Perinatal Infections (PART I &II)

Dr.Ibsa A.(pediatrician)

07/24/2023 Ibsa A. (MD) 1

 outlines
Neonatal sepsis and meningitis-PART I
TORCHS SYNDROMES-PART II
• Epidemiology
• Pathogenesis
• Etiology
• Clinical presentations
• Diagnosis and management

07/24/2023 Ibsa A. (MD) 2

 Postnatal Bacterial Infections
1.NEONATAL SEPSIS
•Sepsis neonatorum is the term used to describe any systemic bacterial infection documented by a positive blood
culture in the first month of life.
•Despite the development of newer, more potent antimicrobial agents, infections are still an important cause of
neonatal morbidity and mortality.
Incidence and Mortality
•Neonatal sepsis can be classified into two relatively distinct illnesses based on the postnatal age at onset
–early-onset sepsis occurs in the first 7 days of life; is usually a fulminant, multisystem infection acquired by
vertical transmission from the mother;
–Late-onset sepsis is usually more insidious but may have an acute onset.
–very-late-onset sepsis, which occurs after 1 months of life and affects premature infants who are of very low birthweight
(VLBW) in the neonatal intensive care unit.
• Very-late-onset sepsis is often caused by Candida species or by commensal organisms such as coagulase-negative
staphylococci (CONS).
•The incidence of neonatal sepsis varies from 1 to 5 cases per 1000 live births.
•Mortality rates decreased dramatically after the introduction of antimicrobial agents and with technological
advances in neonatal care.
•The case fatality rate for infectious neonatal illnesses has continued to decline and now is 5% to 20% for early-
onset sepsis and 5% for late-onset sepsis.
 Neonatal infections are unique:
 Transmission from the mother occurs via diverse modes
 Maternal infections are often not diagnosed during pregnancy
(asymtomatic, non-specific)
 Etiologies are different (bacteria, fungi, virus,protozoa)
 Immature immunity
 Comorbid conditions complicate Dx & Mx of infections
 c/ms are variable (subclinical, mild to severe, focal/systemic,
malformations) & depend on :
 Timing of exposure
 Inoculum size
 Immune status
 Virulence of organisms

07/24/2023 Ibsa A. (MD) 4

 Characteristics of Neonatal Sepsis

EARLY ONSET (<7 LATE ONSET (≥7 DAYS LATE- LATE ONSET
DAYS) TO 30days) (>30-90days)

Intrapartum complications Often present Usually absent Varies

Vertical; organism often

Vertical or through Usually postnatal
Transmission acquired from mother’s
postnatal environment environment
genital tract

Fulminant course,
Insidious or acute, focal
multisystem involvement,
Clinical manifestations infection, meningitis Insidious
pneumonia common,
common(75%)
meningitis (20%)

Case-fatality rate 5%–20% 5% Low

 Microbiology

• group B streptococcus (GBS) and E. coli. emerged as a

perinatal pathogen and continues to be an important
organism in newborn infections
• In neonates of VLBW with early-onset sepsis, GBS was
the most frequent pathogen, followed by E. coli and
Haemophilus influenzae.
• An increase in the incidence of E. coli and a decrease in
GBS has recently been noted
• Other pathogens, including CONS, Candida species, and
S. aureus, are more commonly etiologic agents in late-
onset infection,
 Etiologic Agents in Neonatal Sepsis

ORGANISM NUMBER (%)

Bacteria Causing Early-Onset Neonatal Sepsis *
Group B Streptococcus 166 (41)
Escherichia coli 70 (17)
Viridans streptococci 67 (16)
Enterococcus species 16 (4)
Staphylococcus aureus 15 (4)
Group D Streptococcus 12 (3)
Pseudomonas species 9 (2)
Other gram-negative enteric bacilli 16 (4)
Other 37 (9)
TOTAL 408 (100)
Etiologic Agents in Late-Onset Neonatal Sepsis †
Coagulase-negative Staphylococcus 629 (48)
Staphylococcus aureus 103 (8)
Candida albicans 76 (6)
Escherichia coli 64 (5)
Klebsiella 52 (4)
Candida parapsilosis 54 (4)
Enterococcus species 43 (3)
Pseudomonas 35 (3)
Group B Streptococcus 30 (2)
Other bacteria 197 (15)
Other fungi 30 (2)
 Transmission
• Transplacental transmission is well documented for congenital viral infections
but not for perinatal bacterial infections, with the exceptions of those caused
by Treponema pallidum and Listeria monocytogenes.
• Ascending intra-amniotic infection followed by aspiration of infected amniotic
fluid can result in systemic neonatal infection, especially in the setting of
rupture of membranes (ROM) lasting longer than 18 hours.
• Approximately 1% to 4% of neonates born to mothers with intra-amniotic
infection develop systemic infection.
• Neonatal infection can also be acquired during vaginal delivery from bacteria
colonizing the mother’s lower genital tract.
• Inadequate handwashing by the nursery staff can promote the spread of
microorganisms from an infected to an uninfected infant or from the hands of
colonized caregivers to the newborn.
• The use of instrumentation, including endotracheal tubes, nasogastric feeding
tubes, umbilical catheters, central venous catheters, and Foley catheters, also
increases the risk of neonatal infection.
• Early-onset infection is most often transmitted vertically by ascending amniotic
fluid infection and by delivery through an infected or colonized birth canal.
• The pathogens that cause later-onset disease may be acquired vertically in the
peripartum period or horizontally from fomites in the environment or from
colonized caregivers after delivery.
 Pathogenesis of ascending bacterial infection

