Table 2.
Subject characteristics in the population pharmacokinetic analysis
| Characteristics | Clinical isolates from Japanese patients | End of phase II stage (interim analysis) | Phase III data |
|---|---|---|---|
| Diseasea | – | CAP, SICRD | SICRD |
| Number of subjects (n) | – | 104 | 133 |
| Healthy subjects/Infected patients (n) | – | 49/55 | – |
| Males/females (n) | – | 77/27 | 87/46 |
| Mean ± SD (Min–Max) | Mean ± SD (Min–Max) | ||
| Age (year) | – | 40.0 ± 20.4 (20–74) | 66.3 ± 14.8 (19–94) |
| Body weight (kg) | – | 58.5 ± 10.4 (34–83) | 52.7 ± 13.0 (33–120) |
| CLCR (ml/min) b | – | 102.4 ± 29.7 (34.4–178.7) | 71.1 ± 29.4 (19.3–199.2) |
| Pathogens | MIC90 (Min–Max) [n]c | MIC range [n]d | MIC range [n]e |
| Methicillin-sensitive Staphylococcus aureus (MSSA) | 0.025 (0.0125–0.05) [23] | ≤0.025 [2] | ≤0.06–0.25 [8] |
| Penicillin-sensitive strains of Streptococcus pneumoniae (PSSP) | 0.05 (0.025–0.05) [24] | 0.10 [3] | ≤0.06–0.25 [6] |
| Penicillin intermediately or highly resistant strains of S. pneumoniae (PISP/PRSP) | 0.05 (0.025–0.05) [23] | 0.05 [1] | ≤0.06 [8] |
| Haemophilus influenzae | 0.0125 (0.00313–0.0125) [50] | ≤0.025 [10] | ≤0.06–0.5 [29] |
| Moraxella catarrhalis | 0.10 (≤ 0.00625–0.39) [50] | ≤0.025 [1] | ≤0.06 [7] |
| Klebsiella pneumoniae | 3.13 (0.05–25) [54] | – | 0.12–0.5 [4] |
| Pseudomonas aeruginosa | > 100 (0.78– > 100) [35] | 0.20–0.78 [2] | 0.12–32 [5] |
| Streptococcus pyogenes | – | – | 0.05 [1] |
| Haemophilus parainfluenzae | – | – | 0.20–3.13 [2] |
| Stenotrophomonas maltophilia | – | – | 0.39 [1] |
aCAP, Community-acquired pneumonia; SICRD, secondary infection of chronic respiratory diseases
bCreatinine clearance (CLCR) was calculated by the Cockcroft-Gault equation. Male: CLCR (ml/min) = ([140 – age (years)] × WT (weight, kg)/[72 × serum creatinine (SCr, mg/dl)]. Female: CLCR (ml/min) = ([140 – age (years)] × WT (kg)/[72 × SCr (mg/dl)] × 0.85
cThe pathogens were clinically isolated from Japanese patients during 1994–1997. The minimum inhibitory concentration (MIC) required to inhibit the growth of 90% of organisms (MIC90) was determined by standard agar methods of the Japan Society of Chemotherapy. Other pathogens were: ciprofloxacin (CIP)-susceptible methicillin-resistant Staphylococcus aureus (MRSA) with a MIC of 0.025 (0.0125–0.05) (n = 51), CIP-resistant MRSA 6.25 (0.10–6.25) (n = 26), vancomycin-resistant enterococci (VRE) 3.13 (≤ 0.05–3.13) (n = 24)
dThe pathogens were isolated from 26 patients of the phase II study. The MICs were determined by standard agar methods of the Japan Society of Chemotherapy. Other pathogens were: S. intermedius with a MIC of 0.05 (n = 1), S. constellatus 0.10 (n = 1), K. oxytoca 0.05, 0.10 (n = 2), M. pneumoniae 0.015 (n = 2), and K. pneumoniae whose MIC was not measured (n = 1)
eThe pathogens were isolated from 66 patients who participated in the pharmacokinetic/pharmacodynamics (PK/PD) analysis of the phase III study. The MICs were determined by the Clinical and Laboratory Standards Institute (CLSI)