Dr. Osama Arafa Abd EL Hameed

Consultantof

Pediatrics & Neonatology

Head of Pediatrics Department Port-Fouad Hospital

C R PPort Fouad Pediatric Department

By

Early vs Late onset sepsis Early onset Late onset

Age <72 hours >72 hours Risk factor Prematurity Prematurity Amnionitis, Maternal infection Source Maternal genital Environmental tract (nosocomial) Presentation Fulminant slowly progressive Multisystem focal Pneumonia frequent Meningitis frequent Mortality 5-50% 10-15% 01/05/2023 3

Natural course of sepsis Bacteria Focal infection Bacteraemia sepsis

Sepsis syndrome

Early septic shock

Refractory septic shock

MODS

DEATH01/05/2023 4

Incidence

In India - 3.9 % of all immature l births - 20 – 30 % develop meningitis

In developed countries - 1 in 1000 live births - Term - 4 in 1000 live births - Preterm - 300 in 1000 VLBW babies

01/05/2023 5

Etiology

• Escherichia coli• Staphylococcus aureus• Klebshiella pneumonae

01/05/2023 6

Risk Factors associated with Neonatal Sepsis Maternal Risk Factors 1. Intrapartum Maternal Infection - Purulent / foul smelling liquor - Fever (>380C)

- Leucytosis (WBC >18000 / mm3) 2. Premature rupture of membranes 3. Prolonged rupture of membranes > 12 hours 4. Premature onset of labour (<37 weeks

5. Maternal UTI 01/05/2023 7

Neonatal Risk factors

1. Low Birth Weight Baby

2. Perinatal asphyxia

3. Male gender

01/05/2023 8

Symptoms of Neonatal Sepsis

CNS Lethargy, Refusal to suckle, Limp, Not arousable, poor or high pitch cry, Irritable, Seizures

CVS Pallor, Cyanosis, Cold and clammy skin

Respiratory Tachypnoea, Apnoea, Grunt, Retractions

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Symptoms of Neonatal Sepsis

GIT Vomiting, Diarrhoea, Abdominal distension

Haematological Bleeding, Jaundice

Skin Rashes, Purpura, Pustules

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Laboratory Diagnosis of Neonatal Sepsis

1. Direct methods - Blood culture - CSF culture - Urine culture

2. Indirect methods - Total leucocyte count - Absolute neutrophil count - Total immature neutrophils - Immature to total neutrophols - Neutrophil Morphology - Platelet count - ESR - Acute phase reactants - Smear of gastric aspirate / External ear canal fluid

01/05/2023 11

SEPSIS SCREEN At Birth Major risk factors 1. Rupture of membranes > 24 hours 2. Maternal intrapartum fever > 38.5 c 3. Chorioamninitis

Minor risk factors 1. Rupture of membrane > 12 hours 2. Maternal intrapartum fever > 99.50 F 3. Maternal WBC > 15000 / mm3 4. Low apgar score(< 5 at 1 min, < 7 at 5 min) 5. LBW ( < 1500 g ) 6. Preterm labour ( < 37 weeks) 01/05/2023 12

SEPSIS SCREEN 1. Leucopenia (TLC < 5000 / mm3)

2. Neutropenia (ANC <1800 / mm3) 3. Immature neutrophil to total neutrophil ( I / T) ratio ( > 0.2)

4. ESR ( > 15 mm / 1st hour )

5. CRP - positive

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Approach to Neonatal Sepsis Antenatal Postnatal Mothers with risk factors

Symptomatic Asymptomatic infants infant with risk factors

Term Preterm

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Evaluation of symptomatic infant for sepsis - Sepsis screen - Chest X-ray - Lumbar puncture - Blood culture Begin Antibiotics

Culture positive No risk factors for sepsis Presence of focal infection Culture negative Sepsis screen positive Sepsis screen negative LP abnormal Symptoms resolve by 24 hrs Symptoms persists 72 hrs

