Infections in the Newborn
Routes of neonatal Infection
(1) Vertical: from mother to infant (Intrauterine)
(2) Horizontal: from baby (or other person) to baby
- Maternal Hematogenous Infection (in spite of placental barrier there are pathogens that due cross)
- Transcervical (Ascending infections): through the birth canal, involves the membranes and then the fetus.
Bacterial Neonatal Sepsis and Meningitis
Clinical Syndrome: Occurs in 1st month of life
Neonates are Immunocompromised Hosts: Complement, PMNs, Phagocytosis/bacterial killing, Humoral immunity
- Signs and symptoms of infection (Characterized by temperature instability, may be Ý or ß ); most symptoms vague:
- Poor feeding, irritability Ė non-consolable, lethargy, abd. distention, apnea and bradycardia (can be normal), jaundice
- Labs: Culture of blood and CSF (from LP) diagnostic (infant do have a PMN response). WBC Ý , protein ß , glucose ß . Also look at peripheral WBC and differential.
- Meningitis occurs in 1/3 of bacteremic (bacteria in blood) infants. Bacterial count in blood usually Ý due to ß immunity.
- Ý bacterial count predisposes infants to meningitis.
Blood Brain Barrier: brain microvascular, endothelial barrier that separates the vascular from the subarachnoid space
- these systems are in place but function sluggishly. (e.g. pre-term infants have ß IgG; Term infants have ß IgM, IgA)
- Also, procedures in NICU on pre-term infants predispose them to infection (e.g. intubation).
Epidemiology of Meningitis: ~ 1-10/1000 infants.
- is immature in neonates: they have a Ý level of protein and cells in CSF. So already less protective without infection
- during infection:
- (1) bacteria can move through tight junctions
- (2) organism can be phagocytized so WBCs enter
- (3) receptor-mediated pathogen transcytosis through endothelial cells.
- Relative Risk in Preterm infants is 10 fold higher than term.
- Other risk factors:
- Premature rupture of membranes (PROM), especially > 18h.
- Maternal fever
Diagnosis: See Signs and symptoms of infection under Clinical Syndrome above. Due lumbar puncture, take blood, run labs.
Treatment: Antibiotic needs to cover several bugs, mainly Group B strep, E. coli. and Listeria.
- (1) Genital/urinary colonizers: Group B strep, E. coli.
- E coli with K1 Ag has a Ý risk of causing meningitis than say a UTI. K1 Ag is also on Nisseria meningitisis (in older patients).
- K1 Ag is an adhesion receptor that probably facilitates crossing BBB.
- (2) secondary to maternal bacteremia: Listeria
(30 years experience) is used but Ampicillin and Cefotaxime (15yrs) is preferred in meningitis because beta-lactams dose can be doubled to get enough drug through the BBB.
Supportive Therapy: for septic shock, hypoxia and/or DIC, which require intensive care.
Prevention: Particularly Group B strep. See Epidemiology of Meningitis for risk factors.
- Ampicillin and Gentamicin
- Prevent prematurity and you prevent a lot of these infections.
- Maternal Vaccines: we donít know how to do this yet.
- Intrapartem Antibiotics this is the best approach at present. GBS has been the main target. We will run into this on wards.
- Maternal colonization with GBS is a risk factor as is previous delivery of infant with GBS (also see risk factors above)
- Eliminating GBS from colonized mothers proved impossible with antibiotics (eliminating carrier state is different than treating an infection)
- study in 80ís Þ major ß in GBS colonization and bacteremia in infants of mothers given antibiotics during pregnancy.
- Pediatric and Obstetric groups made recommendations, then CDC developed a widely used consensus regulation.
- (1) All moms (symptomatic or not) with GBS bacteriuria or who had previous infant with GBS should be treated.
- (2) One of 2 strategies should be adopted
- Screen all women at 35-37 weeks
- or treat all who are colonized with GBS (not just women with risk factors)
- (3) Rates of infection have tended to drop as this recommendation is implemented. Metro has gone from 5 to 0/yr.
Intrauterine Infections Ė see Vertical Infections above.
Þ thrombocytopenia Þ hematologic systemÞ blueberry muffin baby
Hepatosplenomegally: due to liver and spleen involvement.
Microcephally: due to CNS involvement Þ severe intrauterine encephalitis
Chorioretinitis due to CNS involvement of the 2nd Nerve Þ blindness
Hearing impairment due to CNS involvement of the 8th Nerve
Owl Eye cells seen in Herpes virus infection (CMV)
Epidemiology is pathogen specific,
- These are the "STORCH" infections: Syphilis, Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, Herpes simplex.
- important Others include HIV, Lime disease, etc.
- Pathogenesis: Transplacental > Ascending
- Host immune factors
- depend on Maternal Immunity (e.g. Rubella, if mother is immune then fetus is protected)
- Timing of infection is important (e.g. syphilis is more likely to transmit during certain periods in pregnancy, Toxoplasmosis only causes problems if transmitted during 1st and 2nd trimester, 3rd is possible but less severe)
- Viral Load concept is most clearly worked out in HIV: maternal viral load correlates with risk of transmission.
- Clinical Features: Though there are many different bugs, they have similar clinical features
- Infection may be Inapparent at birth and many important sequelae are Late Sequela (e.g. syphilis, rubella )
- Asymptomatic maternal infection
- Intrauterine Growth Retardation (often associated with a baby small for gestational age)
- Petechia, palpable purpura: multi-systemic disease
\ is the most important one to know
- CMV is the most common of the intrauterine infections (40,000/yr)
because this is a herpes virus there is a primary infection which can be followed by a secondary infection upon reactivation
- Occurs in 1-2% of infants. Compared to Toxo: 1/3000; HSV 1/3000; Rubella only 10/yr nationwide.
- 10% of total will have severe Sequella, the rest can be quite mild.
- Most important (#1) infectious cause of mental retardation, visual and hearing loss.
Etiologic Diagnosis of Intrauterine Infections (difficult because relies on combo of PCR, cultures and Ab test)
- The maternal primary infection is the one to worry about due to lack of maternal immunity to attenuate infection.
- therefore highest risk is in young teen mothers or older mothers with children in daycare.
Þ Vaccine, it works, Rubella is about gone
HSV Þ No vaccine or screening; rely on judicious use of C-section in women who have history and active lesions
- CMV is the exception because it grows readily in culture (can be picked up in urine), PCR available but not needed.
- Toxoplasmosis: harder because itís a protozoa. Use IgM Ab (too many women have been exposed to it to use IgG), PCR
- HVS: Culture, specific Ab to IgM
- Rubella: Culture, specific Ab to IgM
- Syphilis: VDRL, RTA (Ab test)
- It is almost never helps to look for IgG Ab to TORCH pathogens = "TORCH Titers" - this test is over used
Syphilis Þ easily treated, is screened in 1st and 3rd trimester. Should be less of a problem than it is.
Toxplasmosis Þ transmitted by exposure to litter box or eating uncooked meat, Can be treated by Spiramycin
HIV Þ use anti-retrovirals during pregnancy and C-section. Screen baby and treat.
Syphilis Þ penicillin
HSV Þ Acyclovir
Toxo Þ Pyrimethamine/ sulfa drugs cross placenta
CMV Þ Gnaciclovir
HIV Þ Anti-retroviral therapy (HAART) 3 drug combination including protease inhibitors.
- New approach has been to put women who have had an active lesion on acyclovir to prevent reactivation.