Journal of Prescribing Practice - Antimicrobial treatment of neonatal meningitis

Check your answers on page 42

Neonatal meningitis is characterised as an infection in the meninges, the protective membranes surrounding the brain and spinal cord, occurring within the first 28 days of life. Neonates are at their most susceptible to infection in this period due to the immature activation and function of their immune responses (Verklan et al, 2021).

When neonatal meningitis is suspected, early initiation of antimicrobial therapy is essential. Antibiotic therapy is guided by whether the infection is early onset (less than 7 days of age when the origin may be from in utero, maternal or at birth exposure) or late onset (after 7 days of life and origin of the causative pathogen may be environment, including hospital-acquired infection).

With early onset suspected meningitis, amoxicillin and cefotaxime are the antibiotics of choice until a specific organism is cultured and sensitivity known. Amoxicillin is a semi-synthetic penicillin, with bactericidal activity against both gram-positive and gram-negative organisms (Huttner et al, 2020). Cefotaxime, as a third-generation cephalosporin, has increased antimicrobial activity against gram-negative bacilli in addition to enhanced penetration across the blood–brain barrier when compared to gentamicin (National Institute for Health and Care Excellence (NICE), 2021) (Table 1).

Table 1. Neonatal meningitis antimicrobial therapy (NICE, 2021)

Causative agent	Therapy
Suspected infection with causative agent unknown	IV amoxicillin Neonate up to 7 days: 30 mg/kg every 12 hours. Increase to 60 mg/kg every 12 hours, in severe infection Neonate 7 to 28 days: 30 mg/kg every 8 hours. Increase to 60 mg/kg every 8 hours in severe infectionPLUSIV cefotaxime Neonate up to 7 days: 50 mg/kg every 12 hours Neonate 7 to 20 days: 50 mg/kg every 8 hours Neonate 21 to 28 days: 50 mg/kg every 6–8 hours
Confirmed gram-negative infection	IV cefotaxime Neonate up to 7 days: 50 mg/kg every 12 hours Neonate 7 to 20 days: 50 mg/kg every 8 hours Neonate 21 to 28 days: 50 mg/kg every 6–8 hours
Confirmed gram-positive bacterium	IV amoxicillin Neonate up to 7 days: 30 mg/kg every 12 hours. Increase to 60 mg/kg every 12 hours, in severe infection Neonate 7 to 28 days: 30 mg/kg every 8 hours. Increase to 60 mg/kg every 8 hours in severe infectionPLUSIV cefotaxime Neonate up to 7 days: 50 mg/kg every 12 hours Neonate 7 to 20 days: 50 mg/kg every 8 hours Neonate 21 to 28 days: 50 mg/kg every 6–8 hours
Confirmed positive for group B Streptococcus	IV benzylpenicillin 50 mg/kg every 12 hoursPLUSIV gentamicin* starting dosage of 5 mg/kg every 36 hours**
Confirmed positive for listeria	IV amoxicillin Neonate up to 7 days: 50–100 mg/kg every 12 hours Neonate 7 to 28 days: 50–100 mg/kg every 8 hoursPLUSIV gentamicin Neonate up to 7 days: 5 mg/kg every 36 hours* Neonate 7 to 28 days: 5 mg/kg every 24 hours*

* A dosage of 5 mg/kg every 36 hours is an off-label use of gentamicin. **

Gentamicin subsequent doses and intervals adjusted if necessary based on blood gentamicin concentrations.

***

Gentamicin given in an extended interval dose regime based on response (BNFc, 2024)

There should be regular evaluation of the neonate’s condition and response to treatment. Neonates have altered pharmacokinetic responses with a higher volume of distribution and less efficient metabolism and elimination of medications (Rivera-Chaparro et al, 2017). With the use of nephrotoxic and ototoxic antibiotics, such as gentamicin, regular monitoring of drug concentrations is required to ensure safe and effective therapy. Antibiotic regime may also require reconsideration in relation to local bacterial resistance patterns, as a specific antibiotic may be more appropriate than those recommended by universal guidelines.

Based on the information given in Table 1, what antimicrobial therapy should be prescribed?

QUESTION 1

Baby A, weight 3500 g and 4 days of age, is clinically unwell with suspected neonatal meningitis.

QUESTION 2

Baby B, weight 1700 g and 10 days of age, presents with suspected severe neonatal meningitis.

QUESTION 3

Baby C, weight 2200 g and 12 days of age with meningitis and confirmed gram-negative infection.

QUESTION 4

Baby D, weight 700 g and 2 days of age with meningitis and confirmed gram-positive infection.

QUESTION 5

Baby E, weight 2600 g and 10 days of age with confirmed group B Streptococcus meningitis. Baby E’s gentamicin concentration returns as greater than acceptable levels and the dose should be reduced by 20% prior to next administration. What is the recalculated dose?