neonatal-sepsis-1219225703095484-9

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NEONATAL

SEPSIS

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DR. CRISBERT I. CUALTEROS

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Definition

Neonatal sepsis is a clinical syndrome

of systemic illness accompanied by

bacteremia occurring in the first month

of life.

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Incidence

primary sepsis is 1 - 8 per 1000 live

births

as high as 13-27 per 1000 for infants

weighing

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Pathophysiology

3 Clinical Situations :

A. Early- Onset Disease

B. Late - Onset Disease

C. Nosocomial Sepsis

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Pathophysiology

A. Early-Onset Disease

first 5 7 days of life

is usually a multi-system fulminant illness

with prominent respiratory symptoms

Typically, the infant has acquired the

organism during the intrapartum period from

the maternal genital tract

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Pathophysiology

In this situation, the infant is colonized with thepathogens in the perinatal period..

Several infectious agents.

Treponemes

Viruses

Listeria

Candida

can be acquired transplacentally viahematogenous routes

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Pathophysiology

presence of vernix or meconium impairs thenatural bacteriostatic properties of amnioticfluid.

Finally, the infant may be exposed to vaginalflora as it passes through the birth canal.

PRIMARY SITES of colonization :

1. nasopharynx

2. oropharynx

3. conjuctiva

4. umbilical cord

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Pathophysiology

Trauma to these mucosal surfaces infection

Early-onset disease is characterized by a sudden

onset and fu lm inant course that can

progress rapid ly to sept ic shoc k w i th a

high mortal ity rate.

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Pathophysiology

2. Late - Onset Disease

as early as 5 days of age but common 1stweek of life

although these infants may have a history ofobstetric complications less frequent thanearly-onset disease

infants usually have an identifiable focus, most

often meningitis in addition to sepsis

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Pathophysiology

bacteria responsible for late-onset sepsis

and meningitis include those :

1. acquired after birth from the maternal

genital tract

2. acquired after birth from human contact

or from contaminated equipment

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Pathophysiology

C. Nosocomial Sepsis

occurs in high-risk newborn infants

They are related to :

1. to the underlying illness and debilitation of the

infant

2. the flora in the NICU environment

3. invasive monitoring and other techniques usedin neonatal intensive care

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Pathophysiology

Breaks in the natural barrier function of the

skin and intestine allow this opportunistic

organism to overwhelm the neonate

Infants, especially premature infants, have an

increased susceptibility to infection

underlying illnesses and immature defenses

that are less efficient at localizing and clearing

bacterial invasion.

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Causative Organisms

Agents associated with primary sepsis are usuallyfrom the vaginal flora :

1. group B streptococci (GBS) most

common2. Gram-negative enteric organismsespecially E. coli

3. L is ter ia monocytogenes

4. Staphy lococcus5. other streptococci (including the

enterococci)

6. anaerobes

7. Haemophi lus inf luenzae

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Causative Organisms

The flora causing nosocomial sepsis vary in

each nursery

The Agents are :

1. Staphylococci (especially Staph.

epidermidis)

2. gram-negative rods (including

Pseudomonas, Klebsiella, Serratia, andProteus and fungal organisms predominate

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Clinical Presentation

initial diagnosis of sepsis is, by necessity, a

clinical one because it is imperative to begin

treatment before the results of culture are

available

Clinical S/Sx of sepsis are nonspecific, and the

differential diagnosis is broad

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1. Temperature irregularity. Hypo- or

hyperthermia (greater heat output required by

the incubator or radiant warmer to maintain a

neutral thermal environment or frequentadjustments of the infant servo control probe).

2. Change in behavior. Lethargy, irritability, or

change in tone.

3. Skin. Poor peripheral perfusion, cyanosis,

mottling, pallor, petechiae, rashes, sclerema,

or jaundice.

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4. Feeding problems. Feeding intolerance,vomiting, diarrhea (watery loose stool), orabdominal distention with or without visiblebowel loops.

5. Cardiopulmonary. Tachypnea, respiratorydistress (grunting, flaring, and retractions),apnea within the first 24 h of birth or of newonset (especially after 1 week of age),tachycardia, or hypotension, which tends to belate sign.

