RESUMO
BACKGROUND: Imipenem-cilastatin (referred to hereafter as imipenem) is administered at different doses as monotherapy or with other agents. Limited comparisons of the alternatives exist. The authors compared the efficacy and safety of several imipenem-containing regimens (ICRs) to determine the appropriate dose and the need for combination therapy. METHODS: Between 1985 and 1994, febrile neutropenic patients were given ICRs according to the same methodology on prospective trials at a referral cancer center. The ICRs were high dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV). RESULTS: The overall response rates were comparable (70-77%). There was a univariate trend toward better response among patients with pneumonia and documented infections with unidentified organisms who received HIPV versus LIPV (P=0.06), as well as a significantly better response among patients with gram positive infections who received HIPV versus HIP (P=0.02) and HIPA (P=0.002). HIPV was a more effective treatment for documented infections with identified organisms (P=0.05) and bloodstream infections (P=0.04) than HIP; there was a univariate trend toward better response among patients infected with gram negative organisms who received HIPA versus HIP (P=0.12). Multivariate adjustment for baseline and prognostic factors did not reveal a relative advantage for any regimen. No differences in overall toxicities were observed between HIPV and LIPV. CONCLUSIONS: Imipenem monotherapy is adequate treatment for most febrile neutropenic cancer patients. Low dose imipenem could be effective and safe in uncomplicated cases without pneumonia. Further studies are needed to establish the usefulness of low dose imipenem in this context.
Assuntos
Cilastatina/administração & dosagem , Imipenem/administração & dosagem , Neoplasias/complicações , Neutropenia/tratamento farmacológico , Inibidores de Proteases/administração & dosagem , Tienamicinas/administração & dosagem , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Febre , Humanos , Imipenem/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Estudos Retrospectivos , Tienamicinas/efeitos adversos , Resultado do TratamentoRESUMO
We conducted a prospective, randomized, multicenter study comparing fluconazole and amphotericin B in the treatment of candidal infections. One hundred and sixty-four patients (60 of whom were neutropenic) with documented or presumed invasive candidiasis were assigned to treatment with either fluconazole (400 mg daily) or amphotericin B (25-50 mg daily; 0.67 mg/kg daily for neutropenic patients). Clinical response and survival rates were assessed at 48 hours, after 5 days, and at the end of therapy. Overall response rates to fluconazole and amphotericin B were similar (66% and 64%, respectively). There were no differences in response as related to site of infection, pathogen, time to defervescence, relapse, or survival rates between the groups. Adverse effects were more frequent with amphotericin B (35%) than with fluconazole (5%; P < .0001). The results of this study confirm that fluconazole is as effective as but better tolerated than amphotericin B in the treatment of candidal infections.
Assuntos
Anfotericina B/uso terapêutico , Candidíase/tratamento farmacológico , Fluconazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/efeitos adversos , Feminino , Fluconazol/efeitos adversos , Humanos , Masculino , Estudos Prospectivos , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity. METHODS: A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer. RESULTS: The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001). CONCLUSIONS: Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable.