UNIVERSITY OF MALAYA
MEDICAL CENTRE
NEONATAL INTENSIVE
CARE UNIT NEONATAL SEPSIS MANAGEMENT AND ANTIBIOTICS GUIDANCE
Version/
Revisions
|
Authors
|
Comments
|
1.0 Version 2013
|
Azanna A Kamar, Lai Nai Ming, Choo Yao Mun
|
First Draft
|
2.0 Version July 2020
|
Tan Lay Teng, Azanna A Kamar, Choo Yao Mun, Koh Mia Tuang
Department of Paediatrics
Sasheela Ponnampanalavanar, Department of Infection Control
Jasreena Kaur, Department of Pharmacy
|
Overview of clinical management.
Revisions made based on PPUM NICU antibiogram results
|
1.0 OVERVIEW
Infection in neonates is a leading cause of
mortality in newborns and a major cause of admission to NICU. The term neonatal
sepsis or sepsis neonatorum commonly refers to a condition of bacterial,
viral or fungal infection associated with haemodynamic changes and other
clinical manifestations seen during the neonatal age group or older.
Early
onset neonatal sepsis (EONS): <72 hours of life.
Late
onset neonatal sepsis (LONS) : >72 hours of life.
Note:
Definitions of late onset sepsis occurring at more than 7 days have been
described in epidemiologic studies and in the description of the clinical
course of Group B Streptococcus.
Epidemiology
- The overall incidence of neonatal sepsis varies
from 1 to 5 for every 10,000 live births.
- Globally neonatal sepsis accounts between 13 to
26% of total neonatal deaths, with variable estimates of disease burden between
various income levels. For example, the incidence of neonatal sepsis in Asia
ranges from 7.1 to 38 per 1000 live births in comparison to 6 to 9 cases per
1000 live births in the United States and Australasian countries. A high
proportion of newborns in developing countries die at home post-delivery with neonatal sepsis carrying a high impact on the overall newborn mortality.
- Data from the Malaysian neonatal registry reported
the incidence of sepsis as 16.1% of very low birth weight (VLBW) infants, where
9.8% was EONS and 90.2% was LONS. High mortality rates of up to 43.8% is
observed in infants with GBS EONS. Up to
66.7% of VLBW infants with gram negative sepsis die.
2.0
RISK FACTORS
Risk
factors for early onset sepsis:
Maternal GBS (Group
B Streptococcus) carrier (high vaginal swab [HVS], rectal swab, urine
culture, previous pregnancy of baby with GBS sepsis)
- Prolonged Rupture of Membranes (PROM) (> 18 hours)
- Preterm labour/ Preterm prelabour rupture of membranes (PPROM)
- Maternal pyrexia > 38˚C, maternal peripartum infection,
clinical chorioamnionitis, discoloured or foul-smelling liquor, maternal
urinary tract infection
- Traumatic delivery
- Birth asphyxia
- Low birth weight
- Confirmed sepsis in co-twin (multiple pregnancy)
- Infant with galactosaemia (increased susceptibility to E.
coli)
Risk factors for late onset sepsis:
- Any indwelling intravascular access - central venous line,
arterial line, umbilical catheter
- Low gestational age
- Low birth weight
- Mechanical ventilation
- Prolonged hospital stay
3.0 AETIOLOGY
Table 1: Aetiology of Neonatal Sepsis
Early-onset Pathogens
|
Late-onset Pathogens
|
Group B Streptococcus (Streptococcus
agalactiae)
Escherichia coli
Klebsiella sp
Staphylococcus aureus
Coagulase-negative Staphylococcus (CONS)
Listeria monocytogenes
Enterococci
Other Streptococci: Streptococcus pyogenes, Streptococcus
viridans, Streptococcus pneumoniae
Other gram-negative bacteria:
Haemophilus spp
|
Coagulase-negative Staphylococcus (CONS)
Group B Streptococcus (Streptococcus agalactiae)
Escherichia coli
Klebsiella sp.
