Neonatal_fungal_and_GNB_sepsis [1].pptx

fungal sepsis and gram negative bacterial sepsis in neonates

1. Fungal and Gram negative Bacterial sepsis Presenter: Dr. Henok (MD, pediatrics resident) Jan/2024

2. Outline Objective Introduction Etiology Risk factor Clinical presentation Management Complications Recent studies Recommendation Reference 2

3. Objective To understand the magnitude of fungal and gram negative sepsis To know the value of Infection prevention To be clear with possible treatment options 3

4. Introduction Neonatal sepsis is a clinical syndrome of bacteraemia characterized by systemic signs and symptoms of infection in the first month of life. Is the most common cause of neonatal mortality. Probably responsible for 30 to 50% of the total neonatal deaths each year in developing countries. Most of these deaths can be averted 4

5. CONT…. SIRS: Is an inflammatory cascade that is initiated by the host response to an infectious or noninfectious trigger and patient has to fulfill: 1.Core Temp> 38.5oC or <35.5 2.Tachycardia for age 3.Tachypenea for age 4.WBC elevated or depressed or >10% immature neutrophils Sepsis: is defined as SIRS with suspected/confirmed infection. 5

6. Fungal sepsis Fungal infections in the NICU remain an important health problem associated with substantial morbidity and mortality. Invasive Candida infections occur in two main patient groups in the NICU: Extremely premature infant and Complex gastrointestinal disease such as NEC, gastroschisis, and spontaneous bowel perforation. 6

7. Etiology Largely caused by Candida species and with a small portion caused by Aspergillus , Zygomycetes , Malassezia , and Trichosporin . Candida albicans and C. parapsilosis account for 80%-90% of invasive Candida infections. Less-common Candida species include C. glabrata and C. tropicalis , and a smaller percentage of infections are caused by C. lusitaniae , C. guilliermondii , and C. dubliniensis . Candida auris 7

8. Incidence The incidence of candidiasis correlates with advances in medical therapy and increased survival of ELBW and preterm neonates. The incidence of invasive Candida infections in ELBW infants, not including congenital cutaneous candidiasis, is around 10% in the absence of antifungal prophylaxis. The highest incidence of invasive Candida infections occurs in the most extremely preterm infants and is >20% for infants less than 25 weeks’ gestation. 8

9. Risk factors ELBW and prematurity Presence of central catheter, Delay in enteral feeding, Exposure of broad-spectrum antibiotic H2 blockers, PPI or systemic steroids Endotracheal intubation Complex Gastrointestinal Disease Congenital Heart Disease ECMO 9

10. PAT H O G ENESIS 10

11. Clinical presentation These infections are often classified similar to other neonatal infections into early-onset (<72 hours after birth) and likely vertically transmitted and late onset (≥72 hours after birth) and potentially horizontally transmitted infections. 11

12. CONT…. 12

13. Diagnostic approach Both the total WBC and the differential can be normal early in the course of infection, and although thrombocytopenia is a consistent feature, it is not universally found at presentation. Candida can be cultured from standard pediatric blood culture systems; the time to identification of a positive culture is usually by 48 hours, although late identification (beyond 72 hours) does occur more frequently than with bacterial species. 13

14. Cont.… Both fungal culture and fungal staining (KOH preparation) of urine obtained by SPA can be helpful in making the diagnosis of systemic candidiasis. Specimens obtained by bag urine collection or bladder catheterization are difficult to interpret because they can be readily contaminated with colonizing species. Before the initiation of antifungal therapy, CSF should be obtained for cell count and fungal culture if infant condition allows. 14

15. Management Systemic candidiasis is treated with amphotericin B , 1 mg/kg/day for 14 days after a documented negative blood culture, if there is no evidence of meningitis or other end-organ infection. Otherwise, recommended length of treatment for neonatal candidemia involving the CNS or other end-organ focus is 3 weeks for longer, pending resolution of specific end-organ infection. All common strains of Candida other than some strains of C.lusitaniae , C. glabrata , and C. krusei are sensitive to amphotericin. 15

16. Azole Agents Fluconazole has demonstrated similar efficacy to amphotericin B deoxycholate. Is readily bioavailable and has excellent tissue penetration. It should be reserved and used for prophylaxis primarily and added when combination therapy is desired. Enteral systemic fluconazole treatment is also a good selection when the Candida species is susceptible, infant is tolerating feedings, and IV access is not needed for other reasons. 16

