RESUMO
BACKGROUND: A series of 459 hospitalized adults with complicated intra-abdominal infections participated in a randomized, double-blind, multicenter clinical trial. The present study was conducted to add a pharmacoeconomic analysis to the results. METHODS: A cost-effectiveness analysis from the perspective of the hospital provider was carried out. Decision analysis was used to illustrate outcomes and to provide a basis on which to conduct a sensitivity analysis. Cost-effectiveness ratios, representing the cost per expected successfully treated patient, were calculated to determine the most cost-effective alternative. RESULTS: Among 244 economically evaluable patients, enrolled from 34 centers in the U.S. and Canada, 131 patients received ciprofloxacin-metronidazole (75% clinical success rate), and 113 received piperacillin-tazobactam (65% clinical success rate; p = 0.06). Switch to oral antibiotics was possible for 81 patients who received ciprofloxacin-metronidazole (85% clinical success rate) and 67 piperacillin-tazobactam patients (70% clinical success rate; p = 0.027). The mean hospital cost was US$10,662 +/- 7,793 for patients in the ciprofloxacin-metronidazole group and $10,009 +/- 7,023 for patients in the piperacillin-tazobactam group (p = 0.492). Significantly lower costs were documented for patients who could be switched to oral antibiotics than for those continued on intravenous antibiotic orders ($8,684 +/- 4,120 vs. $12,945 +/- 10,204, respectively; p < 0.001). Patients with appendicitis had lower mean hospital costs than those with other infections ($7,169 +/- 3,705 vs. $12,097 +/- 8,342, respectively; p < 0.001). The cost-effectiveness ratios were $14,216:1 for patients in the ciprofloxacin-metronidazole group and $15,398:1 for patients in the piperacillin-tazobactam group. CONCLUSIONS: The mean hospital costs associated with ciprofloxacin-metronidazole were similar to those of piperacillin-tazobactam for the treatment of adults with complicated intra-abdominal infections. Lower costs were documented for patients able to be switched to oral antibiotics and for patients with appendicitis.
Assuntos
Abscesso Abdominal/tratamento farmacológico , Antibacterianos , Apendicite/tratamento farmacológico , Ciprofloxacina , Metronidazol , Peritonite/tratamento farmacológico , Abscesso Abdominal/complicações , Abscesso Abdominal/microbiologia , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/economia , Antibacterianos/uso terapêutico , Apendicite/complicações , Apendicite/microbiologia , Ciprofloxacina/administração & dosagem , Ciprofloxacina/economia , Ciprofloxacina/uso terapêutico , Análise Custo-Benefício , Método Duplo-Cego , Quimioterapia Combinada , Farmacoeconomia , Feminino , Humanos , Masculino , Metronidazol/administração & dosagem , Metronidazol/economia , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/economia , Ácido Penicilânico/uso terapêutico , Peritonite/complicações , Peritonite/microbiologia , Piperacilina/administração & dosagem , Piperacilina/economia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Resultado do TratamentoRESUMO
Chronic glucocorticoid therapy is prescribed in renal transplant recipients according to empiric dose-tapering schedules, which assume a similar pharmacologic response in men and women. The study objectives were (a) to compare the pharmacokinetics of methylprednisolone in premenopausal renal transplant recipients with previously studied male counterparts and (b) to describe the pharmacodynamic response of the hypothalamic-pituitary-adrenal axis during chronic steroid therapy. Thirteen stable premenopausal subjects (ages 30 to =49 years) receiving chronic glucocorticoid therapy were evaluated for methylprednisolone, cortisol, and adrenocorticotropin hormone (ACTH) over 24 hours after an intravenous infusion of methylprednisolone sodium succinate. Most patients were evaluated during the luteal phase of the menstrual cycle. Pharmacokinetic parameters of methylprednisolone with cortisol and ACTH responses were determined. Results were compared to counterpart male subjects who participated in a prior study. The total clearance of methylprednisolone for the female subjects was 15.6 +/- 5.99 L/h compared to the males with 21.5 +/- 8.67 L/h (P <.05). When normalized for total or lean body weight, no significant difference was noted (P =.614). A 3-fold interpatient variation in weight-adjusted clearance was noted for female subjects. Dose-normalized methylprednisolone a AUC was greater in women (66.1 +/- 19.8 ng*h/mL) than men (46.4 +/- 19.7 ng*h/mL) (P =.174). Total cortisol AUC was not different between groups (P =.599). Despite chronic steroid therapy, 9 of 13 women had a normal cortisol profile and an ACTH AUC of 299 +/- 102 pg*h/mL. It was concluded that methylprednisolone clearance in women was significantly slower compared to men. When drug clearance was normalized for total and lean body weight, no gender difference was noted. These findings are in contrast to prior data indicating a more rapid methylprednisolone clearance in healthy women. These findings suggest that doses of glucocorticoids should be prescribed on a milligram/kilogram basis instead of empiric dosing schedules.