RESUMO
Invasive fungal infections (IFIs) are a common complication in liver transplant recipients. There are no previous randomized trials of an echinocandin for the prevention of IFIs in solid organ transplant recipients. In a randomized, double-blind trial conducted at University-affiliated transplant centers, 200 high-risk liver transplant recipients (100 patients per group) received either anidulafungin or fluconazole for antifungal prophylaxis. Randomization was stratified by Model for End-Stage Liver Disease score ≥30 and receipt of a pretransplant antifungal agent. The primary end point was IFI in a modified intent-to-treat analysis. The overall incidence of IFI was similar for the anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19-1.94, p = 0.40). However, anidulafungin prophylaxis was associated with less Aspergillus colonization or infection (3% vs. 9%, p = 0.08), lower breakthrough IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p = 0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality were similar for both groups. Thus, anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients. Anidulafungin may be beneficial if the patient has an increased risk for Aspergillus infection or received fluconazole before transplantation.
Assuntos
Antibioticoprofilaxia , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Rejeição de Enxerto/epidemiologia , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Micoses/prevenção & controle , Adolescente , Adulto , Idoso , Anidulafungina , Antifúngicos/uso terapêutico , Método Duplo-Cego , Feminino , Seguimentos , Rejeição de Enxerto/microbiologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Hospedeiro Imunocomprometido , Incidência , Hepatopatias/microbiologia , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Micoses/epidemiologia , Micoses/microbiologia , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Transplantados , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Maribavir is an oral benzimidazole riboside with potent in vitro activity against cytomegalovirus (CMV), including some CMV strains resistant to ganciclovir. In a randomized, double-blind, multicenter trial, the efficacy and safety of prophylactic oral maribavir (100 mg twice daily) for prevention of CMV disease were compared with oral ganciclovir (1000 mg three times daily) in 303 CMV-seronegative liver transplant recipients with CMV-seropositive donors (147 maribavir; 156 ganciclovir). Patients received study drug for up to 14 weeks and were monitored for CMV infection by blood surveillance tests and also for the development of CMV disease. The primary endpoint was Endpoint Committee (EC)-confirmed CMV disease within 6 months of transplantation. In a modified intent-to-treat analysis, the noninferiority of maribavir compared to oral ganciclovir for prevention of CMV disease was not established (12% with maribavir vs. 8% with ganciclovir: event rate difference of 0.041; 95% CI: -0.038, 0.119). Furthermore, significantly fewer ganciclovir patients had EC-confirmed CMV disease or CMV infection by pp65 antigenemia or CMV DNA PCR compared to maribavir patients at both 100 days (20% vs. 60%; p < 0.0001) and at 6 months (53% vs. 72%; p = 0.0053) after transplantation. Graft rejection, patient survival, and non-CMV infections were similar for maribavir and ganciclovir patients. Maribavir was well-tolerated and associated with fewer hematological adverse events than oral ganciclovir. At a dose of 100 mg twice daily, maribavir is safe but not adequate for prevention of CMV disease in liver transplant recipients at high risk for CMV disease.
Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/métodos , Ribonucleosídeos/administração & dosagem , Aciclovir/administração & dosagem , Administração Oral , Infecções por Citomegalovirus/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Ganciclovir/administração & dosagem , Rejeição de Enxerto/virologia , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/imunologia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/virologia , Estudos Prospectivos , Medição de Risco , Resultado do TratamentoRESUMO
We report on two patients with no active GVHD and on moderate doses of immunosuppressive drugs who unexpectedly developed fatal CMV meningoencephalitis after umbilical cord blood transplantation. A review of these two cases along with nine other cases of CMV central nervous system (CNS) disease after allogeneic SCT that were mostly reported within the last 8 years suggests that this severe complication of CMV infection may be increasing. CMV CNS disease after allogeneic SCT is a late-onset disease (median time of onset, 210 days) and is usually manifested as encephalitis in the absence of other sites of CMV disease. The development of CMV CNS disease is associated with risk factors (T-cell depletion, anti-thymocyte globulin, umbilical cord blood transplantation) that cause severe and protracted T-cell immunodeficiency (8 of 11 cases), a history of recurrent CMV viremia treated with multiple courses of preemptive ganciclovir or foscarnet therapy (11 of 11 cases), and ganciclovir-resistant CMV infection (11 of 11 cases). Despite therapy with a combination of antiviral drugs (ganciclovir, foscarnet and cidofovir), mortality is high (10 of 11 cases). Given this high mortality, extended prophylaxis with current or novel antiviral drugs and strategies to enhance CMV immunity need to be considered in high-risk patients.
