PAEDIATRIC
PAEDIATRIC
NEONATAL INFECTIONS
1.1 Meningitis
Common organisms:
GBS
E. coli
Listeria
Other Gram-negative bacilli/rod (GNR)
Preferred
Empirical therapy
Benzylpenicillin (Penicillin G) 150,000 units/kg/dose
GA ≤ 34 weeks:
PNA ≤ 7 days: q12h
PNA > 7 days: q8h
GA >34 weeks:
PNA ≤ 7 days: q8h
PNA > 7 days: q6h
OR
Ampicillin
≤ 1 week of age: 200-300mg/kg/day IV in 3 divided doses
> 1 week of age: 300mg/kg/day IV in 4 divided doses
PLUS
Cefotaxime 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
Alternative
Cefepime 50mg/kg/dose IV q12h
SEVERE CNS infections (if hospital-acquired):
Meropenem 40mg/kg/dose IV
< 32 weeks, <14 days: q12h
< 32 weeks, ≥14 days: q8h
≥ 32 weeks: q8h
Comments
Adjust antibiotics and duration accordingly once cultures are known (refer to 2.1.2)
1.2 Necrotising Enterocolitis (NEC)
Common organisms:
Klebsiella
E. coli
Clostridia
Coagulase-negative Staphylococci
Enterococci
Bacteroides
Preferred
Stage 1
Ampicillin 100mg/kg/dose IV
≤ 1 week of age: q12h
>1 week of age: q8h
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
PLUS
Metronidazole
Loading dose: 15mg/kg/dose IV
Maintenance dose:
≤ 34 weeks of age: 7.5mg/kg/dose IV q12h
35-40 weeks of age: 7.5mg/kg/dose IV q8h
> 40 weeks of age: 10mg/kg/dose IV q8h
Stage 2 / Stage 3
Cefotaxime 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
PLUS
Metronidazole
Loading dose:15mg/kg/dose IV
Maintenance dose:
≤ 34 weeks of age: 7.5mg/kg/dose IV q12h
35-40 weeks of age: 7.5mg/kg/dose IV q8h
>40 weeks of age: 10mg/kg/dose IV q8h
Duration: 10-14 days
Alternative
--
Comments
There is insufficient evidence regarding the duration of antibiotic treatment for NEC. This suggested regimen for NEC is empirical. Once culture is known, decisions regarding choice of antibiotics are best guided by culture results.
Use vancomycin if CoNS/MRSA is suspected (substitute Ampicillin with Vancomycin).
1.3 Early Onset Sepsis (< 48 hours)
Common organisms:
Group B Streptococcus (GBS)
Listeria
Streptococcus sp.
E. coli
Haemophilus influenza
Klebsiella sp. etc.
Preferred
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA ≤ 34 weeks:
PNA ≤ 7 days: q12h
PNA >7 days: q8h
GA > 34 weeks:
PNA ≤ 7 days: q8h
PNA >7 days: q6h
OR
Ampicillin 200-300mg/kg/day IV
≤ 1 week of age: in 3 divided doses
> 1 week of age: in 4 divided doses
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
Alternative
--
Comments
Consider stopping antibiotics at 36-48 hours if negative blood culture, initial clinical suspicion not strong and reassuring baby’s condition with low CRP.
If positive blood culture or strong clinical suspicion of sepsis but negative culture, may give 7 days of antibiotics.
Consider antibiotics for more than 7 days if baby not fully recovered and based on pathogen identified on blood culture.
In this empiric therapy - meningitis is not a consideration.
Once cultures are known, adjust antibiotics accordingly.
1.4 Late Onset Sepsis (> 48 hours)
Common organisms:
Methicillin-sensitive/resistant S. aureus (MSSA/MRSA)
Coagulase- negative Staphylococci (CoNS)
Gram-negative rods (Depending on local epidemiological data)
Preferred
First line
Cloxacillin 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
PLUS
Gentamicin 5mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Second line
Piperacillin/tazobactam IV
PMA ≤ 30 weeks: 100mg/kg/dose q8h
PMA > 30 weeks: 80mg/kg/dose q6h
< 30 weeks
0-28 days: 100mg/kg q12h
> 28 days: 100mg/kg q8h
30-36 weeks
0-14 days: 100mg/kg q12h
> 14 days: 100mg/kg q8h
37-44 weeks
0-7 days:100mg/kg q12h
> 7 days: 100mg/kg q8h
≥ 45 weeks: 100mg/kg q8h
Alternative
First line
Amikacin 15mg/kg/dose IV
< 30 weeks of CGA: q48h
30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Second line
Cefepime IV
Term and Prem younger than 28 days of life: 30mg/kg/dose q12h
Term and Prem greater than 28 days of life: 50mg/kg/dose q12h
Comments
For late onset sepsis, the most common organisms are predominantly Gram-positive cocci, namely Staphylococci, especially CONS, in premature neonates and also neonates with central catheters.
Piperacillin/tazobactam is a good second line option in pneumonia and intra-abdominal sepsis (non–CONS sepsis with good coverage against Gram-positive, Gram-negative & anaerobes).
There is possibility of Gram-negative rods with inducible β-lactamases and ESBL producing organism such as Klebsiella, Serratia and E. coli in some NICU in Malaysia hence need to look at local epidemiology before deciding on suitable second line.
Cefepime is the preferred agent when there are Gram-negative bacteria with extended spectrum cephalosporin resistance due to AmpC-β-lactamases (also termed Class C or Group 1).
Duration: If positive blood culture or strong clinical suspicion of sepsis but negative culture, may give 7 days of antibiotics.
Consider antibiotics for more than 7 days if baby not fully recovered, based on site of infection & pathogen identified on blood culture.
1.5 Congenital Syphilis
T. pallidum
Preferred
Benzylpenicillin (Penicillin G) 50,000 units/kg/dose IV
For first 7 days of life: q12h
Thereafter: q8h
Duration: 10 days*
If diagnosed with congenital syphilis after one month of age
Benzylpenicillin (Penicillin G) 200,000-300,000 units/kg/day IV in 4-6 divided doses for 10-14 days.
In infants considered less likely to have syphilis and normal CSF examination including normal physical examination & long bone radiograph
Benzathine penicillin 50,000 units/kg/dose IM in a single dose can be given.
Alternative
Procaine penicillin 50,000 units/kg/dose IM in a single daily dose for 10 days.*
Comments
Only severe cases are clinically apparent at birth.
Refer to algorithm for diagnosing & evaluation.
Re-evaluate & possibly re-treat. Please refer Red Book 2021 & Malaysian Paediatric Protocol 4th edition.
*14 days if CSF abnormal
1.6 Congenital Toxoplasmosis
T. gondii
Preferred
*Pyrimethamine/sulfadoxine (Fansidar®)
*Pyrimethamine 1.25mg/kg/dose PO every 10 days
PLUS
Sulfadoxine 25mg/kg/dose PO every 10 days
PLUS
Folinic acid 50mg PO every 7 days for 12 months*
Alternative
*Pyrimethamine 1mg/kg/day PO for 2 months, followed by 0.5 mg/kg/day PO for 10 months
< 60kg: up to 50mg/day
≥ 60kg: up to 75mg/day
PLUS
*Sulfadiazine 100mg/kg/day PO in 2 divided doses for 12 months*
PLUS
Folinic Acid 50 mg PO every 7 days for 12 months
Comments
Drug regimen is not definitively established. Clinical trials are ongoing.
Prednisolone 0.5 mg/kg (max. 20 mg/dose) q12h can be added if CSF protein ≥ 1g/dL or active severe chorioretinitis. Steroids given till CSF protein < 1g/dL or resolution of severe chorioretinitis.
Fansidar is currently an “orphan” drug that needs special procurement measures to buy. Refer to paediatric ID consultant for treatment and availability of drug.
*Requires DG’s Approval
*Total duration may be extended up to 2 years depending on severity and response to treatment.
1.7 Herpes simplex Neonatal
Localised skin, eye & mouth (SEM)
Central nervous system (CNS) with or without SEM
Disseminated disease involving multiple organs
Preferred
Acyclovir 20mg/kg/dose IV
< 30 weeks: q12h
≥ 30 weeks: q8h
Duration:
Skin, eyes, mouth: 14 days
CNS/disseminated: minimum of 21 days
All infants surviving neonatal HSV infection of any classification should receive oral acyclovir suppression at 300mg/m2/dose administered 3 times daily for 6 months after completion of parenteral therapy (adjust dose monthly to account for growth).
Alternative
--
Comments
Screen for other STDs.
For CNS disease:
Repeat lumbar puncture at end of therapy for HSV PCR. If PCR remains positive, continue IV acyclovir for another one week.
Recurrence of HSV can occur and may be a lifelong problem.
1.8 Tetanus Neonatorum
Preferred
Metronidazole
PMA < 34 weeks:7.5 mg/kg/dose IV q12h
PMA 35-40 weeks: 7.5 mg/kg/dose IV q8h
PMA > 40 weeks: 10mg/kg/dose IV q8h
Duration: 7 to 10 days
Alternative
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA < 34 weeks:
PNA ≤ 7 days: q12h
PNA > 7 days: q8h
GA > 34 weeks:
PNA ≤ 7 days: q8h
PNA > 7 days: q6h
Comments
IM Human Tetanus Immunoglobulin 250-500 IU for neutralizing of unbound toxin.
Antibiotics may fail to eradicate C. tetani unless adequate wound debridement is performed.
1.9 Congenital Gonococcal Ophthalmitis/Conjunctivitis
Preferred
Immediate & frequent saline eye irrigation.
Non-disseminated disease:
Cefotaxime 100mg/kg/dose IV in a single dose.
May need to continue for 48-72h until systemic infection has been ruled out.
Disseminated disease:
Cefotaxime 50mg/kg/dose IV
≤ 1 week of age: q12h
> 1 week of age: q8h
Duration: 7 days. 10–14 days if meningitis is documented.
Alternative
--
Comments
Evaluate for signs of disseminated infection (E.g.: sepsis, arthritis & meningitis).
Screen mother & baby for chlamydial infection.
Screen for other STDs.
Investigate and treat parents.
1.10 Chlamydia trachomatis Conjunctivitis
Preferred
Erythromycin ethylsuccinate 12.5mg/kg/dose q6h PO
Duration: 14 days*
Local eye toilet until discharge stops.
Alternative
Azithromycin 20 mg/kg/day PO, once daily for 3 days. (Limited data on efficacy)
Comments
Initial treatment for chlamydial conjunctivitis should be based upon a positive diagnostic test.
Re-swab after treatment; 20-30% will need a second course to clear infection.
* Second course of treatment might be required
2.1 Streptococcus agalactiae
2.1.1 Sepsis
Preferred
Benzylpenicillin (Penicillin G) 100,000 units/kg/dose IV
GA ≤ 34 weeks:
PNA ≤ 7 days: q12h
PNA > 7 days: q8h
GA >34 weeks:
PNA ≤ 7 days: q8h
PNA >7 days: q6h
OR
Ampicillin
≤ 1 week of age: 200-300 mg/kg/day IV in 3 divided doses
> 1 week of age: 300 mg/kg/day IV in 4 divided doses
PLUS
*Gentamicin 5 mg/kg/dose IV
< 30 weeks of CGA: q48h
> 30-34 weeks of CGA: q36h
≥ 35 weeks of CGA: q24h
Alternative
--
Comments
Duration of treatment for GBS:
Uncomplicated (bacteremia without a defined focus): 14 days
Meningitis: 21 days
*Gentamicin can be discontinued once the infection is under control.
2.1.2 Meningitis
Preferred
Benzylpenicillin (Penicillin G) 150,000 units/kg/dose
≤ 34 weeks of age:
PNA ≤ 7 days: q12h
PNA >7 days: q8h
> 34 weeks of age:
PNA ≤ 7 days: q8h
PNA >7 days: q6h
OR
Ampicillin
≤ 1 week of age: 200-300 mg/kg/day IV in 3 divided doses
> 1 week of age: 300 mg/kg/day IV in 4 divided doses
PLUS
Gentamicin 5 mg/kg/dose IV
< 30 weeks of CGA: q48h
> 30-34 weeks of CGA: q36h
≥ 35 weeks CGA: q24h
Alternative
--
Comments
Duration for treatment: 21 days
For uncomplicated meningitis, may consider repeat lumbar puncture 48-72 hours. If CSF culture negative, gentamicin can be stopped and continue penicillin/ampicillin for 2 weeks
Doses of penicillin for meningitis is higher as recommended by experts (as high as 500,000 unit/kg/day (> 7 days of age).
2.2 E. coli
2.2.1 Sepsis/Meningitis
Preferred
Cefotaxime 50mg/kg/dose IV
All GA with PNA < 7 days: q12h
GA <32 weeks with PNA ≥ 7 days: q8h
GA ≥ 32 weeks with PNA ≥ 7 days: q6h
PLUS
Gentamicin 5 mg/kg/dose IV
≤ 30 weeks of CGA: q48h
> 30-34 weeks of CGA: q36h
≥35 weeks CGA: q24h
Alternative
--
Comments
Duration in bacteremia: 14 days.
Duration for meningitis: 21 days.
All cases of bacteremia need lumbar puncture to exclude meningitis.
Treatment duration of 14 days can be decided on a case-by-case basis if meningitis is excluded and good clinical response.
References:
Congenital syphilis. 2015 Treatment Guidelines. Available at https://www.cdc.gov/std/tg2015/congenital.htm
Yvonne A. Maldonado, MD, FAAP, Jennifer S. Read. Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States. PEDIATRICS Volume 139, number 2, February 2017:e 20163860.
Swetha G. Pinninti, David W. Kimberlin. Neonatal Herpes Simplex Virus Infections. Seminars in Perinatology 42(2018) 168-175
Christina W. Obiero, Anna C. Seale, James E. Berkley. The Pediatric Infectious Disease Journal • Volume 34, Number 6, June 2015
The Sanford Guide to Antimicrobial therapy 2022
IBM Micromedex Neofax version number v103_1904032104
Minocha A. Joint Trust Guidelines for the Management of Necrotising Enterocolitis in Neonates and Infants. NHS Clinical Guidelines and Assessment Panel (CGAP) 2021
CHOC Children’s Hospital. Neonatal Necrotizing Enterocolitis (NEC) Care Guideline 2021
Puopolo KM, et al. Management of Neonates Born at ≥ 35 0/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. American Academy of Pediatrics 2018; volume 142, number 6
American Academy of Paediatrics. Commitee on Infectious Diseases. Red Book: Report of the Committee on Infectious Diseases (2021)
The Royal Hospital for Women. Australasian Neonatal Medicines Formulary (ANMF) 2019
Malaysian Paediatric Association. Paediatric Protocols for Malaysian Hospitals 4th Edition 2018
BNFC 2022-2023
National Institute for Health & Care Excellence (NICE): Neonatal infection: antibiotics for prevention and treatment. Published: 20 April 2021 Last updated: 19 March 2024.