NEONATAL SEPSIS

DR. CRISBERT I. CUALTEROS

Definition
Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia occurring in the first month of life.

Incidence
primary sepsis is 1 - 8 per 1000 live births as high as 13-27 per 1000 for infants weighing <1500 g mortality rate is high (13-25%) higher rates are seen in premature infants and in those with early fulminant disease

Pathophysiology
3 Clinical Situations :
A. Early- Onset Disease B. Late - Onset Disease C. Nosocomial Sepsis

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

Pathophysiology
In this situation, the infant is colonized with the pathogens in the perinatal period.. Several infectious agents. Treponemes Viruses Listeria Candida can be acquired transplacentally via hematogenous routes

Pathophysiology
acquisition of other organisms is associated with the birth process. with rupture of membranes, vaginal flora or various bacterial pathogens may ascend to reach the amniotic fluid and the fetus Chorioamnionitis develops, leading to fetal colonization and infection. aspiration of infected amniotic fluid by the fetus or neonate may play a role in resultant respiratory symptoms.

Pathophysiology
presence of vernix or meconium impairs the natural bacteriostatic properties of amniotic fluid. Finally, the infant may be exposed to vaginal flora as it passes through the birth canal. PRIMARY SITES of colonization : 1. nasopharynx 2. oropharynx 3. conjuctiva 4. umbilical cord

Pathophysiology
Trauma to these mucosal surfaces infection Early-onset disease is characterized by a sudden onset and fulminant course that can progress rapidly to septic shock with a high mortality rate.

Pathophysiology
2. Late - Onset Disease as early as 5 days of age but common 1st week of life although these infants may have a history of obstetric complications less frequent than early-onset disease infants usually have an identifiable focus, most often meningitis in addition to sepsis

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

Pathophysiology
The reasons for delay in development in clinical illness, the predilection for central nervous system (CNS) disease, and the less severe systemic and cardiorespiratory symptoms are unclear.

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 used in neonatal intensive care

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.

Causative Organisms
Agents associated with primary sepsis are usually from the vaginal flora : 1. group B streptococci (GBS) most common 2. Gram-negative enteric organisms especially E. coli 3. Listeria monocytogenes 4. Staphylococcus 5. other streptococci (including the enterococci) 6. anaerobes 7. Haemophilus influenzae

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, and Proteus and fungal organisms predominate

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

Clinical Presentation
1. Temperature irregularity. Hypo- or hyperthermia (greater heat output required by the incubator or radiant warmer to maintain a neutral thermal environment or frequent adjustments 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.

Clinical Presentation
4. Feeding problems. Feeding intolerance, vomiting, diarrhea (watery loose stool), or abdominal distention with or without visible bowel loops. 5. Cardiopulmonary. Tachypnea, respiratory distress (grunting, flaring, and retractions), apnea within the first 24 h of birth or of new onset (especially after 1 week of age), tachycardia, or hypotension, which tends to be late sign. 6. Metabolic. Hypo- or hyperglycemia or metabolic acidosis.

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 obstetric complications. 4. Amniotic fluid problems. Meconiumstained or foul-smelling, cloudy amniotic

Risk Factors :
5. Resuscitation at birth. Infants who had fetal distress, were born by traumatic delivery or were severely depressed at birth and required intubation and resuscitation. 6. Multiple gestation. 7. Invasive procedures. Invasive monitoring and respiratory or metabolic support. 8. Infants with galactosemia (predisposition to E. coli sepsis), immune defects, or asplenia.

Risk factors
9. Iron therapy (iron added to serum in vitro enhances the growth of many organisms). 10. Other factors. males are 4 times more affected than females 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,

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 culture systems shown to identify up to 94% of all microorganisms by 48 hr of incubation

Diagnosis
Cultures

Results may vary because of a number of factors, including maternal antibiotics administered before birth, organisms that are difficult 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

Diagnosis
2. Gram's stain of various fluids helpful for the study of CSF Gram-stained smears and cultures of amniotic fluid or of material obtained by gastric aspiration Adjunctive laboratory tests A. WBC count with differential Neutropenia may be a significant finding with an ominous prognosis when associated with sepsis Serial white blood cell counts several hours apart may be helpful in establishing a trend.

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-reactive protein (CRP), and others that rise in concentration in the serum in response to tissue injury.

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 The standard ESR may be elevated but usually not until well into the illness

II.

Diagnosis
I. CRP increases the most in the presence of inflammation caused by infection or tissue injury highest concentrations in patients with bacterial infections, whereas moderate elevations chronic inflammatory conditions onset of inflammation, CRP synthesis increases within 46 h, doubling every 8
h, and peaks at about 3650 h

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

III.

major mediators of the systemic response to infection Studies have shown that combined use of IL-8 and CRP as part of the workup for bacterial infection reduces unnecessary antibiotic treatment Surface neutrophil CD11 has been shown to be an excellent marker of early infection that correlates well with CRP but peaks earlier.

