Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8–14 days and 52% among infants aged 15–28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.

Infections represent a serious health problem in neonates. Invasive Candida infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive Candida infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different Candida spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment.

The fear of missing sepsis episodes in neonates frequently leads to indiscriminate use of antibiotics, and prescription program optimization is suggested for reducing this inappropriate usage. While different authors have studied how to reduce antibiotic overprescription in the case of early onset sepsis episodes, with different approaches being available, less is known about late-onset sepsis episodes. Biomarkers (such as C-reactive protein, procalcitonin, interleukin-6 and 8, and presepsin) can play a crucial role in the prompt diagnosis of late-onset sepsis, but their role in antimicrobial stewardship should be further studied, given that different factors can influence their levels and newborns can be subjected to prolonged therapy if their levels are expected to return to zero. To date, procalcitonin has the best evidence of performance in this sense, as extrapolated from research on early onset cases, but more studies and protocols for biomarker-guided antibiotic stewardship are needed. Blood cultures (BCs) are considered the gold standard for the diagnosis of sepsis: positive BC rates in neonatal sepsis workups have been reported as low, implying that the majority of treated neonates may receive unneeded drugs. New identification methods can increase the accuracy of BCs and guide antibiotic de-escalation. To date, after 36–48 h, if BCs are negative and the baby is clinically stable, antibiotics should be stopped. In this narrative review, we provide a summary of current knowledge on the optimum approach to reduce antibiotic pressure in late-onset sepsis in neonates.

Staphylococcal infections in neonates might be associated with skin blistering since early antibiotic therapy has been shown to limit infection spread and positively influence outcomes; therefore, neonatologists should be aware of these conditions. This review examines the recent literature on the management of Staphylococcal infections that involve neonatal skin, discussing the most appropriate clinical approach to four cases of neonatal blistering diseases with Staphylococcal infections: a case of Staphylococcal bullous impetigo, a case of Staphylococcal scalded skin syndrome (SSSS), a case of epidermolysis bullosa with overlapping Staphylococcal infection, and a case of burns with overlapping Staphylococcal infection. In treating Staphylococcal infections involving skin in neonates, the presence or absence of systemic symptoms should be considered. In the lack of evidence-based guidelines in this age category, treatment should be individualized according to several factors including the extension of the disease or further skin comorbidities (such as skin fragility), with a multidisciplinary approach.