1. Neonatal Infections Catherine M. Bendel, M.D.
Associate Professor of Pediatrics
Director, Neonatal-Perinatal Medicine Fellowship Program

2. Questions?
Why are infants, especially premies, more susceptible to infections?
What are the clinical manifestations of neonatal infections?
Bacterial?
HSV?
How to prevent infections?
Antibiotics - indications, contraindications, cautions, resistance, etc.
How to interpret labs?
Any precautions with lines?

3. Objectives
To briefly review neonatal immunology and why neonates are so susceptible to infections
To review the epidemiology, clinical presentation, diagnosis and treatment of the most common bacterial and HSV neonatal infections.
To review modes of infection prevention.
To differentiate between preterm and term infants in all these areas

4. “Prematurity is an infectious disease.”
- James Todd, M.D.

5. Why are infants, especially premies, more susceptible to infections?

6. Neonatal Immune System
All neonates relatively immunocompromised
Immature and Ineffective:
Antibodies
Complement
Neutrophils
Skin / mucosal barriers

7. Antibody

8. Immunity Antibodies  Infectious agent 
Figure 1.1 Antibodies (anti- foreign bodies) are produced by host while cells on contact with the invading micro-organism which is acting as an antigen (e.g. generates antibodies). The individual may then be immune to further attacks.
(Modified From: Roitt, I: Essential Immunology, 4th edition, Blackwell Scientific Publications, 1980)

9. No contact with infectious agents = no antibody production
Antibodies  
Infectious agent
Immunity x x
No contact with infectious agents = no antibody production

10. Maternal Transfer of Antibodies
Antibody transfer increases with GA
Most during 3rd trimester
No guarantee maternal antibodies present to the infecting organism
Remington and Klein, Sixth Edition, 2006

11. Complement

14. Neutrophils

15. Neonatal Neutrophils Immature  Chemotaxis  Deformability
 Phagocytosis
 Storage pool
Adults 14-fold > circulating pool
Neonates only 2-fold

16. Manroe et al, J Pediatr, 1979

17. “Normal” VLBW neonates
Mouzinho et al, Pediatr 94:76, 1994

18. “Normal” VLBW neonates
Mouzinho et al, Pediatr 94:76, 1994

19. Neonatal Barriers to Infection

20. Neonatal Anatomic Barriers
Immature skin and mucosal surfaces
layers
junctions between cells
secretory IgA
Umbilical cord
Breaches - catheters, tape

21. Invasive Fungal Dermatitis in a VLBW infant
Figure 1. Invasive fungal dermatitis in an extremely low birth weight infant. Note the erosions and crusts. Blood cultures were also positive.
Figure 2. Skin biopsy from a neonate with invasive fungal dermatitis. Gomori methenamine silver stain shows a cluster of hyphal forms in the dermi
JL Rowen, Sem Perinatal 27: , 2003

22. Epidemiology

23. Neonatal Sepsis: Incidence
2/1000 live births with culture proven sepsis
Bacterial / Viral / Fungal
80% infants develop bacterial sepsis
20% infants perinatally acquired viral infections
~ 25% of infected infants have meningitis
Higher rate with preterm birth
26/1000 preterm infants with BW < 1000g
8-9/1000 preterm infants with BW g
Remington and Klein, Sixth Edition, 2006

24. Neonatal Bacterial Sepsis: Disease Patterns
Early Onset Neonatal Sepsis (EONS)
Fulminant, multi-system illness
< 5 days old
Obstetrical complications
Prematurity
Perinatal acquisition
High mortality, 5-50%
Late Onset Neonatal Sepsis (LONS)
Sepsis or meningitis
5 days to 3 months old
Perinatal or postnatal acquisition
Lower mortality, 2-6%

25. Suppurative Arthritis Cellulitis - - Omphalitis
Neonatal Infections
Sepsis
Meningitis
Pneumonia
Otitis Media
Diarrheal Disease
UTI
Osteomyelitis
Suppurative Arthritis
Conjunctivitis
Orbital Cellulitis
Cellulitis - - Omphalitis
Bacterial / Viral / Fungal

