Download - Congenital and Perinatal Infection
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Congenital and Perinatal Infection
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Congenital Infections: Presentation
• Intrauterine growth retardation• Microcephaly• Hydrocephalus• Intracranial calcifications• Thrombocytopenia• Blueberry muffin skin rash• Hepatosplenomegaly, conjugated hyperbilirubinemia
• Chorioretinitis • Cataracts
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Blueberry Muffin Skin Rash
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Etiologies of Congenital Infection
• Toxoplasmosis T• Syphilis Other• Rubella R• Cytomegalovirus C• Herpes simplex H• HIV• Lymphocytic choriomeningitis virus• Parvovirus B19• Varicella
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Diagnosis of Congenital Infection:General Tests
• CBC
• Total/direct bilirubin, liver enzymes
• Total IgM
• Bone radiographs
• CSF exam
• Eye exam
• CNS imaging
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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
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How Toxoplasmosis is Transmitted
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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
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Toxoplasmosis: Chorioretinitis
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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
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Congenital Syphilis: Snuffles
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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
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Congenital Syphilis: Bone Changes
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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
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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
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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
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Congenital Rubella: skin Lesions
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Congenital Rubella Syndrome
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Congenital Rubella: Diagnosis and Treatment
• Diagnosis:– Rubella specific IgM
– culture: nasopharynx, blood, urine, CSF, throat
• Treatment: supportive
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Cytomegalovirus: Transmission
• Vertical transmission– transplacental and perinatal acquisition
– maternal primary and reactivated CMV
• Incidence: – 2.5%
– most are asymptomatic - 95%
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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
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CMV: Calcifications
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CMV: Hydrocephalus, Calcifications
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Cytomegalovirus: Diagnosis
• CMV titers: – IgM, IgG
– Acute and convalescent
• Urine culture for CMV– Excretion may be intermittent
• CNS imaging
• Eye exam
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Cytomegalovirus: Treatment
• Supportive– Platelet transfusion
• Anti-viral treatment– Ganciclovir may reduce sequelae, but of
limited efficacy
• CMV hyperimmune globulin
• Infectious disease consultation
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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
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Lymphocytic Choriomeningitis Virus -
Hydrocephalus
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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
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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
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Congenital varicella
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Varicella: perinatally acquired
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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
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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
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Herpes Simplex: Clinical Presentation
• Fever
• skin vesicles
• encephalitis
• seizures
• respiratory distress, pneumonia
• hepatitis
• septic shock like syndrome
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Herpes Simplex Skin Lesions
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Herpes Simplex Skin Lesions
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Herpes Simplex Skin Lesions
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Herpes Simplex Conjunctivitis
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Herpes Simplex Oral Lesions
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Herpes Simplex: Encephalitis
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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
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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
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HIV
• Transmission is vertical– In utero, intrapartum (most common), and
postnatal (breastfeeding)
• Risk factors
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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
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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%
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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%
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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
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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
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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
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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
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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
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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
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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
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Etiology of Early Onset Sepsis
• Group B Strep (GBS): 67%
• Non-GBS organisms– E Coli: 25%
– Others: 8%• Enterococcus, staph aureus, strep
pneumonia, candida.
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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
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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
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Maternal GBS Disease
• UTI
• amnionitis
• endometritis
• wound infection
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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
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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
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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
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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
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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
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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
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Failures of GBS Prophylaxis
• Late administration of intrapartum antibiotic prophylaxis (< 4 hr before birth)
• Inadequate dosing
• Failure to recognize mothers at risk
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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)
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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.
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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
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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
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Change in Epidemiology of Early Onset Sepsis
• Does widespread use of Intrapartum Antibiotic Prophylaxis lead to emergence of resistant organisms?
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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
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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
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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)
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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
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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
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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
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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.
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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
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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
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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
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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
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Duration of Antibiotics
• Are negative blood cultures conclusive when the mother has received IAP?
• Ancillary tests– CBC:
• Neutropenia• I:T ratio
– CRP
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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
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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?
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Nosocomial infection in the NICU:Common organisms
• Coagulase negative staphylococcus
• Coagulase positive staphylococcus
• Gram negatives: E coli, Klebsiella, Enterobacter, Serratia, Pseudomonas
• Candida albicans, parapsilosis
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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
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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
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Empiric treatment of suspected nosocomial sepsis
• Ampicillin and gentamicin
• Ampicillin and cefotaxime
• Vancomycin and gentamicin
• Vancomycin and cefotaxime