1. Clinical efficacy and pharmacokinetics of colistimethate sodium 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.
- Author
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Moni M, Sudhir AS, Dipu TS, Mohamed Z, Prabhu BP, Edathadathil F, Balachandran S, Singh SK, Prasanna P, Menon VP, Patel T, Patel P, Kaye KS, and Menon VP
- Subjects
- Administration, Intravenous, Adult, Aged, Anti-Bacterial Agents therapeutic use, Colistin therapeutic use, Female, Gram-Negative Bacteria classification, Gram-Negative Bacteria genetics, Gram-Negative Bacteria isolation & purification, Gram-Negative Bacterial Infections microbiology, Hospitals statistics & numerical data, Humans, India epidemiology, Male, Middle Aged, Prospective Studies, Treatment Outcome, Anti-Bacterial Agents pharmacokinetics, Colistin analogs & derivatives, Colistin pharmacokinetics, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria drug effects, Gram-Negative Bacterial Infections drug therapy
- Abstract
Background: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing., Aim: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function., Materials and Methods: Twenty critically ill adult patients with colistin-susceptible multidrug-resistant (MDR) infections and normal renal function treated with intravenous colistimethate sodium - at a 9 million units (270 mg CBA) loading dose followed by maintenance (MD) of 3 million units 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 the loading dose and at 1, 2 and 8 hours after the eighth and ninth infusion of MD were evaluated. Colistimethate sodium and colistin levels were measured by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS)., Results: Among the 20 patients who were evaluated, 60% had pneumonia. Predominant pathogens were Klebsiella pneumoniae and Acinetobacter spp. Clinical cure was 50% (10/20). Mean peak loading dose concentrations 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 were 2.25 ± 1.3 mg/L and 1.78 ± 1.1 mg/L in 'cure' and 'failure' groups, respectively (p = 0.19). Nephrotoxicity was 5% on day 7 of therapy. However, bacteriological cure could not be correlated with PK/PD., Conclusions: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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