Concentrations in plasma, urinary excretion, and bactericidal activity of linezolid (600 milligrams) versus those of ciprofloxacin (500 milligrams) in healthy volunteers receiving a single oral dose.
In a randomized crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 600 mg of linezolid or 500 mg of ciprofloxacin to assess the concentrations in plasma (up to 24 h), urinary excretion (by high-pressure liquid chromatography), and bactericidal titers in urine (UBT) at intervals up to 120 h. The mean maximum concentration of linezolid in plasma was 13.1 mg/liter, and that of ciprofloxacin was 2.46 mg/liter. The median cumulative levels of renal excretion of the administered dose of the parent drug were 44% for linezolid (range, 28 to 47%; mean +/- standard deviation, 40% +/- 7.8%) and 43% for ciprofloxacin (range, 20 to 56%; mean +/- standard deviation, 40% +/- 9.3%). The UBTs, i.e., the highest twofold dilution (with antibiotic-free urine used as the diluent) of urine that was still bactericidal, were determined for a reference strain and five gram-positive clinical uropathogens for which the MICs of linezolid and ciprofloxacin were as follows: Staphylococcus aureus ATCC 27278, 2 and 0.25 mg/liter, respectively; Staphylococcus aureus (methicillin susceptible), 1 and 16 mg/liter, respectively; Staphylococcus aureus (methicillin resistant), 2 and 64 mg/liter, respectively; Staphylococcus saprophyticus (methicillin susceptible), 1 and 0.25 mg/liter, respectively; Enterococcus faecalis, 2 and 1 mg/liter, respectively; and Enterococcus faecium, 2 and 1 mg/liter, respectively. The median UBTs of linezolid measured within the first 6 h were 1:96 for each of the two enterococcal strains and between 1:128 and 1:256 for the four staphylococcal strains. The median UBTs of ciprofloxacin were 1:64 for the two enterococcal strains; between 1:384 and 1:512 for the two ciprofloxacin-susceptible strains; and 1 (bactericidal activity of undiluted urine only) and 1:2 for the two resistant staphylococcal strains, respectively. The areas under the UBT-time curve (AUBT) for linezolid and ciprofloxacin showed no statistically significant (P<0.05) differences except for a better AUBT for linezolid for the two ciprofloxacin-resistant staphylococcal strains. For linezolid there were no statistically significant differences in UBTs or AUBTs for ciprofloxacin-susceptible and -resistant strains. Thus, the bactericidal activities of linezolid and ciprofloxacin against susceptible strains in urine were comparable, whereas linezolid also exhibited the same good bactericidal activity against ciprofloxacin-resistant strains. Therefore, linezolid should be tested for use as empirical treatment for complicated urinary tract infections due to gram-positive uropathogens in an appropriate clinical trial.
Wagenlehner
Florian M E
FM
Department of Urology, St. Elisabeth Hospital, Straubing, Germany.
Wydra
Stephan
S
Onda
Hajime
H
Kinzig-Schippers
Martina
M
Sörgel
Fritz
F
Naber
Kurt G
KG
D000081:Acetamides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001419:Bacteria / Q000187:drug effects; D002138:Calibration; D002511:Cephalosporins / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011786:Quality Control; D015610:Serum Bactericidal Test
D000081:Acetamides; D000890:Anti-Infective Agents; D002511:Cephalosporins; D023303:Oxazolidinones; D002939:Ciprofloxacin; D000069349:Linezolid