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. DESIGN: Open and prospective. SETTING: Tertiary referral multi-disciplinary ICU. PATIENTS: Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years). INTERVENTIONS: 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. MEASUREMENTS AND 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.

Poor discriminatory performance of the Pediatric Risk of Mortality (PRISM) score in a South African intensive care unit.

OBJECTIVE: The use of the Pediatric Risk of Mortality (PRISM) score or other scoring systems in the intensive care unit (ICU) is of great importance for evaluating the efficacy and efficiency of a particular ICU. However, the PRISM score was developed and validated in the United States and subsequently validated in Europe, but has not been evaluated in a less affluent society. In general, scoring systems should be used only in populations similar to the reference population in which the prediction model was developed. We set out to determine the applicability of the PRISM score at Baragwanath Hospital, South Africa. DESIGN: Prospective, descriptive study. SETTING: Twenty-four-bed multidisciplinary ICU. PATIENTS: We analyzed 1,528 consecutive pediatric admissions from January 1989 to June 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM scores, Therapeutic Intervention Scoring System scores, demographic, and clinical data collected prospectively were entered and stored by means of a commercial software package at the time of admission of each patient. The prediction of actual mortality by PRISM scoring was evaluated by the Hosmer and Lemeshow goodness-of-fit test (chi2[8 degrees of freedom]). Receiver operating characteristic curves were constructed and compared with those curves from pediatric ICU populations in the United States and Europe. Individual receiver operating characteristic curves were constructed for surgical and nonsurgical patients, age categories, and diagnostic categories. Compared with European and American ICU populations, our patients were younger, were mostly nonsurgical emergency admissions, stayed longer in the ICU, and were more severely ill with a higher admission PRISM score and overall mortality rate. Respiratory and septic diagnoses predominated, with very few surgical cases admitted. The Hosmer and Lemeshow goodness-of-fit test showed a significant failure of the PRISM scoring system to accurately predict mortality over a wide range of expected mortality rates (chi2[8 degrees of freedom] = 465, p = 0). Similarly, receiver operating characteristic analysis indicated a poor predictive power (Az = 0.73 +/- 0.01 [SEM]), with an area under the curve significantly less than that for the PRISM reference population (p = 0). PRISM showed equally poor discriminatory function at all age groups and diagnostic categories. CONCLUSIONS: The PRISM score needs to be recalibrated or recalculated for our patient population in view of the high discrepancy and poor discriminatory function shown. Part of the inaccuracy may derive from different demographic characteristics of our ICU population and a different pattern of diseases. It appears that PRISM is not population independent.