6. Metabolic. Hypo- or hyperglycemia ormetabolic acidosis.

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Risk Factors :

1. Prematurity and low birth weight

2. Rupture of membranes. Premature or

prolonged (>18 h) rupture of membranes

3. Maternal peripartum fever(38 C/100.4

F) or infection. Chorioamnionitis, urinary

tract infection (UTI), vaginal colonization

with E..coli. and other obstetriccomplications.

4. Amniotic fluid problems. Meconium-

stained or foul-smelling, cloudy amniotic

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Risk factors

9. Iron therapy (iron added to serum in vitroenhances the growth of many organisms).

10. Other factors.

males are 4 times more affected thanfemales

more common in black than in white

infants

Variations in immune function may play a

role

NICU staff and family members are often

vectors for the spread of microorganisms,

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Diagnosis

A . Laboratory Studies

1. Cultures

Blood and other normally sterile body fluids

should be obtained for culture.. *Positive

bacterial cultures will confirm the diagnosis of

sepsis

Computer-assisted, automated blood culturesystems shown to identify up to 94% of all

microorganisms by 48 hr of incubation

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Diagnosis

Cultures

Results may vary because of a number of

factors, including maternal antibiotics

administered before birth, organisms that aredifficult to grow and isolate (ie., anaerobes),

and sampling error with small sample

volumes (the optimal amount is 1-2

mL/sample).

Therefore, in many clinical situations, infants

are treated for presumed sepsis despite

negative cultures, with apparent clinical

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Diagnosis

2. Gram's stain of various fluids helpful for the study of CSF

Gram-stained smears and cultures ofamniotic fluid or of material obtained bygastric aspiration

Adjunctive laboratory tests

A. WBC count with differential

Neutropenia may be a significant findingwith an ominous prognosis whenassociated with sepsis

Serial white blood cell counts several hoursa art ma be hel ful in establishin a trend.

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Diagnosis

B. Platelet count

decreased platelet count is usually a

late*sign and is very nonspecific

B. Acute-phase reactants

complex multifunctional group comprising

complement components, coagulation

proteins, protease inhibitors, C-reactiveprotein (CRP), and others that rise in

concentration in the serum in response to

tissue injury.

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Diagnosis

remain elevated with ongoing

inflammation, but with resolution they

decline rapidly due to a short half-life of

47 h CRP demonstrates high sensitivity and

negative predictive value

II. The standard ESR may be elevated but usually not until

well into the illness

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Diagnosis

I. C R P

increases the most in the presence ofinflammation caused by infection or tissue

injury highest concentrations in patients with

bacterial infections, whereas moderateelevations chronic inflammatory conditions

onset of inflammation, CRP synthesisincreases within 46 h, doubling every 8h, and peaks at about 3650 h

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Diagnosis

III. Cytokines IL-1, IL-6, IL-8, and TNF

major mediators of the systemic responseto infection

Studies have shown that combined use ofIL-8 and CRP as part of the workup forbacterial infection reduces unnecessaryantibiotic treatment

III. Surface neutrophil

CD11 has been shown to be anexcellent marker of early infection thatcorrelates well with CRP but peaks earlier.

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Diagnosis

IV. Miscellaneous tests.

Abnormal values for bilirubin,

glucose, and sodium may, in the proper

clinical situation, provide supportive

evidence for sepsis.

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Diagnosis

Radiologic Studies

1. Chest X-ray film in case with respiratory

symptoms

2. Urinary Tract Imaging. Imaging with renalultrasound examination, renal scan, or

voiding cystourethrography - should be part

of the evaluation when UTI accompanies

sepsis. Sterile urine for culture must be

obtained by either a suprapubic or catheterized

specimen

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Diagnosis

3. Other studies. Examination of the

placenta and fetal membranes may

disclose evidence of chorioamnionitis

and thus an increased potential forneonatal infection

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Differential Diagnosis

1. Respiratory distress syndrome (RDS)

2. Metabolic diseases

3. Hematologic disease4. CNS disease

5. Cardiac disease

6. other infectious processes (ie. TORCHinfections)

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Management

1. GBS prophylaxis

major pathogen in the late 1960s and currently

remains the most common cause of early-

onset sepsis 10 to 30% of pregnant women are colonized

with GBS in the vaginal or rectal area

incidence of infection has been estimated at0.85.5/1000 live births (unchanged for the

past three decades).

