The most common causes of early-onset neonatal sepsis in the United States are as follows:

Although traditionally group B streptococci accounted for most cases of early-onset sepsis, there has been a recent decline in the incidence of early-onset neonatal group B streptococcal infection. This decline is a result of the successful implementation of routine maternal screening for, and maternal intrapartum antimicrobial prophylaxis against, this organism. Therefore, E. coli is now likely the
most common cause of early-onset sepsis in this country. Other, less common pathogens include viridans streptococci and nontypeable Haemophilus influenzae.

Group B streptococci and L. monocytogenes remain important causes of late-onset neonatal sepsis in previously healthy infants. In high-risk neonates who are hospitalized, the most important causes of late-onset sepsis, in decreasing order of relative frequency, are as follows:

Coagulase-negative staphylococci are the most common cause of late-onset neonatal sepsis in hospitalized high-risk neonates, accounting for almost 50% of hospital-acquired infections in neonatal intensive care settings.

The clinical features of neonatal sepsis are subtle and nonspecific. Respiratory distress, lethargy, an unstable temperature, apnea, jaundice, feeding intolerance, and tachycardia are common. Regardless of the specific pathogen causing the sepsis, the clinical manifestations are similar and also do not differ from those of noninfectious illnesses in neonates. Finally, it is important to remember that the characteristics of neonatal meningitis are indistinguishable from those of sepsis. The specific epidemiologic and clinical features of disease caused by the most common pathogens are discussed in the subsequent text.

The isolation of an organism from the blood or CSF provides definitive evidence of bacterial sepsis. The utility of rapid diagnostic tests such as latex particle agglutination to detect group B streptococcal and E. coli infections is limited by poor sensitivity and specificity. Because 25% to 30% of neonates with bacterial sepsis also have meningitis, a lumbar puncture should be performed whenever sepsis is documented. Even in the absence of a blood culture that is positive for bacteria, examination of the CSF should be strongly considered whenever sepsis is suspected because the blood cultures of 10% to 15% of neonates with meningitis are negative for the bacteria. The hematologic findings associated with neonatal sepsis include an elevated ratio of immature neutrophils to total neutrophils (>0.2), neutropenia, an elevated total neutrophil count, and thrombocytopenia.

Antimicrobial therapy for early-onset neonatal sepsis must include coverage for group B streptococci, E. coli, and L. monocytogenes. Administration of ampicillin/gentamicin provides such coverage. Although gentamicin has no activity against group B streptococci and L. monocytogenes, when it is administered with penicillin, the combination is synergistic.

Antimicrobial coverage for late-onset infection acquired in the neonatal intensive care nursery setting usually includes a combination of oxacillin or vancomycin to provide coverage against gram-positive organisms, including coagulase-negative staphylococci, and an aminoglycoside or thirdgeneration cephalosporin to provide broad gram-negative coverage. Once the organism has been recovered and sensitivity results are available, the regimen can be re-evaluated.

Initial antimicrobial therapy for an infant with late-onset sepsis or meningitis that has not been acquired nosocomially usually includes a combination of ampicillin and an aminoglycoside or third-generation cephalosporin, such as cefotaxime. Ampicillin is required in this situation to cover the possibility of L. monocytogenes infection, against which cephalosporins have no activity.

Most preventive efforts are focused on group B streptococci infection. Currently, group B streptococcal screening with vaginal and rectal cultures is recommended for all pregnant women at 35 to 37 weeks’ gestation, with the exception of mothers who have had group B streptococcal bacteriuria during the current pregnancy or those having had a previous infant with group B streptococcal disease. Mothers who are shown to be carriers of group B streptococci during the current pregnancy should receive intrapartum prophylaxis, unless a planned cesarean delivery is performed in the absence of labor or membrane rupture. Maternal intrapartum antimicrobial prophylaxis is also indicated for mothers with:

If the group B streptococcal status of the mother is unknown at the time of delivery, maternal intrapartum prophylaxis is indicated if any of the following are present:

Neonatal HSV infection is the most feared consequence of gestational genital HSV infection. Because HSV infection closely mimics bacterial sepsis, a delayed diagnosis is common, and despite the availability of antiviral therapy, the associated mortality and morbidity remain high.

Most neonates acquire the virus from an infected maternal genital tract at the time of delivery. HSV 2 accounts for most cases of neonatal HSV infection; approximately 30% of the cases are caused by HSV 1. Viral transmission can follow either primary or recurrent maternal infection. The transmission rate during primary maternal infection is estimated to be 35% to 50%, but 3% to 5% during recurrent maternal infection. The higher rates are likely the consequence of a high viral titer, involvement of the cervix, and the lack of transplacental antibody in the primary maternal infection. Most neonates with HSV infection are born to asymptomatic mothers with no past history of genital HSV infection. This finding is explained by the high prevalence of “silent” maternal genital HSV infection.

