more photolabile in dilute injection, and acute toxicity of dilute injection increased more rapidly than that of concentrated injection during irradiation.

A randomized clinical trial to compare fleroxacin-rifampicin with flucloxacillin or vancomycin for the treatment of staphylococcal infection.

BACKGROUND: Oral combination therapy with fluoroquinolones plus rifampicin is a promising alternative to standard parenteral therapy for staphylococcal infections. METHODS: In a multicenter, randomized trial, we compared the efficacy, safety, and length of hospital stay for patients with staphylococcal infections treated either with an oral combination of a fluoroquinolone (fleroxacin) plus rifampicin or with standard parenteral treatment (flucloxacillin or vancomycin). Patients were included if cultures showed the presence of bacteremia or deep-seated infections with Staphylococcus aureus (104 patients) or catheter-related bacteremia due to drug-susceptible, coagulase-negative staphylococci (23 patients). RESULTS: The cure rate in the intention-to-treat analysis was 78% for the fleroxacin-rifampicin group (68 patients) and 75% for the standard therapy group (59 patients; 47 received flucloxacillin, and 12 received vancomycin); in the population of clinically evaluable patients (n=119), the cure rate was 82% and 80%, respectively; and in the population of microbiologically evaluable patients (n=103), the cure rate was 86% and 84%, respectively. Clinical and bacteriological failures after S. aureus infections were documented in similar proportions of patients. The median length of hospital stay after study entry was 12 days in the fleroxacin-rifampicin group, compared with 23 days in the standard treatment group (P=.006). More adverse events probably related to the study drug were reported in the fleroxacin-rifampicin group than in the standard therapy group (15 of 68 vs. 5 of 59 patients; P=.05). CONCLUSIONS: This study suggests that an oral regimen containing a fluoroquinolone plus rifampicin may be effective for treating staphylococcal infections, allowing earlier discharge from the hospital.

A pilot study of oral fleroxacin once daily compared with conventional therapy in patients with pyogenic liver abscess.

The object of this open-label, randomized, comparative study was to evaluate the efficacy and safety of fleroxacin versus conventional therapy (cefazolin plus gentamicin/cephalexin) in the treatment of patients with bacterial liver abscess. Thirty-one adult patients (26 men and 5 women) received fleroxacin 400 mg orally once daily for 3 weeks, and 30 adult patients (21 men and 9 women) received conventional therapy for 3 to 4 weeks. Patients was assessed on day 3 of treatment, thereafter every week during treatment, and at 7 to 14 days (compulsory follow-up) after treatment for assessment of bacteriologic, clinical, and safety parameters. A total of 20 patients in the fleroxacin group and 22 patients in the conventional therapy group were evaluated. Klebsiella pneumoniae was the predominant pathogen isolated in all evaluable cases. Bacteriologic cure was achieved in 14 (70%) of 20 patients on fleroxacin therapy compared with 18 (81.8%) of 22 patients on conventional therapy (p=0.48). Clinical cure was achieved in 12 (60%) and 18 (81.8%) patients, and improvement in 2 (10%) and 1 (4.5%) patients in the fleroxacin and conventional therapy group, respectively. Most of adverse effects were of mild intensity. Oral fleroxacin once-daily administration is an effective, alternative treatment of bacterial liver abscess.

[Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin mesilate, a new quinolone antibacterial agent for intravenous use: convulsions in mice after intravenous or intracerebroventricular administration].

Convulsant activity of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, in combination with nonsteroidal anti-inflammatory drug (NSAID) was investigated in mice after intravenous or intracerebroventricular administration. Following results were obtained. 1. In combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg. Reference quinolones induced convulsions at the following intravenous doses: Enoxacin (ENX), 3.13 mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX), 6.25 mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX) and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200 mg/kg. 2. PZFX mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice after oral administration of any of 14 kinds of NSAIDs. It induced convulsions at 200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did not with the other 13 kinds of NSAIDs. 3. Convulsion-inducing dose of PZFX mesilate after intracerebroventricular administration was 100 mg/body, which was higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX, levofloxacin, ofloxacin, FLRX and SPFX) and beta-lactam antibiotics (penicillin G, cefazoline, imipenem/cilastatin and panipenem/betamipron). In addition, concurrent dosing of BPAA (1 microgram/body) did not reduce the convulsion-inducing dose of PZFX mesilate. These results suggest that PZFX mesilate has remarkably weak convulsant activity.

Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.

Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy.

Activity of quinolones against viridans group streptococci isolated from blood cultures of patients with haematological malignancy.

