Avaliação da eficácia e segurança da farmacoterapia da leishmaniose visceral / Evaluation of the efficacy and safety of pharmacotherapy of visceral leishmaniasis

A Leishmaniose Visceral Americana (LVA) é uma doença de letalidade significativa e em disseminação no território brasileiro. É causada pela Leishmania infantum chagasi, parasita transmitido por artrópodes (Lutzomyia longipalpis) e tem como reservatórios cães e animais silvestres. Embora endêmica em zonas rurais das Regiões Nordeste, Norte e Centro-Oeste do País há várias décadas, a LVA tem emergido como doença urbana (muitas vezes epidêmica), em áreas anteriormente não afetadas. Nestas últimas, está o Estado de São Paulo, onde os primeiros casos autóctones foram detectados em 1999. As opções terapêuticas para LVA são escassas, e associadas a frequentes recidivas e eventos adversos. Há grande tradição em seu tratamento com antimoniais pentavalentes (mais especificamente o antimoniato de N-metil glucamina). Mais recentemente, as formulações de anfotericina B (deoxicolato e lipossomal), tem sido indicadas para quadros mais severos. No entanto, faltam ensaios clínicos que embasem essa superioridade no tratamento de LVA, e muitas das indicações são feitas por analogia com pesquisa realizada na Índia, África ou Europa. O estudo foi planejado para preencher esse hiato na pesquisa clínica relativa à LVA. Tratou-se de ensaio clínico aberto, multicêntrico, envolvendo instituições nos Estados do Pará, Maranhão e São Paulo. Foram incluídos pacientes com diagnóstico parasitológico de LVA que manifestaram aceite em participar por meio de Termo de Consentimento Livre e Esclarecido (TCLE) aplicado aos próprios sujeitos ou aos seus representantes legais...

American Visceral Leishmaniasis (AVL) is a disease that causes significant mortality. Since the past two decades it is disseminating widely in Brazil. Its etiologic agent is Leishmania infantum chagasi, a vector-borne parasite. Traditionally, AVL was regarded as an endemic disease in Northern and Northeastern States, but it has emerged in urban areas and in Southeastern States. In São Paulo State, autochtonous cases occur since 1999. Therapeutic options for AVL are scarce, and all leishmanicidal drugs are associated with failures, relapses and serious adverse events. Meglumine antominiate has been the first-line therapy in Brazil for many decades. Lately, amphotericin B deoxycholate or in liposomal formulation have been recommended for more severe cases. However, those data are extrapolated from studies conducted in India, Africa and Europe. The study was designed to fulfill this gap. It was a multicenter, randomized, open-label study that compare the efficacy and safety of three therapeutic options: meglumine antimoniate, amphotericin B deoxycholate and liposomal amphotericin B. Patients with parasitological confirmation of AVL were included. Those that were coinfected with HIV or who had immune-supressing conditions or pregnancy were excluded. We also excluded those for whom governmental guidelines recommended the use of amphotericin B. Patients were followed with physical examination and laboratory tests on days 0, 3 , 14, 30, 90 and 180. We included 59 subjects, 33 of whom completed follow-up (11 in each arm). Clinical response was similar for all groups. However, those receiving amphotericin were more likely to have early recovery of hemoglobin dosage and white cell counts, as well as serum albumin...

Case-case-control study of risk factors for nasopharyngeal colonization with methicillin-resistant Staphylococcus aureus in a medical-surgical intensive care unit

Nasopharyngeal colonization with methicillin-resistant Staphylococcus aureus (MRSA) often precedes the development of nosocomial infections. In order to identify risk factors for MRSA colonization, we conducted a case-case-control study, enrolling 122 patients admitted to a medical-surgical intensive care unit (ICU). All patients had been screened for nasopharyngeal colonization with S. aureus upon admission and weekly thereafter. Two case-control studies were performed, using as cases patients who acquired colonization with MRSA and methicillin-susceptible S. aureus (MSSA), respectively. For both studies, patients in whom colonization was not detected during ICU stay were selected as control subjects. Several potential risk factors were assessed in univariate and multivariable (logistic regression) analysis. MRSA and MSSA were recovered from nasopharyngeal samples from 27 and 10 patients, respectively. Independent risk factors for MRSA colonization were: length-of-stay in the ICU (Odds Ratio [OR]=1.12, 95 percentConfidence Interval[CI]=1.06-1.19, p<0.001) and use of ciprofloxacin (OR=5.05, 95 percentCI=1.38-21.90, p=0.015). The use of levofloxacin had a protective effect (OR=0.08, 95 percentCI=0.01-0.55, p=0.01). Colonization with MSSA was positively associated with central nervous system disease (OR=7.45, 95 percentCI=1.33-41.74, p=0.02) and negatively associated with age (OR=0.94, 95 percentCI=0.90-0.99, p=0.01). In conclusion, our study suggests a role for both cross-transmission and selective pressure of antimicrobials in the spread of MRSA.

