Neonatal sepsis : overview of epidemiology, pathogenesis, pathophysiology, clinical approaches, diagnosis challenges and rationalizing treatment

Neonatal sepsis : overview of epidemiology, pathogenesis, pathophysiology, clinical approaches, diagnosis challenges and rationalizing treatment

1. Neonatal sepsis
Prepared by
Dr Gabriel K. Shamavu, Paediatrics Resident

Jinja Regional Referral Children hospital / Nalufenya
Continue Medical Education (CME)
Supervisors :
Dr TENWA, Paediatrics Cardiologist
Dr William, Paediatrician
Dr Egessa Ivan, Paediatrician
November 2022

2. •Introduction: Definition, Epidemiology, Pathophysiology and Classification
•Pathogenesis : Factors and aetiology (microbiology)
•Clinical manifestations
•Diagnostic
•Management
•Prevention / Gaps and recommendations
•Conclusion



2
Outline

3. Introduction
•Sepsis is an important cause of neonatal morbidity and mortality
•With several identifiable risk factors and Most are preventable
•Many challenges in diagnosis and management: unspecific manifestations and
rapidity of deterioration in newborn
Sunday, November 20, 2022 3

4. Definition
There is No consensus definition for neonatal sepsis (NS)
Neonatal sepsis may be defined as a clinical syndrome in an infant 28 days of life
or younger, manifested by systemic signs of infection and isolation of a bacterial
pathogen from the bloodstream (bacteremia).
Note : even viral or fungal origin also (other authors)



Sunday, November 20, 2022 4

5. Contact with the pathogen
Sunday, November 20, 2022 5
A systemic and extensive
dysregulated Immune response
SRIS Organ Dysfunction
Metabolic and
endocrine responses
to stress
Bloodstream
SEPSIS
Particularity of Neonatal sepsis :
•Immature/Ongoing development organs
•Deteriorate Rapidely
•Variety/unspecific manifestations
Pathophysiology
Local infection
Pneumonia
Meningitis
Soft tissues
UTI
Direct action of the
pathogen
Recognition and activation of
immune system
Respiratory
Cardiovascular
Neurologic
Renal
Liver
Adrenal

6. Sunday, November 20, 2022 6
Sepsis related cardiovascular Organ Dysfunction
Septic
shock
Pathophysiology
Production of toxin
Peripheral
Vascular dysfunction
Central
Myocardial dysfunction
Warm shock
Cold shok
Vasodilatation

Cytokines
Nitric Oxyd
↓SVR but ↑CO
Flash CRT
Warm/normal extremities

↑ or ↓ SVR but ↓CO
Flash CRT
Cold extremities

Assiociated organ
dysfunction
Respiratory
failure
Direct action of the
pathogen Dysregulated Immune
response (SRIS)
Endothelial injury Cardiomyocyte injury
Hypoxia

7. Classification
in first 72h or 7 days of age
(other authors)
Source: usually maternal genital
tract
Sunday, November 20, 2022 7
after 72 hours or 7 days of age
(other authors)
Source: Either hospital or
community acquired
Early-onset sepsis (EOS) Late-onset sepsis (LOS)

8. 1.The National Institute of Child Health and Human Development and Vermont Oxford Network:
The onset of sepsis at ≤72 hours of life. In term infants, it can be extended to <7 days of life.
2.The Centers for Disease Control and Prevention: Blood culture– and/or cerebrospinal fluid (CSF)
culture–proven infection occurring in the newborn at <7 days.
3.The American Academy of Pediatrics (2018): Blood or CSF culture obtained within 72 hours after
birth that is growing a pathogenic bacterial species.
4.AAP definition of GBS EOS (2019). Isolation of group B Streptococcus organisms from the blood,
cerebrospinal fluid, or another normally sterile site from birth through 6 days of age
Sunday, November 20, 2022 8
Early-onset sepsis

9. Pathogenesis
Early-onset sepsis (EONS)
Sunday, November 20, 2022 9
Intrapartum / Vertically transmitted
Ascending contaminated amniotic fluid after Rupture of Membranes
(vaginal flora or colonizing bacterial)

Or During vaginal delivery from bacteria colonizing or infecting the
mother's lower genital tract
GBS +++
Antepartum Transplacentally by hematogenous spread:






T- toxoplasmosis
O- others infections (GBS, Listeria, candida, Lyme)
R- rubella
C- cytomegalovirus
H- herpes simplex
S- Syphilis
C- chickenox and shingles
H- hepatitis C, D, E
E- enterovirus
A- AIDS/HIV
P- parvivirus B19
Pathogenesis

10. Late-onset infections can be acquired by the following mechanisms:
•Vertical transmission, resulting in initial neonatal colonization that
evolves into later infection
•Horizontal transmission, from contact with individuals and
environment: Health care related (nosocomial) or community acquired
Pathogenesis
Late-onset sepsis (LONS)
Sunday, November 20, 2022 10

11. Maternal / antenatal
•Low socioeconomic status
•Power antenatal care
•Poor nutrition
•Substance abuse
Sunday, November 20, 2022 11
Intrapartum
•PROM
•Maternal fever
•Chorioamnionitis
•Prolonged labor
•Premature labor
•maternal UTI
Postnatal / Neonatal
•Prematurity and/or LBW
•Twin
•Male
•Low Apgar / Birth asphyxia
•Meconium aspiration
•Congenital abnormalies
•Hospitalization / invasive
Procudures
•Community: Poor hygiene,
Low socioeconomic status
Risk factors for Neonatal sepsis

12. Minor
•PROM > 12hrs
•LBW / Prematurity
•Low apgar score
•Maternal WBC > 15000
•Multiple gestation
Major
•PROM > 24hrs (18hrs)
•Maternal fever > 38ºC or 100.4ºF (last 2weeks)
•Chorioamnionitis (Foul smell Liquor)
•Fetal distress : FHR > 160/min
•Multiple obstetric procedures
Sunday, November 20, 2022 12
Assessing the risk factors for Early-onset sepsis (EONS)
Risk factors for Neonatal sepsis

13. Community acquired
•Poor hygien
•Poor cord care
•Bottle feeding
•Tradutional practice : *false teeth extraction
Nosocomial
•Hosptitalization
•LBW/ Prematurity
•Mechanical ventilation
•Invasive procedures
•Inappropriate and abuse of Antibiotics


Late-onset sepsis (LONS)
Sunday, November 20, 2022 13
Risk factors for Neonatal sepsis

14. 14
AAP Neonatal Early Onset SEPSIS risk assessment
The America Academy of Pediatric (AAP) report
acknowledges and endorses 3 commonly used
approaches to risk assessment among infants born at
≥35 weeks’ gestation as follows:
A: Categorical risk assessment
B: Multivariate risk assessment Calculator
C: Risk assessment based on clinical condition
(enhanced observation)
≥35 weeks’ gestation

15. 15
Multivariate risk assessment (the Neonatal Early-Onset Sepsis Calculator):
Multivariate risk assessment integrates the individual infant’s combination of objective quantifiable risk factors and
his/her clinical examination to estimate the individual infant’s risk of EOS (including EOS secondary to GBS).
•Predictive models based on gestational age at birth (weeks and days), highest maternal intrapartum temperature
(centigrade or Fahrenheit), maternal GBS colonization status (positive, negative, uncertain), duration of ROM
(hours), and type and duration of intrapartum antibiotic therapies (1 of 4 categories) have been developed and
validated.
•The models are available as web-based Neonatal Early-Onset Sepsis Calculator
neonatalsepsiscalculator.kaiserpermanente.org

≥35 weeks’ gestation
Neonatal Early Onset SEPSIS risk assessment

16. 16
Neonatal risk assessment for infants born at ≤ 34 6/7 weeks’ gestation
Neonatal Early Onset SEPSIS risk assessment

