International Journal of Infectious Diseases | |
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 | |
Zubair Mohamed1  Sabarish Balachandran2  Merlin Moni3  Binny Pushpa Prabhu3  T.S. Dipu3  Vidya P Menon4  Payal Patel5  Fabia Edathadathil6  Sanjeev K Singh6  Preetha Prasanna6  A Sangita Sudhir7  Veena P Menon7  Twisha Patel8  Keith S Kaye9  | |
[1] Department of Anaesthesiology and Critical Care, Amrita Institute of Medical Sciences, Kochi, India;Department of Emergency Medicine, Amrita Institute of Medical Sciences, Kochi, India;Department of General Medicine, Division of Infectious Diseases, Amrita Institute of Medical Sciences, Kochi, India;Department of Internal Medicine, Lincoln Medical Center, NY, USA;Department of Internal Medicine, University of Michigan Health System, MI, USA;Department of Medical Administration, Amrita Institute of Medical Sciences, Kochi, India;Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Institute of Medical Sciences, Kochi, India;Department of Pharmacy Services, University of Michigan Health System, MI, USA;Division of Infectious Diseases, University of Michigan Medical School, MI, USA; | |
关键词: Therapeutic drug monitoring; Pharmacokinetics; Colistimethate sodium; Colistin; Multidrug-resistant infections; Clinical efficacy; | |
DOI : | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown