Infection: NICU Handbook

Charles Grose, MD, Herman A. Hein MD, and Jennifer Bermick, MD
Peer Review Status: Internally Peer Reviewed Revised 2022

Congenital infections

The infant suspected of being infected with syphilis, rubella, herpesviruses (HSV, VZV, CMV), HIV or other agents, particularly the enteroviruses, represents a risk to other infants and hospital personnel, particularly pregnant women. Because it is not possible to isolate all newborns who might have one of these congenital infections, the purpose of these policies is to minimize the risk of nosocomial transmission.

Rubella immunity

All personnel working in UIHC must be immune to Rubella (required to have at least 1 dose of rubella or MMR vaccine or have a positive blood test indicating immunity).

Varicella Immunity

All personnel working in UIHC must be immune to Varicella (required to have two doses of vaccine, positive blood test indicating immunity or have a documented diagnosis of either shingles or chickenpox by a healthcare provided).

Precautions

The infant with known or suspected infection or with known or strongly suspected congenital syphilis, rubella, or enterovirus infection should be placed in strict isolation. If the clinical condition allows, the infant may be placed in strict isolation with their mother. Pregnant women should not have contact with these infants and a notice to this effect should be posted at the entrance to the room.

The infant suspected of having a congenital syphilis, rubella or enterovirus infection may be segregated within an incubator or admitted to an isolation room and placed on excretion-secretion precautions. Pregnant women should not have contact with these infants. The incubator or heater bed should have a secretions precautions label affixed and a label prominently posted stating that no pregnant women should have contact with this patient.

The requirements for isolation or segregation for other viral or bacterial pathogens can be found in the Hospital Isolation Manual.

Universal precautions

Universal infection precautions should be used with all infants. Those include wearing gloves when performing invasive procedures (such as drawing blood or starting IVs) or when handling a newly born infant who has not been bathed for the first time. A mask, gloves and goggles (or eyeglasses) should be worn when performing procedures where blood may be propelled or splashed into the eyes (such as insertion of arterial catheters).

HIV infection

While congenital HIV infection is an uncommon disease in Iowa, knowledge about caring for these infants is very important. Vertical transmissions from an infected mother to her child is the cause of over 90% of AIDS cases in children; it has become the primary cause of new cases as other modes of transmission have been eliminated, e.g., transfusion of contaminated blood products.

The perinatal transmission rate is estimated to be 13-39%. Intrauterine, intrapartum, and postpartum infections contribute to this perinatal transmission rate, which is reduced by approximately two-thirds with zidovudine therapy of seropositive pregnant women and their newborns. The newborn therapy involves 6 weeks of oral zidovudine.

Breastfeeding by sero-positive mothers is contraindicated in the U.S. where safe, alternative sources of feeding are available. HIV has been detected in breast milk and transmission of HIV by this route has been demonstrated.

When a baby is born to an HIV seropositive mother, the nursery health care personnel should always wear gloves when handling the newborn infant. If possible, the baby should room in with the mother. Diagnosis and testing of a newborn infant of a seropositive mother should include an infectious disease physician consultation as they will play an active role in the infant’s follow-up. Testing of newborn infants by virologic tests, initially with PCR or culture is recommended at 1 month of age and then between 4 and 6 months of age with subsequent serologic testing and the initiation of antiretroviral therapy if and when indicated.

Coinfection with other bacteria or viruses is possible e.g., CMV and excretion-secretion precautions are indicated.

(≥ 35 weeks Gestation During the First Few Hours of Life) 

Download Evaluation and Management of Possible Neonatal Sepsis diagram

Edward F. Bell, MD, Jonathan M. Klein, MD, and Jennifer Bermick, MD
Peer Review Status: Internally Peer Reviewed

The following guidelines are suggested for selecting inpatients to receive humanized RSV monoclonal antibody (SynagisTM) to reduce the risk of serious RSV infection during RSV season. 

