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.

Safety of fleroxacin in clinical trials.

This article reviews the safety of fleroxacin in clinical trials. Data from 4,450 patients treated with oral fleroxacin and 650 treated with intravenous fleroxacin were analyzed. The overall rate of adverse reactions for patients treated with oral fleroxacin was 20% for those given 200 mg daily and 20% for those given a daily dose of 400 mg. The adverse reaction rate with the intravenous formulation was 20%. The most frequent adverse reactions involved the gastrointestinal tract (11%) and the central nervous system (9%). All events were reversible. Insomnia was the most commonly reported adverse event. The safety profile of fleroxacin was similar to that reported with other fluoroquinolones.

A sequential study of intravenous and oral fleroxacin in the treatment of complicated urinary tract infection.

This study enrolled patients with complicated urinary tract infections (UTIs) in a trial to determine the efficacy and safety of sequential therapy with intravenous fleroxacin (first 3 days) followed by oral fleroxacin, for a total course of 7-14 days, both administered at a dosage of 400 mg once a day. We enrolled 68 patients with complicated UTIs or acute pyelonephritis, 32 of whom were evaluable for bacteriologic and clinical efficacy. The pathogens isolated included Escherichia coli, 15; enterococci, 9; miscellaneous, 15. Intravenous fleroxacin was given for a mean of 3.2 days, followed by oral fleroxacin for a mean of 5.3 days. A total of 27 patients were clinically cured (84%), two improved, and three failed. A total of 26 patients were bacteriologically cured (81%), and six failed (19%). The bacteria that were not eradicated included enterococci, 4; Staphylococcus epidermidis, 1; and Pseudomonas species, 1. One enterococcal isolate became resistant to fleroxacin. Four patients were bacteremic (E. coli, 3; Proteus mirabilis, 1); the pathogen was eradicated in all cases. Two patients developed urinary enterococcal superinfections. A total of 12 patients experienced 16 adverse reactions remotely, possibly, or probably related to fleroxacin (insomnia, 3; dizziness, 2; miscellaneous, 11). One patient had a grand mal seizure after aspirating gastric contents; the seizure was thought to be only remotely related to the study drug. Fleroxacin was discontinued in two patients because of adverse effects (phlebitis at intravenous access site, 1; anxiety and insomnia, 1). Only minor and asymptomatic laboratory abnormalities were observed. All clinical and laboratory abnormalities resolved with discontinuation of the study drug. Fleroxacin is a safe and effective antibiotic for sequential intravenous and oral treatment of acute pyelonephritis and complicated UTIs. Enterococci may be problematic pathogens, as reported with other fluoroquinolones.

Efficacy of oral fleroxacin in bone and joint infections.

Bone and joint infections have traditionally required long-term parenteral antimicrobial therapy, which is often expensive and inconvenient. Because of their excellent absorption and tissue penetration, oral quinolones may provide an alternative to parenteral therapy. This multicenter study was designed to evaluate the efficacy and safety of oral fleroxacin in osteomyelitis and septic arthritis. A total of 96 patients with either septic arthritis or acute or chronic osteomyelitis from 17 U.S. centers were enrolled in a noncomparative study using oral fleroxacin 400 mg per day. Patients with implantable devices were excluded. Proof of infection for evaluability required clinical findings in addition to bacteriologic recovery of a susceptible organism from synovial fluid or bone. Treatment lasted 2-12 weeks. Clinical and bacteriologic outcomes were judged at the conclusion of therapy and in the 6-week follow-up period. A total of 30 patients qualified for efficacy analysis (26 osteomyelitis, 4 septic arthritis). Bacteriologic cure was achieved in 77% of the osteomyelitis group and 50% of the septic arthritis group. Clinical cures were reported in 54% of the osteomyelitis group and 50% of the septic arthritis group. Staphylococcus aureus was the most frequently recovered pathogen (62% evaluable cases). Safety was evaluated in 96 patients. The most common side effects were nausea, vomiting, and skin reactions. Oral fleroxacin may be a safe, effective, and certainly less expensive alternative to standard intravenous antimicrobial therapy in patients with bone and joint infections.

Efficacy and toxicity of fleroxacin in the treatment of travelers' diarrhea.

