In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 47, No. 12 ( 2003-12), p. 3789-3794
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.47.12.3789-3794.2003
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2003
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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