08 Neonatal sepsis presentation ppt.pptx

this is neonatal sepsis presentation and management slides

1. NEONATAL SEPSIS Dr. Yohanes Hailu(pediatrician) Arba Minch university College of medicine and health science Department of pediatrics and child health 3/6/2019 1

2. Neonatal sepsis It’s a systemic bacterial infection documented by a positive blood culture in the first month of life . Incidence and Mortality Neonatal sepsis can be classified into two: Early-onset sepsis occurs in the first 7 days of life; is usually a fulminant, multisystem infection acquired by vertical transmission from the mother; and has a higher case fatality rate than late-onset sepsis . Late-onset sepsis is usually more insidious but may have an acute onset & occur after 7 days. 3/6/2019 2

3. Cont… Very-late-onset sepsis occurs after 3 months of life and affects premature VLBW infants in the NICU. It is often caused by Candida species or by CONS. It’s usually been associated with prolonged instrumentation, such as indwelling intravascular lines and endotracheal intubation. The incidence of neonatal sepsis varies from 1 to 5 cases per 1000 live births. The case fatality rate is 5% to 20% for early-onset sepsis and 5% for late-onset sepsis. 3/6/2019 3

4. Cont… EARLY ONSET (<7 DAYS) LATE ONSET (≥7 DAYS TO 3 MONTHS) VERY LATE ONSET (>3 MONTHS Intrapartum complications Often present Usually absent Varies Transmission Vertical from mother’s genital tract Vertical or through postnatal environment Usually postnatal environment Clinical manifestations Fulminant course, multisystem involvement, pneumonia common Insidious or acute, focal infection, meningitis common Insidious Case-fatality rate 5%–20% 5% Low 3/6/2019 4

5. Microbiology Etiologic Agents in Neonatal Sepsis Bacteria Causing Early-Onset Neonatal Sepsis Group B Streptococcus Escherichia coli Enterococcus species Viridans streptococci Staphylococcus aureus Pseudomonas species 3/6/2019 5

6. Cont… Etiologic Agents in Late-Onset Neonatal Sepsis Escherichia coli Klebsiella Group B Streptococcus Coagulase-negative Staphylococcus Staphylococcus aureus Candida albicans Enterococcus species Pseudomonas 3/6/2019 6

7. Transmission Transplacental T. pallidum and Listeria monocytogenes . Ascending intra-amniotic infection followed by aspiration of infected amniotic fluid: Especially if ROM lasts longer than 18/24hours . ~1 % to 4% of neonates born to mothers with intra-amniotic infection develop systemic infection . Acquired during vaginal delivery from bacteria colonizing the mother’s lower genital tract . The use of instrumentation 3/6/2019 7

8. Cont… Cross contamination from an infected to an uninfected infant or from the hands of colonized caregivers to the newborn. Early-onset infection is most often transmitted vertically by ascending amniotic fluid infection and by delivery through an infected or colonized birth canal. 3/6/2019 8

9. Risk Factors Maternal GBS infection are higher among blacks Maternal malnutrition and recently acquired STD. Maternal GBS colonization. Immunoglobulin against gram negative bacteria is formed in the form of IgM which can’t cross the placental barrier to the neonate as passive immunity. 3/6/2019 9

10. Cont… Peripartal Untreated or incompletely treated focal infections of the mother (UTI, vaginal, or cervical infections), as well as systemic infections( septicemia or maternal fever without a focus). Uncomplicated ROM lasting >24 hours is associated with a 1% incidence of neonatal sepsis . 3/6/2019 10

11. Cont… Coexist of both chorioamnionitis and prolonged ROM increases risk by fourfold. Prematurity and low birth weight. Use of fetal scalp electrodes is associated with a 4.5% risk of sepsis. Cephalhematomas and PNA. NEONATAL RISK FACTORS M>F Impairment of the oxidative respiratory burst of neonatal neutrophils is a factor in the increased risk of sepsis, especially in preterm infants. 3/6/2019 11

12. Cont… Decreased ability of neonatal neutrophils to phagocytose gram-negative (but not gram-positive) bacteria in the presence of infectious or noninfectious stress. Decreases in adhesion, aggregation, and deformability of neonatal neutrophils , which may delay the response to infection. Impaired opsonic activity because of low level of complement. 3/6/2019 12

13. Cont… OTHER RISK FACTORS Bottle feeding Use of prepared formula which has no protective immunity. Prolonged hospital stay. High infant to nurse ratio. Presence of foreign materials(VP shunt, CVC, ET tube etc.) 3/6/2019 13

