Neonatal Infections

The basic function of the immune system is to protect the body from harm caused by an infection invading microorganisms such as bacteria, viruses, fungi, protozoa, and parasites. During gestation, the fetus grows and develops within the usually protective environment of its mother's uterus. However, during the birth process and subsequently, the neonate is exposed to various microorganisms. The neonate's extrauterine existence is dependent on the equilibrium between its host defense mechanisms and the hostile microorganisms in its environment.

The host defense mechanisms begin to develop early in gestation, but many do not function as efficiently at birth as they do in the older infant, child, or adult. The immaturity of the immune system becomes apparent in light of the high incidence of infectious disease during the perinatal period. Neonatal sepsis occurs in 1 to 21 infants per 1,000 live births. Identifying and caring for the infected newborn can be one of the most significant challenges for modern neonatal care providers, with mortality rates as high as 30% to 69% of affected infants. Developing countries have both the highest incidence and the highest mortality rates. Many attempts have been made to devise accurate and sensitive clinical and laboratory indices to identify infants likely to have sepsis (Singh, 2019). None of these have been successful. Nurses are often the first to recognize something wrong with an infant, and subsequently, the symptoms are investigated. Usually, treatment is begun once a presumptive diagnosis of infection is made.

The following terms describe neonatal sepsis (Tesini, 2018).

• Infection – the body's response to the invasion of any microorganism, including bacterial, fungal, protozoan, or viral agents, causes clinical infection signs.
• Clinical signs of infection – generalized signs and symptoms are seen with any infectious process, including respiratory distress, lethargy or irritability, poor muscle tone, feeding intolerance, apnea, bradycardia, tachycardia, and pallor, cyanosis, poor perfusion, and temperature instability.
• Maternal risk factors – factors that, when present, increase the risk for infection in the infant and are associated with an increased risk of early-onset sepsis in the infant. These include prolonged rupture of membranes (PROM) > 18 hours, maternal fever, chorioamnionitis, maternal vaginal culture positive for group B streptococcus, history of a previous infant with group B streptococcus disease, and premature delivery < 37 weeks gestation.
• Sepsis – a bacterial bloodstream infection identified by one or more positive blood cultures in the presence of clinical signs of infection.
• Early-onset sepsis – sepsis that occurs within the first three days of life. It is associated with birth canal organisms acquired in utero or during delivery. Group B streptococcus remains the primary causative agent. One or more maternal risk factors are usually present. Term and preterm infants often present with respiratory distress, which can progress quickly to multisystem involvement within the first 24 hours.
• Late-onset sepsis occurs after the first 3-5 days of life and is associated with nosocomially acquired microorganisms. It occurs more frequently in premature and low birth weight (LBW) infants and often includes meningitis. Coagulase-negative staphylococci are the primary causing bacteria. The presentation of signs of infection is slow and insidious.
• Mixed Nonspecific Presentation- sepsis may present at any time and may present with septic arthritis, osteomyelitis, cellulitis, omphalitis, breast abscess, conjunctivitis, myocarditis, endocarditis, otitis media, scalp abscess, UTI or impetigo.

There are many reasons for the increased susceptibility of the newborn to widespread infection. The infant's birth weight, chronologic, and gestational age at the onset of sepsis also impact the expected mortality rate. Between 5% and 50% of infants with early-onset sepsis will succumb, compared with a mortality rate of 10% to 20% with late-onset sepsis. The rate of sepsis in term infants is 0.8 cases per 1,000 live births, and the mortality rate is 2.3%. Two or more maternal risk factors escalate the risk from 4% to 5%(Camacho-Gonzalez et al., 2013).

Low-birthweight (LBW) infants are at the highest risk for early- and late-onset neonatal sepsis. This risk is caused, in part, by mechanical factors such as an increased skin fragility and development of pulmonary atelectasis; immunologic factors such as a depressed function of neutrophils, lack of prior exposure to illness and dependence of the fetal antibody spectrum upon that received from the mother; and a prolonged hospital stay with increased exposure to the neonatal intensive care unit (NICU) environment, including various invasive devices and procedures. The National Institute of Child Health and Human Development (NICHD) found that of very low-birthweight (VLBW) infants, 19 cases of early-onset sepsis per 1,000 live births, and 25 cases of late-onset sepsis per 1,000 live births in infants 401 and 1,500 grams. Fifty percent of infants weighing between 405 and 750 grams developed late-onset sepsis(Camacho-Gonzalez et al., 2013).

The organisms responsible for neonatal infection have changed over the past 60 years, and there are marked regional variations. Today, microorganisms commonly responsible for early-onset infection include Group B streptococcus (GBS), Escherichia coli, coagulase-negative Staphylococcus, Haemophilus influenza, or Listeria monocytogenes. Late-onset infections are most often caused by staphylococci, pseudomonas, or bacteroides fragilis (anaerobes). Coagulase-negative staphylococcal species, especially Staphylococcus epidermidis, is the leading cause, responsible for greater than 50% of LOS cases in industrialized countries (Singh, 2019).