The efficacy and safety of fleroxacin in brief self-treatment of travelers' diarrhea were studied. In The Gambia, 195 tourists with acute diarrhea were randomized in a double-blind, controlled trial into three treatment groups: fleroxacin 400 mg for 1 day, fleroxacin 400 mg daily for 2 days, and placebo. Microbiology of stools was assessed only at recruitment. In the fleroxacin-treated groups, stool consistency was normal in 67% and 71% of the volunteers after 48 hours, as compared to 37% in the placebo group (p < 0.01). The time to total relief of diarrhea and of all symptoms was also significantly shorter in fleroxacin-treated patients. Adverse events, particularly slight neuropsychiatric reactions (headache, insomnia) were more frequent in the fleroxacin-treated groups (p < 0.05). There was no statistically significant difference in efficacy and tolerance if fleroxacin was administered for 1 or 2 days. A single dose of fleroxacin 400 mg may be recommended for the self-treatment of travelers' diarrhea.

Comparison of fleroxacin and amoxicillin in the treatment of uncomplicated urinary tract infections in women.

Fleroxacin, 400 mg, was compared with amoxicillin, 3,000 mg, each administered orally in a single dose, for the treatment of women with acute uncomplicated symptomatic urinary tract infections. A total of 142 patients were randomized to receive fleroxacin, and 147 patients to receive amoxicillin. Of these, 33 in the fleroxacin group and 39 in the amoxicillin group were considered bacteriologically evaluable. Cure at 5-9 days after treatment was achieved in 32 (97%) of the fleroxacin-treated patients and in 22 (56%) of the amoxicillin-treated patients (p < 0.001). For the most frequently isolated pathogen (Escherichia coli), all 24 isolates were eradicated in the fleroxacin group, as were 11 of 25 in the amoxicillin group. At 6 weeks after therapy, bacteriologic cure was maintained in 20 (95%) of the 21 evaluable patients who received fleroxacin and in 8 (89%) of 9 evaluable patients who received amoxicillin. There were no reinfections in either group. A total of 280 patients were assessed for safety. Clinical adverse events were reported in 32 (23%) of 137 patients in the fleroxacin group and in 19 (13%) of the 143 patients in the amoxicillin group. In both groups, the most common adverse effects were gastrointestinal, while adverse events involving the central nervous system were more frequent in patients who received fleroxacin. On the basis of this study, it appears that fleroxacin is demonstrably more effective than amoxicillin as single-dose therapy for uncomplicated urinary tract infection.

Fleroxacin versus norfloxacin in the treatment of urinary tract infections: a multicenter, double-blind, prospective, randomized, comparative study.

In a multicenter, double-blind, prospective, randomized, comparative study, fleroxacin, 400 mg once daily orally, was compared with norfloxacin, 400 mg twice daily orally. Each drug was given for 10 days to study efficacy and safety in the treatment of uncomplicated, recurrent, or complicated urinary tract infection (UTI). A total of 587 patients from 22 centers were enrolled and randomly assigned to fleroxacin (n = 291) or norfloxacin (n = 296). Of these, 163 patients in each group were included in the efficacy analysis, and 287 in the fleroxacin group and 292 in the norfloxacin group were included in the safety analysis. There was no difference between the two groups in terms of bacteriologic or clinical efficacy, with cure rates for each diagnostic subgroup of 93-100% in the fleroxacin group and 91-96% in the norfloxacin group. Superinfection, reinfection, or relapse, as well as development of resistance to the administered drugs, were infrequent and comparable in the two groups. Adverse events were documented in a significantly higher number of patients treated with fleroxacin and involved mainly the digestive system, the central nervous system, and the skin. However, > 90% of such adverse events were judged as mild or moderate in severity and did not lead to premature termination of treatment. Fleroxacin exhibited a clinical and bacteriologic efficacy comparable to that of norfloxacin in this group of patients, with cure rates similar to those of other 4-quinolones, suggesting a promising role for fleroxacin in the treatment of both uncomplicated and complicated UTIs. However, the higher incidence of adverse events with fleroxacin warrants further investigation with special focus on adverse reactions.

Comparison of intravenous fleroxacin with ceftazidime for treatment of complicated urinary tract infections.

