Serum Inhibitory and Bactericidal Activity of Ciprofloxacin following Intravenous Administration

Dudley, Michael N.; Mandler, Hilary D.; Mayer, Kenneth H.; Zinner, Stephen H.

doi:10.1177/106002808902300603

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Analysis of serum bactericidal titers on samples from the central compartment confirmed previous in vivo observations on the poor serum bactericidal activity of iv doses of ciprofloxacin (200 mg) alone against P. aeruginosa [17] and the additive or synergistic activity with azlocillin at clinically relevant concentrations [38]. These measurements of the central compartment of the model also provided some insight into pharmacokinetic measurements linked to the kinetics of bacterial killing and the selection of bacterial resistance.…”

Section: Pharmacodynamicssupporting

confidence: 59%

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Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

Dudley¹,

Blaser²,

Gilbert³

et al. 1991

Journal of Infectious Diseases

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The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv) every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum" compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal {j-lactam with ciprofloxacin against P. aeruginosa.

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Section: Pharmacodynamicssupporting

confidence: 59%

“…The microdilution technique using MHB-S as the diluent was used for these studies [17). Bacterial inocula were prepared from frozen samples as described.…”

Section: Methodsmentioning

confidence: 99%

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

Dudley¹,

Blaser²,

Gilbert³

et al. 1991

Journal of Infectious Diseases

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Pharmacokinetics and serum bactericidal titers of ciprofloxacin and ofloxacin following multiple oral doses in healthy volunteers

Israel

Gillum

Turik

et al. 1993

Antimicrob Agents Chemother

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Fourteen adult males participated in a randomized three-way crossover study to compare the pharmacokinetics and serum bactericidal titers (SBTs) of 500 mg of ciprofloxacin (regimen A), 750 mg of ciprofloxacin (regimen B), and 400 mg of ofloxacin (regimen C) administered every 12 h for seven doses. Mean steady-state peak concentrations in serum for regimens A, B, and C were 3.0, 4.4, and 6.5 ,g/ml, respectively (P < 0.01, all comparisons) and mean half-lives were 4.5, 4.3, and 6.5 h, respectively (P < 0.05, C versus A and B). Mean steady-state areas under the concentration-time curve were 14.1, 21.1, and 48.1 ,g/h/ml for regimens A, B, and C, respectively (P < 0.05, all comparisons). SBTs were determined at different times postdose for three isolates each of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coi, Enterobacter cloacae, and Pseudomonas aeruginosa. Mean steady-state peak SBTs for regimens A, B, and C, respectively, were as follows: S. pneumoniae, <1:2, 1:8, 1:8; S. aureus, 1:16, 1:16, 1:16; E. coli, 1:2 128, 1:2 128, 1:64; E. cloacae, 1:2 128, 1:2 128, 1:64; P. aeruginosa, 1:8, 1:8, 1:2. These differences in SBTs within each genus were statistically significant. The majority of predicted SBTs were within one dilution of measured SBTs. Areas under the serum bactericidal time curves forE. coli, E. cloacae, and P. aeruginosa were significantly higher for ciprofloxacin; areas under the serum bactericidal time curves for S. pneumoniae and S. aureus were significantly greater for ofloxacin. Ofloxacin achieved higher concentrations in serum than ciprofloxacin, but differences in in vitro activity were a more important determinant of SBTs.Ciprofloxacin and ofloxacin are fluoroquinolone antibiotics which are well absorbed by the oral route and are active against a broad range of pathogenic bacteria (7). Since these quinolones differ in both pharmacokinetics and in vitro activity, measurement of serum bactericidal titers (SBTs) integrates both characteristics and allows for direct comparison of their pharmacodynamic properties (1,4,16). The purpose of this study was to compare the pharmacokinetics and SBTs of ciprofloxacin and ofloxacin in healthy volunteers after multiple-dose oral administration.(A portion of this manuscript appeared as an abstract in the program of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, Calif., October 1992 [6a].)

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Serum Inhibitory and Bactericidal Activity of Ciprofloxacin following Intravenous Administration

Cited by 2 publications

References 13 publications

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

Pharmacokinetics and serum bactericidal titers of ciprofloxacin and ofloxacin following multiple oral doses in healthy volunteers

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