TABLE 2.
Survival of mice challenged with S. pneumoniae 1064 and pneumococcal killing effects of erythromycin and azithromycin in vivo and in vitro
| No. of dosesa | In vivo data
|
In vitro change in log CFU at 6 h (95% CI) | Pharmacokinetic parametersb
|
|||||
|---|---|---|---|---|---|---|---|---|
| No. of mice dead/total (%) within 6 days | Change in log CFU at 6 h in blood/peritoneal fluid (95% CI)c | Cmax (mg/liter) (× MIC) | T>MIC (h) | T>max-kill (4 × MIC) (h) | AUC0–6 (mg/liter · h) | AUC0–∞ (mg/liter · h) | ||
| Azithromycin | ||||||||
| 1 | 37/85 (44) | 0.5 (0.4 to −1.3)/0.02 (−1.3 to 1.3) | −2.4 (2.8–2.1) | 0.8 (26) | 4.2 | 2.5 | 1.2 | 1.2 |
| 2 | 29/54 (54) | NDd | −1.6 (2.0–1.3) | 0.4 (13) | 6.9 | 3.6 | 1.2 | 1.2 |
| 4 | 30/55 (55) | 0.5 (0.5 to 0.5)/−0.6 (−2.8 to −1.6) | −1.6 (2.3–0.9) | 0.2 (6.5) | 7.5 | 3.2 | 0.9 | 1.2 |
| 8 | 41/55 (75) | ND | −1.6 (1.7–1.5) | 0.1 (3.3) | 7.5 | 0 | 0.6 | 1.2 |
| Erythromycin | ||||||||
| 1 | 24/30 (80) | −0.2 (−0.5 to 0.1)/−1.2 (−4.9 to −0.8) | −1.9 (2.2–1.9) | 0.8 (26) | 3.2 | 2.0 | 1.0 | 1.0 |
| 4 | 24/30 (80) | −0.9 (−1.6 to −0.2)/−1.2 (−2.2 to −0.2) | −2.3 (2.5–2.1) | 0.2 (6.5) | 6.4 | 3.6 | 1.0 | 1.0 |
a
The total amount of each drug given in each case was 4 mg/kg.
b
Calculated from simulated curves.
c
CI, confidence interval.
d
ND, not done.