Diagnosis
IV. Miscellaneous tests. Abnormal values for bilirubin, glucose, and sodium may, in the proper clinical situation, provide supportive evidence for sepsis.

Diagnosis
Radiologic Studies 1. Chest X-ray film in case with respiratory symptoms 2. Urinary Tract Imaging. Imaging with renal ultrasound 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

Diagnosis
3. Other studies. Examination of the placenta and fetal membranes may disclose evidence of chorioamnionitis and thus an increased potential for neonatal infection

Differential Diagnosis
1. 2. 3. 4. 5. 6. Respiratory distress syndrome (RDS) Metabolic diseases Hematologic disease CNS disease Cardiac disease other infectious processes (ie. TORCH infections)

Management
1. GBS prophylaxis major pathogen in the late 1960s and currently remains the most common cause of earlyonset sepsis 10 to 30% of pregnant women are colonized with GBS in the vaginal or rectal area incidence of infection has been estimated at 0.85.5/1000 live births (unchanged for the past three decades). Case fatality rate ranges from 515%

Management
Consensus guidelines regarding management of GBS were published by CDC in 1996 and were supported by American Association of Pediatrics and American College of Obstetricians and Gynecologists. 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)

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 for fever and presumed choriomanionitis, as well as for those born to mothers who receive intrapartum antibiotic prophylaxis (IAP) because of GBS colonization, they are clinically using an algorithm in their hospital based on AAP guidelines, with some alterations based on clinical experiences.

Maternal IAP Mother asymptomatic

Signs & Symptoms of sepsis in infant
yes

Maternal IAP Mother w/ ssx of chorioamnionitis

Maternal temp <102 F S/sx of sepsis in infant no yes
Maternal temp >102F

no

Full dx eval. Emperic Tx <37 wks Limited eval Observe 48H If sepsis suspected, full eval & empiric Rx

Gestational age

>37 wks

No evaluation No therapy Observe min, 48 H

Limited eval. Observe 48H If sepsis suspected, full eval & empiric Rx

Full eval. w/ empiric Rx

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 or disposing of needles or other sharp instruments

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 NICU must be considered: however, generally, staphylococcal coverage with Vancomycin plus either an Aminoglycoside or a 3rd Gen. ephalosporin

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.

Management
When GBS is documented as the causative agent Penicillin is the DOC Aminoglycoside is often given as well because of documented synergism

Complications and Supportive Therapy

1. RESPIRATORY Ensure adequate oxygenation with blood gas monitoring and initiate O2 therapy or ventilator 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.

Complications and Supportive Therapy

3. Hematologic a. DIC one may observe generalized bleeding at puncture sites, the gastrointestinal tract, or CNS sites. In the skin, large vessel thrombosis gangrene.

Lab. parameters consistent with DIC include : thrombocytopenia, inc. PT, and inc. Partial Thromboplastin Time

Complications and Supportive Therapy

Measures include treating the underlying disease; fresh-frozen plasma, 10 mL/kg; vitamin K; platelet infusion; and possible exchange transfusion.

Complications and Supportive Therapy

b) Neutropenia Multiple factors contribute to the increased susceptibility of neonates to infection, including developmental quantitative and qualitative neutrophil defects. Studies suggest use of recombinant human granulocyte colony-stimulating factor (rhGCSF) or recombinant human granulocytemacrophage colony-stimulating factor (rhGMCSF) can partially counterbalance these defects and reduce morbidity and mortality.

Complications and Supportive Therapy

4. CNS Implement seizure control measures Phenobarbital, 20 mg/kg loading dose monitor for the syndrome of inappropriate antidiuretic hormone (SIADH) : i. decreased urine output, ii. hyponatremia, iii. decreased serum osmolarity, and iv. increased urine specific gravity and osmolarity

Complications and Supportive Therapy

4. METABOLIC Monitor for and treat hypo- or hyperglycemia. Metabolic acidosis may accompany sepsis and is treated with bicarbonate and fluid replacement.

Future Developments
Immunotherapy progress continues in the development of various hyperimmune globulins, monoclonal antibodies to the specific pathogens causing neonatal sepsis They may prove to be significant adjuvants to the routine use of antibiotics for the treatment of sepsis Research is also ongoing into blocking some of the body's own inflammatory mediators that result in significant tissue injury, including endotoxin inhibitors, cytokine inhibitors, nitric oxide synthetase inhibitors, and neutrophil adhesion inhibitors.

.Thank you