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Biomedical subjects

K G Naber

Publications and source records attributed to K G Naber.

At least 19 recordsLinked to original sources
PubMed1999

Ciprofloxacin once versus twice daily in the treatment of complicated urinary tract infections. German Ciprofloxacin UTI Study Group.

Ciprofloxacin is considered to be the standard treatment for patients with complicated urinary tract infections (UTI). This multicentre, randomized clinical study was designed to compare a once-daily regimen with 500 mg to the usual twice-daily regimen with 250 mg orally for 7-20 days. A total of 215 patients with significant bacteriuria (> or = 10(5) c.f.u./ml for females and > or = 10(4) c.f.u./ml for males) were included in the study. Eradication of bacteriuria was shown in 84.0% of patients treated with 500 mg q.i.d. and in 90.9% of patients treated with 250 mg b.i.d. Clinical cure or improvement was achieved in 97.3% of those treated with 500 mg q.i.d. versus 95.5% of those treated with 250 mg b.i.d. More superinfections occurred in patients treated with 500 mg q.i.d., mostly caused by gram-positive cocci. The statistical analysis concerning the elimination of bacteriuria using the 95% confidence interval showed a difference of up to 18.4% between the two treatment groups in favour of the 250-mg b.i.d. regimen. Ciprofloxacin was well tolerated with only mild to moderate side-effects (mostly gastrointestinal) in 8% of the patients. When using ciprofloxacin in patients with complicated UTI, its administration in two divided doses can be further recommended as a standard regimen.

Anti-Infective Agents↗
PubMed1998

Urinary bactericidal activity and pharmacokinetics of enoxacin versus norfloxacin and ciprofloxacin in healthy volunteers after a single oral dose.

In an open, randomised monocentric crossover study in six male and six female healthy volunteers, the urinary antibacterial activity and pharmacokinetics of enoxacin, norfloxacin and ciprofloxacin were assessed. Urine was collected up to 6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg/l) demonstrated the highest peak concentration (median) in the urine (0-6 h), followed by ciprofloxacin (237 mg/l) and norfloxacin (157 mg/l) as determined by the HPLC assay. The total amount (mean) excreted by the kidneys as parent drugs were as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and norfloxacin 22% of dose. The mean plasma concentrations decreased from 1 to 4 h after administration for enoxacin from 1.9 to 1.4 mg/l, for ciprofloxacin from 2.0 to 0.8 mg/l and for norfloxacin from 1.3 to 0.5 mg/l. The antibacterial activity in urine was determined as urinary bactericidal titers (UBT), i.e. the highest 2-fold dilution of urine still bactericidal for the reference organism (E. coli ATCC 25,922) and for five uropathogens with minimal inhibitory (MIC) and bactericidal (MBC) concentrations ranging from highly susceptible to resistant cultured from the urine of patients with complicated urinary tract infections (UTI). For the E. coli ATCC 25,922, the organism with the lowest MIC, median UBTs of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of enoxacin for 2 days, decreasing from 1:256 to 1:4, and that of norfloxacin for 2 days, decreasing from 1:128 to 1:2. For the five uropathogens (with increasing MICs: K. pneumoniae, P. mirabilis, E. coli (resistant to nalidixic acid), P. aeruginosa and E. faecalis), the UBTs decreased in general, according to MICs, demonstrating the same relations of UBTs for ciprofloxacin (highest) versus enoxacin (medium) versus norfloxacin (lowest) with one exception (P. mirabilis) for which norfloxacin showed higher UBTs than enoxacin. The minimal urinary bactericidal concentrations (MUBC), as derived from urinary concentrations, and UBTs showed a fairly wide inter- and intraindividual range and were generally higher than the corresponding MBCs as determined in Mueller Hinton broth. In conclusion, according to antibacterial activity in urine determined as UBTs, a single oral dose of ciprofloxacin (500 mg) generally resulted in the highest and longest-lasting UBTs followed by that of enoxacin (400 mg) and norfloxacin (400 mg). A dose of 400 mg enoxacin can be expected to be at least equivalent if not superior to that of 400 mg norfloxacin. Only enoxacin and ciprofloxacin exhibited urinary bactericidal activity against all test organisms up to 12 h in all individuals. Therefore, clinical comparison of enoxacin versus ciprofloxacin in the treatment of complicated UTI could be worth testing.

Administration, Oral↗
PubMed1998

Urinary excretion and bactericidal activities of a single oral dose of 400 milligrams of fleroxacin versus a single oral dose of 800 milligrams of pefloxacin in healthy volunteers.

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects' urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 micrograms/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.

