Neonatal Sepsis

Definition

• Neonatal sepsis is defined as a clinical syndrome of bacteremia with systemic signs and symptoms of infection in the first 4 weeks of life.

• When pathogenic bacteria gain access into the blood stream, they may cause overwhelming infection without much localization (septicemia) or may get predominantly localized to the lung (pneumonia) or the meninges (meningitis).

Classification

• Neonatal sepsis can be classified into two sub-types depending upon whether the onset of symptoms is before 72 hours of life (early onset) or later (late onset).

Etiology • The microorganisms most commonly associated with early-

onset infection include group B Streptococcus (GBS), Escherichia coli , coagulase-negative Staphylococcus, Haemophilus influenzae.

• Meningoencephalitis and neonatal sepsis syndrome can also be caused by infection with adenovirus, enterovirus, or coxsackievirus.

• Additionally, sexually transmitted diseases (eg, gonorrhea, syphilis, herpes simplex virus [HSV], cytomegalovirus [CMV], hepatitis, human immunodeficiency virus [HIV], rubella, toxoplasmosis, Trichomonas vaginalis, Candida species) have all been implicated in neonatal infection.

Early onset Sepsis

• Early-onset infections are caused by organisms prevalent in the maternal genital tract or in the delivery area.

• The associated factors for early-onset sepsis include– low birth weight,– prolonged rupture of membranes, – foul smelling liquor, – multiple per vaginum examinations,– maternal fever, – difficult or prolonged labour – aspiration of meconium.

• Early onset sepsis manifests frequently as pneumonia and less commonly as septicemia or meningitis.

Late Onset Sepsis• Late-onset septicemia is caused by the organisms thriving in the external

environment of the home or the hospital.• The infection is often transmitted through the hands of the care-providers. • The associated factors of late-onset sepsis include:

– low birth weight, – lack of breastfeeding, – superficial infections (pyoderma, umbilical sepsis), – aspiration of feeds, – disruption of skin integrity with needle pricks – use of intravenous fluids.

• These factors enhance the chances of entry of organisms into the blood stream of the neonates whose immune defences are poor as compared to older children and adults.

PathoPhysiology

• Numerous host factors predispose the newborn infant to sepsis:

• It involves all levels of host defense, including – cellular immunity, – humoral immunity, – barrier function.

Cellular immunity• Is mainly divided into 4 main components: • neonatal neutrophil or polymorphonuclear (PMN) cell:

– is vital for effective killing of bacteria– is deficient in chemotaxis and killing capacity– neutrophil reserves are easily depleted because of the diminished response of

the bone marrow, especially in the premature infant.

• Neonatal monocyte – concentrations are at adult levels; however, – macrophage chemotaxis is impaired and continues to exhibit decreased function

into early childhood. – The absolute numbers of macrophages are decreased – The chemotactic and bacteriocidal activity and the antigen presentation by these

cells are also not fully competent at birth.

Cellular immunity• T cells

– Found in early gestation and incrase till 6months of life– Cell are immature – Do not proliferate as readily as adult T cells– The cytotoxic function of the T celss are only 50% of the adult T cell– Important factor is that new borns are lacking of memory T cells

• Natural Killer Cells– Found in sma;; numbers– Functionally immature as they produce very low levels of interferon

Gamma upon primary stimulation compared to adult NK cells

Humoral immunity• fetuses has some preformed immunoglobulin present,

primarily acquired through nonspecific placental transfer from the mother

• Ability of the neonate to generate Ig in response to antigenic stimulation is intact but response is initially decreased and rapidly rises with increasing postnatal age.

• The neonate is also capable of synthesizing immunoglobulin M (IgM) in utero at 10 weeks' gestation; however, IgM levels are generally low at birth, unless the infant was exposed to an infectious agent during the pregnancy

Humoral immunity• Most of the IgG is acquired from the mother during late

gestation• The neonate may receive immunoglobulin A (IgA) from

breastfeeding but does not secrete IgA until 2-5 weeks after birth.

• Complement protein production can be detected as early as 6 weeks' gestation; however, the concentration of the various components of the complement system widely varies among individual neonates.

• Mature complement activity is not reached until infants are aged 6-10 months.

Barrier function

• Phisical an chemical barriers are present in infants but are immature

• In premature infants, skin and mucous membranes are easily broken down

• Invasive procedures cause an increased risk of contracting an infection especially in those who are clinically ill and are in the hospital.

Clinical features • The manifestations of neonatal septicemia are often vague and

therefore demand a high index of suspicion for early diagnosis.• The most common and characteristic manifestation is an alteration in

the established feeding behavior in late onset sepsis and respiratory distress in early onset sepsis.

• Hypothermia is a common manifestation of sepsis, whilst fever is infrequent.