Staphylococcus aureus
Candida albicans
Enterococci
Pseudomonas aeroginosa
Acinetobacter sp
Others : Enterobacter, Citrobacter, Serratia
Other Candida species (Non-albicans Candida)
e.g. C glabrata, C parapsilosus, C kruseo, C tropicalis
Aspergillus fumigatus, Aspergillus spp
|
4.0 ASSESSMENT AND EVALUATION Early recognition is essential as sepsis
onset is often subtle, with extremely rapid progression. Approximately 1% of
well-appearing healthy infants at birth may develop signs of infection
occurring after a variable time period. Peripartum risk factors places an infant
to be at higher risk of sepsis, e.g. prolonged rupture of membranes of more
than 18 hours places an infant to be at 10-fold higher risk of sepsis Careful perinatal history, and clinical
examination is essential. Sepsis risk calculators e.g. Kaiser
Permanante study group neonatal sepsis calculator, may be used to calculate
probability of sepsis risk.
;)
Figure 2: Clinical Features of Neonatal Sepsis
5.0 INVESTIGATIONS
(A) Evidence of Infection and Inflammation White blood
cell count and differentials: There is poor positive predictive
value in total white cell count as an indicator of neonatal sepsis. Low
white blood cell count of <5000/mm3 is associated with the
diagnosis of sepsis. Often, the trend of white cell count taken 8 to 12
hours apart is a better indicator. The neutrophils are responsible for
digestion of bacteria. However, its chemotaxis may be immature with poor
response, especially in preterm infants resulting in release of immature
neutrophils. White blood cell parameters which may be used to guide
diagnosis include a) Absolute
neutrophil count (ANC) – neutropaenia (<1800/mm3 at birth
and <7800/mm3 at 12 – 14 hours), has better specificity
compared with elevated neutrophils. Neutropaenia indicate depletion of
the neutrophil storage pool which places the infant to be at risk of
dying of sepsis b) Immature to
total neutrophil ratio (I/T ratio)
IT ratio = [ Metamyelocytes + Band neutrophils ] / Total neutrophils
IT Ratio > 0.20: Infection highly suspicious
IT Ratio > 0.8: High risk of death from sepsis
I/T ratio has the best sensitivity amongst the neutrophil indices with high
negative predictive value of up to 99%. However, it has a low positive
predictive value of 25%. It indicates the proportion of immature neutrophils
(metamyelocytes and band neutrophils) which are released from the neutrophil
storage pool which are too immature to effectively ward off infection.
;)
Figure 3: Neutrophil levels of neonates born at > 36 weeks’
gestation during the first 72 hours at birth.
(Source : Schmutz, N., Henry, E., Jopling, J., & Christensen,
R.D. (2008). Expected ranges for blood neutrophil concentrations of neonates:
the Manroe and Mouzinho charts revisited. Journal of Perinatology, 28,
275-281.)
- Platelet Count: Low
platelet count is a common manifestation of neonatal sepsis. This is more
commonly associated with gram positive organism sepsis. The phenomenon may
still be observed with gram negative organisms. The mechanism is
uncertain,but is said to be caused by bacterial endothelial damage leading
to platelet adhesion and aggregation. It has also been shown to be caused
by presence of circulating of immune complex in the septic neonate.
- Blood culture
and sensitivity: A positive culture growing from blood or sterile body fluid
remains the criteria in diagnosing neonatal sepsis. Up to two-thirds of
younger infants <2 months of age have colony forming units of <10
CFU>ml. Therefore, an optimal amount of blood of 1 ml should be drawn
for purpose of culture or else cultures may remain negative. Cultures may
also remain negative in view of prenatal antibiotics administration. It
may be difficult to determine whether positive culture is a contaminant,
especially if coagulase negative Staphylococcus (CONS) is grown. Term
infants without any indwelling catheters are less likely to grow CONS.
- Lumbar
puncture: In bacteraemic infants, the incidence of associated
meningitis is as high as 23%. Therefore, performing a lumbar puncture for
cerebrospinal fluid (CSF) examination (gram stain, culture, cell count and
biochemistry – protein and glucose concentration), may be necessary in an
infant with a positive blood culture, abnormal laboratory data, or in
infants with a clinical course that is strongly suggestive of sepsis. If
there is already a strong suspicion of clinical infection or meningitis
from the outset, a CSF sample is best obtained before commencement of
antibiotics but should not result in undue delay in antibiotics
initiation.