After seven days of age, the nosocomial influence of organisms is important to consider. These organisms include staphylococcus epidermidis, particularly with invasive tubes or lines; S. aureus (common skin contaminant); and the spectrum of gram-negative bacilli: Klebsiella, Pseudomonas, Serratia, and E. coli. Preterm infants are often affected by repeated bouts of sepsis. Often the organism is unidentified by blood culture but is simply responsive to antibiotic treatment. Escherichia coli and Group B streptococcus account for 70 percent of all infections (Camacho-Gonzalez et al., 2013).

One of the predisposing newborn factors for infection is prematurity. Premature infants are far more likely to be jeopardized by the invasion of foreign agents. Because of being born too soon, these infants have missed out on passive transmission of maternal exposure to antigens and subsequent creation of an antibody defense system. Also, the cellular immune system is not well developed in the preterm infant, exhibiting decreased phagocytic cellular defenses (Camacho-Gonzalez et al., 2013).

Prolonged rupture of the fetal membranes (PROM) is a well-known risk factor for the development of infection. The fetus is at increased risk because the break in the amniotic sac provides a pathway for the migration of organisms up the vaginal vault. The current trend permitting PROM to persist in the presence of a preterm fetus creates the potential environment for bacterial proliferation and subsequent neonatal infection. Many facilities have guidelines for mandatory septic workups for all preterm infants with PROM and term infants with prolonged rupture of membranes (Neonatal sepsis, 2020).

A mother with a fever or who has been ill prior to delivery can pass the infection on to her infant. A septic workup may be indicated if a maternal temperature of 101 ° F is noted at delivery. Maternal cervical or amniotic fluid cultures may be necessary to determine the causative agent of elevated temperature. If maternal illness suggests viral infection, neonatal viral cultures may be drawn. Early identification of causative agents in the mother may help manage the infant (Tesini, 2018).

The presence of foul-smelling amniotic fluid indicates neonatal antimicrobial therapy in symptomatic infants. Routine blood cultures and a complete blood count with differential may be indicated to identify neonatal infection. Under these circumstances, the placenta should be sent for pathologic evaluation (UpToDate, 2020).

CDC guidelines for an early onset sepsis evaluation based on maternal risk factors are unclear and lead to increased laboratory workup and initiation of antibiotics. Increased antibiotics use leads to separation of the mother, and the baby decreases breastfeeding rates, increases antibiotic resistance, and ultimately increases health care costs. A neonatal sepsis calculator published by Kaiser Permanente group based on a large multicenter study is being used at several Neonatal Intensive Care Units (NICU) nationwide. This available online tool is free and can be used to assess EOS in newborns based on maternal and neonatal risk factors. This calculator has been proven to decrease the antibiotic use for EOS in several NICUs. Calculation of maternal temperature, length of rupture of membranes, and gestational age calculate the neonatal risk of sepsis. The results tell whether an infant is at a low, moderate, or high risk of infection (Simpson et al., 2018).

Other risk factors associated with neonatal infection are antenatal or intrapartal asphyxia, iatrogenic complications of treatment modalities, and postnatal invasive procedures. A predisposition to developing sepsis has been noted in low birth weight babies placed on Indomethacin therapy to treat patent ductus arteriosus. Stress inhibits the newborn's ability to fight infection for several reasons. It increases the metabolic rate, thus requiring more oxygen and energy to support or sustain the body's vital functions. If the newborn is severely compromised and the oxygen levels continue to be low, regional tissue damage can result. Ischemic or necrotic areas in the lungs, heart, brain or gastrointestinal system provide a receptive environment for colonization and overgrowth of normal bacterial flora. This overgrowth of bacteria is one of the most common sources of neonatal sepsis. Damaged tissue can be repaired only if the infectious process is reversed and adequate tissue perfusion is restored (Neonatal Sepsis, 2019).

There are several known maternal factors associated with neonatal sepsis and infection: low socioeconomic status, malnutrition, no prenatal care, substance abuse, rupture of membranes prior to 37 weeks, substance abuse, presence of urinary tract infection at delivery, peripartum infection, clinical amnionitis, and general bacterial colonization. Neonatal risk factors include antenatal, intrapartal stress (perinatal asphyxia), congenital anomalies, male sex, multiple gestations, concurrent neonatal disease processes, prematurity, immune system immaturity, and invasive admission procedures, and antimicrobial therapies (Neonatal Sepsis, 2019).

Summary of risk factors:

1. Preterm labor
2. Prolonged rupture of membranes > 12-18 hours (the loss of intact membranes allows vaginal bacterial direct access to the fetus)
3. Maternal fever – chorioamnionitis, maternal septicemia transient bacteremia
4. Multiple gestations
5. Previously infected infant
6. Prematurity
7. Premature rupture of membranes
8. Birth asphyxia (hypoxia and acidosis may depress cellular immune functions)
9. Coitus occurring close to delivery carries an uncertain risk for maternal colonization and ultimately for fetal or neonatal infection
10. Postnatal procedures such as intubation, chest tube insertion, and catheterization of umbilical vessels

Signs and symptoms identified in an infected newborn include hypothermia and the inability of the neonate to maintain a temperature in the neutral thermal zone (usually between 97.7 and 99 °F axillary). Newborns do not have febrile mechanisms. Premature infants often present with a low body temperature as illness ensues. Hyperthermia can occur in term newborns, with temperatures over 100.1 ° F, but is relatively rare in preterm infants (Singh, 2019).