There are three clinical forms of neonatal HSV infection (Table 22.1):

Infants with disseminated disease usually present during the first 2 weeks of life with nonspecific symptoms. Irritability, apnea, poor feeding, unstable temperature, jaundice, hepatosplenomegaly, disseminated intravascular coagulation, hepatic failure, seizures, and shock are common features. A vesicular rash occurs in about 60% of the cases but is often absent at the time of presentation. Seizures occur in 22% of patients with disseminated disease. Even with appropriate antiviral therapy, the mortality rate associated with this form of HSV infection is 30%.

Neonates with disease localized to the CNS most commonly present between the second and third weeks of life, usually with lethargy, fever, and seizures. CSF pleocytosis with an elevated CSF protein is the rule. Approximately 65% of these infants have skin vesicles at any time during the course of the disease. It is important to remember that neonatal HSV causes diffuse encephalitis, without localization to the temporal lobes, unlike HSV encephalitis beyond the neonatal period. The mortality rate for this form of disease is 5%, but at least two thirds of the survivors have long-term neurologic sequelae.

Neonates with HSV disease localized to the SEM usually present between 1 and 2 weeks after birth with vesicular lesions, forming singly or in clusters, on an erythematous base (Fig. 22.1). Ocular involvement, in the form of keratitis, conjunctivitis, or chorioretinitis, occurs in 10% to 15% of these infants. Patients with SEM disease have the best prognosis; infants treated early in the course with antiviral agents uniformly survive. However, cutaneous lesions may recur in 10% to 15% of treated infants during the first year of life, and they are at risk for long-term neurologic sequelae. If SEM disease is not treated, it progresses to the disseminated and CNS form.

The diagnosis of neonatal HSV infection is difficult, especially in the absence of vesicular lesions. Therefore, a high index of clinical suspicion is warranted in any neonate in whom sepsis is suspected, especially in the setting of negative bacterial cultures. Viral culture is the most reliable method of making the diagnosis. The virus can be isolated from cutaneous lesions or from the nasopharynx, CSF, conjunctivae, or maternal genital tract. When vesicular lesions are present, a direct fluorescent antibody test can provide a rapid diagnosis. Polymerase chain reaction testing for HSV DNA in the CSF is sensitive and is the diagnostic method of choice for establishing CNS disease.

Parenteral acyclovir is the antiviral agent of choice in the treatment of neonatal HSV infection. The currently recommended dosage of acyclovir is 60 mg/kg per day given in three divided doses. The duration of the therapy is 14 days for SEM disease and 21 days for disseminated or CNS disease. Neonates treated with this dosage of acyclovir should be monitored closely for the development of neutropenia. It must be stressed that despite appropriate and timely antiviral therapy, the mortality and morbidity rates associated with these infections remain high.

Nonpolio enteroviruses are a common cause of benign febrile infections in older infants and children but have the potential to cause more severe infections in neonates. These viruses are transmitted by the fecal-oral and oral-oral routes, and newborns most commonly acquire them during the birth process. In temperate climates, enteroviral diseases are most common in the summer and fall. Echoviruses 9, 11, 30, and Coxsackie virus B are the most common causes of enteroviral neonatal disease.

Most neonatal enteroviral infections are mild and cause nonspecific symptoms. However, 20% of infections are severe and life threatening, and these occur in neonates who acquire the infection without the maternal antibody. Fever, feeding intolerance, abdominal distension, and irritability are the common presenting features. Diarrhea, vomiting, shock, disseminated intravascular coagulation, hepatomegaly, jaundice, and apnea may follow. A rash is present in 40% of the infants; macular and maculopapular rashes are most common, but petechial and vesicular exanthems have also been described. Hepatitis, hepatic necrosis, myocarditis (especially with coxsackievirus B), and meningoencephalitis may be evident.

Distinguishing the enteroviral illness from HSV infections and bacterial sepsis is difficult. The following features are more suggestive of an enteroviral infection:

Isolation of the virus from the nasopharynx, throat, stool, rectal swab, blood, urine, or CSF confirms the diagnosis. Polymerase chain reaction assays for the presence of enterovirus RNA on CSF is more sensitive than the viral culture in infants with meningoencephalitis. The management of these infants relies on meticulous intensive care. A neonate with myocarditis, encephalitis, or hepatic involvement has a poor prognosis.