Pharmacodynamics of Finafloxacin, Ciprofloxacin, and Levofloxacin in Serum and Urine against TEM- and SHV-Type Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae Isolates from Patients with Urinary Tract Infections

Abstract

The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing Escherichia coli and Klebsiella pneumoniae strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count–versus–time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log10 titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.

Sanjin Tablets for Acute Uncomplicated Lower Urinary Tract Infection (Syndrome of Dampness-Heat in the Lower Jiao): Protocol for Randomized, Double-Blind, Double Dummy, Parallel Control of Positive Drug, Multicentre Clinical Trial

“…All researchers are clinical doctors and receive standardized training for the diagnostic interview before the start of the trial. Levofloxacin tablets are licensed for UTI with proven curative effect and safety [32]. Therefore, levofloxacin have been selected as the active control medicine.…”

Sanjin tablets for acute uncomplicated lower urinary tract infection (syndrome of dampness-heat in the lower jiao): protocol for randomized, double-blind, double dummy, parallel control of positive drug, multicentre clinical trial

“…All researchers are clinical doctors and receive standardized training for the diagnostic interview before the start of the trial. Levofloxacin tablets are licensed for UTI with proven curative effect and safety [32].Therefore, levofloxacin had been selected as the active control medicine. Participants in the experimental group will receive SJT plus LT placebo orally four times a day for 7 days.…”

Mesostructured ZnO/Au nanoparticle composites with enhanced photocatalytic activity

“…The photocatalytic degradation of ciprofloxacin and levofloxacin (isoelectric points (zwitterion): 7.4 and 6.8, respectively) [18], applying the ZnO/Au composite nanowires as catalysts, was studied using a continuous flow reactor. For comparative studies, neat ZnO nanotubes and Degussa P25 (TiO2 based photocatalyst) were used.…”

“…For ciprofloxacin the isoelectric point of the zwitterion is at a pH value of 7.4. [18] Thus, a catalyst bearing a positive surface charge at a pH of 8 is advantageous, as this will enhance the electrostatic interactions between antibiotic and catalyst. Previous studies showed that in contrast to Degussa P25, a TiO2 catalyst with its point of zero charge (PZC) at a pH of 6.9, ZnO fulfils this requirement as its PZC is 9.2.…”