BACTERIAL INFECTION IN NEWBORNS Neonatal sepsis Prof. H.A. Pavlyshyn

Neonatal sepsis, sepsis neonatorum, neonatal septicemia are terms that have been used to describe the systemic response to infection in the newborn infant

Sepsis is a syndrome caused by metabolic and hemodynamic consequences of infection

Criteria for neonatal sepsis should include documentation of infection in a newborn infant with a serious systemic illness in which noninfectious explanations for the abnormal pathophysiologic state are excluded or unlikely

Neonatal Sepsis is a clinical syndrome of systemic illness accompanied by bacteremia occurring in the first month of live.

Neonatal sepsis is common in premature infants Neonatal sepsis is common in premature infants. Sepsis in term infants is rare, occurring in less than 1%. The incidence of neonatal sepsis varies according to definition from 1-4/1000 live births in developed countries.

Neonatal sepsis may be divided into: Early onset Late onset Nosocomial 0 to 4 days of age > 5 days of age

Early-onset disease Presents in the first 5 days of life and is usually a multisystem fulminant illness with prominent respiratory symptoms. Early-onset disease is characterized by a sudden onset and fulminant course that can progress rapidly to septic shock with a high mortality rate.

Late-onset disease may occur as early as 5 days of age; however, it is more common after the first week of life. Although these infants may have a history of obstetric complications. These infants usually have an identifiable focus, most often meningitis in addition to sepsis.

Nosocomial sepsis This form of sepsis occurs in high-risk newborn infants. Its pathogenesis is related to the underlying illness and debilitation of the infant, the flora in the neonatal intensive care (NICU) environment, and invasive monitoring and other techniques used in neonatal intensive care.

Breaks in the natural barrier function of the skin and intestine allow this opportunistic organism to overwhelm the neonate.

Nosocomial sepsis Infants, especially premature infants, have an increased susceptibility to infection because of underlying illnesses and immature immune defenses that are less efficient at localizing and clearing bacterial invasion.

Predisposing factors of sepsis Maternal infection during gestation or parturition (type and duration of antimicrobal therapy). Maternal peripartum fever (38 °C/100.4 °F) or infection. Chorioamnionitis, urinary tract infection (UTI), vaginal colonization with GBS, E. coli, N. gonorrhoeae, herpes simplex and other obstetric complications. Amniotic fluid problems. Meconium-stained or foul-smelling, cloudy amniotic fluid. Prematurity and low birth weight. Prematurity is the single most significant factor correlated with sepsis. Rupture of membranes. Premature or prolonged (>18 h) rupture of membranes. Premature labor. Resuscitation at birth. Infants who had fetal distress, were born by traumatic delivery, or were severely depressed at birth and required intubation and resuscitation.

Predisposing factors of sepsis Invasive procedures. Invasive monitoring and respiratory or metabolic support. Infants with galactosemia (predisposition to E. coli sepsis), congenital immune defects, congenital anomalies. Fetal tachycardia (distress) Medical intervation (vascular access, endotracheal untubation, parental nutrition, surgery, intrauterine monitoring – pressure catheter or scalp electrode) Omphalitis Male sex - males are 4 times more affected than females

Prematurity is risk factor for both early-onset and late-onset sepsis

Early Onset Neonatal Sepsis - Incidence Percent Incidence: 1 - 10 per 1000 Live Births Term NB: 0.2 % ( 0.2/100 LB) VLBW Infants : 2 % (2/100 LB) [x10] ELBW : 20 % (20/100 LB) [x100]

Viruses: Herpes simplex, enterovirus, adenovirus Fungi: Candida Infection ( Sepsis) Bacteria: Group B streptococci, Escherichia coli, Listeria, Negative staphylococcus, Treponema pallidum Viruses: Herpes simplex, enterovirus, adenovirus Fungi: Candida Protozoa: Malaria, Borrelia

Etiologic agents for early-onset sepsis (0 to 4 days of age) Group B streptococci (GBS) Escherichia coli 60% to 70% of infections Listeria Klebsiella Enterococcus Staphylococcus aureus Streptococcus pneumoniae group A streptococci

