6.0 - Neonatal Antibiotic Guideline

A/Prof Lai Nai Ming, Dr. Choo Yao Mun and Dr. Azanna Ahmad Kamar.

Overview
Infections in neonatal intensive care unit (NICU) are classified according to the time of onset.
Early onset blood stream infection (BSI) is defined as a positive result on one or more blood cultures of specimens drawn within the first 72 hours of life with clinical signs or symptoms suggestive of infection.1
Late onset BSI is defined as infection occurring after 72 hours as per above.
Incidence of early onset BSI in NICU UMMC was 1.7%2. The most common organism in early onset BSI in NICU UMMC was Group B streptococcus accounting for 42%. Other less common organisms were Haemophilus parainfluenza, Listeria monocytogenes, Moraxella sp, Bacilus sp, Pseudomonas aeruginosa, Streptococcus pneumoniae and Acinetobacter baumanii.2
Incidence of late onset BSI was 4.8%3 to 6.5%2. The most common organism in late onset BSI was Methicillin resistant Staph. Epidermidis (MRSE) accounting for 71.2% followed by Multi-drug resistant Acinetobacter baumanii (9.6%). Other less common organisms were Enterobacter sp (ESBL), Sternotrophomonas maltophilia, Enterobacter cloacae, Enterococcus faecalis, Staphylococcus aureus, Serratiamarcenens, Candida albican, Candida tropicalis, Citrobacterfreundii, Streptococcus mitis and Escherichia coli.2,3 
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.

Major Indications For The Use of Antibiotics In The NICU

Indications

Preferred

Alternative

Comments


Suspected early onset sepsis - empirical treatment

C-Penicillin
+ Gentamicin

Cloxacillin
Cefotaxime
Amikacin

Cloxacillin may be indicated early if there are risk factors for sepsis from skin organisms like staph aureus, e.g. multiple venepuncture or other invasive procedures.

 
Suspected late onset sepsis - empirical treatment

 
Vancomycin
+ Cefotaxime
 
Meropenem
 
Targeting MRSE and gram negative organisms respectively
 
Meningitis 
 
C-Penicillin
Cefotaxime
 
Meropenem
 
 
Ventilator-associated pneumonia
 
Target the recent throat swab or tracheal secretion 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 suspected late onset sepsis.

 
Aspiration pneumonia
 
Cloxacillin
+ Gentamicin

   
 
Catheter related blood stream and local infections

 
Vancomycin
   
 
Necrotising enterocolitis and other intra-abdominal sepsis
 
Vancomycin
+ Meropenem
+ Metronidazole if there is high risk of GI perforation on clinical assesment

   
 
Fungal sepsis

 
Fluconazole
 
Amphotericin B
 

Risk factors for early onset sepsis (< 72 hours of life)4:
  • Maternal GBS (Group B Streptococcus) carrier (high vaginal swab [HVS], urine culture, previous pregnancy of baby with GBS sepsis)
  • Prolonged Rupture of Membranes (PROM) (> 18 hours)
  • Preterm labour / PPROM
  • Maternal pyrexia > 38˚C, maternal peripartum infection, clinical chorioamnionitis, discoloured or foul-smelling liquor, maternal urinary tract infection
  • Septic or traumatic delivery, fetal hypoxia
  • Infant with galactosaemia (increased susceptibility to E. coli)
Risk factors for late onset sepsis (72 hours of life and beyond)4:
  • Any indwelling intravascular access - central venous line, arterial line, umbilical catheter 
  • Low gestational age 
  • Low birth weight 
  • Mechanical ventilation
General Guide On Recommended Duration of Antibiotic Treatment

Types of Infection

Days


 Suspected sepsis
 
3 (preliminary blood culture results negative) to 10

 
Meningitis
 
14 - 21
(depending on organism isolated)

 
Pneumonia
 
5 - 10

 
Catheter related blood stream infections
 
10 - 14

 
Catheter related local infections
 
7 - 14

 
Other specific infections such as urinary tract, skin and eye infections

 
5 - 10

Recommended Dosages For Common Antibiotics Prescribed In The NICU

Drug Name

Gestational Age

Dose


C-Penicillin



100,000 units/kg/dose 12 hourly


Gentamicin*

< 30 weeks


2.5 mg/kg/dose daily

30 - 35 weeks


3.5 mg/kg/dose daily

> 35 weeks


4 mg/kg/dose daily

Amikacin*

< 30 weeks

7.5 mg/kg/dose daily

30 - 35 weeks

10 mg/kg/dose daily


> 35 weeks


15 mg/kg/dose daily

Cefotaxime

0 – 1 week


50 mg/kg/dose 12 hourly

> 1 week


50 mg/kg/dose every 8 hours

Meropenem

0 – 1 week


20 mg/kg/dose 12 hourly

> 1 week

20 mg/kg/dose 8 hourly


Vancomycin* Regimen5
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

* Blood for therapeutic drug monitoring must be performed if gentamycin, amikacin and vancomycin are chosen as the therapeutic agent of choice. 
The dosage may be changed in accordance to the drug’s peak and trough blood levels.

Group B Streptococcal Sepsis Screening
We follow the algorithm developed by the Centre of Disease Control, USA6, as detailed below, for infants whose mothers have positive high vaginal swab for Group B Streptococcus (GBS):


* Full blood count and differentials, blood culture, Chest X Ray (if respiratory signs are present) and lumbar puncture (if patient is stable enough to tolerate procedure)
** The first line antibiotic is C Penicillin and Gentamicin.
Full blood count and differentials, blood culture. 

If ≥ 37 weeks’ gestation, observation may occur at home after 24 hours if other discharge criteria have been met, access to medical care is readily available, and a person who is able to comply fully with instructions for home observation will be present. If any of these conditions is not met, the infant should be observed in the hospital for at least 48 hours and until discharge criteria are achieved.

Other Specific Conditions 
For example, congenital syphilis, congenital varicella infection and infants of mothers with Hepatitis B, Malaysian Paediatric Protocol 3rd edition4 is used as reference and the soft copy is available in “NICU protocol” folder at the computer in NICU.

References
1. Kaufman D, Fairchild K. Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants. ClinMicrobiol Rev. 2004;17(3):638–680.
2. Zaqrul P. Neonatal Blood Stream Infection, Early and Late Onset in Special Care Nursery University Malaya Medical Centre, Kuala Lumpur from 1st January 2005 to 30th September 2009. Masters of Paediatrics University Malaya Thesis May 2010.
3. Tan CL, Choo YM, Salleh S, Lim CT. Audit of 12-months Review of Early and Late Onset Blood Stream Infection Year 2011 in Neonatal Unit in University Malaya Medical Centre.
4. Hussain Imam MI, Ng HP, Thomas T. Paediatric protocols for Malaysian Hospitals, 3rd Edition. Malaysian Ministry of Health.
5. 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.
6. Centers for Disease Control and Prevention. Group B Strep: Guidelines – Neonatal Providers. http://www.cdc.gov/groupbstrep/clinicians/neonatal-providers.html