1. 1. Neonatal Infections DR. MAHMOUD MOHAMED OSMAN MBBCh, MSc (Pedia), MRCPCH (UK), FRCP (Edinburgh) Consultant Pediatrician & Neonatologist Al Yammamah Hospital, MOH 1

2. Learning Objectives: 1. Definition of Neonatal sepsis 2. Early-onset infections 3. Late-onset infections 4. Clinical Presentations 5. Investigations for Neonatal sepsis 6. Management of Neonatal sepsis 2

3. 3 I- Neonatal Infections

4. 1. Definition of Neonatal Sepsis: 1. Definition of Neonatal Sepsis: It is a clinical syndrome of systemic illness accompanied by bacteremia or septicemia occurring in the first month of life.

5. 2. Clinical Situations : Early- Onset Disease Late - Onset Disease Very late - Onset Disease  Infection can present in many different ways and may involve almost any system in the body.  Infection must be considered in almost every differential diagnosis of any condition.  Infection poses a significant risk of mortality and is associated with major morbidity.

6. 6 3- Incidence:  The incidence of infection is approximately. 5 /1000 live births.  It is more common in premature infants;. 13-27/1000 for infants weighing <1500 gm.  Mortality rate is high (13-25%); and higher rates are seen in premature infants and in those with early fulminant disease

7. Early-onset (Perinatal) Infection 7

8.  Neonatal infections were originally divided arbitrarily into infections occurring before and after 1 wk of life.  It is more useful to separate early-onset and late-onset infections according to peripartum pathogenesis.  Early-onset infections are acquired before or during delivery (vertical mother-to-child transmission).  Late-onset infections develop after delivery from organisms acquired in the hospital or the community.  Very-late-onset infections develop after 1 month of life in VLBW preterm or term infants requiring prolonged intensive care. 8 1- INTRODUCTION: 1- INTRODUCTION:

9.  The age at onset depends on the timing of exposure and virulence of the organism.  A newborn infant with early-onset infection may be initially asymptomatic or has any of the clinical signs and symptoms of infection. 2. RISK FACTORS:  The presence of a number of maternal and neonatal risk factors significantly increases the risk of infection in the newborn period.

10. A - Maternal risk factors for early-onset infection: Maternal features of sepsis or chorioamnionitis: Fever ≥38°C, High white cell count, Tender uterus, Offensive or purulent liquor Preterm labour <37 weeks’ gestation Membranes ruptured for more than 18–24 hs Prolonged labour beyond 12 hs Frequent vaginal examinations Group B streptococcus (GBS) colonization Bacteriuria in current pregnancy Previous infant with early-onset GBS disease Amniotic fluid problems. Meconium-stained or foul-smelling amniotic fluid.

11. B - Neonatal risk factors for early-onset infection: B - Neonatal risk factors for early-onset infection: 1. Prematurity and low birth weight 2. Resuscitation at birth. Infants who had fetal distress, were born by traumatic delivery or were severely depressed at birth and required intubation and resuscitation. 3. Invasive procedures. Invasive monitoring and respiratory or metabolic support. 4. 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, as a result of improper hand washing

12. 3.Clinical Presentation:  Initial diagnosis of sepsis is, by necessity, a clinical one because it is imperative to begin treatment before the results of cultures are available.  Clinical Presentation of sepsis are nonspecific, and the differential diagnosis is broad.  Common Clinical Presentation of sepsis include: 1. Temperature irregularity. Hypo- or hyperthermia. 2. Change in behavior. Lethargy, irritability, crying or change in tone.

13. 3. Skin. Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, sclerema, or jaundice. 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, tachycardia, or hypotension, which tends to be late sign. 6. Metabolic. Hypo- or hyperglycemia or metabolic acidosis.