Assuntos
Infecções do Sistema Nervoso Central/induzido quimicamente , Infecções por Citomegalovirus/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções do Sistema Nervoso Central/etiologia , Infecções por Citomegalovirus/etiologia , Resistência a Medicamentos , Humanos , Hospedeiro Imunocomprometido , Infecções OportunistasRESUMO
BACKGROUND: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting. OBJECTIVE: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. DESIGN: An open randomized, controlled, multicenter trial, powered for equivalence. SETTING: 60 oncology centers in 10 countries. PATIENTS: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. INTERVENTION: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution. MEASUREMENTS: Defervescence, breakthrough fungal infection, drug-related adverse events, and death. RESULTS: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P = 0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P = 0.001). Significantly more amphotericin B recipients had nephrotoxicity (P < 0.001). Breakthrough fungal infections (5 patients in each group) and mortality rates (19 deaths in the itraconazole group and 25 deaths in the amphotericin B group) were similar. Sixty-five patients switched to oral itraconazole solution after receiving the intravenous formulation for a median of 9 days. CONCLUSIONS: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.
Assuntos
Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Ácido Desoxicólico/administração & dosagem , Itraconazol/administração & dosagem , Micoses/tratamento farmacológico , Neoplasias/complicações , Neutropenia/imunologia , Infecções Oportunistas/tratamento farmacológico , Administração Oral , Anfotericina B/efeitos adversos , Antibacterianos/uso terapêutico , Antifúngicos/efeitos adversos , Antineoplásicos/efeitos adversos , Ácido Desoxicólico/efeitos adversos , Combinação de Medicamentos , Febre/etiologia , Humanos , Infusões Intravenosas , Itraconazol/efeitos adversos , Micoses/complicações , Neoplasias/tratamento farmacológico , Infecções Oportunistas/complicações , Fatores de Risco , Falha de TratamentoRESUMO
Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease (GVHD) and infections, but the minimally effective dose has not been established. In this multicenter, randomized, double-blind trial, patients undergoing allogeneic marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500 mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days and then monthly until 1 year after transplant. Six hundred and eighteen patients were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of 206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344). Among patients with unrelated marrow donors, a higher dose of intravenous immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The incidences of chronic GVHD, infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin. The dose of intravenous immunoglobulin also had no effect on the types of infection, relapse of hematological malignancy or survival. Except for more frequent chills (P = 0.007) and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin, adverse events were similar for all three doses. These results suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants. These results should be considered when designing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Imunoglobulinas Intravenosas/uso terapêutico , Infecções/epidemiologia , Leucemia/terapia , Linfoma/terapia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Teste de Histocompatibilidade , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Terapia de Imunossupressão/métodos , Depleção Linfocítica , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Transplante HomólogoRESUMO
In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients.
Assuntos
Agranulocitose/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Fluoroquinolonas , Imipenem/uso terapêutico , Tienamicinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/microbiologia , Anti-Infecciosos/efeitos adversos , Contagem de Células Sanguíneas , Canadá , Método Duplo-Cego , Feminino , Humanos , Imipenem/efeitos adversos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tienamicinas/efeitos adversos , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer. PATIENTS AND METHODS: A total of 317 neutropenic patients (<500 cells/mm3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criteria, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patient was afebrile, had no clinical or microbiological evidence of fungal infection, and did not require study termination due to lack of efficacy, drug toxicity, or death. RESULTS: A satisfactory response occurred in 68% of the patients treated with fluconazole (107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of 159 patients). Progressive or new fungal infections during therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse events related to study drug (especially fever, chills, renal insufficiency, electrolyte disturbances, and respiratory distress) occurred more often in patients treated with amphotericin B (128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but only 1 (1%) patient treated with fluconazole were terminated from the study owing to an adverse event (P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole versus 34 [21%] patients treated with amphotericin B) and mortality from fungal infection (7 [4%] patients treated with fluconazole versus 5 [3%] patients treated with amphotericin B) were similar in each study group. CONCLUSIONS: Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients. However, because fluconazole may be ineffective in the treatment of Aspergillus, patients at risk for that infection should be evaluated by chest radiograph, computed tomographic scanning, and cultures before the use of empiric fluconazole therapy.
