PREVALENCE AND PREDICTIVE FACTORS ASSOCIATED WITH POSITIVITY OF SARS-COV-2 SEROLOGICAL MARKERS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AT AN IBD REFERRAL CENTER.

BACKGROUND: Data related to SARS-CoV-2 exposure rates in patients with inflammatory bowel diseases (IBD) are scarce. Objective - Our aim was to determine the prevalence of serological markers of SARS-Cov-2 and the predictive factors for positivity in patients with IBD. METHODS: This is a cross-sectional, observational study carried out from May to September 2020. SARS-CoV-2 serological markers were determined using chemiluminescence immunoassay in 233 IBD patients without evidence of COVID-19 symptoms. Patient age was 36.6±11.1 years, 118 patients were male (50.6%), and 63.1% had Crohn's disease. Patient clinical data were extracted from individual electronic medical records and complemented by a structured interview. RESULTS: Twenty-six out of the 233 patients with IBD had positive serum markers for SARS-CoV-2 (11.2%). Female sex (P<0.003), extra-intestinal manifestations (P=0.004), use of corticosteroids (P=0.049), and previous contact with individuals with flu-like symptoms (P<0.001) or confirmed diagnosis of COVID-19 (P<0.001), were associated with a significant increased rate of positive SARS-Cov-2 serological markers. No significant difference was observed regarding to adherence to protection measures and positivity of SARS-Cov-2 serological markers (P>0.05). CONCLUSION: SARS-CoV-2 previous infection in IBD patients was not that uncommon, and its prevalence was 11.2% in our series. Positivity to SARS-CoV-2 serological markers was associated with female sex, extra-intestinal manifestations, use of corticosteroids, and contact with individuals with suspected or confirmed COVID-19. Studies with longer follow-up periods are needed to confirm these findings.

Prevalêncıa e fatores predıtıvos assocıados à posıtıvıdade dos marcadores serológıcos do SARS-COV-2 em pacıentes com doença ınflamatórıa ıntestınal em um centro de referêncıa em DII / Prevalence and predictive factors associated with positivity of sars-cov-2 serological markers in patients with inflammatory bowel disease at an ibd referral center

ABSTRACT Background: Data related to SARS-CoV-2 exposure rates in patients with inflammatory bowel diseases (IBD) are scarce. Objective - Our aim was to determine the prevalence of serological markers of SARS-Cov-2 and the predictive factors for positivity in patients with IBD. Methods: This is a cross-sectional, observational study carried out from May to September 2020. SARS-CoV-2 serological markers were determined using chemiluminescence immunoassay in 233 IBD patients without evidence of COVID-19 symptoms. Patient age was 36.6±11.1 years, 118 patients were male (50.6%), and 63.1% had Crohn's disease. Patient clinical data were extracted from individual electronic medical records and complemented by a structured interview. Results: Twenty-six out of the 233 patients with IBD had positive serum markers for SARS-CoV-2 (11.2%). Female sex (P<0.003), extra-intestinal manifestations (P=0.004), use of corticosteroids (P=0.049), and previous contact with individuals with flu-like symptoms (P<0.001) or confirmed diagnosis of COVID-19 (P<0.001), were associated with a significant increased rate of positive SARS-Cov-2 serological markers. No significant difference was observed regarding to adherence to protection measures and positivity of SARS-Cov-2 serological markers (P>0.05). Conclusion: SARS-CoV-2 previous infection in IBD patients was not that uncommon, and its prevalence was 11.2% in our series. Positivity to SARS-CoV-2 serological markers was associated with female sex, extra-intestinal manifestations, use of corticosteroids, and contact with individuals with suspected or confirmed COVID-19. Studies with longer follow-up periods are needed to confirm these findings.