Use of fluoroquinolones for antimicrobial prophylaxis during neutropenia is often cited as a significant predisposing factor for viridans group streptococcus (VGS) bacteraemia. Newer compounds in this class are reputed to have enhanced activity against Gram-positive bacteria, and we determined the minimal inhibitory concentrations (MICs) for ciprofloxacin and three of the newer compounds: trovafloxacin, fleroxacin and clinafloxacin, against 44 isolates of VGS. On a gravimetric basis, clinafloxacin was most active (MIC90 0.19 mg/l), whereas ciprofloxacin and fleroxacin were the least active (both MIC90 16 mg/l). Clinafloxacin warrants further study as an agent of prophylaxis against bacterial infection in neutropenic patients.

[Fluoroquinolones as etiology of tendinopathy]. / Fluoroquinolone als Ursache von Tendinopathien.

Tendinopathies as a result of fluoroquinolone therapy represent a new clinical entity. We report on tendinitis and tendon rupture in six fluoroquinolone treated patients of our outpatient and dialysis service between 1995 and 1997. The most important risk factors for tendinopathies were renal failure in all cases, glucocorticosteroid therapy in five patients, secondary hyperparathyroidism in three patients, advanced age in two patients, and diabetes mellitus in another patient. Latency periods of 2 to 60 days between onset of fluoroquinolone therapy and emergence of symptoms suggest significant involvement of these agents and are compatible with previously published case reports. Therefore, care should be used in prescribing fluoroquinolones to older renal transplant or hemodialysis patients with additional risk factors for tendinopathies. These drugs should be stopped when symptoms of tendinitis occur, particularly to prevent tendon rupture. The incidence of fluoroquinolone induced tendinopathies in patients without renal diseases is unknown.

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

In vitro activity of enoxacin versus ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, pefloxacin, and rufloxacin against uropathogens.

Minimum inhibitory concentrations (MIC) of enoxacin, ciprofloxacin, fleroxacin, lomefloxacin, ofloxacin, pefloxacin and rufloxacin were determined against 400 uropathogens cultured from the urine of patients with complicated and/or hospital-acquired urinary tract infections (UTI) using an agar dilution method. The bacterial spectrum consisted of Entero-bacteriaceae (34.5%), enterococci (31.5%), staphylococci (21.2%) and non-fermenting bacteria (12.8%). Enoxacin inhibited all but one strain (Enterobacter cloacae) of Enterobacteriaceae up to an MIC of 1 mg/l (MIC90 0.25 mg/l). Regarding the total bacterial spectrum, enoxacin inhibited 54.5, 59.5, 76.0 and 83.8% up to an MIC of 1, 2, 4 and 8 mg/l, respectively. If the same breakpoint of resistance for ofloxacin according to DIN 58,940 (NCCLS), i.e. MIC > or = 4 mg/l (> or = 8 mg/l), is also taken for the other fluoroquinolones, and the 126 strains of enterococci are excluded, for which alternative agents, e.g. aminopenicillins, should be considered instead, the following resistance rates were found: ciprofloxacin and enoxacin 15.3% (15.0%), ofloxacin 17.2% (15.3%), pefloxacin 18.2% (15.3%), fleroxacin 19.3% (15.3%), lomefloxacin 19.7% (17.9%) and rufloxacin 31.8% (27.4%). According to their in vitro activity, all fluoroquinolones tested besides rufloxacin show similar rates of resistance against uropathogens and can therefore be considered good alternative agents for the treatment of complicated UTI.

Fleroxacin 400 mg once daily versus ofloxacin 400 mg twice daily in skin and soft tissue infections.

The efficacy and safety of 10 days' oral treatment with fleroxacin 400 mg once daily were compared with those of ofloxacin 400 mg twice daily in adults with skin and soft tissue infections. The most common diagnoses were skin abscess, cellulitis and wound infection. The most commonly-isolated pathogens were Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci. Overall bacteriological cure rates in patients with susceptible pathogens were 89% for 158 fleroxacin-treated patients and 97% for 157 ofloxacin-treated patients (treatment difference 8%; 95% confidence intervals 2-14%; p < 0.05). Clinical cure rates were 78% for fleroxacin and 83% for ofloxacin (treatment difference 5%; 95% confidence intervals-5-14%, not statistically significant). The overall safety profiles were similar and the most frequently reported events were insomnia, headache, dizziness, and digestive system disorders. More fleroxacin-treated patients experienced phototoxicity and treatment-limiting adverse events. In conclusion, compared to twice-daily ofloxacin, fleroxacin had similar clinical efficacy and the advantage of once-a-day dosing, but with slightly lower bacteriological cure rate and a higher rate of treatment-limiting adverse events.

Once-daily fleroxacin versus twice-daily ciprofloxacin in the treatment of complicated urinary tract infections.

PURPOSE: We compared the efficacy and safety of once-daily fleroxacin and twice-daily ciprofloxacin in patients with complicated urinary tract infections. MATERIALS AND METHODS: Using a prospective, open, randomized, multicenter study design, 133 patients (67 fleroxacin, 66 ciprofloxacin) were treated with doses of either 200 mg. of fleroxacin once daily or 250 mg. of ciprofloxacin twice daily in phase 1. In phase 2, 211 patients (103 fleroxacin, 108 ciprofloxacin) received 400 mg. of fleroxacin once daily or 500 mg. of ciprofloxacin twice a day. RESULTS: In phase 1, bacteriological efficacy was excellent only against sensitive pathogens, such as Escherichia coli (84% with fleroxacin, 88% with ciprofloxacin), but high failure rates were observed in infections caused by Pseudomonas species (56% with fleroxacin, 67% with ciprofloxacin) and gram-positive organisms (52% with fleroxacin, 67% with ciprofloxacin). In phase 2, bacteriological overall success rate was 88% in the fleroxacin group and 84% in the ciprofloxacin group. Clinical overall success was observed in more than 90% of patients in both groups (94% with fleroxacin, 93% with ciprofloxacin). No statistically significant differences between the drugs were observed in efficacy during phase 2, including a 4 to-6-week followup. Tolerance was also similar for fleroxacin and ciprofloxacin, with about 20% of patients reporting adverse events. CONCLUSIONS: The results suggest that both fleroxacin and ciprofloxacin are safe and effective for the treatment of complicated urinary tract infections at the higher doses used in phase 2, with fleroxacin offering the advantage of a once-daily dosing regimen. Lower doses of fleroxacin (200 mg. once daily) should only be used to treat urinary tract infections caused by gram-negative organisms with minimum inhibiting concentrations of less than 0.5 mg./l.

[Single dose of fleroxacin for the treatment of adult acute diarrhea]. / Monodosis de fleroxacina para el tratamiento de la diarrea aguda estival en el adulto.

The purpose of this work was to evaluate the efficacy and safety of a single dose of 400 mg of fleroxacin for the empiric antibiotic treatment of acute diarrhea in adult patients. A prospective, double-blind, placebo-controlled, randomized trial was designed. All the adult patients who consulted in our hospital for acute diarrhea from December 1994 to April 1995 were included. 72 patients were randomized to receive a single dose of fleroxacin 400 mg and 73 were placebo. Thirty-eight patients in each group were evaluable for efficacy. Between both groups there were not statistically significant differences in age, sex, number of loose stools per day at inclusion, days since the onset of symptoms up to inclusion, other symptoms than diarrhea at inclusion, percentages of bacterial pathogens and parasites isolated and symptomatic treatment indicated. At the third day since inclusion, clinical cure occurred in 72.2% of the patients receiving fleroxacin, compared with 36.4% of those receiving placebo; p = 0.002. The mean +/- SD time to cure was 2.2 +/- 1.2 days in the fleroxacin group and 3.2 +/- 2.0 days in the placebo group; p = 0.01. Twenty-eight and 16.7% of patients reported adverse effects in the fleroxacin and placebo groups respectively; p = 0.3. It is concluded that a single dose of fleroxacin 400 mg is an effective and safe alternative for the empiric antibiotic treatment of acute diarrhea in adults.

Rapid and simple determination of fleroxacin in rat plasma using a solid-phase extraction column.

We studied the use of high-performance liquid chromatography (HPLC) with a spectroflurometric detector, using a solid-phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of plasma fleroxacin (FLRX) levels in rats. Extracted aliquots were analyzed by HPLC, using a reverse phase octadecyl silica column. The analytical mean recovery of FLRX added to the blank plasma averaged 101.4%. The detection limit was 58 ng/ml in the plasma. The reproducibilities (C.V.) were 0.50-3.22% in the within-day assay and 2.87 C.V.% in the between-day assay, indicating that the analysis method was effective in the determination of FLRX plasma levels.