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Febre/tratamento farmacológico , Fluconazol/uso terapêutico , Micoses/tratamento farmacológico , Neoplasias/complicações , Neutropenia/complicações , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Causas de Morte , Feminino , Febre/etiologia , Fluconazol/efeitos adversos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Micoses/prevenção & controle , Resultado do TratamentoRESUMO
The efficacy and safety of quinupristin/dalfopristin for treatment of infections due to vancomycin-resistant Enterococcus faecium were evaluated in 24 hospitalized patients with documented infections (19 bacteremias, 5 localized infections) caused by vancomycin-resistant E. faecium that was susceptible to quinupristin/dalfopristin in vitro. Patients received iv quinupristin/dalfopristin at a dosage of either 7.5 mg/kg every 8 h or 5 mg/kg every 8 h. A favorable clinical response (cure or improvement) occurred in 19 (83%) of 23 evaluable patients; bacteriologic eradication occurred in 17 (74%) of 23 evaluable patients. A favorable clinical response was observed in 12 (80%) of 15 patients who were treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h and in 7 (88%) of 8 patients treated with 5 mg/kg of quinupristin/dalfopristin every 8 h. Two of four treatment failures were associated with a decrease in the in vitro susceptibility of vancomycin-resistant E. faecium to quinupristin/dalfopristin. Superinfections developed in 6 patients (26%), but only one was caused by Enterococcus faecalis that was resistant to quinupristin/dalfopristin. Myalgias and arthralgias were the only adverse events related to quinupristin/dalfopristin. These conditions occurred in 8 (33%) of 24 patients and were dose-related (8 cases in 16 patients treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h, no cases in 8 patients treated with 5 mg/kg every 8 h). Mortality associated with vancomycin-resistant E. faecium infection was 17% (4 of 23 patients), whereas mortality from other causes was 52% (12 of 23 patients). These results suggest that quinupristin/dalfopristin is effective as treatment for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying conditions. Except for myalgias and arthralgias at higher dosages, the drug is well-tolerated.
Assuntos
Quimioterapia Combinada/uso terapêutico , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Resistência a Vancomicina , Virginiamicina/uso terapêutico , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Criança , Pré-Escolar , Quimioterapia Combinada/farmacologia , Feminino , Infecções por Bactérias Gram-Positivas/mortalidade , Hospitalização , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Resultado do Tratamento , Virginiamicina/farmacologiaAssuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Fosfatidilcolinas/uso terapêutico , Fosfatidilgliceróis/uso terapêutico , Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Fluconazol/uso terapêutico , Humanos , Lipossomos , Fosfatidilcolinas/efeitos adversos , Fosfatidilgliceróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Among persons who receive solid organ transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective. OBJECTIVE: To evaluate the efficacy and safety of prophylactic fluconazole in liver transplant recipients. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University-affiliated transplantation center. PATIENTS: 212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, drug-related side effects, and death. RESULTS: Fungal colonization increased in patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003). CONCLUSIONS: Prophylactic fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.
Assuntos
Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Transplante de Fígado , Micoses/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Antifúngicos/efeitos adversos , Ciclosporina/sangue , Feminino , Fluconazol/efeitos adversos , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Modelos de Riscos Proporcionais , Convulsões/induzido quimicamente , Estatísticas não Paramétricas , Tremor/induzido quimicamenteRESUMO
BACKGROUND: Infection and rejection are two common complications after liver transplants. In a preliminary study, administration of granulocyte colony-stimulating factor (G-CSF) to liver transplant recipients was associated with a decrease in sepsis episodes, sepsis-related deaths, and rejection compared with a historical control group of patients. The purpose of this study was to evaluate further the efficacy of G-CSF in liver transplant patients in a randomized, placebo-controlled, double-blind, multicenter trial. METHODS: Adult patients with a United Network Organ Sharing classification of 1 or 2 were randomized to receive a placebo, 100 microg/day of G-CSF or 300 microg/day of G-CSF. The study drug was started preoperatively and then continued after the transplant for a maximum of 21 days. Patients were evaluated for microbiologically-documented infection, biopsy-proven rejection, number of treatments for rejection, length of stay in the intensive care unit and hospital, graft survival, death, and adverse events. RESULTS: During the first 30 days after the transplant, the median peak white blood cell count was 16.5x10(9)/L, 34.6x10(9)L, and 54.8x10(9)/L for the placebo, low-dose G-CSF, and high-dose G-CSF patients, respectively. The incidence of infection was 30% in G-CSF patients (34 of 114 patients) and 34% in placebo patients (20 of 58 patients). Except for more nosocomial pneumonias in the G-CSF patients (7 in 114 patients vs. 0 in 58 patients, P=0.056), the types of infections and causative organisms were also similar in both