NEONATAL SEPTICEMIA

Neonatal septicemia is a clinical diagnosis with features of sepsis with or without positive blood/CSF cultures during first month of life.

According to the time of onset, it may be divided in early onset sepsis (EOS) manifesting lt;72 hours of delivery or late-onset sepsis (LOS), with different predisposing factors and microbial etiology.

Risk factors: Neonatal sepsis is the commonest cause of neonatal mortality in India, with an estimated incidence of ~2-10%, depending on risk factors (Table 12.44). Premature rupture of membranes, foul­smelling liquor amnii and complicated delivery with neonatal resuscitation are most important risk factors for EOS, while LOS is predominantly associated with

TABLE 12.44: Risk factors for neonatal septicemia

Early-onset sepsis

• Maternal factors

- Maternal fever lt;14 days before delivery

- Foul smelling/meconium stained L. amnii

- Prolonged rupture of membranes gt;24 hours

• Obstetrical factors

- Prolonged, difficult or instrumental delivery

- Repeated unclean vaginal examinations

Late-onset sepsis

• Neonatal factors

- Preterm or small-for-date delivery

- Superficial infections, e.g. umblical sepsis

- Postnatal (milk) aspiration

• Nosocomial factors

- Neonatal resuscitation procedures

- Invasic Intensive care procedures

- Prolonged antibiotic therapy prematurity/low birth weight, umbilical sepsis and nosocomial infections.

Microbial etiology depends on the source and timing of infection.

EOS is usually caused by maternal flora of the genital tract, e.g. E. coli, Klebsiella, Enterobacter, Listeria, etc. Group B streptococci—the commonest cause of EOS in developed countries, is relatively uncommon in India.

LOS is usually a nosocomial infection due to organisms prevalent in hospital environment, e.g. Staph. aureus, Klebsiella, Pseudomonas, Acinetobacter, enterococci, coagulase negative staphylococci (CONS), etc.

Microbial profile of neonatal septicemia also depends on locally prevalent flora and infection-control practices. In general, Klebsiella (~30%), S. aureus (~15%) and pseudo­monas (~15%) are common pathogens in India, with rising incidence of acenobactor, enterococci and CONS.

Clinical presentation of neonatal sepsis extends from silent bacteremia to multi-organ dysfunction, though most cases present with:

• Early clinical indicators, e.g. refusal to feed, sluggish activity or irritability, excessive or high-pitched cry, respiratory distress or apneic spells, seizures, diarrhoea and/or vomiting.

• Signs of systemic stress, e.g. hypothermia, sclerema, pallor, cold-clammy skin, circumoral cyanosis, exaggerated icterus and purpuric spots. Peripheral perfusion may be poor with capillary filling time exceeding 3 seconds.

• Signs of localized infection, e.g. umbilical sepsis or pyoderma, pneumonia, meningitis (~20-3#952;%), necrotizing enterocolitis and bleeding diathesis, e.g. DIC. Pneumonia and meningitis is more common in EOS and LOS respectively.

Diagnosis of neonatal septicemia usually rests on clinical suspicion and presence of high-risk factors.

However, laboratory confirmation requires:

• Indirect evidences, e.g. peripheral smear, are useful screening tests for early diagnosis of neonatal septicemia. A combination of indirect evidences is often termed sepsis screen (Table 12.45), with specificity

TABLE 12.45: Sepsis screen in newborns

• Hematological findings (criteria)

- Leukopenia (lt;5000 cells/mm³)

- Absolute neutropenia (lt;1800 cells/mm³)

- Immature (Band) cell count gt;20% (I:T Ratio gt; 2)

- Thrombocytopenia lt;1,00,000 cells/mm³

• Positive acute phase reactants

- C-reactive protein (CRP) gt;8 mg/L

- Micro ESR gt; 15 mm/FHR

I:T ratio: Immature to total neutrophil count ratio.

and sensitivity of gt;90%, if at least two parameters are fulfilled.

• Direct evidences, i.e. positive culture from blood, CSF, pus, etc. is the gold standard for diagnosis of neonatal sepsis. However, a sterile culture does not exclude the diagnosis, specially if empirical antimicrobial therapy was started before sample collection. BACTEC radiometry, though costly, is very useful for earlier microbial identification than conventional culture.

