Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia

Aims-To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febr ile neutropenia in children with cancer. Subjects-59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) wi th febrile neutropenia (neutrophil count < 0.5 x 10(9)/l) after chemotherap y. Methods-Over one year, 113 febrile neutropenic episodes were treated empiri cally with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours. Results-86 of the 113 episodes settled with the first line antibiotic regim en. In 29 episodes. blood cultures identified a causative bacterial pathoge n; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining e ight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseud omonas aeruginosa. In 27 episodes (24%), resolution was obtained by the emp irical introduction of a second line regimen of ceftazidime and a glycopept ide antibiotic, and/or amphotericin. Gentamicin concentrations were measure d in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), seru m creatinine rose transiently by more than 50% of the baseline concentratio n. Although there was no vestibular toxicity, three of 30 children who unde rwent pure tone audiometry reported high frequency hearing loss in one ear. Conclusion-OD gentamicin can be used safely and effectively to treat febril e neutropenia in children with cancer. When used for a short period (< 5 da ys), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.