congenital and perinatal infection
DESCRIPTION
Congenital and Perinatal Infection. Congenital Infections: Presentation. Intrauterine growth retardation Microcephaly Hydrocephalus Intracranial calcifications Thrombocytopenia Blueberry muffin skin rash Hepatosplenomegaly, conjugated hyperbilirubinemia Chorioretinitis Cataracts. - PowerPoint PPT PresentationTRANSCRIPT
Congenital and Perinatal Infection
Congenital Infections: Presentation
• Intrauterine growth retardation• Microcephaly• Hydrocephalus• Intracranial calcifications• Thrombocytopenia• Blueberry muffin skin rash• Hepatosplenomegaly, conjugated hyperbilirubinemia
• Chorioretinitis • Cataracts
Blueberry Muffin Skin Rash
Etiologies of Congenital Infection
• Toxoplasmosis T• Syphilis Other• Rubella R• Cytomegalovirus C• Herpes simplex H• HIV• Lymphocytic choriomeningitis virus• Parvovirus B19• Varicella
Diagnosis of Congenital Infection:General Tests
• CBC• Total/direct bilirubin, liver enzymes• Total IgM• Bone radiographs• CSF exam• Eye exam• CNS imaging
Diagnosis of Congenital Infection:Specific Tests
• Toxoplasmosis IgM, IgG• RPR• Rubella IgM• Rubella culture: eye, urine, nasopharynx• Urine culture for CMV• Herpes simplex IgM, IgG• CSF: routine studies, quantitative VDRL, HSV PCR• Parvovirus B19 PCR• Lymphocytic choriomeningitis virus: infant IgM and IgG,
mother IgG
How Toxoplasmosis is Transmitted
Toxoplasmosis• Toxoplasma gondii, protozoan, cats are host• 70-90% asymptomatic• Symptoms: maculopapular rash,
thrombocytopenia, lymphadenopathy, hepatomegaly, splenomegaly, jaundice, hydrocephalus, microcephaly, chorioretinitis, seizures, deafness
• Diagnosis: IgM, IgG, intracranial calcifications• Treatment: pyrimethamine, sulfadiazine
Toxoplasmosis: Chorioretinitis
Congenital Syphilis: Symptoms
• Asymptomatic 50%• Fever, lymphadenopathy, irritability, failure to thrive• Jaundice, hepatosplenomegaly• Mucocutaneous: palmar/plantar bullae, maculopapular
rash trunk/limbs, mucosal lesions, condylomata lata• Anemia (BM arrest, hemolysis), thrombocytopenia,
low/high WBCs• Meningitis• “Snuffles” (serous rhinitis)• Bone changes: osteochondritis of humerus, tibia
Congenital Syphilis: Snuffles
Congenital Syphilis: Diagnostic Studies
• Quantitative RPR• CSF exam: cell count, protein, VDRL• CBC, platelets, liver enzymes• Long bone radiographs• Demonstration of spirochetes: tissue/fluid• HIV testing
Congenital Syphilis: Bone Changes
Congenital Syphilis: Treatment and Follow-up of the Newborn
• Choice of regimens for confirmed or probable congenital syphilis:– Penicillin G 100-150,000 unit/kg/day x 10-14 days
(50,000 unit/kg/dose IV BID x 7 days, then TID for a total of 10 days)
– Procaine penicillin G 50,000 unit/kg/day IM once daily x 10 days (may not adequately treat CNS)
– ampicillin is not a suitable alternative• RPR at 3, 6, 12 months• Complicated cases should be referred to specialist
Congenital Rubella: Clinical Findings
• Asymptomatic: 50% at birth• Sensorineural hearing loss• Mental retardation• PDA, peripheral pulmonic stenosis• Ocular: cataracts, chorioretinitis, glaucoma• Microcephaly• Blueberry muffin rash• Metaphyseal radiolucencies
Congenital Rubella: Vertical Transmission
• Transplacental passage of virus• Greatest risk for congenital defects and hearing
loss early in the pregnancy• Non-immune pregnant women
– do not immunize during pregnancy– no cases of malformation due to rubella vaccine
in women immunized during pregnancy– avoid exposure to rubella– post-partum vaccine
Congenital Rubella: skin Lesions
Congenital Rubella Syndrome
Congenital Rubella: Diagnosis and Treatment
• Diagnosis:– Rubella specific IgM– culture: nasopharynx, blood, urine, CSF,
throat• Treatment: supportive
Cytomegalovirus: Transmission
• Vertical transmission– transplacental and perinatal acquisition– maternal primary and reactivated CMV
• Incidence: – 2.5% – most are asymptomatic - 95%
Cytomegalovirus: Clinical Findings In Symptomatic Infants
• Microcephaly, intracranial calcifications• Thrombocytopenia, petechiae, purpura• Conjugated hyperbilirubinemia, elevated liver enzymes,
liver failure• Interstitial pneumonitis• Hearing loss• Mental retardation• Neurologic impairment, cerebral palsy• Chorioretinitis • Intestinal pseudo-obstruction like illness
CMV: Calcifications