Administration, Oral↗
PubMed1998

The role of antibiotics in the treatment of chronic prostatitis: a consensus statement.

Practical guidelines for the diagnosis and treatment of chronic prostatitis are presented. Chronic prostatitis is classified as chronic bacterial prostatitis (culture-positive) and chronic inflammatory prostatitis (culture-negative). If chronic bacterial prostatitis is suspected, based on relevant symptoms or recurrent UTIs, underlying urological conditions should be excluded by the following tests: rectal examination, midstream urine culture and residual urine. The diagnosis should be confirmed by the Meares and Stamey technique. Antibiotic therapy is recommended for acute exacerbations of chronic prostatitis, chronic bacterial prostatitis and chronic inflammatory prostatitis, if there is clinical, bacteriological or supporting immunological evidence of prostate infection. Unless a patient presents with fever, antibiotic treatment should not be initiated immediately except in cases of acute prostatitis or acute episodes in a patient with chronic bacterial prostatitis. The work-up, with the appropriate investigations should be done first, within a reasonable time period which, preferably, should not be longer than 1 week. During this period, nonspecific treatment, such as appropriate analgesia to relieve symptoms, should be given. The minimum duration of antibiotic treatment should be 2-4 weeks. If there is no improvement in symptoms, treatment should be stopped and reconsidered. However, if there is improvement, it should be continued for at least a further 2-4 weeks to achieve clinical cure and, hopefully, eradication of the causative pathogen. Antibiotic treatment should not be given for 6-8 weeks without an appraisal of its effectiveness. Currently used antibiotics are reviewed. Of these, the fluoroquinolones ofloxacin and ciprofloxacin are recommended because of their favourable antibacterial spectrum and pharmacokinetic profile. A number of clinical trials are recommended and a standard study design is proposed to help resolve some outstanding issues.

Anti-Bacterial Agents↗
PubMed1997

Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women.

PURPOSE: We evaluated and compared the efficacy of post-intercourse and daily oral ciprofloxacin prophylaxis against recurrent lower urinary tract infections in 135 sexually active premenopausal women. MATERIALS AND METHODS: Post-intercourse (group 1, 70 patients) and daily (group 2, 65 patients) prophylactic regimens of 125 mg. ciprofloxacin were started following a curative, conventional treatment of the initial acute urinary tract infection. Prophylaxis was maintained for 12 months and during this period patients were followed clinically and bacteriologically with urine and introital samples. Patients were subsequently followed for an additional year after the end of preventive treatment. RESULTS: While 3.67 urinary tract infections per patient in group 1 and 3.74 in group 2 occurred during an identical mean time of 12.2 months before start of the corresponding prophylactic regimen, only 0.043 infection per patient in group 1 and 0.031 in group 2 developed during prophylaxis (p < 0.0001). Before prophylaxis 86% of the vaginal vestibule cultures yielded gram-negative Enterobacteriaceae, equally distributed between both treatment arms, compared to 5.6% and 2.5% during postcoital and daily prophylaxis, respectively. The overall improvement in the incidence of the urinary infections per patient and the rate of introital colonization with enteric gram-negative bacteria was maintained after the end of prophylaxis, with a mean incidence of infections of 0.44 per patient (occurring in 34% of the total patient population), while 36% of all women had abnormal introital colonization. CONCLUSIONS: Long-term post-intercourse prophylaxis with ciprofloxacin proved to be equally effective as daily prophylaxis, and the major advantage of the former therapy was use of only a third of the amount of drug consumed in daily prophylaxis.

Adolescent↗
PubMed1997

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.

Aged↗
PubMed1996

Comparative efficacy of sparfloxacin versus ciprofloxacin in the treatment of complicated urinary tract infection.

A total of 686 adult patients with complicated urinary tract infections were enrolled in a double-blind, randomised, multicentre study to compare sparfloxacin (200 mg loading dose on day 1 followed by 100 mg daily) with ciprofloxacin (500 mg orally twice daily) for 10 to 14 days. Urinary tract infection was defined as pyuria and bacteriuria (cfu > or = 10(5)/mL). Evaluations were performed at four time-points. The clinical efficacy of the two antibacterial agents was equivalent at the end of treatment: clinical cure in 88.6% of the intent-to-treat population and 87.3% in the evaluable population treated with sparfloxacin compared to 85.4% and 84.8% of the intent-to-treat and evaluable populations, respectively, treated with ciprofloxacin. The clinical results were also equivalent at follow-up. The bacteriological efficacy of the two agents was not equivalent. At the end of treatment, bacteriological cure was observed in 72.6% of the intent-to-treat and 72.1% of the evaluable populations treated with sparfloxacin and in 81.4% and 80.8% of the intent-to-treat and evaluable populations, respectively, treated with ciprofloxacin. The difference was primarily because of a higher number of persisting pathogens, which included Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and enterococci, which exhibited moderate susceptibility to sparfloxacin. Tolerability was similar in the two treatment groups.

