Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy.

OBJECTIVES: Apricitabine (ATC) is a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor (NRTI) with significant antiviral activity in vitro, including activity against HIV-1 with reverse transcriptase mutations that confer resistance to other NRTIs. ATC has shown promising antiviral activity and good tolerability when given as monotherapy for 10 days in treatment-naïve HIV-1-infected patients. METHODS: In this Phase II randomized, double-blind study, 51 treatment-experienced HIV-1-infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice-daily 600 mg ATC, 800 mg ATC or 150 mg 3TC for 21 days. Patients remained on their existing background regimen until day 21, when background therapy could be optimized according to genotype at screening. RESULTS: At day 21, the mean change in viral load was -0.71 and -0.90 log(10) HIV-1 RNA copies/mL in the 600 and 800 mg ATC groups, respectively, compared with a -0.03 log(10) change in the 3TC group. In patients with at least three thymidine analogue mutations (TAMs) at baseline, greater reductions in viral load were observed in the 800 mg ATC group at day 21 than in the 600 mg ATC group. Few genotypic changes were detected at day 21 [two patients (600 mg ATC) lost and three patients (800 mg ATC) gained a TAM] and all patients with detectable virus retained the M184V mutation. The safety profiles of the two ATC doses were similar to that of 3TC. CONCLUSIONS: Over the 21-day treatment period, ATC showed promising antiviral activity and was well tolerated in treatment-experienced patients with M184V, with or without additional TAMs.

Chagas disease in bone marrow transplantation: an approach to preemptive therapy.

The efficacy of preemptive therapy was evaluated in bone marrow transplantation (BMT) recipients associated with Chagas disease (CD). The criterion to include patients in the protocol was the serological reactivity for CD in recipients and/or donors before transplant. After BMT, the monitoring was performed using the direct Strout method (SM), which detects clinical levels of Trypanosome cruzi parasitemia, and CD conventional serological tests. Monitoring took place during 60 days in ABMT and throughout the immunosuppressive period in allogeneic BMT. Reactivation of CD was diagnosed by detecting T. cruzi parasites in blood or tissues. In primary T. cruzi infection, an additional diagnostic criterion was the serological conversion. A total of 25 CD-BMT patients were included. Two ABMT and four allogeneic BMT recipients showed CD recurrences diagnosed by SM. One patient also showed skin lesions with T. cruzi amastigotes. Benznidazole treatment (Roche Lab), an antiparasitic drug, was prescribed at a dose of 5 mg/kg/day during 4-8 weeks with recovery of patients. Primary T. cruzi infection was not observed. This report proves the relevance of monitoring CD in BMT patients and demonstrates that preemptive therapy was able to abrogate the development of clinical and systemic disease.

One-year outcome following biological or mechanical valve replacement for infective endocarditis.

BACKGROUND: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. METHODS AND RESULTS: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). CONCLUSIONS: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

Chagas' disease after bone marrow transplantation.

Chagas' disease is caused by Trypanosoma cruzi. It is endemic in Latin America where 16 to 18 million people are infected. Immunocompromised patients such as BMT recipients are at risk of Chagas' disease either due to reactivation or transfusion. We report a case of acute Chagas' disease in the setting of BMT.

Multidrug-resistant tuberculosis in bone marrow transplant recipient.

Multidrug-resistant tuberculosis (TB) is an increasing problem worldwide, however only three cases have been previously described in transplant recipients, especially involving lung and heart transplant. We describe a case of multidrug-resistant TB in an allogenic bone marrow transplant recipient with good response to second-line therapy.

[Microbiology and conservative surgery of serious infections of the diabetic foot]. / Microbiología y cirugía conservadora en infecciones graves del pie diabético.

Between June of 1987 and August 1988 we evaluated 31 diabetic patients hospitalized for severe foot infections to determine the etiologic agents, the value of the bacteriologic samples obtained, the benefits of conservative surgery and variable predictors of a major amputation. Sixteen patients suffered from necrosis, 16 osteomyelitis, 14 ulcers, 5 cellulitis, and/or abscesses and 22 had vascular compromise. Samples were taken from these infections excluding necrotic material. We isolate 76 microorganisms (2.4/pt), 57% Gram-positive cocci (predominantly S. aureus and enterococci), and 43% Gram-negative bacilli. Anaerobes were not isolated probably secondary to the exclusion of necrotic samples. There was high incidence of skin and soft tissue sampling (79%) bone (13/16) and surgical curettage (11/11). In 9 patients the correlation of soft tissue sampling and bone sampling was assessed with a positive correlation with respect to Gram-positive cocci. Twenty-one patients required conservative surgeries of the foot (9 underwent revascularization), 67% of which avoided a mayor amputation. However no significant variables predictive of a major amputation were detected in this study. In summary, the conservative surgery allowed to 2 out of 3 patients to preserve the foot.

Reactivation of chronic Chagas' disease following allogeneic bone marrow transplantation and successful pre-emptive therapy with benznidazole.

This report shows the early detection of reactivation of chronic Chagas' disease (CCd) in a 27-year-old man with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation (ABMT). Pre-emptive therapy with benznidazole during a period of 7 weeks led to a rapid recovery of the patient, who remains free of parasitemia 2 years after the bone marrow transplantation.

Concentración plasmática de isoniacida en los tuberculosos de edad avanzada / Plasma concentration of isoniazid in aged patients with tuberculosis

Enfermos tuberculosos que tenían entre 60 y 90 años de edad, sin enfermedades asociadas, ni alteraciones hepáticas y renales, recibieron dosis únicas de 300 y 200 mg de Isoniacida y se midieron en ellos las concentraciones plasmáticas a los 0, 90, 180 y 300 minutos de la toma de la droga. Un grupo control, que tenía entre 25 y 50 años de edad, recibió 300 mg de Isoniacida y se midió en ellos la concentración plasmática a los mismos tiempos. En los pacientes de edad avanzada, tanto en los acetiladores lentos como en los rápidos, la dosis de 300 mg produjo picos de concentración similares a los que se observaron con la misma dosis en los pacientes más jóvenes; cuando recibieron 200 mg de Isoniacida los picos de concentración fueron más bajos pero con valores eficaces desde el punto de vista terapéutico. Estos hallazgos sugierem que todos los tuberculosos de edad avanzada deben ser tratados con 200 mg de Isoniacida, pues esta dosis, además de ser eficaz, producirá menos reacciones adversas

Concentración plasmática de isoniacida en los tuberculosos de edad avanzada / Plasma concentration of isoniazid in aged patients with tuberculosis

Enfermos tuberculosos que tenían entre 60 y 90 años de edad, sin enfermedades asociadas, ni alteraciones hepáticas y renales, recibieron dosis únicas de 300 y 200 mg de Isoniacida y se midieron en ellos las concentraciones plasmáticas a los 0, 90, 180 y 300 minutos de la toma de la droga. Un grupo control, que tenía entre 25 y 50 años de edad, recibió 300 mg de Isoniacida y se midió en ellos la concentración plasmática a los mismos tiempos. En los pacientes de edad avanzada, tanto en los acetiladores lentos como en los rápidos, la dosis de 300 mg produjo picos de concentración similares a los que se observaron con la misma dosis en los pacientes más jóvenes; cuando recibieron 200 mg de Isoniacida los picos de concentración fueron más bajos pero con valores eficaces desde el punto de vista terapéutico. Estos hallazgos sugierem que todos los tuberculosos de edad avanzada deben ser tratados con 200 mg de Isoniacida, pues esta dosis, además de ser eficaz, producirá menos reacciones adversas (AU)