Treat pneumonia 7-10 days Treat for 48-72 hrs Septicaemia 10-14 days and discharge Meningitis 14-21 days

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Supportive Care

- Keep the neonate warm

- Start IV Fluid, Infuse 10% Dextrose 2ml / Kg

stat to maintain normoglycaemia

- Maintain fluid and electrolyte balance and tissue perfusion

If CRT > 3 sec infuse 10 ml / Kg normal saline

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Supportive Care

- Avoid enteral feed, if sick

- Start oxygen by hood, if cyanosed and support breathing - Consider exchange blood transfusion, if there is sclerema, DIC, Neutropenia

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Choice of Antibiotics

Pneumonia or Sepsis Penicillin + Aminoglycoside (Ampicillin or Cloxacillin) (Gentamicin or Amikacin)

Meningitis

Ampicillin + Gentamicin or

Cefotaxime + Gentamicin or Amikacin

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Superficial Infections

- Pustules - After puncturing, clean with betadine and apply antimicrobial

- Conjunctivitis- Chloramphenicol eye drops

- Oral thrush - Local application of Nystatin or Clotrimazole

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Prevention of Infection

- Exclusive breastfeeding

- Keep cord dry

- Hand washing by care givers

- Hygiene of Baby

- No unnecessary intervention

- Better management of IV Lines

- Disinfection of Equipments 01/05/2023 20

Hand Washing

- Single most important means of preventing nosocomial infections

- Very Simple

- Cheap

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Hand Washing

- Two minutes, hand washing to be done before entering baby care area

- 10 seconds hand washing to be done before and after touching every baby, and after touching unsterile surfaces and fomites

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Frequent Blood Drawing??

Medication preparation ( Prepare IV fluid under aseptic conditions )

- Never use stock solution for flushing

- Do not use a single bottle for > 24 hrs - Label bottle with date / time

- After seal is removed, use betadine soaked sterile cotton to cover the stopper of bottle

- Use disposable needle each time01/05/2023 24

Better management of IV Lines

- Thorough hand washing

- Wear gloves

- Use disposable IV cannula

- Thorough skin preparation

- All IV ports should be wiped with alcohol

- Early identification of extravasation

- Avoid unnecessary IV infusion 01/05/2023 25

Conclusion

- High index of clinical suspicion

- Look for Lab evidence of sepsis

- Start parenteral antibiotics (intravenous) - Provide supportive care

- Review culture reports

- Practise barrier nursing to prevent Cross–infection 01/05/2023 26

CRP• C-reactive protein (CRP) belongs to the

pentraxin family of proteins, which has five identical subunits. It was named because it reacts with the somatic C polysaccharide of Streptococcus pneumonae, and was first discovered in 1930 by Tillet and Francis.

• Plasma levels begin increasing within 4-6 hours following acute inflammatory stimulus and the half-life of CRP is 5-7 hours, therefore the level of CRP in the blood is regulated solely by its own synthesis.

Acute Phase ResponseFollowing injury, trauma or infection of a tissue, a

complex series of reactions occur in an effort to prevent ongoing tissue damage, and activate the repair processes. This cumulative homeostatic process is known as inflammation, and the early of reactions are known as the acute phase response (APR).

The cells that most commonly initiate the APR are tissue macrophages and blood monocytes. These cells release cytokines such as IL-1 and TNF that control the migration of leukocytes into tissue and orchestrate the inflammatory response. Fever and leuckocytosis are among the most obvious consequences. The biosynthetic activity of the liver is profoundly affected.

Acute Phase Response cont…The pro-inflammatory cytokines IL-1 and TNF act

on hepatocytes to greatly increase production of acute phase proteins such as CRP and serum amyloid A protein .

These proteins are particularly useful for reflecting inflammation because of the increase of up to 1000 fold from resting levels.

There are more moderate increases in the level of other proteins such as ferritin which may affect assessment of iron status in the presence of inflammation.