An infected infant often presents with lethargy, poor feeding, and perhaps a poor Moro reflex. The infant may eat well in the morning but by evening suckles poorly or has residuals if gavage fed. A newborn that is beginning to focus energy on fighting off infection may have abdominal distention, delayed gastric emptying time, and perhaps diarrhea or loose green or brown stools. Over a longer period, it may be identified that a particular infant has poor weight gain. Hypoglycemia or hyperglycemia and glycosuria are often a sign of a septic infant who is unable to compensate for the overload of an invasion of infectious organisms. Small preterm infants who are septic often present early with problems handling glucose loads (Singh, 2019).

Vascular perfusion is typically affected when an infant is a septic. Often, a sick neonate will appear gray, mottled, or ashen in color. A sick infant may have poor perfusion and hypotension. Infants can present as cyanotic and develop petechiae and, potentially, thrombocytopenia. Infections can cause Disseminating Intravascular Coagulopathy (DIC), thereby affecting the prothrombin time, partial thromboplastin time, and split fibrin product laboratory values of the newborn. Neonates can subsequently develop hemolytic anemia, thereby significantly affecting oxygen-carrying capacity in the tiny preterm infant (Neonatal Sepsis, 2019).

Apnea in a term infant in the first few hours of life can be a serious sign of inability to regulate the brain's respiratory center. Respiratory distress can be an early sign of pneumonia and should be considered carefully. A preterm infant who demonstrates apnea in the first 24 hours of life is likely to be infected with foreign organisms. Shock can be a sudden clinical sign of fulminant sepsis and demands immediate attention, even to double volume exchange or WBC or granulocyte transfusion (Neonatal Sepsis, 2019).

An infant who has bradycardia for unexplained reasons may be sending a signal of possible sepsis. Sclerema and sudden purpura, rash, or Petechiae can also be early signs of sepsis. Signs and symptoms identified in the infected infant are listed below (Neonatal Sepsis, 2019).

1. CNS
   1. Lethargy or irritability
   2. Early and persistent apnea (at less than 24 hours of age)
   3. Fever
   4. Temperature instability
   5. Warm trunk with cold extremities
   6. Poor Moro reflex
   7. Seizures
   8. Poor spontaneous movement
2. Respiratory
   1. Tachypnea
   2. Grunting
   3. Labored breathing
   4. Apnea
   5. Nasal flaring
3. Gastrointestinal
   1. Feeding intolerance
   2. Vomiting
   3. Poor feeding
   4. Large (>50%) gastric residuals of prior feeding suggest ileus
   5. Diarrhea
   6. Hematochezia
   7. Abdominal distention
4. Skin
   1. Gram-negative bacteria, especially pseudomonas, may produce small necrotic lesions on the face and trunk
   2. Petechiae
   3. Pustulosis
   4. Edema
   5. Jaundice
   6. Sclerema
5. Circulatory
   1. Bradycardia
   2. Tachycardia
   3. Hypotension
   4. Cyanosis
   5. Decreased perfusion
6. Physical exam
   1. Local infections – scalp abscess
   2. Joint immobility
   3. Localized erythema (omphalitis)

One of the initial diagnostic clues to infection can be obtained from a complete blood count (CBC). As many as 50% of all CBCs may be normal initially. A septic infant may demonstrate leukopenia, especially neutropenia (Neonatal Sepsis, 2019).

The diagnosis of sepsis in a newborn is very difficult to make and is most often based on clinical hunches. The following may be laboratory findings in a septic newborn (Antibiotic Use, 2016).

• Increased total neutrophils – neutrophilia
• Decreased total neutrophils – neutropenia
• Increased immature forms (bands, metamyelocytes, sometimes promyelocytes, and myeloblasts)
• A rise in C-reactive protein
• Leukopenia, especially neutropenia (< 2000 total neutrophils and bands)
• Extreme leukocytosis (> 20,000 neutrophils and bands)
• Increased (> 0.2) ratio of immature neutrophils to mature forms
• Thrombocytopenia (< 100,000 platelets/mm3)
• Metabolic acidosis
• Erythrocyte sedimentation rate (ESR) is not helpful as an isolated test
• Jaundice (not a reliable sign of bacterial sepsis in newborns)
• The presence of WBC in gastric aspirate obtained shortly after birth indicates amnionitis. The absence of WBC helps in the decision to observe rather than treat some infants
• Latex agglutination test for Group B streptococcus (GBS) – urine must be concentrated 25 times and free from skin contamination. One-tenth ml of CSF is required
• CSF protein 150-200 mg/L for term infants or 300 mg/L for preterm infants is frequently seen
• CSF glucose 50-60% or more of blood glucose level

No single clinical sign or abnormal laboratory test is highly associated with sepsis, but combinations of the above signs strongly suggest sepsis or meningitis. Therefore, a prudent physician identifies infants at high risk and provides for extremely close observation of vital signs and the overall status of those children in the first 24 hours of life.