• Birth canal is colonized with aerobic & anaerobic pathogens

• Result in amniotic infection and/or colonization of the neonate at birth

• Vertical transmission of bacteria that infect amniotic fluid and/or vaginal canal

may occur inutero or during labor/delivery (common)

• Aspiration or ingestion of bacteria in amniotic fluid congenital pneumonia GI
infection or systemic infection
• c/ms may be:
 Before delivery (fetal distress, tachycardia)
 At delivery (PNA)
 After delivery ( eg;respiratory distress, shock ,sepsis,menengitis etc.)

07/24/2023 Ibsa A. (MD) 9

 maternal infection

Bacteremia
No fetal

Or placental infection Fetal infection placental infection

No effect Effects on growth & viability

On growth/viability No fetal infection

07/24/2023 Ibsa A. (MD) 10

 Effects on growth & Viability

Embryonic death
And resorption Abortion & SB Preterm Term

IUGR developmental congenital normal infant

anomalies disease

Persistent postnatal infection eradication of infection

Progressive tissue damage No apparent disease sequelae of infection

(sequelae/death)

07/24/2023 Ibsa A. (MD) 11

 Risk Factors

MATERNAL RISK FACTORS

• Maternal factors such as malnutrition, low socioeconomic status, and recently
acquired sexually transmitted diseases can also increase the risk of infection.
• Maternal colonization with GBS has been well documented as a risk factor for
neonatal sepsis.
• Colonization during the third trimester without any complications of pregnancy
carries approximately a 1% risk of infection; this risk is increased if colonization is
associated with prematurity, maternal fever, or prolonged ROM.
• Asymptomatic bacteriuria has been associated with premature birth
PERIPARTUM RISK FACTORS
• untreated or incompletely treated focal infections of the mother (including urinary
tract, vaginal, or cervical infections), as well as systemic infections, such as maternal
septicemia or maternal fever without a focus.
• Uncomplicated ROM lasting longer than 18 hours has been associated with a 1%
incidence of neonatal sepsis.
• The risk of infection increases fourfold if chorioamnionitis and prolonged ROM
coexist.
• Perinatal asphyxia,
• Prolonged labor(>24hrs)
 Con...

NEONATAL RISK FACTORS

• For reasons that remain unclear, the rates of invasive early-onset
GBS infection are higher among blacks than in other racial groups.
• preterm delivery,
• low birthweight,
• perinatal asphyxia,
• Immaturity of the immune system of the newborn host,
• Metabolic disorders
• Congenital annomalies
• Instruemental delivery
• Umblical catheterization
.

Host Responses to Bacterial infection in the Neonate

COMPONENT FUNCTION STATUS IN NEONATE CLINICAL SIGNIFICANCE

Decreased production of
Decreased complement components,
Complement Opsonization, chemoattraction chemotactic factors, decreased
especially in preterm infants
opsonization of bacteria

Lack of antibody to specific

IgG concentration decreased in preterm
pathogens results in increased
Opsonization, complement infants, term infants have higher
Antibody risk of iinfection .Increased risk of
activation concentration than adults; IgA absent
mucosal colonization with
from secretions
potential pathogens

Decreased inflammatory
Impaired migration, impaired binding to
Neutrophil Chemotaxis response, inability to localize
chemotactic factors
infection
Normal with sufficient quantities of
Phagocytosis
opsonin
Normal in healthy neonates, diminished
Bacterial killing
in stressed neonates

