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

Well, Michaela; Naber, Kurt G.; Kinzig‐Schippers, Martina; Sörgel, Fritz

doi:10.1016/s0924-8579(98)00014-4

Cited by 40 publications

(6 citation statements)

References 4 publications

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“…This is expected given fosfomycin's bactericidal activity and is consistent with previous studies (17). Therefore, barring any influence of urine on bacterial growth and/or antimicrobial activity, the UBT should be roughly equal to the corresponding urine drug concentration divided by the pathogen's MIC for bactericidal drugs (18)(19)(20)(21). In the present study, the average urine concentrations of fosfomycin during the 4-to 8-h collection interval were Ͼ400 mg/ liter, and the MICs against the two wild-type E. coli strains were 4 and 2 mg/liter, respectively, which should translate into UBT values of Ն100 to 200.…”

Section: Discussionsupporting

confidence: 82%

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

Wenzler

Meyer

Bleasdale

et al. 2020

Antimicrob Agents Chemother

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The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant’s drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.)

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Section: Discussionsupporting

confidence: 82%

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

Wenzler

Meyer

Bleasdale

et al. 2020

Antimicrob Agents Chemother

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“…By using the same indicator organisms, i.e. E. coli ATCC 25922, E. coli 523 NalR, K. pneumoniae 595, P. mirabilis 414, P. aeruginosa 568 and E. faecalis 60, the AUBT 24 calculated for ciprofloxacin at the pH values of freshly voided urine following an oral dose of 500 mg were within the same range as, or tended to be lower than, those calculated for 800 mg finafloxacin [16,30,31,37]. A considerable intra- and interstudy variability is evident from the published data.…”

Section: Discussionmentioning

confidence: 98%

“…Higher urinary concentrations of magnesium, which are commonly in the range of 8–10 m M , in combination with a low pH value account in large part for this reduction in activity [7,22,23]. For the treatment of UTI, the bactericidal activity of an antibacterial agent measured in urine is therefore considered to be a helpful pharmacodynamic parameter [16,17,30] that has also been shown to be accurate and reproducible [31]. The urine AUC/minimal bactericidal concentration (MBC) ratio relates directly to the AUBT because the reciprocal UBT indicate the urinary concentrations divided by the MBC as determined in urine.…”

Section: Discussionmentioning

confidence: 99%

“…A considerable intra- and interstudy variability is evident from the published data. For example, in three different studies, the mean ciprofloxacin AUBT 24 for E. coli 523 NalR ranged from 528 to 1,632 h, and those for E. coli ATCC 25922 ranged from 7,680 to 12,288 h [16,31,37]; the intrastudy variability was also comparably high, ranging from 342 to 996 h for E. coli ATCC 25922, and from 120 to 570 h for E. coli 523 NalR [16]. This high variability of UBT and AUBT values is probably due to the highly variable urinary pH values affecting activity, as well as highly variable urinary concentrations recorded in this and all other UBT studies quoted.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Pharmacokinetics and Bactericidal Activity of Finafloxacin (200 and 800 mg) in Healthy Volunteers Receiving a Single Oral Dose

Wagenlehner

Wagenlehner²,

Blenk³

et al. 2011

Chemotherapy

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Background: Finafloxacin is a novel 8-cyano-fluoroquinolone under investigation for treatment of urinary tract infection. Methods: Urinary concentrations and urinary bactericidal titers (UBT) of finafloxacin 200- and 800-mg single doses in 6 healthy volunteers were measured up to 48 h. UBT were determined for a reference strain and 9 selected clinical uropathogens at the pH of native, acidified (pH 5.5) and alkalinized (pH 8.0) urine. Results: The mean maximum urine concentrations for 200 and 800 mg finafloxacin were 69.3 mg/l (0–2 h) and 150 mg/l (4–8 h). Median UBT were between 0 and 1:>2,048 and were in general agreement with minimal inhibitory concentrations of strains and urinary pH values. UBT in alkaline urine were significantly lower than those in native or acidic urine, except for Enterococcus faecalis.Conclusions: Finafloxacin exhibited significant bactericidal activity against susceptible uropathogens. The urinary bactericidal activity of finafloxacin was enhanced in acidic urine and significantly lower in alkaline urine.

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“…Results are shown in Table 2. It exhibited good correlation coefficients (0.9913-0.9995) for the concentration range of 40-1000 g L −1 [30][31][32][33][34]. The LOD varied from 7.4 to 31.5 g L −1 at a signal-to-noise (S/N) of 3.…”

Section: Application To Real Samplesmentioning

confidence: 92%

Application of single drop liquid–liquid–liquid microextraction for the determination of fluoroquinolones in human urine by capillary electrophoresis

Gao

Chen

et al. 2011

Journal of Chromatography B

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

Cited by 40 publications

References 4 publications

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

Urinary Pharmacokinetics and Bactericidal Activity of Finafloxacin (200 and 800 mg) in Healthy Volunteers Receiving a Single Oral Dose

Application of single drop liquid–liquid–liquid microextraction for the determination of fluoroquinolones in human urine by capillary electrophoresis

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