Comparative analysis of the antimicrobial resistance and virulence traits in ESBL-producing-Klebsiella pneumoniae ST307 strains colonizing the gastrointestinal tract and causing a fatal bloodstream infection in a leukemia patient.

Klebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_HM-1) in a leukemia patient. All strains belonged to ST307, carried a transferable IncF plasmid containing the blaCTX-M-15 gene (pKPN3-307 TypeA-like plasmid) and showed a multidrug-resistance phenotype. Phylogenetic analysis demonstrated that Kp_HM-1 was more closely related to Kp_FZcro-1 than to the other colonizing strains. The Kp_FZcol-2 genome showed 81 % coverage with the Kp_HM-1 246,730 bp plasmid (pKp_HM-1), lacking most of its putative virulence genes. Searching public genomes with similar coverage, we observed the occurrence of this deletion in K. pneumoniae ST307 strains recovered from human colonization and infection in different countries. Our findings suggest that strains lacking the putative virulence genes found in the pKPN3-307 TypeA plasmid are still able to colonize and infect humans, highlighting the need to further investigate the role of these genes for the adaptation of K. pneumoniae ST307 in distinct human body sites.

Severe form of lymphocutaneous sporotrichosis: a case report

ABSTRACT Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. It is caused by species of the genus Sporothrix. Infection in humans occurs through the entry of the fungus into the skin. Zoonotic outbreaks involving cats in the transmission of the disease have been frequently reported. The lymphocutaneous form is the most commonly observed and the upper limbs are the most affected sites. We report a case of a 64-year-old healthy female patient with a lymphocutaneous form with rapid progression of lesions, which was refractory to initial treatment with itraconazole. Treatment with liposomal amphotericin B was performed with a satisfactory resolution, but aesthetic and functional sequelae in the left upper limb were installed.

Impacto de Marcadores Inflamatórios no Prognóstico de Pacientes Oncológicos Internados no Instituto Nacional de Câncer com SARS-CoV-2 na Primeira Onda da Pandemia no Brasil / Impact of Inflammatory Markers on the Prognosis of Patients with Cancer Admitted to the National Cancer Institute with SARS-CoV-2 in the First Wave of the Pandemic in Brazil / Impacto de los Marcadores Inflamatorios en el Pronóstico de Pacientes con Cáncer Ingresados en el Instituto Nacional del Cáncer con SARS-CoV-2 en la Primera Ola de la Pandemia en el Brasil

Introdução: O intenso processo inflamatório desencadeado pela covid-19 tem sido apontado por diversos autores. Objetivo: Avaliar o impacto de marcadores inflamatórios no prognóstico de pacientes com tumores sólidos internados com SARS-CoV-2/covid-19 na primeira onda da pandemia no Brasil. Método: Estudo de coorte com pacientes maiores de 18 anos com câncer, internados em um centro público de referência no tratamento oncológico, com SARS-CoV-2/covid-19, no período de março a setembro de 2020. Os seguintes marcadores inflamatórios foram analisados: razão neutrófilo-linfócito (RNL), derivação da razão neutrófilo-linfócito (dRNL) e razão plaqueta-linfócito (RPL). Foi considerado desfecho deste estudo a ocorrência de óbito durante a internação hospitalar. A associação entre as variáveis independentes e o desfecho foi analisada por meio de regressão logística univariada e múltipla. Resultados: Dos 185 pacientes, a maioria apresentava idade < 65 anos (61,1%), performance status (PS) ≥ 2 (82,4%) e estavam em tratamento oncológico (80,0%). O câncer de mama foi o tumor mais frequente (26,5%). Para a maior parte dos casos, o tempo de internação foi ≥ 5 dias (59,5%) e ocorreu em unidade de tratamento intensivo (84,3%). Durante a internação, 86 (46,5%) pacientes evoluíram para óbito. Na análise ajustada, apenas a RNL elevada (≥ 4,44) esteve associada ao risco de morrer (OR 3,54; IC 95%; 1,68 - 7,46; p = 0,001). Conclusão: A RNL se mostrou um importante marcador prognóstico, e níveis acima do seu valor mediano estiveram relacionados ao aumento do risco de morte durante a internação hospitalar