Monocyte Chemotaxis Decreased Decreased inflammatory response

Phagocytosis Controversial Uncertain

Bacterial killing Controversial Uncertain

Ig, immunoglobulin.
 Con..
OTHER RISK FACTORS
 bottle feeding.
 Breast milk contain several important biologic factors found in colostrum, such as
bacterial agglutinins and iron-binding proteins, which have a local gastrointestinal
protective effect against gram-negative enteric bacilli.
 Breast milk also contains immunoglobulins, macrophages, and lymphocytes, all of
which play a role in immunologic defense.
 prior antimicrobial use
 high infant-to-nurse ratio in the neonatal intensive care unit;
 the presence of foreign materials such as endotracheal tubes and
ventriculoperitoneal shunts.
 Contaminated parenteral fluids
 Infants who acquire early-onset disease often have at least one major risk factor
associated with pregnancy and delivery, such as prolonged ROM or maternal
peripartum infection.
 By contrast, late-onset disease is seldom associated with obstetric complications.
 C/MS of neonatal infections
 General
Fever (50%), temperature instability
Poor feeding
edema
Respiratory system:
◦ Apnea, dyspnea,tachypnea
◦ Cyanosis
CVS:
 In overwhelming sepsis, an initial early phase characterized by pulmonary hypertension, decreased
cardiac output, and hypoxemia may occur
◦ Pallor, mottling
◦ Cold, clammy skin
◦ Tachy-/brady-cardia
◦ Hypotension
GIT
◦ Abdominal distension
◦ Vomiting
◦ Dirrhea
◦ HSM
• Renal
– Oliguria
– ATN
• CNS
– Letharhy Hyporeflexia
– Irregular respiration High-pitched cry
– Bulged fontanel Seizures
– Irritability Hypotonia
• Hematologic
– Jaundice purpura
– Pallor bleeding
– Petechae

07/24/2023 Ibsa A. (MD) 17

 DIFFERENTIAL DIAGNOSIS

• Because the signs and symptoms of neonatal sepsis are nonspecific,

noninfectious etiologies should be considered in the differential.
• pneumonia , transient tachypnea of the newborn, and meconium aspiration.
• Central nervous system (CNS) symptoms caused by intracranial
hemorrhage, drug withdrawal, and inborn errors of metabolism, as well as
meningitis.
• Intestinal obstruction, gastric perforation, and necrotizing enterocolitis can
present with some of the gastrointestinal signs and symptoms seen with
sepsis.
• Some nonbacterial infections, such as disseminated herpes simplex virus
(HSV) infection, can be indistinguishable from bacterial sepsis and must be
considered in the differential diagnosis
• MSS and cutaneous infection etc..
 dx
MICROBIOLOGIC TESTS
1.Cultures
•A definitive diagnosis of neonatal sepsis can be made only with a positive blood culture.
•blood, urine, and CSF should be obtained from all infants suspected of having sepsis
•A minimum of 0.5 mL of blood per bottle is recommended.
•growth can be detect as early as 8 hours and almost always within 24 to 48 hours after
collection.
•Urine should be obtained in a sterile manner. Urine cultures can be positive in infants with
sepsis in the absence of primary urinary tract infection,.
•CSF should be obtained before antibiotic administration and sent for blood cell count,
differential, and chemistry determinations, as well as for Gram stain and culture
•Although controversial, some believe that lumbar puncture may be postponed or excluded
from the evaluation of an infant with suspected early-onset disease manifested by
pneumonia.
•meningitis accompanies sepsis in approximately 10% of infants with early-onset disease and
more often with late-onset disease;
•meningitis cannot be diagnosed or excluded solely on the basis of the symptomatology; and
blood cultures can be sterile in 10% to 15% of infants with early-onset and in one third of
infants of VLBW with late-onset meningitis.
 Con...
• Cultures of tracheal aspirates should be obtained in intubated
neonates with a clinical picture suggestive of pneumonia.
• Aspirates or biopsies of skin and soft tissue lesions can be sent
for stains and cultures.
• If a joint infection is suspected, evaluation of the joint aspirate
is helpful.
• Stool cultures assist in the diagnosis of neonatal septicemia
caused by enteric pathogens such as Shigella, Salmonella, and
Campylobacter, but most often the bacteria recovered from
stool cultures reflect gastrointestinal colonization rather than
infection.
• Cultures of gastric aspirates obtained on the first day of life
reflect amniotic fluid infection and do not predict the
development of neonatal infection.
 Con...