SynagisTM 15 mg/kg IM is provided to high-risk inpatient infants (less than 2 years old) monthly during peak RSV season (maximum of 5 doses per season)

High risk infants include:

• Premature infants < 29 weeks gestation who are ≥ 1 month old
• Premature infants 29 – 31 6/7 weeks gestation with chronic lung disease (bronchopulmonary dysplasia defined as receiving supplemental oxygen for at least 28 days after birth who are ≥ 1 month old)
• Severe lung disease/tracheostomy
• Post-ECMO
• Pulmonary hypoplasia
• Hemodynamically significant cardiac disease (excludes small VSD, ASD or PDA)
• Congenital diaphragmatic hernia
• Pulmonary hypertension
• Neuromuscular disorder/disease
• Congenital anatomic pulmonary abnormality

References 
Groothuis JR, Simoes EAF, Hemming VG, et al. Prophylactic administration of respiratory syncytial virus (RSV) immune globulin in high risk infants and young children. N Engl J Med. 1993; 329:1524-30. SynagisTM Product Information. MedImmune, Inc. Gaithersburg, MD. 1998 (19 June).(Pediatrics 1998 Sep;102(3 Pt 1):531-7, AAP Policy Statement, Pediatrics 2003;112:1442-46, Pediatrics 2004;114:e554-e556, Red Book: 2006 Report of the Committee on Infectious Diseases, 27th Edition), National Perinatal Association 2018 RSV Prevention Clinical Practice Guideline, Neonatology Today 2017;12(10):1-14, (Pediatrics 2014;134(2):e620-638, Pediatrics 2014;134(2):415-420 and Red Book: 2018-21, Report of the Committee on Infectious Diseases, 31st Edition) 

Charles Grose, MD
Peer Review Status: Internally Peer Reviewed

Mothers are routinely tested for the Hepatitis B surface antigen (HBsAg) status during their pregnancy. There is a risk of both vertical perinatal transmission to the newborn from a mother who is HBsAg -positive, and horizontal transmission to the infant during the first 5 years of life. Thus, it is critical that the infants born to mothers who are HBsAg -positive are recognized and therapy initiated.

Preterm Infants

For preterm infants born to HBsAg-positive mothers, both HBIG and Hep B vaccines should be given within 12 h. For those born to HBsAg-unknown mothers, the first vaccine should be given within 12 h and if the maternal status cannot be determined within 12 h, HBIG should be given.

Infants born to HBsAg-positive mothers should be serologically tested for anti-HBs and HBsAg 1 to 3 months after completion of the vaccination series; further vaccinations may be required.

Chetan A. Patel MD and Edward F. Bell, MD
Peer Review Status: Internally Peer Reviewed

Maternal IgG is the major source of fetal and neonatal IgG; hence, the antibody profile of the neonate is dependent on the profile of antibodies in the maternal circulation. Since significant transfer of maternal IgG across the placenta to the fetus does not begin until the 32nd week of gestation, VLBW (<1500 g) infants are born with relatively low levels of IgG compared with full-term infants. Furthermore, in all infants, serum immunoglobulin levels decline further after birth. In term infants, the postnatal physiologic trough occurs at 4 - 6 months of age, but serum IgG levels usually remain above 400 mg/dl. Preterm infants can have levels as low as 60 mg/dl by 3 months of age.

Infectious diseases are a significant cause of morbidity and mortality among preterm infants. The risk of neonatal sepsis is 4 to 10 times higher among infants < 2500 g than in term infants. The incidence of sepsis is gestational age dependent, infection rates reported as high as 50% in infants <1000 g. The survival of low birth weight infants has improved greatly in recent years. But the care of these infants involves procedures (endotracheal intubation, catheters, lines, broad-spectrum antibiotics) that increase their risk of nosocomial infection.

Together, the increased risk factors for sepsis and the relative quantitative and qualitative IgG deficiency in preterm infants (that increases with postnatal age) provide a rationale for intravenous immunoglobulin (IVIG) therapy as a means for prophylaxis and treatment of neonatal sepsis. However, clinical studies have failed to substantiate consistently a beneficial effect of prophylactic use of IVIG in reducing the incidence of hospital-acquired infections in VLBW infants (Baker 1992; Fanaroff, 1994). A meta-analysis of studies done does however suggest a demonstrable benefit of prophylactic IVIG in preventing sepsis in LBW newborns (Jensen, 1997).

Recent evidence suggests that the use of immunoglobulin may be appropriate in the following group of infants. The use of IVIG must be cleared by the attending physician. This list and the references below are not meant to be comprehensive.

Prophylaxis

Prophylaxis to prevent nosocomial infections in preterm infants with BW < 750 g: IVIG 500 mg/kg IV over 3 - 4 hours (@ 10 ml/kg volume), starting the first week of life and every 2 weeks as long as the infant has an indwelling IV line (maximum of 5 doses).