Intravenous fleroxacin, 400 mg once daily, was compared with intravenous ceftazidime, 0.5-2 g three times a day or 1-2 g twice a day, administered for 4-21 days for treatment of complicated urinary tract infections (UTIs) due to susceptible organisms. Fleroxacin also was tested in an uncontrolled trial. The trial was a multicenter, randomized, open-label study of adults with pyelonephritis or signs and symptoms of UTI and complicating factors. In the controlled trial, 474 patients were randomly assigned in a 2:1 ratio to receive fleroxacin (n = 320) or ceftazidime (n = 154). The microbiologic criterion for diagnosis of UTI was the isolation of > or = 10(5) colony-forming units (CFU) of pathogenic bacteria/mL of urine. The efficacy analyses included 165 fleroxacin-treated and 82 ceftazidime-treated patients in the controlled trial and 97 patients in the uncontrolled trial. In the controlled trial, 317 fleroxacin-treated and 150 ceftazidime-treated patients were included in the safety analysis. In the controlled trial, the respective rates of bacteriologic cure (< or = 10(4) CFU/mL of urine 48-96 hours after first dose and 2-5 days posttherapy) were 94% (confidence interval [CI], 89-97%) and 95% (CI, 88-99%) in the fleroxacin and ceftazidime groups, and those of clinical cure were 86% (CI, 80-91%) and 89% (CI, 80-95%). Rates of clinical and bacteriologic cure in the uncontrolled study were 95%. In the controlled trial, 9% of the patients in each treatment group experienced one or more adverse events possibly or probably related to the study drug. The percentage of patients terminating therapy prematurely was higher in the fleroxacin than in the ceftazidime group. Once-daily dosing with 400 mg of intravenous fleroxacin was equivalent to a standard multidose regimen with respect to rates of bacteriologic and clinical cure in the treatment of complicated UTI.

Systemic antimicrobial therapy for skin and skin structure infections: comparison of fleroxacin and ceftazidime.

Intravenous fleroxacin, 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times a day or 1-2 g twice a day, for the treatment of skin and skin structure infections. Duration of treatment was 4-21 days. The study was a multicenter, unblinded comparison. Of the 316 patients enrolled, 212 were randomized to treatment with fleroxacin and 104 to ceftazidime (2:1 ratio); 92 fleroxacin-treated patients and 50 ceftazidime-treated patients were included in the standard analysis of efficacy. The most common diagnoses were wound infections and cellulitis, which affected 36% and 30% of the fleroxacin group, and 24% and 24% of the ceftazidime group, respectively. In the fleroxacin group, 82% of the infecting organisms were eradicated, and in the ceftazidime group, 79%. The overall rates of bacteriologic cure, by infection, were 79% for the fleroxacin group and 74% for the ceftazidime group, and those for clinical cure were 82% and 73%, respectively. It could not be concluded with 95% confidence that the two regimens resulted in equivalent cure rates because the range of between-group differences was outside the stipulated limits of +/- 15%. The percentage of patients with one or more adverse events was approximately twice as high (17% vs. 9%) in the fleroxacin group than in the ceftazidime group. The most frequent event in both groups was nausea. In this study, intravenous therapy with fleroxacin or ceftazidime produced similar bacteriologic and clinical cure rates, but the statistical requirements permitting a conclusion of equivalence at protocol levels were not met.

Multicenter trial of fleroxacin versus ceftriaxone in the treatment of uncomplicated gonorrhea.

In a multicenter, randomized, open, comparative trial, patients with uncomplicated gonorrhea were treated with 400 mg of oral fleroxacin or 250 mg of intramuscular ceftriaxone. A total of 458 men and 447 women were enrolled. Of these, 312 men (68%) and 245 women (55%) were evaluable for efficacy. The treatment groups were demographically similar. Among evaluable men, fleroxacin eradicated 154 of 155 (99%; 95% confidence interval [CI]: 98.1-100%) urethral and 2 of 2 pharyngeal infections, while ceftriaxone eradicated 156 of 156 (95% CI: 99.4-100%) urethral and 5 of 5 pharyngeal infections. Among evaluable women, fleroxacin eradicated 127 of 128 (99%; 95% CI: 97.7-100%) cervical, 20 of 20 anorectal, 16 of 16 urethral, and 7 of 7 pharyngeal infections, while ceftriaxone eradicated 108 of 108 (95% CI: 99.1-100%) cervical, 24 of 24 anorectal, 25 of 25 urethral, and 9 of 9 pharyngeal infections. Adverse events were reported by 68 (16%) of 426 subjects in the fleroxacin group and 20 (5%) of 380 in the ceftriaxone group (p < 0.0001). The most common adverse events reported by the patients who received fleroxacin were nausea (5%), headache (3%), and vaginitis (3%). One patient had severe vomiting, 19 participants had adverse reactions classified as moderate, and 48 patients had mild adverse reactions. Fleroxacin was highly effective in the treatment of uncomplicated gonorrhea and represents an oral alternative to ceftriaxone. Adverse events were more common with fleroxacin than with ceftriaxone.

