Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection

Abstract

The increasing frequency of penicillin-resistant pneumococcus continues to be of concern throughout the world. Newer fluoroquinolone antibiotics, such as levofloxacin, have shown enhanced in vitro activity against Streptococcus pneumoniae. In this study, the bactericidal characteristics and pharmacodynamic profiles of levofloxacin, ciprofloxacin, and ampicillin against four isolates of S. pneumoniae were compared by using an in vitro model of infection. Standard antibiotic dosing regimens which simulated the pharmacokinetic profile observed in humans were used. Control and treatment models were sampled for bacterial CFU per milliliter over the duration of each 24-or 48-h experiment. In addition, treatment models were sampled for MIC determinations and drug concentration. Regrowth of all isolates as well as an increase in MICs throughout the study period was observed in the ciprofloxacin experiments. A limited amount of regrowth was noted during levofloxacin therapy for one isolate; however, no change in MIC was detected for any isolate. Ampicillin showed rapid and sustained bactericidal activity against all isolates. In this study, ratios of effective fluoroquinolone area under the concentration-time curve (AUC):MIC values ranged from 30 to 55. Levofloxacin, owing to its larger AUC 0-24 values, has excellent and sustained activity against different pneumococcal strains superior to that of ciprofloxacin.

Optimizing outcomes with antimicrobial therapy through pharmacodynamic profiling

“…Results from a number of studies conducted in vitro, 18,19 in animals, 17,23 and in humans with lower respiratory tract infection 22 show that the maintenance of AUC : MIC Ն 40 optimizes the antibacterial killing of S. pneumoniae by fluoroquinolones. This figure is much lower than the target for the management of Gram-negative infections (Ͼ125).…”

The effect of pharmacokinetic/pharmacodynamic (PK/PD) parameters of gatifloxacin on its bactericidal activity and resistance selectivity against clinical isolates of Streptococcus pneumoniae

“…It was suggested that AUC/MIC ratios of 30-60 were sufficient to eradicate S. pneumoniae. [5][6][7][8][9] However, because fluoroquinolones kill bacteria in a concentration-dependent manner, 4 not only the AUC/MIC but also the C max /MIC might affect their pharmacodynamics. Therefore, it was important to consider the effect of the AUC/MIC ratio and the C max /MIC ratio on the pharmacodynamics of fluoroquinolones against S. pneumoniae.…”

“…Our results agreed with the ideas from previous PK/PD studies in which AUC/MIC ratios of approximately 30 to 60 were sufficient for the eradication of S. pneumoniae. [5][6][7][8][9] Resistance selectivity is one of the important PD factors in antibacterial agents. Pharmacokinetic parameters, as well as the target preference of quinolones, are thought to be associated with their resistance selectivity.…”

“…The 24h area under the concentration-time curve (AUC) 24h /minimum inhibitory concentration (MIC) ratios have been identified as possible predictors of the bactericidal effect of quinolones. [5][6][7][8][9] The optimal efficacy of quinolones has been observed at AUC 24h /MIC ratios of 30-60. [5][6][7][8][9] Some investigators have also suggested that maximum concentration in serum (C max )/MIC ratios ranging from 2 to 10 are required to prevent the selection of resistance to quinolones.…”

“…[5][6][7][8][9] The optimal efficacy of quinolones has been observed at AUC 24h /MIC ratios of 30-60. [5][6][7][8][9] Some investigators have also suggested that maximum concentration in serum (C max )/MIC ratios ranging from 2 to 10 are required to prevent the selection of resistance to quinolones. 5,[10][11][12] In this study, we investigated the effect of pharmacokinetic/pharmacodynamic (PK/PD) parameters of gatifloxacin on its bactericidal activity and resistance selectivity against S. pneumoniae, and compared its efficacy with those of levofloxacin and ciprofloxacin by simulating the serum concentration according to the Japanese clinical regimen.…”