Table 2: Normal CSF Ranges in Neonates
|
RBC/mm3
|
Median WBC/µL (IQR)
|
Median Protein g/L (IQR)
|
Term < 7 days
|
9 (0-50)
|
3 (1-6)
|
0.78 (0.60-1.0)
|
Term >7 days
|
<10
|
2 (1-4)
|
0.57 (0.42-0.77)
|
Preterm < 7 days
|
30 (0-333)
|
3 (1-7)
|
1.16 (0.93-1.38)
|
Preterm > 7 days
|
30
|
3 (1-4)
|
0.93 (0.69-1.22)
|
ELBW < 7 days
|
|
3 (1-8)
|
1.62 (1.15-2.22)
|
ELBW > 7 days
|
|
4 (0-14)
|
1.59 (0.95 – 3.70)
|
“Bloody
Tap”: Calculate WBC to RBC ratio. Allow 1:500, if unsure treat as meningitis.
CSF
glucose: Blood glucose ratio > 0.6; CSF glucose > 2.5
mmol/L.
ELBW:
Extremely low birth weight. Preterm= Infants <37 weeks gestation.
|
Adapted from: Chess PR 2019, Avery’s Neonatology Board Review.
Srinivasan et al., J Pediatr 2012. Rodriguez et.al., J Pediatr 1990. Royal
Berkshire NHS Sepsis Guidelines 2018.
5. C-Reactive Protein (CRP): CRP is an acute
phase reactant produced in the liver. Approximately 10 to 12 hours is required
for CRP to change significantly after the onset of an infection with low
sensitivity during early stages, and is therefore, a late indicator of sepsis. A sequential analysis is more useful in
interpretation compared with a single reading. Bacterial sepsis is less likely
in infants with persistently low CRP of <1 mg/dL and is therefore often used
as a guide to discontinue antibiotics therapy. Caution in interpretation should
be taken especially in preterm infants where the response may be less apparent
or in infants with meconium aspiration, intraventricular haemorrhage or
perinatal asphyxia where the CRP may be responsively raised. 6. Procalcitonin
(PCT): Release of PCT by parenchymal cells is triggered by bacterial
toxins and are therefore a useful marker in neonates. Although the
response more rapid than CRP where its concentrations increases within 2-4
hours with peaks at 6- 8 hours post-exposure, like CRP, a sequential or
serial reading is more useful. In very low birth weight infants, PCT value
of >2.4 ng/mL indicates a high risk of neonatal sepsis. Like CRP, it can also be falsely elevated in non-infective conditions. If used in
conjunction with CRP, a positive level increases the diagnostic value up
to 92%.
(B) Evidence of
Multiorgan System Disease
The following may be performed based on
clinical suspicion of associated organ involvement.
1. Blood gas analysis
and lactate: Should be performed to determine extent of condition. Metabolic
acidosis with lactic acidaemia indicating progression to anaerobic metabolism.
2. Renal function,
liver function tests: Impairment indicating possible involvement.
3. Haematologic indices
and coagulation profile: Manifested as anaemia and thrombocytopaenia, as well
as disseminated intravascular coagulopathy.
4. Chest X-ray and/or
Abdominal X-ray: If accompanying respiratory or abdominal signs are seen.
5. Liver and renal
ultrasound – in cases of persistent sepsis
6. Echocardiography -
In cases of persistent sepsis
6.0 MANAGEMENT
Preventive strategies have been described earlier with emphasis on
recognition of peripartum risk factors. Initiation of antibiotics must be
prompt. Recognition of complications before progression to organ failure may be
difficult, but important as progression may be rapid.
Aims of Management
- Early
recognition with timely initiation of treatment
- Supportive
therapy a) Prevent
development of septic shock b) Recognise and
halt progression of complication (1)
(1) Early Recognition
with Timely Initiation of Treatment
Initiation of antibiotics
- Consideration
of early or late-onset presentation as well as exposures e.g. nosocomial
infection determines the choice of antibiotics. See antibiotic guidance in
section 7.0
- Avoid undue
delay in antibiotics initiation and initial empiric therapy should be
initiated with penicillin and aminoglycoside for EONS. However, in babies
determined not to have sepsis, antibiotic exposure should be minimised.
- Third generation
cephalosporin should only be reserved for suspected gram- negative
meningitis. The emergence of cephalosporin resistant organisms (e.g.
Enterobacter cloacae, Klebsiella, and Serratia sp) can occur when
cefotaxime is routinely used.
- Blood culture results should be traced within 48 to 72 hours and
antibiotics regimen adjusted based on susceptibility pattern. Therapy may be
discontinued should the results return as negative with no other parameters to
support the diagnosis of sepsis.