Etiologic agents for late-onset sepsis ( > 5 days of age) Staphylococcus Aureus GBS E. Coli Klebsiella Pseudomonas Serratia Staph.epidermidis Haemophilus influenzae Herpes simplex virus Enteroviruses In very low-birthweight infants: - Candida - coagulase-negative staphylococci

The presentation may include irritability, vomiting, poor feeding, poor temperature control, lethargy, apneic spells and hypoglycemia. May progress to respiratory distress, poor perfusion, abdominal distension, jaundice, bleeding, petechiae or seizures. Bulging fontanel is a very late sign of neonatal meningitis, and Brudzinski’s sign or Kernig’s sign is rarely found. Внутрішньоутробні інфекції Signs and symptoms Павлишин Г.А.

Clinical presentation Clinical signs and symptoms most often mentioned include the following: Temperature irregularity hypo- or hyperthermia Change in behavior - lethargy, irritability, or change in tone. Feeding problems. Feeding intolerance, vomiting, diarrhea (watery loose stool), or abdominal distention with or without visible bowel loops. Clinical signs and symptoms of sepsis are nonspecific Clinical presentation

Clinical signs and symptoms most often mentioned include the following: Skin. Poor peripheral perfusion, Cyanosis, mottling, pallor, petechiae, rashes, sclerema, jaundice.

and symptoms of sepsis are nonspecific Clinical presentation Clinical signs and symptoms of sepsis are nonspecific Clinical signs and symptoms most often mentioned include the following: 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, hypotension which tends to be a late sign. Metabolic - hypo- or hyperglycemia or metabolic acidosis. Clinical presentation

When there is multisystem involvement or when the cardiorespiratory signs are consistent with severe illness, sepsis should be considered !!! The initial presentation may be limited to only one system, such as apnea, tachypnea with retractions, or tachycardia, but a full clinical and laboratory evaluation will usually reveal other abnormalities.

Late manifestations of sepsis include cerebral edema and/or thromboses respiratory failure as a result of acquired RDS pulmonary hypertension septic shock adrenal hemorrhage with adrenal insufficiency cardiac failure renal failure liver disease with hyperbilirubinemia and elevated enzymes prolonged prothrombin time (PT) and partial thromboplastin time (PTT) bone marrow failure (thrombocytopenia, neutropenia, anemia) disseminated intravascular coagulation (DIC).

The laboratory evaluation for neonatal sepsis should include: 1. CBC - complete blood count (neutropenia or an elevated ratio of immature to total neutrophils, thrombocytopenia suggest sepsis) and repeat in 5 hours, C-reactive protein, ESR 2. Lumbar puncture (for cell count, protein, glucose, culture. Consider sending CSF for viral studies). Cultures of blood, urine and any other site as indicated. Latex agglutination test for pneumococcus, E. coli, H. influenzae, group B streptococci, and meningococcus in blood, urine, and CSF is done even though the usefulness is questionable. Negative latex agglutination tests do not rule out infection, but positive results may help guide therapy. Chest radiograph Gastric aspirate (at the time of delivery) for neutrophil count, Gram stain, and culture. Gram stain and culture of a tracheal aspirate, if the infant is intubated.

Treatment of neonatal sepsis may be divided into antimicrobal therapy (for the suspected or known pathogen) supportive care The initial diagnosis of sepsis is, by necessity, a clinical one because it is imperative to begin treatment before the results of culture appear

Treatment of sepsis newborns 1. Should be tailored to age of onset, clinical setting, and initial findings. 2. There should be NO DELAY in antibiotic therapy. Begin empiric therapy after cultures are obtained or before cultures if any delay is anticipated. 3. There are isolates of Streptococcus pneumoniae that are resistant to penicillin and cephalosporins. 4. As of 1997, the American Academy of Pediatrics recommends adding vancomycin with or without rifampincin to these regimens when meningitis or pneumococcal sepsis is suspected until sensitivities are known. Never use rifampincin alone since resistance can rapidly develop.

