RESUMO
OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antiprotozoários/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Enteropatias Parasitárias/tratamento farmacológico , Microsporidiose/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Adolescente , Adulto , Animais , Antiprotozoários/efeitos adversos , Cicloexanos , Diarreia/complicações , Diarreia/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos Insaturados/efeitos adversos , Humanos , Enteropatias Parasitárias/complicações , Masculino , Microsporida/efeitos dos fármacos , Microsporidiose/complicações , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Sesquiterpenos , Resultado do TratamentoRESUMO
The MICs of fluconazole for strains of Candida species and the levels of fluconazole in serum were determined at day 0 and day 14 for 23 human immunodeficiency virus-infected patients with oral candidiasis who were treated orally with 100 mg of fluconazole per day for 14 days. Among the 23 patients, 11 (48%) were not clinically cured and had persistent isolation of Candidiasis albicans (n = 10) and/or presence of non-C. albicans (n = 6). Clinical response could be predicted by the susceptibility of the strain to fluconazole determined at day 0. All 12 patients who were cured were infected with a strain for which the MIC was < 0.78 mg/liter. All four patients who were infected with a strain for which the MIC was > 3.12 mg/liter experienced clinical failure. These data suggest that a C. albicans strain could be defined as being susceptible when the MIC of fluconazole is < 0.78 mg/liter and as being resistant when the MIC is > 3.12 mg/liter.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Fluconazol/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Antifúngicos/farmacologia , Candida/isolamento & purificação , Candida albicans/isolamento & purificação , Candidíase Bucal/microbiologia , Feminino , Fluconazol/administração & dosagem , Fluconazol/sangue , Fluconazol/farmacologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de TratamentoRESUMO
RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacteria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-susceptible streptococcal isolates or their constitutively erythromycin-resistant Tn916 delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bactericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 prophylaxis successfully prevented endocarditis due to both the erythromycin-susceptible parent strains and their erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals challenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standard macrolidelincosamide-streptogramin antibiotics used for endocarditis prophylaxis in humans. An oral form of RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed.
Assuntos
Endocardite Bacteriana/prevenção & controle , Eritromicina/farmacologia , Infecções Estreptocócicas , Virginiamicina/uso terapêutico , Animais , Conjugação Genética , Resistência Microbiana a Medicamentos , Endocardite Bacteriana/sangue , Feminino , Testes de Sensibilidade Microbiana , Ratos , Ratos Wistar , Streptococcus/efeitos dos fármacos , Streptococcus/genética , Vancomicina/sangue , Vancomicina/uso terapêutico , Virginiamicina/sangueRESUMO
The scientific basis for using folinic acid in combination with the antiparasitic drugs prescribed to AIDS patients has been reviewed. In vitro and experimental data are unclear. On the basis of folinic acid metabolism and pharmacology and of clinical experience, we suggest that folinic acid should not be systematically added to the curative treatment of pneumocystosis with cotrimoxazole. Folinic acid may be added to prophylactic regimens using high-dose cotrimoxazole (i.e. 800 mg sulfamethoxazole twice a day) and in malnourished patients. It should be administered as soon as cytopenia occurs in the course of treatment. Concerning toxoplasmosis, the addition of folinic acid is recommended in doses of 10 to 20 mg/day in acute therapy and 5 to 10 mg/day in maintenance therapy. Dosage must be adjusted to the results of blood counts.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Doenças Hematológicas/prevenção & controle , Leucovorina/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Quimioterapia Combinada , Ácido Fólico/metabolismo , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/complicações , Humanos , Leucovorina/farmacocinética , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/metabolismo , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/metabolismo , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/tratamento farmacológico , Toxoplasmose Cerebral/metabolismo , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
A prospective open study carried out over 5 years and including 20 patients suffering from chronic bone suppuration following orthopaedic surgery has confirmed the value of the new quinolones (NQ) in these indications. The patients received pefloxacin or ciprofloxacin most often combined with rifampicin or fusidic acid for a mean period of 7 months. Single or multiple organism infections were documented in 14 patients, the majority being Staph. aureus (n = 13) and Pseudomonas (n = 14). Samples were sterile in 6 cases. Fourteen therapeutic successes and 5 failures were observed. In one patient, improvement was noted but the post-treatment follow-up insufficient to pronounce a cure. Success was obtained in 14 out of 16 patients who had sensitive organisms or sterile samples. The mean post-treatment follow-up (16 months) was satisfactory but insufficient to speak of cure. However, in these patients for whom further surgery, however desirable, is often refused, NQ constitute an improvement which raises hopes of cure or allows further surgery.