Adjunctive Treatment Strategies • Exchange
transfusion may be performed should sepsis be accompanied with late features
such as sclerema neonatorum. Exchange transfusion has been associated with
significantly less mortality of up to 50% in the exchange group compared to 95%
infants without exchange transfusion amongst infants who have developed
sclerema.
• IVIg augments
antibody dependent cytotoxicity with improvement on neutrophilic function.
However, sufficient evidence for its use in reducing death in neonatal sepsis
remains unproven (2) Supportive Therapy
- Sepsis with
rapid progression of its associated complications is termed fulminant
sepsis, which may lead to death within 48 hours of its onset.
- Infants who
acquire nosocomial sepsis, of lower gestation (extremely low gestational
age/ELGAN), and lower birth weight (extremely low birth weight/ELBW
<1000grams) are at higher risk of fulminant sepsis.
- Complications
associated with fulminant sepsis include:
- Worsening
respiratory status
- Haemodynamic
instability leading to septic shock
- Cardiac
dysfunction
- Coagulopathy
- Multiple organ
dysfunction
General supportive therapy aims to prevent
progression of fulminant sepsis by ensuring adequate ventilation and
maintenance of cardiovascular function.
Strategies to prevent multiorgan dysfunction
include:
- Maintenance of
the thermoneutral environment: Maintenance of
thermoneutral environment is required to prevent the sequelae of anaerobic
metabolism which worsens lactate acidaemia. The septic neonate often
develop temperature instability due to the infant’s inability to
auto-regulate the body temperature. Therefore, close temperature
monitoring and provision of adequate warmth which may be provided via
servo/auto-control warmer should be initiated.
- Provision of
adequate haemodynamic support: An infant who
has been determined to have sepsis should have close monitoring of vital
signs and blood pressure. Timely intervention with crystalloids is
required with signs of intravascular volume depletion, such as poor
perfusion, prolonged capillary refill time, poor pulse volume and
increasing tachycardia. There is insufficient evidence to support
aggressive and repeated volume expansion in the hypotensive preterm
neonate due to its possible association with intraventricular haemorrhage.
Therefore, after an initiation of fluid bolus, unless there is evidence of
acute volume loss, the neonate who remain hypotensive may be supported
with inotropic support.
- Provision of
adequate respiratory support: Septic infants often will have
accompanying pneumonia and/or recurrent apnoea with poor respiratory
effort. Ensure timely and adequate provision of respiratory supportive
therapy and oxygenation e.g. intubate the infant with repeated apnoeic
episodes.
- Glucose
monitoring: Glucose is an essential brain fuel and the increasing
metabolic demands can result in hypoglycaemia in the septic neonate.
Conversely, the resultant increase in production of stress hormones such
as adrenaline, cortisol and glucagons result in hyperglycaemia.
- Monitoring of
urine output: Strict charting of the infant’s input and output is required
to monitor for evidence of renal impairment. Fluids should be adjusted
accordingly based on the infant’s haemodynamic and renal status.
7.0 ANTIBIOTICS GUIDANCE
The following tables cover the major indications, duration and
dosages of common antibiotics used in the neonatal intensive care unit. The
list is not exhaustive, and management strategies for other specific infections
need to be discussed with the specialist in-charge.
The Four Moments/Principles of Antibiotics Decision and Administration
1. Identify source
of infection
2. Ensure blood cultures and cultures from appropriate anatomical
site performed and commence empiric therapy
3. Reassess at 48-72 hr:
a) Stop: if no evidence of
infection
b) Targeted therapy: based on culture results
c) Narrow spectrum: based on clinical response (based on site of
infection and if culture results negative (or no culture taken)
4. Duration of antibiotics based on the site of infection and types
of microorganism isolated
Escalation of therapy: consider escalation
of therapy if persistent or worsening signs of infection or deranged sepsis
parameters after 48 -72 hours of adequate antibiotic therapy and source
control.
7.1 Major Indications for the Use of Antibiotics in the NICU
Indications
|
Preferred
|
Alternative
|
Comments
|
Early onset sepsis
Commonest organisms: Group B Streptococcus Gram
negative rods (E. coli, Klebsiella sp.)
Less common: Staphylococci Streptococci Enterococci Haemophilus influenza Listeria monocytogenes
|
C-Penicillin
AND
Gentamicin*
|
C-Penicillin
AND
Cefotaxime
|
Targeting infecting organism acquired antenatally or intrapartum (The commonest organisms are from the
vaginal flora).
Ampicillin is preferred choice and
to replace Penicillin if Listeria infections suspected.
