Table 2.

Suggested Loading and Daily Doses of Colistimethate for a Desired Target colistin C_ss,avg of 2 mg/L in Various Categories of Critically ill Patients

Dose	Category of Critically Ill Patient	Dosing Suggestionsa
Loading dose	All patient categories	Equation 1: Loading dose of CBA (mg) = Css,avg target (mg/L) × 2.0 × ideal body weight (kg) To achieve a Css,avg of 2 mg/L in a patient with an ideal body weight of 75 kg, the loading dose would be 300 mg CBA (9 million IU), the suggested maximum loading dose. The 1st regular daily dose should be administered 12 h later.
Daily doseb	Not receiving RRT	Equation 2c: Daily dose of CBA (mg) = Css,avg target (mg/L) × 10(0.0048 × CrCl + 1.825) See Table 3 (“look-up” table) for the daily dose to target a plasma colistin Css,avg of 2 mg/L, depending on the patient’s creatinine clearance.
	Receiving RRT	The baseline daily dose of colistimethate for a Css,avg of 2 mg/L in a patient with creatinine clearance of 0 mL/min is 130 mg/d of CBA (3.95 million IU/d) (see Table 3)d; the supplement to the baseline daily dose needed during receipt of RRT is 10% of the baseline dose per 1 h of RRT.
	Intermittent hemodialysis	Nondialysis day: CBA dose of 130 mg/d (3.95 million IU/d), ie, baseline dosing for a Css,avg of 2 mg/L; dialysis day supplement: add 30% or 40% to baseline daily dose after a 3- or 4-h session, respectively.e The dialysis session should occur toward the end of a colistimethate dosing interval, and the supplement to the baseline (nondialysis) daily dose should be administered with next regular dose, after the dialysis session has ended.
	SLED	During SLED: add 10% per 1 h of SLED replacement to baseline daily dose for a Css,avg of 2 mg/Lf; for a patient receiving a 10-h nocturnal SLED session each day and receiving colistimethate every 12 h, the dose would be (baseline CBA dose of 130 mg/d for a patient with creatinine clearance of 0 mL/min + supplemental dose comprising 10% of the baseline dose per h × 10 h); ie, for this case the CBA dose would be 260 mg/d (7.9 million IU/d). It is suggested that the SLED session begin 1–2 h after the afternoon/evening dose; in such a case, it may be most convenient and safe to administer 130 mg CBA (3.95 million IU) every 12 h.
	CRRT	During CRRT: add 10% per 1 h of CRRT to the baseline daily dose for a Css,avg of 2 mg/Lg; the suggested CBA dose is 440 mg/d (~13 million IU/d).

Abbreviations: CBA, colistin base activity; CrCl, creatinine clearance (mL/min); CRRT, continuous renal replacement therapy; C_ss,avg, average steady-state plasma concentration of colistin; RRT, renal replacement therapy; SLED, sustained low-efficiency dialysis.

^aSuggested doses are based on the population pharmacokinetic (PK) analysis for 214 critically ill patients. Doses are expressed primarily as milligrams of CBA for various categories of critically ill patients; doses are also provided in millions of international units.

^bDaily dose administered in 2 divided doses 12 h apart.

^cEquation 2 is based on the regression equation in Figure 2B, with the intercept adjusted from 1.667 to 1.825 and with creatinine clearance (CrCl) expressed in mL/min.

^dBased on use of Equation 2 and setting CrCl to 0.

^eSupplemental dose of colistimethate to achieve a similar C_ss,avg on a dialysis day as occurs on a nondialysis day, based on the population PK analysis for 16 critically ill patients in whom intermittent hemodialysis dialysate clearance of colistimethate and colistin was determined.

^fBased on the population PK analysis for 4 critically ill patients in whom SLED dialysate clearance of colistimethate and colistin was determined.

^gBased on the population PK analysis for 9 critically ill patients in whom CRRT dialysate clearance of colistimethate and colistin was determined.