There is a corresponding decrease in the synthesis of some other proteins, most notably albumin which may reach low levels in the presence of sustained inflammation.

Result interpretation

CRP (mg/L) < 5

ESR (mm/hour)

Female Male

Child 1 -10 1 – 10 1 - 10

Adult < 50 years

1 – 20 1 – 15

Adult > 50 years

1 - 30 1- 10

CRP and ESR Reference ranges

CRP and ESR patterns of responseBoth CRP and ESR have characteristic

patterns of response .

CRP begins to rise within 4-6 hours of stimulus, peaks within 36-50 hours, and returns to normal 3-7 days following resolution.

ESR shows a much slower response, taking up to a week to peak, and up to several weeks to return to normal.

CRP is a better measure of acute phase response

• CRP is more sensitive than ESR to subtle changes in the acute phase response

• There are distinct ranges of normal and abnormal in CRP reference ranges, without variations for age and gender.

• CRP is not affected by conditions such as pregnancy, intercurrent drug use, anaemia and plasma protein variations.

Figure 1: CRP and ESR patterns of response

Figure 2: The acute phase proteins

CRP is reported to have several main functions

• Anti-infective: CRP can opsonise particles for phagocytosis, and activate complement via the classical pathway.

• Anti-inflammatory actions: CRP helps in preventing systemic inflammation. CRP aids in the release of neutrophils from blood vessels, while preventing white cell adhesion to vessels in non-inflamed tissues. It is also able to stimulate the release of anti-inflammatory molecules from monocytes.

• Scavenging actions: Although CRP does not bind to normal cell membranes, it can bind avidly to cells that are undergoing apoptosis or necrosis, possibly because it recognises particular receptors that appear on the surface of dying cells. This in turn binds and activates complement, initiating an inflammatory reaction that attracts neutrophils and monocytes to the site.

Non infection associated elevation of CRP

• In neonates, non infection associated elevation of CRP was described in conditions of maternal and perinatal distress, neonatal hypoxia, and tissue damage. Several authors have described links of CRP to maternal fever, stressful delivery, prolonged rupture of membranes and/or prolonged labor, asphyxia, meconium aspiration syndrome, intraventricular hemorrhage, pneumothorax, and tissue injury.

• Perinatal asphyxia/ shock • Maternal fever during labor • Prolonged rupture of membranes • Stressful delivery or fetal distress • Prolonged labor • Clinically silent meconium aspiration• Surfactant application • Intra-ventricular hemorrhage • Pneumo-thorax.• Tissue injury

CRP is particularly useful for ruling out an infection and for monitoring the response to treatment and guiding the duration of the antibiotic therapy. Two consecutive values <10 mg/l determined more than 24 hours apart identify infants unlikely to be infected or in whom infection has resolved.

CRP values undergo a physiological 3-day-rise after birth and non-infectious confounders such as meconium aspiration syndrome and perinatal maternal risk conditions may elevate CRP values in otherwise healthy newborns.

C R P facts.

Preterm neonates have lower baseline CRP values and a lower CRP response to infection in compared to term newborns.

Data on non infectious CRP elevations in otherwise healthy newborns are inconsistent and does currently not allow drawing recommendations on the continuation or withdrawal of antibiotics in these infants.

Up to date the most used cut-off value is 10 mg/l irrespective of the gestational and postnatal age of the neonate. Cut-off values adapted to the gestational and postnatal age may better reflect neonatal physiology.

Sensitivity is low during the early phase of infection. The performance of serial determinations 24 to 48 hours after the onset of symptoms is recommended, as it clearly improves diagnostic accuracy.

In order to compensate for the diagnostic weakness during the early phases of infection initial CRP determination should be combined with determination of early and sensitive markers. Suitable markers include but are not limited to PCT, IL6, and IL8. Many further parameters may provide similar good results but are not yet sufficiently examined to be applied to clinical practice