17. Sunday, November 20, 2022 17
Early-onset sepsis (EONS) Late-onset sepsis (LONS)
GRAM
POSITIVE

Group B Streptococci (GBS)
Coagulase positive Staphylococi : S. aureus, MRSA
Enterococci
Listeria monocytogen (meningitis)
Group B Streptococci (GBS)
Coagulase negative staph : S. epidermidis, …
Coagulase negative staph: S. aureus,MRSA
Enterococci
GRAM
NEGATIVE
E. Coli
Klebsiella pneumoniae
Pseudomonas aergunosa
E. Coli
Klebsiella pneumoniae
Pseudomonas aergunosa
Serratia
Proteus
others Fungal
Virus
Fungal
Virus
Common Aetiologies

18. Sunday, November 20, 2022 18
Common Aetiologies
Bacterial species
Early-onset Late-onset
Group B Streptococcus +++ +++
Escherichia coli +++ ++
Klebsiella spp. + +
Enterobacter spp. + +
Listeria monocytogenes + +
Other enteric gram-negatives + +
Non-enteric gram-negatives* + +
Viridans streptococci + +
Staphylococcus aureus + +++
Citrobacter spp. 0 +
Salmonella spp. 0 +
Coagulase-negative staphylococci 0 +
Enterococcus spp. 0 +
Common bacterial agents causing neonatal sepsis in term infants

19. Region
Common isolated pathogens among neonates with sepsis

Studies / year
Gram positive Gram negative
Asia :
India, Pakistan, Bangladesh, Nepal,
Srilanka
MRSA Klebiella
E. Coli
103 studies included
Neonatal sepsis in South Asia: huge burden and spiralling antimicrobial
resistance, doi: https://doi.org/10.1136/bmj.k5314
Uganda
(Mulago National Hospital/Kampala)
S. Aureus
Enterococci
Neisseria
E. Coli
Klebsiella
Pseudomonas
Neonatal sepsis at Mulago national referral hospital in Uganda:
Etiology, antimicrobial resistance, associated factors and case fatality
risk https://doi.org/10.1371/journal.pone.0237085
Uganda
KIU-Teaching Hospital, Ishaka,
Bushenyi

S. aureus
enterococci
E. Coli
Klebsiella
Pseudomonas
Susceptability patterns of common bacterial pathogens and treatment
outcome of neonatal sepsis at kampala international university teaching
hospital, western uganda. (samuel kisia )
DR Congo
Butembo
S. Aureus (29%) E. Coli (13%)
Pseudomonas
Klebsiella spp.
Bunduki and Adu-Sarkodie , Clinical outcome and isolated pathogens
among neonates with sepsis in Democratic Republic of the Congo: a
cross-sectional study, BMC Res Notes (2019) 12:303
https://doi.org/10.1186/s13104-019-4346-5
DR Congo
Bukavu
S. aureus(4%)
S. Epidermidis (4%)
Enterococci (2%)
Streptococci (2%)
Enterobacter (43%)
Klebsiella (18%)
Serratia marcescens (12%)
E. coli (4%)
Mulinganya, at al. Etiology of Early-Onset Neonatal Sepsis and
Antibiotic
Resistance in Bukavu, Democratic Republic of the Congo, Oxford
University Press for the Infectious Diseases Society of America , 2021
DOI: http://dio.org/10.1093/cid/ciab114

Sunday, November 20, 2022
19
Review: common isolated bacteria, mostly documented

20. Sunday, November 20, 2022 20
Clinical manifestations
and Diagnosis
Of neonatal sepsis
Dr Gabriel K. Shamavu, MD
MbChB University of Goma, 2019
Mmed Student in Paediatrics and Child Health, KIU