2.Buffy Coat Examination

• Leukocyte smears made from the buffy coat layer of centrifuged, anticoagulated
blood can be stained with Gram stain and methylene blue or with acridine orange,
then examined microscopically for intracellular bacteria.
• A positive buffy coat smear supports the diagnosis of sepsis and identifies the
morphologic and Gram stain characteristics of the organism, but does not identify
the infectious agent or include or exclude other foci of infection.
3.Antigen Detection Assays
• Immunoassays that detect bacterial cell wall or capsule carbohydrate antigens in
body fluids are an adjunct to diagnosis.
• A positive result should be taken to indicate the presence of antigen and not
necessarily the presence of viable organisms.
4.OTHER LABORATORY TESTS
 Leukocyte Counts
• Leukocytosis or leukopenia, defined as more than 20,000/mm3 and fewer than
5000/mm3, respectively,but are insensitive and nonspecific.,
• the absolute total neutrophil count, absolute total immature neutrophil count, and
the ratio of immature to total neutrophils (I:T) for neonates during two time
periods: the first 60 hours of life and from 60 hours to 28 days of life
 Reference Ranges for Neutrophil (per mm 3) Indexes in the Neonate

≥120
INDEX BIRTH 12 HOURS 24 HOURS 48 HOURS 72 HOURS
HOURS

7800– 7200–
ANC 1800–5400 4200–9000 1800–7000 1800–5400
14,400 12,600
INC ≤1120 ≤1440 ≤1280 <800 <500 <500

I:T <0.16 <0.16 <0.13 <0.13 <0.13 <0.12

ANC, absolute neutrophil count (mature and immature forms); INC, immature neutrophil
count (all neutrophils except segmented ones); I:T, ratio of INC divided by ANC.

