Comparative Renal and Auditory Safety of Once‑Daily Gentamicin at 5 mg/kg Versus 4 mg/kg in Neonatal Sepsis: A Prospective Cohort Study in Tanzania

Abstract

Neonatal sepsis remains a major cause of newborn morbidity and mortality in resource-limited settings, where gentamicin is widely used as empirical therapy. In Tanzania, once-daily gentamicin (4–5 mg/kg) is recommended, but the 5 mg/kg regimen is commonly used without routine therapeutic drug monitoring (TDM), raising concerns about nephrotoxicity and ototoxicity. Although the 4 mg/kg once-daily regimen has generally been associated with a lower risk of aminoglycoside-related toxicity than higher-dose regimens, its use in Tanzania remains limited, with the 5 mg/kg regimen more commonly employed. This variation between international evidence and local prescribing practice highlights the importance of evaluating whether the lower-dose regimen may offer a safer therapeutic option for Tanzanian neonates. The growing recognition of medication-related kidney injury in children further highlights the need for safer antimicrobial strategies. However, local evidence comparing the 5 mg/kg and 4 mg/kg regimens remains limited. This study compared the renal and auditory safety of these regimens in term neonates. This prospective observational cohort study included 375 term neonates receiving gentamicin 5 mg/kg (n=125), gentamicin 4 mg/kg (n=125), or ceftriaxone/cefotaxime (n=125). Renal function was assessed using serum creatinine and urinary kidney injury molecule-1 (uKIM-1), while auditory function was evaluated using automated auditory brainstem response (AABR). Nephrotoxicity was defined using kidney disease: Improving Global Outcomes (KDIGO) criteria and ototoxicity as ≥20 dB AABR threshold increase from baseline. Acute kidney injury (AKI) was more frequent and severe in the 5 mg/kg group, with stage I, II, and III AKI occurring in 35.2%, 14.4%, and 1.6%, respectively. The 4 mg/kg group had 2.4% stage I AKI with no stage II/III cases, while no AKI occurred in the comparison group (p<0.001). Ototoxicity occurred in 4.0% receiving 5 mg/kg, with no cases in other groups (p<0.05). The 5 mg/kg regimen was associated with greater renal and auditory toxicity than 4 mg/kg, supporting lower-dose strategies where TDM is unavailable.