Introduction: The intense inflammatory process triggered by COVID-19 has been pointed out by several authors. Objective: To evaluate the impact of inflammatory markers on the prognosis of patients with solid tumors hospitalized with SARS-CoV-2/COVID-19 in the first wave of the pandemic in Brazil. Method: A cohort study of patients >18 years old with cancer, hospitalized at a public cancer treatment reference center, with SARS-CoV-2/COVID-19 from March to September 2020. The following inflammatory markers were analyzed: neutrophil-lymphocyte ratio (NLR), derivation of the neutrophil-lymphocyte ratio (dNLR) and platelet-lymphocyte ratio (PLR). The outcome of this study was death during hospitalization. The association between the independent variables and the outcome was analyzed using univariate and multiple logistic regression. Results: Of the 185 patients, most were aged < 65 years (61.1%), had performance status (PS) ≥ 2 (82.4%) and were in cancer treatment (80.0%). Breast cancer was the most frequent tumor (26.5%). For the majority of the cases, the length of hospital stay was ≥ 5 days (59.5%) and occurred in the intensive treatment unit (84.3%). During hospitalization, 86 (46.5%) patients progressed to death. In the adjusted analysis only high NLR (≥ 4.44) was associated with the risk of death (OR 3.54; 95% CI; 1.68 - 7.46; p = 0.001). Conclusion: NLR proved to be an important prognostic marker, and levels above its median value were related to an increased risk of death during hospitalization

Introducción: El papel de la inflamación desencadenada por la COVID-19 ha sido señalado por varios autores. Objetivo: Evaluar el impacto de los marcadores inflamatorios en el pronóstico de pacientes con tumores sólidos hospitalizados por SARS-CoV-2/COVID-19 en la primera ola de la pandemia en el Brasil. Método: Estudio de cohorte con pacientes >18 años con cáncer, ingresados en un centro público de referencia en el tratamiento del cáncer, con SARS-CoV-2/COVID-19 de marzo a septiembre de 2020. Se evaluaron los siguientes marcadores inflamatorios: relación neutrófilos-linfocitos (RNL), derivación de la relación neutrófilos-linfocitos (dRNL) y relación plaquetas-linfocitos (RPL). Se consideró como desenlace de este estudio la ocurrencia de muerte durante la hospitalización. La asociación entre las variables independientes y el desenlace se analizó mediante regresión logística univariada y múltiple. Resultados: De los 185 pacientes hospitalizados, la mayoría tenía una edad < 65 años (61,1%), un performance status (PS) ≥ 2 (82,4%) y estaban en tratamiento oncológico (80,0 %). El cáncer de mama fue el tumor más frecuente (26,5%). Para la mayoría de los casos, el tiempo de hospitalización fue ≥ 5 días (59,5%) y ocurrió en la unidad de tratamiento intensivo (84,3%). Durante la hospitalización, 86 (46,5%) pacientes terminaron falleciendo. En el análisis ajustado, solo una RNL alta (≥ 4,44) se asoció con el riesgo de muerte (OR 3,54; IC 95%; 1,68 - 7,46; p = 0,001). Conclusión: La RNL demostró ser un importante marcador pronóstico, y los niveles por encima de su valor medio se relacionaron con un mayor riesgo de muerte durante la hospitalización

Molecular aspects of Chikungunya virus infections in cancer patients.

BACKGROUND: Chikungunya virus (CHIKV) is an arbovirus that can cause chronic and debilitating manifestations. The first autochthonous case in Rio de Janeiro state was diagnosed in 2015, and an outbreak was declared in 2016. OBJECTIVE: The aim of this work was to evaluate CHIKV viral load in serum, plasma and urine in cancer patients to determine the best sample for diagnosis, as well as perform molecular characterisation and phylogenetic analysis of circulating strains. METHODS: Paired serum, plasma and urine collected from 31 cancer patients were tested by real-time quantitative polymerase chain reaction (qPCR) and a segment of the CHIKV E1 gene was sequenced. FINDINGS: We detected 11 CHIKV+ oncological patients. Paired samples analyses of nine patients showed a different pattern of detection. Also, a higher viral load in plasma (6.84 log10) and serum (6.07 log10) vs urine (3.76 log10) was found. Phylogenetic analysis and molecular characterisation revealed East/Central/Southern Africa (ECSA) genotype circulation and three amino acids substitutions (E1-K211T, E1-M269V, E1-T288I) in positive patients. MAIN CONCLUSION: The results indicate the bioequivalence of serum and plasma for CHIKV diagnosis, with urine being an important complement. ECSA genotype was circulating among patients in the period of the 2016 outbreak with K211T, M269V and T288I substitution.