Cefotaxime should be used judiciously in the
neonatal unit. It is associated with increased rates of colonization with
strains resistant to the empirical therapy, with higher rates of Extended
Spectrum Beta Lactamase (ESBL) infections, invasive candidiasis and death.
However, it should be considered in infants with meningitis.
|
Late onset sepsis
· Coagulase negative Staphylococci, Staphylococcus aureus
· Gram negative rods (Pseudomonas
aeruginosa)
· Enterococci
· Candida spp.
|
C-Penicillin
OR
Cloxacillin
AND
Gentamicin*
OR
Amikacin*
|
C-Penicillin
OR
Cloxacillin
AND
Cefotaxime
|
Cloxacillin may be indicated if there are risk factors for sepsis from skin
organisms, e.g. multiple venepuncture or other invasive procedures.
Reserve
cephalosporin ONLY for treatment of meningitis. Consider adding cefotaxime if
meningitis is suspected.
Cefotaxime should be used
judiciously in the neonatal unit. It is associated with increased rates of
colonization with strains resistant to the empirical therapy, with higher
rates of Extended Spectrum Beta Lactamase (ESBL) infections, invasive
candidiasis and death.
Ceftriaxone
should be avoided in neonate because it displaces bilirubin from albumin
binding sites, resulting in a higher free bilirubin with subsequent blood
brain barrier penetration.
|
Hospital acquired/ nosocomial sepsis
|
Vancomycin*
AND
Cefepime
|
Escalation of therapy: Vancomycin
AND
Piperacillin-Tazobactam
OR
Meropenem
|
Targeting
nosocomial infections and
translocation of organisms across the immature gut wall. Associated
with indwelling lines, catheters and ET tubes.
Piperacillin-Tazobactam is a
reasonable second line option in pneumonia & intraabdominal sepsis
(non-CONS sepsis with good coverage against Gram positive, Gram negative
& anaerobes) with good sensitivity for Klebsiella, E.coli and moderate sensitivity for Acinetobacter from UMMC antibiogram.
Cefepime is the preferred
agent when there are Gram negative bacterial with extended spectrum
cephalosporin resistance due to AmpC-β-lactamases (Antibiogram shows reduced
sensitivity for Cefotaxime to Acinetobacter baumanii and Escherichia coli).
Targeted
therapy for Acinebacter baumanni is Ampicillin-Sulbactam
|
Meningitis
|
C-Penicillin
AND Cefotaxime
|
Hospital
Acquired:
Vancomycin*
AND
Meropenem
|
Consider
Vancomycin and Meropenem in hospital acquired sepsis with meningitis.
|
Ventilator-associated/ Nosocomial pneumonia
|
Target the recent tracheal secretion or throat swab culture result, if
negative, target the most prevalent organisms in the unit. If there is no specific
pattern of colonization or infection, follow the regime for hospital acquired
infection.
|
Catheter related blood stream and local skin and soft tissue infections
|
Vancomycin*
|
|
Vancomycin
is preferred for catheter related blood stream infection, but to descalate
therapy if culture is Methicillin Sensitive Staphylococcus Aureus (MSSA).
|
Necrotising enterocolitis and other intra-abdominal sepsis
Klebsiella spp. Escherichia coli Clostridia
spp. Coagulase negative Staphylococci Enterococci Bacteroides
|
First 7 days of life: Ampicillin AND Gentamicin* AND Metronidazole
> 7 days of
life: Cefepime
AND Metronidazole WITH/WITHOUT Vancomycin*
|
Escalation of therapy *Meropenem or Piperacillin-Tazobactam
WITH or
WITHOUT Vancomycin*
|
Use Vancomycin instead of ampicillin for
suspected MRSA and ampicillin-resistant enterococcal infection.
*Meropenem has the propensity to select out
multi-drug response organisms. To be used if persistent signs of infection or
deranged sepsis parameters after 48 -72 hours
of adequate antibiotic therapy and source control.
Consider adding antifungal if patient
continue to deteriorate despite on appropriate antibiotic or second line
therapy.
|
Fungal sepsis
|
Fluconazole
|
Escalation of therapy
Lipid
complex amphotericin B
|
In
infants with persistent signs, deranged sepsis parameters, and without
improvement in clinical symptoms despite on adequate antibiotic coverage and source control, fungal sepsis should be considered.