RESUMO Contexto: Dados relacionados às taxas de exposição ao SARS-CoV-2 em pacientes com doenças inflamatórias intestinais (DII) são escassos. Objetivo Nosso objetivo foi determinar a prevalência de marcadores sorológicos do SARS-Cov-2 e os fatores preditivos de positividade em pacientes com DII. Métodos: Este foi um estudo transversal observacional realizado no período de maio a setembro de 2020. Os marcadores sorológicos SARS-CoV-2 foram determinados por imunoensaio de quimioluminescência em 233 pacientes com DII sem evidência de sintomas de COVID-19. A idade dos pacientes foi 36,6±11,1 anos, 118 pacientes eram do sexo masculino (50,6%) e 63,1% tinham doença de Crohn. Os dados clínicos dos pacientes foram extraídos de prontuários médicos eletrônicos individuais e complementados por meio de uma entrevista estruturada. Resultados: Vinte e seis dos 233 pacientes com DII apresentaram marcadores sorológicos positivos para SARS-CoV-2 (11,2%). Sexo feminino (P<0,003), manifestações extra-intestinais (P=0,004), uso de corticosteroides (P=0,049) e contato prévio com indivíduos com sintomas gripais (P<0,001) ou diagnóstico confirmado de COVID -19 (P<0,001), foram associados a um aumento significativo da taxa de positividade para marcadores sorológicos do SARS-Cov-2. Não foi observada diferença significativa em relação à adesão às medidas de proteção e positividade dos marcadores sorológicos para o SARS-Cov-2 (P>0,05). Conclusão: A infecção prévia pelo SARS-CoV-2 não é tão incomum em pacientes com DII e sua prevalência em nossa série foi de 11,2%. A positividade aos marcadores sorológicos SARS-CoV-2 foi associada ao sexo feminino, manifestações extra-intestinais, uso de corticosteroides e contato com indivíduos com suspeita ou diagnóstico confirmado de COVID-19. Estudos com períodos de acompanhamento mais longos são necessários para confirmar esses achados.

Does ascitic fluid filtration improve the microbiological diagnosis of spontaneous bacterial peritonitis? An experimental laboratory study / A filtração do líquido ascítico melhora o diagnóstico microbiológico da peritonite bacteriana espontânea? Um estudo experimental laboratorial

Background: Spontaneous Bacterial Peritonitis (SBP) is a serious and frequent complication among cirrhotic patients with ascites and can be diagnosed by cytological analysis of the ascitic fluid. The microbiological culture of ascitic fluid, however, is positive in less than 40% of SBP cases, which often results in inappropriate antimicrobial therapy. Empirical therapy may be suboptimal, increasing patient's risk of aggravation, or overestimated, unnecessarily boosting bacterial resistance. Objective: This experimental laboratory study aimed to standardize and verify the technical feasibility of ascitic fluid vacuum filtration, as a way to optimize the etiological diagnosis of SBP, compared to the automated method. Method: The method evaluated and standardized in this study was ascitic fluid vacuum filtration. Its principle is the concentration of bacteria on a filter membrane. Results: This study included 36 cirrhotic patients treated at a public university hospital between 11.13.2017 and 06.30.2019. Among them, 47.2% (17/36) presented cytology test results compatible with SBP. For these patients, culture sensitivity using the automated method was 35.3% (6/17), against 11.8% (2/17) with the vacuum filtration method. Conclusion: In conclusion, vacuum filtration does not improve the microbiological diagnosis of SBP in this population compared to the automated method (AU)

Contexto: A Peritonite Bacteriana Espontânea (PBE) é uma complicação grave e frequente entre pacientes cirróticos com ascite, diagnosticada por meio da análise citológica do líquido ascítico. A cultura microbiológica do líquido ascítico, por sua vez, é positiva em menos de 40% dos casos de PBE, o que resulta frequentemente na instituição de terapia antimicrobiana inapropriada. A terapia empírica pode ser subótima, aumentando o risco de agravamento do paciente, ou superestimada, impulsionando desnecessariamente a resistência bacteriana. Objetivo: Estudo experimental laboratorial, propôs padronizar e verificar a viabilidade técnica da filtração a vácuo do líquido ascítico, como forma de otimizar o diagnóstico etiológico na PBE, comparativamente ao sistema automatizado de culturas de sangue. Método: O método avaliado e padronizado neste estudo foi a da filtragem a vácuo do líquido ascítico. Esse tem como princípio a concentração da bactéria em uma membrana filtrante. Resultados: Nesse estudo, foram incluídos 36 pacientes cirróticos atendidos em um hospital público universitário, entre 13.11.2017 e 30.06.2019. Entre eles, 47,2% (17/36) apresentaram citologia compatível com PBE. Nesses, a sensibilidade da cultura pelo método semi-automatizado foi de 35,3% (6/17) e da cultura pelo método da filtragem a vácuo foi de 11,8% (2/17). Conclusão: Em conclusão, a filtragem a vácuo não melhora o diagnóstico microbiológico da PBE em relação ao método automatizado (AU)

Assessment of preauthorization and 24-hour expert consultation as a restrictive antimicrobial stewardship bundle in a Brazilian tertiary-care hospital: an interrupted time series analysis.

