Abstract Clostridium difficile is a leading cause of diarrhea in hospitalized patients worldwide. While metronidazole and vancomycin are the most prescribed antibiotics for the treatment of this infection, teicoplanin, tigecycline and nitazoxanide are alternatives drugs. Knowledge on the antibiotic susceptibility profiles is a basic step to differentiate recurrence from treatment failure due to antimicrobial resistance. Because C. difficile antimicrobial susceptibility is largely unknown in Brazil, we aimed to determine the profile of C. difficile strains cultivated from stool samples of inpatients with diarrhea and a positive toxin A/B test using both agar dilution and disk diffusion methods. All 50 strains tested were sensitive to metronidazole according to CLSI and EUCAST breakpoints with an MIC90 value of 2 μg/mL. Nitazoxanide and tigecycline were highly active in vitro against these strains with an MIC90 value of 0.125 μg/mL for both antimicrobials. The MIC90 were 4 μg/mL and 2 μg/mL for vancomycin and teicoplanin, respectively. A resistance rate of 8% was observed for moxifloxacin. Disk diffusion can be used as an alternative to screen for moxifloxacin resistance, nitazoxanide, tigecycline and metronidazole susceptibility, but it cannot be used for testing glycopeptides. Our results suggest that C. difficile strains from São Paulo city, Brazil, are susceptible to metronidazole and have low MIC90 values for most of the current therapeutic options available in Brazil.

Rothia aeria is an uncommon pathogen mainly associated with endocarditis in case reports. In previous reports, endocarditis by R. aeria was complicated by central nervous system embolization. In the case we report herein, endocarditis by R. aeria was diagnosed after acute self-limited diarrhea. In addition to the common translocation of R. aeria from the oral cavity, we hypothesize the possibility of intestinal translocation. Matrix-assisted laser desorption ionization-time of flight mass spectrometry and genetic sequencing are important tools that can contribute to early and more accurate etiologic diagnosis of severe infections caused by Gram-positive rods.

RESUMOÉ importante a pesquisa de novos métodos laboratoriais para o diagnóstico de recidivas em casos de co-infecção leishmaniose visceral (LV) e vírus da imunodeficiência humana (HIV), que permitam o diagnóstico precoce das recidivas, utilizando métodos menos invasivos. Descrevemos aqui, o caso de paciente co-infectada que apresentou recidivas após o tratamento da LV e onde a PCR qualitativa demonstrou bom desempenho. A kDNA PCR parece ser ferramenta útil para o diagnóstico de recidivas de LV após o tratamento em pacientes co-infectados com sintomas clínicos da doença.

SUMMARYIt is important to develop new methods for diagnosing relapses in the co-infection of visceral leishmaniasis (VL) and HIV to enable earlier detection using less invasive methods. We report a case of a co-infected patient who had relapses after VL treatment, where the qualitative kDNA PCR showed a good performance. The kDNA PCR seems to be a useful tool for diagnosing VL and may be a good marker for predicting VL relapses after treatment of co-infected patients with clinical symptoms of the disease.

OBJECTIVES: Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16). METHODS: Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively. RESULTS: On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients Cirrhosis (115.88 ±22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ±24.18 mm) (p= 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p=0.005). CONCLUSION: Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.

Lower urinary tract infections are very common diseases. Recurrent urinary tract infections remain challenging to treat because the main treatment option is long-term antibiotic prophylaxis; however, this poses a risk for the emergence of bacterial resistance. Some options to avoid this risk are available, including the use of cranberry products. This article reviews the key methods in using cranberries as a preventive measure for lower urinary tract infections, including in vitro studies and clinical trials.

Apresentamos o caso de uma paciente do sexo feminino, que apresentou quadro de febre hemorrágica da dengue, evoluindo com icterícia e importantes alterações da coagulação. O diagnóstico de dengue foi realizado pela presença de anticorpos IgM antidengue (MAC-ELISA). Esta doença deveria ser considerada no diagnóstico diferencial das icterícias febris agudas.

We describe the case of a female patient who presented a condition of dengue hemorrhagic fever that evolved with jaundice and significant coagulation abnormalities. Dengue was diagnosed through the presence of anti-dengue IgM antibodies (MAC-ELISA). This disease needs to be taken into consideration in the differential diagnosis for acute febrile jaundice.

A síndrome hemofagocitária associada a vírus é uma doença hematológica grave relacionada com algumas síndromes virais. É doença caracterizada por febre persistente, pancitopenia, esplenomegalia, hiperferritinemia e hemofagocitose na medula óssea, fígado e/ou linfonodos. A síndrome hemofagocitária associada ao vírus da hepatite A é raramente descrita, apesar da alta incidência desta infecção viral na população como um todo. Não existem consensos na literatura a respeito do tratamento desta morbidade. Neste artigo, os aspectos clínicos, patogênese, critérios diagnósticos e tratamento da síndrome hemofagocitária associada a vírus, incluindo a descrição de casos publicados da síndrome associada ao vírus da hepatite A.

