5.0 - Neonatal Antibiotic Guideline

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

  1. 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.)

 

  1. 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.
  2. 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.
  3. 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

  1. Early recognition with timely initiation of treatment
  2. Supportive therapy                                                                                                                                                                                                                                                                                                    a) Prevent development of septic shock                                                                                                                                                                                                                                                                                                                                                               bRecognise 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

< 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

 

15mg/kg/dose IV x 1

 

 

7.5mg/kg/dose IV q48h

7.5mg/kg/dose IV q24h

 

7.5mg/kg/dose IV q24h

7.5mg/kg/dose IV q12h

 

7.5mg/kg/dose IV q24h

7.5mg/kg/dose IV q12h

 

7.5mg/kg/dose IV q8h

 

 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

 

  1. 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.
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  6. 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.
  7. Hsu AJ, Tamma PD. Antibiotics Guidelines – Treatment Recommendations for Hospitalised Children. Johns Hopkins Medicine.
  8. Neomed Consensus Group. Australasian Neonatal Medicines Formulary. https://slhd.nsw.gov.au/rpa/neonatal/NeoMedPapeCopy.html. Accessed in May 2020.
  9. 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.