Intravenous fleroxacin versus ceftazidime in the treatment of acute nonpneumococcal lower respiratory tract infections.

Fleroxacin, administered intravenously at a dosage of 400 mg once a day, was compared with ceftazidime, 0.5-2 g three times daily or 1-2 g twice daily, administered for 4-21 days, for treatment of nonpneumococcal lower respiratory tract infections. A total of 319 patients were enrolled and randomized to receive treatment with fleroxacin or ceftazidime in a 2:1 ratio. Of those enrolled, 68 fleroxacin- and 49 ceftazidime-treated patients were included in the efficacy analysis. The most common diagnoses were pneumonia or pneumonitis (47% of the fleroxacin group and 57% of the ceftazidime group) and exacerbation of chronic bronchitis (38% and 33%, respectively). In the fleroxacin group, 59 (88%) of 67 patients were bacteriologic cures, and in the ceftazidime group, 40 (90%) of 49 were bacteriologic cures. It could be concluded with 95% confidence that the bacteriologic outcomes, by infection, for the two groups were equivalent (fleroxacin, 88%; ceftazidime, 90%). The rates of clinical cure were 59 (88%) of 67 for the fleroxacin group and 40 (82%) of 49 in the ceftazidime group, but since the 95% confidence limit around the between-group difference was greater than the stipulated +/- 15%, it could not be concluded that the outcomes were equivalent. The percentage of patients who experienced adverse clinical or laboratory events was similar in the two treatment groups (12% and 13%). The bacteriologic outcomes, by infection, were equivalent for the two treatment groups. Protocol requirements permitting a determination of equivalence of the outcomes for clinical cure were not met, although the rates were similar.

Open trial of oral fleroxacin versus amoxicillin/clavulanate in the treatment of infections of skin and soft tissue.

In a multicenter, prospective, randomized trial, fleroxacin was compared with amoxicillin/clavulanate potassium (AMX/CP) for the treatment of infections of skin and soft tissue. Fleroxacin was given at a dosage of 400 mg once daily, and AMX/CP was given at a dosage of 500 mg/125 mg three times a day. Each was administered for 4-21 days. Adult patients with the clinical diagnosis of skin or soft tissue infections were eligible for enrollment. Patients were randomized in a 2:1 ratio. A total of 191 patients were enrolled; 126 took fleroxacin, and 65 took AMX/CP. Of these patients, 42 in the fleroxacin group and 26 in the AMX/CP group were evaluable for both clinical and bacteriologic efficacies. Patients with abscesses comprised the largest single category in each group. Principle reasons for exclusion included: patients lost to follow-up (17 [13%] fleroxacin, 12 [18%] AMX/CP); failure to isolate a causative pathogen (19 [15%] fleroxacin, 9 [14%] AMX/CP); and resistance to study drug (11 [9%] fleroxacin, 2 [3%] AMX/CP). Staphylococcus aureus was the most commonly isolated pathogen. Streptococcus group A, Staphylococcus coagulase-negative, Escherichia coli, and Proteus species, in decreasing order, were the next most common pathogens. Clinical and bacteriologic efficacy was excellent in both groups, with a cure rate of > or = 90%. There were two bacteriologic failures in each group. Patients taking fleroxacin complained of slightly more adverse events, which involved primarily the digestive and central nervous systems. The rate of withdrawal from the study because of adverse events was 4% in both groups. Fleroxacin, 400 mg given once daily, is safe and as effective as AMX/CP in the treatment of skin and soft tissue infections in adults.

Treatment of acute bacterial diarrhea: a multicenter international trial comparing placebo with fleroxacin given as a single dose or once daily for 3 days.

This study was designed to test the efficacy of 400 mg fleroxacin given orally as a single dose or once daily for 3 days against acute bacterial diarrhea. A group of 508 adults with acute diarrhea were entered into a randomized, double-blind, placebo-controlled, multicenter trial. Patients were examined and asked about numbers of liquid stools daily for 3 days and at 5 days after start of treatment. Repeat stool samples were obtained for culture on days 3 and 5 after start of treatment. A total of 332 patients showed stool cultures positive for bacterial pathogens sensitive to fleroxacin and completed their treatments. Patients treated with fleroxacin, both single-dose and 3-day regimens, showed faster clinical improvement than did placebo-treated patients, as shown by earlier cessation of diarrhea (p < 0.001) and reduction in mean number of loose stools per day on days 2, 3, and 5 after start of therapy (p < 0.05). Bacteriologic efficacy was demonstrated by negative stool cultures for initial pathogens on days 3 and 5 after start of therapy in 94% of patients treated with single doses of fleroxacin and in 93% of patients treated with three doses of fleroxacin as compared with 57% of patients treated with placebo (p < 0.001). Patients with cholera, shigellosis, and infections due to Vibrio parahaemolyticus showed both clinical and bacteriologic responses to fleroxacin treatment, whereas patients with salmonellosis showed only bacteriologic responses. The good overall clinical and bacteriologic responses of most patients with acute bacterial diarrhea of fleroxacin indicate that this convenient single-dose therapy should be advantageous for empiric treatment of certain diarrheal illnesses.