BACKGROUND: Worldwide, healthcare facilities face high and often inappropriate consumption of antimicrobials. However, there are limited antimicrobial stewardship (ASP) studies from low- and middle-income countries that include restrictive measures and their impacts on antimicrobial consumption. AIM: This study aims to assess the impact of a restrictive bundle (preauthorization requirements and offering consultation with an infectious diseases physician 24 hours a day) on antimicrobial consumption, in a tertiary hospital in Brazil. METHODS: We conducted an interrupted time series analysis (ITS) with pharmacy-based data from January 2010 to December 2018 to evaluate changes of level and slope in antimicrobial consumption (expressed in DDD/1,000 patient-days) after the implementation of the restrictive bundle in September 2014. Fourteen restricted antimicrobials (amphotericin B deoxycholate, liposomal amphotericin B, micafungin, voriconazole, ganciclovir, amikacin, ampicillin/sulbactam, daptomycin, ertapenem, levofloxacin, linezolid, piperacillin/tazobactam, polymyxin B, and tigecycline) and eight unrestricted were analysed. FINDINGS: Among the 14 restricted antimicrobials, four presented a significant negative level change: micafungin (-2,14, p=.027), voriconazole (-14.72, p<.001), ertapenem (-1.89, p=.007) and amikacin (-13.98, p<.001). The only negative slope change was observed for the liposomal amphotericin B, -0.532 (p=.009). The restricted antibiotics group presented an increased consumption trend (1.068, p=.002) compared to the pre-intervention period, a similar change was observed for the unrestricted antibiotics group (1.360, p<.001). CONCLUSION: Preauthorization and 24 hour expert consultation were partially effective as a restrictive antimicrobial stewardship bundle in a Brazilian tertiary-care hospital. Increased consumption of unrestricted antimicrobials was observed as a side effect of the intervention.

Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil.

INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Histoplasmosis Related to Immunosuppression in a Patient with Crohn's Disease: A Diagnostic Challenge.

BACKGROUND Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) alpha with proven efficacy and known safety profile, is currently widely used in the treatment of inflammatory bowel diseases. Increased risk for serious infections and malignant neoplasms secondary to immunosuppression is a major concern during therapy with this medication. Histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum. Disseminated forms of the disease have immunodepression as a major risk factor. CASE REPORT A 39-years-old man had been followed with refractory fistulizing ileocolonic Crohn's disease using combination therapy (infliximab plus azathioprine) and also receiving short courses of steroids. After 2 years of this immunosuppressive therapy, the patient presented with high fever (39.5ºC) for 5 days, associated with profuse sweating, and moderate pain in the left hypochondrium. The patient was hospitalized. Diagnoses of tuberculosis, malignancy, autoimmune diseases, and bacterial and viral infections were rapidly discarded after investigation. Clinical, laboratory, and image signs of liver involvement prompted a guided percutaneous biopsy, which revealed granulomatous hepatitis, with the presence of fungal structures suggestive of Histoplasma capsulatum. Upon treatment with liposomal amphotericin followed by itraconazole, the patient showed an impressively positive clinical response. CONCLUSIONS TNF blockers, particularly when associated with other immunosuppressors, are a serious risk factor for opportunistic infections. This unusual case of disseminated histoplasmosis in a patient with Crohn's disease using infliximab in combination with azathioprine and steroids emphasizes the need for surveillance of this uncommon but potentially lethal complication before starting TNF blockers therapy.

Prevalence of virological and serological markers of SARS-CoV-2 infection in the population of Ribeirão Preto, Southeast Brazil: an epidemiological survey.

INTRODUCTION: This epidemiological household survey aimed to estimate the prevalence of the current and past SARS-CoV-2 infections in Ribeirão Preto, a municipality of southeast Brazil. METHODS: The survey was conducted in two phases using a clustered sampling scheme. The first phase spanned May 1-3 and involved 709 participants. The second phase spanned June 11-14, 2020, and involved 646 participants. RESULTS: During the first phase, RT-PCR performed on nasopharyngeal swabs was positive at 0.14%. The serological tests were positive in 1.27% of the patients during the first phase and 2.79% during the second phase. People living in households with more than five members had a prevalence of 10.83% (95%CI: 1.58-74.27) higher than those living alone or with someone other. Considering the proportion of the positive serological test results with sex and age adjustments, approximately 2.37% (95%CI: 1.32-3.42) of the population had been cumulatively infected by mid-June 2020, which is equivalent to 16,670 people (95%CI: 9,267-24,074). Considering that 68 deaths from the disease in the residents of the city had been confirmed as at the date of the second phase of the survey, the infection fatality rate was estimated to be 0.41% (95%CI: 0.28-0.73). Our results suggest that approximately 88% of the cases of SARS-CoV-2 infection at the time of the survey were not reported to the local epidemiological surveillance service. CONCLUSIONS: The findings of this study provide in-depth knowledge of the COVID-19 pandemic in Brazil and are helpful for the preventive and decision-making policies of public managers.