treatment groups. Although the number of treatments for clinically suspected or proven rejection was similar in the G-CSF and placebo patients, biopsy-proven rejection occurred more often in G-CSF patients (34 of 114 patients or 30%) than placebo patients (11 of 58 patients or 19%) (P=0.093). There were no cases of graft loss caused by rejection. G-CSF had no effect on length of stay in the intensive-care unit or hospital. There were 22 G-CSF patients (18%) and 10 placebo patients (15%) who died within 120 days after the transplant. No serious adverse events were attributed to G-CSF. CONCLUSION: Despite producing substantial increases in the white blood cell count after the transplant, G-CSF had no beneficial effects on infection, rejection, or survival in this study. Biopsy-proven rejection and nosocomial pneumonias were more common in patients treated with G-CSF compared with those taking the placebo. No serious adverse events were attributed to G-CSF.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Fígado , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-IdadeAssuntos
Anfotericina B/economia , Antifúngicos/economia , Micoses/tratamento farmacológico , Anfotericina B/administração & dosagem , Antibioticoprofilaxia/economia , Antifúngicos/administração & dosagem , Portadores de Fármacos/economia , Custos de Medicamentos , Febre/tratamento farmacológico , Humanos , Lipossomos/economia , Micoses/prevenção & controle , Neutropenia/tratamento farmacológicoRESUMO
In a prospective, randomized, controlled trial, we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile, granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g every 12 hours) and 102 patients received imipenem (500 mg every 6 hours). Documented infections were present in 40% of patients treated with sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40 of 102). The number of pretherapy gram-positive pathogens (52 isolates) was twice the number of pretherapy gram-negative pathogens (26 isolates). The overall favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients, or 88%) and imipenem (84 of 104 patients, or 81%) were similar. Both drugs were generally well tolerated. However, diarrhea occurred more often in patients treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs. 15 of 102 patients, or 15%; P = .007), while seizures developed only in patients receiving imipenem (0 of 101 patients vs. 3 of 102 patients, or 3%). Superinfections developed in 16% of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli (two cases with sulbactam/cefoperazone therapy and six cases with imipenem). These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients.
Assuntos
Agranulocitose/tratamento farmacológico , Cefoperazona/uso terapêutico , Quimioterapia Combinada/uso terapêutico , Imipenem/uso terapêutico , Sulbactam/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/microbiologia , Cefoperazona/efeitos adversos , Feminino , Febre/tratamento farmacológico , Febre/microbiologia , Humanos , Imipenem/efeitos adversos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Sulbactam/administração & dosagem , Sulbactam/efeitos adversos , SuperinfecçãoRESUMO
A randomized placebo-controlled trial was conducted to determine the benefit of ganciclovir (5 mg/[kg x d]) for 30 days in addition to intravenous immune globulin (IVIG) for 16 weeks for prevention of primary cytomegalovirus (CMV) disease in children receiving liver transplants. Patients were monitored for 6 months after transplantation. The two groups of patients (recipients of 29 ganciclovir plus IVIG and 27 recipients of IVIG alone) were similar in terms of age, sex, and underlying disease. The incidence of CMV disease among the ganciclovir plus IVIG recipients and the IVIG alone recipients was 17% and 26%, respectively, and the time to disease in these recipients was 46 days and 32 days, respectively. There was no difference between groups in terms of survival; episodes of rejection, bacteremia, or fungemia; use of immunosuppressive agents; and incidence of leukopenia or thrombocytopenia. These results suggest that a 4-week course of ganciclovir with IVIG is not more effective than IVIG alone for prevention of primary CMV disease. Since short-term prophylaxis with ganciclovir may delay the onset of CMV disease, further studies with a longer course of ganciclovir prophylaxis are warranted.
Assuntos
Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Fígado , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Resultado do TratamentoRESUMO
Eight (0.59%) of 1,347 patients who underwent liver transplantation at the UCLA Medical Center (Los Angeles) developed coccidioidomycosis. Whereas only one case occurred during the first 8 years and 10 months of the UCLA Liver Transplant Program (February 1984 to December 1992), seven cases occurred within the following 23-month period (December 1992 to November 1994). The median time of onset for infection after transplantation was 8 weeks (range, 4-312 weeks). Clinical presentations of patients with coccidioidomycosis included pneumonia (six cases), pneumonia with meningitis (one case), hepatitis (one case), and monoarticular arthritis (one case). Despite therapy with amphotericin B alone (six cases) or amphotericin B plus fluconazole (two cases), infection was fatal in four of eight cases. As of this writing, the four surviving patients are receiving chronic maintenance therapy with either fluconazole (three patients) or itraconazole (one patient). These experiences show that coccidioidomycosis can be a serious and frequently fatal infection after liver transplantation and that the incidence of this disease appears to be increasing.