14. SYMPTOMS AND SIGNS Nonspecific Temperature may be elevated, depressed, or normal. Fever that is sustained longer than an hour is frequently associated with infection. Fever without other signs of infection is infrequent. Respiratory signs, including cyanosis or apnea. 3/6/2019 14

15. Cont… Septic infants can present with seizures and full fontanels even in the absence of meningitis. GI symptoms like hepatomegaly, abdominal distention, vomiting, diarrhea, guaiac-positive stools, and jaundice may be present. The presence of certain focal infections can suggest the causative agent, such as streptococci with cellulites, staphylococci with abscesses, and Pseudomonas aeruginosa with necrotic skin lesions. 3/6/2019 15

16. Diagnosis Cultures Blood, urine, and CSF should be obtained from all infants suspected of having sepsis. Cultures of gastric aspirates obtained on the first day of life reflect amniotic fluid infection and do not predict the development of neonatal infection. 2. Buffy Coat Examination 3. Antigen Detection Assays 3/6/2019 16

17. Cont… 4. Complete blood count Reference Ranges for Neutrophil (per mm 3 ) Indexes ANC, absolute neutrophil count (mature and immature forms); INC, immature neutrophil count (all neutrophils except segmented ones); I:T, ratio of INC divided by ANC. INDEX BIRTH 12 HOURS 24 HOURS 48 HOURS 72 HOURS ≥120 HOURS ANC 1800–5400 7800–14,400 7200–12,600 4200–9000 1800–7000 1800–5400 INC ≤1120 ≤1440 ≤1280 <800 <500 <500 I:T <0.16 <0.16 <0.13 <0.13 <0.13 <0.12 3/6/2019 17

18. Clinical Factors Affecting Neutrophil Counts Total Neutrophils Total Immature Neutrophils I:T Ratio * DURATION (hours) Decreased Increased Increased Increased Maternal hypertension + + + + + + 72 Maternal fever, healthy neonate + + + + + + + + + 24 ≥6 Hours of intrapartum oxytocin + + + + + + + + 120 Stressful labor + + + + + + + + + + + 24 Asphyxia (5-min Apgar score <5) + + + + + + + + 24–60 MAS + + + + + + + + + 72 Pneumothorax with uncomplicated respiratory distress syndrome + + + + + + + + + + + + 24 Periventricular hemorrhage + + + + + + + + + + 120 +, 0%–25%; + +, 25%–50%; + + +, 50%–75%; + + + +, 75%–100% 3/6/2019 18

19. +, 0%–25%; + +, 25%–50%; + + +, 50%–75%; + + + +, 75%–100% Total Neutrophils Total Immature Neutrophils I:T Ratio * DURATION (hours) Decreased Increased Increased Increased Seizures + + + + + + + + + + 24 Prolonged crying (≥4 min) + + + + + + + + + + + + 1 Asymptomatic hypoglycemia (≤30 mg/ dL ) + + + + + + + + 24 Hemolytic disease + + + + + + + + + 7–28 days Surgery + + + + + + + + + + + 24 High altitude + + + + + + + + 6 3/6/2019 19

20. Cont… The upper limit of normal of I:T ratio for neonates of 32 weeks’ gestation or less is slightly higher, at 0.2 therefore I:T ratio of >0.2 always is abnormal for all neonates. 5. Acute-Phase Reactants(APR) APRs are proteins produced by hepatocytes in response to inflammation. Are elevated but doesn't distinguish between infectious and noninfectious causes of inflammation. 3/6/2019 20

21. Cont… C-Reactive Protein Normal concentrations are 1 mg/ dL or lower. The serum half-life is 5 to 7 hours. An increasing value is usually detectable within 6 to 18 hours, and the peak CRP is seen at 8 to 60 hrs after onset of the inflammatory process . b. Fibronectin Fn has been found to be decreased in neonates with infection and also in neonates with asphyxia, respiratory distress syndrome, and bronchopulmonary dysplasia. 3/6/2019 21

22. Cont… c. Erythrocyte Sedimentation Rate It reflects changes in many serum protein APRs. A micro-ESR has been developed for use in infants. The maximal normal rate in the first 2 weeks of life can be obtained by adding 3 to the age of the newborn in days. Beyond 2 weeks of life, the maximal rate varies between 10 and 20 mm per hour. Micro-ESR values vary inversely with the hematocrit 3/6/2019 22