Unexpected findings of hepatitis B and delta infection in northeastern Brazil: A public health alert.

INTRODUCTION AND OBJECTIVES: Research has shown that hepatitis B (HBV) and Delta virus (HDV) are a worldwide public health problem. This study aims to estimate the prevalence rates of HBV and HDV infection in five municipalities of Maranhão, Northeastern Brazil. MATERIALS AND METHODS: A total sample between 3856 and 4000 individuals. Questionnaires were used to register sociodemographic characteristics and factors associated with transmission. Patients were tested for hepatitis B virus surface antigen (HBsAg), anti-hepatitis B core antigen (anti-HBc), and antibodies against hepatitis Delta virus (anti-HDV). Factors associated with HBV were detected by means of multivariate Poisson regression. RESULTS: Overall, 3983 subjects were included. Ninety-two of the participants were HBsAg-positive (2.30%, 95% CI 1.80-2.80), and anti-HBc was detected in 1535 (38.50%, 95% CI 37-40). The factors associated with the presence of anti-HBc were: (1) Municipality (P<0.001); Age (P<0.001); School education (P<0.001); Illicit drug use (P=0.001); non-HBV vaccine (P=0.041). Among the HBsAg carriers, eight were anti-HDV-positive (8.69%, 95% CI 2.90-14.40). The most frequent HBV genotype was D4. The only HDV genotype was HDV-8. CONCLUSION: HBV exhibited intermediate endemicity in the studied region. Traditional factors were associated with exposure to the virus. The presence of the HDV was confirmed. The most frequent HBV and HDV genotypes were unlike the ones currently described in Brazil.

Cryptococcosis by Cryptococcus neoformans/Cryptococcus gattii Species Complexes in non-HIV-Infected Patients in Southeastern Brazil

Abstract INTRODUCTION: The clinical manifestations of cryptococcosis are usually associated with the infecting agents Cryptococcus neoformans (CN) and C. gattii (CG) species complexes and the host. In this study, non-HIV-infected patients, at a university hospital in southeastern Brazil, had epidemiological and clinical data associated with cryptococcal disease and isolated Cryptococcus species: CN - 24 patients and CG - 12 patients. METHODS: The comparison was comprised of demographic data, predisposing factors, clinical and laboratory manifestations, and outcomes of cryptococcosis patients treated between 2000 and 2016. Immunocompetent and immunosuppressed patients were also compared, irrespective of the infecting species. Cryptococcus spp. were genotyped by PCR-RFLP analysis of the URA5 gene. RESULTS: Infections by the CN species complex (100% VNI genotype) were associated with drug immunosuppression and fungemia, and patients infected with the CG species complex (83% VG II and 17% VGI genotypes) had more evident environmental exposure and higher humoral response. CN and CG affected patients with or without comorbidities. CONCLUSIONS: Diabetes mellitus, other chronic non-infectious diseases, and alcoholism were likely predisposing factors for infection by both CN and CG species. Immunocompetent patients, independent of the infecting Cryptococcus species complexes, showed a higher occurrence of meningitis and a trend toward less fungal dissemination and longer survival than immunosuppressed hosts.

Influence of antiretroviral therapy on bone metabolism of patients with chronic hepatitis B: a review.

Hepatitis B is a major public health problem worldwide and associated with significant mortality. To prevent or delay the deleterious effects of chronic infection by the hepatitis B virus, patients should be carefully followed, and antiviral therapy indicated according to specific recommendations. Currently, available drugs inhibit viral replication and slow or stop the progression of inflammation and fibrosis of the liver. However, the drugs for oral use in the treatment of hepatitis B, jointly referred to as nucleoside/nucleotide analogs, are indicated for prolonged use and have potential side effects. The reduction in bone mineral density was associated with the use of tenofovir, already evaluated in patients infected with HIV because the drug is also part of the therapeutic arsenal for this viral infection. There are few studies on the effects of tenofovir in patients with mono hepatitis B. Therefore, this literature review proposes to examine how hepatitis B acts in the body and the mechanisms by which antiretroviral drugs (especially tenofovir) can affect bone metabolism.

