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-acquired 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 AUC0-24/MICall). Monte Carlo simulations were then used to analyse target attainment both of gatifloxacin and levofloxacin to achieve free-drug AUC0-24/MICall ≥ 30 against S. pneumoniae in patients with CAP. Dosing regimens for gatifloxacin were 400 mg once daily (qd) administered to younger patients (<65 years) and gatifloxacin 200 mg qd to elderly patients (≥65 years). Dosing regimens for levofloxacin were simulated as 500 mg, 750 mg and 1000 mg qd administered to elderly patients as well as younger patients. Monte Carlo simulations using gatifloxacin 400 mg against S. pneumoniae yielded probabilities of achieving free-drug AUC0-24/MICall of 30 of 96.6% for all patients, 92.3% for younger patients and 97.7% for elderly patients. When administered to elderly patients, a reduced dose of gatifloxacin 200 mg qd could achieve a target attainment potential of 91.4%. Monte Carlo simulation using levofloxacin 500 mg qd yielded probabilities of achieving free-drug AUC0-24/MICall of 30 of 92.3% for all patients, 95.7% for elderly patients compared with 72.7% for younger patients. Using levofloxacin 750 mg and 1000 mg qd had probabilities of achieving free-drug AUC0-24/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 AUC0-24/MICall of 100 was low both with gatifloxacin and levofloxacin, except in the case of elderly patients receiving levofloxacin in a dose of 1000 mg qd (78.5%). We conclude that gatifloxacin and levofloxacin pharmacokinetics in elderly patients with CAP are markedly different from those of younger patients. Higher gatifloxacin/levofloxacin AUC and longer half-life (t1/2) values in elderly patients with CAP compared with younger patients provide better pharmacodynamic parameters (free-drug AUC0-24/MIC) leading to a higher probability of pharmacodynamic target attainment and improved bacteriological outcome against S. pneumoniae. Gatifloxacin 400 mg 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 dose of 200 mg qd in elderly patients could still be successful in producing a favourable antibacterial effect. Levofloxacin administered at a dose of 750 mg qd results in a high probability of target attainment and improved bacteriological outcome against S. pneumoniae in all patients with CAP.