21. •Temperature instability: Hypo / hyper thermia
•Lethargy , poor cry, Hypotonia, Poor reflexes,
•Irritability, Seizures
•Respiratory distress / failure
•Failure or Refused to suck / Food intolerance
•Jaundice
•CVS dysfunction: Poor peripheral perfusion/ Shock/ Hypotension (late), Brady or tachycardia
•Petechiae, purpura
•Abdominal distention
•Bleeding disorders,…
Sunday, November 20, 2022 21
Clinical manifestations Early-Onset NS

22. •Temperature irregularity.
•Change in behavior. Lethargy, irritability, or change in tone.
•Skin. Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, sclerema, and jaundice
•Feeding problems: Feeding intolerance, vomiting, diarrhea, or abdominal distention with or without visible
bowel loops.
•Cardiopulmonary. Tachypnea, respiratory distress (grunting, flaring, and retractions), new onset of apnea,
bradycardia and desaturation episodes (ABD [apnea, bradycardia, desaturation] spells), tachycardia, and
hypotension singularly or in combinations should suggest sepsis.
•Metabolic. Metabolic findings include hypoglycemia, hyperglycemia, or metabolic
acidosis.
• Focal infections. These may precede or accompany LOS. Look for cellulitis, impetigo, soft tissue abscesses,
omphalitis, conjunctivitis, otitis media, meningitis, or
osteomyelitis.





Sunday, November 20, 2022 22
Clinical manifestations Early-Onset NS

23. Differential diagnosis
•HIE and other birth asphyxia related systemic organ dysfunction
•Respiratory symptoms:
RDS, TTN ,Meconium aspiration syndrome (MAS)
Aspiration pneumonia
•CHD
•Feeding intolerance, bloody stool : NEC, GI obstruction, Gastrointestinal
perforation
•In-born errors of metabolism…
Sunday, November 20, 2022 23

24. Diagnosis: principles and challenges
•Carefull history / assessing predicting risk factors (identify newborn at risk)
•Proper physical examination, monitoring (remember: Unspecific clinical manif)
•A practical screening / routine or orientation
•Bacteriological Confirmation
•Complications assessement: R/O Meningitis, organ dysfunction, metabolic
response to the biological stress (hypoglycemia)
•Follow-up



Sunday, November 20, 2022 24

25. Diagnosis: principles and challenges
Gold Standard = Blood culture
•A definitive diagnosis of neonatal sepsis is established by a positive blood culture.
•The sensitivity of a single blood culture to detect neonatal bacteremia is approximately 90 percent.
•Number of cultures – We obtain at least one culture prior to initiating empiric antibiotic therapy in
neonates with a high clinical suspicion for sepsis, although other institutions may routinely obtain
two blood cultures.


current mainstreams
Not additional laboratory testing other than blood culture (and lumbar puncture, if clinically indicated).
There are no recommendations regarding early cessation of antibiotics based on additional laboratory
testing, or continuing empiric antibiotics in the presence of a negative blood culture due to abnormal
secondary laboratory testing.
Sunday, November 20, 2022 25

26. Lumbar punction


•Many institutions perform LPs only on infants who are clinically ill, infants
who have CNS symptoms such as apnea or seizures, or in cases of
documented positive blood cultures or if the decision is made to extend
antibiotics beyond 48 hours for presumptive clinical sepsis.

Sunday, November 20, 2022 26
Diagnosis: principles and challenges

27. CBC:
•Abnormally low or high WBC count is worrisome. Values <6000 cells/mm3 or >30,000 cells/mm3 in
the first 24 hours of life are abnormal.
•Only half of infants with Abnormal WBC count have positive blood cultures. And 50% of infants with
culture-proven sepsis have normal WBC counts.
•Septic infants with a WBC count <5000 cells/mm3 are more likely to have bacterial meningitis.
•Total neutrophil count is more sensitive than the total leukocyte count but is too often normal in cases
of infection. It peaks in 12 hours, and it has a poor sensitivity and poor predictive accuracy for EOS.
Sunday, November 20, 2022 27
Diagnosis: principles and challenges