• Diarrhea, vomiting and abdominal distension may occur. • Episodes of apneic spells or gasping may be the only manifestation of

septicemia. • In sick neonates, the skin may become tight giving a hide-bound feel

(sclerema) and the perfusion becomes poor (capillary refill time of over 3 seconds).

Clinical Features in localized sepsis• The additional features of pneumonia or meningitis may be present • The evidence of pneumonia includes

– tachypnea, – chest retractions, – grunting, – early cyanosis – apneic spells– Cough is unusual.

• Meningitis is often silent, the clinical picture being dominated by manifestations of associated septicemia.

• However, the appearance of excessive or high-pitched crying, fever, seizures, blank look, neck retraction or bulging anterior fontanel are highly suggestive of meningitis.

WHO study published in 2003 • identified nine clinical features which predict severe bacterial

illness in young infants 1. Feeding ability reduced 2. No spontaneous movement 3. Temperature >38 C 4. Prolonged capillary refill time 5. Lower chest wall in drawing 6. Resp rate > 60/minute 7. Grunting 8. Cyanosis 9. H/o of convulsions

Investigations• The CSF findings in infectious neonatal meningitis are an elevated WBC count

(predominately PMNs), an elevated protein level, a decreased CSF glucose concentration, and positive culture results.

• An absolute neutrophil count of < 1800 per cmm is an indicator of infection. • Immature neutrophils (Band cells + myelocytes + metamyelocytes) to total neutrophils

ratio (l/T) > 0.20 • Platelet count of less than 100,000 per cmm • C-reactive protein (CRP) which has a high degree of sensitivity for neonatal sepsis • A practical positive "sepsis screen" takes into account two or more positive tests as

given below: 1. Leukopenia (TLC <5000/cmm)

2. Neutropenia (ANC <1800/cmm) 3. Immature neutrophil to total neutrophil (I/T) ratio (> 0.2) 4. Micro ESR (> 15mm 1st hour) 5. CRP +ve

Treatment

• No investigation is required as a prerequisite to start treatment in a clinically obvious case.

• Supportive care and antibiotics are two equally important components of the treatment.

• It should be realized that antibiotics take at least 12 to 24 hours to show any effect and it is the supportive care that makes the difference between life and death early in the hospital course.

Supportive care

• The purpose of supportive care is to:– normalize the temperature, – stabilize the cardiopulmonary status, – correct hypoglycemia and – prevent bleeding tendency

Supportive care of a septic neonate

1. Provide warmth, ensure consistently normal temperature 2. Start intravenous line. 3. Infuse normal saline 10 ml/kg over 5-10 minutes, if perfusion is poor as

evidenced by capillary refill time (CRT) of more than 3 seconds. Repeat the same dose 1-2 times over the next 30-45 minutes, if perfusion continues to be poor.

4. Infuse glucose (10 percent) 2 ml/kg stat. 5. Inject Vitamin K 1 mg intramuscularly. 6. Start oxygen by hood or mask, if cyanosed or grunting. 7. Provide gentle physical stimulation, if apneic. 8. Provide bag and mask ventilation with oxygen if breathing is inadequate. 9. Avoid enteral feed if very sick, give maintenance fluids intravenously 10. Consider use of dopamine if perfusion is persistently poor. 11. Consider exchange transfusion if there is sclerema.

Treatment• Antibiotic therapy should cover the common causative bacteria, namely,

Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. • A combination of ampicillin and gentamicin is recommended for

treatment of sepsis and pneumonia. • In cases of suspected meningitis, cefotaxime should be used along with

an aminoglycoside.• On confirmation of sensitivity pattern, appropriate antibiotics are used

singly or in combination. • In a baby in whom the antibiotics were started on low suspicion, these

may be stopped after 3 days, if baby is clinically well • if a baby appears ill even though the cultures are negative, antibiotic

therapy should be continued for 7 to 10 days .

Superficial infections • Superficial infections can be treated with local application

of antimicrobial agents. • Pustules can be punctured with sterile needles and

cleaned with spirit or betadine. • Purulent conjunctivitis can be treated with neosporin or

chloramphenicol ophthalmic drops. • Oral thrush responds to local application of clotrimazole or

nystatin (200,000 units per ml) and hygienic precautions. • Superficial infections must be adequately managed; if

neglected they can lead to sepsis or even an epidemic.

Prevention of infections • A good antenatal care goes a long way in decreasing the

incidence, morbidity and mortality from neonatal sepsis. • All mothers should be immunized against tetanus. • All types of infections should be diagnosed early and

treated vigorously in pregnant mothers. • Babies should be fed early and exclusively with

expressed breast milk (or breastfed) without any prelacteal feeds.

• Cord should be kept clean and dry. Unnecessary interventions should be avoided.

Hand washing

• This is the simplest and the most effective method for control of infection in the hospital.

• All persons taking care of the baby should strictly follow hand washing policies before touching any baby.

• The sleeves should be rolled above the elbows. • Rings, watches and jewellery should be removed. • Hand should be washed with a thorough scrub for 2

minutes before starting to see patients and washed again for 20 second in between patients.