17. Voriconazole Has a broader spectrum of antifungal activity, and it is the first-line treatment option in cases of Aspergillus infection. Tends to accumulate in infants with renal insufficiency; drug levels should be monitored. Suggested dosing is 6 mg/ kg every 12 hours (for 24 hours), followed by 4 mg/kg every 12 hours, with monitoring of serum hepatic enzymes weekly and drug levels obtained if there is oliguria or renal impairment . 17

18. Complications Invasive candidiasis is associated with overall poorer neurodevelopmental outcomes and higher rates of threshold retinopathy of prematurity, compared to matched control infants. The incidence of neurodevelopmental impairment is 57% with candidemia versus 29% in non infected ELBW infants . Candida-Related Mortality Marked difference in overall and attributable mortality between infants less than 1000 grams and larger and more mature infants. 18

19. Prevention Minimizing use of broad-spectrum antibiotics and H2 blockers Changing infusions of lipid suspensions every 12 hrs to minimize microbial contamination. Solutions of parenteral nutrition and lipid mixtures should be changed every 24 hours. Prophylactic fluconazole administration to prevent invasive fungal infection in VLBW infants. 19

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21. Gram negative Bacterial sepsis Newborns are dependent on innate immunity and trans-placental IgGs . Maternal IgG more protective against Gm+ve than Gm- ve hence newborns are prone for gram negative septicemia. Preterm babies have low IgGs and decreased functions of neutrophils. It accounts for more than half of the instance of EONS and around one third of LONS. 21

22. Etiology 22

23. Prevalence 23

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26. Risk factors Birth weight Gestational age Central line Catheterization for more than 10 days Use of PPI or H 2 blockers Total parental nutrition GI pathology including NEC Duration of stay at NICU Use of broad spectrum antibiotics Use of intrapartal Abx prophylaxis ??? 26

27. Transmission Maternal GI and genitalia flora water humidifier Arteficial fingernails and jewelry Cell phone 27

28. Pathophysiology Endotoxin produced by GNB is the bacterial LPS. LPS induces a systemic inflammatory strom that is responsible for mortality and morbidity. 28

29. Clinical presentation specific to GNB They will have a fulminant clinical course than any other infections with a lethality in 48hr. P.auroginosa is associated with highest mortality compared to other GNB ( 52% vs 24%). Citrobacter koseri has a propensity to invade CNS resulting in meningitis, brain abscess and liquefaction necrosis of the brain. 29

30. Investigation modalities Blood culture is the gold standard but has limited sensitivity antepartum antibiotic use inadequate sample WBC count and indices predict sepsis with sensitivity -17-90% specificity - 31-100% CRP sensitivity -60% ( serial 84%) positive predictive value and specificity 83%- 100% CSF analysis and culture 30

31. Antimicrobial therapy Decision to start antibiotics is based upon clinical features and/or a positive septic screen. The choice of antibiotics depends on the prevailing flora responsible for sepsis in the given unit and their antimicrobial sensitivity. Duration of antibiotic therapy is dependent upon the presence of a positive blood culture and meningitis. 31

32. Empiric therapy 32

33. CONT…. Duration Rx: 33

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35. Newer drugs Ceftolozane and tazobactam Meropenem and vaborbactam . Imipenem and relebactam Plazomicin 35

36. Summary Invesive fungal infection accounts for 10-20% of infections The commonest etiology is Candidia spp It is highly associated with BW and Gestational age Clinical presentation is almost similar with bactremia Definitive diagnosis is based on blood culture Treatment of choice is Amphotrecine B Has higher mortality and neurodevelopmental sequele prevented/reduced by effective Infection prevention measures and prophylaxis 36

37. GNB accounts for about 79.8 % They will have fulminant course Blood culture is the gold standard diagnostic modality Treatment is based on the prevailing bacteria Is assocaited with higher antimicrobial resistance 37

38. Recommendation Changing of MF should be q 12hrs Changing of humidifier water q12-24hr Sending separate sample of blood culture for fungal growth Need to have high index of suspection if these are present Maternal treatment in breast feeding mothers Prophylactic use of fluconazole 38

39. References Fanaroff & Martin’s neonatal-perinatal medicine 11 th e Cloharty and Stark’s manual of neonatology 9 th e SPHMMC, Empiric antimicrobial treatment guidelines for pediatric critical infectious conditions, 2023 Nelson’s Pediatric Antimicrobial Therapy,28th Edition,2022 Clinical Reference Manual for Advanced Neonatal Care in Ethiopia, MOH,2021 Expert reviews, management of neonatal sepsis by gram negative pathogens, 2008 WHO official website Google image 39