Neonatal Sepsis

DR. Agelebe E

Bowen University Teach Hosp Ogbomoso

INTRODUCTION:

The Newborn is relatively immunoalegic owing towell documented immunoincompetences of that agegroup. Consequently, susceptibility to infections ishigh and the spread of infections is rapid such thateven a localized or regionalized infection rapidlybecomes systemic and fulminant.

INTRODUCTION

• Infections are a frequent and important cause of M&M in the neonatal period

• >25% NNM due to infections, 40% in preterms

• 1/3rd of septic neonates develop meningitis

DEFINITION

• Neonatal septicaemia (NNS) is a systemic disease characterized by the presence and persistence of bacteria in the blood steam of a newborn in the first 28 days of life.

CLASSIFICATION– Early onset NNS(<72hrs of age).

• Due to infection acquired before and during delivery/resuscitation.

– Late onset NNS (>72hrs of age) • Due to infection acquired after delivery• (nosocomial /community sources)

IMMUNOINCOMPETENCES OF THE NEWBORN:

Both Cellular and Humoral factors exhibitinadequacies in quantity and functionality in allgroups of Newborns with this exaggerated withincreased prematurity. Some of these are listed as:

(1) Neonatal serum shown to be inefficient in killing E.coli because of a deficiency of non-IgG serumcomponents, e.g. complement factor 9.

IMMUNOINCOMPETENCES OF THE NEWBORN

(2) Physiologic deficiencies of the classic andalternative pathways of complement activation inneonates contributing to inefficient bacterialopsonization.

(3) Organisms, e.g. GBS and E. coli with high capsularsialic acid content tend to be poor activators of thealternative complement pathway.

IMMUNOINCOMPETENCES OF THE NEWBORN

(4) Fibronectin (a nonimmune opsonin and amultifunctional glycoprotein found in the plasmaand on the surface of certain epithelial cells,basement membranes, and connective tissues)acts in plasma as a nonspecific opsonin thatenhances chemoatractance for phagocytic cells andinduces the expression of complement receptors.

FIBRONECTIN IS DEFICIENT IN NEONATAL PLASMA,MUCH LOWER IN SEPTIC INFANTS and is alsogestation related, being lower in preterms.

IMMUNOINCOMPETENCES OF THE NEWBORN

(5)Quantitative and Qualitative deficiencies in neonatal neutrophils contribute to the immaturity of the immune system of newborns. The abnormalities become most pronounced at times of stress and during infections in the areas of:

- impaired chemotaxis

- decreased deformability

- reduced C3bi receptor expression

- depressed bacterial killing by phagocytes

- Oxidative metabilic abnormalities

Neutrophil storage pool is markedly depleted and stem cell proliferation rates are near maximal capacity and cannot increase appreciably in response to infection.

The under listed are predisposition of the Newborn to Sepsis:(i) Mode of delivery

(ii) Instrumentation and Manipulations

(iii) Congenital Malformations - Ectopia Vesicae

- Nural Tube defects

- Cutis Aplasia

- Obstructive problems

(GIT, GUT, CVS, etc.)

(iv) Nursery and/or Environmental circumstances/Practices (Soap & Water, spacing, etc.)

(v) Prom, Maternal factor/Infection

MAJOR RISK FACTORS:

- ROM > 24 hr

- Intrapartum maternal fever (>38.0ºC [>100.4ºF],

- Chorioamnionitis

- Sustained fetal heart rate > 160 beats/min

MINOR RISK FACTORS:

Intrapartum matrnal fever (>37.5ºC [>90.5ºF]

- Twin Gestation

- Prematurity (>37/40)

- Maternal WBC > 15,000

- ROM > 12 hr

- Tachypnoea (< 1 hour) (↑RDS is symptomatic)

- Maternal GBS colonization

- Low APGAR (<5 at 1 min)

- Low birth weight (< 1500gm)

- Offensive Lochia

with proportionate risks.

Also, Family history of sibling with systemic bacterial disease under 3 months of age.

Premature or prolonged time between rupture of membranes and delivery.

Chorioamnionitis

Urinary tract infection

Labor characteristics

Preterm labour

Fetal tachycardia without maternal fever, blood loss, hypotension, or tachycardia-inducing medication

Infant characteristicsApgar < 6 at 5 minutesMeconium-stained amniotic fluidOxygen requirementNeutropeniaMale sexCongenital anomalies that cause breakdown of anatomic barriers to infection

Polymorphonuclear leucocytes and intracellular organisms in gastric aspirate.The above portend increased risk of systemic Bacterial Infections in the Newborn infant during the first seven days of life.

CAUSATIVE ORGANISMS

EARLY ONSET LATE ONSET

Staphylococcus aureus Staphylococcus aureus

Escherichia coli Escherichia coli

Listeria monocytogenes Coag neg staphylococcus

Klebsiella pneumoniae

Gp B streptococci Pseudomonas aerigenosa

Haemophilius influenza

Candida

Gp B streptococci

Anaerobes

CLINICAL SIGNS

• Non-specific S&S

• High index of suspicion needed

• Respiratory distress is the most common symptom, occurring in abt 90% of cases

CLINICAL PRESENTATION

GENERAL SYMPTOMS METABOLIC SYMPTOMS DERMATOLOGICALSYMPTOMS

Thermal instability Hypo/ Hyperglycaemia Ecchymotic patches

Pallor Jaundice Sclerema

Poor weight gain Metabolic acidosis

Poor activity

CLINICAL PRESENTATIONRESPIRATORY SYMPTOMS

GASTROINTESTINAL SYMPTOMS

CNSSYMPTOMS

HAEMATOLOGIST SYMPTOMS

CVSSYMPTOMS

Respiratory distress

Abdominal distension

Irritability /Lethargy

Petechiae Hypotension

Cyanosis Feed intolerance

Seizures Shock

Apnea Vomiting/ diarrhoea

Hyper/hypotonia

Purpura Tachycardia

Bloody stools Tense, fullanterior frontanelle

Prolonged bleeding from puncture sites

Bradycardia

Table 2

ESTABLISH A DIAGNOSIS….

