Amikacin Treatment With or Without Aminophyllibe in Neonates With Suspected Sepsis at Korle-BU Teaching Hospital: A Pharmacokinetic and and Pharmacodynamic Study

ABSTRACT

Background: Sepsis is a major cause of death among neonates. In neonates, symptoms of sepsis are often non-specific and diagnosis requires a high index of suspicion. Thus, the role of additional diagnostic markers is important. Amikacin is used as first-line treatment of neonatal sepsis and it is usually co-administered with aminophylline in preterm neonates in Ghana. Amikacin dosing is well established, however, optimal effect requires specific dose titration and maintenance therapy should be individualized. Aim: To describe the PK and evaluate selected aspects of the PD of amikacin in neonates with suspected sepsis. Methods: Neonates with suspected sepsis (n=322) and requiring amikacin or amikacin with aminophylline treatment were recruited at the Neonatal Intensive Care Unit, KorleBu Teaching Hospital, Ghana. Admission clinical and demographic information was collected, using case record forms. Blood culture and sensitivity, selected hematological (FBC), and biochemical [urea, creatinine, total bilirubin, C-reactive protein (CRP) and procalcitonin (PCT)] parameters were measured before treatment. A standard dose of amikacin was administered as per local guidelines. Brainstem auditory evoked potential was done before treatment commencement and seven days later in a randomly selected group of neonates. Serum amikacin concentration was measured at specified times after treatment initiation and amikacin concentration data was analyzed, using population PK modeling. Results: A total of 163 (50.6%) of admitted neonates were born preterm, of which 14 (4.3%) were extreme preterm. A total of 79 (24.5%) had signs/symptoms consistent with birth asphyxia. There was 13.6% (41/302) culture positivity. Among neonates v categorized as having ―highly probable‖, ―probable‖ or ―less probable‖ sepsis, mean PCT was significantly different (P