Comparison of gatifloxacin and levofloxacin administered at various dosing regimens to hospitalised patients with community-acquired pneumonia:: pharmacodynamic target attainment study using North American surveillance data for Streptococcus pneumoniae

This work aimed at determining the target attainment potential of gatifloxacin and levofloxacin in specific age-related patient populations such as elderly (>= 65 years) versus younger (< 65 years) hospitalised patients with)community-required pneumonia (CAP), Previously described population pharmacokinetic models of gatifloxacin and levofloxacin administration in patients with serious CAP were utilised to simulate gatifloxacin and levofloxacin pharmacokinetics. Pharmacokinetic simulations and susceptibility data for Streptococcus pneumoniae from the ongoing national surveillance study, Canadian Respiratory Organism Susceptibility Study ((CROSS). were then used to produce pharmacodynamic indices of free-drug area under the curve over 24 h relative to the minimum inhibitory concentration (free-drug AUC(0.24)/MICall) Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC(0.24)/MICall >= 30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (old) administered to younger patients (< 65 years) and gatifloxacin 200 mg old to elderly patients (>= 65 years). Dosing regimens for levofloxacin were simulated as 5(X) mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 4(X) mg against S. pneumoniae yielded probabilities of achieving free-drug AUC(0-24)/MICall of 30 of 96,6% for all patients. 92.31% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200 mg Lid could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC(0.24)/MICall) of 30 of 92,3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxac in 750 mg and 1(X)0 mg qd had probabilities of achieving free-drug AUC(0-24)/MICall of 30 of 97.0% and 98.3%, 98.1% and 99.2%,and 90.1% and 95,2% for all patients. elderly patients and younger patients, respectively. The probability of achieving free-drug AUC(0.24)/MICall of 100 was low berth with gatifloxacin and levofloxacin, except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg (Id (78.5%). We conclude that gatifloxacin and levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patient,, Higher gatifloxacin/levofloxacin AUC and longer half-life (t(1/2)) values in elderly patients with CAP compared with younger patients provide better pharmacodynamic parameters (free-drug AUC(0-24)=MIC) leading to a higher probability or pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae. Gatifloxacin 400mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae both in young and elderly CAP patients. However, gatifloxacin administered at a lowered close of 2(X) mg old in elderly patients could still be successful in producing a favourable antibacterial effect. Levofloxacin administered at a dose of 750 mg old results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae in all patients with CAR (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.