CMV: Hydrocephalus, Calcifications
Cytomegalovirus: Diagnosis
• CMV titers: – IgM, IgG– Acute and convalescent
• Urine culture for CMV– Excretion may be intermittent
• CNS imaging• Eye exam
Cytomegalovirus: Treatment
• Supportive– Platelet transfusion
• Anti-viral treatment– Ganciclovir may reduce sequelae, but of
limited efficacy• CMV hyperimmune globulin• Infectious disease consultation
Lymphocytic choriomeningitis virus
• Arenavirus, shed by rodents• Symptoms in adults: influenza like illness - fever,
malaise, myalgia, retro-orbital headache, photophobia
• Congenital infection: hydrocephalus, chorioretinitis, intracranial calcifications, microcephaly, mental retardation, neurologic sequelae, visual loss
• Diagnosis: culture, acute and convalescent titers• Treatment: supportive
Lymphocytic Choriomeningitis Virus -
Hydrocephalus
Parvovirus B19• Associated with multiple disorders:
– Erythema infectiosum (fifth disease)– Aplastic crisis (hemolytic disorders, sickle cell)– Chronic anemia in immunosuppressed– Acute arthritis
• Fetal hydrops and death due to anemia– (?)Efficacy of intrauterine transfusion– Spontaneous recovery of fetal hydrops can
occur
Varicella• Maternal varicella before 20 weeks: congenital
anomalies reported to be 1-2%– Cicatricial skin lesions– Limb hypoplasia– CNS, ocular, neurologic
• Maternal varicella in last 5 days of pregnancy to 2 days post partum:– VZIG 125 units IM indicated in exposed infants– Skin lesions, pneumonitis, dissemination reported– Add acyclovir if signs or symptoms develop
Congenital varicella
Varicella: perinatally acquired
Perinatally Acquired Infection: Basic Principles
• Maternal colonization or infection: – Amniotic fluid– Blood– Genital tract secretions– Breast milk– Direct skin contact, environment
• Timing and duration of exposure• Interventions, prophylaxis
Herpes Simplex: Epidemiology
• Vertical transmission most common– perinatal exposure with ROM and delivery– 50% risk if infant exposed to primary maternal HSV– <1-5% risk if infant exposed to recurrent maternal HSV– increased risk in premature infants (reduced IgG)– C-section reduces risk if ROM < 4-6 hour
• Horizontal transmission reported– nursery outbreaks
• Time of onset: 2 days - several weeks
Herpes Simplex: Clinical Presentation
• Fever• skin vesicles • encephalitis• seizures • respiratory distress, pneumonia• hepatitis• septic shock like syndrome
Herpes Simplex Skin Lesions
Herpes Simplex Skin Lesions
Herpes Simplex Skin Lesions
Herpes Simplex Conjunctivitis
Herpes Simplex Oral Lesions
Herpes Simplex: Encephalitis
Neonatal Herpes Simplex: Treatment
• Acyclovir 60 mg/kg/day divided q 8 hr x 14 days (21 days for systemic or CNS)
• Ocular HSV: add ophthalmic trifluridine, iododeoxyuridine, or vidarabine
• Supportive: control seizures, respiratory and cardiovascular support
• Reduce cutaneous or ocular spread• High mortality rate for CNS or systemic HSV, even
with treatment
Management of HSV Exposure
• Recurrent maternal HSV– risk is very low; observation only
• Primary maternal disease– risk is high– viral throat culture at 24-48 hr of age– empiric therapy is controversial
• Premature infant - risk may be greater
HIV
• Transmission is vertical– In utero, intrapartum (most common), and
postnatal (breastfeeding)• Risk factors
Zidovudine (AZT) for reduction of perinatal HIV transmission
• pregnancy: begin 200 mg PO 3x/day at 14-34 wk, continue throughout pregnancy
• intrapartum: 2 mg/kg x 1 h, then 1 mg/kg/h IV until delivery
• newborn: 2 mg/kg 4x/day PO begining at 8-12 h of age until 6 weeks of age
• referral to pediatric HIV center
HIV: perinatal prophylaxis
• Reduction of vertical transmission with AZT as compared to placebo in women with mildly symptomatic disease– Connor EM et al. NEMJ 1994;331:1173
• placebo 25.5%• prenatal, intrapartum, postnatal8.3%
HIV: Benefit persists even with abbreviated prophylaxis
• DNA PCR on HIV exposed infants with incomplete prophylaxis.– Wade NA et al. NEJM 1998;339:1409
• prenatal 6.1%• intrapartum 10.0%• < 48 h postnatal 9.3%• > 48 h postnatal 18.4%
HIV: mode of delivery
• Metanalysis of 15 NA/European studies• 8533 mother-child pairs• adjusted for antiretroviral Rx, maternal
stage of disease and birth weight• elective C-section: prior to labor or ROM• International Perinatal HIV Group