28. •C-Reactive Protein (CRP)
•Procalcitonin : elevated in sepsis and have been used as a marker for sepsis. A single value is not
helpful, whereas serial negative values are associated with absence of EOS.
Both CRP and procalcitonin concentrations can be increased in response to infections or noninfectious
conditions such as asphyxia, pneumothorax, ischemic tissue injuries, hemolysis, and meconium aspiration
syndrome.
•Others :
Cytokines interleukin-6, interleukin-8, and tumor necrosis factor
Neutrophil surface antigens CD11, CD14, and CD64
Inflammation Acute phase reactants (C-reactive protein and procalcitonin) as
biomarkers of sepsis
Sunday, November 20, 2022 28
Diagnosis: principles and challenges

29. Previous mainstreams suggested a “Practical sepsis screening” :
CBC
WBC< 5000/mm3,
Neutropenia with I/T>0.2 (Immature / total neutrophil)
PLT normal or low
C-Reactive protein : > 1mg/dl
Micro- ESR: >15mm/1
st
hour
Low count as per Manroe
chart for term and
Mouzinho’s chart for
VLBW
Sunday, November 20, 2022 29
Diagnosis: principles and challenges

30. Others investigations :
•Imaging studies : Chest radiograph, …
•Metabolic dysfunction : Baseline serum glucose, …
•Organ dysfunction : Arterial blood gas, RTFs, LFTS, Bilirubin, electrolytes…
•Urine culture
•Erythrocyte sedimentation rate (ESR)
•Gastric aspirate analysis
•Molecular assays include conventional and real-time PCR, PCR followed by
post-PCR processing, multiplex PCR, staphylococcal PCR, and fungal PCR…


Sunday, November 20, 2022 30
Diagnosis: principles and challenges

31. •CVS: Septic shock, Cardiac failure
•Respiratory distress to failure
•Renal : AKI to failure, Acid-base/electrolytes distrurbances
•Hepatic dysfunction
•NEC
•Adrenal hemorrhage and/or insufficiency
•Bone marrow dysfunction (netropenia, anemia, thrombocytopenia)
•Bleeding disorders: DIC
Sunday, November 20, 2022 31
Neonatal Sepsis related Organs dysfunction
Complications

32. Sunday, November 20, 2022 32
Management
Of neonatal sepsis
Dr Gabriel K. Shamavu, MD
MbChB University of Goma, 2019
Mmed Student in Paediatrics and Child Health, KIU
•Supportive treatment
•Adequate rationalizing antibiotic
prescription
•Treatment of comorbidity /
control source of infection
•treatment of complications
•Follow up

33. •Respiratory: ensure an adequate / optimal oxygenation
•Cardiovascular: Maintenance of adequate perfusion
•CNS: seizure control,
•Metabolic: correct Hypoglycaemia (IV D10%), metabolic acidosis (bicarbonate)
•Maintain a thermal neutral environment
•Adequate nutrition
•Monitor vitals –
•SPO2, RR,PR, Temp
•Drug toxicity (e.g. gentamicin)
•Fluid In-put/Output
•Infection source control: skin lesions, cord, …
Supportive treatment and treatment of complications
Sunday, November 20, 2022 33
Management

34. Empirical antibiotherapy for Early onset neonatal sepsis
Sunday, November 20, 2022
34
First line Antibiotics :
IV Ampicillin 50-150mg/kg BD IV
Gentamicin 4 -5mg/kg/day
+ Draw lab samples
•If neonate (A) remains asymptomatic , repeat CRP
after 72hours and if normal discontinue antibiotics.
•If CRP : elevated >10mg/dl complete 7days
treatment + furthers investigations
For Neonate (B) Continuing therapy is based
on culture and sensitivity results, clinical
course
HOW?
WHEN?
(A) Presumed sepsis (Asymptomatic but has risk factors)
(B) Probable sepsis ( risk factors + clinical sign of infection )
First line
Antibiotics

35. Empirical antibiotherapy for Early onset neonatal sepsis
Sunday, November 20, 2022
35
WHEN?
Second line
Antibiotics
Second line:
Ampicilllin plus cefotaxime (50 mg/kg )

Greater risk of staphylococcus infection
IV cloxacillin and gentamicin for at least 7–10
days

If meningitis
Ampicilin + cefotaxime at least 14days
HOW?