• HISTORY

• PHYSICAL EXAM

• INVESTIGATIONS

• TREATMENT

INVESTIGATIONSRESULTS CONSISTENT WITH INFECTION :

• FBC+ DIFF, platelets

Anaemia

Total WBC < 5000/mm3

Absolute neutrophil count <2000

Bands : Total neutrophil ratio > 0.2

Day1-3: N>L, Day 4,5:N=L, Day6-8yrs:L>N

Platelets<100,000/mm3

Toxic granulations of neutrophils

INVESTIGATIONS• MICRO ESR: >3 + age of child in days ( 1st week of life)

• BLOOD CULTURE: b4 commencement of antibiotics

• LUMBAR PUNCTURE:any organism on gram stain,hypoglycorrachiawbc:>25/mm3(term)>30 cells/mm3(prem) mostly neutrophils(>70-90%),protein >120mg/dl(term)>150mg/dl(preterm)

• URINE M/C/S( suprapubic specimen) leucocyturia

• CXR: pneumonic changes

• C-Reactive Protein, Haptoglobulilin.

THERAPEUTIC INTERVENTIONS:

(i) DIRECT ANTIMICROBIALS:

Factors determining selection of antibiotic therapyin the Newborn:

- General experience with pathogens

causing infections in the nursery

- Antimicrobial susceptibility of

commonly encountered pathogens

- Physician’s familiarity with antibioticpharmacokinetics innewborn infants

- Physician’s knowledge of maternal infections, courseof labour, and antibiotic treatment administered tothe mother.

Factors modulating schedule modification:- Gastrointestinal and chronologic age of the infant- Specific suspected or documented microbe- Tissue site of infection being treated- Status of excretory (hepatic and/or renal function of

infant- Cardiopulmonary stability of the infant.

Table 3

(ii) SUPPORTIVE MEASURES:

(a) Definitive and purposive fluid therapy

(b) Monitors/Management of Septic Shock including ICU management and ventilatory support

(c) Blood support/replacement:-

- Polymorphonuclear leucocytetransfusion

- Exchange blood transfusion

- Immune globulin replacement therapy

(d) Treatment with recombinant cytokines.

SEVERE SEPSIS/SEPTIC SHOCK:

International guidelines of the “Surviving SepsisCampaign” recommends based on definitions ofSevere Sepsis (acute organ dysfunction secondary toinfection) and Septic Shock (Severe Sepsis plushypotension not reversed with fluid resuscitation)measures aimed at improving outcome:

Sepsis-induced hypotension is systolic blood pressure< 90mmHg or mean arterial. Pressure < 70 mmHg orSBP decrease > 40 mmHg or < 25 D below normal.

These include:

MANAGEMENT OF SEVERE SEPSIS (SUMMARY)

(A) Initial Resuscitation

(B) Diagnosis

(C) Antibiotic Therapy

(D) Source Control

(E) Fluid Therapy

(F) Vassopressors

(G) Inotropic therapy

(H) Corticosteroids

(I) Recombinant Human Activated Protein (rLAPC)

(J) Blood Product Administration

(i) Early goal directed and intensiveresuscitation within first six hours afterrecognition

(ii) Appropriate, Intensive and controlled broad-spectrum antibiotic therapy within one hour of diagnosis of Septic Shock.

(iii) Antibiotic review as appropriate/duration of therapy tailoring.

(iv) Vasopressor therapy (noradrenalin or Dopamine with target:

(v) Blood cultures before antibiotic administration with imaging studies to localize infection/source.- Central venous pressure 8 – 12 mmHg- Mean arterial pressure (MAP) ≥ 65 mmHg- Urine output ≥ 0.5ml/kg/1 hr

Debutamine at maximum 20 μg/kg/min and if fluidtherapy does not achieve target responses, packedred blood cells to achieve hemotocrit of ≥ 30% mayoften help.

Risk factors• HIGH PREDICTIVE RISK FACTORS

• Maternal peripartum pyrexia>37.5C

• Fetal tachycardia>160/min

• Foul smelling purulent amniotic fluid

• Uterine tenderness

OTHER FACTORS

•Prolonged rupture of

membranes>24hrs

•Antepartum haemorrhage

•Perinatal asphyxia

•Prolonged ±obstructed labour

•Open congenital anomalies

•TERM/

•PRETERMTERM PRETERM

FBC, Blood culture, urine

m/c/s,LP ,mESR and

commence antibiotics

Treat for 7-10 days/ 5 days after

defervescence

Limited sepsis workup (FBC,

mESR, blood culture) and

observe closely

If sugg FBC± + clinical signs,

commence AB, treat for 7-10 days/

5 days after defervescence

FBC, mESR, blood

culture ,urine m/c/s,

LP and commence

antibiotics

Treat for 7-10 days/ 5 days

after defervescence

- cinical

signs

+ clinical

signs

No hx+ clinical signs