Whenever possible, administer doses on Mondays to reduce cost by allowing multiple infants to be treated from the same vial of IVIG.

Further rationale for prophylatic use of IVIG and the results of several large clinical trials are described in the references cited at the end of this section.

Treatment

Treatment for infants with proven early-onset neonatal sepsis (esp. with Group B strep infection or with accompanying neutropenia): IVIG 500 mg/kg IV over several hours.

The immunoglobulins serve both a therapeutic role (enhancing humoral immunity and clearing the organism) as well as a prophylactic role in helping to prevent superimposed infections. Shortening the bacteremic phase may also limit damage from secondary immune or nonimmune factors contributing to the shock-like state. Total IgG titers in treated, septic neonates remain elevated for ª 10 days. Meta-analysis of the effectiveness of IVIG in the treatment of early-outset sepsis shows that the addition of IVIG to standard therapies increases the survival nearly six-fold (Jensen 1997).

Download Late Onset Sepsis Prophylaxis and Treatment 2022

Download Evaluation and Management of Possible NeonatalHerpes Simplex Infection (within 4 to 6 weeks of birth) PDF

Edward F. Bell, MD
Peer Review Status: Internally Peer Reviewed

RSV infection causes bronchiolitis and pneumonia in infants. Morbidity is high in infants with chronic pulmonary disease or congenital heart disease. RSV infection can be quickly diagnosed in the virology laboratory, by rapid antigen testing on a nasopharyngeal swab. A respiratory panel culture can also diagnose RSV. Infants hospitalized with RSV should be placed in strict isolation. Infants who are at high risk for significant morbidity and/or mortality should be identified and treated prophylactically.

Two prophylactic therapies are available:

• RespiGam^TM is RSV immunoglobulin that also may afford protection against other viral pathogens. It requires intravenous administration over 3-4 hours every 4 weeks. Hence, its use is limited to infants with evidence of more severe chronic lung disease. See "Guidelines for Immunoprophylaxis against RSV".
• Synagis^TM is RSV monoclonal antibody that is specific against RSV. It requires intramuscular injections every 4 weeks. It should be considered for preterm infants without evidence of significant chronic lung disease. See "Guidelines for Immunoprophylaxis against RSV".

Charles Grose, MD
Peer Review Status: Internally Peer Reviewed

Situation I

Oral maternal herpes, or presence of genital vesicles or culture positive genital herpes, with infant delivered by C-section with intact membranes.

Management:

1. Secretion precautions for both baby and mother.
2. Newborn to room in with mother if possible; baby can go to and from mother’s room in bassinet; mother not allowed in nursery.
3. Mother should be instructed on the importance of careful hand washing before and after caring for their infant and wear a clean loving gown to help avoid contact of the infant with lesions or secretions.
4. Mother with herpes labialis should wear a mask when touching her infant and should not kiss or nuzzle the infant until the lesions are cleared.
5. Ask obstetrician to culture any maternal vesicles (if not already done); culture baby’s nasopharynx 24 hours after delivery. If the infant is asymptomatic, obtain surface cultures 24-48 hours after delivery and initiate antiviral therapy if cultures are positive.

Situation II

Presence of genital vesicles or culture positive genital herpes with infant delivered per vagina or by C-section after rupture of membranes.

Management:

1. Strict isolation of the baby from other infants; secretion precautions for the mother.
2. Baby to room with mother; mother not allowed in nursery.
3. Mother should use gloves when handling her baby.
4. Ask obstetrician to culture any maternal vesicles (if not already done); culture baby 24-48 hours after birth, sooner if symptomatic or acyclovir therapy is to be started.
5. For an infant delivered vaginally whose mother has primary, first-episode infections (risk of infection 30-50%), consider empiric acyclovir treatment after cultures are obtained.
6. For an infant delivered vaginally to mothers with active recurrent genital herpes, the risk of infection is ≤5% and emperic treatment is not required.

Situation III

History of previous genital herpes with unknown culture result and infant delivered vaginally or by C-section after rupture of membranes.

Management:

1. Secretion precautions for baby and mother until maternal culture is negative for >72 hours. Observe infant closely and obtain surface cultures 24-48 hours after delivery.
2. Baby can go to and from mother’s room in a bassinet; mother is not allowed in the nursery until her culture is negative for >72 hours.
3. If maternal culture is positive, initiate antiviral therapy and revert to management as in Situation II. Notify the senior staff obstetrician and neonatologist.

