RESUMO
Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34-465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p < 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p < 0.001), and arsenobetaine in urine (rho = 0.33, p < 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p < 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed.
Assuntos
Arsênio , Arsenicais , Poluentes Ambientais , Ácidos Graxos Ômega-3 , Iodo , Mercúrio , Compostos de Metilmercúrio , Selênio , Animais , Gravidez , Feminino , Humanos , Ácidos Graxos , Estudos Prospectivos , Micronutrientes , Alimentos Marinhos , Peixes , Iodo/urina , BiomarcadoresRESUMO
BACKGROUND: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new ß-lactam/ß-lactamase inhibitors may improve outcomes. METHODS: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. RESULTS: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50â hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). CONCLUSIONS: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.
Assuntos
Bacteriemia , Infecções por Klebsiella , Humanos , Klebsiella pneumoniae , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Ceftazidima/uso terapêutico , beta-Lactamases/genética , Proteínas de Bactérias/genética , Compostos Azabicíclicos/uso terapêutico , Combinação de Medicamentos , Inibidores de beta-Lactamases/uso terapêutico , Bacteriemia/tratamento farmacológico , Testes de Sensibilidade MicrobianaRESUMO
OBJECTIVE: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. METHODS: A nested ALS case-control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. RESULTS: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08-3.87) and lead (OR = 1.89, 95% CI = 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. INTERPRETATION: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a-n/a.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/etiologia , Exposição Ambiental , Mercúrio/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , RiscoRESUMO
BACKGROUND: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. OBJECTIVES: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. METHODS: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. RESULTS: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31-1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. DISCUSSION: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.
Assuntos
Coorte de Nascimento , Fluoretos , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Parto , Gravidez , Suécia , Hormônios Tireóideos , Tireotropina , TiroxinaRESUMO
The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.84; 95% confidence interval [CI], 0.67 to 1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa coefficient, 0.90; 95% CI, 0.77 to 1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa coefficient, 0.76; 95% CI, 0.56 to 0.96). Previously identified mutations in the rpoB rifampin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampin-resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates, and our findings support the use of WGS for the detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.
Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Humanos , Masculino , Metronidazol , Testes de Sensibilidade Microbiana , Mutação , New York , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética , Adulto JovemRESUMO
From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.
Assuntos
Brucella/isolamento & purificação , Brucelose/diagnóstico , Técnicas de Laboratório Clínico/normas , Infecção Laboratorial/microbiologia , Exposição Ocupacional/estatística & dados numéricos , Brucella/crescimento & desenvolvimento , Brucelose/etiologia , Contagem de Colônia Microbiana , Humanos , Cidade de Nova Iorque , Exposição Ocupacional/prevenção & controle , Fatores de Risco , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, methylate inorganic arsenic to mono-, di-, and trimethylated arsenic metabolites, which the organism can excrete. In humans and other eukaryotic organisms, the arsenite methyltransferase (AS3MT) protein methylates arsenite. AS3MT sequences from eukaryotic organisms group phylogenetically with predicted eubacterial AS3MT sequences, which has led to the suggestion that AS3MT was acquired from eubacteria by multiple events of horizontal gene transfer. In this study, we evaluated whether 55 (out of which 47 were predicted based on protein sequence similarity) sequences encoding putative AS3MT orthologues in 47 species from different kingdoms can indeed methylate arsenic. Fifty-three of the proteins showed arsenic methylating capacity. For example, the predicted AS3MT of the human gut bacterium Faecalibacterium prausnitzii methylated arsenic efficiently. We performed a kinetic analysis of 14 AS3MT proteins representing two phylogenetically distinct clades (Group 1 and 2) that each contain both eubacterial and eukaryotic sequences. We found that animal and bacterial AS3MTs in Group 1 rarely produce trimethylated arsenic, whereas Hydra vulgaris and the bacterium Rhodopseudomonas palustris in Group 2 produce trimethylated arsenic metabolites. These findings suggest that animals during evolution have acquired different arsenic methylating phenotypes from different bacteria. Further, it shows that humans carry two bacterial systems for arsenic methylation: one bacterium-derived AS3MT from Group 1 incorporated in the human genome and one from Group 2 in F. prausnitzii present in the gut microbiome.