26. Etiologic Agents of Neonatal Sepsis
Frequency(%)
 Group B Streptococci
 Escherichia coli
Streptococcus viridans
Staphylococcus aureus
Enterococcus spp
Coagulase-negative staphylococci
Klebsiella pneumoniae
Pseudomonas spp
Serratia marcescans
Others
*Schuchat et al, Pediatrics 105: 21-26, 2000

27. Etiologic Agents of Neonatal Meningitis
Gram Positive Bacteria; Frequency (%)
 Group B Streptococci
Listeria monocytogenes
Miscellaneous gram-positives
Gram Negative Bacteria:
 Escherichia coli
Klebsiella species
Haemophilus influenzae
Miscellaneous gram-negatives
Anaerobes
Feigen & Cherry, Fifth Edition, 2004

28. Incidence of Neonatal Group B Streptoccal Sepsis
5-35% Pregnant women colonized
1/ colonized women will have an infant with early onset disease
1-7/1000 live births in 1993
0.44/1000 live births in 1999
Remington and Klein, Sixth Edition, 2006

29. Rate of Early- and Late-onset GBS Disease in the 1990s, U.S.
Group B Strep Association formed
1st ACOG & AAP
statements
CDC draft
guidelines published
Consensus
guidelines
RATE OF EARLY- AND LATE-ONSET GBS DISEASE IN THE 1990s, U.S.
More important than changes in policies are changes in disease incidence.
This slide shows a graph plotting the incidence of early-and late-onset GBS disease in the ABCs areas from 1989 to 2000.
Late-onset disease is represented by the blue line in this graph.
Even with the implementation of guidelines recommending GBS prophylaxis, late-onset disease rates remain stable during the 1990s at approximately 0.3 cases per 1000 live births.
The white line represents early-onset disease.
The incidence of early-onset GBS disease in the United States since 1993 has declined 70% (from 1.7 cases per 1000 live births in 1993 to 0.45 cases per 1000 live births in 1999) , coinciding with increased prevention activities.
As of 2000, the graph shows that the rates have plateaued at 0.5 cases per 1000 live births.
This graph was originally published by Schrag in New England Journal of Medicine, 2000, 342:
Schrag, New Engl J Med : 15-20

30. Rate of Early-Onset Disease by Race 1993-1998
Black
White
Healthy People 2010
RATE OF EARLY-ONSET DISEASE BY RACE,
This slide shows a graph plotting the incidence of early-onset invasive GBS disease in black Neonates and white Neonates in four active surveillance areas (California, Georgia, Tennessee, and Maryland), 1993 through 1998.
The incidence of early-onset disease declined more steeply among black neonates than among white neonates during this period, and the difference between blacks and whites in the incidence of early-onset disease was reduced by 75 percent.
The Healthy People 2010 objectives, released by the U.S. Department of Health and Human Services, set national objectives for early-onset GBS. The HP2010 objective is 0.5 cases/1000 births for all races.
In 1998 the rate of early-onset disease in both black neonates (0.8 per 1000 live births) and white neonates (0.5 per 1000 live births) already approached the Healthy People 2010 objective of a reduction in the incidence of early-onset disease to 0.5 case per 1000 live births for all races
This data is taken from Schrag, NEJM 2000, 342: 15-20
Schrag, New Engl J Med : 15-20

31. Current Estimates of Annual GBS Early-Onset Disease in the U. S
Current Estimates of Annual GBS Early-Onset Disease in the U.S. (2001 provisional, from ABCs/EIP Network)
~4,400 cases prevented per year
1720 cases still occurring annually
deaths
Current Estimates of Annual GBS Early-Onset Disease in the U.S. (2001 provisional, from ABCs/EIP Network)
~4,400 cases prevented per year
1720 cases still occurring annually
deaths
Remains leading infectious cause of neonatal morbidity and mortality
Remains leading infectious cause of neonatal morbidity and mortality