Influence of antiretroviral therapy on bone metabolism of patients with chronic hepatitis B: a review

Abstract Hepatitis B is a major public health problem worldwide and associated with significant mortality. To prevent or delay the deleterious effects of chronic infection by the hepatitis B virus, patients should be carefully followed, and antiviral therapy indicated according to specific recommendations. Currently, available drugs inhibit viral replication and slow or stop the progression of inflammation and fibrosis of the liver. However, the drugs for oral use in the treatment of hepatitis B, jointly referred to as nucleoside/nucleotide analogs, are indicated for prolonged use and have potential side effects. The reduction in bone mineral density was associated with the use of tenofovir, already evaluated in patients infected with HIV because the drug is also part of the therapeutic arsenal for this viral infection. There are few studies on the effects of tenofovir in patients with mono hepatitis B. Therefore, this literature review proposes to examine how hepatitis B acts in the body and the mechanisms by which antiretroviral drugs (especially tenofovir) can affect bone metabolism.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients.

INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

The HLA-G 14-base pair deletion allele and the deletion/deletion genotype are associated with persistent HBe antigenemia in chronic hepatis B infection.

BACKGROUND AND AIMS: HLA-G has well-recognized immunomodulatory properties, and this molecule is frequently expressed in the livers of hepatitis B virus (HBV)-infected patients. Because the HLA-G 14 bp-insertion/deletion polymorphism (rs371194629) has been associated with the magnitude of HLA-G expression, we evaluated this polymorphism in the recognized evolutionary forms of chronic HBV infection. METHODS: We studied 196 chronic HBV-infected patients (118 HBeAg-negative chronic hepatitis, 53 HBeAg-positive chronic hepatitis and 25 inactive carriers exhibiting low levels of serum HBVDNA and persistently normal ALT levels), and 202 healthy individuals. Chronic hepatitis HLA-G typing was performed using PCR-amplified DNA hybridized with specific primers. RESULTS: The frequencies of the insertion/deletion alleles and genotypes were very similar in patients and controls. After patient stratification according to the evolutionary form of the chronic HBV infection, the frequencies of the deletion allele (P=0.0460; OR=1.26; 95%CI=1.01-1.45) and of the deletion/deletion genotype (P=0.0356; OR=2.08; 95%CI=1.05-4.09) were overrepresented in HBeAg-positive patients when compared to HBeAg-negative patients. No differences were observed when HBV inactive carriers were compared to HBeAg-negative chronic hepatitis patients. CONCLUSIONS: Because the 14-bp deletion allele has been associated with increased HLA-G production and because HLA-G may down regulate the cytotoxic activity of TCD8 and NK cells, patients exhibiting the 14-bp deletion allele at single or double doses are at increased risk for developing chronic forms of HBV associated with persistent viremia and worse prognoses.

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility.

UNLABELLED: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

Secular trends in Klebsiella pneumoniae isolated in a tertiary-care hospital: increasing prevalence and accelerated decline in antimicrobial susceptibility

Abstract: INTRODUCTION Klebsiella pneumoniae has become an increasingly important etiologic agent of nosocomial infections in recent years. This is mainly due to the expression of virulence factors and development of resistance to several antimicrobial drugs. METHODS This retrospective study examines data obtained from the microbiology laboratory of a Brazilian tertiary-care hospital. To assess temporal trends in prevalence and antimicrobial susceptibility, K. pneumoniae isolates were analyzed from 2000 to 2013. The relative frequencies of K. pneumoniae isolation were calculated among all Gram-negative bacilli isolated in each period analyzed. Susceptibility tests were performed using automated systems. RESULTS: From 2000-2006, K. pneumonia isolates comprised 10.7% of isolated Gram-negative bacilli (455/4260). From 2007-2013, this percentage was 18.1% (965/5331). Strictly considering isolates from bloodstream infections, the relative annual prevalence of K. pneumoniae increased from 14-17% to 27-32% during the same periods. A progressive decrease in K. pneumoniae susceptibility to all antimicrobial agents assessed was detected. Partial resistance was also observed to antimicrobial drugs that have been used more recently, such as colistin and tigecycline. CONCLUSIONS Our study indicates that K. pneumoniae has become a major pathogen among hospitalized patients and confirms its recent trend of increasing antimicrobial resistance.

IL-18, TNF, and IFN-γ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury.