14. Summary of Clinical signs of neonatal sepsis

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

16. 5- Investigations: 5- Investigations: 1. A blood culture (>1mL): Should be collected before antibiotics commenced. 2. A complete blood count (CBC): Abnormal findings can include: Increased white cell count or neutropenia, Increased numbers of immature neutrophils ( Bands, blasts, myelocytes, metamyelocytes, [shift to the left] ) Increased immature : mature/ total neutrophil ratios. Toxic granulation, vacuolation, Dohle bodies, intracellular organisms Thrombocytopenia.

17. 17  Mature neutrophilBand cell Toxic granulation

18. 3. An elevated C-reactive protein (CRP): May be a marker of infection. 4. Lumbar puncture: Should be considered and is essential if the blood culture becomes positive or if the baby has signs or symptoms of meningitis. 5. Imaging studies: X-rays, US, CT, or isotopic imaging. 18

19. 6 - COMMENEST AGENTS IN EARLY-ONSET: 1- Group B β-haemolytic streptococcus 1- Group B β-haemolytic streptococcus 2- Escherichia coli 2- Escherichia coli 3- Listeria monocytogenes 3- Listeria monocytogenes 4- Herpes simplex virus (HSV) 4- Herpes simplex virus (HSV) 5- Chlamydia trachomatis 5- Chlamydia trachomatis 6- Other agents 6- Other agents 19

20. 1-Early-onset group B β-haemolytic streptococcus: Group B β-haemolytic streptococcus (GBS) is the most common cause of early-onset sepsis. Although the prognosis has improved, it is still fatal in 10–20% of cases depending on gestational age and age of onset. Vaginal or rectal colonization with GBS is found in 15–30% of pregnant women depending on the local population, and 10–20% of infants born to colonized women will be colonized.

21. Early-onset GBS infection in the neonate occurs in only 1% of colonized women. In areas that are known to have high rates of colonization (e.g. USA), routine screening for GBS in pregnancy is often undertaken. Intrapartum antibiotics prophylaxis for women with risk factors significantly reduces the risk of early-onset infection, but does not eliminate it. 21

22. Early neonatal sepsis with multi-organs failure 22

23. 2- Escherichia coli  E.coli (particularly K1 strain), is associated with perinatal infection.  E.coli may cause septicemia or meningitis.  The incidence of E.coli infection appears to be increasing, due to the increasing use of antibiotics aimed at preventing GBS.  The sensitivity of E.coli to antibiotics is variable. 23

24. 3- Listeria monocytogenes This is a not uncommon perinatal pathogen and may invade the fetus through intact membranes. Characteristically, infected infants pass meconium in utero, and if this is seen in premature infants listeria should be strongly suspected. The organism has a predilection for the lungs and brain. Hydrocephalus is a common sequel to listeria meningitis. The organism is usually sensitive to Ampicillin. 24

25. 4- Herpes simplex virus (HSV) Neonatal herpes simplex infection is a rare but devastating condition. It occurs as a result of HSV type 1 and 2 in equal proportion. In most babies with neonatal HSV, there is no history of genital herpes and their mothers are asymptomatic Caesarean section reduces the risk of infection if there is active maternal shedding of HSV. The virus enters the baby through skin, eye or mouth and may disseminate to the brain or other organs. The risk of an infant being infected from a parent, nurse or midwife with cold sores is small, but not negligible.

26. Neonatal HSV presents in one of three ways: Neonatal HSV presents in one of three ways: Systemic symptoms. In the first few days of life with signs of major over- whelming illness including shock, respiratory failure and often severe hepatitis and coagulation disorders. Neurological symptoms. Approximately one third of babies present with encephalopathic signs of meningoencephalitis, most commonly at 10–14 days. Cutaneous symptoms. Include rash and keratoconjunctivitis. These babies present in the second week of life; and rarely become seriously ill. 26

27. 5- Chlamydia trachomatis Chlamydia is found in the vagina of 4% of pregnant women. Up to 70% of infants born through an infected cervix will acquire chlamydia, but with no symptoms. Chlamydia conjunctivitis and, less commonly, pneumonia occur in a small proportion of infants. The conjunctivitis is purulent and is indistinguishable from that of gonococcal ophthalmia. Specific culture media are necessary for this organism Diagnosis can be made by detecting DNA with PCR. Infants should be treated with tetracycline eye ointment and oral erythromycin.