The organisms responsible for neonatal infection have changed over the past 60 years, and there are marked regional variations. When there is a high suspicion of infection, identification of the microorganism and early institution of therapy provides the best outcome. The evaluation for infection generally includes the following components (Neonatology, 2020).

• Obtain blood cultures. The blood volume should not be less than 10 percent of the culture medium volume.
• Obtain blood for complete blood count with differential and platelet count.
• Through a lumbar puncture, collect spinal fluid for at least a culture and Gram stain. A gram stain of the cerebrospinal fluid (CSF) can indicate the type of microorganism responsible for the infection. Then perform a cell count and protein and glucose determination. Pressure measurement is of little diagnostic use in newborns.
• It may be wise to alert the clinical laboratory that only a small amount of spinal fluid will be available for analysis.
• Urine obtained by suprapubic bladder aspiration is unlikely to demonstrate bacteria by culture or Gram stain when obtained immediately after birth. An evaluation for sepsis performed several days after birth should include an aspiration as part of the diagnostic evaluation.
• A chest radiograph is required to rule out pneumonia. The pneumonic pattern of GBS may mimic hyaline membrane disease (HMD). Parenchymal densities must be considered pneumonia and treated until cultures, or clinical course proves otherwise.
• Other tests that may be useful include latex agglutination or counter immunoelectrophoresis of urine or CSF, erythrocyte sedimentation rate, and acute-phase proteins.
• Other nonspecific findings, such as hypoglycemia, hypocalcemia, thrombocytopenia, hyponatremia, or metabolic acidosis, may also be present.
• A definitive diagnosis is based on the recovery of a microorganism in blood, CSF, urine, or other body fluid.

Comprehensive management must include supportive care with fluids, glucose, electrolytes, blood pressure and tissue perfusion support. Collaborative management for an infected infant focuses on ventilatory support, oxygen therapy, correction of acidosis, immune therapy, volume expanders, extracorporeal membrane oxygenation if persistent pulmonary hypertension is present, and antimicrobial agents. The exact management plan is based on individual signs, symptoms, and laboratory tests.

The provision of adequate warmth and correction of hypotension, if observed, should be the priorities of care. If such monitoring has not been instituted, central arterial pressure monitoring should be considered. Long-term effects of vasopressor agents on neonates are relatively undocumented, but such agents may be indicated for hypotension and oliguria. Dopamine 5 to 15 mcg/kg/min infused into a secure intravenous site. Assisted ventilation may be necessary if severe apnea or sepsis is complicated by severe pneumonia (Ford-Jones, 1999).

The selection of antimicrobials is based on the microorganism present and the infant's response to therapy. Infectious microorganisms fall into two broad classes: gram-positive and gram-negative. The organism's shape categorizes it as either a coccus or a rod. Generally, gram-positive organisms respond to broad-spectrum antibiotics such as penicillin analogs, first-generation cephalosporins, and beta-lactamase penicillins. The gram-negative microorganisms are most often susceptible to aminoglycosides, cephalosporins, and chloramphenicol.

Tests must be run to determine the specific sensitivity of an organism to the antimicrobial selected. Initial antibiotics for infections of undetermined etiology should be ampicillin and gentamycin so that both gram-positive and gram-negative organisms are covered. This combination of antimicrobials has a synergistic effect, increasing the efficacy of either drug therapy used alone. Additional therapy or selection of other agents is necessary if a staphylococcal infection is suspected. If a staphylococcal infection is strongly suspected, consider methicillin. If staphylococcus epidermidis is recovered in cultures and is resistant to methicillin, consider vancomycin. The presence of indwelling catheters, the infant's postnatal age, and CSF findings should influence the treatment decisions (Camacho-Gonzalez et al., 2013).

Aminoglycoside antibiotics have poor or variable CSF penetration and are therefore of limited usefulness in gram-negative meningitis. Third-generation cephalosporins effectively penetrate the CSF.

Correct coagulation abnormalities should be anticipated with significant sepsis of any bacterial etiology or enter-viral infections. Platelet transfusions, fresh frozen plasma, or cryoprecipitate transfusions for correction of abnormal prothrombin or partial thromboplastin times are indicated based on the specific abnormalities detected and the availability of these products (Camacho-Gonzalez et al., 2013).

If sepsis is suspected in the presence of "soft signs" of infection, then cultures should be obtained, and antibiotics should be given for a minimum of 3 days while awaiting culture results.

A "healthy-appearing" neonate with bacteremia can become an infant in septic shock within a few hours. An early sign of untreated sepsis is death. Overwhelming sepsis in neonates includes respiratory failure, acidosis, extremely poor perfusion, hypotension, grunting respirations, evidence of hemorrhage petechiae, purpura, pulmonary bleeding, neutropenia, and eventually sclerema. These infants lack specific antibodies in their pool of trans-placentally acquired immunoglobulin. This lack limits the ability of the neutrophils to ingest and destroy bacteria. The extremely rapid growth of common infecting agents (Group B streptococcus, E-coli) may create a large body burden of organisms that relative antibiotic resistance results. Toxins already circulating may cause profound cardiopulmonary changes that are unresponsive to treatment.

