TABLE 2.
Recommended dosing for the most frequently used drugs against carbapenem-resistant Enterobacteriaceae (CRE) for patients with normal renal functiona
| Drug | Usual/standard dose(s) | Dosing for CRE and comments |
|---|---|---|
| Meropenem | 1 g/8 h | 2 g/8 h by EI (isolates with MICs of 2–8 mg/liter; for isolates with higher MICs, it is probably not efficacious) |
| Ertapenem | 1 g/24 h | Consider 2 g/day for double-carbapenem regimens |
| Colistinb | From the EMA, loading dose, 6–9 MU, and then 9 MU/day in 2–3 doses; from the FDA, 2.5–5 mg of colistin base activity/kg/day | EMA dose is recommended for severe CRE infections; the need for a loading dose and high continuation dose in patients without severe infection/shock is controversial |
| Polymyxin Bc | From the FDA, 1.5–2.5 mg/kg/day in 2 doses | For mild infections and isolates with MICs of ≤1 mg/liter, the FDA dose is probably appropriate; for severe infections and isolates with MICs of up to 4 mg/liter, a loading dose of 2–2.5 mg/kg followed by 3 mg/kg/day in 2 doses is recommended (controversially) |
| Tigecycline | 100-mg loading dose and then 50 mg/12 h | For HAP, cUTI, BSI, or shock, consider a 200-mg loading dose and then 100 mg/12 h |
| Gentamicin, tobramycin | 5–7 mg/kg/day | For HAP or shock without other options, higher doses (10–15 mg/kg) might be considered, but the risk of toxicity is high; TDM is recommended |
| Amikacin | 15–20 mg/kg/day | For HAP or shock without other options, higher doses (25–30 mg/kg) might be considered, but the risk of toxicity is high; TDM is recommended |
| Fosfomycin | 4 g/6 h to 8 g/8 h | Use in combination; high sodium concn |
| Temocillin | 2 g/8–12 h | KPC producers are occasionally susceptible; continuous infusion improves PK-PD target attainment |
| Aztreonam | 1–2 g/8 h | MBL producers are susceptible if they are not ESBL or AmpC producers |
| Ceftazidime | 1–2 g/8 h | OXA-48 producers are susceptible if they are not ESBL or AmpC producers |
| Ceftazidime-avibactam | 2.5 g/8 h | KPC and OXA-48 producers are frequently susceptible |
| Meropenem-vaborbactam | 2/2 g/8 h | KPC producers are frequently susceptible |
a
Please refer to the text for explanations and references. EI, extended infusion; EMA, European Medicines Agency; FDA, U.S. Food and Drug Administration; HAP, hospital-acquired pneumonia; cUTI, complicated urinary tract infection; BSI, bloodstream infection; MU, million units; TDM, therapeutic drug monitoring; MBL, metallo-β-lactamase.
b
One million units of colistimethate sodium = 80 mg colistimethate sodium = 34 mg of colistin base activity.
c
One million units of polymyxin B = 100 mg of colistin base activity.