32. What do we know about trends in “other pathogens”?
Most studies: stable rates of ‘other’ sepsis
Concerns for increased rates of E. coli, all gram negatives, or amp-R infections
Population-based (multicenter) studies find stable rates of total non-GBS and E. coli
One multicenter study of very LBW infants found a decrease in GBS by 4.2 /1,000, but an increase in E coli rates of 3.6/1,000 (Stoll et al, NEJM, 2002, 347:240-7)
% of E. coli sepsis w/ amp resistance may be increasing
Increases restricted to low birth weight or preterm deliveries
WHAT DO WE KNOW ABOUT TRENDS IN “OTHER PATHOGENS”?
Most studies find stable rates of sepsis caused by other pathogens
A few single hospitals found increased rates or case counts of E coli, all gram negatives, or of amp R pathogens; one multicenter study of very low birth weight infants found an increased incidence of E. coli in the 1990s (Stoll et al., NEJM 347:240-7)
Other population-based (multicenter) studies find stable rates of total nonGBS and E coli
Proportion of E. coli neonatal sepsis with amp resistance may be increasing
Increases restricted to low birth weight or preterm deliveries; increases may not be related to GBS prophylaxis
See CDC’s revised GBS guidelines (MMWR Aug. 16,2002 (RR-11)) for a detailed review of these studies that includes references

33. Ampicillin Susceptibility of E
Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Selected Counties CA and GA,
Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases, Full-Term Infants, ABCs, Selected Counties CA and GA,
This bar chart shows a stable trend (P=0.52) in the number of ampicillin resistant E. coli early onset sepsis infections among full term infants in selected counties of CA and GA from These data are from T. Hyde et al., Pediatrics 2002;110(4):690-5.
In 1998 surveillance detected 8 cases, 4 were ampicillin resistant
In 1999 surveillance detected 8 cases, 3 were ampicillin resistant
In 2000 surveillance detected 6 cases, 2 were ampicillin resistant
N=22, p=0.52, linear trend
Hyde et al, Pediatrics 2002;110(4):690-5.

34. Ampicillin Susceptibility of E
Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases Preterm Infants, ABCs, Selected Counties CA and GA,
Ampicillin Susceptibility of E. coli from Early-Onset Sepsis Cases Preterm Infants, ABCs, Selected Counties CA and GA,
This bar chart shows a significantly increasing trend (P=0.02) in the number of ampicillin resistant E. coli early onset sepsis infections among preterm infants in Pediatrics 2002;110(4):690-5.
selected counties of CA and GA from These data are from T. Hyde et al., In 1998 surveillance detected 6 cases, 1 was ampicillin resistant
In 1999 surveillance detected 12 cases, 10 were ampicillin resistant
In 2000 surveillance detected 18 cases, 15 were ampicillin resistant
N=37, p=0.02, linear trend
Hyde et al, Pediatrics 2002;110(4):690-5.

35. Susceptibility of GBS: ABC/EIP Isolates, 1995-2000
1280 isolates from MN, GA, NY, OR (1173 invasive, 107 colonizing):
All susceptible to penicillin, ampicillin, cefotaxime and vancomycin
19% erythromycin resistance
11% clindamycin resistance
SUSCEPTIBILITY OF GBS: Isolates from the ABCs,
1280 isolates from MN, GA, NY, OR (1173 invasive, 107 colonizing)
All susceptible to penicillin, ampicillin, cefotazime and vancomycin
19% erythromycin resistance
11% clindamycin resistance

36. Risk Factors for Early Onset Neonatal Sepsis
Primary (significant)
Prematurity or low birth weight
Preterm labor
Premature or prolonged rupture of membranes
Maternal fever / chorioamnionitis
Fetal hypoxia
Traumatic delivery
Secondary
Male
Lower socioeconomic status
African-American race
Remington and Klein, Sixth Edition, 2006

