Prediction of flucytosine-induced thrombocytopenia using creatinine clearance

To evaluate and investigate the efficacy and accuracy of an earlier derived relationship between thrombocyte nadir and mean creatinine clearance in order to make it possible to predict flucytosine (5-FC)-related thrombocytopenia.

The earlier derived relationship between thrombocyte nadir and mean creatinine clearance is validated using a patient population of 35 intensive care unit (ICU) patients. Patients have to meet the inclusion criteria as defined in the initial study (i.e., developing thrombocytopenia during 5-FC treatment or remaining within the normal thrombocyte range; individual pharmacokinetic parameters within certain limits; a minimum of three measured 5-FC serum levels).

Of a total of 35 patients, 11 are eligible since they meet the inclusion criteria as defined in the initial study. A significant relationship between the observed and predicted thrombocyte nadir values can be derived: Y(pred) = 0.608.X(obs) + 24. 330 (r = 0.615; t(obs) = 2.337; t at p < 0.05 and 9 degrees of freedom = 2.262). The predicted value of the thrombocyte nadir corresponds with a mean prediction error (bias) of -18.3 (95% CI -45.9; 9.4) and a root mean squared prediction error (precision) of 48.3 (95% CI 23.9-63.9).

The earlier derived relationship between thrombocyte nadir and mean creatinine clearance is accurate and precise. However, due to the strict inclusion criteria used to derive and validate this relationship, it cannot be applied to all 5-FC-treated patients.