23. Treatment Empirical antimicrobial therapy should be instituted immediately after obtaining samples for culture. The choice of empirical therapy is based on: timing and setting of the disease (e.g., early onset, late onset community acquired, health care associated late or very late onset), microorganisms most frequently encountered, susceptibility profiles for those organisms, site of the suspected infection and penetration of the specific antibiotic to that site, and safety of the antibiotic. Availability of the drug and its affordability. 3/6/2019 23

24. Cont… The combination of ampicillin and an aminoglycosides( gentamicin) is the commonly used drugs. Vancomycin and gentamicin /Ceftazidime are commonly used as initial therapy for the treatment of nososcomial infection, if not available possible to use cloxacillin with gentamicin/Ceftazidime. The dosage and frequency of antimicrobial agents vary with gestational age, postnatal age, birth weight, and status of hepatic and renal function. 3/6/2019 24

25.  Indications, Pharmacology, and Toxicity of Antibiotics Commonly Used in Newborn Infants ANTIBIOTIC INDICATIONS PHARMACOLOGY TOXICITY COMMENTS Ampicillin Initial treatment of sepsis and meningitis; gram-positive organisms except staphylococci; gram-negative organisms if susceptible (Salmonella, Shigella, Hemophilus, Escherichia coli) Renal excretion Seizures when high dosages are given Cefotaxime Sepsis, meningitis caused by susceptible gram-negative organisms Primarily renal excretion; good penetration into CSF   Active against streptococci; routine use can result in emergence of resistant gram-negative organisms 3/6/2019 25

26. Cont… ANTIBIOTIC INDICATIONS PHARMACOLOGY TOXICITY COMMENTS Ceftazidime Can be used in combination with an aminoglycoside for treatment of Pseudomonas infection Renal excretion; penetrates blood-brain barrier Ceftriaxone Sepsis, meningitis, soft tissue and bone/joint infections caused by susceptible organisms; not effective against staphylococci, Listeria sp, enterococci, or Pseudomonas sp 30%–65% excreted by the kidneys, the remainder excreted in bile; penetrates blood-brain barrier Potential gallbladder sludging May displace bilirubin from albumin-binding sites in neonates 3/6/2019 26

27. Cont… ANTIBIOTIC INDICATIONS PHARMACOLOGY TOXICITY COMMENTS Clindamycin Treatment of susceptible anaerobic infections   Pseudomembranous colitis in older children but rare in neonates Gentamicin Can be used for initial treatment of neonatal sepsis; not effective alone but can be synergistic when used with ampicillin against group B streptococci, enterococci, and Listeria sp Renal excretion; activity low in CSF Possible ototoxicity, nephrotoxicity, and neuromuscular blockade Toxicity rare if the appropriate dosage is used and blood concentrations are monitored 3/6/2019 27

28. Cont… ANTIBIOTIC INDICATIONS PHARMACOLOGY TOXICITY COMMENTS Nafcillin, oxacillin, cloxacillin Penicillin-resistant Staphylococcus aureus infections; active against streptococci, but not a first-line agent Excretion is renal and hepatic for nafcillin and oxacillin; nafcillin and oxacillin are highly protein bound Penicillin G Most streptococci, Treponema pallidum, Bacteroides spp (except Bacteroides fragilis ), Neisseria meningitidis Renal excretion; fair penetration of inflamed meninges   Can be used to treat infections caused by susceptible organisms 3/6/2019 28

29. Cont… ANTIBIOTIC INDICATIONS PHARMACOLOGY TOXICITY COMMENTS Vancomycin Effective against coagulase-negative staphylococci, methicillin-resistant S. aureus; most gram-positive aerobic organisms are susceptible Renal excretion Possible ototoxicity; previous preparations associated with nephrotoxicity Flushing or hypotension may result from rapid infusion 3/6/2019 29

30. PREVENTION Intrapartum antibiotic prophylaxis (IAP) for prevention of early-onset GBS disease. Indication: Positive lower vaginal and rectal cultures obtained at 35 to 37 weeks’ gestation. Delivery of a previous infant with invasive disease and GBS bacteriuria. Not indicated for planned cesarean section before ROM and onset of labor. Risk factors (labor onset or ROM before 37 weeks’ gestation, ROM 18 hours or more before delivery, or intrapartum fever) should be used only when the results of cultures are not known at the onset of labor. 3/6/2019 30