Because of the extremely high mortality of such infants, several ancillary therapies have been tried in addition to the conventionally accepted treatments of assisted ventilation, crystalloid fluid administration, and infusions of bicarbonate, antibiotics, and vasopressor agents. The first of these approaches consists of a treatment to replace or supply specific immune factors. This treatment may mean granulocyte transfusions in infants with neutropenia, total body depletion of neutrophils reflected in absent or decreased bone marrow stores, or infusion of pooled adult hyperimmune globin to collect specific antibody defenses (Camacho-Gonzalez et al., 2013).

The second approach is to correct these defects and alter the infant's blood's oxygen-hemoglobin and oxygen tissue delivery characteristics by complete exchange transfusion (Tesini, 2018).

The microorganisms most often responsible for congenital infections have been grouped as TORCH infections. These include toxoplasmosis, others, rubella, cytomegalovirus, and herpes. The "others" category includes various microorganisms that have been responsible for congenital infections. However, the list of microorganisms implicated in congenital infections has grown, so the acronym is no longer inclusive. It still means all infections acquired by the fetus in utero (Ford-Jones, 1999).

Acute toxoplasmosis in a pregnant woman often goes undetected and undiagnosed. Maternal transmission occurs from the consumption of poorly cooked meat or ingesting infected cat feces. The risk of transmission is highest in the third trimester. First-trimester transmission usually ends in spontaneous abortion. Clinical questioning after identifying an infected infant often leads to reflection and memories of a period of enlarged lymph nodes and fatigue but no fever. Women often report a mononucleosis-like syndrome that may have a febrile course, with malaise, headache, fatigue, sore throat, and sore muscles (Congenital toxoplasmosis, 2019).

In an infant, toxoplasmosis can present with hydrocephalus, chorioretinitis, and intracranial calcification. There is an incredible variety of clinical signs in the scope of the disease. Severe erythroblastosis, hydrops fetalis, and other clinical signs can occur from a normal picture at birth. Neurological signs similar to encephalitis may be the only significant presentation of this clinical problem, including seizures, bulging fontanels, nystagmus, and abnormal increase in circumference of the head. If the infant is treated, signs and symptoms may disappear, allowing normal cerebral growth and development (Congenital toxoplasmosis, 2019).

The delayed disease may occur in the first two months of life in term infants and is usually milder. Clinical signs may include generalized sepsis, enlarged liver, spleen, late-onset jaundice, enlarged lymph nodes, or late-onset central nervous system problems, including hydrocephalus and eye lesions. Infants with congenital toxoplasmosis may have new lesions appearing until age five years.

The typical presentation of the rubella virus is mild, with malaise, low-grade fever, headache, and conjunctivitis. In 1 to 5 days, a macular rash appears on the face and usually disappears after 3 to 4 days. Natural viremia is necessary for placental and fetal primary disease. Most cases occur following primary disease. Skin rashes that resemble rubella may occur due to adenovirus, enterovirus, or other respiratory virus infections. Laboratory titers are recommended to confirm the diagnosis of rubella infection since there is a strong possibility of subclinical infection. It takes about 4 to 6 weeks to obtain clinical confirmation of rubella isolation. The detection of rubella antibodies confirms the presence of the infection (Congenital rubella, 2020).

A fetus infected with rubella often has cardiac defects and deafness. The central nervous system seems particularly vulnerable to the rubella virus, especially if the virus is acquired prior to the first 16 weeks of gestation. The CDC describes congenital rubella syndrome as hearing loss, mental retardation, cardiac malformations, and eye defects. The rubella virus can slow cell replication. This slowed replication causes intrauterine growth retardation and cell differentiation failure during fetal organ formation. Tissue damage seems to occur from the inflammatory response to the infection. Myocarditis, pneumonitis, hepatosplenomegaly, and vascular stenosis can also be present. As seen with other severe congenital infections, signs and symptoms may continue to develop until 10 or 20 years of age. This disease's late clinical signs include insulin-dependent diabetes, thyroid abnormalities, hypoadrenalism, hearing loss, and eye damage (Congenital rubella, 2020).

Cytomegalovirus (CMV), a member of the herpes family, is a very common infection. More damage occurs to the fetus when the exposure to and acquisition of CMV occur from a primary lesion. Congenital CMV occurs in about 0.2 to 2.2 percent of all newborn infants. Primary lesions cause intrauterine growth retardation, microcephaly, periventricular calcifications, deafness, blindness, congenital cataracts, profound mental retardation, hepatosplenomegaly, and jaundice. A characteristic pattern of Petechiae, called "blueberry muffin" syndrome, is associated with congenital CMV. Severe complications at birth are seen in approximately 5 percent of congenital infections. Urine culture for CMV is the most rapid and sensitive indicator of infection. IgG and IgM antibody titers are also indicated. Elevated IgM levels alone denote exposure to CMV but are not diagnostic because there is no method to determine the timing of the exposure. Elevate IgG titers indicate perinatally acquired CMV infection. The transmission of CMV via infected blood products has been significantly decreased through CMV-negative donors or irradiation of blood products. Premature and low birth weight infants are especially vulnerable to the infusion of this virus in blood products. The best prevention method is the institution of standard precautions, including good hand washing (Congenital cytomegalovirus, 2019).

