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Keywords Kúcové slová: * E-mail: email@example.com © Acta Facultatis Pharmaceuticae Universitatis Comenianae Acta Fac. Pharm. Univ. Comen. LXII, 2015 (2): 1-4. An adjustment of vancomycin dosing regimen for a young patient with augmented... INTRODUCTION Vancomycin has been widely used for many years as a firstchoice antibiotic for nosocomial infections caused by grampositive bacteria. Achieving the correct serum level can be a difficult task, particularly in severely septic patients who manifested augmented renal clearance (ARC) (1). ARC is a recently reported condition in pathophysiology of critically ill patients in the intensive care unit (ICU) (2). ARC refers to the enhanced renal elimination of circulating solutes. These patients are either young or previously healthy people who have undergone surgery or multiple trauma. Baptista et al. (6) have considered ARC value of creatinine clearance value above 130mL/min/1.73 m2. According to Udy (2010), augmented CrCl was defined as >150 mL/min/1.73 m2 in women and >160 mL/min/1.73 m2 in men (8, 9). It might induce sub-optimal concentrations of drugs eliminated by glomerular filtration mainly antibiotics (3, 4). The incidence rate of ARC in patients with different medical conditions in relation to vancomycin levels or possible risk factors were analysed (2, 4). Literature survey revealed that only few reports are available on individual case reports of patients with ARC. Cook et al. (2013) have recently reported that the patient with severe traumatic brain injury can be treated with vancomycin (7). In this case report, we have described our study on a very young patient with devastating injuries to the lower extremities without traumatic brain injury, who have overcome crush injury. Figure 1: Evolution of estimated creatinine clearance (mL/ min/1.73 m2 - Cocroft-Gault) during vancomycin therapy. CASE REPORT A 16-year old male patient (weight 89 kg, height 182 cm) was brought by the Air Rescue Service to the Teaching Hospital Nitra, Slovak Republic, after he had been crushed by a tractor. In the clinical picture, devastating injury of the right lower limb with the oppression of the nerve vascular bundle dominated. Condition of this patient revealed an open fracture of the right tibia and a number of lacerations and contusions all over his body. He gradually developed a serious crush syndrome with the washout of large amounts of myoglobin from the damaged tissues of the right lower limb, renal impairment and an acute renal insufficiency. The patient was continually dialysed. Three days later, the trauma surgeon indicated an exarticulation of the right lower limb because of extensive gangrene and the adverse effect of reperfusion syndrome on vital functions recovery. The patient's condition was concluded as a serious polytrauma, crush syndrome and septic shock. Gradually, the complex support of vital functions led to the stabilisation of the patient, the diuresis was restored and kidneys were resumed their function. Creatinine clearance during the sepsis state reached the values that indicated the ARC. ARC was recorded (138.04 mL/min/1.73 m2) at the day 29 after hospitalisation and reached the highest values (339.81mL/min/1.73 m2) at the days 41, 46, 49 and 51 after hospitalisation. The values of creatinine clearance (Cocroft-Gault) in response to administration of vancomycin are depicted in Figure 1. During the hospitalisation in the ICU, as a precautionary treatment, different antibiotics and antimycotics were administered to the patient, which included amikacin, ampicillin/sulbactam, ceftazidime, ciprofloxacin, colistin, imipenem, penicillin and piperacillin/tazobactam in order to treat the infection caused by Acinetobacter baumannii, Corynebacterium xerosis, Enterobacter cloacae, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas mendocina, coagulase-negative Staphylococcus (methicillin resistant), Stenotrophomonas maltophilia, Candida parapsilosis and Candida dubliniensis. During the ARC, the patient's hemoculture test showed positive for Staphylococcus hominis, coagulase-negative staphylococcus, which is resistant to the beta-lactam antibiotics. Vancomycin was included in the patient's treatment regime from the day 42 after hospitalisation. Physicians in the ICU started administering vancomycin to the patient in a conventional dosing regime of 1 g per 12 hours. The residual measured concentration of vancomycin was very low 1.5 mg/L. Clinical pharmacist doubled the dose of vancomycin to 2 g per 12 hours. After one day, the residual concentration reached the required level 15.43 and 9.93 mg/L. Two days later, increase in the creatinine clearance was observed, and the vancomycin concentration decreased to 4.88 mg/L. The dose of vancomycin had to be readjusted to triple the original dose to 2 g per 8 hours (67 mg/kg/day). For determination of the required dose adjustment according to the patient's pharmacokinetic parameters, the Abbottbase Pharmacokinetic Program (Figure 2) was used. After this dose readjustment, the vancomycin concentration reached 18.7 mg/L. Vancomycin at this dose was administered to the patient for one more day. After the concentration reached 21.90 mg/L, the dosing schedule was adjusted to 2 g of vancomycin per 12 hours. The patient was hospitalised in the ICU for more than two months. The whole healthcare team was efficiently involved to save the patient's life. Long-term hospitalisation in the ICU automatically represented a potential risk of nosocomial Maria Goboova et al. Figure 2: The calculated dose and predictions of levels according to Abbottbase Pharmacokinetic Program for our patient with ARC. infections. Vancomycin was one of the last antibiotics that were administered to the patient. He was transferred in a good health state to the rehabilitation centre, where he has learned to use his prosthetic. DISCUSSION In this case report, we have described a severe pathophysiology of a young patient with severe polytrauma, overcome crush syndrome and sepsis, who demonstrated ARC. This patient was treated with conventional doses of vancomycin, which proved to be insufficient to reach the desired effective therapeutic concentration levels. The effective concentrations of vancomycin were achieved after increasing the doses to triple the amounts of the conventional dose. The management of nosocomial infection in the ICU represents an ongoing challenge for critical care clinicians. The critically ill represent a unique population, either presenting with infection complicated by systemic inflammation (sepsis) or being predisposed to such complications by the virtue of the underlying disease process (5). In the young patient with polytrauma after the kidney insufficiency because of the crush syndrome, the renal
Acta Facultatis Pharmaceuticae Universitatis Comenianae – de Gruyter
Published: Dec 1, 2015
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