Extended-Interval Gentamicin Administration in Preterm Neonates < 34 Weeks Gestational Age
Gladys El-Chaar, Department of Clinical Pharmacy Practice, College of Pharmacy and Health Sciences, Lalithambal Venugopalan, Tingnong Supaswud, and Susana Castro-Alcaraz, Neonatology, Schneider Children's Hospital, New Hyde Park
Background: Gentamicin is an aminoglycoside antibiotic with bactericidal activity against gram-negative bacteria. The drug's pharmacodynamics are optimal when a ratio of maximum serum concentration (Cmax) to minimum inhibitory concentration of 8:1 to 10:1 or an Area-Under-The-Curve (AUC) of 80 to 100 mg/hr/L and a drug-free period for the post antibiotic effect are achieved. Extended-interval gentamicin administration (EIGA) has been adopted to optimize these properties; however, dosing remains complex and non-uniform. This study had two cohorts of neonates. We previously presented data from GA >35 weeks. Herein, we present the data on GA <34 weeks.
Our hypothesis is that a uniform dose of gentamicin will reduce the number of elevated trough gentamicin concentrations from 50% using traditional dosing to 10% using an EIGA regimen. Aims are to improve gentamicin's pharmacodynamics and safety and simplify the dosage.
This prospective, randomized, controlled study compared traditional dosing (control group) to EIGA (study group) in neonates <34 weeks GA. Sample size of 46 neonates is needed. Traditional dosing includes a loading dose and maintenance doses every 12 to 24 hours while EIGA is 5 mg/kg/dose every 36 hours. Inclusion criteria: Neonates <34 weeks and <6 months postnatal age. Exclusion criteria: neonates previously enrolled or endocarditis. Hearing screens and renal function were followed.
45 neonates were enrolled to date; 22 in EIGA group, 23 in traditional group. Elevated trough levels were found in 13% vs 4.5% in the traditional and EIGA groups, respectively. Although 3 neonates (two in traditional, one in EIGA) had positive blood cultures, none had gram-negative infections. Cmax and AUC were 9.1 + 1.7 mg/L vs 7.4+1.2 mg/L and 128+34 mg/hr/L vs 155+38.5 mg/hr/L in the traditional and EIGA groups, respectively. Dosage changes were necessary in 52% vs 27% of neonates in the traditional and EIGA groups, respectively to maintain therapeutic peak and trough concentrations. One child in the traditional group failed the hearing screen. One child in the EIGA had transient elevation in serum creatinine levels. None of the findings were statistically significant.
Although the primary hypothesis was not proven, we achieved improved Cmax levels and reduced the number of dosage changes in the EIGA group. There were no differences in adverse effects. This dosage regimen is simple and uniform.