Non-Susceptibility of Early-Onset Sepsis Pathogens to the Combination of Ampicillin and Gentamicin Among Neonates in Thailand

<b>Background/Objectives</b>: Empirical antimicrobial therapy for neonatal early-onset sepsis (EOS) comprises ampicillin and gentamicin. However, multidrug-resistant organisms are increasing worldwide, thus inflicting a global burden. We identified the incidence and risk factors of neonates with pathogenic isolates that were not susceptible to treatment comprising a combination of ampicillin and gentamicin (non-susceptible group). <b>Methods</b>: This retrospective study included neonates diagnosed with EOS between 2004 and 2023. All patients with EOS and positive culture results within 72 h of birth were reviewed. Patients in the non-susceptible and susceptible groups were analyzed using a multivariable logistic regression model. <b>Results</b>: Sixty pathogenic isolates and 55 neonates with EOS were observed over the course of 20 years. The incidence and case fatality rates of EOS were 0.88 per 1000 live births and 41.8%, respectively. <i>Acinetobacter baumannii</i> was the most common EOS pathogenic isolate (19/60 pathogenic isolates; 12/19 resistant to carbapenems). Pathogenic isolates were susceptible to ampicillin or gentamicin (59%), ampicillin or cefotaxime (42%), and ampicillin or amikacin (72%). Data regarding susceptibility to ampicillin and gentamicin of 49 neonates were available. A multivariable analysis revealed that patients in the non-susceptible group (<i>n</i> = 18) were more likely to experience late-onset EOS (48-72 h; <i>p</i> = 0.01) and require endotracheal intubation on day 1 (<i>p</i> = 0.04) compared to patients in the susceptible group (<i>n</i> = 31). <b>Conclusions</b>: In areas with high multidrug resistance, broader-spectrum antibiotic therapy (ampicillin plus amikacin) should be considered for neonates who develop clinical sepsis within 48-72 h of birth and experience respiratory failure at birth.