Clinical efficacy and pharmacokinetics of CMS and colistin in critically ill patients in an Indian hospital with high endemic rates of multidrug-resistant gram-negative bacterial infections-A Prospective Observational Study.

Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing.
20 critically ill adult patients with colistin susceptible multidrug resistant (MDR) infections and normal renal function treated with intravenous CMS (colistimethate sodium) as 9MU(270 mg CBA) loading dose (LD) followed by maintenance (MD) 3MU t.i.d, 24 hours later, were evaluated for clinical cure (CC) at the end of therapy. Patient characteristics and plasma colistin levels at 0, 0.5, 1, 2,4, 8 and 12 hours after LD and at 1, 2 and 8 hours after 8 and 9 infusion of MD were evaluated. CMS and colistin levels were measured by HPLC-MS/MS.
Among 20 patients evaluated, 60% had pneumonia. Predominant pathogens wereKlebsiella pneumoniae and Acinetobacter spp. Clinical cure (CC) was 50% (10/20). Mean peak loading dose concentration were 3 ± 1.1 mg/L (1.75-5.14) and 2.37 ± 1.2 mg/L (1.52- 5.54) for ‘cure’ and ‘failure’ groups respectively (p = 0.13) while mean steady-state (Cssavg) concentrations was 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in ‘cure’ and ‘failure’ group respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD.
Subtherapeutic Cssavgwith clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.

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