Should monitoring of vancomycin be delayed? A case of likely nephrotoxicity occasioned by morbid obesity and minimal monitoring

Abstract

The nephrotoxicity of vancomycin was thought to be largely due to impurities in older formulations but recent evidence suggests that even with modern, purified formulations, vancomycin is nephrotoxic, especially at high doses. Recent recommendations advise using actual body weight for obese patients as the basis for dose size and because MICs for important pathogens are increasing, larger doses are frequently recommended nowadays. Therapeutic drug monitoring is important for ensuring appropriateness of dosing and limiting nephrotoxicity but the most recent recommendations advise monitoring should not be performed until steady-state has been achieved.In late 2009, a 54 year old, morbidly obese patient (approximately 150 kg) was referred to our Hospital because of increasing tiredness, abdominal cramps, ulcerated leg and per rectum bleeding. She had been discharged just 9 days earlier following an admission for pneumonia at which time she had been also been diagnosed with atrial fibrillation and an ischaemic finger for which enoxaparin and warfarin were started. Warfarin was withheld because the INR was 3.4 and haemoglobin concentration had fallen from 143 g l -1 to 103 g l -1 over the preceding 9 days. The provisional diagnosis was a retroperitoneal bleed for which a CT scan (using 100 ml of nonionic, low osmolar, Iopromide contrast) was ordered. This revealed a rectus sheath haematoma. She was taking many drugs including paracetamol/doxylamine/codeine, warfarin, verapamil, digoxin, hydroxychloroquine, prednisolone, nitrazepam, oxazepam, furosemide and nystatin.At presentation, serum creatinine was 65 mmol l -1 , temperature 38°C and CRP was 200 mg l -1 . Vancomycin was prescribed because of a history of MRSA. According to Hospital protocol (15 mg kg -1 actual body weight twice daily), 2 g twice daily was ordered and the plan was to administer for 7 days. At that time, the hospital protocol advised not to monitor if treatment was planned for <7 days. However one sample was taken 11 h after the first dose and was reported at 14.2 mg l -1 .The temperature did not settle and vancomycin (as the sole antibiotic) was continued for a total of 17 doses over 10 days (three doses were omitted due to failure of i.v. access). The serum creatinine concentration increased (by >50% over baseline) on days 9 (121 mmol l -1 ) and 10 (173 mmol l -1 ) at which time vancomycin was stopped. Serum creatinine peaked on day 15 (252 mmol l -1 ) (Figure 1) then slowly fell though it did not reach baseline, pre-admission concentrations even 6 months later. Serum vancomycin concentrations were checked 27 h after the last dose (54.8 mg l -1 ), 24 h later (46.2 mg l -1 ) and a further 48 h later (29.6 mg l -1 ). Vancomycin is primarily renally cleared and the relationship between creatinine clearance (CLcr) and vancomycin clearance is so good, it has been suggested monitoring is not needed because dose can be calculated from CLcr [1]. A recent wide-ranging US review [2] advises trough monitoring be performed at 'steady-state' (generally four d...