Adolescent↗
PubMed1996

Fleroxacin overview.

Fleroxacin is a new oral and intravenous trifluorinated 4-quinolone, which acts by inhibiting the essential bacterial enzyme DNA gyrase. Fleroxacin exhibits a broad spectrum of action, characterized by pronounced activity against aerobic gram-negative bacteria, but also against gram-positive pathogens such as staphylococci. Fleroxacin is distinguished by its excellent bioavailability, high concentrations in the plasma and other body fluids, good tissue penetration, and a long half-life of 10-12 h, thus allowing once-a-day administration. A single oral dose of 400 mg fleroxacin is effective in uncomplicated cystitis in women, uncomplicated gonococcal infections, bacterial enteritis, and traveler's diarrhea. A single daily dose of 200 mg administered for 3 days is effective in uncomplicated urinary tract infection (UTI), while longer treatment and higher doses may be required in acute uncomplicated pyelonephritis and complicated UTI. Skin, soft tissue, bone and joint infections, and lower respiratory tract infections including exacerbation of chronic bronchitis and non-pneumococcal pneumonia are further indications for fleroxacin.

Animals↗
PubMed1995

Effect of probenecid on the distribution and elimination of ciprofloxacin in humans.

OBJECTIVE: Probenecid-sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers. METHODS: A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (M1) by reversed-phase HPLC. RESULTS: Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume of distribution did not differ significantly with and without coadministration of probenecid. Peak plasma concentration, plasma area under the concentration-time curve, and elimination half-life of M1 were increased (p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma. CONCLUSIONS: Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug-drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.

Adult↗
PubMed1995

Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers.

The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat, and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, distribution of enoxacin in saliva was found to be time and pH dependent. In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics.

Adult↗
PubMed1994

Clinical significance and spread of fluoroquinolone resistant uropathogens in hospitalised urological patients.

The minimum inhibitory concentrations (MIC) of ciprofloxacin were determined for 441 uropathogens from patients with complicated and/or hospital acquired urinary tract infections (UTI). None of the Enterobacteriaceae was resistant (MIC > or = 4 mg/l), but 21.7% of enterococci, 28.3% of Pseudomonas spp. and 38.5% of staphylococci were. Subtyping of the strains revealed that with staphylococci there was no clonal spread of resistant strains. In the case of enterococci and Pseudomonas spp., however, cross infections played a major role (46% and 40% respectively). In a retrospective analysis of 370 UTI episodes caused by Pseudomonas aeruginosa (74), enterococci (185) or staphylococci (111) there was no difference between sensitive and resistant strains with respect to clinical aspects and rates of elimination by appropriate anti-bacterial therapy. The rates of spontaneous disappearance without antibacterial therapy ranged from 28% in the case of P. aeruginosa up to 63% in the case of coagulase-negative staphylococci. This implies that especially in UTI caused by gram-positive cocci an indication for antibacterial therapy should be weighted thoroughly and fluoroquinolones should only be used in accordance with sensitivity testing.

Anti-Infective Agents↗
PubMed1993

Fleroxacin versus ofloxacin in patients with complicated urinary tract infection: a controlled clinical study.

This prospectively randomized study compared fleroxacin, 400 mg once daily, with ofloxacin, 200 mg twice daily, administered orally for 7-14 days for the treatment of complicated urinary tract infection (UTI) in hospitalized, urologic patients. A total of 80 patients were enrolled in the study. Of these, 30 patients treated with fleroxacin and 35 treated with ofloxacin could be evaluated for therapeutic efficacy. Of the causative organisms, 29 of 30 in the fleroxacin group and 33 of 35 in the ofloxacin group were eliminated. One relapse occurred in the fleroxacin group and two in the ofloxacin group. Reinfection with gram-positive isolates was seen in five patients treated with fleroxacin and in one treated with ofloxacin. Thus, the cure rate was 24 (80%) of 30 in the fleroxacin group and 32 (91%) of 35 in the ofloxacin group. In general, both antibiotics were well tolerated. Four patients in the fleroxacin group and five in the ofloxacin group claimed mild, possibly drug-related adverse effects. The treatment of one patient in the ofloxacin group had to be discontinued because of an adverse effect (headache). Both fleroxacin and ofloxacin are effective and well-tolerated antibiotics for the treatment of complicated UTI.

Adult↗