Urine bactericidal activity of pefloxacin versus norfloxacin in healthy female volunteers after a single 800-mg oral dose

Abstract

In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strain Escherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each of E. coli resistant to nalidixic acid (Nal-R), Klebsiella pneumoniae Nal-R, and Staphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate of Enterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs.

Urinary Excretion and Bactericidal Activities of Gemifloxacin and Ofloxacin after a Single Oral Dose in Healthy Volunteers

“…However, the bactericidal and inhibitory activities of antimicrobial agents derived from the comparison of data derived from cultures in nutrient broth and individual concentrations in urine sometimes hardly reflect the variability of individual responses to the treatment of UTIs in clinical situations. The estimation of UBTs by use of dilutions with the individual's antimicrobial-free urine may be considered more appropriate for approximation of the expected in vivo activity of an antimicrobial agent (7,8,10,13). Contrary to the results of MIC testing in vitro, the estimation of UBTs yielded higher values for gemifloxacin only for gram-positive strains, whereas for gram-negative uropathogens, UBTs were higher for ofloxacin.…”

“…Determination of UBTs. A logarithmic serial dilution (dilution range, 1:2 to 1:1,024) was prepared by taking a 1:1 mixture of the urine sample and the individual's antimicrobial-free urine collected prior to drug administration (7,10,13). UBTs were then determined by microdilution, with each well of the microplates containing 100 l of the prepared dilution.…”

“…As the antibacterial activities of fluoroquinolones may be inhibited in urine in relation to its pH and contents (8), the antibacterial activities of these agents should be assessed directly in urine. To combine pharmacokinetic and pharmacodynamic properties, the concentrations in urine and urinary bactericidal titers (UBTs) for isolates of the most common uropathogenic bacterial species were determined to approximate more closely their antibacterial activities at the site of infection (7,10,13). In the phase I comparative study with a crossover design described here, these parameters were determined after administration of a single oral dose of gemifloxacin (320 mg) and a single oral dose of ofloxacin (400 mg) to healthy volunteers.…”

Infections à Staphylococcus saprophyticus

“…MIC values of main antibacterial agents against 101 S. saprophyticus isolates [45]. des publications récentes ont mis en évidence l'efficacité clinique des fluoroquinolones dans le traitement des infections urinaires non compliquées de la femme jeune, probablement en raison des taux élevés atteints dans l'urine [53]. S. saprophyticus présente une résistance naturelle à la fosfomycine, mais le niveau de résistance à la fosfomycine est variable, avec des différences selon les études (de 80,5 à 97 %).…”

Pharmacokinetics of pefloxacin mesylate in human urine using capillary electrophoresis electrochemiluminescence detection

“…At present, HPLC and bactericidal method [3][4][5] are the primary means for measurements of pharmacokinetics of PM. However, because the mobile phase used in HPLC usually contains acetonitrile which is a well known toxic substance, it is important to develop alternative method with innocuity, high sensitivity and selectivity for studying pharmacokinetics of PM.…”