36. AAP Suggested empirical antimicrobial regimens in the management of neonatal
sepsis
Sunday, November 20, 2022
36
Empiric therapy Antibiotic regimen
Early onset (<7 days) Ampicillin + gentamicin
Late onset (≥7 days): Admitted from the community Ampicillin + gentamicin
Late onset (≥7 days): Hospitalized since birth Gentamicin + vancomycin
Special circumstances:
Suspected meningitis - early onset Ampicillin + gentamicin*
Suspected meningitis - late onset, admitted from the community Ampicillin, gentamicin, + cefotaxime
Suspected meningitis - late onset, hospitalized since birth Gentamicin, vancomycin, + cefotaxime
Suspected pneumonia
Ampicillin + gentamicin
•Alternatives: Ampicillin + cefotaxime, OR
•Vancomycin + cefotaxime
¶
, OR
•Vancomycin + gentamicin
Suspected infection of soft tissues, skin, joints, or bones (S. aureus is a
likely pathogen)
Vancomycin or vancomycin + nafcillin
Suspected intravascular catheter-related infection Vancomycin + gentamicin
Suspected infection due to organisms found in the gastrointestinal tract (eg,
anaerobic bacteria)
Ampicillin, gentamicin, + clindamycin
•Alternatives: Ampicillin, gentamicin, + metronidazole OR
•Piperacillin-tazobactam + gentamicin

37. Drugs used for empirical treatment of neonatal sepsis: dose and frequency

Drug

Route

Dose
(mg/kg)




Dosing Frequency

Duration
(days)
Term Preterm or LBW
≤7 days >7 days ≤7 days >7 days
Ampicillin IV 50 BD TDS BD TDS 7-10
Benzylpenicillin IV 25-50 BD TDS BD TDS 7-10
Cloxacillin IV 50 BD TDS BD TDS 7-10
Gentamicin IV 5 OD OD OD OD 7-10
Vancomycin IV 10-20 BD TDS BD TDS 7-10
IV=intravenous; OD=once daily; BD=twice daily; TDS=three times daily

Sunday, November 20, 2022 37

38. Administration of vancomycin in newborn / Challenges

Sunday, November 20, 2022 38
•Scr <0.7 mg/dL – 15 mg/kg/dose IV every 12 hours
•Scr 0.7 to 0.9 mg/dL – 20 mg/kg/dose IV every 24 hours
•Scr 1 to 1.2 mg/dL – 15 mg/kg/dose IV every 24 hours
•Scr 1.3 to 1.6 mg/dL – 10 mg/kg/dose IV every 24 hours
•Scr >1.6 mg/dL – 15 mg/kg/dose IV every 48 hours
For preterm infants
Gestational age ≤28 weeks:
•Scr <0.5 mg/dL: 15 mg/kg/dose IV every 12 hours
•Scr 0.5 to 0.7 mg/dL: 20 mg/kg/dose IV every 24 hours
•Scr 0.8 to 1 mg/dL: 15 mg/kg/dose IV every 24 hours
•Scr 1.1 to 1.4 mg/dL: 10 mg/kg/dose IV every 24 hours
•Scr >1.4 mg/dL: 15 mg/kg/dose IV every 48 hours
•Scr >1.6 mg/dL: 15 mg/kg/dose every 48 hours
Gestational age >28 weeks :
•Scr <0.7 mg/dL: 15 mg/kg/dose IV every 12 hours
•Scr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours
•Scr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours
•Scr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours
For term infants >7 days of life
Vancomycin dosing is based on gestational age and serum creatinine (Scr; which will take approximately five days after
birth to reflect neonatal renal function):
Alternative weight-directed dosing recommendations
are also available