37. Factors associated with early-onset GBS disease: multivariable analysis
Characteristic
Adjusted RR (95% CI)
GBS screening
0.46 ( )
Prolonged ROM (> 18 h)
1.41 ( )
Pre-term delivery
1.50 ( )
Black race
1.87 ( )
Maternal age <20 y
2.22 ( )
Previous GBS infant
5.54 ( )
Intrapartum fever
5.36 ( )
FACTORS ASSOCIATED WITH EARLY-ONSET GBS DISEASE: MULTIVARIABLE ANALYSIS
This table shows the factors significantly associated with early-onset GBS disease in multivariable analysis, as reported by Schrag et al, NEJM 2002, 347:233-9
Prenatal GBS screening was significantly protective.
The relative risk associated with screening was 0.46 (95% CI: )
A number of other factors were associated with increased risk of early-onset disease
The relative risk associated with prolonged rupture of membranes (ROM) was 1.41 (95% CI: )
The relative risk associated with pre-term delivery was 1.50 (95% CI: )
The relative risk associated with Black race was 1.87 (95% CI: )
The relative risk associated with maternal age less than 20 was 2.22 (95% CI: )
The relative risk associated with previous GBS infant was 5.54 (95% CI: )
The relative risk associated with intrapartum fever was 5.36 (95% CI: )
Schrag et al, NEJM 2002, 347:233-9

38. Early Onset Neonatal Sepsis: Risk Factors - Maternal Fever
Maternal fever is a significant risk factor for EONS and may add in the identification of infected but initially asymptomatic infant.
5.36 = adjusted RR
25% of asymptomatic infants, with culture positive sepsis, had maternal fever as the ONLY criteria for evaluation.
Chen et al, J of Perinatal, 2002, 22:

39. Early Onset Neonatal Sepsis: Presentation and Diagnosis

40. Early Onset Neonatal Sepsis: Signs/Symptoms?

41. Early Onset Neonatal Sepsis: Signs/Symptoms
Strongly suggestive
hypoglycemia / hyperglycemia
hypotension
metabolic acidosis
apnea
shock
DIC
hepatosplenomegaly
bulging fontanelle
seizures
petechiae
hematochezia
respiratory distress

42. Early Onset Neonatal Sepsis: Signs/Symptoms
Nonspecific
lethargy, irritability
temperature instability -- hypothermia or fever
poor feeding
cyanosis
tachycardia
abdominal distention
jaundice
tachypnea

43. Early Onset Neonatal Sepsis: Signs/Symptoms - Fever
The infant with sepsis may have an elevated, depressed or normal temperature.
Fever is seen in up to 50% of infected infants.
Fever is more common in term infants, while hypothermia is more common in preterm infants
A single elevated temperature reading or fever as an isolated finding is infrequently associated with sepsis.
Persistent fever for greater than 1 hour is more frequently associated with infection.
Fever occurs more frequently with LONS or with viral, rather than bacterial, sepsis.
Klein, Sem in Perinat, 5:3-8

44. Early Onset Neonatal Sepsis: Laboratory Evaluation
 Cultures 
Chest Radiograph
Complete Blood Cell Count
Glucose
Bilirubin
Liver Function Tests
Coagulation studies
C-reactive Protein (CRP)

45. Early Onset Neonatal Sepsis: Cultures -- Who and Which?
Blood culture -- indicated in ALL infants with suspected sepsis. Repeat cultures indicated if initial culture positive.
Urine culture -- low yield in EONS
+ in 1.6% EONS compared to 7.47% LONS
Klein, Sem in Perinat, 5:3-8

46. Early Onset Neonatal Sepsis: Cultures -- Who and Which?
CSF culture -- should always be considered Meningitis frequently accompanies sepsis
50-85% meningitis cases have + blood culture
Yield reportedly low if respiratory distress is the only major sign of infection
Specific signs & symptoms occur in less than 50% of infants with meningitis
Using “selective criteria” for obtaining CSF may result in missed or delayed diagnosis in up to 37% of infants with meningitis
Wiswell et al, Pediatrics, 1995

47. Laboratory Diagnosis of Neonatal Meningitis
CSF > 32 WBC/mm3
> 60% PMN
glucose < 50% - 75% of serum
protein > 150 mg/dl
organisms on gram stain

