Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Transpl Infect Dis ; : e13256, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32034865

RESUMO

We describe a rare instance of donor-derived OXA-23-producing carbapenem-resistant Acinetobacter baumannii transmission during lung transplantation and the subsequent public health response. This investigation highlights how transplantation can introduce rare multidrug-resistant organisms into different healthcare facilities and regions.

2.
Nat Med ; 25(12): 1858-1864, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31768064

RESUMO

Multidrug resistant organisms are a serious threat to human health1,2. Fast, accurate antibiotic susceptibility testing (AST) is a critical need in addressing escalating antibiotic resistance, since delays in identifying multidrug resistant organisms increase mortality3,4 and use of broad-spectrum antibiotics, further selecting for resistant organisms. Yet current growth-based AST assays, such as broth microdilution5, require several days before informing key clinical decisions. Rapid AST would transform the care of patients with infection while ensuring that our antibiotic arsenal is deployed as efficiently as possible. Growth-based assays are fundamentally constrained in speed by doubling time of the pathogen, and genotypic assays are limited by the ever-growing diversity and complexity of bacterial antibiotic resistance mechanisms. Here we describe a rapid assay for combined genotypic and phenotypic AST through RNA detection, GoPhAST-R, that classifies strains with 94-99% accuracy by coupling machine learning analysis of early antibiotic-induced transcriptional changes with simultaneous detection of key genetic resistance determinants to increase accuracy of resistance detection, facilitate molecular epidemiology and enable early detection of emerging resistance mechanisms. This two-pronged approach provides phenotypic AST 24-36 h faster than standard workflows, with <4 h assay time on a pilot instrument for hybridization-based multiplexed RNA detection implemented directly from positive blood cultures.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , RNA Bacteriano/isolamento & purificação , Antibacterianos/efeitos adversos , Genótipo , Humanos , Aprendizado de Máquina , Fenótipo , RNA Bacteriano/efeitos dos fármacos
3.
Sci Rep ; 9(1): 4516, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872641

RESUMO

Rapid bacterial identification remains a critical challenge in infectious disease diagnostics. We developed a novel molecular approach to detect and identify a wide diversity of bacterial pathogens in a single, simple assay, exploiting the conservation, abundance, and rich phylogenetic content of ribosomal RNA in a rapid fluorescent hybridization assay that requires no amplification or enzymology. Of 117 isolates from 64 species across 4 phyla, this assay identified bacteria with >89% accuracy at the species level and 100% accuracy at the family level, enabling all critical clinical distinctions. In pilot studies on primary clinical specimens, including sputum, blood cultures, and pus, bacteria from 5 different phyla were identified.

4.
Clin Infect Dis ; 68(8): 1327-1334, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30204838

RESUMO

BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.

5.
Open Forum Infect Dis ; 5(6): ofy139, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29992175

RESUMO

Background: In 2010, the Clinical Laboratory and Standards Institute recommended a 3-fold lowering of ceftriaxone breakpoints to 1 mcg/mL for Enterobacteriaceae. Supportive clinical data at the time were from fewer than 50 patients. We compared the clinical outcomes of adults with Enterobacteriaceae bloodstream infections treated with ceftriaxone compared with matched patients (with exact matching on ceftriaxone minimum inhibitory concentrations [MICs]) treated with extended-spectrum agents to determine if ceftriaxone breakpoints could be increased without negatively impacting patient outcomes. Methods: A retrospective cohort study was conducted at 3 large academic medical centers and included patients with Enterobacteriaceae bacteremia with ceftriaxone MICs of 2 mcg/mL treated with ceftriaxone or extended-spectrum ß-lactams (ie, cefepime, piperacillin/tazobactam, meropenem, or imipenem/cilastatin) between 2008 and 2014; 1:2 nearest neighbor propensity score matching was performed to estimate the odds of recurrent bacteremia and mortality within 30 days. Results: Propensity score matching yielded 108 patients in the ceftriaxone group and 216 patients in the extended-spectrum ß-lactam group, with both groups well-balanced on demographics, preexisting medical conditions, severity of illness, source of bacteremia, and source control interventions. No difference in recurrent bacteremia (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.49-2.73) or mortality (OR, 1.27; 95% CI, 0.56-2.91) between the treatment groups was observed for patients with isolates with ceftriaxone MICs of 2 mcg/mL. Only 6 isolates (1.6%) with ceftriaxone MICs of 2 mcg/mL were extended-spectrum ß-lactamase (ESBL)-producing. Conclusions: Our findings suggest that patient outcomes are similar when receiving ceftriaxone vs extended-spectrum agents for the treatment of Enterobacteriaceae bloodstream infections with ceftriaxone MICs of 2 mcg/mL. This warrants consideration of adjusting the ceftriaxone susceptibility breakpoint from 1 to 2 mcg/mL, as a relatively small increase in the antibiotic breakpoint could have the potential to limit the use of large numbers of extended-spectrum antibiotic agents.