Situation IV

History of previous genital herpes with unknown culture result and infant delivered by C-section with intact membranes.

Management:

1. No isolation required.
2. If maternal culture is positive, revert to management as in Situation I.

Situation V

History of previous genital herpes but no active lesions at delivery.

Management:

1. No isolation required.
2. Monitor infant for signs of neonatal HSV infection.
3. No routine cultures of an asymptomatic newborn recommended.

Mother in Situations I, II or III should be in a private room if available.

Neonates with documented HSV infection or those suspected of HSV infection (even if no risk factors are present) should be in an isolation room with secretion precautions. Neonates with a low suspicion of HIV infection but who are being treated with acyclovir can be placed in the nurseries in an isolette with secretion precautions. Since neonatal HSV infection can occur as late as 6 weeks after delivery, physicians must be vigilant and not ignore a new rash or symptoms that might be caused by HSV.

Download Reference Range for WBC Indices PDF

Robert D. Roghair, MD and Herman A. Hein, MD
Peer Review Status: Internally Peer Reviewed

Electronic fetal heart rate monitoring and instrumented deliveries are integral components of high risk obstetric management. Between 0.1% and 5.2% of infants develop an abscess at the site of scalp electrode placement, depending on factors including the duration of membrane rupture. Infections typically present as fluctuant or indurated masses 2-10 days following delivery.

The differential diagnosis includes the vesicular lesions that may be seen with Herpes simplex virus infection. Microbiology of scalp abscesses typically reflects polymicrobial contamination by recto-vaginal bacterial flora (predominantly Streptococcus sp, enteric gram negative rods, and occasionally anaerobes).

If the infant is clinically ill, both sepsis and meningitis are potential complications, and cultures should be obtained prior to incision, drainage and initiation of systemic antibiotics, including ampicillin and gentamicin.

If the infant is clinically well, the primary therapeutic modality is surgical incision and drainage, followed by local wound care. Antimicrobial therapy can be tailored to the sensitivities of the cultured organisms. Care givers must remain vigilant for signs of intracranial extension and consider neuroimaging if the infants condition warrants further evaluation. Parental instruction in wound care and local physician follow-up are critical components of successful management.

1. Cordero L, Anderson CW, Zuspan FP. Scalp abscess: a benign and infrequent complication of fetal monitoring. Am J Obstet Gynecol 1983; 146:126-30.
2. Brook I, Frazier EH. Microbiology of scalp abscess in newborns. Pediatr Infect Dis J 1992; 11:766-8.

Edward F. Bell, MD, Jonathan M. Klein, MD, Robert D. Roghair, MD
Peer Review Status: Internally Peer Reviewed 2012

Term or preterm infants with clinical signs of sepsis

A sepsis work-up should be performed to include a CBC with differential, a blood culture and CSF for analysis and culture, and antibiotic therapy initiated. The infant should be reassessed at 48-72 hours.

Consideration can be given to discontinuing antibiotics if the clinical course has not been suggestive of infection, there are no maternal risk factors identified, (e.g., +GBS, chorioamnionitis), lab results are reassuring, e.g., normal I:T ratio on CBC, normal serial CRPs at 24-72 hours, and the infant’s cultures are negative. Be aware that the cultures may be negative if there was maternal pretreatment with intrapartum antibiotics.

If the infant’s cultures are positive, if signs of sepsis persist or strong maternal risk factors are identified, longer courses of antibiotics are warranted.

Term infants without clinical signs of sepsis with or without pretreatment with intrapartum antibiotics

These infants should be closely observed without the need for cultures or antibiotics for 48 hours if they are asymptomatic. A screening CBC with differential should be obtained.

If the infant becomes symptomatic or if the CBC with differential has an I:T >15%, a sepsis work-up as outlined above should be performed. The length of antibiotic therapy will depend upon the clinical course, lab results, maternal risk factors and infant’s cultures.

Flow sheet for management decisions

Jonathan M. Klein, MD
Peer Review Status: Internally Peer Reviewed

Due to various factors, newborn infants, both preterm and full-term, are highly susceptible to sepsis during the newborn period. In contrast to older infants, children and adults, the signs of sepsis in the newborn are vague and nonspecific. The earliest signs may be apnea, respiratory distress or poor feeding. Other signs and symptoms include lethargy, temperature instability, hyperbilirubinemia, bradycardia, seizures and acidosis.