48. Early Onset Neonatal Sepsis: Complete Blood Cell Counts
Is the CBC helpful as an indicator of early onset neonatal sepsis?
Thrombocytopenia frequently associated with sepsis
WBC may be high, low or “normal” --timing of the sample important
Persistent low WBC more predictive of sepsis than elevated WBC (ANC < 1200)
I:T quotient unreliable

50. Early Onset Neonatal Sepsis: Complete Blood Cell Counts

51. Early Onset Neonatal Sepsis: Complete Blood Cell Counts
Single or serial neutrophil values DO NOT assist in the diagnosis of EONS or determining the duration of therapy
99% of asymptomatic, culture-negative neonates > 35 weeks GA had 1 or more “abnormal” WBC values

52. Early Onset Neonatal Sepsis: C-Reactive Protein

53. Early Onset Neonatal Sepsis: C-Reactive Protein
Measure of inflammation -- NOT specific for infection
Elevated CRP, > 10 mg/L (>1 mg/dl), highly associated with sepsis --- but NOT diagnostic
Limited by lack of “normal” reference values for <24 hours old or preterm infants
Trend with multiple samplings correlates with infection as takes time to rise -- two samples ~24 hours apart useful
Potentially useful when maternal antibiotics given - pretreatment interferes with cultures

54. Early Onset Neonatal Sepsis: Empiric Treatment
Initial:
Ampicillin and Gentamicin IV
(Cefotaxime discouraged)
Duration:
“Rule out sepsis” hours
Pneumonia days
Sepsis days
Meningitis days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
?CRP-guided determination of duration?
Remington and Klein, Sixth Edition, 2006

55. Early Onset Neonatal Sepsis: Supportive Therapy
Ventilation
BP support - fluids, Dopamine/Dobutamine/HCTZ
TPN
FFP - clotting factors, C3, antibodies
G-CSF - stimulate WBC production/release
Steroids not indicated as anti-inflammatory
Remington and Klein, Sixth Edition, 2006

56. Treatment of GBS Infections
Initial
- Ampicillin and Gentamycin IV
(Gent synergy for first 3 days)
- May switch to Penicillin G IV
(with confirmation of diagnosis/sensitivities)
Duration (from first negative culture)
Uncomplicated sepsis days
Meningitis 14 days minimum

57. Treatment of E. Coli Infections
Ampicillin and an Aminoglycoside IV
With confirmation of diagnosis /sensitivities:
- drop Amp
- substitute a third generation cephalosporin
Duration (from first negative culture)
Uncomplicated sepsis days
Meningitis 21 days minimum

58. Treatment of Listeria Monocytogenes Infections
Ampicillin and an Aminoglycoside IV
Duration (from first negative culture)
Uncomplicated sepsis days
Meningitis 14 days minimum

59. Early Onset Neonatal Sepsis: C-Reactive Protein
Pediatrics, 1997, 99:

60. Early Onset Neonatal Sepsis: C-reactive Protein
CRP levels <10mg/L, determined >24 hours after beginning therapy correctly identified 99% of infants not needing further therapy.
May be useful in determining end-point for “rule-out sepsis” evaluations, especially with maternal antibiotic treatment.
CRP-guided determination of length of therapy, shortened the treatment course for most infected infants without increasing the rate of relapse.
Limitations: no studies evaluating meningitis or infections other than bacterial sepsis.

61. Early Onset Neonatal Sepsis: Treatment & CRP
“Exposure to antibiotics during labor did not change the clinical spectrum of disease or onset of clinical signs of infection within 24 hours of birth for term infants with EOGBS infection.”
Normal CRP values at 24 hours of age supported these observations.
Pediatrics, 2000, 106:

62. Prognosis Neonatal Sepsis
Mortality % overall - highest in premature infants
Morbidity ?? 25% ??
Neonatal Bacterial Meningitis
Mortality % - - 5% if infant survives the first 24 hr
Morbidity up to 50%
% mild to moderate neurologic sequelae
5 - 10% severe neurologic impairment

63. Early Onset Neonatal Sepsis: Prognosis - Prematurity
Organism
Mortality for BW <1500g
Mortality for BW g
Mortality for BW >2500g
Group B
Streptococci
73%
20%
10%
Escherichia coli
42%
13%
Staphylococcus aureus
44%
15% 5%
Other
67%
33%
Total
28%
Remington and Klein, Sixth Edition, 2006

