Gentamicin dosage intervals in neonates: Longer dosage interval—less toxicity

Abstract

Objectives: The aim of this study was to determine the incidence of toxic trough serum gentamicin levels in neonates in the first week of life, with different dosage intervals. Methods: This was a retrospective study of neonates born between 01.07.95 and 31.12.95, who received gentamicin. Data were collected on birth weight, gestation, gentamicin dose, the trough level of gentamicin, serum creatinine and urine output. A trough serum gentamicin level of ≥1.5 mg/L was considered toxic. Results: One hundred and seventy infants met the study criteria. All 21 infants in group one (24-29 weeks) received gentamicin with a dosage interval of 24 h. Sixteen (76%) infants had toxic trough serum gentamicin levels. In group two (30-34 weeks) 8 infants had gentamicin q12hly and all (100%) had toxic trough serum gentamicin levels. Fourteen infants had gentamicin every 18 h and 13 (93%) had toxic trough serum gentamicin levels. Sixty-one infants had gentamicin q24hly and 25 (41%) had toxic trough serum gentamicin levels. The differences in proportions with toxic levels were statistically significant. In group three (≥35 weeks) 29 infants had gentamicin q12hly and 25 (86%) had toxic trough serum gentamicin levels. Six infants had gentamicin every 18 h and 2 (33%) had toxic trough serum gentamicin levels. Thirty-one infants had gentamicin q24hly and 4 (13%) had toxic trough serum gentamicin levels. The differences in proportions comparing infants having gentamicin q12hly with those having it q24hly were statistically significant. Conclusions: A starting gentamicin dosage interval of 12 h in infants of any gestational age, or a starting dosage interval of 24 h for infants of less than 30 weeks gestational age, leads to most having toxic trough serum gentamicin levels. In infants of 30 weeks gestational age or greater, most have safe non-toxic trough serum gentamicin levels if started on a dosage interval of 24 h.

Pharmacological differences between once daily and twice daily gentamicin dosage in newborns with suspected sepsis

“…Similar findings have been shown in recent studies focusing on the neonatal subgroup, suggesting that ODD regimen may provide higher peak levels and lower trough levels of serum gentamicin concentrations (SGC) compared to the more conventional MDD regimen [2,4,10,11]. Furthermore, in newborns the ODD regimen may be associated with less failure to attend recommended peak levels of SGC of at least 5 lg/ml, and less failure to achieve safe trough levels of\2 lg/ml [7,10]. Recent studies have shown no increase in ototoxicity and nephrotoxicity in ODD compared to MDD regimen [9][10][11].…”

“…This treatment provides synergetic coverage against the common neonatal pathogens, such as group B streptococci, staphylococci, Echerichia coli, Enterobacter cloacae, Klebsiella species and Serratia species [1][2][3]. Gentamicin exhibits both a concentration-dependent bacterial killing and a speciesspecific post-antibiotic effect, in which the bacterial growth for a period of time is suppressed despite concentrations below the minimal inhibitory concentration for a given bacteria [4][5][6][7][8]. A low trough level is important to reduce the risk for ototoxic and nephrotoxic effects of gentamicin in newborns [3,8].…”

Identification of Risk Factors for Elevated Neonatal Gentamicin Trough Concentrations

“…This study defined an elevated gentamicin trough concentration as ≥1.5 mg/L. This is consistent with the work of Davies et al, 3 who have associated gentamicin concentrations of ≥1.5 mg/L with toxicity. Other investigators have used ≥2 mg/L to define elevated gentamicin concentrations.…”

“…1 A combination of intravenous ampicillin and intravenous gentamicin comprises standard initial therapy for suspected or documented sepsis in the neonate. 2 The literature 3 suggests that gentamicin trough concentrations of greater than 1.5 mg/L are associated with an increased risk of toxicity. The most commonly reported 4 toxicities associated with gentamicin use include ototoxicity and nephrotoxicity.…”

Nonparametric Population Pharmacokinetic Analysis of Amikacin in Neonates, Infants, and Children

“…Several factors account for the pharmacokinetic variabilities of other aminoglycosides in this population (50). The pharmacokinetics of netilmicin and gentamicin depend on gestational age, postnatal age, weight, renal clearance, and Apgar score (6,9,11,12,14,18,21,43,46,47,(51)(52)(53). Very few data are available concerning the effects of clinical and biological covariates on the pharmacokinetics of amikacin in neonates and the changes in the pharmacokinetic profile of amikacin that occur from birth into infancy.…”