Assuntos
Arsênio/metabolismo , Metiltransferases/metabolismo , Animais , Faecalibacterium prausnitzii/enzimologia , Microbioma Gastrointestinal , Humanos , Hydra/enzimologia , Metilação , Metiltransferases/genética , Filogenia , Rodopseudomonas/enzimologiaRESUMO
We characterized a case of neonatal conjunctivitis in New York, USA, caused by Neisseria meningitidis by using whole-genome sequencing. The case was a rare occurrence, and the isolate obtained belonged to an emerging clade (N. meningitidis US nongroupable urethritis) associated with an increase in cases of urethritis since 2015.
Assuntos
Conjuntivite/epidemiologia , Conjuntivite/microbiologia , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis , Conjuntivite/história , Feminino , Genoma Bacteriano , História do Século XXI , Humanos , Recém-Nascido , Masculino , Infecções Meningocócicas/história , New York/epidemiologia , Filogenia , Polimorfismo de Nucleotídeo Único , Uretrite/epidemiologia , Uretrite/microbiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Bioresorbable vascular scaffolds (BVS) implantation in selected patients with stable angina has been demonstrated feasible and safe. However, limited data are currently available on long-term outcomes after BVS implantation for ST-elevation myocardial infarction (STEMI). Therefore, we sought to assess the safety, efficacy and long-term results of BVS implantation in STEMI patients. METHODS: Retrospective review of all STEMI patients treated with the Absorb® BVS (Abbott Vascular, Santa Clara, CA) or conventional drug eluting stent (DES) between 1 April 2013 and 30 March 2014. Primary outcomes were procedural success, device thrombosis and device-oriented composite endpoint (DOCE) including cardiac death, target vessel myocardial infarction and target lesion revascularization. The study included 54 BVS patients and 121 DES patients. RESULTS: Patients were slightly younger in the BVS group (60 vs. 63 years old, p = .03). Other baseline characteristics were comparable between the two groups. Procedural success was achieved in all patients. Median follow-up was 901 days and 849 days for BVS and DES patients, respectively (p = .01). The cumulative incidence of DOCE was not significantly different between the BVS and DES groups (7.5% vs. 9.1%, hazard ratio [HR]: 0.74 [95% confidence interval (CI): 0.26-2.2], p = NS). Rate of probable/definite device thrombosis were not statistically different between both groups (3.7% vs. 3.3%, p = NS). CONCLUSIONS: The results of this single-centre retrospective study, one of the first assessing long-term safety and efficacy of BVS in STEMI, seems reassuring with similar long-term results as compared with patients treated with conventional DES.
Assuntos
Implantes Absorvíveis , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Alicerces Teciduais , Idoso , Angiografia Coronária , Eletrocardiografia , Feminino , Seguimentos , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Quebeque/epidemiologia , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 µg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Enterobacter/metabolismo , Enterobacteriaceae/genética , Enterobacteriaceae/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana , Epidemiologia MolecularRESUMO
A 39-year-old female presented with a 5-day history of left inferonasal periocular swelling and associated intermittent itching. Ophthalmologic examination demonstrated a 4 × 8 mm subcutaneous painless mass localized anterior to the medial left lower orbital rim. An excision of the mass was performed, and pathology revealed Dirofilaria. The patient improved over the 3 months of postoperative follow-up. Although several human cases of pulmonary dirofilariasis have been reported in the United States, periocular dirofilariasis has been rarely reported in the United States. The case report is in compliance with the Health Insurance Portability and Accountability Act.
Assuntos
Dirofilaria repens/isolamento & purificação , Dirofilariose/diagnóstico , Infecções Oculares Parasitárias/diagnóstico , Doenças Orbitárias/diagnóstico , Adulto , Animais , Diagnóstico Diferencial , Dirofilariose/cirurgia , Infecções Oculares Parasitárias/cirurgia , Feminino , Humanos , New York , Doenças Orbitárias/cirurgiaRESUMO
A bloodstream infection with Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is a serious condition that carries a high mortality rate and is also associated with significant hospital costs. The rapid and accurate identification and differentiation of methicillin-susceptible S. aureus (MSSA) and MRSA directly from positive blood cultures has demonstrated benefits in both patient outcome and cost-of-care metrics. We compare the next-generation Xpert MRSA/SA BC (Xpert) assay to the GeneOhm StaphSR (GeneOhm) assay for the identification and detection of S. aureus and methicillin resistance in prospectively collected blood culture broths containing Gram-positive cocci. All results were compared to routine bacterial culture as the gold standard. Across 8 collection and test sites, the Xpert assay demonstrated a sensitivity of 99.6% (range, 96.4% to 100%) and a specificity of 99.5% (range, 98.0% to 100%) for identifying S. aureus, as well as a sensitivity of 98.1% (range, 87.5% to 100%) and a specificity of 99.6% (range, 98.3% to 100%) for identifying MRSA. In comparison, the GeneOhm assay demonstrated a sensitivity of 99.2% (range, 95.2% to 100%) and a specificity of 96.5% (range, 89.2% to 100%) for identifying S. aureus, as well as a sensitivity of 94.3% (range, 87.5% to 100%) and a specificity of 97.8% (range, 96.1% to 100%) for identifying MRSA. Five of six cultures falsely reported as negative for MRSA by the GeneOhm assay were correctly identified as positive by the Xpert assay, while one culture falsely reported as negative for MRSA by the Xpert assay was correctly reported as positive by the GeneOhm assay.
