Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia

Abstract

Aims-To evaluate the pharmacokinetics of once daily (OD) gentamicin and its eVectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer. Subjects-59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 × 10 9 /l) after chemotherapy. Methods-Over one year, 113 febrile neutropenic episodes were treated empirically 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 regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; 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 eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured 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%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear. Conclusion-OD gentamicin can be used safely and eVectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary. (Arch Dis Child 1999;80:125-131)

Clinical Issues Surrounding Once‐Daily Aminoglycoside Dosing in Children

“…49 The remaining 24% of patients required vancomycin and ceftazidime due to unresolved fever with or without the presence of organisms resistant to first-line agents. 49 Others demonstrated 92% of febrile episodes (272/303) resolving clinically without a change in empiric antibiotic treatment. 50 Similarly, a clinical cure rate of 100% (25/25) was achieved in patients treated with once-daily amikacin.…”

“…6,11,[44][45][46][47][48][49][50][51][52][53][54][55][56] This regimen also was investigated in neonates up to 1 month of age but is not discussed here due to the decreased renal function in that patient population. Infectious processes included neutropenic fever, suspected or confirmed gramnegative infections, cystic fibrosis, and suspected or confirmed surgical infections.…”

“…Nine studies evaluated clinical and/or microbiologic efficacy of ODD in approximately 450 children ( Table 2). [44][45][46][47][48][49][50][51] It is important to note that the studies were not adequately powered to show a true statistical difference due to a limited number of subjects.…”

“…48 Four additional studies evaluating clinical efficacy did not compare dosing regimens, but administered aminoglycosides only once/day. [49][50][51][52] In one trial, 76% of febrile episodes (86/113) responded to first-line treatment (gentamicin plus ceftriaxone) with resolution of fever after 48 hours. 49 The remaining 24% of patients required vancomycin and ceftazidime due to unresolved fever with or without the presence of organisms resistant to first-line agents.…”

“…[49][50][51][52] In one trial, 76% of febrile episodes (86/113) responded to first-line treatment (gentamicin plus ceftriaxone) with resolution of fever after 48 hours. 49 The remaining 24% of patients required vancomycin and ceftazidime due to unresolved fever with or without the presence of organisms resistant to first-line agents. 49 Others demonstrated 92% of febrile episodes (272/303) resolving clinically without a change in empiric antibiotic treatment.…”