– NEJM 1999;340:977
HIV: mode of delivery
• other mode (vag, non-elective C/S) 16.7%• elective C-section 8.4%• other mode, complete retroviral Rx 7.3%• elective C/S, complete retroviral Rx 2.0%• International Perinatal HIV Group
– NEJM 1999;340:977
Hepatitis B
• Vertical transmission– Blood exposure during labor and delivery– In utero transmission: < 2% of cases
• Maternal HBsAg+ HBeAg+70-80%• Maternal HBsAg+ HBeAg- 5-20%• Chronic carrier, hepatitis, cirrhosis,
hepatocellular carcinoma
Infant born to HBsAg + mother: management
• Avoid skin to skin until infant bathed• Hepatitis B vaccine within 12 hr• HBIG given at separate site• Complete standard HBV schedule
– Preterm < 2 kg: 1st dose not counted, total 4 doses• HBsAg and anti-HBsAg at 9-15 months of age• Breast feeding not precluded: controversial
Infant born to HBsAg unknown mother: management
• Avoid skin to skin until infant bathed• HBV within 12 hours• If mother HBsAg +, HBIG within 7 days• Premature infant < 2 kg: give both HBV and HBIG
within 12 hours, if unable to determine maternal status by 12 hours.
• Complete standard HBV schedule– Preterm < 2 kg: 1st dose not counted, total 4 doses
Hepatitis C
• Prevalence in adults in U.S. - 1.8%• Vertical transmission - 5% of infants born to
mothers with hepatitis C• No specific preventive measures• Breast feeding is allowed
– Transmission not proven– Cracked or bleeding nipples: may be risk
• Test infant at 18 months: anti-HCV– Earlier testing with HCV RNA PCR
Enterovirus• Commonly occurs in summer and fall seasons• History of maternal illness late in pregnancy• Perinatal vertical transmission from mother to infant• Outbreaks reported in NICU’s• Presents in the first 2 weeks• Neonatal symptoms: fever, lethargy, poor feeding,
respiratory distress• Clinical syndromes: aseptic meningitis, “sepsis,”
cardiomyopathy, hepatitis, pneumonia, pulmonary hypertension
Etiology of Early Onset Sepsis
• Group B Strep (GBS): 67% • Non-GBS organisms
– E Coli: 25%– Others: 8%
• Enterococcus, staph aureus, strep pneumonia, candida.
Epidemiology of Group B Strep
• Maternal Colonization:15-40%• 50-75% of newborns born to colonized
mothers become colonized during birth• Attack Rate (# infected nb/# colonized
mothers): 1-2% • Neonatal Early Onset Disease:
– 1-4 per 1000
Risk Factors for Neonatal Infection in Colonized Mothers• Prolonged rupture of membranes > 18 hr• Premature birth esp < 34 weeks• Intrapartum fever• African-American Race• Maternal age < 20 yr• Previous birth of GBS infected infant• Heavy maternal colonization, e.g. bacteruria• Low levels of anti-GBS capsular antibody
Maternal GBS Disease
• UTI• amnionitis• endometritis• wound infection
Neonatal GBS Disease
• Early Onset Disease– symptomatic infection occurring during 1st
week– results from vertical transmission during labor
or delivery– constitutes 80% of neonatal GBS infection– pneumonia and overwhelming sepsis more
common
Prevention of early onset group B strep
• GBS is sensitive to Ampicillin and Penicillin• Failure of prenatal administration of
Amp/PCN to eradicate colonization• Failure of immediate postnatal treatment
with Penicillin– Lack of treatment efficacy in several studies– increased morbidity from Penicillin resistant
organisms in one study
Prevention of early onset group B strep
• Only success at maternal treatment is intrapartum antibiotic prophylaxis– Boyer and Gottof, 1986
• Reduces maternal colonization• Reduces neonatal colonization• Reduces attack rate of GBS by 80-95%
– Allen et al, meta-analysis, 1993: 30 fold decrease in neonatal infection
Strategies to Reduce GBS Disease
• AAP, 1992– 26-28 week cultures of all pregnant women– intrapartum prophylaxis for:
• positive cultures• ROM > 12 hr• onset of labor or ROM < 37 wks• intrapartum fever• previous birth of an infant with GBS disease
– Will treat approx 3.4% of all mothers, to prevent 50% of Early Onset GBS disease
Strategies to Reduce GBS Disease
• ACOG– Prophylaxis for:
• preterm labor < 37 wks• PROM < 37 wks• ROM > 18 hr• previous child with GBS disease• maternal fever during labor
– Note: cultures not included in decision – Will treat approximately 18.3% of mothers and
prevent 68.8% of early onset GBS disease
Risks of Maternal Treatment - Why not treat all mothers?
• Fatal anaphylaxis to Ampicillin: 1 per 100,000
• Pseudomembraneous enterocolitis (Clostridium dificile)
• incidence of other less severe maternal reactions
• risk of antibiotic resistance among GBS or other organisms
Failures of GBS Prophylaxis
• Late administration of intrapartum antibiotic prophylaxis (< 4 hr before birth)
• Inadequate dosing• Failure to recognize mothers at risk
Prophylaxis Failures
• Importance of hospital guidelines• Surveillance study, 1997
– 165 hospitals surveyed– 96 (58%) had established departmental
guidelines for maternal prophylaxis– Lower early onset GBS incidence in hospitals
with guidelines• .58/1000 vs 1.29/1000 (p=.006)
Factor SE, et al, OB GYN 2000;95:377-82)
Failures of Intrapartum Prophylaxis
• CDC study 1998-1999; 629,912 births• 312 infants with GBS early onset
sepsis (0.5/1000 births)– 62% had no maternal risk factors– 52% of women were screened for GBS
• Relative Risk of neonatal GBS in screened vs risk based approach was 0.48 (0.38-0.61)
Schrag SJ, et al, NEJM 2002;347:233-9.
Failure of Intrapartum Prophylaxis
• Reasons for failure of risk-based approach:– Incidence of GBS colonization in mothers
who have no risk factors on presentation– Failure of identification of risk factors
when present
CDC Guidelines Updated 2002
• All pregnant women should be cultured at 35-37 weeks gestation
• Penicillin prophylaxis preferred, due to narrow spectrum• Prophylaxis recommended for
– Positive cervical culture for GBS– GBS bacteruria during gestation– Previous infant born with invasive GBS disease– Risk factors in absence of culture results
• Gestation < 37 wks• Fever• ROM > 18 hr
• Prophylaxis not needed for Cesarean sections for culture positive mothers with intact membranes
Change in Epidemiology of Early Onset Sepsis
• Does widespread use of Intrapartum Antibiotic Prophylaxis lead to emergence of resistant organisms?
Stoll B, et al, Changes in Pathogens Causing Early Onset Sepsis in Very Low Birthweight
Infants, NEJM 2002;347:240-7
• 5447 VLBW infants born 1998-2000
• Compared to 7606 VLBW infants born 1991-93
15.4NS
19.3Total early onset
6.8P=.004
3.2E. Coli
1.7P<.001
5.9GBS
98-00Inf./1000 live births
91-93Inf./1000 live births
Explanations for Ampicillin Resistance
• Selection of resistant organisms from maternal GU tract– Especially in preterm infants
• Change in NICU resistance patterns• Change in resistance patterns of
ambulatory patients• Change in general resistance patterns
Hyde T, et al, Trends in Incidence and Antimicrobial Resistance of Early-onset Sepsis: Population Based
Surveillance in San Francisco and Atlanta, Ped 2002;110:690-5.
• CDC Emerging Infection Program Network, 1998-2000– All hospitals with a delivery service in 3
county area of San Francisco (39,768)– All 10 birthing hospitals in the 8 county
Atlanta area (42, 960)
Hyde et alEarly Onset Sepsis
(positive blood culture in 1st 7 days of life)
• N = 408• 166/408 (40.7%) were GBS• 70/409 (17.2%) were E. Coli• No change in E. Coli or GBS rates over
the 3 yr period• 78% of ampicillin resistant organisms
were in prematures
Changing Epidemiology of Early Onset Sepsis
• Term deliveries – 3.9 million per year– Incidence of early onset sepsis: 1/1000
live births– 3,900 term infants per year
• Antibiotic resistance does not appear to be a problem in term infants
Changing Epidemiology of Early Onset Sepsis
• VLBW Infants– 48,000 births/yr < 1500 gm– Incidence of Early Onset Sepsis: 15/1000 (Stoll data)– 720 preterm infants/yr
• Antibiotic resistance is a problem in VLBW infants– Due to GBS prophylaxis vs background changes in
microbial resistance patterns?• Strategies to prevent GBS must address the majority of
susceptible infants (5 out of every 6 susceptible infants is term)
• Strategies must reflect the potential for resistance in preterm infants
Management of Newborn Whose Mother Received Prophylaxis
• Diagnostic evaluation and empiric antibiotics if:– signs and symptoms of sepsis– < 35 weeks gestation
• Limited Evaluation and 48 hr observation if:– Duration of prophylaxis < 4 hr before delivery– Asymptomatic infant
• No evaluation, but 48 hr observation if: > 4 hr antibiotics prophylaxis
Diagnostic Eval: CBC, Diff, Bld Cult, plus CXR, LP etc, as indicated Limited Eval: CBC, diff and Bld Cult.
Maternal IAP for GBSMaternal antibiotics
for suspectedchorioamnionitis
Signs of neonatalsepsis
Gestational age< 35 weeks
Duration of IAP beforedelivery < 4 hr
No evaluationNo therapy
Observe 48 hr
Full diagnosticevaluation
Empiric therapy
Limited evaluationObserve 48 hr
If sepsis is suspected, fulldiagnostic evaluation and empiric
therapy
Yes
No
No
No
Yes
Yes
Yes
Yes
Is an LP necessary in evaluation for sepsis in the newborn?
• Pro– Risk of meningitis in absence of positive blood
cultures or CNS symptoms– Wiswell et al:
• 5 yr review of U.S. Army Hospitals; 169,849 births• Incidence of meningitis: 0.25/1000 live births• 8/43 (19%) were term infants with no CNS
symptoms and negative blood cultures
Wiswell TE et al, Ped 1995;95:803-6
Is an LP necessary in evaluation for sepsis in the newborn?
• Con:– Metanalysis of 6 papers excluding Wiswell et al
• 4913 LP’s successfully performed• 19 cases of culture positive meningitis (259 LP’s per
case of meningitis)• 16/19 cases had positive blood cultures• Thus, 1638 successful LP’s are needed to diagnose
one case of meningitis in the absence of a positive blood culture
• Better blood culture technique lessens the need for LP’s
Blood Culture Technique
• Appropriate prep:– 30 seconds vs 10 seconds x 2
• Appropriate volume:– At least 1 ml
• Obtain from peripheral stick and central line if line is in more than 12 hr
Duration of Antibiotics
• Are negative blood cultures conclusive when the mother has received IAP?
• Ancillary tests– CBC:
• Neutropenia• I:T ratio
– CRP
C-Reactive Protein in Suspected Sepsis
• CRP performed on 2 successive days in early onset sepsis:– Sensitivity: 88.9%– Specificity: 73.8%– Positive predictive ability: 6.0%– Negative predictive ability: 99.7%
• Conclusions: – In episodes where CRP was positive, only 6% turned out to
have sepsis– In episodes where CRP was negative, 99.7% did not have
sepsis
Benitz et al, Ped, 1998
Decision to stop antibiotics• Negative blood cultures at 48-72 hr
• Symptoms of mild severity (tachypnea, brief O2 dependency, poor feeding)– D/C antibiotics and observe 24-48 hr
• If moderate-severe symptoms – decision to D/C or continue antibiotics depends on other factors:– Presence of chorioamniotis?– Elevated CRP?– Neutropenia or elevated I:T ratio?
Nosocomial infection in the NICU:Common organisms
• Coagulase negative staphylococcus• Coagulase positive staphylococcus• Gram negatives: E coli, Klebsiella,
Enterobacter, Serratia, Pseudomonas• Candida albicans, parapsilosis
Risk factors for nosocomial infection
• Central lines– Duration of insertion– Type of catheter: Broviac, silastic
• Ventilation, endotracheal intubation• Exposure to antibiotics• Surgical procedures: intestinal• Use of intravenous lipids
Strategies to reduce nosocomial infection
• Remove central lines ASAP• Limit entries into central lines
– Medications via PIV– Limit number of ports into central line– Use ports rather than stopcocks
• Good handwashing• Respiratory care, suctioning techniques• Limit use of IV lipids
Empiric treatment of suspected nosocomial sepsis
• Ampicillin and gentamicin• Ampicillin and cefotaxime• Vancomycin and gentamicin• Vancomycin and cefotaxime