Monodosis de fleroxacina para el tratamiento de la diarrea aguda estival en el adulto / Silgle dose of fleroxacine for the treatment of adult acute diarrhea

El propósito de este trabajo fue evaluar la eficacia y seguridad de fleroxacina en monodosis de 400 mg para la terapéutica antibiótica empirica de pacientes adultos con diarrea aguda. Se diseño un estudio prospectivo, randomizado, doble ciego, controlado con placebo, incluyéndose los pacientes adultos que concurrieron al hospital por diarrea aguda. Valores de p <0,05 fueron considerados estadísticamente significativos, 72 casos fueron asignados a fleroxacina y 73 a placebo. Se logró evaluar la respuesta al tratamiento en 38 casos de cada grupo, no habiendo entre los mismos diferencias significativas en relación a edad, sexo, deposiciones diarias al momentos de la inclusión, días transcurridos desde el inicio del cuadro y la consulta, otros síntomas además de diarrea, porcentaje de casos con copro y parasitológico positivo y utilización de tratamiento sintomático. Al tercer día desde la inclusión presentó criterios de curación el 72,2 por ciento de los pacientes del grupo fleroxacina y el 36,4 por ciento del grupo placebo; p=0,002. Entre los que recibieron fleroxacina y placebo, los promedios + DE de duración del cuadro fueron 2,2 + 1,2 y 3,2 + 2,0 días respectivamente, p=0,01. El porcentaje de pacientes que refirieron efectos adversos fue de 28 por ciento en el grupo fleroxacina y 16,7 por ciento en el grupo placebo; p=0,3. Se concluye que fleroxacina en monodosis de 400 mg es una alternativa eficaz y segura para el tratamiento antibiótico empírico de la diarrea aguda en el adulto.

Monodosis de fleroxacina para el tratamiento de la diarrea aguda estival en el adulto / Silgle dose of fleroxacine for the treatment of adult acute diarrhea

El propósito de este trabajo fue evaluar la eficacia y seguridad de fleroxacina en monodosis de 400 mg para la terapéutica antibiótica empirica de pacientes adultos con diarrea aguda. Se diseño un estudio prospectivo, randomizado, doble ciego, controlado con placebo, incluyéndose los pacientes adultos que concurrieron al hospital por diarrea aguda. Valores de p <0,05 fueron considerados estadísticamente significativos, 72 casos fueron asignados a fleroxacina y 73 a placebo. Se logró evaluar la respuesta al tratamiento en 38 casos de cada grupo, no habiendo entre los mismos diferencias significativas en relación a edad, sexo, deposiciones diarias al momentos de la inclusión, días transcurridos desde el inicio del cuadro y la consulta, otros síntomas además de diarrea, porcentaje de casos con copro y parasitológico positivo y utilización de tratamiento sintomático. Al tercer día desde la inclusión presentó criterios de curación el 72,2 por ciento de los pacientes del grupo fleroxacina y el 36,4 por ciento del grupo placebo; p=0,002. Entre los que recibieron fleroxacina y placebo, los promedios + DE de duración del cuadro fueron 2,2 + 1,2 y 3,2 + 2,0 días respectivamente, p=0,01. El porcentaje de pacientes que refirieron efectos adversos fue de 28 por ciento en el grupo fleroxacina y 16,7 por ciento en el grupo placebo; p=0,3. Se concluye que fleroxacina en monodosis de 400 mg es una alternativa eficaz y segura para el tratamiento antibiótico empírico de la diarrea aguda en el adulto. (AU)

Pharmacodynamic effects of ciprofloxacin, fleroxacin and lomefloxacin in vivo and in vitro.

The present study investigates the postantibiotic effect (PAE) in vivo, and the postantibiotic subinhibitory concentration effects (PA-SE) in vitro and SE in vivo of three 4-fluoroquinolones (ciprofloxacin, fleroxacin and lomefloxacin) against standard strains of Staphylococcus aureus and Escherichia coli. In vivo killing kinetics have also been performed using two different short administrations to study if the PAE duration could cover the time that the antibiotic was below the minimal inhibitory concentration (MIC) in serum. The results show that the three antimicrobial agents induced long PAEs (1.9-3.1 h) against the two microorganisms. Moderate but significant in vitro PA-SEs were also produced (1-->9 h). The in vivo SEs were not significant except when the effect of lomefloxacin on E. coli was assayed (0.54 h). Finally, the in vivo killing kinetics showed that the administrations that included the PAE duration were as effective as the schedule that maintained the antibiotic levels in serum above the MIC. Only when fleroxacin and S. aureus were assayed, this last administration was more effective (+0.9 log10 colony-forming units/thigh).