When newborns acquire syphilis from hematogenous spread across the placenta, the effects are on the major organ systems of the fetus, especially the central nervous system. Common presentations of the infected infant are hepatosplenomegaly, jaundice, low birth weight, intrauterine growth retardation, anemia, and osteochondritis. There is often a bilaterally superficial peeling of the skin on the neonatal palms and soles. Nonimmune hydrops is a very common presentation in congenital syphilis. The symptomatology of perinatal syphilis is similar to that of any other viral infection that spreads hematogenously from the mother to the placenta and onto the developing fetus. A lumbar puncture for CSF analysis and radiographs of the long bones facilitate the definitive diagnosis. Congenital neurosyphilis is always a consideration, and the CSF should be examined for the presence of spirochetes. X-ray changes such as blurring the epiphyseal borders demonstrate recent fetal infection, and periostitis represents prolonged involvement (Congenital syphilis, 2017).

Acquisition of the herpes simplex virus in utero can result in spontaneous abortion, preterm birth, or a normal baby. Manifestations of the disease are very broad. The clinical presentation of the congenital acquisition of the infection includes skin vesicles or scarring, hypopigmentation, chorioretinitis, microcephaly, and hydranencephaly. Greater than 20 percent of newborns with the disseminated disease do not develop skin vesicles, making identifying positive infants more difficult. Laboratory tests are the most common way to differentiate HSV from other bacterial and viral infections. The most rapid method includes a cytologic exam. Routine cultures should include any vesicles on the skin, oropharyngeal or eye secretions, or stool. Viral typing is only done for epidemiologic purposes. Intrapartal transmission is more likely to occur in the presence of ruptured membranes. Other risk factors include intrauterine fetal monitoring (scalp electrodes and intrauterine pressure catheters) and fetal scalp sampling. It is not recommended that women infected with HSV be monitored by these methods. Transmission from mother to infant from an infected breast lesion and oral lesions has been reported (UpToDate, 2018).

Varicella is a member of the herpes virus family that commonly causes chickenpox and varicella-zoster. Most women of childbearing age have been exposed to or have contracted this virus; those that have not should receive the varicella vaccine prior to pregnancy. Symptoms of varicella are usually present 10 to 20 days after exposure and include fever, malaise, and an itchy rash. The maculopapular rash eventually forms vesicles and crusts over. Potential complications include pneumonia, encephalitis, arthritis, and bacterial cellulitis. If the virus is contracted early in pregnancy, the damage is likely to be cutaneous musculoskeletal, neurological, and ocular. Infants have intrauterine growth retardation, microcephaly, cerebellar and cortical atrophy, cataracts, and chorioretinitis. Viral infection in the last three weeks of pregnancy will infect one in four newborns. The timing of the exposure determines the severity of the newborn disease. Infections are generally severe if contracted within four days before delivery and two days after delivery. Severe viral respiratory distress with significantly depleted maternal passive antibody transmission puts the infant at greater risk for other complications (Blumental and Lepage, 2018).

Gonorrhea appears most frequently in young adults, ages 15 to 24 years. Symptoms are mild, but in the pregnant woman can cause inflammation and weakening of the fetal membranes and early rupture. Gonococcal conjunctivitis in the newborn has historically been a risk from transmission via the birth canal. Prophylaxis has been mandated by law, with the use of silver nitrate 1 percent solution or erythromycin in both eyes at birth. Fetal scalp electrodes have been identified as a potential method of organism transmission to the fetus.

Hepatitis B Virus (HBV) infection early in pregnancy causes a 50 percent risk of neonatal HBV and a 90 percent risk of developing HBV by their first birthday. Untreated infants are likely to become carriers, eventually leading to primary hepatocellular carcinoma. Treatment for these infants should be HBV vaccine with hepatitis B immunoglobulin. Prematurity, low birth weight, and hyperbilirubinemia are clinical signs of HBV infection. Hepatosplenomegaly is also a common presenting symptom of an infant that is infected. An infected infant may be asymptomatic or present with a picture of fulminant sepsis (Tesini, 2018b).

Human Papilloma Virus (HPV) – genital warts can cause laryngeal papillomatosis in the newborn, demonstrated by a weak cry or hoarseness if the mother is not treated. The newborn may have stridor or other respiratory symptoms. The presence of these warts during vaginal delivery can be extremely uncomfortable. Intrapartal transmission is possible if the warts are visible. Prenatal treatment is associated with low complications and recurrence rates. The treatment alleviates the need for cesarean delivery. Examination, treatment, and follow-up of sexual partners are important aspects of treatment because 50 percent of partners are infected (LaCour and Trimble, 2012).

Chlamydia is a bacterium that grows between cells. It is one of the most common sexually transmitted diseases. Chlamydia conjunctivitis can present in the newborn with a very watery discharge that may progress to purulent exudates. Application of erythromycin ointment at birth for ocular prophylaxis will successfully treat both Chlamydia and gonococcal conjunctivitis. Pneumonia can occur in newborns that have contracted Chlamydia from their mother's genital tract. The typical presentation is tachypnea, barrel chest, and an increased oxygen requirement. The infant may have interstitial infiltrations, hepatosplenomegaly, and increased eosinophils. Diagnosis is based on physical examination and conjunctivitis (Chlamydial Infections, 2015).