Virus-Associated Hemophagocytic Syndrome (VAHS) is a severe hematological disorder related to some viral infections. It is an illness characterized by persistent fever, pancytopenia, splenomegaly, hyperferritinemia and, the most important, hemophagocytosis observed in the bone marrow, liver and/or lymph nodes. VAHS associated with hepatitis A virus infection is rarely described, despite the high incidence of this viral infection in the population in general. There is no consensus in the literature regarding the optimal treatment of VAHS. In this article the clinical features, presumed pathogenesis, diagnostic criteria and treatment of VAHS are discussed, including description of cases of VAHS related to hepatitis A virus infection found in the medical literature.

Abscesso subcutâneo por Candida é infecção muito rara mesmo em pacientes imunocomprometidos. Alguns casos são relatados quando ocorre dano na pele, como celulite bacteriana ou abscesso, procedimentos iatrogênicos, trauma e abuso de substância parenteral. Relatamos caso de abscesso subcutâneo por Candida albicans sem fungemia, que pode estar associado com cateter venoso central.

Subcutaneous candidal abscess is a very rare infection even in immunocompromised patients. Some cases are reported when breakdown in the skin occurs, as bacterial cellulites or abscess, iatrogenic procedures, trauma and parenteral substance abuse. We describe a case of Candida albicans subcutaneous abscess without fungemia, which can be associated with central venous catheter.

A osteomielite de osso frontal é uma complicação rara da sinusite frontal. As complicações intracranianas mais comuns da osteomielite frontal são: meningite, empiema epidural, empiema subdural e abscesso cerebral. Relatamos um caso de osteomielite frontal com abscesso cerebral cujo agente etiológico foi o Staphylococcus aureus. Houve melhora significativa após drenagem guiada por agulha e antibiótico por oito semanas e para a osteomielite crônica por quatro meses.

Frontal osteomyelitis is a rare complication of sinusitis. Common intracranial complications of the frontal osteomyelitis are meningitis, epidural empyema, subdural empyema and brain abscess. We described a case of frontal osteomyelitis with brain abscess caused by Staphylococcus aureus with improve after needle aspiration and antibiotics to brain abscess for eight weeks and for chronic osteomyelitis for four months.

We made an open label, multicenter, non-comparative study to assess the efficacy and safety of oral gatifloxacin, 400mg PO given once-daily during 7 to 14 days for the treatment of adult outpatients with community-acquired pneumonia at five Brazilian medical facilities. Among the 86 subjects available for clinical evaluation, 84 (98%) were cured. The bacteriological eradication and presumed eradication rate was 98% (52/53) among the 44 (51%) patients who were bacteriologically evaluated. Drug-related adverse events were reported by 27% of the patients, diarrhea being the most frequent, occurring in 12% of patients. Adverse events were considered mild (89%) or moderate (11%). We conclude that a 7-14 day course of gatifloxacin, 400mg PO given once daily is safe and effective for the treatment of community-acquired pneumonia. The drug had a favorable safety profile and a good clinical and bacteriological efficacy.

Há alguns anos tem-se verificado um aumento progressivo da resistência de alguns cocos gram-positivos a determinados antimicrobianos. Este aumento da resistência tem sido observado principalmente no ambiente hospitalar, e as bactérias mais comumente envolvidas são os Staphylococcus spp. e os Enterococcus spp. Devido a este fato, novos antimicrobianos são avaliados para o tratamento de infecções causadas por estas cepas multirresistentes. A associação quinupristina/dalfopristina (Q/D), também conhecida como Synercid®, é um antibacteriano da classe das estreptograminas, de uso endovenoso, composto por dois derivados semi-sintéticos da pristinamicina. A combinação das estreptograminas B e A na razão de 30:70 tem atividade antimicrobiana voltada para cocos gram--positivos, como Staphylococcus spp., Streptococcus spp., incluindo S. pneumoniae e Enterococcus faecium, sendo o E. faecalis habitualmente resistente. Neste estudo foi avaliada a atividade in vitro de Q/D e outros oito antimicrobianos frente a 631 amostras de cocos gram-positivos isoladas de cinco centros brasileiros, complementadas com outras 20 cepas de E. faecium resistentes à vancomicina, provenientes dos Estados Unidos. Para a avaliação da sensibilidade aos antimicrobianos foi determinada a concentração inibitória mínima (MIC) pelo método do Etest (AB Biodisk, Solna, Suécia) e as cepas testadas foram: Staphylococcus aureus (n = 267), Staphylococcus coagulase negativo (n = 131), Streptococcus pneumoniae (n = 130), Streptococcus beta-hemolíticos (n = 28), Enterococcus faecalis (n = 44) e E. faecium (n = 51). A Q/D demonstrou excelente atividade contra Staphylococcus spp., independente de serem sensíveis ou resistentes à oxacilina. Para S. pneumoniae, a Q/D apresentou igualmente uma ótima atividade, inclusive para as cepas com resistência intermediária ou total para penicilina. Entre as cepas de E. faecium sensíveis à vancomicina, o MIC90 de Q/D obtido foi de 3µg/ml, sendo que 45% das cepas testadas foram sensíveis e 55% apresentaram sensibilidade intermediária à associação. Desta forma, pode-se afirmar que a associação Q/D representa uma nova opção para o tratamento endovenoso de infecções causadas por cocos gram-positivos, principalmente para as cepas multirresistentes, sendo também uma alternativa ao uso de glicopeptídeos.