Assuntos
Coccidioidomicose/etiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Anfotericina B/uso terapêutico , Coccidioidomicose/terapia , Feminino , Fluconazol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We conducted a trial of long-term ganciclovir prophylaxis for prevention of primary cytomegalovirus (CMV) disease in CMV-seronegative liver transplant recipients with CMV-seropositive donors. METHODS: Patients received intravenous ganciclovir at a dose of 6 mg/kg once a day from day 1 to day 30 after transplant, and then at a dose of 6 mg/kg once a day, Monday through Friday, until day 100. Forty-seven consecutive patients were evaluated. Due to the primary physician's decision or administrative error, 10 patients received less than 7 weeks of ganciclovir (mean duration, 3 weeks). RESULTS: Four of the 10 (40%) patients who received less than 7 weeks of ganciclovir developed CMV disease (hepatitis). In contrast, none of the 37 patients given 100 days of prophylactic ganciclovir developed CMV disease while receiving ganciclovir. Two patients (5.4%) subsequently developed CMV disease (hepatitis) 21 and 88 days, respectively, after completing their ganciclovir prophylaxis. Reversible neutropenia in three patients (8.1%) was the only side effect associated with long-term ganciclovir. Complications from central intravenous catheters did not occur. CONCLUSIONS: These results reaffirm the efficacy and safety of long-term ganciclovir prophylaxis for prevention of primary CMV disease in a large number of high-risk CMV-seronegative liver transplant recipients with CMV-seropositive donors.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus , Ganciclovir/uso terapêutico , Transplante de Fígado , Adolescente , Adulto , Idoso , Anticorpos Antivirais/análise , Criança , Pré-Escolar , Infecções por Citomegalovirus/transmissão , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Pessoa de Meia-IdadeRESUMO
The effect of ganciclovir prophylaxis on reinfection of hepatic allografts by hepatitis B virus (HBV) was studied in 26 patients undergoing orthotopic liver transplantation (OLT) for decompensated cirrhosis due to HBV. Patients were randomized to receive either ganciclovir (6 mg/kg/day intravenously for a total of 100 days) or acyclovir (10 mg/kg every 8 hours intravenously until discharged and then 800 mg orally every 6 hours) for a total of 100 days after OLT as part of a study of prophylaxis against cytomegalovirus infection. All patients received hepatitis B immunoglobulin (HBIG), 10,000 units intravenously, during the anhepatic phase, daily for the first 7 days, after OLT, and then every 4 weeks for 6 months, Seven of 12 (58%) patients in the ganciclovir group developed recurrent HBV, compared with 6/14 (46%) of the acyclovir group (nonsignificant). No significant difference was observed in time to recurrent HBV in the ganciclovir group (mean 13.2 months) compared to the acyclovir group (mean 11 months). Our results suggest that ganciclovir administered prophylactically for 100 days after OLT does not prevent or delay graft reinfection by HBV.
Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Hepatite B Crônica/prevenção & controle , Transplante de Fígado/efeitos adversos , Administração Oral , Adulto , Idoso , Sequência de Bases , Esquema de Medicação , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/virologia , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/cirurgia , Humanos , Infusões Intravenosas , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Taxa de Sobrevida , Transplante Homólogo , Falha de TratamentoRESUMO
We conducted a trial of long-term ganciclovir prophylaxis for prevention of cytomegalovirus (CMV) disease in liver transplant recipients receiving OKT3 therapy for rejection. Intravenous ganciclovir (6 mg/kg once a day, Monday through Friday) was initiated on the same day OKT3 therapy was started and continued for 4 or more weeks. Fifty-one consecutive adult patients (80% CMV seropositive, 20% CMV seronegative) were evaluated. Due to the patient's noncompliance or the primary physician's decision, 6 patients received less than 2 weeks of ganciclovir. Three of these 6 (50%) developed CMV disease (hepatitis 1, CMV syndrome 2). In contrast, of 45 patients receiving 4 or more weeks of prophylactic ganciclovir, only 1 (2.2%) developed CMV disease (hepatitis). There were no cases of CMV disease among 29 patients who received 6 or more weeks of ganciclovir. Reversible neutropenia in 2 patients (4.4%) was the only side effect associated with long-term ganciclovir. Complications from central intravenous catheters did not occur. These results suggest that CMV can be eliminated as a significant pathogen in liver transplant recipients receiving OKT3 for rejection by the long-term administration of prophylactic gnaciclovir, which is safe.