Upper limit of normal of I:T is 0.2 & is increased during infection

 Con....
 The total neutrophil count has been used to help predict the presence of infection.
 Neutropenia, especially if it occurs in the first hours of life and is associated with respiratory
distress, can be worrisome because of a strong association with early-onset GBS sepsis.
 However, many noninfectious processes are associated with both neutropenia and
neutrophilia. On the other hand, many infants with documented sepsis have normal total
neutrophil counts at the time of the initial evaluation. Therefore, the absolute total
neutrophil count has not been found helpful in diagnosing or excluding neonatal sepsis.
 The absolute total immature neutrophil count, defined as the absolute number of all
neutrophils excluding the segmented neutrophils, .
 Infected neonates may have an increase above the upper limits of normal in immature cells
released from the bone marrow in response to infection,
 it is unusual for uninfected infants to have an elevated absolute total immature neutrophil
count above the reference ranges; therefore, if such a finding is present, further evaluation
for occult infection should be considered.
 The I:T ratio has been investigated as an early predictor of sepsis.
 The maximal I:T ratio in uninfected neonates is 0.16 in the first 24 hours, decreasing to 0.12
by 60 hours. The upper limit of normal for neonates is at 0.2.
 Because most infected neonates have an elevated I:T ratio some time during the infection,
repeatedly normal I:T ratios can be reassuring.
 The usefulness of this test is limited because many noninfectious processes, including
prolonged induction with oxytocin, stressful labor, and even prolonged crying, are associated
with increased I:T ratios.
 Con..
 Acute-Phase Reactants
• The acute-phase response is a response of the body to infection or trauma and are proteins produced by hepatocytes
• There are many different APRs, including C-reactive protein (CRP), fibrinogen, C3 complement, α 1-acid glycoprotein, α1-
antitrypsin, and elastase α1-proteinase inhibitor (Eα1-PI)
• unfortunately, an elevated APR does not distinguish between infectious and noninfectious causes of inflammation.
 C-Reactive Protein
• CRP is a globulin so named because it forms a precipitate in the presence of the C-polysaccharide of Streptococcus
pneumoniae. Its function is not entirely clear, but it is believed to be a carrier protein involved in removing potentially
toxic material.
• There is minimal, if any, transplacental passage of maternal CRP, and concentrations are unaffected by gestational age.
• Normal concentrations in neonates are 1 mg/dL or lower.
• An increasing CRP value is usually detectable within 6 to 18 hours, and the peak CRP is seen at 8 to 60 hours after onset
of the inflammatory process.
• The serum half-life is 5 to 7 hours.
• Although the CRP decreases promptly in the presence of appropriate therapy, few clinical studies have been performed
evaluating discontinuation of therapy based on CRP normalization.
• CRP is significantly elevated at the time of the initial evaluation in 50% to 90% of infants with systemic bacterial
infections. Serial determinations of CRP at 12-hour intervals after the onset of signs of sepsis increased the sensitivity of
CRP in detecting sepsis.
• Nonbacterial infections can elicit a variable CRP response, with normal values in culture-positive viral meningitis and
increased values in minor viral infections.
• Noninfectious processes, including meconium aspiration pneumonitis, can have an elevated CRP up to 10 times the
normal concentration.
• CRP has a low positive predictive value and should not be used alone to diagnose sepsis.
 Con..
 Erythrocyte Sedimentation Rate
• The erythrocyte sedimentation rate (ESR) is not a direct measure of an APR but rather reflects changes in many
serum protein APRs.
• A micro-ESR has been developed for use in infants. An approximation of the maximal normal rate in the first 2
weeks of life can be obtained by adding 3 to the age of the newborn in days. Beyond 2 weeks of life, the maximal
rate varies between 10 and 20 mm per hour.
• The ESR is limited in that other factors unrelated to inflammation (anemia, hyperglobulinemia) can affect the rate.
Micro-ESR values vary inversely with the hematocrit but are affected little, if at all, by birthweight or gestational age.
• Although the ESR is usually elevated at some point in systemic bacterial infections, it is frequently normal on initial
evaluation.
 Fibrinogen
• Plasma fibrinogen concentrations are known to increase in association with infection
• but some factors can result in a low fibrinogen level despite severe infection, including disseminated intravascular
coagulation, exchange transfusion, and respiratory distress syndrome.
 Fibronectin
• Fibronectin (Fn) is a multifunctional, high–molecular-weight glycoprotein produced primarily by the liver and endothelial cells
• Fn is involved in hemostasis, vascular integrity, and wound healing,embryogenesis, directing cell migration,
proliferation, and differentiation. Fn aids in the immune response by augmenting macrophage and neutrophil
phagocytosis and acting as a nonspecific opsonin for the reticuloendothelial system.
• Fn has been found to be decreased in neonates with infection and also in neonates with asphyxia, respiratory
distress syndrome, and bronchopulmonary dysplasia.
 Cytokines
• Although cytokine kinetics have not been thoroughly investigated in neonates, it is believed by many that
measuring cytokine concentrations can be helpful in the early diagnosis of neonatal sepsis.
• the combination of IL-6 ,Il-8,TNFα and CRP determinations may be helpful in the early diagnosis of sepsis while
awaiting culture results
• Many investigators have evaluated colony-stimulating factors in the neonatal period.
 Treatment
EMPIRICAL ANTIMICROBIAL THERAPY
• Empirical antimicrobial therapy should be instituted immediately after obtaining samples for culture rather than
waiting for the culture results.
• The choice of empirical therapy should be based on several factors:
– the timing and setting of the disease (e.g., early onset, late onset community acquired, health care associated late or very late
onset),
– the microorganisms most frequently encountered,
– the susceptibility profiles for those organisms,
– the site of the suspected infection and
– the penetration of the specific antibiotic to that site, and
– the safety of the antibiotic.
• For early-onset disease
– the antimicrobial regimen should provide coverage against GBS, E. coli and other gram-negative enteric bacilli, and L.
monocytogenes. The combination of ampicillin and an aminoglycoside is frequently used.
– Listeria organisms and GBS are uniformly susceptible to ampicillin, whereas the susceptibility of E. coli to ampicillin is less
reliable.
– The aminoglycoside provides coverage against most gram-negative enteric bacilli and, with gentamicin specifically, has been
found to act synergistically with ampicillin against GBS and Listeria organisms .
– Gentamicin is used most frequently, with tobramycin and amikacin reserved for treatment of multidrug-resistant bacteria.
– If meningitis is suspected, especially gram-negative bacillary meningitis, many add or replace the aminoglycoside with the third-
generation cephalosporin, cefotaxime, for better CNS penetration.
• Empirical therapy for late-onset disease acquired in the community
– should provide coverage for the same neonatal pathogens as discussed earlier and also for potential community-acquired
pathogens, such as S. pneumoniae and Neisseria meningitidis.
– Because meningitis frequently is a component of late-onset sepsis, antibiotics with good CNS penetration should be selected.
– Ampicillin and a third-generation cephalosporin (e.g., cefotaxime) are commonly recommended.
 Con..

• Health care-associated late-onset disease

– can be caused by the usual neonatal pathogens but also by CONS, enterococci, gram-negative enteric
bacilli (including drug-resistant strains), and fungi. Empirical therapy depends on the presence of risk
factors for commensal organisms such as CONS (use of catheters or shunts) and the susceptibility profiles
for common nosocomial pathogens isolated from the nursery.
– Vancomycin and gentamicin are commonly used for initial therapy.
– Vancomycin generally is active against all staphylococcal species, streptococci, and most enterococci,
– Cefotaxime or ceftriaxone may be included when gram-negative meningitis is a concern.
– Cefotaxime does not have activity against L. monocytogenes, enterococci or Pseudomonas species.
– Ceftazidime with an aminoglycoside should be used if Pseudomonas infection is suspected.
– One disadvantage cephalosporins is an increased risk for development of gastrointestinal colonization and
perhaps subsequent infection with fungi and drug-resistant bacteria and
– With ceftriaxone, in particular, there is a theoretical risk of bilirubin displacement from albumin because of
the drug’s high protein-binding capacity.
– On the other hand, these cephalosporins are safe and effective against many of the common neonatal
pathogens, and there is extensive experience with cefotaxime use during the neonatal period. Because the
third-generation cephalosporins do not cause the dose-related toxicities seen with agents such as the
aminoglycosides, monitoring of serum concentrations is not necessary.
• Empirical therapy usually may be narrowed to one drug once final culture identification and susceptibility results
are available.
• The dosage and frequency of administration of antimicrobial agents vary with the newborn’s gestational age,
postnatal age, birthweight, and status of hepatic and renal function.
 Recommended Dosage Schedule for Antimicrobial Agents Frequently Used to Treat Neonatal Sepsis