Case fatality rate ranges from 515%

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ManagementConsensus guidelines regarding

management of GBS were published byCDC in 1996 and were supported by

American Association of Pediatrics and

American College of Obstetricians andGynecologists. The guidelines

recommended one of two approaches:

a) the prenatal screening approach

(screening all pregnant women for GBS

infection at 3537 weeks gestation and

treatment of those women with positive

cultures)

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Management

b) identifying women who present with risk

factors treating them during labor

To ensure appropriate treatment for neonates

born to mothers who receive antibiotics forfever and presumed choriomanionitis, as well

as for those born to mothers who receive

intrapartum antibiotic prophylaxis (IAP)

because of GBS colonization, they areclinically using an algorithm in their hospital

based on AAP guidelines, with some

alterations based on clinical experiences.

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Maternal IAP Maternal IAP

Mother asymptomatic Mother w/ ssx of chorio-

amnionitisSigns & Symptoms of

sepsis in infant

yesno

Full dx

eval.

Emperic Tx

Gestational

age

37

wks

Limited eval

Observe 48HIf sepsis

suspected, full

eval & empiric

Rx

No evaluation

No therapyObserve min, 48

H

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Management

2. Standard precautions

have been mandated by the U.S.

Occupational Safety and Health

Administration (OSHA) and apply to

blood, semen, vaginal secretions, wound

exudate and CSF and amniotic fluids

caution to prevent injuries when using ordisposing of needles or other sharp

instruments

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Management

3. Initial therapy Treatment is most often begun before a

definite causative agent is identified.

Penicillin, usually Ampicillin, plus an

Aminoglycoside such as Gentamicin.

In nosocomial sepsis flora of the NICUmust be considered: however, generally,

staphylococcal coverage with Vancomycin plus either an

Aminoglycoside or a 3rd Gen. ephalosporin

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Management

3. Continuing therapy is based on culture

and sensitivity results, clinical course,

and other serial lab studies (eg., CRP).

Monitoring for antibiotic toxicity is

important as well as monitoring levels of

aminoglycosides and vancomycin.

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Management

When GBS is documented as the

causative agent Penicillin is the DOC

Aminoglycoside is often given as well

because of documented synergism

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Complications and Supportive

Therapy1. RESPIRATORY Ensure adequate oxygenation with blood

gas monitoring and initiate O2 therapy orventilator support if needed

2. CARDIOVASCULAR Support BP and perfusion to prevent

shock. Use volume expanders, 10-20 mL/kg(normal saline, albumin, and blood), and

monitor the intake of fluids and output of urine. Pressor agents such as dopamine or

dobutamine may be needed.

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Therapy3. Hematologic

a. DIC

one may observe generalized bleeding atpuncture sites, the gastrointestinal tract, orCNS sites. In the skin, large vessel

thrombosis gangrene.

Lab. parameters consistent with DIC include :

thrombocytopenia, inc. PT, and inc. Partial

Thromboplastin Time

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Therapy

Measures include treating the underlying

disease; fresh-frozen plasma, 10 mL/kg;

vitamin K; platelet infusion; and possible

exchange transfusion.

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Therapyb) Neutropenia

Multiple factors contribute to the increasedsusceptibility of neonates to infection, includingdevelopmental quantitative and qualitativeneutrophil defects.

Studies suggest use of recombinant humangranulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can partially counterbalance thesedefects and reduce morbidity and mortality.

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Therapy4. CNS

Implement seizure control measures

Phenobarbital, 20 mg/kg loading dose

monitor for the syndrome of inappropriateantidiuretic hormone (SIADH) :

i. decreased urine output,

ii. hyponatremia,iii. decreased serum osmolarity, and

iv. increased urine specific gravity and osmolarity

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Therapy

4. METABOLIC

Monitor for and treat hypo- or

hyperglycemia. Metabolic acidosis

may accompany sepsis and is treated

with bicarbonate and fluid replacement.

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Future Developments

Immunotherapy progress continues in thedevelopment of various hyperimmuneglobulins, monoclonal antibodies to the specificpathogens causing neonatal sepsis

They may prove to be significant adjuvants tothe routine use of antibiotics for the treatmentof sepsis

Research is also ongoing into blocking someof the body's own inflammatory mediators thatresult in significant tissue injury, includingendotoxin inhibitors, cytokine inhibitors, nitricoxide synthetase inhibitors, and neutrophiladhesion inhibitors.

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.Thank you

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