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 

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 

Adjust antibiotics and duration accordingly once cultures are known (refer to 2.1.2)

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 

--

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).

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

--

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.  

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

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

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.

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.

Procaine penicillin 50,000 units/kg/dose IM in a single daily dose for 10 days.*

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 

*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*

*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

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.

 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).

--

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. 

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 

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

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. 

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.

--

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. 

Erythromycin ethylsuccinate 12.5mg/kg/dose q6h PO

Duration: 14 days*

Local eye toilet until discharge stops. 

Azithromycin 20 mg/kg/day PO, once daily for 3 days. (Limited data on efficacy) 

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

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

--

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. 

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

--

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).

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 

--

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.