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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.
- Source :
-
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases [Int J Infect Dis] 2020 Nov; Vol. 100, pp. 497-506. Date of Electronic Publication: 2020 Aug 08. - Publication Year :
- 2020
-
Abstract
- Background: Safe and effective use of colistin requires robust pharmacokinetic (PK) and pharmacodynamic (PD) data to guide dosing.<br />Aim: To evaluate the pharmacokinetics of colistimethate sodium and colistin in critically ill patients and correlate with clinical efficacy and renal function.<br />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).<br />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.<br />Conclusions: Subtherapeutic Cssavg with clinical failure and lower efficacy without significant nephrotoxicity highlights the need for therapeutic drug monitoring to guide colistin dosing.<br /> (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3511
- Volume :
- 100
- Database :
- MEDLINE
- Journal :
- International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 32781161
- Full Text :
- https://doi.org/10.1016/j.ijid.2020.08.010