Clinical and microbiological characteristics of patients colonized or infected by Stenotrophomonas maltophilia: is resistance to sulfamethoxazole/trimethoprim a problem?

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in the last decade. Increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) has been reported in S. maltophilia strains in the past few years, leading to few therapeutic options. We conducted a prospective multicenter study at two Brazilian teaching hospitals that identified S. maltophilia isolates and evaluated their antimicrobial susceptibility profile, SMX/TMP resistance genes and their clonality profile. A total of 106 non-repeated clinical samples of S. maltophilia were evaluated. Resistance to SMX/TMP was identified in 21.6% of the samples, and previous use of SMX/TMP occurred in 19 (82.6%). PCR detected the sul1 gene in 14 of 106 strains (13.2%). Of these isolates, nine displayed resistance to SMX/TMP. The resistant strains presented a polyclonal profile. This opportunistic pathogen has emerged in immunocompromised hosts, with few therapeutic options, which is aggravated by the description of emerging resistance mechanisms, although with a polyclonal distribution profile

Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?

OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), although the frequencies of these symptoms were comparable in patients with and without this infection (p&gt;0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p&gt;0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding, and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population.FAPESPCNPQFederico FoundationWyet

Immunogenicity and safety of influenza A H1N1/2009 vaccine in rheumatic diseases patients under anti-TNF therapy

\\OBJETIVOS: Avaliar a imunogenicidade e a segurança a curto prazo da vacina H1N1 pandêmica em pacientes com artrite reumatóide (AR) e espondiloartrites [ESa - artrite psoriática (AP) e espondilite anquilosante (EA)] recebendo classes distintas de terapia anti-TNF, assim como comparação com pacientes que receberam drogas modificadoras de doenças reumáticas (DMARDs) e controles saudáveis. MÉTODOS: Cento e vinte pacientes (AR, n=41; EA, n=57 e artrite psoriática - AP, n=22) em uso de agentes anti-TNF (monoclonal, n=94 e receptor solúvel, n=26) foram comparados com 116 pacientes com artrite inflamatórias em uso de DMARDs e 117 controles saudáveis. Soroproteção (SP), soroconversão (SC), médias geométricas dos títulos (MGTs), fator de aumento (FI) das MGT e eventos adversos foram avaliados 21 dias após a vacinação. RESULTADOS: Após a imunização, as taxas de SC (58,2% vs 74,3%, p=0,017) foram significativamente menores nos pacientes com espondiloartrites que receberam a terapia anti-TNF, enquanto nenhuma diferença foi observada em pacientes com AR que recebem esta terapia, em comparação com controles saudáveis (p=0,067). Pacientes com espondiloartrites que receberam anticorpos monoclonais (infliximabe/adalimumabe) tiveram uma taxa de SC significativamente menor em comparação com controles saudáveis (51,6% vs. 74,3%, p=0,002) ou para aqueles em uso de DMARDs (51,6% vs. 74,7%, p=0,005), por sua vez não houve diferença para pacientes em uso de etanercepte (86,7% vs. 74,3%, p=0,091). Uma análise dos pacientes com espondiloartrites que apresentaram SC e os que não apresentaram SC revelou que o primeiro grupo teve maior média de idade (p=0,003), maior frequência de anti-TNF (p=0,031) e anticorpos monoclonais (p=0,001), e uma menor frequência de metotrexate (p=0,028). Na regressão logística multivariada, apenas a idade avançada (p=0,015) e tratamento anticorpos monoclonais (p=0,023) permaneceram fatores importantes para a não SC em pacientes com espondiloartrites. CONCLUSÕES: Este estudo mostrou um padrão distinto da resposta imune à vacina contra a gripe pandêmica em pacientes com artrite inflamatória que receberam agentes anti-TNF, com uma imunogenicidade reduzida apenas em pacientes com espondiloartrites usando anticorpos monoclonaisOBJECTIVES: To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in rheumatoid arthritis (RA) and spondyloarthritis patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. METHODS: One hundred and twenty patients (RA, n=41; ankylosing spondylitis - AS, n=57 and psoriatic arthritis - PsA, n=22) under anti-TNF agents (monoclonal, n=94 and soluble receptor, n=26) were compared to 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection (SP), seroconversion (SC), geometric mean titre (GMT), factor increase (FI) in GMT and adverse events were evaluated 21 days after vaccination. RESULTS: After immunisation, SC rates (58.2% vs. 74.3%, p=0.017) were significantly lower in spondyloarthritis patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared to healthy controls (p=0.067). Spondyloarthritis patients receiving monoclonal antibodies (infliximab/adalimumab) had a significantly lower seroconversion rate compared to healthy controls (51.6% vs. 74.3%, p=0.002) or to those under DMARDs (51.6% vs. 74.7%, p=0.005), whereas no difference was observed for patients under etanercept (86.7% vs. 74.3%, p=0.091). Further analysis of non-seroconverting and seronconverting spondyloarthritis patients revealed that the former group had a higher mean age (p=0.003), a higher frequency of anti-TNF (p=0.031) and monoclonal antibodies (p=0.001), and a lower frequency of methotrexate (p=0.028). In multivariate logistic regression, only older age (p=0.015) and monoclonal antibodies treatment (p=0.023) remained significant factors for nonseroconversion in spondyloarthritis patients. CONCLUSIONS: This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in spondyloarthritis patients using monoclonal antibodie

Excess mortality by specific causes of deaths in the city of São Paulo, Brazil, during the COVID-19 pandemic.

BackgroundTo investigate the excess of deaths by specific causes, in the first half of 2020 in the city of São Paulo-Brazil, during the COVID-19 pandemic.MethodsEcological study conducted from 01/01 to 06/30 of 2019 and 2020. Population and mortality data were obtained from DATASUS. The standardized mortality ratio (SMR) by age was calculated by comparing the standardized mortality rate in 2020 to that of 2019, for overall and specific mortality. The ratio between the standardized mortality rate due to COVID-19 in men as compared to women was calculated for 2020. Crude mortality rates were standardized using the direct method.ResultsCOVID-19 was responsible for 94.4% of the excess deaths in São Paulo. In 2020 there was an increase in overall mortality observed among both men (SMR 1.3, 95% CI 1.17-1.42) and women (SMR 1.2, 95% CI 1.06-1.36) as well as a towards reduced mortality for all cancers. Mortality due to COVID-19 was twice as high for men as for women (SMR 2.1, 95% CI 1.67-2.59). There was an excess of deaths observed in men above 45 years of age, and in women from the age group of 60 to 79 years.ConclusionThere was an increase in overall mortality during the first six months of 2020 in São Paulo, which seems to be related to the COVID-19 pandemic. Chronic health conditions, such as cancer and other non-communicable diseases, should not be disregarded