Comparison of oral fleroxacin with oral amoxicillin/clavulanate for treatment of skin and soft tissue infections.

Oral fleroxacin, 400 mg once a day, and oral amoxicillin/clavulanate potassium (AMX/CP), 400 mg/125 mg three times a day, administered for 4-21 days, were compared for efficacy and safety in the treatment of skin and soft tissue infections. A total of 113 patients were enrolled in a multicenter, randomized, double-blind trial; 57 were assigned to fleroxacin and 56 to AMX/CP. A total of 22 and 33 patients in the fleroxacin and AMX/CP groups, respectively, were evaluable for efficacy. The most common diagnoses were skin abscess (14; 62%) and wound infections (5; 23%) in the fleroxacin group and skin abscess (17; 52%) and skin ulcer (9; 27%) in the AMX/CP group. A total of 20 (91%) of the fleroxacin-treated patients and 29 (88%) of the AMX/CP-treated patients were bacteriologically cured (two fleroxacin- and one AMX/CP-treated patients developed super-infection). The eradication rate for Staphylococcus aureus was 100% (11 of 11) in the fleroxacin group and 89% (17 of 19) in the AMX/CP group; 18 (82%) of the fleroxacin group and 25 (76%) of the AMX/CP group were clinically cured. Adverse events were seen in 22% (12 of 54) of the fleroxacin group and 25% (13 of 53) of the AMX/CP group. None were serious. Bacteriologic and clinical cure rates and safety results for the two groups were similar. The small sample size precluded statistical analysis at the 95% confidence level.

Comparative efficacy and safety of oral fleroxacin and amoxicillin/clavulanate potassium in skin and soft tissue infections.

The objective of this open-label, randomized, multicenter study was to compare the efficacy and safety of fleroxacin, 400 mg administered orally once daily, and amoxicillin/clavulanate potassium (AMX/CP), 500 mg/125 mg administered orally three times daily, for 4-21 days to patients with skin and soft tissue infections (SSTIs). The specific diagnoses in both groups were primarily skin abscess, impetigo, and skin ulcer, as well as wound infection erysipelas, folliculitis, cellulitis, and lymphangitis. A total of 285 patients were randomized to treatment in a 2:1 ratio, 190 in the fleroxacin group and 95 in the AMX/CP group. Adult male or female inpatients or outpatients were included in the trial and were followed up after 3-5 days of therapy and 3-9 days after completion of therapy for assessment of bacteriologic, clinical, and safety parameters. The most frequently isolated pathogen in both treatment groups was Staphylococcus aureus. Bacteriologic cures were observed in 87 (76%) of 115 evaluable patients in the fleroxacin group and in 41 (72%) of 57 evaluable patients in the AMX/CP group. Clinical cure was seen in 86 (75%) of 114 patients in the fleroxacin group and 45 (79%) of 57 patients in the AMX/CP group. Clinical adverse events related to the trial medication were reported by 40 (21%) of 189 patients in the fleroxacin group and by 16 (17%) of 95 patients in the AMX/CP group. In both groups, most adverse events were mild or moderate in severity and involved the digestive system (primarily diarrhea, nausea, and vomiting). In the fleroxacin group, adverse events affecting the central nervous system (mainly dizziness, insomnia, somnolence) also were reported. In this study, both fleroxacin and amoxicillin/clavulanate potassium were effective and well tolerated in the treatment of skin and soft tissue infections.

Fleroxacin clinical pharmacokinetics.