• Antigen-detection tests (Latex-agglutination test, ELISA) or polymerase chain reaction (PCR) are specially useful to identify causative pathogens in culture-sterile cases.

• Evidence of focal infections, e.g. abnormal CSF findings, urine-analysis, pus cells in umbilical discharge, gastric wash, etc. CSF examination is indicated in all cases of severe sepsis, though reports should be interpreted carefully, as newborns, specially preterms, have higher protein and cell content in CSF, than in older children.

Management of neonatal septicemia may be divided into antimicrobial therapy and supportive management.

• Antimicrobial therapy should be started empirically after collection of cultures and modified after culture/ sensitivity reports. Choice for empirical therapy may vary in different centers, based on local flora and sensitivity patterns (Table 12.46). In all cases, antibiotics should be given via IV route and continued for minimum 10 days in cases without meningitis and for minimum 21 days in presence of meningitis.

• Supportive therapy depends on individual needs and includes:

± Maintenance of temperature with warmer care,

± Oxygen/ventilatory support

TABLE 12.46: Antimicrobial therapy in neonatal septicemia

Empirical therapy

NS without meningitis (minimum 7-10 days)

First-line : Ampicillin + Aminoglycoside

Second-line : Piperacillin tazobactam + Aminoglycoside

NS with meningitis (minimum 21 days)

First-line : Cefotaxime + Aminoglycoside or Vancomycin + Aminoglycoside

Second line : Meeropenem + Aminoglycoside or Specific therapy

E.

Listeria : Ampicillin

Daily IV doses in newborn (in 2-3 divided doses):

Ampicillin/Cloxacillin/Piperacillin all (100-150 mg/kg/d), Cefotaxime/Ceftazidime/Ceftriaxone all (100-150 mg/kg)

Gentamycin (5-8 mg/kg), Amikacin (15 mg/kg),

Meropenem (120 mg/kg), Vancomycin (30 mg/kg)

± Circulatory support with IV fluids, volume expanders (blood/plasma) and vasopressors.

± Fluid and electrolyte correction

± Adequate oral or parenteral nutrition

± Treatment of complications, e.g.

#9632; Hypoglycemia (IV dextrose 10% 2 ml/kg stat)

#9632; Apneic spells (stimulation, aminophylline)

#9632; Hyperbilirubinemia (phototherapy/exchange)

#9632; Bleeding tendency (vitamin K, FFP, platelets)

#9632; Seizures (anticonvulsants)

± Surgical interventions, e.g. drainage of pus, etc.

Role of immunoglobulins and exchange transfusion in neonatal septicemia is controversial but may be useful in some critically sick cases.

Prevention of neonatal septicemia involves: (a) early detection and management of high-risk factors, (b) six “cleans” at the time of delivery (clean hands, clean delivery surface, clean perineum, clean blade to cut the cord, clean/dry cord and clean towels), and (c) prevention of nosocomial infections.

Role of prophylactic antibiotics is controversial though may be indicated in presence of high-risk factors for neonatal septicemia. However, intrapartum antibiotic prophylaxis with a single dose Penicillin or cefazolin, 4 hours before delivery is indicated to prevent GBS sepsis in cases of PROM, maternal fever and antenatal GBS colonization in rectovaginal swabs.

Listeriosis (L. monocytogenes) is an emerging cause of meningitis/ septicemia in newborns (or immunodeficient children). It is primarily an epizootic infection, trans­mitted to humans via consumption of infected animal products, e.g. milk or faeces-contaminated vegetables. Maternal listeriosis is asymptomatic, but with higher risk of abortion, stillbirth or premature delivery.

Neonatal listeriosis is acquired during delivery via infected birth-canal or as nosocomial infection and typically presents as meningitis with septicemia. diagnosis rests on blood and CSF cultures, along with simultaneous cultures from maternal genital tract. Treatment of choice is Ampicillin alone or with an aminoglycoside, followed by vancomycin in non-responders. Listeria is not susceptible to third-generation cephalosporins.

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