39. Specific treatment
Choice of antibiotics according to the pathogen isolated and the sensitivity
Sunday, November 20, 2022 39
Pathogen-specific therapy
Group B Streptococcus Penicillin G
Escherichia coli: Ampicillin-sensitive Ampicillin
Escherichia coli: Ampicillin-resistant
Cefotaxime
¶

•Alternative: Meropenem
Multidrug-resistant gram-negative bacilli (including
ESBL-producing organisms)
Meropenem
Listeria monocytogenes Ampicillin AND gentamicin
Methicillin-susceptible S. aureus (MSSA) Nafcillin OR cefazolin
Methicillin-resistant S. aureus (MRSA) Vancomycin
Coagulase-negative staphylococci Vancomycin

40. Sunday, November 20, 2022 40
Management of common Complications
Neonatal septic shock
Initial steps in the treatment of septic shock in the newborn

41. Sunday, November 20, 2022 41
Management of common Complications
Complexity of Decision
making in Circulatory
Management

42. Sunday, November 20, 2022 42
Respiratory distress
Position of the head
Suctioning of secretion
Airway adjuncts
Oxygen supplementation
Non-invasive Ventillation/nCPAP


Mechanical ventilation
After Endo tracheal intubation
Step 1
Basic Life support
Step 2
Advanced Life support
Step 3
Mechanical ventialation by mask
and ambubag
Use of Extra Corporeal Membrane
of oxygenation (ECMO)
Montitor: SpO2, RR, blood gazes
HEART RATE (informs about
Myocardia oxygenation)
If < 60bpm
Start Chest compression (CPR)

Management of common Complications

43. Sunday, November 20, 2022 43
Hematologic complications
Management of common Complications
Complications Treatment options
Bleeding disorders
Thrombocytopenia and / or DIC
Fresh-frozen plasma ; vitamin K, platelet
infusion; and possible exchange
transfusion
Anemia Blood transfusion: Packed RBC
Neutrophilia
•Granulocyte colony-stimulating factor (G-CSF)
•Granulocyte-macrophage colonystimulating factor
(GM-CSF)

44. Sunday, November 20, 2022 44
TORCH and infections
Infection Treatment
Toxoplasmosis sulfadiazine (50 mg/kg, twice daily), pyrimethamine (2 mg/kg/d for 2
days, then 1 mg/kg/d for 2–6 months, then 1 mg/kg/d 3 times a week),
and folinic acid (10 mg, 3 times weekly) for a minimum of 12 months
Others GBS : Peni G, Ampicillin
L. Monocytogen:
Candida : nystatin, fluconazol
Rubella
CMV Oral valganciclovir: 16 mg/kg BD for 6 months
OR ganciclovir at 6 mg/kg/dose
Herpes virus Acyclovir or valacyclovir
Syphilis IV aqueous crystalline penicillin G 50,000 U/kg/dose
BD during the first 7 days of life and every 8 hours thereafter for a total of 10
days (preferred treatment) or procaine penicillin G
50,000 U/kg/dose intramuscularly (IM) in a single daily dose for 10 days.

45. •Mortality is 2% to 3% in term infants, with 75% of deaths attributable to EOS in VLBW infants.
•Mortality estimates based on gestational age are as follows: 1.6% at ≥37 weeks, 2% to 3% at ≥35
weeks, 30% at 25 to 28 weeks, and 50% at 22 to 24 weeks.
•Mortality by birthweight is as follows: 3.5% if born weighing >1500 g and 35% if weighing <1500 g.
•Up to 60% of term infants and 95% of preterm infants require neonatal intensive care unit (NICU)
care for respiratory distress and/or blood pressure support.
Sunday, November 20, 2022 45
Outcomes