Nasopharyngeal colonization with methicillin-resistant staphylococcus aureus and mortality among patients in an intensive care unit / Colonización nasal por el staphylococcus aureus resistente a la meticilina y mortalidad en pacientes de una unidad de terapia intensiva / Colonização nasal por staphylococcus aureus resistente à meticilina e mortalidade em pacientes de uma unidade de terapia intensiva

Nasopharyngeal colonization with Methicillin-resistant Staphylococcus aureus (MRSA) is common in critically ill patients, but its effect on patient prognosis is not fully elucidated. A retrospective cohort study was carried out enrolling 122 patients from an intensive care unit who were screened weekly for nasopharyngeal colonization with MRSA. The outcomes of interest were: general mortality and mortality by infection. Several exposure variables (severity of illness, procedures, intercurrences and MRSA nasopharyngeal colonization) were analyzed through univariate and multivariable models. Factors significantly associated with mortality in general or due to infection were: APACHE II and lung disease. The performance of surgery predicted favorable outcomes. MRSA colonization did not predict mortality in general (OR=1.02; 95 percentCI=0.35-3.00; p=0.97) or by infectious causes (OR=0.96; 95 percentCI=0.33-2.89; p=0.96). The results suggest that, in the absence of severity of illness factors, colonization with MRSA is not associated with unfavorable outcomes.

La colonización nasofaríngea por el Staphylococcus aureus resistente a la meticilina (Methicillin-resistant S.aureus - MRSA) es común en pacientes críticamente enfermos, pero su efecto sobre el pronóstico no está completamente esclarecido. Fue realizado un estudio de Cohorte retrospectivo con 122 pacientes de una Unidad de Terapia Intensiva que realiza semanalmente exámenes para constatar la colonización nasofaríngea por MRSA. Lo encontrado de interés fue: mortalidad general y mortalidad por causas infecciosas. Diversas variables de exposición (gravedad, procedimientos ocurrencias y colonización nasofaríngea por MRSA) fueran analizadas en modelos univariados y multivariados. Los factores asociados significativamente a la mortalidad en general o por causas infecciosas fueran: APACHE II y enfermedad pulmonar. La realización de cirugía predijo mejor el pronóstico. La colonización por MRSA no predijo la mortalidad en general (OR=1.02; IC95 por ciento=0.35-3.00; p=0.97) o por causas infecciosas (OR=0.96; IC95 por ciento=0.33-2.89; p=0.96). Los resultados sugieren que, en la ausencia de factores de gravedad, la colonización por MRSA no se asocia al peor pronóstico.

A colonização de nasofaringe por Staphylococcus aureus, resistente à meticilina (Methicillin-resistant S.aureus - MRSA), é comum em pacientes criticamente doentes, mas seu significado prognóstico não é inteiramente conhecido. Realizou-se estudo de coorte retrospectivo com 122 pacientes de uma unidade de terapia intensiva que realizaram triagem semanal para colonização por MRSA. Os desfechos de interesse foram: mortalidade geral e mortalidade por infecção. Diversas variáveis de exposição (gravidade, procedimentos, intercorrências e colonização nasofaríngea por MRSA) foram analisadas em modelos univariados e multivariados. Fatores significativamente associados à mortalidade geral ou por infecção foram: APACHE II e doença pulmonar. A colonização por MRSA não foi preditora de mortalidade geral (OR=1,02; IC95 por cento=0,35-3; p=0,97) ou por infecção (OR=0,96; IC95 por cento=0,33-2,89; p=0,96). Os resultados sugerem que, na ausência de fatores de gravidade, a colonização por MRSA não caracteriza pior prognóstico.

Risk factors of oropharyngeal carriage of Pseudomonas aeruginosa among patients from a Medical-Surgical Intensive Care Unit

Oropharyngeal carriage of Pseudomonas aeruginosa is associated with increased risk of infection and may provide a source for spread of drug-resistant strains. In order to assess the incidence and risk factors of oropharyngeal carriage, we conducted a retrospective cohort study based on results of surveillance cultures (oropharyngeal swabs) from a medical-surgical intensive care unit, collected from March 2005 through May 2006. Variables investigated included demographic characteristics, comorbid conditions, invasive procedures, use of devices and use of antimicrobials. Thirty case patients with P. aeruginosa carriage were identified. Other 84 patients with surveillance cultures negative to P. aeruginosa were enrolled as control subjects. Case patients were more likely to have a solid malignancy (Odds Ratio [OR] = 12.04, 95 percent Confidence Interval [CI] = 1.93-75.09, p=0.008), Acquired Immunodeficiency Syndrome (AIDS, OR = 7.09, 95 percent CI= 1.11-45.39, p = 0.04), central nervous system disease (OR = 4.51, 95 percent CI = 1.52-13.39, p = 0.007), or to have a central venous catheter placed (OR = 7.76, 95 percent CI = 1.68-35.79, p=0.009). The use of quinolones was a protective factor (OR = 0.13, 95 percent CI = 0.03-0.47, p = 0.002). The predominance of comorbidities as risk factors points out a group of patients to whom preventive measures should be directed.