Adenovirus and Rotavirus can be enteric and can cause significant viral gastroenteritis. Breastfeeding can protect against these organisms. Early signs of illness include lethargy, irritability, and poor feeding, followed by passage of watery yellow or green stools free of blood but containing mucus. Vomiting and a slight fever may accompany diarrhea. Rotavirus has been shown to cause necrotizing enterocolitis (Censoplano, 2018).

Candida albicans is a fungus that may result from prolonged broad-spectrum antibiotic use in small premature infants. Yeast infections can localize in any organ system. Administration of hyperalimentation, frequent use of indwelling venous lines, and invasive procedures may also predispose the infant to Candida. The infants may present with thrush or cutaneous (perianal area) or acute disseminated candidiasis (systemic infection). The infant presents with signs and symptoms of sepsis, often worsening with no presence of positive cultures. The infant may have respiratory distress, abdominal distention, guaiac-positive stools, carbohydrate intolerance, candiduria, temperature instability, and hypotension. Cutaneous infection may be treated with Nystatin, but systemic infection requires treatment with Amphotericin (Greenberg and Benjamin, 2014).

HIV/AIDS offers the infant three modes of transmission: a) transplacental, b) intrapartal, where there is exposure to maternal blood and vaginal secretions, and c) postnatal through maternal secretions like breast milk. HIV causes immunosuppression in the neonate. An HIV mom is more susceptible to other opportunistic organisms, such as CMV and HSV, which put the infant at risk. Neonates born to HIV-positive mothers are usually asymptomatic. Infant symptoms usually do not appear until 4-6 months of age. These later symptoms include failure to thrive, persistent thrush, hepatosplenomegaly, recurrent diarrhea, recurrent bacterial infections, and hepatitis. These infants should be treated immediately after birth with AZT if the mother's HIV status is known. If the mother was treated during pregnancy with AZT, the baby has a better chance of not getting the virus. Immunizations for HIV-exposed infants should NOT be a live virus (Initial Postnatal Management, 2019).

Both colonization and infection are nosocomial events, meaning "of or related to a hospital." The common meaning of the term nosocomial is "hospital-acquired." Nursery-acquired infections are reported to the Center for Disease Control, which has a National Nosocomial Infections Surveillance System.

The incidence of nosocomial infections in NICUs is 5 to 25 percent. Infants who are critically ill remain in a pathogen-filled environment and are often in jeopardy because of their prolonged length of stay in the hospital. Mortality associated with these infections is anywhere from 5 to 20 percent, depending on the geographic area and specific weight groups (UpToDate, 2018).

Coagulase-negative staphylococcus has been identified as a major cause of nosocomial infections. Low birth weight, multiple gestations, and prolonged hospitalization are significant factors for nosocomial infection. Yeast infections often occur if previous antibiotic therapy has been given. This infection is also associated with colonization of vascular catheters, assisted ventilation, and necrotizing enterocolitis(UpToDate, 2018).

Gram-negative and gram-positive or viral organisms can cause nursery epidemics because they can colonize or infect human skin or the gastrointestinal tract; the ability to be carried from person to person by hand contact; and characteristics that allow existence on the hands of personnel or in fluids or on inanimate objects, including intravenous fluids, respiratory support equipment, solutions used for medications, disinfectants, and banked breast milk (UpToDate, 2018).

Resistance to antibiotics is a serious problem in many NICUs, particularly with gram-negative enteric pathogens. Aminoglycoside resistance is a problem in many urban nurseries, and colonization and infection with methicillin-resistant staph aureus. Respiratory infections have occurred in many nurseries, including RSV, influenza, Parainfluenza, rhinovirus, and echovirus. These are more difficult to identify and thus more difficult to report. CMV (cytomegalovirus) infection has been reported as a transfusion-related problem in low birth weight infants and thus has prompted the current policy using CMV-screen donors. Hepatitis A has also been reported as a transfusion-related problem that may develop in infants and staff in NICUs. Thus, given the right environment and support, almost any organism can become a transmitted nosocomial infection (UpToDate, 2018).

Based on the recommendations of the American Academy of Pediatrics and the Centers for Disease Control, the hospital infection control committee should set policies and procedures in nurseries. The significance of these policies to newborns should be detailed in a hospital policy book. The following topics should be covered.

• Ocular prophylaxis
• Skin and cord care
• Nursery staff
• Nursery design and environment
• Hand washing
• Staff apparel
• Isolation
• Visitors
• Employee health
• Epidemic control

Many factors place the neonate at high risk for infection. The nurse is in a unique role in implementing methods for the prevention of infection in nurseries, detecting early signs and symptoms of infection, and participating in infection control. An understanding of risk factors, methods of perinatal transmission, microorganisms, signs and symptoms of infections, and appropriate therapy provides the healthcare providers with a sound basis for management of care and the development of hospital infection control policies for the NICU.