31. Cont… The management of infants born to women receiving IAP depends on the infant’s status at birth, the duration of prophylaxis, and the gestational age of the infant. If a woman receives IAP for suspected chorioamnionitis, her infant should have a full diagnostic evaluation and empirical therapy pending culture results. 3/6/2019 31

32. Cont… Evaluations with CBCD and blood culture plus observation for at least 48 hours is indicated for asymptomatic infants of <35 weeks’ gestation and for those whose mothers received chemoprophylaxis for less than 4 hours before delivery. Observation is appropriate for asymptomatic infants of at least 35 weeks’ gestation whose mothers received chemoprophylaxis at least 4 hours before delivery. 3/6/2019 32

33. Meningitis INCIDENCE Meningitis presents in as many as 25% of cases of neonatal sepsis. Higher in the first month of life than at any other age. Premature newborns with LBW have a 10-fold higher risk of meningitis than do term infants. ETIOLOGY Caused by the same pathogens associated with neonatal sepsis. 3/6/2019 33

34. PATHOGENESIS There are three mechanisms by which the meninges can become infected: Primary sepsis with hematogenous seeding; Focal infection outside the CNS, with either secondary bacteremia and resulting hematogenous dissemination or direct extension (e.g., from an infected sinus); and Direct inoculation after head trauma or neurosurgery, or from an open congenital defect such as myelomeningocele or dermal sinus. 3/6/2019 34

35. PATHOLOGY Subarachnoid exudate. Ventriculitis. Diffuse encephalopathy Hydrocephalus. Thrombosis and cerebral. 3/6/2019 35

36. CLINICAL MANIFESTATIONS Clinical feature: lethargy, reluctance to feed, emesis, respiratory distress, irritability, and temperature instability. Signs suggestive of a CNS process are less common, out of 255 neonates with meningitis convulsion, bulged fontanel, and nuchal rigidity was observed in 40%,25% and 15% respectively. 3/6/2019 36

37. DIAGNOSIS CSF analysis Gram-stained smear Culture Polymerase chain reaction (PCR) assay GBS HSV-71-100% sensitive but 98-99% specific. Enteroviruses 3/6/2019 37

38. Normal CSF value Opening pressure Newborn ………80-110 mm H2O Infant ………......<200 mm H2O Glucose Premature ….....24-63 mg/ dL (CSF-blood ratio 55-105%) Term ……………....44-128 mg/ dL (CSF-blood ratio 44-128%) Protein Premature ……….65-150 mg/ dL Term …………………20-170 mg/ dL White blood cell count Premature ………..0-25 mm3 (57% PMNs) Term ………………….0-22/mm3 (61% PMNs) 3/6/2019 38

39. Cont… Blood culture 15-30% of infants with CSF-proven meningitis have negative blood cultures. 3/6/2019 39

40. TREATMENT Empirical therapy should provide coverage for GBS, gram-negative bacillary enteric organisms, and L . monocytogenes . High dose ampicillin, gentamicin, and Cefotaxime pending final culture and susceptibility reports is the preferred combination by most clinicians but in our set up we use high dose ampicillin with gentamicin. The minimum duration in uncomplicated GBS or Listeria meningitis is 14 days. 3/6/2019 40

41. Cont… The duration of therapy for gram negative bacteria should be a minimum of 3 weeks, or 2 weeks after documented sterilization of CSF, whichever is longer. PROGNOSIS Poor prognosticators of GBS meningitis are: comatose or semi comatose state, poor perfusion, total peripheral leukocyte count <5000/mm 3 , absolute neutrophil count <1000/mm 3 , and CSF protein >300 mg/ dL . 3/6/2019 41

42. Cont… Poor prognosticators of gram-negative bacillary meningitis include : CSF profile of: protein level > 500 mg/ dL , leukocyte count >10,000/mm 3 , Persistent positive CSF cultures, and Presence and persistence of elevated IL-1α and TNF. Late complications of meningitis occur in 40-50% of survivors and include hearing loss, abnormal behavior, developmental delay, cerebral palsy, focal motor disability, seizure disorders, and hydrocephalus . 3/6/2019 42

43. Pneumonia ETIOLOGY Causes congenital pneumonia : CMV, rubella virus, and T. pallidum Microorganisms causing pneumonia acquired during labor and delivery GBS is the most common. E . coli, gram-negative enteric aerobes, Listeria monocytogenes, T . pallidum, genital Mycoplasma, Chlamydia trachomatis, CMV, HSV, enteroviruses, adenovirus, and rubella, Candida species. Chlamydia trachomatis , Mycoplasma species, CMV, HSV,. 3/6/2019 43