Fleroxacin is a new member of the class of fluoroquinolones. The drug has good activity (i.e. minimum inhibitory concentrations at less than 2 mg/L against 90% of strains) against a wide range of Gram-positive and Gram-negative bacteria. High performance liquid chromatography is used to determine concentrations of fleroxacin and its metabolites in biological fluids. Absorption of orally ingested drug is rapid as the peak plasma concentration of approximately 5 mg/L is reached in 1 to 2h after a single dose of 400mg. The systemic availability is close to 100%. Fleroxacin is poorly bound to plasma proteins (23%) and exhibits excellent tissue distribution. Renal clearance accounts for 60 to 70% of elimination. The drug is metabolised to form antimicrobially active N-demethyl-fleroxacin and inactive N-oxide-fleroxacin. In multiple dose studies the accumulation ratio of a once-daily dosage regimen is about 1.3, as predicted from the elimination half-life of 10 to 12h. Compared with ciprofloxacin, fleroxacin has a greater systemic availability and a longer half-life. Fleroxacin concentrations are higher in elderly patients, but further studies are needed to establish whether a dosage reduction should be recommended for this age group. In patients with renal disease dosage adjustment is recommended since a decreased renal clearance of fleroxacin leads to a significant prolongation of the elimination half-life. Fleroxacin is only poorly eliminated by peritoneal dialysis or haemodialysis. The most important drug-drug interaction is a decrease in systemic availability of fleroxacin after ingestion of aluminium- or magnesium-containing antacids. There is no evidence of a significant interaction between fleroxacin and theophylline. Only limited data are available on adverse reactions of fleroxacin. The most important adverse effects appear to be photosensitivity and a dose-dependent incidence of central nervous system reactions including sleep disorders.

Intravenous fleroxacin versus ceftazidime for lower respiratory tract and skin and soft-tissue infections.

Fleroxacin, a new quinolone antimicrobial agent, was evaluated as part of a multicenter, comparative, open-label, randomized trial with ceftazidime in the treatment of lower respiratory tract infections and skin and soft-tissue infections. After written informed consent was obtained, 20 patients were entered at our center. Twelve patients were assigned to the fleroxacin group; 6 in each infection category. Of these 12 patients, 2 with pneumonia and 3 with skin and soft-tissue infection were not clinically evaluable. The mean duration of therapy was 5.7 +/- 3.0 days in the fleroxacin group versus 7.9 +/- 2.0 days in the ceftazidime group. The gram-positive organisms responsible for those infections not evaluable were methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and group F streptococcus, all of which were resistant to fleroxacin. In total, 6 gram-positive isolates were resistant to fleroxacin. All but 2 S aureus isolates were susceptible to ceftazidime. Adverse reactions in both groups were negligible. Fleroxacin was found to be as effective as ceftazidime against a variety of gram-negative pathogens, but local susceptibility patterns for quinolones should be checked before empiric use of fleroxacin against gram-positive pathogens such as streptococci.

Clinical evaluation of fleroxacin in the treatment of bone and joint infections.

The objective of this open label, non-comparative study was to evaluate the efficacy and safety of fleroxacin 400mg administered orally once daily to patients with acute osteomyelitis and/or acute septic arthritis. Nineteen patients (10 males and 9 females) were evaluable for the analysis of clinical efficacy and safety. Of these, 7 (36.8%) had osteomyelitis and 12 (63.2%) had septic arthritis. Bacteriological cures were reported in 6 of 7 patients (85.7%) with osteomyelitis and in 8 of 11 patients (72.7%) with septic arthritis. The median duration of treatment for the clinical cures in osteomyelitis and septic arthritis were 29.5 days and 46 days respectively. The eradication rate for the most common pathogens, Salmonella enteritidis and Staphylococcus aureus were 77.7% and 80.0%, respectively. The clinical response was cure in 4 of 7 patients (57.1%) evaluable for osteomyelitis, and in 9 of 12 patients (75.0%) evaluable for septic arthritis at the three-month follow-up after treatment. Adverse reactions were minimal. It is concluded that fleroxacin appears to be an effective and safe in the treatment of acute osteomyelitis and acute septic arthritis.

[Encephalopathy induced by fleroxacin in a patient with Machado-Joseph disease].

Convulsive seizure with unconciousness is an adverse effect of new quinolone antibiotics including fleroxacin. A block of GABA receptor in CNS has been reported as pathomechanism. A 48-year-old female patient with Machado-Joseph disease (MJD) had encephalopathy induced by fleroxacin. She revealed unconsciousness after the administration of fleroxacin (200mg/day) for three days. Electroencephrogram (EEG) showed diffuse slow waves. The administration was discontinued and her consciousness became clear after a day. The abnormal findings on EEG disappeared gradually. The concentrations of fleroxacin were within normal limits in serum and cerebrospinal fluid. The patient with MJD might have a tendency to develop encephalopathy by fleroxacin, because the GABA-ergic nervous system could be involved in MJD.

[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.