7.
J Clin Microbiol ; 56(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29118172

RESUMO

The purpose of this study was to develop the modified carbapenem inactivation method (mCIM) for the detection of carbapenemase-producing Pseudomonas aeruginosa (CP-PA) and carbapenemase-producing Acinetobacter baumannii (CP-AB) and perform a multicenter evaluation of the mCIM and Carba NP tests for these nonfermenters. Thirty P. aeruginosa and 30 A. baumannii isolates previously characterized by whole-genome sequencing from the CDC-FDA Antibiotic Resistance Isolate Bank were evaluated, including CP isolates (Ambler class A, B, and D), non-carbapenemase-producing (non-CP) carbapenem-resistant isolates, and carbapenem-susceptible isolates. Initial comparison of a 1-µl versus 10-µl loop inoculum for the mCIM was performed by two testing sites and showed that 10 µl was required for reliable detection of carbapenemase production among P. aeruginosa and A. baumannii Ten testing sites then evaluated the mCIM using a 10-µl loop inoculum. Overall, the mean sensitivity and specificity of the mCIM for detection of CP-PA across all 10 sites were 98.0% (95% confidence interval [CI], 94.3 to 99.6; range, 86.7 to 100) and 95% (95% CI, 89.8 to 97.7; range, 93.3 to 100), whereas the mean sensitivity and specificity among CP-AB were 79.8% (95% CI, 74.0 to 84.9; range, 36.3 to 95.7) and 52.9% (95% CI, 40.6 to 64.9; range, 28.6 to 100), respectively. At three sites that evaluated the performance of the Carba NP test using the same set of isolates, the mean sensitivity and specificity of the Carba NP test were 97.8% (95% CI, 88.2 to 99.9; range, 93.3 to 100) and 97.8% (95% CI, 88.2 to 99.9; range, 93.3 to 100) for P. aeruginosa and 18.8% (95% CI, 10.4 to 30.1; range, 8.7 to 26.1) and 100% (95% CI, 83.9 to 100; range, 100) for A. baumannii Overall, we found both the mCIM and the Carba NP test to be accurate for detection of carbapenemase production among P. aeruginosa isolates and less reliable for use with A. baumannii isolates.


Assuntos
Acinetobacter baumannii/enzimologia , Antibacterianos/farmacologia , Proteínas de Bactérias/análise , Carbapenêmicos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/enzimologia , beta-Lactamases/análise , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Carbapenêmicos/metabolismo , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/normas , Pseudomonas aeruginosa/efeitos dos fármacos , Sensibilidade e Especificidade , beta-Lactamases/metabolismo
9.
Clin Infect Dis ; 65(6): 1040-1042, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28520901

RESUMO

Candida auris is an emerging, often multidrug-resistant pathogen with important public health implications. Infections are associated with high mortality, and prevention of transmission requires stringent infection control measures, making C. auris a potential barrier to transplantation. We describe the first donor-derived C. auris transmission in a lung transplant recipient.


Assuntos
Candida/isolamento & purificação , Candidíase/transmissão , Transplante de Pulmão/efeitos adversos , Obtenção de Tecidos e Órgãos , Idoso , Candidíase/microbiologia , Evolução Fatal , Humanos , Masculino
10.
J Clin Microbiol ; 55(8): 2321-2333, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28381609

RESUMO

The ability of clinical microbiology laboratories to reliably detect carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) is an important element of the effort to prevent and contain the spread of these pathogens and an integral part of antimicrobial stewardship. All existing methods have limitations. A new, straightforward, inexpensive, and specific phenotypic method for the detection of carbapenemase production, the carbapenem inactivation method (CIM), was recently described. Here we describe a two-stage evaluation of a modified carbapenem inactivation method (mCIM), in which tryptic soy broth was substituted for water during the inactivation step and the length of this incubation was extended. A validation study was performed in a single clinical laboratory to determine the accuracy of the mCIM, followed by a nine-laboratory study to verify the reproducibility of these results and define the zone size cutoff that best discriminated between CP-CRE and members of the family Enterobacteriaceae that do not produce carbapenemases. Bacterial isolates previously characterized through whole-genome sequencing or targeted PCR as to the presence or absence of carbapenemase genes were tested for carbapenemase production using the mCIM; isolates with Ambler class A, B, and D carbapenemases, non-CP-CRE isolates, and carbapenem-susceptible isolates were included. The sensitivity of the mCIM observed in the validation study was 99% (95% confidence interval [95% CI], 93% to 100%), and the specificity was 100% (95% CI, 82% to 100%). In the second stage of the study, the range of sensitivities observed across nine laboratories was 93% to 100%, with a mean of 97%; the range of specificities was 97% to 100%, with a mean of 99%. The mCIM was easy to perform and interpret for Enterobacteriaceae, with results in less than 24 h and excellent reproducibility across laboratories.