A woman arrives in the labor and delivery unit. She is a grava six para 3, 24-year-old with limited prenatal care. Her description of the care she received is unclear. She has a history of 3 vaginal births. She thinks she is between 36- and 37-weeks' gestation. Her GBS status is unknown. She is 9cm/100% effaced and +1 station when she arrives. She states that she thinks her water broke two days before her arrival, but she did not start contracting until earlier this morning. Her BP is 128/88, resp 20, pulse 122, and temp 97.2°F. She quickly progresses to fully dilated and delivers the baby before receiving any medications.

The baby is born and has a weak cry at delivery with good HR and poor tone and color. The baby is brought to the radiant warmer and is initially examined. The baby has a HR of 170, resp 72, and temp 101 °F. The baby is taken to the NICU for observation.

What is the differential diagnosis? What tests are needed?

This mother has an unknown GBS status and arrives with a fever. Her amniotic sac has likely been ruptured for at least two days. This baby could have a GBS infection if the woman was positive because she was untreated. The woman could also have chorioamnionitis, which can have caused the newborn to become infected. E. coli is a likely culprit.

This baby has to be worked up for sepsis. The baby will need a CBC, blood cultures, and chest x-ray. The newborn may need a lumbar puncture to test the CSF fluid. This baby will then likely be started on antibiotics. Initial antibiotics for infections of undetermined etiology should be ampicillin and gentamycin so that both gram-positive and gram-negative organisms are covered. The baby will need an IV, thermoregulation, and respiratory support.

• Antibiotic Use for Sepsis in Neonates and Children: 2016. Published 2016. Accessed February 16, 2020. Visit Source.
• Blumental S, Lepage P. Management of varicella in neonates and infants. BMJ Paediatrics Open. Published May 1, 2019. Accessed February 16, 2020. Visit Source.
• Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatric Clinics of North America. Published April 2013. Accessed February 16, 2020. Visit Source.
• Censoplano N, Gorga S, Waldeck K, Stillwell T, Rabah-Hammad R, Flori H. Neonatal adenovirus infection complicated by hemophagocytic lymphohistiocytosis syndrome. American Academy of Pediatrics. Published April 1, 2018. Accessed February 16, 2020. Visit Source.
• Chlamydial Infections - 2015 STD Treatment Guidelines. Centers for Disease Control and Prevention. Published June 4, 2015. Accessed 16, 2020. Visit Source.
• Congenital cytomegalovirus: MedlinePlus Medical Encyclopedia. MedlinePlus. Published April 2019. Accessed February 16, 2020. Visit Source.
• Congenital rubella: MedlinePlus Medical Encyclopedia. MedlinePlus. Published April 2019. Accessed February 16, 2020. Visit Source.
• Congenital toxoplasmosis: MedlinePlus Medical Encyclopedia. MedlinePlus. Published April 4, 2019. Accessed February 16, 2020. Visit Source.
• Congenital syphilis: MedlinePlus Medical Encyclopedia. MedlinePlus. Published December 2017. Accessed February 16, 2020. Visit Source.
• Ford-Jones EL. An approach to the diagnosis of congenital infections. Pediatrics & Child Health. Published March 1999. Accessed February 16, 2020. Visit Source.
• Greenberg RG, Benjamin DK Jr. Neonatal candidiasis: diagnosis, prevention, and treatment. J Infect. 2014;69 Suppl 1(0 1): S19–S22. doi:10.1016/j.jinf.2014.07.012.
• Initial Postnatal Management of the Neonate Exposed to HIV Management of Infants Born to Women with HIV Infection Perinatal. National Institutes of Health. Published December 24, 2019. Accessed February 16, 2020. Visit Source.
• LaCour DE, Trimble C. Human papillomavirus in infants: transmission, prevalence, and persistence. J Pediatr Adolesc Gynecol. 2012;25(2):93–97. doi:10.1016/j.jpag.2011.03.001.
• Neonatal Sepsis. Background, Pathophysiology, Etiology. Published November 13, 2019. Accessed February 16, 2020. Visit Source.
• Neonatal sepsis: MedlinePlus Medical Encyclopedia. MedlinePlus. Published 2020. Accessed February 16, 2020. Visit Source.
• Neonatology. Intrauterine (Congenital) Infections. Published 2017. Accessed February 16, 2020. Visit Source.
• Simpson E, Akangire G, Bohning J, et al. Neonatal sepsis calculator in reduction of antibiotics use in EOS (early onset sepsis). American Academy of Pediatrics. Published May 1, 2018. Accessed February 17, 2020. Visit Source.
• Singh M. Neonatal Sepsis. StatPearls [Internet]. Published November 25, 2019. Accessed February 16, 2020. Visit Source.
• Tesini BL, Last full review/revision Jul 2018| Content last modified Jul 2018. Overview of neonatal infections - pediatrics. Merck Manuals Professional Edition. Accessed February 16, 2020. Visit Source.
• Tesini BLLast full review/revision Jul 2018| Content last modified Jul 2018b. Neonatal Hepatitis B Virus (HBV) Infection - Pediatrics. Merck Manuals Professional Edition. Published July 2018. Accessed February 16, 2020. Visit Source.
• UpToDate. Accessed February 16, 2020. Visit Source.
• UpToDate. Published September 2018. Accessed February 16, 2020. Visit Source.
• UpToDate. Published September 2018. Accessed February 16, 2020. Visit Source.