Empiric therapy Empiric early (0 to 4 days old). Ampicillin 50 mg/kg/day (100 mg/kg/day in meningitis) twice a day IV and gentamicin 5 mg/kg/day twice a day IV. Or cefotaxime 50mg/kg/d twice a day + ampicillin as above (preferred by some authors). Ceftriaxone is an alternative to cefotaxime. Empiric late (5 days old). Depends on cause (for example, methicillin-resistant Staph. aureus outbreak requires vancomycin). General guidelines include ampicillin -100 to 200 mg/kg/day (every 6 h – 4 times a day) plus cefotaxime 150 mg/kg/day IV (every 8 h – 3 times a day) or ampicillin-gentamicin as above usually adequate. Ceftriaxone 100 mg/kg/day IV (every 12h – 2 times a day) is an alternative to cefotaxime.

Supportive therapy Respiratory Cardiovascular Hematologic Metabolic Oxygen and ventilation as necessary Cardiovascular Support blood pressure with volume expanders and/or pressors Hematologic Treat DIC CNS Treat seizures with phenobarbital Metabolic Treat hypoglycemia/hyperglycemia and metabolic acidosis

Necrotizing enterocolitis and meningitis are usually accompanied by the systemic manifestations of sepsis

NEC – stage I

NEC - stage II

NEC - stage III

Forced posture of newborn with meningitis The clinical presentation is usually nonspecific. Meningitis must be excluded in any infant being evaluated for sepsis or infection. Signs and symptoms of meningitis generally are similar to those reported for sepsis. Forced posture of newborn with meningitis

Diagnosis CSF examination is critical in the investigation of possible meningitis. Approximately 50 % of all infants with positive CSF cultures for bacteria have negative blood cultures.

Diagnosis Gram-stained smear can be helpful in making a more rapid definitive diagnosis and identifying the initial classification of the causative agent. Cerebrospinal glucose levels must be compared with serum glucose levels. Normal CSF values are one half to two thirds of serum values. CSF protein is usually elevated, although normal values for infants, especially preemies, may be much higher than in later life, and the test may be confounded by the presence of blood in the specimen. CSF pleocytosis is variable. Normal values range from 8-32 white blood cells in various studies, some of which may be polymorphonuclear cells. Pleocytosis may also be an irritant reaction to CNS hemorrhage.

Lumbar puncture

Diagnosis 5. Rapid antigen tests are available for several organisms and should be done on spinal fluid. 6. Ventricular tap, with culture and examination fluid, is indicated in patients not responding to treatment. Radiologic studies Cranial ultrasound examination has been useful in the diagnosis of ventriculitis. Computed tomography (CT) scan of the head may be indicated to rule out abscess, subdural effusion, or an area of thrombosis, hemorrhage, or infarction.

Dilation lateral ventricles up to 25 mm

Plain CT of a 2 week old baby with Listeria meningitis Plain CT scan of baby with Listeria meningitis at age 2 weeks Ventricles fairly normal in size Periventricular enhancement suggests ventriculitis. (normal to have enhancement in choroid plexus and basal sinuses) Diffuse parenchymal hypodensity (seen by decreased density of white matter) hypodensity extends to the edges of the brain instead of just visible sulci Sulci and gyri are a little small suggesting edema and fluid Periventricular enhancement suggests ventriculitis Diffuse parenchymal hypodensity. Edema.

Treatment Empiric therapy. Optimal antibiotic selection depends on culture and sensitivity testing of causative organisms. Ampicillin and gentamicin are usually started as empiric therapy for suspected sepsis or meningitis. Gram-positive meningitis (GBS and Listeria). Penicillin or ampicillin is the drug of choice. These infections usually respond well to treatment. Administration for 14-21 days is indicated. Gram-negative meningitis. Most clinicians would use ampicillin plus cefotaxime as initial therapy. In general, approximately 3 days are required to sterilize the CSF in infants with gram-negative meningitis, whereas in gram-positive meningitis sterilization usually occurs within 36-48 h.

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