Colistimethate Sodium Dosing and Nephrotoxicity among in-Patients at Tertiary Care Hospital Karachi, Pakistan

Introduction: Colistimethate sodium (CMS) is a polymyxin group of antibiotics which were throw out for many years, due to their potential adverse reaction neurotoxicity and nephrotoxicity. The different guidelines were reported regarding CMS dosing some based on Creatinine clearance (CrCl) and some on weight and CrCl. There are many discrepancies in the prevalence of nephrotoxicity that has been reported which included various definitions of acute renal injury and many CMS doses used in a variety of literature. In EMA guideline they suggested the dose as 9 MIU which is equivalent to 300 mg of CBA given as a maintenance dose with normal renal function patients. In FDA standard dosing of CMS remains 5 mg/kg CBA per day used and also dose is dependent on patient weight. The aim of this study was to evaluate the dosing criteria of colistimethate sodium associated with nephrotoxicity.

Methodology: A prospective observational study was conducted in private sector tertiary care hospital in Karachi, Pakistan, for duration of six months from July 2020 to December 2020. Sample size was comprised of 157 patients, calculated at 35% prevalence, 95% Confidence Interval and 7% margin of error. Patient included were ≥ 18 years of age, who have received intravenous CMS therapy for greater than 48 hours. Patients having an acute kidney injury or on dialysis (at start of therapy) were excluded. Loading dose and daily dose of CMS was calculated by using actual body weight and Creatinine clearance (CrCl). Cockcroft and Gault equation was used to estimate CrCl before and after the therapy. Nephrotoxicity was assessed by using the RIFLE criteria. SPSS-20 was used for frequency distribution and percentage calculation to show categorical variable.

Results: Among 157 enrolled patients, 101 (64.3%) were male and 56(35.7%) were female (Table 1). Table 2. represents that 68(43.3%) patients were admitted in intensive care unit (ICU) and 89(56.7%) were in medicinal ward; 22.9% patients were in between the age range 60-70 years (Table 3). Among all patients 63(40.1%) patients were at risk of nephrotoxicity, 27(17.2%) patients were developing injury and 14(8.9%) patients were diagnosed to kidney failure and 53(33.8%) patients were found not to developed nephrotoxicity (Table 4). Table 5 exhibits that 48.4% of the patients were receiving dose of CMS using EMA guideline while 51.6% patients were receiving dose of CMS 2.5-5 mgCBA/kg/day according to FDA. Nephrotoxicity was high among FDA regimen (44.5%).

Conclusion: It was concluded that CMS dosing criteria have a significant impact on nephrotoxicity. Close monitoring of renal function, particularly the first week of CMS therapy should be considered to evaluate the renal toxicity of CMS.