This study evaluated the association of polymorphisms in the IL-18 (-607C/A and -137C/G), IFNγ (+874 A/T), and TNF (-238 A/G and -308 A/G) genes with susceptibility to HBV infection and severity of liver injury. A total of 259 chronic HBV-infected patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy individuals were studied. Four Single Nucleotide Polymorphisms (SNPs) were amplified by Polymerase Chain Reaction (PCR). Liver biopsy was performed in 212 HBV-infected patients and classified according to severity of liver fibrosis (scores 0-4) and necroinflammatory activity (HAI scores 0-18). TNF-308*A allele (P < 0.001; OR = 2.16) and TNF -308 AA genotype (P = 0.026; OR = 5.43) were associated with susceptibility to HBV infection. An association was found between severe liver fibrosis when compared to mild fibrosis and the following polymorphisms: Alleles IL-18 -137*G (P = 0.004; OR = 3.45), TNF -308*A (P < 0.001; OR = 3.39), and IFNγ +874*T (P = 0.029; OR = 1.85) and IL-18 -137 GG genotype (P = 0.009; OR = 3.70). No significant association was found between IL-18 (-607 A/C) polymorphism and severity of liver fibrosis. Alleles IL-18 -137*G (P = 0.028; OR = 2.64) and TNF-308*A (P = 0.002; OR = 3.06) and IL-18 -137 GG genotype (P = 0.011; OR = 4.20) were associated with severe necroinflammatory activity (HAI>12) when compared to mild necroinflammatory activity (HAI 1-8). The results suggest that IL-18 -137C/G, TNF-308 G/A and IFNγ +874 A/T SNPs were associated to more severe liver injury in chronic HBV infection. TNF -308*A allele and TNF -308 AA genotype could play a role in the susceptibility to HBV infection.

Histoplasmosis in immunocompetent individuals living in an endemic area in the Brazilian Southeast.

INTRODUCTION: The distribution of infection by Histoplasma capsulatum in Brazil is heterogeneous, and the number of cases affecting immunocompetent individuals is relatively small. This study reports the epidemiological and clinical data regarding histoplasmosis in non-immunosuppressed individuals. METHODS: The study included only the immunocompetent patients with histoplasmosis who were diagnosed between 1970 and 2012 at a university hospital located in Ribeirão Preto, State of São Paulo, Brazil. Clinical and epidemiological data were collected retrospectively from the patient records. RESULTS: Of the 123 patients analyzed, 95 had an active disease that manifested in the different clinical forms of histoplasmosis. Men were the predominant gender, and most patients resided in the Northeast of the State of São Paulo and in the nearby municipalities of the State of Minas Gerais. The risk factors for acquiring histoplasmosis and prolonged contact in a rural environment were recorded in 43.9% and 82.9% of cases, respectively. Smoking, alcoholism, and comorbidity rates were high among the patients with the chronic pulmonary and subacute/chronic disseminated forms of histoplasmosis. Many patients achieved clinical cure spontaneously, but 58.9% required antifungals; the disease lethality rate was 5.3%. CONCLUSIONS: Immunocompetent individuals manifested the diverse clinical forms of histoplasmosis over a period of 4 decades, revealing an additional endemic area of this fungal disease in the Brazilian Southeast.

Histoplasmosis in immunocompetent individuals living in an endemic area in the Brazilian Southeast

Introduction The distribution of infection by Histoplasma capsulatum in Brazil is heterogeneous, and the number of cases affecting immunocompetent individuals is relatively small. This study reports the epidemiological and clinical data regarding histoplasmosis in non-immunosuppressed individuals. Methods The study included only the immunocompetent patients with histoplasmosis who were diagnosed between 1970 and 2012 at a university hospital located in Ribeirão Preto, State of São Paulo, Brazil. Clinical and epidemiological data were collected retrospectively from the patient records. Results Of the 123 patients analyzed, 95 had an active disease that manifested in the different clinical forms of histoplasmosis. Men were the predominant gender, and most patients resided in the Northeast of the State of São Paulo and in the nearby municipalities of the State of Minas Gerais. The risk factors for acquiring histoplasmosis and prolonged contact in a rural environment were recorded in 43.9% and 82.9% of cases, respectively. Smoking, alcoholism, and comorbidity rates were high among the patients with the chronic pulmonary and subacute/chronic disseminated forms of histoplasmosis. Many patients achieved clinical cure spontaneously, but 58.9% required antifungals; the disease lethality rate was 5.3%. Conclusions Immunocompetent individuals manifested the diverse clinical forms of histoplasmosis over a period of 4 decades, revealing an additional endemic area of this fungal disease in the Brazilian Southeast. .