64. Early Onset Neonatal Sepsis: Summary
GBS is still the predominant organism isolated in EONS
Our efforts at IAP have reduced, but not eliminated, early onset GBS sepsis
Obstetrical risk factors, including premature/near-term delivery and maternal intrapartum fever, help to identify the infants at highest risk for EONS
Ancillary laboratory evaluations, including the CRP value, may assist in determination of the most appropriate length of therapy

65. Late Onset Neonatal Sepsis

66. Late Onset Neonatal Sepsis
Perinatal acquisition with later onset
Term or preterm
Bacterial: GBS, Chlamydia
Viral: HSV, CMV, HepB, HIV
Fungal: Candida
Nosocomial acquisition
Health care associated infections
Preterm or sick term infant

67. Late Onset GBS
Transmission - Perinatally or postnatally -- intrapartum prophylaxis or neonatal treatment of early onset disease does not decrease risk of late onset disease
Symptoms - 7days - 3 months. Typically 3-4 weeks old.
Occult bacteremia or meningitis most common. However, focal infections (pneumonia, UTI, cellulitis, osteomylelitis, septic arthritis) may occur.
Diagnosis - Culture of blood, sputum, urine, abscess or other body fluid.
Treatment - Penicillin, as with early onset disease.

68. Herpes Simplex Virus (HSV)
Incidence
1/ ,000 live births
1/200 pregnant women
> 75% asymptomatic
Enveloped DS-DNA
75% HSV II
HSVI
Transmission
5-8% transplacental (congenital)
85-90% perinatally
Primary infection (risk 30-50%)
Secondary infection (risk <5%)
Impossible to distinguish 1o vs 2o
5-10% postnatally
Parent, caregiver
Usually non-genital - hand, mouth
Nosocomial spread from other infants via hands of health care professionals

69. HSV Specific Symptoms Disseminated Disease
Multi-organ involvement
Sepsis syndrome, DIC
Liver, CNS, lung predominance
Severe liver & CNS dysfunction common
Wide temp variations characteristic
Localized Central Nervous System Disease
Seizures common
Disease localized to the skin, eye and mouth
Vesicles, cloudy cornea.conjunctivitis, ulcers
Onset 1-4 weeks of age
Clinical overlap exists
Skin lesions absent or appear late with
disseminated/CNS disease

70. HSV Diagnosis High index of suspicion PE - classic vesicular lesions
History ±
Age (1-4 weeks)
Sepsis Syndrome unresponsive to antibiotic therapy
PE - classic vesicular lesions
Culture - readily grows within 1-3 days
Mouth, nasopharynx, conjunctivae rectum -- swabs >48 hours of age
Skin vesicles, urine, stool, blood and CSF
PCR - diagnostic method of choice - best on CSF, other fluids possible
CSF pleocytosis (especially monos) and elevated protein
Coagulopathy/DIC, thrombocytopenia, severe liver dysfunction
EEG

71. HSV Therapy - Prognosis
Acyclovir IV
21 days for disseminated or CNS
14 days for skin, eye and mouth
Mimimal toxicity - primarily liver - large volume IV
Decreases mortality with disseminated disease from ~75% to 25-40%
Decreases morbidity from 90% to 65%
Improvements in both mortality and morbidity dependent upon early initiation of Acyclovir

72. Neonatal Herpes: Number of Patients and Outcome by Body Site Involved in Infants with a Pre-Mortem Diagnosis and Not Treated with Antivirals*
* Modified from Nahmias et al. 265
† Primary severe neurologic sequelae.
‡ No apparent sequelae from available follow-up information.
Feigen & Cherry, Fifth Edition, 2004

73. Neonatal Nosocomial Infections

74. Risk Factors for Neonatal Nosocomial Sepsis
Prematurity
ELBW > VLBW
Increased LOS
Abdominal surgery / NEC
Hyperalimentaion / Intralipids
Neutropenia, Thrombocytopenia
Catheters
UAC, UVC, ETT, Foley, CT, Peritoneal drains, etc

