Development of a once daily gentamicin regimen for paediatric surgery patients

S. Kasuji, P. Gadaria. Pharmacy department, Leeds Children's Hospital

Aims

Method

Results

Conclusion

References

1. Winter ME. Basic clinical pharmacokinetics. Fourth edition. San Francisco. Lippincott Williams & Wilkins. 2004. 2. Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, et al. Extended interval aminoglycoside administration for children: a meta-analysis. Pediatrics. 2004;114:111-118.

A once daily gentamicin regimen of 7mg/kg was found to achieve therapeutic levels in paediatric surgery patients who met the inclusion criteria when administered in accordance with the local prescription chart. A further audit is planned to determine if the new dosage regimen affects the clinical outcome.

Intravenous gentamicin is given as a 5 day course to paediatric patients who have undergone abdominal surgery. There was an impression that the multiple daily dosing regimen in use at the time (2.5mg/kg three times a day) did not provide therapeutic levels in this patient cohort therefore the aim was to develop a dosing regimen that did.

A retrospective audit of pre- and post-dose gentamicin levels in patients on a multiple daily dose regimen was undertaken. Data was gathered using a microbiology database and children aged between 1 month and 16 years who had gentamicin prophylaxis following abdominal surgery between January 2005 and January 2010 were included.. Following on from the initial audit a once daily gentamicin dosing regimen was introduced for all patients who met the inclusion criteria: child aged over 1 month of age without ascites, cystic fibrosis, endocarditis, major burns or significant renal impairment and not pregnant. The once daily dose chosen was based on BNF-c guidance and an administration guideline was incorporated into a prescription chart. A survey of 9 hospitals and a literature review (table 1) was conducted to determine when gentamicin levels were monitored. Once the regimen had been in place for 12 months a prospective audit of trough levels was undertaken.

Hospital Dose Max dose Problems with high levels

etc.

Time of first gentamicin

level

Lab processing hours

Bristol Royal Hospital for

Children

No written policy dose

varies from 4mg/kg to

5mg/kg once daily

- no Pre-second dose. Wait for

level to come back before

second dose given.

24/7 (biochemistry)

Royal Liverpool Children’s

Hospital

7mg/kg once daily

420mg no 18-24 hours after dose

given. Wait for levels to

return before second dose

given

24/7 (biochemistry)

Royal Victoria Hospital

(Newcastle)

7mg/kg once daily

- no Pre-second dose. Second

dose is given before levels

return

8.30am to 10pm

(microbiology). After

10pm must contact the on

call microbiologist who

will decide whether the

assay is urgent.

North Staffordshire

7mg/kg once daily

- no Pre-dose level taken

before third dose. Don’t

wait for levels to return

before third dose given.

On-call service overnight

Whittington Hospital 7mg/kg once daily

400mg no Pre-second dose. Second

dose is given before levels

return

Not processed over night

Newcastle upon Tyne 7mg/kg once daily

N/A - - -

Sheffield Children’s

Hospital

6mg/kg once daily

N/A

In-house nomogram used Level taken 12-24 hours

after dose given; wait for

levels to return before

second dose given

1pm and 4pm daily; if

required outside of these

hours contact the on call

microbiologist

University Hospital

Leicester

7mg/kg once daily

- Hartford nomogram used Levels taken 6-12 hours

after first dose as per

nomogram

Doses not withheld whist

waiting for levels.

Royal hospital for sick

children (Glasgow)

7mg/kg once daily

- no Level taken before second

dose. Out of hours sample

taken and stored in fridge

until the morning and

then sent to lab.

Not overnight

Guys and St Thomas’ and

Lewisham hospitals

5-8mg/kg once daily - no Processed 24/7 - results

usually available In 8

hours

Table 1 (data collected in 2010). – indicates no data

Multiple day dosing 336 children were reviewed, of these 35 had incomplete data and were excluded. Data was analysed from 301 children, 207 (68.7%) had a post dose below the recommended therapeutic range (5-10mg/L) and the dose was increased by 10%. 132/207 of this subset had a second post dose measured. See Chart 1 below: Overall, only 31.2% of children had gentamicin levels within the therapeutic range during the course of treatment.

Once daily dosing The Hartford nomogram has not been validated for use in children therefore it cannot it be applied to this patient cohort. The literature review and survey of practice revealed that with once daily dosing a peak gentamicin level does not need to be measured, as it is assumed that with a 7mg/kg dose the pharmacodynamic goal of achieving a peak to minimum inhibitory concentration ratio greater than 104 will be achieved1,2. Therefore, it is routine practice to only measure the trough level1 to ensure there is no toxicity. Thirty patients were audited after the introduction of the once daily regimen and 100% of patients had a trough level of ≤1mg/L.