44. PATHOGENESIS AND PATHOLOGY Pneumonia may be acquired : Transplacentally Aspiration of contaminated amniotic fluid Aspiration of infected materials Inhalation of infected aerosols Hematogenously (septicemia or from another focus of infection). 3/6/2019 44

45. Cont…. Pathology Areas of densely cellular exudate with bacteria. Vascular congestion, hemorrhage, and necrosis can be observed. Micro abscesses and empyema ( S . aureus or Klebsiella pneumoniae) . Pneumatocele formation( S . aureus , E . coli and Klebsiella species). Fatal cases of GBS pneumonia have had evidence of hyaline membranes disease. 3/6/2019 45

46. CLINICAL MANIFESTATIONS Those with congenital pneumonia often die in utero or are critically ill at birth. Spontaneous respirations may not occur or may be established with difficulty. If respirations are established, tachypnea, moderate retractions, and grunting may be observed. Fever may or may not be noted but is often a prominent sign of neonatal herpes simplex and enteroviral disease. Cough is not common. Cyanosis 3/6/2019 46

47. Cont… Infants who acquire the infection during delivery or postnatally may have systemic signs, including fever, reluctance to feed, and lethargy and Respiratory signs including coughing, grunting, costal and sternal retractions, flaring of the alae nasi, tachypnea or irregular respirations, rales, decreased breath sounds, and cyanosis. Aspiration during or after delivery can result in bronchopneumonia 3/6/2019 47

48. Cont… Chlamydial pneumonia present at 4 to 11 weeks of age with a prodrome of nasal congestion followed by tachypnea and a paroxysmal, staccato cough. Conjunctivitis is present or occurred earlier in approximately half of these infants. Rales may be present, but expiratory wheezes are not commonly seen. Infants are afebrile and frequently gain weight slowly. 3/6/2019 48

49. DIAGNOSIS Chest x ray radiographic abnormalities are visible by 24 to 74 hours. bilateral homogeneous consolidation when pneumonia is acquired in utero diffuse bronchopneumonia with postnatally acquired disease. Bilateral, symmetric interstitial infiltrates in C . trachomatis pneumonia. Pneumonia caused by GBS has similar radiographic feature of ARDS. 3/6/2019 49

50. Cont… MAS mimics bronchopneumonia, but the radiologic changes tend to be maximal early and disappear rapidly during the ensuing days where as the patchy opacifications noted with bronchopneumonia tend to be minimal early and become more impressive during the subsequent days. Blood cultures Gram-stained smears of tracheal secretions if obtained before 8 hours of age. Culture or antigen detection from nasopharyngeal samples or from secretions obtained by deep tracheal suctioning for diagnosis of Chlamydia pneumonia. 3/6/2019 50

51. TREATMENT Ampicillin and either an aminoglycoside or cefotaxime. Vancomycin and an aminoglycoside for late-onset nosocomial infection. Erythromycin for pneumonia caused by Chlamydia or Pertussis organisms. Acyclovir if HSV pneumonia is suspected. Treatment for bacterial pneumonia is continued for 10 to 14 days. 3/6/2019 51

52. PROGNOSIS Poor prognosticators: Congenital pneumonia Prematurity. 3/6/2019 52

53. Prevention of infection in neonates Maternal immunization( rubella, hepatitis B, VZV) as well as Tetanus Appropriate diet and avoidance of exposure to cat feces. Chemoprophylaxis for malaria and use of insecticide-treated bed nets. Selective intrapartum chemoprophylaxis for GBS. Identification and treatment of infected pregnant women( C. trachomatis, syphilis). PMTCT 3/6/2019 53

54. Principles for the prevention of nosocomial infection Adherence to universal precautions with all patient contact Avoiding nursery crowding and limiting nurse-to-patient ratios Strict compliance with hand washing Meticulous neonatal skin care Minimizing the risk of catheter contamination 3/6/2019 54

55. Cont… Decreasing the number of venipunctures and heel sticks Reducing the duration of catheter and mechanical ventilation days Encouraging appropriate advancement of enteral feedings Providing education and feedback to nursery personnel, and Ongoing monitoring and surveillance of nosocomial infection rates in the NICU. 3/6/2019 55

56. Thank you for your attention!!!!!!! 3/6/2019 56