Assuntos
Proteínas de Bactérias/análise , Carbapenêmicos/farmacologia , Enterobacteriaceae/enzimologia , Testes de Sensibilidade Microbiana/métodos , beta-Lactamases/análise , Proteínas de Bactérias/metabolismo , Carbapenêmicos/metabolismo , Humanos , Hidrólise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , beta-Lactamases/metabolismo
11.
Clin Chem Lab Med ; 55(7): 956-961, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-27988503

RESUMO

BACKGROUND: Differences between the designs of hepatitis C virus (HCV) viral load assays can result in genotype-related variability in RNA quantification. We tested paired aliquots of plasma specimens from HCV-infected individuals using two versions (v1.0 and v2.0) of the Roche COBAS AmpliPrep/COBAS TaqMan HCV Test (CAP/CTM HCV) and noted variability between results for a subset of specimens; we then sought to determine whether discrepant results were more prevalent among specific HCV genotypes. METHODS: Archived and prospectively-collected plasma samples from 114 unique patients were tested using CAP/CTM HCV v1.0 and v2.0. The HCV genotype result for each patient was determined by retrospectively reviewing laboratory records. RESULTS: All (46/46) specimens with quantifiable viral loads from patients with genotype 1 or 2 infection had CAP/CTM HCV v1.0 and v2.0 results that were within 0.5 log10 IU/mL; in contrast, only 3/11 (27.3%) from patients with HCV genotype 3 (mean difference, 0.56 log10 IU/mL higher with v2.0) and 0/3 (0%) from patients with HCV genotype 4 (mean difference, 0.91 log10 IU/mL higher with v2.0) had results within 0.5 log10 IU/mL. Among specimens with detectable HCV RNA below the lower limit of quantification with v1.0, greater proportions of genotype 3 (4/7, 57.1%) and genotype 4 (3/4, 75.0%) specimens than genotype 1 or 2 specimens (6/30, 20.0%) had v2.0 results within the quantifiable range. CONCLUSIONS: In patients infected with HCV genotype 3, sequential CAP/CTM HCV viral load results should be compared with caution and interpreted in the context of the specific assay version used.


Assuntos
Genótipo , Hepacivirus/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/genética , Taq Polimerase/metabolismo , Hepacivirus/fisiologia , Humanos , Limite de Detecção , RNA Viral/análise , RNA Viral/sangue , Estudos Retrospectivos , Carga Viral
12.
N Engl J Med ; 375(17): 1697, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27783904

Assuntos
Humanos , Masculino
20.
Pediatrics ; 131(3): e959-63, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23420912

RESUMO

A 15-year-old previously healthy male presented with fever, vomiting, diarrhea, malaise, and altered mental status. In the emergency department, the patient appeared acutely ill, was febrile, tachycardic, hypotensive, and slow to respond to commands. He was quickly transferred to the ICU where initial evaluation revealed elevated white blood cell count and inflammatory markers, coagulopathy, abnormal liver function, and renal failure. Head computed tomography, cerebrospinal fluid studies, and blood cultures were negative. He was quickly stabilized with intravenous fluids and broad-spectrum antibiotics. When his mental status improved, the patient consented to HIV testing and was found to be negative using laboratory-based and rapid third-generation HIV type 1 (HIV-1)/HIV type 2 antibody assays. The specimen was subsequently shown to be positive for HIV by a newly licensed fourth-generation antigen/antibody test. HIV-1 Western blot performed on this sample was negative, but molecular testing for HIV-1 RNA 4 days later was positive and confirmed the screening result. The patient was later determined to have a viral load of 5 624 053 copies/mL and subsequently admitted to unprotected receptive anal intercourse 2 weeks before admission. This case demonstrates an atypically severe presentation of acute HIV infection with important lessons for pediatricians. It highlights the need to consider acute HIV infection in the differential diagnosis of the critically ill adolescent and for appropriate testing if acute infection is suspected. This case also illustrates the shortcomings of testing adolescents based only on reported risk and supports Centers for Disease Control and Prevention and American Academy of Pediatrics recommendations for routine testing.


Assuntos
Estado Terminal , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Doença Aguda , Adolescente , Estado Terminal/terapia , Infecções por HIV/sangue , Infecções por HIV/terapia , Humanos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA