Protective effects of IL18-105G > A and IL18-137C > Ggenetic variants on severity of COVID-19.

OBJECTIVE AND DESIGN: A cross-sectional study evaluated the IL18-105G > A (rs360717) and IL18-137C > G (rs187238) variants on Coronavírus Disease 2019 (COVID-19) severity. SUBJECTS AND METHODS: 528 patients with COVID-19 classifed with mild (n = 157), moderate (n = 63) and critical (n = 308) disease were genotpyed for the IL18-105G > A and IL18-137C > G variants. RESULTS: We observed associations between severe + critical COVID-19 groups (reference group was mild COVID-19) and the IL18-105G > A (p = 0.008) and IL18-137C > G (p = 0.01) variants, which remained significant after adjusting for sex, ethnicity and age. Consequently, we have examined the associations between moderate + critical COVID-19 and the genotypes of both variants using different genetic models. The IL18-105G > A was associated with severe disease (moderate + critical), with effects of the GA genotype in the codominant [Odds ratio (OR), (95 % confidence interval) 0.55, 0.34-0.89, p = 0.015], overdominant (0.56, 0.35-0.89, p = 0.014) and dominant (0.60, 0.38-0.96, p = 0.031) models. IL18-105 GA coupled with age, chest computed tomograhy scan anormalities, body mass index, heart diseases, type 2 diabetes mellitus, hypertension, and inflammation may be used to predict the patients who develop severe disease with an accuracy of 84.3 % (sensitivity: 83.3 % and specificity: 86.5 %). Therefore, the presence of the IL18-105 A allele in homozygosis or heterozygosis conferred about 44.0 % of protection in the development of moderate and severe COVID-19. The IL18-137C > G variant was also associated with protective effects in the codominant (0.55, 0.34-0.89, p = 0.015), overdominant (0.57, 0.36-0.91, p = 0.018), and dominant models (0.59, 0.37-0.93, p = 0.025). Therefore, the IL18-137 G allele showed a protective effect against COVID-19 severity. CONCLUSION: The IL18-105G > A and IL18-137C > Gvariants may contribute with protective effects for COVID-19 severity and the effects of IL18-137C > G may be modulating IL-18 production and Th1-mediated immune responses.

Microbiological environmental contamination in a Pediatric Intensive Care Unit / Contaminação ambiental microbiológica em Unidade de Terapia Intensiva Pediátrica / Contaminación ambiental microbiológica en una Unidad de Cuidados Intensivos Pediátricos

Background and objectives: inanimate surfaces and equipment in the hospital environment are considered reservoirs of resistant and pathogenic microorganisms. In Pediatric Intensive Care Units, the risk of infection is also related to the severity of pathologies associated with the immaturity of the immune system of this population. This study aimed to investigate microbiological environmental contamination in a Pediatric Intensive Care Unit. Method: this is an exploratory cross-sectional study, carried out in a Pediatric Intensive Care Unit of a highly complex university hospital, located in southern Brazil. To assess environmental contamination, sterile swabs were rubbed on surfaces corresponding to the patient unit and in the common area. Results: twenty-eight surfaces were analyzed, 12 of which were located in units occupied by patients at the time of collection and 16 surfaces in the common use area. In the total number of surfaces analyzed by microbiological cultures, the patient unit showed 66.67% contamination by microorganisms, while surfaces in the common area showed 56.25%. Regarding the microbiological profile, all isolated microorganisms were Gram-positive and showed resistance, namely Staphylococcus aureus and coagulase-negative Staphylococcus. Conclusion: there was evidence of a high frequency of contamination on inanimate surfaces and equipment near and far from patients, essentially by pathogenic and multi-resistant microorganisms to antimicrobials.(AU)

Justificativa e objetivos: superfícies e equipamentos inanimados no ambiente hospitalar são considerados reservatórios de microrganismos resistentes e patogênicos. Nas Unidades de Cuidados Intensivos Pediátricos, o risco de infeção também está relacionado com a gravidade das patologias associadas à imaturidade do sistema imunitário desta população. Este estudo teve como objetivo investigar a contaminação microbiológica ambiental em uma Unidade de Terapia Intensiva Pediátrica. Método: trata-se de um estudo exploratório transversal, realizado em uma Unidade de Terapia Intensiva Pediátrica de um hospital universitário de alta complexidade, localizado no Sul do Brasil. Para avaliar a contaminação ambiental, foram esfregados swabs estéreis nas superfícies correspondentes à unidade do paciente e na área comum. Resultados: foram analisadas vinte e oito superfícies, sendo 12 localizadas em unidades ocupadas por pacientes no momento da coleta e 16 superfícies em área de uso comum. No total de superfícies analisadas por culturas microbiológicas, a unidade paciente apresentou 66,67% de contaminação por microrganismos, enquanto as superfícies da área comum apresentaram 56,25%. Quanto ao perfil microbiológico, todos os microrganismos isolados eram Gram-positivos e apresentavam resistência, nomeadamente Staphylococcus aureus e Staphylococcus coagulase-negativa. Conclusão: houve evidência de elevada frequência de contaminação em superfícies inanimadas e equipamentos próximos e distantes dos pacientes, essencialmente por microrganismos patogênicos e multirresistentes aos antimicrobianos.(AU)

Fundamento y objetivos: las superficies y equipos inanimados del ambiente hospitalario son considerados reservorios de microorganismos resistentes y patógenos. En las Unidades de Cuidados Intensivos Pediátricos el riesgo de infección también se relaciona con la gravedad de patologías asociadas a la inmadurez del sistema inmunológico de esta población. Este estudio tuvo como objetivo investigar la contaminación ambiental microbiológica en una Unidad de Cuidados Intensivos Pediátricos. Método: se trata de un estudio exploratorio transversal, realizado en una Unidad de Cuidados Intensivos Pediátricos de un hospital universitario de alta complejidad, ubicado en el sur de Brasil. Para evaluar la contaminación ambiental se frotaron hisopos estériles en las superficies correspondientes a la unidad de pacientes y en el área común. Resultados: se analizaron veintiocho superficies, 12 de las cuales estaban ubicadas en unidades ocupadas por los pacientes en el momento de la recogida y 16 superficies en el área de uso común. Del total de superficies analizadas por cultivos microbiológicos, la unidad de pacientes presentó un 66,67% de contaminación por microorganismos, mientras que las superficies del área común presentaron un 56,25%. En cuanto al perfil microbiológico, todos los microorganismos aislados fueron Gram positivos y presentaron resistencia, concretamente Staphylococcus aureus y Staphylococcus coagulasa negativo. Conclusión: se evidenció alta frecuencia de contaminación en superficies inanimadas y equipos cercanos y lejanos de los pacientes, esencialmente por microorganismos patógenos y multirresistentes a los antimicrobianos.(AU)

High Prevalence of Panton-valentine Leukocidin-encoding Genes in Methicillin-resistant Staphylococcus aureus Isolated from Inpatients with Invasive Infections at a University Hospital in Southern Brazil.

BACKGROUND: Staphylococcus aureus is a major cause of a wide diversity of infections in humans, and the expression of Panton-Valentine Leukocidin (PVL) has been associated with severe clinical syndromes. OBJECTIVES: The present study aimed to investigate the prevalence of PVL-encoding genes in S. aureus isolated from clinical samples of inpatients with invasive infections in a teaching hospital in Southern Brazil. Furthermore, phenotypic and genotypic characteristics of bacterial isolates were analyzed. METHODS: A total of 98 S. aureus isolates recovered from different body sites were characterized according to their antimicrobial susceptibility profile, methicillin-resistance and SCCmec typing, genetic relatedness and occurrence of virulence-encoding genes, such as icaA, lukS-PV/lukF-PV, and tst. RESULTS: Sixty-eight (69.4%) isolates were classified as methicillin-resistant, and among them, four (5.9%) did not harbor the mecA gene. The mecA-harboring methicillin-resistant S. aureus (MRSA) isolates were grouped into SCCmec types I (6.3%), II (64.1%), III (6.3%), IV (15.6%), V (4.7%), and VI (1.6%). One isolate (1.6%) was classified as non-typeable (NT). Seventy isolates (71.4%) were classified as multidrug-resistant. The overall prevalence of virulence-encoding genes was as follows: icaA, 99.0%; tst, 27.5%; and lukS-PV/lukF-PV, 50.0%. The presence of tst gene was significantly higher (p < 0.001) in methicillin-susceptible S. aureus (MSSA) compared to MRSA isolates. CONCLUSION: The present study reports a high prevalence of multidrug-resistant S. aureus harboring lukS-PV/lukF-PV and tst genes in invasive infections. The continuous monitoring of the antimicrobial susceptibility profile and virulence of S. aureus is an important measure for the control of infections caused by this bacterium.

In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach.

In coronavirus disease (COVID-19), the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute infections are accompanied by a sickness symptom complex (SSC) which is highly conserved and protects against infections and hyperinflammation. The aim of this study is to delineate the associations of COVID-19, SSC and NLPR3 rs10157379 T > C and NLPR3 rs10754558 C > G variants; and the protective role of SSC in SARS-CoV-2 infection. We recruited COVID-19 patients, 308 with critical, 63 with moderate and 157 with mild disease. Increased SSC protects against SARS, critical disease, and death due to COVID-19. Increasing age, male sex and rs10754558 CG significantly reduce SSC protection. The rs10157379 CT and rs10754558 GG genotypes are positively associated with SARS. Partial Least Squares analysis shows that a) 41.8% of the variance in critical COVID-19 symptoms is explained by SSC and oxygen saturation (inversely associated), inflammation, chest computed tomography abnormalities, increased body mass index, SARS and age (positively associated); and b) the effects of the NLRP3 rs10157379 and rs10754558 variants on critical COVID-19 are mediated via SSC (protective) and SARS (detrimental). SSC includes anosmia and dysgeusia, and maybe gastrointestinal symptoms. In conclusion, intersections among the rs10754558 variant, age, and sex increase risk towards critical COVID-19 by attenuating SSC. NLRP3 variants play an important role in SARS, and severe and critical COVID-19 especially in elderly male individuals with reduced SSC and with increased BMI, hypertension, and diabetes type 2.

Nasal Carriage by Staphylococcus aureus among Healthcare Workers and Students Attending a University Hospital in Southern Brazil: Prevalence, Phenotypic, and Molecular Characteristics.

BACKGROUND: Staphylococcus aureus can asymptomatically colonize the human anterior nares and skin, and nasal colonization by this bacterium represents a potential risk for development of invasive infections. The aim of this study was to determine the prevalence of S. aureus nasal carriage among healthcare workers and students attending a university hospital and to characterize the isolates phenotypically and molecularly. METHODS: A cross-sectional study was performed with 324 volunteers. Cultures from nasal samples were obtained and S. aureus isolates were characterized according to their antimicrobial susceptibility profile and four virulence factors-encoding genes. MRSA isolates were characterized regarding their oxacillin/cefoxitin susceptibility, SCCmec, and REP-PCR types. Potential risks for S. aureus and MRSA carriage were analyzed. RESULTS: Of 324 nasal samples, 42.9% were identified as S. aureus, of which 28.8% were MRSA. S. aureus carriers were significantly higher in males and students (OR = 2.898, 95%CI 1.553-5.410); however, no variables were associated with MRSA carriage. All isolates were susceptible to vancomycin and the highest rate of resistance was observed for penicillin (90.6%). All isolates harbored the coa gene, and 97.8%, the icaA gene; 15.8% and 6.5% were positive for tst and lukS-PV/lukF-PV genes, respectively. Among MRSA isolates, 45% carried the mecA gene but were phenotypically susceptible to oxacillin/cefoxitin; two harbored the tst and none had lukS-PV/lukF-PV genes. All MRSAs were distributed into six SCCmec types and type I (62.5%) was the most frequent. REP-PCR typing identified four main clusters among MRSA isolates. CONCLUSION: High prevalence of healthcare workers and students were identified as nasal carriers of S. aureus exhibiting different antimicrobial resistance profiles, including mecA-positive oxacillin-susceptible S. aureus (OS-MRSA) and the presence of virulence-encoding genes. Both cohorts may represent potential sources for the emergence of a successful S. aureus strain highly adapted to the hospital environment.

Fatal sepsis caused by mecA-positive oxacillin-susceptible Staphylococcus aureus: First report in a tertiary hospital of southern Brazil.

mecA-positive oxacillin phenotypically susceptible Staphylococcus aureus (OS-MRSA) is increasingly reported worldwide. This bacterium poses a therapeutic threat, as it can be misidentified as an oxacillin-susceptible organism by phenotypic methods that are routinely used in the majority of clinical microbiology laboratories. Herein, we report the first case of fatal sepsis in a 43-year-old female patient caused by an OS-MRSA SCCmec type IVa/ST1/CC1 in a tertiary hospital in southern Brazil, which highlights the difficulties involved in diagnosing this bacterium. Blood cultures and phenotypic susceptibility tests on admission yielded a penicillin-resistant S. aureus. Although vancomycin therapy was initiated, this antibacterial was replaced by oxacillin, based on the susceptibility result. However, the clinical conditions of the patient deteriorated rapidly evolving to fatal septic shock. Clinical microbiology laboratories should consider the use of additional tests to accurately distinguish between various antimicrobial phenotypes of S. aureus.

Disseminated Clonal Complex 5 (CC5) methicillin-resistant Staphylococcus aureus SCCmec type II in a tertiary hospital of Southern Brazil.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of human infections worldwide, with major dominant lineage circulating in particular geographical regions. The Brazilian Epidemic Clone (BEC, SCCmec III, ST 239) has been predominant in most Brazilian hospitals. Here, we report the prevalence of MRSA SCCmec type II exhibiting different STs, most of them belonging to CC5 in a tertiary hospital in Southern Brazil.

Bacteremia causada por Staphylococcus aureus: Uma análise de quinze anos da sensibilidade a antimicrobianos em um hospital terciário do Brasil / Bacteremia caused by Staphylococcus aureus: a fifteen-year analysis of antimicrobial susceptibility in a tertiary hospital in Brazil / Bacteremia causada por Staphylococcus aureus: Un análisis de quince años de la sensibilidad a los antimicrobianos en un hospital terciario de Brasil

Justificativa e Objetivos: Infecções da corrente sanguínea por Staphylococcus aureus constituem uma das principais causas de morbidade e mortalidade em todo mundo. O tratamento de infecções por S. aureus é complexo, em parte, devido à elevada prevalência de resistência aos antimicrobianos. Compreender a epidemiologia e os padrões de resistência deste microrganismo é um ponto crítico para a prescrição empírica adequada de antimicrobianos. Assim, este estudo teve por objetivo avaliar a evolução de resistência antimicrobiana de S. aureus em um período de quinze anos. Métodos: Foram analisados os perfis de sensibilidade para os antimicrobianos ciprofloxacina (5µg); clindamicina (2µg); eritromicina (15µg); gentamicina (10µg); oxacilina (30µg); penicilina (10U); rifampicina (5µg); sulfametoxazol-trimetoprima (23.75/1.25µg) e tetraciclina (30µg) em 720 isolados de S. aureus provenientes de hemoculturas em um hospital terciário do sul do Brasil. Os valores de sensibilidade adotados foram aqueles contidos no CLSI, 2017. Os dados foram obtidos do Sistema de Informação AGTA Healthcare, módulo LABHOS®. Resultados: A frequência média de S. aureus resistente a meticilina foi de 43,74%. Com exceção de penicilina, ocorreu variação significativa da resistência para todos os antimicrobianos no período avaliado (ρ<0,001). Ciprofloxacina (51,14%), eritromicina (44,99%) e clindamicina (39,85%) apresentaram os maiores índices de resistência com tendência de aumento. Surpreendentemente, gentamicina (4%) e sulfametoxazol-trimetoprima (4%) apresentaram queda significativa nos percentuais de resistência. Para vancomicina, do ano 2010 a 2015, observou-se um aumento das concentrações inibitórias mínimas. Conclusão: Embora o índice de resistência tenha aumentado nos quinze anos para a maioria dos antimicrobianos, para sulfametoxazol-trimetoprima e gentamicina ocorreu redução significativa. Este estudo evidenciou, ainda, a emergência do fenótipo S. aureus com resistência intermediária a vancomicina.(AU)

Background and Objectives: Bloodstream infections caused by Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Treatment of S. aureus infections is complex, in part, due to the high prevalence of antimicrobial resistance. Understanding the epidemiology and resistance patterns of this microorganism is a critical point for the proper empirical prescription of antimicrobials. Thus, this study aimed to evaluate the evolution of antimicrobial resistance of S. aureus in a period of fifteen years. Methods: Antimicrobial susceptibility profiles was determined for cefoxitin (30µg), penicillin (10 U), erythromycin (15 µg), clindamycin (2 µg), gentamycin (10 µg),ciprofloxacin (5 µg), sulfamethoxazole-trimethoprim (23.75/1.25 µg), rifampicin (5 µg), and tetracycline (30µg) in 720 S. aureus isolated from blood cultures in a tertiary hospital in southern Brazil were analyzed. Sensiblity values was determined according to Clinical Laboratory Standards Institute (CLSI, 2017).The data were obtained from the AGTA Healthcare Information System, LABHOS® module. Results: The mean frequency of methicillin-resistant S. aureus was 43.74%. Except for penicillin, there was a significant variation of resistance for all antimicrobials in the period evaluated (ρ<0.001). Ciprofloxacin (51.14%), erythromycin (44.99%) and clindamycin (39.85%) had the highest rates of resistance, with tendency to increase. Surprisingly, gentamicina (4%) and sulfamethoxazole-trimethoprim (4%) showed a significant percentage decrease in resistance. For vancomycin, from 2010 to 2015, it was observed an increase in minimum inhibitory concentrations. Conclusion: Although the resistance rate increased in the fifteen years for most antimicrobials, for sulfamethoxazole-trimethoprim and gentamicin a significant reduction occurred, indicating a possible clonal change. This study also evidenced the emergence of S. aureus with intermediate resistance to vancomycin phenotype.(AU)

Justificación y objetivos: Infecciones del flujo sanguíneo por Staphylococcus aureus constituyen una de las principales causas de morbilidad y mortalidad en todo el mundo. El tratamiento de las infecciones por S. aureus es complejo, en parte debido a la elevada prevalencia de resistencia a los antimicrobianos. Comprender la epidemiología y los patrones de resistencia de este microorganismo es un punto crítico para la prescripción empírica adecuada de antimicrobianos. Así, este estudio tuvo por objetivo evaluar la evolución de resistencia antimicrobiana de S. aureus en un período de quince años. Métodos: Se analizaron los perfiles de sensibilidad a los antimicrobianos ciprofloxacino (5µg); clindamicina (2µg); eritromicina (15 µg); gentamicina (10µg); oxacilina (30µg); penicilina (10U); rifampicina (5µg); sulfametoxazol-trimetoprima (23.75 / 1.25 µg) y tetraciclina (30µg) de 720 S. aureus aislados de hemocultivos de un hospital terciario del sur de Brasil. Los valores de sensibilidad adoptados fueron aquellos contenidos en el Clinical Laboratory Standards Institute (CLSI, 2017). Los datos fueron obtenidos del Sistema de Información AGTA Healthcare, módulo LABHOS®. Resultados: La frecuencia media de S. aureus resistente a meticilina fue de 43,74%. Con excepción de la penicilina, hubo variación significativa de la resistencia para todos los antimicrobianos en el período evaluado (ρ<0,001). Ciprofloxacino (51,14%), eritromicina (44,99%) y clindamicina (39,85%) presentaron los mayores índices de resistencia con tendencia de aumento. Sorprendentemente, gentamicina (4%) y sulfametoxazol-trimetoprim (4%) presentaron una caída significativa en los porcentajes de resistencia. Para vancomicina del año 2010 a 2015 se puede evidenciar un aumento de las concentraciones inhibitorias mínimas. Conclusiones: Aunque la resistencia a antimicrobianos aumentó en los quince años para la mayoría de los antimicrobianos, para sulfametoxazol-trimetoprim y gentamicina se produjo una reducción significativa, indicando un posible cambio clonal. Este estudio evidenció, además, la emergencia del fenotipo S. aureus con resistencia intermedia a vancomicina.(AU)