A randomised, controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants

Area of Science:

• Pharmacology
• Pediatrics
• Infectious Diseases

Background:

• Gentamicin is a crucial antibiotic for treating severe sepsis in neonates and infants.
• Routine therapeutic drug monitoring for gentamicin is often unavailable in resource-limited settings.
• Optimizing gentamicin dosing regimens is essential for efficacy and safety in vulnerable infant populations.

Purpose of the Study:

• To evaluate the suitability and safety of a simple, once-daily (OD) gentamicin regimen for young infants.
• To determine if OD gentamicin can achieve therapeutic concentrations without increasing toxicity in settings lacking drug monitoring.
• To establish an appropriate gentamicin dosing guide for resource-poor environments.

Main Methods:

• An open, randomized, controlled trial was conducted in a Kenyan rural district hospital.
• Infants with suspected severe sepsis received either a novel OD gentamicin regimen or standard multi-dose (MD) regimens.
• Pharmacological endpoints, including plasma gentamicin concentrations at various time points, were analyzed.

Main Results:

• The OD gentamicin regimen achieved higher initial plasma concentrations (9.0 microg/ml) compared to MD regimens (4.7 microg/ml).
• Fewer infants in the OD group had sub-therapeutic concentrations (<4 microg/ml) after the first dose (5% vs. 28%).
• Pre-dose concentrations indicative of potential toxicity (> or =2 microg/ml) were lower with OD gentamicin (6% vs. 24%), with minimal observed renal toxicity (<2%).

Conclusions:

• A "two, four, six, eight" OD gentamicin regimen is a suitable and safe prescribing guide for premature infants and neonates.
• This simplified regimen is appropriate for resource-poor settings where routine therapeutic drug monitoring is not feasible.
• The OD gentamicin approach balances efficacy and safety in young infants with severe sepsis.