Efficacy and Safety of Daptomycin in the Neonatal Population

Gram-positive sepsis remains a leading cause of morbidity and mortality in neonates. Vancomycin is the standard of care, yet drug monitoring challenges and rising resistance demand alternatives. Daptomycin has potent bactericidal activity, low resistance development and high efficacy in biofilm-associated infections. Experience in the neonatal period is scarce.

This retrospective study focuses on infants with confirmed Gram-positive infection admitted between January 2019 and December 2024. All patients received daptomycin (6 mg/kg every 12 hours) after vancomycin treatment failure or contraindication due to side effects. Demographic, microbiologic, antibiotic treatment features, adverse events and neonatal outcome data were extracted from the infants' medical records.

Fifty-three infants (median gestational age 29 weeks; interquartile range [IQR] 25-37.5) received daptomycin. Staphylococcus epidermidis accounted for 77.4% of isolates; 90% were methicillin-resistant. Median vancomycin exposure before antibiotic switch was 5 days. Blood cultures cleared in 47/52 assessable episodes (90.4%) after a median of 4 days on daptomycin; 1 additional case required adjunctive linezolid. Liver enzyme elevations occurred in 24% of infants, and a self-limited rash occurred in 2%; all were transient and resolved without treatment discontinuation. No muscular or neurologic toxicity was observed. Overall mortality was 24.5% (13/53), but infection-attributable mortality was confined to 4 cases (7.5%); no infection-related deaths occurred after 2020.

In this neonatal cohort, which included a high proportion of very preterm infants, daptomycin achieved rapid microbiologic clearance and was generally well tolerated, although liver enzyme elevations were observed in approximately 1 of 4 patients. These findings support its potential role as an alternative when vancomycin fails or cannot be used. Earlier use in high-risk, catheter-associated infections merits prospective evaluation.