75. Umbilical Arterial and Venous Catheters
Life-saving tools on the NICU
Necessary evil
Increased of infections
Minimally at 7 days
Significantly at days or when clot present
UVC > UAC
Stasis, hyperal/IL, thrombin formation

76. Umbilical Arterial and Venous Catheters
Require strict protocols regarding use and care to reduce infection rates
Remove:
when no longer needed
when evidence of infection or clot formation
Replace when required >14 days
PICC / broviac / percutaneous a-line

77. Neonatal Infections Sepsis Meningitis Pneumonia
Otitis Media
Diarrheal Disease
 UTI 
Osteomyelitis
Suppurative Arthritis
Conjunctivitis
Orbital Cellulitis
Cellulitis - - Omphalitis
Bacterial / Viral / Fungal
Multi-organ involvement common

78. Neonatal Nosocomial Infections: Microbiology
Skin flora
Coagulase negative Staphylococcus
Candida spp
Methicillin-resistant Staphylococcus aureus
Source: infant, care-givers, parents
Gram-negative bacteria
Enterococcus spp, Enterobacter spp, E. coli
Pseudomonas spp, Klebsiella spp, Seratia spp
Source:
Infant GI tract
Person-to-person transmission from Nursery personnel
Nursery environmental sites: sinks, multiple use solutions, countertops, respiratory therapy equipment…

79. Late Onset Neonatal Sepsis: Empiric Treatment
Initial:
Vancomycin and Aminoglycoside IV
(Cefotaxime discouraged)
Duration (from first negative culture):
“Rule out sepsis” hours
Pneumonia days
Sepsis days
Meningitis days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
?CRP-guided determination of duration?
Remington and Klein, Sixth Edition, 2006

80. Concerns for Antibiotic-resistant organisms
Vancomycin- resistant enterococcus (VRE)
Theoretic risk on NICU
 risk with multiple course of vanco
Strict contact isolation
Methicillin-resistant Staphylococcus aureus (MRSA)
Real risk on NICU
Community / maternal acquired
Vanco use required
Strict contact isolation

81. Treatment of Coagulase Negative Staphylococcal Infections
Vancomycin IV
(± Rifampin if difficult to clear)
Duration (from first negative culture)
Uncomplicated sepsis days
Meningitis days
Removal of indwelling intravascular catheters

82. Treatment of Gram-Negative Infections
Aminoglycoside IV + “something” (based on sensitivities)
Duration (from first negative culture)
Uncomplicated sepsis days
Meningitis days
Removal of indwelling intravascular catheters

83. Prognosis Dependent upon organism and early initiation of
appropriate therapy
LOS increased in all cases
Morbidity also variable dependent upon organ
involvement - worse with meningitis

84. Thanks for all your excellent care on the NICU!

85. Indications for GBS Intrapartum Prophylaxis
AAP Redbook, 2006 Report of the Committee on Infectious Diseases

86. Empiric management of the infant after maternal IAP
AAP Redbook, 2006 Report of the Committee on Infectious Diseases

87. Common Manifestations of Viral Infections in the Newborn Infant
Specific Features (acute)
Hyper- or hypothermia
General: irritability, lethargy, jitters, poor feeding, vomiting
CNS: seizures, hyper- or hypotonia, full fontanelle, meningitis, encephalitis
Skin: icterus, petechiae, purpura, vesicle, maculopapular rash
Eye: conjunctivitis, keratitis
Heart: myocarditis, hypotension
Abdomen: hepatosplenomegaly, hepatitis
Lung: pneumonitis, respiratory distress, cyanosis
Feigen & Cherry, Fifth Edition, 2004

88. Early Onset Neonatal Sepsis: Enteroviral infections
Diagnosis:
Culture of stool, rectum pharynx best
Culture of urine, blood and CSF may be positive
Culture of mother may be diagnostic
PCR more rapid, but less specific
Therapy: supportive only

89. Time/Mode of Acquisition of Viral Agent