Dosage (mg/kg per day) and Intervals of Administration

Body Weight ≤2000 g Body Weight >2000 g
ANTIBIOTIC ROUTE 0–7 Days 8–28 Days 0–7 Days 8–28 Days >28 Days

Ampicillin IV, IM 100 div q 12h 150 div q 8h 150 div q 8h 200 div q 6h 200 div q 6h

Aztreonam IV 60 div q 12h 90 div q 8h 90 div q 8h 120 div q 6h 120 div q 6h

Cefotaxime IV, IM 100 div q 12h 150 div q 8h 100 div q 12h 150 div q 8h 150 div q 6h

Ceftazidime IV, IM 100 div q 12h 150 div q 8h 100 div q 8h 150 div q 8h 150 div q 8h

100 once
Ceftriaxone IV, IM 50 once daily 50 once daily 50 once daily 75 once daily
daily
Clindamycin IV, IM, PO 10 div q 12h 15 div q 8h 15 div q 8h 20 div q 6h 30 div q 6h
Erythromycin IV, PO 20 div q 12h 30 div q 8h 20 div q 12h 40 div q 8h 40 div q 6h

Metronidazole IV, PO 15 div q 12h 15 div q 12h 15 div q 12h 30 div q 12h 30 div q 6h

Mezlocillin IV, IM 150 div q 12h 225 div q 8h 150 div q 12h 225 div q 8h 300 div q 6h

Nafcillin IV 50 div q 12h 75 div q 8h 75 div q 8h 150 div q 6h 150 div q 6h

200,000 U
Penicillin G IV 100,000 U div q 12h 200,000 U div q 8h 150,000 U div q 8h 200,000 U div q 6h
div q 6h
50,000 U (one 50,000 U (one 50,000 U
Benzathine penicillin G IM 50,000 U (one dose) 50,000 U (one dose)
dose) dose) (one dose)
50,000 U q
Procaine penicillin G IM 50,000 U q 24h 50,000 U q 24h 50,000 U q 24h 50,000 U q 24h
24h

Ticarcillin IV, IM 150 div q 12h 225 div q 8h 225 div q 8h 300 div q 6h 300 div q 6h

Div, divided.
 Recommended Dosage Schedule for Aminoglycosides and
Vancomycin in the Treatment of Neonatal Sepsis
Dosage for Weeks’ Gestation or Postconceptional Age

