RESUMO

Background: Healthcare-associated infections by carbapenem-resistant Klebsiella pneumoniae are difficult to control. Virulence and antibiotic resistance genes contribute to infection, but the mechanisms associated with the transition from colonization to infection remain unclear. Objective: We investigated the transition from carriage to infection by K. pneumoniae isolates carrying the K. pneumoniae carbapenemase-encoding gene bla KPC (KpKPC). Methods: KpKPC isolates detected within a 10-year period in a single tertiary-care hospital were characterized by pulsed-field gel electrophoresis (PFGE), multilocus sequencing typing, capsular lipopolysaccharide and polysaccharide typing, antimicrobial susceptibility profiles, and the presence of virulence genes. The gastrointestinal load of carbapenem-resistant Enterobacteriaceae and of bla KPC-carrying bacteria was estimated by relative quantification in rectal swabs. Results were evaluated as contributors to the progression from carriage to infection. Results: No PGFE type; ST-, K-, or O-serotypes; antimicrobial susceptibility profiles; or the presence of virulence markers, such yersiniabactin and colibactin, were associated with carriage or infection, with ST437 and ST11 being the most prevalent clones. Admission to intensive and semi-intensive care units was a risk factor for the development of infections (OR 2.79, 95% CI 1.375 to 5.687, P=0.005), but higher intestinal loads of carbapenem-resistant Enterobacteriaceae or of bla KPC-carrying bacteria were the only factors associated with the transition from colonization to infection in this cohort (OR 8.601, 95% CI 2.44 to 30.352, P<0.001). Conclusion: The presence of resistance and virulence mechanisms were not associated with progression from colonization to infection, while intestinal colonization by carbapenem-resistant Enterobacteriacea and, more specifically, the load of gastrointestinal carriage emerged as an important determinant of infection.

Assuntos

Enterobacteriáceas Resistentes a Carbapenêmicos , Infecção Hospitalar , Infecções por Klebsiella , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , beta-Lactamases/genética

RESUMO

BACKGROUND: Since renal failure is one of the main causes of death in patients with Fabry disease (FD), renal follow-up is an important part of clinical monitoring in these patients. Despite its known limitations, serum creatinine is still the most widely used biomarker. While new renal biomarkers are described, their effectiveness has not yet been fully evaluated in relation to FD. OBJECTIVES: This study aimed to compare renal biomarkers commonly and rarely used in the evaluation of FD patients. METHOD: The usual biomarkers for renal monitoring (microalbuminuria, proteinuria, and creatinine) and some more rarely used (cystatin C, beta 2-microglobulin [ß2M], neutrophil gelatinase-associated lipocalin/lipocalin-2) were quantified in the blood and/or urine samples of 40 FD patients, 39 controls without chronic kidney disease (CKD) paired by age and sex and 38 controls with CKD undergoing hemodialysis. RESULTS: Significant statistical differences (p < 0.05) were observed for cystatin C and lipocalin-2 in plasma levels, for ß2M and serum creatinine levels and by estimated glomerular filtration rate when compared FD patients and control group with CKD and for proteinuria and microalbuminuria in urine samples and for lipocalin-2 in plasma levels when compared FD patients and control group without CKD. Urine creatinine (UCreat), pH, and urine specific gravity did not present a significant statistical difference between groups. CONCLUSION: Considering serum creatinine as gold standard, all renal parameters evaluated, including receiver operating characteristic curve, indicated ß2M as the best biomarker, followed by cystatin C, proteinuria and microalbuminuria, while the results for lipocalin-2 and UCreat do not indicate good predictors of renal impairment. It suggests that at least 2 altered biomarkers should be considered to characterize a renal alteration, thereby establishing a better therapeutic course for FD patients. If possible, along with serum creatinine, measurement of ß2M or cystatin C for renal evaluation of Fabry's patients should be considered.

Assuntos

Cistatina C/sangue , Doença de Fabry/sangue , Doença de Fabry/complicações , Lipocalina-2/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Microglobulina beta-2/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Creatinina/urina , Terapia de Reposição de Enzimas , Doença de Fabry/terapia , Feminino , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto Jovem

RESUMO

RATIONALE: Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked multisystem disorder, caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). The clinical manifestations of this disease are severe skeletal deformities, airway obstruction, cardiomyopathy, and neurologic deterioration. PATIENT: The patient was 5 years and 6 months boy, with developmental delay, hearing loss, hepatosplenomegaly, and skeletal dysplasia. He was diagnosed with mucopolysaccharidosis type II based on clinical manifestations, biochemical and genetic analysis. OUTCOMES: The patient carries a new mutation (c.879-1210_1007-218del) in hemizygosis in the IDS gene, which was defined as pathogenic according to the 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines and as responsible for the mucopolysaccharidosis type II phenotype in the patient.