46. •Routine ANC – Identify & treat infections
•Universal antepartum screening for GBS at 36 0/7 to 37 6/7 weeks of gestation
•GBS prophylaxis: Penicillin, Vaccination, …
•Chlorhexidine wipes for vaginal exams (lbr)
•Sterility for all procedures
•Strict hand hygiene for all caregivers
•Breastfeeding
•Remove IV access if no longer required
•Good cord care practices
•Improve rational use of antibiotics


Sunday, November 20, 2022 46
Prevention

47. •


GAPS Actions plan
Lack of quality research on common etiology &
suseptability of EONS on our NICU/SCU

Research on common etiology and susceptibility for care
quality improvement other than academic research

Blood culture is expensive The cost of blood culture should be subsidized
Poor documentation: relevant information about risk
factors of infections are not usually recorded in the
mother’s file.
Standard transferred documents with relevant
information about neonatal sepsis.
Delay of the result of blood culture The laboratory should be able to give us the preliminary
results within 72 hours.
Recurrent stock out of the bottles for blood culture The bottles should be available
Lake of guideline and stewardship for antibiotics
rationalizing prescriptions
Organize more CMEs, make a local protocoles /
guidelines for rational use of antibiotics, prevent and
management of infections in newborn
Institutional gaps/problems
Sunday, November 20, 2022 47

48. Sunday, November 20, 2022 48
•Most of Risk factors for Neonatal sepsis can be prevented
•The positive blood culture is the gold standard for diagnosis of
neonatal sepsis (limited access/financial issues)
•In limited ressources settings: Knowledge and prevention of risk
factors and rationalizing therapeutic interventions can help to
reduce the incidence, morbidity and mortality

Conclusion

49. Main References
•ROBERT M. KLIENGMAN, at al. Nelson textbook of Pediatrics, 21
st
edition, Elsevier, 2020
•GOMELLA TL., EYAL FG., at al., Gomella’s Neonatology: Management, Procedures, On-Call Problems, Diseases, and Drugs , 8
th
edition,
McGraw-Hill Education , 2020
•Edwards MS., at al., Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants, ©UpToDate_2018, Topic 5043 Version
46.0 Literature review current through: Feb 2018. | This topic last updated: Nov 30, 2017.
•EDWARDS MS, BAKER CJ. Sepsis in the Newborn. In: Krugman's Infectious Diseases of Children, 11th ed, Gershon AA, Hotez PJ, Katz SL (Eds),
Mosby, Philadelphia 2004. p.545.
•PUOPOLO K. M., BENITZ W. E, ZAOUTIS T. E, Committee on Fetus and newborn and Committee on Infectious Diseases (2018). Management of
neonates born at 35 0/7 Weeks' gestation with suspected or proven early-onset bacterial sepsis. Pediatrics, 142.
•World Health Organisation (2017). WHO recommendations on newborn health: Guidelines approved by the WHO guidelines review
committee. Geneva: World Health Organization.
•Fuchs A., Bielicki J., Mathur S., Sharland M., Van Den Anker J. N. (2016). Antibiotic use for sepsis in neonates and children: 2016 evidence update.
WHO reviews
•GOMELLA, T. L., CUNNINGHAM, M. D., EYAL, F. G., & TUTTLE, D. J. (Eds.). (2013). Neonatology: Management, procedures, on-call problems,
diseases, and drugs. (7th ed.). McGraw-Hill.
•Kamalakannan S.K (2018). Neonatal sepsis past to present. Biomed J Sci & Tech Res 3(3), 3309-3314
•KAREN M. PUOPOLO. Bacterial and fungal infections. In Cloherty, John P., Eichenwald, Eric C., Hansen, Anne R., Stark, Ann R. (Eds). (2012).
Manual of neonatal care (7th ed.). Philadelphia, PA: Lippincott Williams and Wilkins
`
`
`
Sunday, November 20, 2022 49
Thank you