Concentrations in Plasma, Urinary Excretion, andBactericidal Activity of Linezolid (600 Milligrams) versusThose of Ciprofloxacin (500 Milligrams) inHealthy Volunteers Receiving a Single OralDose

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 antibioticfree 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.The incidence of nosocomial and complicated urinary tract infections (UTIs) caused by gram-positive bacteria resistant to the antibiotics available at present is increasing (7,19). Thus, gram-positive bacteria deserve more attention today than they did in the past. Linezolid, the first member of the class of oxazolidinones to be marketed, is active against gram-positive bacteria resistant to other drugs (1,4,5,8,9,29) and ther...

Effect of Ciprofloxacin-Induced Prostaglandin E2on Interleukin-18-Treated Monocytes

“…TOPO II-targeting drugs are apoptosis-inducing drugs, and both isoforms of TOPO II, alpha and beta, are inhibited by the chemotherapeutic agent etoposide (22). We found that etoposide had no effect on COX expression, adhesion molecule expression, and cytokine production in the absence and presence of IL-18 (data not shown).…”

Urinary Bactericidal Activity of Extended-Release Ciprofloxacin (1,000 Milligrams) versus Levofloxacin (500 Milligrams) in Healthy Volunteers Receiving a Single Oral Dose

“…The drug concentrations in serum and urine samples were measured by comparison with a serum and urine calibration row, respectively (24). MICs, minimal bactericidal concentrations (MBCs), and urinary bactericidal titers were determined as published previously (17,26).The bacterial strains used in this study and ciprofloxacin and levofloxacin MICs are depicted in Table 1. The MBCs of levofloxacin and ciprofloxacin were similar to the corresponding MICs for all strains tested.…”

“…The drug concentrations in serum and urine samples were measured by comparison with a serum and urine calibration row, respectively (24). MICs, minimal bactericidal concentrations (MBCs), and urinary bactericidal titers were determined as published previously (17,26).…”

In Vitro and In Vivo Activities of a Bi-Aryl Oxazolidinone, RBx 11760, against Gram-Positive Bacteria

“…Oxazolidinones active against Gram-positive bacteria may be considered for use in the treatment of cUTIs because of the presence of Gram-positive uropathogens (45,46). In a mouse pyelonephritis infection model, RBx 11760 and linezolid showed comparable efficacy, resulting in stasis when administered at 20 mg/kg four times a day.…”