A progressive increase of resistance among Gram-positive cocci (GPC) towards some antimicrobial agents has been observed for the past few years. This rise of resistance, most often seen in Staphylococcus spp., and Enterococcus spp., has mainly been noticed in hospital environments. Due to these recent patterns of resistance, newly developed antimicrobial agents need to be evaluated for the treatment of infections caused by these multi-resistant microorganisms. Quinupristin/dalfopristin (Q/D), also known as Synercid®, is an antimicrobial agent of intravenous administration, composed of two semi-synthetic derivatives of pristinomycin belonging to the group of streptogramins. The combination of streptogramins B and A at 3:7 ratio has an antimicrobial activity against gram-positive cocci. This combination has potent activity against gram-positive cocci such as Staphylococcus spp., Streptococcus spp. including Streptococcus pneumoniae, and Enterococcus faecium. However, strains of E. faecalis are usually resistant to this compound. The aim of this study was to evaluate the in vitro activity of Q/D and other eight antibiotics against 631 strains of GPC isolated from five Brazilian centers. Additionally, 20 vancomycin-resistant strains of E. faecium provided by a reference center from the United States were also included in this study. Minimal Inhibitory Concentrations (MICs) were determined by E-test methodology (AB Biodisk, Solna, Sweden), using standardized and controlled procedures. The evaluated strains were as follows: Staphylococcus aureus (267), coagulase negative Staphylococcus (131), Streptococcus pneumoniae (130), b-hemolytic Streptococcus (28), Enterococcus faecalis (44), and E. faecium (51). Quinuprintin/dalfopristin presented an excellent activity against Staphylococcus spp., regardless if these were susceptible or not to oxacillin. Against S. pneumoniae, Q/D also presented excellent activitiy regardless of their susceptibility to penicillin. Among vancomycin susceptible E. faecium studied, the MIC90 was 3mg/ml where 45% of the strains were susceptible, and 55% revealed intermediate resistance to quinupristin/dalfopristin. Overall, Q/D showed good activity against Staphylococcus spp., Streptococcus spp. including S. pneumoniae, and Enterococcus faecium representing a new option for the treatment of infections caused by multi-resistant gram-positive cocci, as well as an alternative for the use of glycopeptides.

Dez pacientes com leishmaniose tegumentar americana, acometidos de lesão em mucosa, foram tratados por meio do isotionato de pentamidina na dose de 4mg/kg, em dias alternados, por via endovenosa. A posologia média correspondeu a 2.140mg. A cicatrização das lesões ocoireu em 9 (90%) dos pacientes que completaram o tratamento. Não houve recidiva no período de acompanhamento de 1 a 24 meses (média de 7, 7 meses). Uma paciente interrompeu o tratamento, antes da cicatrização da lesão, por ter desenvolvido diabetes melito. Em 3 (30%) pacientes, o exame de sangue mostrou aumento da uréia e da creatinina e leucopenia, corrigido pelo espaçamento da administração do medicamento. O isotionato de pentamidina é eficiente na cicatrização das lesões, mas hã necessidade de melhor avaliação de seu valor na prevenção das recidivas.

Ten patients with mucosal lesions caused by American tegumental leishmaniasis were treated with pentamidine isothianate at the dose 4 mg/kg on alternate days by the intravenous route. The mean posology was 2,140mg. Healing of the lesions occurred in 9 (90%) of the patients who completed treatment. There was no recurrence during a follow- up time of 1 to 24 months (mean, 7,7 months). One patient discontinued treatment before healing of the lesion because he developed diabetes mellitus. In 3 (30%)patients, blood exams showed increased urea and creatinine levels and leucopenia, which were corrected by increasing the interval between administrations of the drug. Pmtamidine isothianate is efficient in bringing about cicatrization of the lesions but needs further evaluation in terms of its value in preventing recurrence.

