In a prospective randomized trial parenteral trimethoprim/sulphamethoxazole was added to amikacin plus piperacillin in order to compare triple-drug antibiotic combination with a standard regimen as empiric therapy of fever in patients with granulocytopenia. One hundred and sixty-one episodes were evaluated; 74 episodes with amikacin plus piperacillin and 87 episodes with amikacin plus piperacillin plus trimethoprim/sulphamethoxazole. The overall response to therapy (63% vs. 84%) as well as the response of microbiologically documented infections (60% vs. 82%) was significantly better in patients treated with the triple-drug combination (p less than 0.05). However, no statistically significant differences in response to antibiotics at different infection sites or with regard to any single pathogen was found between the two groups. Trimethoprim/sulphamethoxazole seemed to be responsible for additional toxicity (nausea and vomiting) when added to amikacin plus piperacillin, but these side-effects were clearly related to the rate of infusion of trimethoprim/sulphamethoxazole. The findings of this study support the use of a three-drug versus a two-drug combination as empiric antibiotic regimen in febrile granulocytopenic patients.
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