Neonatal Infection

The clinical presentation depends on the type of infection, but manifestations such as dyspnea, increased temperature, jaundice, feeding difficulties, seizures, skin rash and a bulging fontanelle may be present [7].

A detailed physical examination is crucial in order to make an initial diagnosis, but microbiological studies should be performed to determine the underlying cause, mainly consisting of blood and cerebrospinal fluid cultures [3]. In addition, various inflammatory markers have been used to support the diagnosis. Procalcitonin is becoming a reliable early indicator of bacterial infections. C-reactive protein (CRP) is an acute-phase reactant, while interleukins 6 and 8 (IL-6 and IL-8, respectively), interferon gamma (IFN-γ), CD64 and several other are showing promising results, but their role needs to be established [3] [4].

The choice of therapy depends on the clinical presentation and microbiological studies, but initial empiric therapy must be given early on. If a suspicion toward bacterial pathogens exists, antibiotic therapy targeting the most common etiological agents (E. coli and group B streptococcus) should be initiated. Ampicillin combined with cefotaxime is recommended, especially if more severe forms of infection are present [8]. Acyclovir is the drug of choice for HSV [1], while ribavirin may be used for RSV [8]. Amphotericin B deoxycholate is used for neonatal candida infection [3].

The majority of infections seen during newborn period are noninvasive and are treated effectively [6], but serious forms may be fatal if left untreated. Neonatal HSV infection carries only a 40 percent survival rate if untreated [1], emphasizing the importance of an early diagnosis and appropriate treatment.

Numerous pathogens have been described as causes of neonatal infection [1] [5]:

• Bacterial - Escherichia coli and Group B Streptococcus are responsible for about 70% of all neonatal infections [5]. Streptococcus viridans, Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, Enterococcus spp., Enterobacter spp., Haemophilus influenzae, Treponema pallidum and Listeria monocytogenes are other notable pathogens.
• Viral - Herpes simplex virus (HSV), cytomegalovirus (CMV), enteroviruses, parechoviruses, influenza virus, respiratory syncytial virus (RSV), adenovirus, rotavirus, hepatitis B virus, human immunodeficiency virus (HIV).
• Fungal - Candida spp.
• Parasitic - Toxoplasma gondii.

Neonatal infections are the primary cause of death in neonates, with more than 1.4-1.6 million fatalities being reported every year [2] [4]. Infections of the respiratory, gastrointestinal and central nervous system are most common [4].

The pathogenesis model depends on the pathogen responsible for the infection, but the immune system during the newborn period is quite weak and fully relies on maternal immunoglobulins received through transplacental transfer and breastfeeding. A myriad of other factors plays a role in the pathogenesis of neonatal infections, with one of the most important being the mode of acquisition. Infection may be acquired transplacentally prior to birth with examples being toxoplasmosis, syphilis, listeriosis, malaria, and CMV infection, while HIV, hepatitis B, and chlamydia trachomatis infections are acquired during the process of birth. Postnatal infection through breastfeeding is also an important route, especially during early life.

Regular vaccination protocols have markedly reduced the incidence of neonatal infections and deaths worldwide. Maternal screening and antimicrobial prophylaxis for group B streptococcus have additionally reduced the rates of neonatal infections in newborns [3]. The use of intravenous immunoglobulin (IVIG), lactoferrin, probiotics, glutamine, antistaphylococcal agents and granulocyte-macrophage colony stimulating factor have been proposed as preventive modes regarding neonatal infection [7]. Prophylactic use of fluconazole is recommended for infants with a very low birth weight, in whom a significantly higher risk of neonatal infection is present [7].

An infection within 28 days of birth is considered to be a neonatal infection. Bacterial, viral, or fungal microorganisms, as well as parasites, may be the causative agents [1] [2] [3]. Neonatal infections are responsible for approximately 1.4-1.6 million deaths throughout the world every year [2] [4], and they are the most common cause of neonatal death [2]. The diagnosis is made by a thorough examination and a meticulous laboratory workup, including detection of inflammatory markers and microbiological investigations [4]. Symptomatic care and the use of antibiotics, antiviral, antifungal or antiparasitic agents are mainstays of therapy [5].

Neonatal infection is a term describing the onset of an infection within the first 28 days from birth, and a range of microbiological organisms, including bacteria, viruses, and fungi may be responsible. Group B streptococcus and Escherichia coli are responsible for about 70% of cases. Neonatal infections are the most common cause of death in neonates, with more than 1.4 million fatalities every year worldwide. The infections of the respiratory, gastrointestinal and central nervous system are most common. Feeding difficulties, inadequate breathing, diarrhea, fever fluctuations and jaundice can be reported as manifestations and the initial diagnosis is made clinically. Various tests in order to identify the underlying cause should be made, as treatment principles significantly differ. Antibiotics should be given for a bacterial infection while certain viruses may be targeted with antiviral agents, but supportive care is equally important in the first few days of illness. Maternal screening for group B streptococcus and subsequent prophylaxis is one of the main preventive strategies.

1. Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med. 2009;361(14):1376-1385.
2. Shah BA, Padbury JF. Neonatal sepsis: An old problem with new insights. Virulence. 2014;5(1):170-178.
3. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-Onset Neonatal Sepsis. Clin Microbiol Rev. 2014;27(1):21-47.
4. Meem M, Modak JK, Mortuza R, Morshed M, Islam MS, Saha SK. Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics. J Glob Health. 2011;1(2):201-209.
5. Sinha A, Yokoe D, Platt R. Epidemiology of neonatal infections: experience during and after hospitalization. Pediatr Infect Dis J. 2003;22(3):244-251.
6. Vergnano S, Sharland M, Kazembe P, Mwansambo C, Heath P. Neonatal sepsis: an international perspective. Arch Dis Child Fetal Neonatal Ed. 2005;90(3):F220-F224.
7. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis. Pediatr Clin North Am. 2013;60(2):367-389.
8. Gilbert DN, Chambers HF, Eliopoulos GN, Saag MS. The Sanford Guide to Antimicrobial Therapy 2015. 45th ed. Antimicrobial Therapy, Inc, Sperryville, VA. 2015.