O propósito do presente trabalho é colaborar para o estudo da patogenia da plaquetopenia que ocorre na Leptospirose. A pesquisa foi feita de maneira prospectiva e o grupo de casos foi constituído por 30 pacientes internados com hipótese diagnostica de Leptospirose na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Investigou-se a possibilidade de haver consumo de plaquetas por coagulação intravascular disseminada, ou a possibilidade de destruição periférica de plaquetas por anticorpos e, se poderia haver inibição da produção de plaquetas em nível medular. Para a investigação desejada foram utilizados os seguintes exames: contagem de plaquetas, tempo de protrombina, tempo de recalcificação, tempo de trombina, tempo de tromboplastia parcial ativada, dosagem do fibrinogênio, dosagem do fator V, dosagem do fator VIII, dosagem dos produtos de degradação da fibrina, dosagem da antitrombina III, mielograma e pesquisa de anticorpos antiplaquetas. Foram ainda estudados o hemograma, a dosagem de uréia, a dosagem de creatinina, a dosagem das enzimas hepáticas (aspartatoaminotransferase, alaninaaminotransferase, desidrogenase láctica, gamaglutamiltranspeptidade e fosfatase alcalina), e a dosagem das bilirrubinas. A análise dos dados obtidos no presente trabalho permitiu-se chegar às seguintes constatações e conclusões: 1ª) A plaquetopenia é freqüentemente encontrada na forma grave de Leptospirose ocorrida em nosso meio (86,6%). 2ª) A plaquetopenia da Leptospirose não parece ser mediada por anticorpos antiplaquetas. 3ª) A avaliação dos dados obtidos não mostrou haver evidências clínicas e laboratoriais de ocorrência de coagulação intravascular disseminada. 4ª) Verificou-se existência da relação de dependência entre a plaquetogênese medular e a contagem de plaquetas no sangue periférico (P = 0,0261). A possibilidade de haver inibição da plaquetogênese medular por algum produto bacteriano (toxina) não pode ser totalmente afastada, porém acreditamos que o exame estático da medula óssea não pode dar-nos uma idéia precisa do mecanismo dinâmico da formação de plaquetas na presença de "consumo periférico". 5ª) Embora a plaquetopenia possa representar um fator contribuinte para a síndrome hemorrágica, não chegamos a uma diferença estatisticamente significativa entre a contagem das plaquetas nos pacientes plaquetopênicos que sangraram e nos que não apresentaram sangramento. 6ª) Na maioria dos casos (86,3%) a normalização da contagem das plaquetas ocorreu no período de sete dias após a internação. 7ª) Não houve diferença significativa entre as médias dos tempos de normalização da contagem de plaquetas nos pacientes que apresentaram e nos que não apresentaram sangramento. 8ª) Houve diferença significativa, entre as médias das contagens das plaquetas nos pacientes de níveis séricos menores e os níveis séricos mais elevados de uréia, sendo maior no primeiro grupo (t22 = 1,818 > t22:0.05 = 1,717). 9ª) A média do nível sérico dos pacientes que apresentaram sangramento foi maior do que a média do nível sérico de uréia dos pacientes que não sangraram, podendo-se afirmar que a uremia contribui para agravar o quadro hemorrágico na Leptospirose. A vasculite deve ser considerada como fator mais importante na patogênese dos distúrbios hemorrágicos da Leptospirose1,2,8,23, porém, acreditamos que a trombocitopenia, a uremia e os distúrbios da coagulação, isoladamente ou em conjunto, devem ser incluídos entre os fatores que agravam o quadro hemorrágico o qual representa hoje a principal causa de óbito na doença.

The present study has intended to contribute to the elucidation of the pathogenic mechanisms, involved in the thrombocytopenia and in the bleeding diathesis seen in the course of Leptospirosis. The group of cases included in the present prospective study consisted of 30 patients with Leptospirosis, admitted to the Infectious and Parasitic Diseases Ward, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. The following possible mechanisms of thrombocytopenia have been considered and therefore investigated: platelet consumption, due to disseminated intravascular coagulation; immune-mediated platelet destruction, due to platelet-associated antibodies and an inhibited platelet production in the bone marrow. Thrombocytopenia occurred in 86.6% of 30 patients and did not seem to be immune-mediated by platelet-associated antibodies. Furthermore it did not seem to be due to a disseminated intravascular coagulation consumption. Although there was a statistically-significant correlation between bone marrow platelet production and platelet counts we think that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood. Vasculitis should be considered as the most important factor for the pathogenesis of the bleeding disturbances in Leptospirosis. However, we believe that thrombocytopenia, uremia and coagulation disorders, individually or as a group, should be included among the contributing factors that lead to and worsen bleeding episodes, which represent the leading cause of death in this disease.