Abstract
Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m2 for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45–95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2–2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.
Highlights
Colistin has emerged as a last resort drug for the treatment of infections caused by multidrug and extensively drug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii [1,2]
All of them had infections caused by extensively drug-resistant Pseudomonas aeruginosa: pneumonia in 14 (23.7%), acute bronchitis in 14 (23.7%), urinary tract infection in 16 (27.1%), bacteremia in three (5.1%), skin and soft tissue infections in five (8.6%)
Colistin use has reemerged in recent years for the treatment of multidrug-resistant Gram-negative infections [1,2,20], which has prompted the performance of a large number of clinical and PK studies of its use in the last decade
Summary
Colistin has emerged as a last resort drug for the treatment of infections caused by multidrug and extensively drug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii [1,2]. Studies performed in the last few years have led to new dosage schedule recommendations for both patients with normal and reduced renal function, including those undergoing renal replacement therapies [8,11,12] These new guidelines recommend CMS dose selection and adjustment based on baseline estimated glomerular filtration rate (GFR) or creatinine clearance, as well as on the target colistin plasma concentration (Css ). This value, based on different data from in vitro and in vivo PK, pharmacodynamic (PD) and toxicodynamic (TD) studies has been defined as 2 mg/L [16]. A recent publication has suggested that current recommendations on the use of colistin in patients with reduced renal function are likely to be inadequate [11] and have updated the dosing guidelines of both the European and American regulatory agencies [18,19]
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