Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much ciprofloxacin is enough?
OBJECTIVE
To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis.


METHODS
Open and prospective.


METHODS
Tertiary referral multi-disciplinary ICU.


METHODS
Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years).


METHODS
Timed blood samples were taken for pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then between days 6-8.


RESULTS
Ciprofloxacin serum levels were measured by high performance liquid chromatography. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (C(max)) for group A were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (C(min)) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3, 18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. C(max) in these patients were higher than the average C(max). The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease.


CONCLUSIONS
There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.
Lipman
J
J
Intensive Care Facility, Royal Brisbane Hospital, Anaesthesiology and Critical Care, University of Queensland, Herston Road, Herston 4029, Brisbane, Queensland, Australia. j.lipman@mailbox.uq.edu.au
Gous
A G S
AG
Mathivha
L R
LR
Tshukutsoane
S
S
Scribante
J
J
Hon
H
H
Pinder
M
M
Riera-Fanego
J F
JF
Verhoef
L
L
Stass
H
H
D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002675:Child, Preschool; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D011446:Prospective Studies; D012640:Seizures / Q000139:chemically induced; D018805:Sepsis / Q000378:metabolism*
D000890:Anti-Infective Agents; D002939:Ciprofloxacin