<30 30–37 >37

ANTIBIOTIC ROUTE

Amikacin *

IV, IM
≤7 days 15 mg/kg q 24h 15 mg/kg q 18h 15 mg/kg q 12h
*

>7 days ‡ 15 mg/kg q 18h 15 mg/kg q 12h 15 mg/kg q 8h

Gentamicin or tobramycin †

IV, IM
≤7 days 3 mg/kg q 24h 3 mg/kg q 18h 2.5 mg/kg q 12h

>7 days 3 mg/kg q 18h 2.5 mg/kg q 12h 2.5 mg/kg q 8h

Vancomycin ‡

IV
≤7 days 20 mg/kg q 24h 15 mg/kg q 18h 15 mg/kg q 12h

>7 days 20 mg/kg q 18h 15 mg/kg q 12h 15 mg/kg q 8h

 Con..
SUPPORTIVE THERAPY
• Ventilatary support particularly for infants with fulminant early-onset disease.
• IV hydration and perhaps parenteral nutrition,
• monitoring of electrolytes and glucose should be considered.
• Septic shock, if present, should be treated appropriately with fluids and inotropes as
indicated by the clinical situation.
IMMUNOTHERAPY
 Intravenous Immune Globulin
• There have been a number of studies evaluating IVIG for treatment of infected
neonates. A beneficial effect from IVIG and appropriate antibiotics was observed in
several studies compared with antibiotics used alone for the treatment of sepsis.
 Other Agents in Development
• human monoclonal IgM antibody and hyperimmune globulin specific for the
infecting pathogen..
• Fn administration may be of use in the prevention and treatment of neonatal sepsis
because of its multifunctional roles, including nonspecific opsonization that aids in
clearing debris in the reticuloendothelial system, augmentation of phagocytic
activity, and hemostasis.
• More recently, the use of recombinant human granulocyte colony-stimulating factors
or granulocyte-macrophage colony-stimulating factors as an adjunctive therapy in
the treatment of septic neutropenic neonates has been considered.
 Con..
PREVENTION
• Intrapartum antibiotic prophylaxis (IAP) for prevention of early-onset GBS disease
• The guidelines issued in 1996 recommended screening of pregnant women for
GBS colonization either by means of lower vaginal and rectal cultures obtained at
35 to 37 weeks’ gestation or by assessing clinical risk factors to identify
candidates for IAP
• All pregnant women identified as GBS carriers should receive IAP at the time of
labor or ROM. Penicillin (5 million units initially and then 2.5 million units every 4
hours until delivery) is recommended. Ampicillin (2 g initially and then 1 g every 4
hours until delivery) is an acceptable alternative.
• clindamycin and erythromycin are less effective as alternative agents.
• Delivery of a previous infant with invasive disease and GBS bacteriuria is always
an indication for IAP.
• IAP is not indicated for planned cesarean section before ROM and onset of labor.
• Risk factors (labor onset or ROM before 37 weeks’ gestation, ROM 18 hours or
more before delivery, or intrapartum fever) should be used only when the results
of cultures are not known at the onset of labor.
• The management of infants born to women receiving intrapartum
chemoprophylaxis depends on the infant’s status at birth, the duration of
prophylaxis, and the gestational age of the infant.
 Con..
• If a woman receives IAP for suspected chorioamnionitis, her infant should have a full
diagnostic evaluation and empirical therapy pending culture results based on the infant’s
exposure to established infection.
• Symptomatic infants should undergo full diagnostic evaluation and empirical therapy started.
• A lumbar puncture, if feasible, should be performed.
• Limited evaluation consisting of complete blood count with differential and blood culture and
observation for at least 48 hours is indicated for asymptomatic infants of less than 35 weeks’
gestation and for those whose mothers received chemoprophylaxis for less than 4 hours
before delivery.
• Observation is appropriate for asymptomatic infants of at least 35 weeks’ gestation whose
mothers received chemoprophylaxis at least 4 hours before delivery.
• Exposure to antibiotics during pregnancy has not changed the clinical spectrum of GBS
disease or the onset of clinical signs of infection within 24 hours of birth for term infants with
early-onset GBS infection.
• In reports that document increases in non-GBS sepsis, the increase has occurred only in
infants born prematurely or with low birthweight.
• Among multicenter studies of the incidence of non-GBS sepsis, the only one that identified a
significant increase in the rate of E. coli early-onset disease evaluated only infants with VLBW.
• A comprehensive program for prevention of neonatal bacterial infections awaits the
development and licensure of vaccines, some of which are now under testing, and of
strategies to prevent premature delivery.
 2.Neonatal Meningitis
INCIDENCE
• Neonatal meningitis occurs in approximately 1 of every 2500 live births, or approximately one fourth as frequently as
neonatal sepsis.
• Meningitis has a predilection for young age; the incidence is higher in the first month of life than at any other age.
• Furthermore, premature newborns with low birthweight have approximately a 10-fold higher risk of meningitis than
do term infants.
ETIOLOGY
• Neonatal meningitis is caused by the same pathogens associated with neonatal sepsis
PATHOGENESIS
• For meningitis in any age group, there are three mechanisms by which the meninges can become infected:
• (1) primary sepsis with hematogenous seeding;
• (2) focal infection outside the CNS, with either secondary bacteremia and resulting hematogenous dissemination or
direct extension (e.g., from an infected sinus); and
• (3) direct inoculation after head trauma or neurosurgery, or from an open congenital defect such as
myelomeningocele or dermal sinus.
• Because the most common mechanism in neonates is hematogenous spread associated with a primary bacteremia,
the perinatal risk factors that predispose an infant to neonatal sepsis also influence the risk of acquiring meningitis.
• Certain microbial factors have been associated with increased risk of meningeal invasion. Exam.
– the K1 strain of E. coli is isolated in as many as 70% of neonates with meningitis.
– Similarly, GBS meningitis of early or late onset is most often associated with serotype III.
– The IVb serotype of L. monocytogenes is more frequently isolated in late-onset Listeria meningitis than are the other serotypes.
 CLINICAL MANIFESTATIONS

• Similar to that of neonatal sepsis

• The early signs and symptoms of neonatal meningitis
are nonspecific.
• The signs most frequently observed include lethargy,
reluctance to feed, emesis, respiratory distress,
irritability, and temperature instability.
• Signs suggestive of a CNS process are less commonly
observed in neonatal meningitis
 DIAGNOSIS

• A specific diagnosis of neonatal meningitis requires growth of the

microorganism from the CSF.
• A presumptive diagnosis can be made when the CSF indexes are
suggestive of a bacterial process and a pathogen is isolated from
a blood culture.
• A thorough evaluation of CSF for the presence of infection
includes bacterial culture and Gram-stained smear, cell count
with leukocyte differential, and glucose and total protein
determinations.
• Normal values for CSF indices in the neonate are different from
those in older infants or children and may be difficult to interpret
if the age of the patient is not considered.
.