28. 6- Other Agents: Pneumococcus, Haemophilus influenzae: are probably haematogenously spread from maternal septicaemia. They may cause profound shock in the infant, indistinguishable clinically from Group B β-haemolytic streptococcus (GBS). Anaerobes: are contracted from the birth canal and require special culture media. 28

29. IV. Late-onset (Postnatal) Infection 29

30. 1. The definition of late-onset infection: The most common definition is “signs of infection developing at least 7 days after birth”. 2. The risk factors of nosocomial infection: Direct contamination by the hands of medical staff or parents. Frequently performed procedures. Cross-infection.

31. 3.Clinical features - There are no pathognomonic signs of infection or any totally reliable way to make an early diagnosis in the laboratory. - The doctor must have a high level of suspicion for infection and not be too reliant on blood tests to make the diagnosis. - If in doubt, treat the baby 31

32. 4. Commenest agents in late-onset: Late-onset group B β-haemolytic streptococcus infection Coagulase-negative staphylococci Staphylococcus aureus Others include: Pseudomonas, Proteus, Klebsiella, Serratia, and Candida. 32

33. 5. Common presentation: Meningitis. Lower respiratory tract infection. Urinary tract infection. Conjunctivitis (‘sticky eyes’). Infection of the skin and subcutaneous tissues. Gastroenteritis. Systemic candidiasis.

34. 34 Late-onset GBS Septicemia, and Meningitis with Convulsion

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36. 36 Late Onset Neonatal Sepsis Pneumoccoci

37. 37 Management of Neonatal Infections

38. 1.GBS prophylaxis: - The most common cause of early-onset sepsis - Incidence of infection has been estimated at 1-5 /1000 live births (unchanged for the past three decades). - Case fatality rate ranges from 5—15% The guidelines recommended one of two approaches: 1- The prenatal screening approach: (screening all pregnant women for GBS infection at 35-37 weeks gestation and treatment of women with positive cultures) 2- Identifying women who present with risk factors: and treating them during labor.

39. 2. Initial therapy:  Treatment is most often begun before a definite causative agent is identified.  Penicillin, usually Ampicillin, plus an Aminoglycoside are commonly used.  In nosocomial sepsis: Flora of the NICU must be considered. However, staphylococcal coverage with Vancomycin plus a 3rd Generation cephalosporin are commonly used. 39

40. 3. Continuing therapy:  It is based on culture and sensitivity results, clinical course, and other serial lab studies (CRP).  Monitoring of antibiotic levels and toxicity are important.  When GBS is documented as the causative agent. Penicillin is the DOC Aminoglycoside is often given as well because of documented synergism. 40

41. 4. Supportive Therapy & Complications: 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.

42. 3. Hematologic: a) DIC: Generalized bleeding at puncture sites, gastrointestinal tract, or CNS sites. - In the skin, large vessel thrombosis  gangrene. - Lab. parameters consistent with DIC include : thrombocytopenia, prolonged PT, and PTT. - Measures include: treating the underlying disease; fresh-frozen plasma, 10 mL/kg; vitamin K; platelet infusion; and possible exchange transfusion. b) Neutropenia: Studies suggest the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) can reduce morbidity and mortality.

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

44. IN SUMMARY  Infection is a commonl problem in neonatal medicine. It has significant morbidity and mortality.  Signs and symptoms may be present at or shortly after birth or may occur at any time during admission.  Staff looking after neonates must have a high suspicion index of infection, as prompt treatment is required.  A number of measures have been proven to decrease the risk of nosocomial infection with the most important being careful hand-washing. 44

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