Risk
factors for fungal sepsis including use of TPN, gut perforation/ abdominal
surgical intervention, mechanical ventilation and prolonged use of broad
spectrum antibiotics.
|
7.2 General Guidance on the Recommended Duration of Antibiotic
Treatment
Types of Infection
|
Days
|
Suspected sepsis
|
If negative
blood culture, initial clinical suspicion not strong, reassuring clinical
condition & low CRP, consider stopping antibiotics at 48 hours
If negative blood
culture, very strong clinical suspicion of sepsis or elevated CRP, consider 5
days of antibiotics
|
Gram Positive Bacteraemia
Gram Negative
Bacteraeemia
Fungaemia
|
Repeat blood
culture at 48 to 72 hours of antibiotic.
At least 7 days of
antibiotics as guided by microorganism, clinical response, CRP and repeated
blood culture.
Repeat blood
culture at 48 to 72 hours of antibiotic.
At least 7-10 days
of antibiotics as guided by microorganism, clinical response, CRP and
repeated blood culture.
Repeat blood
culture every 72 hours of antifungal therapy.
Screening for
invasive fungal infection including opthalmological examination and
ultrasound abdomen.
At least 3 weeks
of antifungal from the time of negative blood culture.
|
Meningitis
Gram positive
meningitis
Gram negative
meningitis
Listeria
meningitis
|
Repeat CSF
biochemistry and culture at 48 hours of antibiotics.
14 days
21 days
21 days
|
Pneumonia
|
5 – 10 days depending on screening and extent of infection.
|
Catheter related blood stream infections
|
As in bacteraemia. At least 7 to 10 days of antibiotics as guided by
microorganism, clinical response, CRP and repeated blood culture. Remove
catheter (source control) if persistent bacteraemia.
|
Joint infection (Septic arthritis/ osteomyelitis)
|
4 – 6 weeks
|
Other specific infections such as urinary tract, skin and eye infections
|
5 – 10 days
|
7.3
Recommended Dosages for Common Antibiotics Prescribed in Neonates
Drug Name
|
Postmenstrual Age
|
Postnatal Day
|
Dose
|
C-Penicillin
|
|
|
100,000 units/kg/dose IV q12h
|
Ampicillin
|
< 30 weeks
30 – 36 weeks
37 – 44 weeks
≥ 45 weeks
|
0 – 28 days
> 28 days
0 – 14 days
> 14 days
0 to 7 days
> 7 days
All
|
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose IV q6h
|
Gentamicin*
|
< 30 weeks
30 – 35 weeks
> 35
weeks
|
|
2.5 mg/kg/dose IV
q24h
3.5 mg/kg/dose IV
q24h
4mg/kg/dose IV q24h
|
Amikacin*
|
< 30 weeks
30 – 35 weeks
> 35
weeks
|
|
7.5 mg/kg/dose IV
q24h
10 mg/kg/dose IV
q24h
15 mg/kg/dose IV
q24h
|
Cefotaxime
|
< 30 weeks
30 – 36 weeks
37 – 44 weeks
≥ 45 weeks
|
0 – 28 days
> 28 days
0 – 14 days
> 14 days
0 to 7 days
> 7 days
All
|
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose IV q12h
50mg/kg/dose IV q8h
50mg/kg/dose
IV q6h
|
Metronidazole
|
Loading dose
Maintenance dose
< 27 weeks
27 – 33 weeks
34 – 40 weeks
≥ 41 weeks
|
0 – 26 days
0 – 14 days
0 to 7 days
All
|
15mg/kg/dose IV x
1
7.5mg/kg/dose IV
q24h
7.5mg/kg/dose IV
q12h
7.5mg/kg/dose q8h
7.5mg/kg/dose IV q6h
|
Piperacillin + Tazobactam
|
< 30 weeks
30 – 36 weeks
37 – 44 weeks
≥ 45 weeks
|
0 – 28 days > 28 days
0 – 14 days
> 14 days
0 to 7 days
> 7 days
All
|
100mg/kg/dose IV q12h
100mg/kg/dose IV q8h
100mg/kg/dose IV q12h
100mg/kg/dose IV q8h
100mg/kg/dose IV q12h
100mg/kg/dose IV q8h
100mg/kg/dose IV q8h
|
Cefepime
|
|
0 – 28 days > 28 days
|