Cerebrospinal Fluid Indexes in High-Risk Neonates without

Meningitis

TERM PRETERM

White blood cells (cells/mm3)

Mean 8.2 9.0

Range 0–15 0–30

75%
lymphocyte 75%

Protein (mg/dL)
*
Mean 90 115

Range 20–170 65–150

Glucose (mg/dL)

Mean 52 50

Range 34–119 24–63

CSF/blood glucose ratio (%)

Mean 81 74

Range 44–248 55–105

CSF, cerebrospinal fluid;

PMNC 2.2+_3.8%
 TREATMENT

• When choosing empirical antimicrobial therapy for neonatal meningitis, potential

etiologic pathogens and their susceptibility patterns and the achievable
concentrations of the drugs in CSF must be consider
• Dose is doubled and duration is prolonged
• empirical therapy should provide coverage for GBS, gram-negative bacillary
enteric organisms, and L. monocytogenes.
• Ampicillin reliably covers both GBS and Listeria organisms, but its activity against
gram-negative enterics organism is variable.
• When used for meningitis, ampicillin must be given in a higher dosage than that
used for infections outside the nervous system to achieve adequate CSF
concentrations.
• Although gentamicin is active against most gram-negative enteric organisms,
aminoglycosides in general do not achieve satisfactory activity in CSF and thus are
rarely used alone for treatment of meningitis.
• When gram-negative bacillary meningitis is suspected, many clinicians favor using
ampicillin, gentamicin, and cefotaxime pending final culture and susceptibility
reports.
 Con..

• Empirical therapy for hospitalized neonates with late-onset meningitis should

provide coverage against nosocomial pathogens as well as the usual pathogens
described earlier.
– Vancomycin and an aminoglycoside are frequently chosen to provide activity against
CONS in addition to GBS and enterococci.
– If GBS is suspected, ampicillin should be included in the empiric regimen..
• The duration of therapy for culture-proved bacterial meningitis depends on the
etiologic agent recovered and the infant’s clinical response.
– The minimum duration in uncomplicated GBS or Listeria meningitis is 14 days.
– Gram-negative bacillary organisms are more difficult to eradicate from CSF.
• These infants often have persistently positive CSF cultures 3 to 4 days after the initiation of
appropriate antimicrobial agents.
• In an uncomplicated case, the duration of therapy should be a minimum of 3 weeks, or 2 weeks
after documented sterilization of CSF, whichever is longer.
• Examination of CSF, Gram-stained smears, and culture should be repeated near completion of
treatment of meningitis.
• Supportive care of the newborn with meningitis is similar to that described for
sepsis.
• In addition, treatment of seizures and inappropriate secretion of antidiuretic
hormone may be necessary .
 PROGNOSIS

• The mortality rate of neonatal meningitis has declined ,however, neurologic sequelae are still
common.
• A poor outcome after GBS meningitis has been associated with several features observed at
presentation, including
– comatose or semicomatose state, poor perfusion,
– total peripheral leukocyte count less than 5000/mm3,
– absolute neutrophil count less than 1000/mm3, and
– CSF protein greater than 300 mg/dL.
– Seizures at presentation,
– the burden of bacteria observed on Gram stain
– the severity of hypoglycorrhachia on the initial CSF sample were not predictive of outcome.
• Factors associated with poor outcome in gram-negative bacillary meningitis include
– CSF protein level greater than 500 mg/dL,
– CSF leukocyte count greater than 10,000/mm3,
– persistence of positive CSF cultures, and
– presence and persistence of elevated IL-1α and tumor necrosis factor.
• For E. coli meningitis,
– the presence and persistence of K1 capsular polysaccharide antigen and
– the concentration of endotoxin in the CSF correlated with poor outcome.
• One fourth to one third of the survivors of both gram-negative and gram-positive neonatal
meningitis experience permanent sequelae resulting in significant neurologic damage, including
hearing loss, language disorders, mental retardation, motor impairment, seizures, and
hydrocephalus.
• Both clinical follow-up and neurodevelopmental assessment are appropriate after this disease.