When sepsis is suspected, a sepsis work-up should be performed to include a CBC with differential, blood culture and CSF for analysis and culture. Antibiotics should be started as soon as the work-up is complete. Urine culture may be omitted from sepsis work-ups done at birth but should be included in subsequent sepsis work-ups. If there are other circumstances indicating the origin of the sepsis, additional appropriate cultures should be obtained, such as tracheal fluid or from an area of cellulitis.

Infants with sepsis frequently have an elevated absolute band count, and/or depressed absolute neutrophil count, or increased I:T ratio (See Total Granulocyte Count, p. 106, and reference values for WBC indices, p. 107). However, a normal WBC count in an infant with signs of sepsis (see I), does not rule out infection, and thus antibiotics should be started while awaiting culture results.

The antibiotic regimen for sepsis work-ups performed at birth, or admitted as a neonate less than 30 days old, is ampicillin and gentamicin.
If the infant has been in the nurseries and sepsis is suspected, the antibiotic regimen should include vancomycin and gentamicin. Piperacillin should also be considered if there is suggestion of possible gram-negative infection, e.g., in a tracheal aspirate gram-stain, or if pseudomonas is present in the nursery.
Acyclovir therapy should be considered if HSV infection is possible, pending the results of a work-up for HSV. This work-up should include surface cultures for HSV, liver function tests and CSF for cell count and HSV PCR.

When a sepsis work-up has been performed, the infant should be reassessed at 72 hours. Consideration can be given to discontinuing antibiotics if the clinical course has not been suggestive of infection and the cultures are negative.
If the blood cultures are positive, treat for 10 days. Obtain a repeat blood culture after 24-48 hours of therapy to insure effective therapy.
If the CSF culture is positive, treat for 14-21 days.

In infants with positive cultures, antimicrobial therapy is adjusted according to the sensitivities. Serum levels of antibiotics should be followed as recommended on page XX.

If C-reactive proteins (CRP) are obtained, an initial CRP of <1 is not a definite confirmation of the absence of infection. If obtained, serial levels 24 to 72 hours after the sepsis work-up is performed should be obtained, and these values along with the clinical course of the patient and the results of CBCs and cultures will determine the duration of antibiotic therapy.

Isolation requirements will be determined according to the organism and the site of infection. Please consults the isolations manual.

If the patient is neutropenic, several therapies are possible:

• G-CSF at a dose of 10 µg/kg subQ or IV qday to b.i.d. can be administered until the ANC is >1500.
• IVIG can be administered to augment the immune system until the ANC has recovered.
• A granulocyte transfusion can be considered following discussion with the staff neonatologist if definite or strongly suspected infection is present. See Guidelines for Neonatal Transfusion Therapy, p. 203.

If the absolute neutrophil count is very low, a granulocyte transfusion may be considered. This option should be discussed with the staff neonatologist.

Reference:

Manroe BL, et al. The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr 1979;95:89-98.

Chetan A. Patel MD and Edward F. Bell, MD
Peer Review Status: Internally Peer Reviewed

IVIG should be administered by itself, with careful monitoring during the infusion. Vital signs should be monitored during the infusion (preferably q 15 min. X 2, then q hr). In the large multicenter trials involving infants, very few adverse reactions were noted during infusion. These consisted of mild increases or decreases in blood pressure, heart rate, or temperature (that were reversed by slowing the rate of infusion) or acute fluid overload. Since the dose of IVIG is equivalent to an approximately 10 ml/kg fluid bolus, the infusion is administered over several (typically 3 - 4) hours. 

References:

Jensen HB, Pollock BH. Meta-analysis of the effectiveness of intravenous immunoglobulin for prevention and treatment of neonatal sepsis. Pediatrics, 1997; 99:E2.

Baker CJ, Melish ME, Hall RT, et al. Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. N Engl J Med 1992; 327:213-9.

Fanaroff AF, Korones SB, Wright LL, et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in VLBW infants. N Engl J Med 1994; 330:1107-1113.

Kliegman RM and Clapp DW. Rational principles for immunoglobulin prophylaxis and therapy of neonatal infections. Clin Perinatol 1991; 18:303-24.

Weisman LE, Stoll BJ, Keuser TJ, et al. Intravenous immune globulin therapy for early-onset sepsis in premature neonates J Pediatr 1992; 121:434-43.