TABLE 4.
Meropenem dosing regimens and pharmacokinetic parameters for three different simulated levels of renal function used in the HFIM against P. aeruginosa 1280a
| Meropenem regimen (amt, dosing interval)b | CLCRc (ml/min) | CLmeropenem (liters/h) | t1/2d (h) | fCmax (mg/liter) | fCmin (mg/liter) | fCmin/MIC | fCss,avg (mg/liter) | %fT>MIC | %fT>5×MIC | fAUC24 (mg·h/liter) | Outcomee |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 2 g, 8 h | 285 | 34.0 | 0.6 | 51.3 | 0.01 | 0.04 | 7.1 | 62 | 45 | 170.7 | RR |
| 1 g, 8 h | 285 | 34.0 | 0.6 | 25.7 | 0.00 | 0.00 | 3.6 | 54 | 38 | 85.3 | RR |
| 0.5 g, 8 h | 285 | 34.0 | 0.6 | 12.8 | 0.00 | 0.00 | 1.8 | 47 | 30 | 42.7 | RR |
| 2 g, 8 h | 120 | 16.3 | 1.1 | 70.1 | 0.50 | 2.0 | 15.5 | 100 | 82 | 372.4 | SR |
| 1 g, 8 h | 120 | 16.3 | 1.1 | 35.0 | 0.25 | 1.0 | 7.8 | 100 | 69 | 186.2 | RR |
| 0.5 g, 8 h | 120 | 16.3 | 1.1 | 17.5 | 0.12 | 0.48 | 3.9 | 87 | 56 | 93.1 | RR |
| 2 g, 8 | ∼10 | 4.1 | 4.0 | 114.5 | 31.5 | 126.0 | 64.9 | 100 | 100 | 1556.9 | SR |
| 1 g, 8 h | ∼10 | 4.1 | 4.0 | 57.2 | 15.7 | 62.8 | 32.4 | 100 | 100 | 778.5 | SR |
| 0.5 g, 8 h | ∼10 | 4.1 | 4.0 | 28.6 | 7.9 | 31.6 | 16.2 | 100 | 100 | 389.2 | SR |
| 1 g, 12 h | ∼10 | 4.1 | 4.0 | 49.1 | 6.8 | 27.2 | 21.6 | 100 | 100 | 519.3 | SR |
For P. aeruginosa 1280, the meropenem MIC is 0.25 mg/liter. All values presented are concentrations simulated at steady state. Abbreviations: t1/2, half-life; fCmax, unbound maximal concentration at steady state; fCmin, unbound minimal concentration; fCss,avg, unbound average concentration at steady state; %fT>MIC, the percentage of time that unbound concentrations exceeded the MIC; AUC24, the area under the unbound piperacillin concentration-versus-time curves over 24 h.
The infusion time for all regimens was 0.5 h.
A creatinine clearance (CLCR) of 285 ml/min represents patients with augmented renal clearance, a CLCR of 120 ml/min represents patients with normal renal clearance, and a CLCR of ∼10 ml/min represents patients with renal impairment.
Samples for viable counting were collected at 0, 1.5, 5, 7, 13, 23, 29, 31, 47, 53, 71, 95, 119, 143, 167, 191, 215, and 239 h. Samples for pharmacokinetic determinations were collected at 0.66, 1, 2, 3.5, 5, 7, 8.66, 13, 23, 24.66, 47, 48.66, 49, 50, 51.5, 53, 55, 71, 72.66, 95, 119, 143, and 167 h for the CLCR of 285 ml/min. For the CLCR at 120 and ∼10 ml/min, samples were collected as for the 285-ml/min CLCR, as well as at 29 and 31 h. For growth controls, the flow rates for the respective renal functions were maintained.
RR, regrowth, with resistance; SR, suppression of regrowth.