Molecular aspects of Chikungunya virus infections in cancer patients

BACKGROUND Chikungunya virus (CHIKV) is an arbovirus that can cause chronic and debilitating manifestations. The first autochthonous case in Rio de Janeiro state was diagnosed in 2015, and an outbreak was declared in 2016. OBJECTIVE The aim of this work was to evaluate CHIKV viral load in serum, plasma and urine in cancer patients to determine the best sample for diagnosis, as well as perform molecular characterisation and phylogenetic analysis of circulating strains. METHODS Paired serum, plasma and urine collected from 31 cancer patients were tested by real-time quantitative polymerase chain reaction (qPCR) and a segment of the CHIKV E1 gene was sequenced. FINDINGS We detected 11 CHIKV+ oncological patients. Paired samples analyses of nine patients showed a different pattern of detection. Also, a higher viral load in plasma (6.84 log10) and serum (6.07 log10) vs urine (3.76 log10) was found. Phylogenetic analysis and molecular characterisation revealed East/Central/Southern Africa (ECSA) genotype circulation and three amino acids substitutions (E1-K211T, E1-M269V, E1-T288I) in positive patients. MAIN CONCLUSION The results indicate the bioequivalence of serum and plasma for CHIKV diagnosis, with urine being an important complement. ECSA genotype was circulating among patients in the period of the 2016 outbreak with K211T, M269V and T288I substitution.

Risk Factors of Death in Bloodstream Infections Caused by AmpC ß-Lactamase-Producing Enterobacterales in Patients with Neoplasia.

PURPOSE: The infections caused by ESCPM Enterobacterales (Enterobacter spp., Serratia spp., Citrobacter spp., Providencia spp. and Morganella spp.) have limited therapeutic options. Patients with neoplastic diseases are particularly vulnerable to bloodstream infections (BSIs). OBJECTIVE: To analyze determinant factors of death in patients with neoplasia complicated with BSI caused by ESCPM Enterobacterales. PATIENTS AND METHODS: A cohort study of patients aged 18 years or older with neoplasia and BSI due to ESCPM group was conducted at the Cancer Hospital I of the National Cancer Institute, Brazil, from September 2012 to December 2017. The variables associated with death were analyzed using multivariate logistic regression. RESULTS: Of the 103 patients included in the cohort, 67.0% were male, the median age was 63 years and 67.0% had solid tumors. Of the 107 BSI episodes evaluated, 70.1% were hospital-acquired infections, 54.2% were secondary to extravascular focus of infection, gastrointestinal tract (19.6%), mainly. Enterobacter spp. (n: 49, 45.4%) was the most frequent agent isolated followed by Serratia spp. (n: 34, 31.5%), Morganella morganii (n: 16, 14.9%), Citrobacter freundii. (n: 7, 6.5%) and Providencia spp. (n: 2, 1.8%). Ten (9.3%) BSI episodes were caused by multidrug-resistant ESCPM Enterobacterales (MDR-ESCPM). The 7-day and 30-day mortality were 9.3% and 21.5%, respectively. The BSIs caused by MDR-ESCPM were independently associated with 7-day death (OR = 21.62 95% CI: 1.81-258.51 P = 0.01). Monotherapy with piperacillin-tazobactam tended to be associated with 7-day death (OR = 10.46 95% CI: 0.97-112.91 P = 0.05) and 30-day death (OR = 2.73 95% CI: 0.96-7.70 P = 0.05). CONCLUSION: BSIs due to ESCPM group have high mortality and when caused by MDR-ESCPM are independently associated with 7-day death. The possible association of piperacillin-tazobactam monotherapy for BSI-ESCPM with death needs to be better studied.

The impact of ageing on the incidence and mortality rate of bloodstream infection: A hospital-based case-cohort study in a tertiary public hospital of Brazil.

