Pharmacokinetics and Pharmacodynamics of Gatifloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a Granulocyte-Rich Exudate

Abstract

The pharmacokinetics of gatifloxacin were assessed in serum and in skin blister fluid (SBF), as was the pharmacodynamic activity in SBF. Five hours after a single dose of gatifloxacin, SBF killed 2.5 logs of Streptococcus pneumoniae and 1.5 log of Staphylococcus aureus during a 2-h incubation ex vivo.Gatifloxacin is active against gram-positive and gram-negative organisms, including anaerobes (5, 17); Mycoplasma, Chlamydia, and Legionella (14,16); and mycobacteria (9). Like other quinolones, gatifloxacin penetrates well into leukocytes, which can deliver active drug to sites of infection and play an important role in the treatment of intracellular pathogens (21).We analyzed the pharmacokinetic parameters of gatifloxacin in serum and skin blister fluid (SBF), and the pharmacodynamic activity in SBF. Time-kill curves were obtained by inoculation of 3 ϫ 10 6 CFU/ml for studies with a clinical isolate of Streptococcus pneumoniae and by inoculation of 1.5 ϫ 10 6 CFU/ml for studies with a methicillin-susceptible laboratory strain of Staphylococcus aureus. The MICs and minimal bactericidal concentrations (MBCs) of gatifloxacin for both test strains were established by a standard macrodilution assay in Mueller-Hinton broth (MHB; Becton Dickinson), with a final inoculum of approximately 5 ϫ 10 5 CFU/ml and incubated at 37°C for 24 h (12). Gatifloxacin was obtained as crystalline powder for in vitro testing from Grünenthal GmbH, Aachen, Germany. For the volunteer study, we used film-coated tablets containing 400 mg of gatifloxacin as an active ingredient obtained from the same manufacturer.Approval for this study was obtained from the Ethics Committee of the University Hospitals. Twenty healthy Caucasian volunteers participated in the study. All subjects completed the study, and no adverse events were reported. Skin blisters were induced by applying eight plasters (1 by 1 cm) impregnated with 0.2% cantharidin ointment (Adler Pharmacy, Alf an der Mosel, Germany) to the forearm of each volunteer, as previously described (7). Fourteen hours later, the plasters were removed, and SBF was sampled by puncture of the blisters. The pharmacokinetic parameters were calculated from the serum and SBF samples of all 20 volunteers. The pharmacodynamic activity of SBF from the first and second groups of 10 subjects was determined against S. pneumoniae and S. aureus, respectively. One aliquot of the SBF was analyzed without centrifugation (i.e., containing leukocytes), a second was centrifuged (12,000 ϫ g for 3 min at 4°C) before incubation with the test strain, and a third was stocked after centrifugation for the pharmacokinetic measurements.Eight milliliters of venous blood was collected through an indwelling catheter for determination of concentrations of gatifloxacin in serum at the following time points in relation to the time of drug administration: before (0 h); 15, 30, and 60 min after; and 2, 3, 5, 7, 9, and 24 h after drug intake. Blood samples were collected in plain tubes (Vacutainers), immediately cooled on ice, and then cent...

Bactericidal Activities of Methoxyfluoroquinolones Gatifloxacin and Moxifloxacin against Aerobic and Anaerobic Respiratory Pathogens in Serum

“…Gatifloxacin provides higher peak concentrations following a single 400-mg dose, but the area under the concentration-time cure is similar for these methoxyfluoroquinolones (28,31). In this study, we found that gatifloxacin had higher concentrations in serum at the 2-h time point, but the serum levels at the other sampling times were similar for these two agents.…”

Determination of gatifloxacin in human serum and urine by high-performance liquid chromatography with ultraviolet detection

“…Although numerous pharmacokinetic studies of gatifloxacin have been published in the past several years [3][4][5][6][7][8][9][10][11][12][13][14][15], only two published papers [16,17] have described the complete methodology for a validated assay procedure, one employing liquid chromatography with electrospray tandem mass spectrometry, the other using HPLC with fluorescence detection. Several of the gatifloxacin pharmacokinetic studies referenced above describe the assay methodology within the pharmacokinetic paper and all used either fluorescence detection [7][8][9][10][11][12]18] or a microbiological assay [6,19].…”