30mg/kg/dose IV q12h
50mg/kg/dose IV q12h
(Meningitis and
severe infection due to Pseudomonas aeruginosa / Enterobacter spp):
50mg/kg/dose IV q12h
|
Meropenem
|
< 32 weeks
≥ 32 weeks
|
< 14 days
≥ 14 days
< 14 days
≥ 14 days
|
20-40 mg/kg/dose q12h
20-40 mg/kg/dose
q8h
20-40 mg/kg/dose
q8h
30-40 mg/kg/dose
q8h
|
Vancomycin
Loading dose: Birth weight < 1 kg - 15 mg
Birth weight > 1 kg - 15 mg/kg
Post Menstrual Age
(weeks)
|
Appropriate For
Gestational Age
|
Small For
Gestational Age < 10th Centile
|
< 26
|
12.5 mg/kg daily
|
10 mg/kg daily
|
26 to < 27
|
15 mg/kg daily
|
12.5 mg/kg daily
|
27 to < 28
|
15 mg/kg daily
|
12.5 mg/kg daily
|
28 to < 29
|
10 mg/kg 12 hourly
|
15 mg/kg daily
|
29 to < 30
|
10 mg/kg 12 hourly
|
15 mg/kg daily
|
30 to < 31
|
12.5 mg/kg 12 hourly
|
10 mg/kg 12 hourly
|
31 to < 32
|
12.5 mg/kg 12 hourly
|
10 mg/kg 12 hourly
|
32 to < 33
|
15 mg/kg 12 hourly
|
10 mg/kg 12 hourly
|
33 to < 34
|
15 mg/kg 12 hourly
|
12.5 mg/kg 12 hourly
|
34 to <37
|
Loading dose 20 mg/kg then
20 mg/kg 12 hourly
|
15 mg/kg 12 hourly
|
Lo YL, van Hasselt JGC,
Heng SC, Lim CT, Lee TC, Charles BG. Population Pharmacokinetics of Vancomycin
in Premature Malaysian Neonates: Identification of Predictors for Dosing
Determination. Antimicrob.Agents Chemother.2010;54:2626-2632.
* Blood
for therapeutic drug monitoring must be performed if gentamycin, amikacin and
vancomycin are chosen as the therapeutic agent of choice. Closer
monitoring may especially be required in infants with hypoxia/ encephalopathy
and those undergoing therapeutic hypothermia.
The dosage may be changed in accordance to the drug’s peak and
trough blood levels.
REFERENCES
- Shane AL,
Sanchez PJ, Stoll BJ. (2017). Neonatal Sepsis. The Lancet. Oct
14;390(10104):1770-1780. doi: 10.1016/S0140-6736(17)31002-4.
- Wynn JL, Wong
HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA.(2014). Time for a
neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med;
15: 523–28
- Wynn JL, Wong
HR. Pathophysiology and Treatment of Septic Shock in Neonates. (2010).
Clin Perinatol; June ; 37(2): 439–479. doi:10.1016/j.clp.2010.04.002
- Boo NY, Cheah
IGS. (2016) Factors Associated with Inter-Institutional Variations In
Sepsis Rates Of Very-Low-Birth-Weight Infants In 34 Malaysian Neonatal
Intensive Care Units. Singapore Med J; 57(3): 144-152. doi:
10.11622/smedj.2016056
- Camacho-Gonzalez,
A., Spearman, P. W., & Stoll, B. J. (2013). Neonatal Infectious
Diseases. Evaluation of Neonatal Sepsis. Pediatric Clinics of North
America, 60(2), 367–389. doi:10.1016/j.pcl.2012.12.003
- Lo YL, van
Hassen JGC, Heng SC, Lim CT, Lee TC, Charles BG. Population
Pharmacokinetics of Vancomycin in Premature Malaysian Neonates:
Identification of Predictors for Dosing Determination. Antimicrob. Agents
Chemother. 2010; 54:2626-2632.
- Hsu AJ, Tamma
PD. Antibiotics Guidelines – Treatment Recommendations for Hospitalised
Children. Johns Hopkins Medicine.
- Neomed
Consensus Group. Australasian Neonatal Medicines Formulary. https://slhd.nsw.gov.au/rpa/neonatal/NeoMedPapeCopy.html.
Accessed in May 2020.
- Edwards MS.
(2019). Management and Outcomes of Sepsis in Term and Late Preterm
Infants. UptoDate. https://www.uptodate.com/contents/management-and-outcome-of-sepsis-in-term-and-late-preterm-infants/print.
Accessed in Jan 2019.
|