OBJECTIVE: Over the past few decades, life expectancy in Brazil has increased from 48 years in 1950s to 76 years in 2017. The aim of this study was to investigate the impact of ageing on: (1) the frequency of hospitalisations due to bloodstream infection (BSI); (2) the incidence of hospital-acquired BSI (H-BSI); (3) the incidence of BSI caused by multidrug-resistant (MDR) agents and (4) the mortality rate of BSI in a public hospital. METHODS: A hospital-based case-cohort study was conducted between 1 December 2013 and 31 December 2015. The data were analysed using multivariable logistic regression. RESULTS: A total of 500 BSI episodes were detected, among 11,102 hospitalizations. The incidence of hospitalisations resulting from BSI was significantly higher in older than younger patients (3.7/100 vs. 2.0/100, p < 0.01). Similarly, the incidence of hospital-acquired BSI was significantly higher in older patients (2.7/100 vs. 0.9/100, p < 0.01). Klebsiella pneumoniae (15.9%), Staphylococcus aureus (14.3%), Escherichia coli (13.1%) and Acinetobacter spp. (12.1%) were the most common agents isolated. MDR agents caused 37.6% of the BSI episodes; enteric Gram-negative bacilli resistant to third- or fourth-generation cephalosporins (9.7%) and carbapenem-resistant Acinetobacter spp. (9.2%) were the most common MDR agents. The following complications were independently associated with ageing: Charlson comorbidity index (OR = 1.16; 95% CI = 1.09-1.24); BSI secondary to urinary tract infection (OR = 2.14; 95% CI = 1.29-3.55); BSI secondary to pneumonia (OR = 1.77; 95% CI = 1.07-2.93) and 30-day mortality following BSI (OR = 2.19; 95% CI = 1.43-3.36). CONCLUSIONS: These data suggest ageing has a significant impact on hospitalisations due to BSI, H-BSI incidence and mortality from BSI in older patients attending a Brazilian public hospital. Age was not significantly associated with MDR-related BSI. These results indicate that age plays an important role in the increase in morbidities and mortality resulting from BSI in Brazil and that with the increased life expectancy observed over recent decades in Brazil, the burden of BSI will be expected to continue to increase. This dynamic needs to be better understood with additional studies.

Characterization of Ciprofloxacin-Resistant and Ciprofloxacin-Susceptible Uropathogenic Escherichia coli Obtained from Patients with Gynecological Cancer.

The objective of this work was to assess the genetic characteristics of uropathogenic Escherichia coli, ciprofloxacin resistance or susceptibility, obtained from patients with gynecological cancer and urinary tract infection (UTI). Seventy-seven E. coli ciprofloxacin-resistant isolates and 38 ciprofloxacin-susceptible were analyzed by polymerase chain reaction (PCR) to determine the phylogenetic groups, virulence factors as iucC, fyuA, hlyC, cnf1 genes, and pks pathogenicity island. The presence of genes related to ciprofloxacin resistance such as qnrA, qnrB, qnrS, aac(6')-Ib-cr, and qepA, and the sequencing of DNA gyrase genes and topoisomerase IV were determined. The genetic profile of the isolates was determined by pulsed-field gel electrophoresis (PFGE). Statistical analysis was performed using Fisher's exact test and Chi-square test. Phylogenetic group B2 was the most prevalent although a great genetic diversity was observed by PFGE. Only genes associated to siderophores were found in ciprofloxacin-resistant isolates; however, in ciprofloxacin-susceptible isolates, genes related to siderophores and toxin, were detected. Additionally qnrB was detected in both populations, ciprofloxacin resistant and susceptible. DNA mutations in gyrA were Ser-83-Leu and Asp-87-Asn and in parC were Ser-80-Ile and Glu-84-Val, Glu-84-Lys. In conclusion, it was observed a high prevalence of qnrB in the population studied; in addition, it was the first time the pks island was observed only in ciprofloxacin-susceptible isolates.

Time-based distribution of Staphylococcus saprophyticus pulsed field gel-electrophoresis clusters in community-acquired urinary tract infections

The epidemiology of urinary tract infections (UTI) by Staphylococcus saprophyticus has not been fully characterised and strain typing methods have not been validated for this agent. To evaluate whether epidemiological relationships exist between clusters of pulsed field gel-electrophoresis (PFGE) genotypes of S. saprophyticus from community-acquired UTI, a cross-sectional surveillance study was conducted in the city of Rio de Janeiro, Brazil. In total, 32 (16%) female patients attending two walk-in clinics were culture-positive for S. saprophyticus. Five PFGE clusters were defined and evaluated against epidemiological data. The PFGE clusters were grouped in time, suggesting the existence of community point sources of S. saprophyticus. From these point sources, S. saprophyticus strains may spread among individuals.