Prevention of infection in hospital • The nursery environment should be clean and dry with 24 hour

water supply and electricity. • The nursery temperature should be maintained between 30+2°C. • All procedures should be performed after wearing mask and

gloves. • Unnecessary invasive interventions such as needle pricks and

setting up of intravenous lines should be kept to the barest minimum.

• Every baby must have separate thermometer and stethoscope( if possible) and all barrier nursing measures must be followed.

Congenital Pneumonia

Defination

• Pneumonia is an inflammatory pulmonary process that may originate in the lung or be a focal complication of a contiguous or systemic inflammatory process within the first 24 – 48 hours of life.

Pathogenesis

• In neonatal pneumonia, pulmonary and extrapulmonary injuries are caused directly and indirectly by invading microorganisms or foreign material and by poorly targeted or inappropriate responses by the host defense system that may damage healthy host tissues as badly or worse than the invading agent.

• Direct injury by the invading agent usually results from synthesis and secretion of microbial enzymes, proteins, toxic lipids, and toxins that disrupt host cell membranes, metabolic machinery, and the extracellular matrix that usually inhibits microbial migration.7,8

• Indirect injury is mediated by structural or secreted molecules which may alter local vasomotor tone and integrity, change the characteristics of the tissue perfusate, and generally interfere with the delivery of oxygen and nutrients and removal of waste products from local tissues.

Risk Factors• Unexplained preterm labor• Rupture of membranes before the onset of labor• Membrane rupture more than 18 hours before delivery• Maternal fever (>38°C/100.4°F)• Uterine tenderness• Foul-smelling amniotic fluid• Infection of the maternal genitourinary tract• Previous infant with neonatal infection• Nonreassuring fetal well-being test results• Fetal tachycardia• Meconium in the amniotic fluid• Recurrent maternal urinary tract infection• Gestational history of illness consistent with an organism known to have

transplacental pathogenic potential

Clinical signs & symptoms• may be pulmonary or systemic• Pulmonary:• Persistent tachypnea (respiratory rate >60/min) • Expiratory grunting may occur.• Accessory respiratory muscle recruitment, such as nasal flaring and retractions at subcostal, intercostal, or

suprasternal sites, may occur.• Airway secretions may vary substantially in quality and quantity.• If aspiration of meconium, blood, or other proinflammatory fluid is suspected, other colors and textures reflective

of the aspirated material may be seen.• Rales, rhonchi, and cough are all observed much less frequently in infants with pneumonia than in older

individuals. • Cyanosis of central tissues, such as the trunk, implies a deoxyhemoglobin concentration of approximately 5 g/dL or

more and is consistent with severe derangement of gas exchange from severe pulmonary dysfunction as in pneumonia,

• Infants may have external staining or discoloration of skin, hair, and nails with meconium, blood, or other materials when they are present in the amniotic fluid.

• Increased respiratory support requirements such as increased inhaled oxygen concentration, positive pressure ventilation, or continuous positive airway pressure are commonly required before recovery begins.

• Infants with pneumonia may manifest asymmetry of breath sounds and chest excursions, which suggest air leak or emphysematous changes secondary to partial airway obstruction.

Systemic findings

• Similar to signs and symptoms seen in sepsis or other severe infectionsTemperature instability– Skin rash– Jaundice at birth– Tachycardia– Glucose intolerance– Abdominal distention– Hypoperfusion– Oliguria

Laboratory Studies

• Aspiration Culture• Blood culture• Culture of specimens from lumbar puncture• Urine culture • Imaging Studies– Radiography– Ultrasonography• Ultrasonography is particularly useful for identifying and

localizing fluid in the pleural and pericardial spaces.

Treatment• Antimicrobial therapy

– initial empiric therapy consists of ampicillin and either gentamicin or cefotaxime– Drainage of a restrictive or infected effusion or empyema may enhance

clearance of the infection and improves lung mechanics.• Respiratory support

– Criteria for institution and weaning of supplemental oxygen and mechanical support are similar to those for other neonatal respiratory diseases.

• Hemodynamic support– Delivery of adequate amounts of glucose and maintenance of thermoregulation,

electrolyte balance, and other elements of neonatal supportive care are also essential aspects of clinical care.

• Nutritional support: – Attempts at enteral feeding often are withheld in favor of parenteral nutritional

support until respiratory and hemodynamic status is sufficiently stable.

Complications• Restrictive pleural effusion• Infected pleural effusion• Empyema• Systemic infection with metastatic foci• Pulmonary Hypertension, Persistent-newborn• Air leak syndrome, including pneumothorax, pneumomediastinum,

pneumopericardium, and pulmonary interstitial emphysema• Airway injury• Obstructive airway secretions• Hypoperfusion• Chronic lung disease• Hypoxic-ischemic and cytokine-mediated end-organ injury