Assuntos
Bacteriemia/diagnóstico , Técnicas Bacteriológicas/métodos , Sangue/microbiologia , Resistência a Meticilina , Técnicas de Diagnóstico Molecular/métodos , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Bacteriemia/microbiologia , Criança , Pré-Escolar , Humanos , Lactente , Estudos Prospectivos , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genéticaRESUMO
BACKGROUND: Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CR-Kp)-mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains. METHODS: Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage-mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by co-immunization with 2 CPSs, and cross-reactivity was investigated. RESULTS: MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs. CONCLUSIONS: CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.
Assuntos
Antibacterianos/farmacologia , Cápsulas Bacterianas/metabolismo , Carbapenêmicos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Resistência beta-Lactâmica , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antibacterianos/imunologia , Biofilmes/crescimento & desenvolvimento , Atividade Bactericida do Sangue , Feminino , Genótipo , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/isolamento & purificação , Lepidópteros , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Retrospectivos , Análise de Sobrevida , Estados Unidos , VirulênciaRESUMO
The global spread of Klebsiella pneumoniae carbapenemase (KPC) is predominately associated with K. pneumoniae strains genotyped as sequence type 258 (ST258). The first ST258-associated plasmid, pKpQIL, was described in Israel in 2006, but its history in the northeastern United States remains unknown. Six pKpQIL-like plasmids from four K. pneumoniae isolates (three ST258 and one ST234), one Escherichia coli isolate, and one Enterobacter aerogenes isolate, collected from 2003 to 2010 in New York (NY) and New Jersey (NJ) hospitals, were completely sequenced. The sequences and overall sizes of the six plasmids are highly similar to those of pKpQIL; the major difference is that five of six NJ/NY strains harbor blaKPC-2, while pKpQIL contains blaKPC-3. Moreover, a 26.7-kb fragment was inverted in pKpQIL-234 (from ST234 K. pneumoniae), while a 14.5-kb region was deleted in pKpQIL-Ec (from ST131 E. coli). PCR screening of 284 other clinical K. pneumoniae isolates identified 101 (35.6%) harboring pKpQIL-like plasmids from 9 of 10 surveyed hospitals, demonstrating the wide dissemination of pKpQIL in this region of endemicity. Among the positive isolates, 87.1% were typed as ST258 and 88.1% carried blaKPC-2. The finding of pKpQIL-like plasmid in this study from strains that predate the initial report of KPC in Israel provides evidence that pKpQIL may have originated in the United States. Our findings demonstrate that pKpQIL plasmids are both spreading clonally in ST258 strains and spreading horizontally to different sequence types and species, further highlighting the clinical and public health concerns associated with carbapenem resistance.
Assuntos
Proteínas de Bactérias/genética , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Plasmídeos/genética , beta-Lactamases/genética , Genótipo , Hospitais , Dados de Sequência Molecular , New Jersey , New York , Reação em Cadeia da PolimeraseRESUMO
We report the nucleotide sequence of a novel bla(KPC-2)-harboring IncFII(K1) plasmid, pBK32179, isolated from a carbapenem-resistant Klebsiella pneumoniae ST258 strain from a New York City patient. pBK32179 is 165 kb long, consists of a large backbone of pKPN3-like plasmid, and carries an 18.5-kb bla(KPC-2)-containing element that is highly similar to plasmid pKpQIL. pBK32179-like plasmids were identified in 8.3% of strains in a collection of 96 K. pneumoniae isolates from hospitals in the New York City area.
Assuntos
Klebsiella pneumoniae/genética , Plasmídeos/genética , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , Antibacterianos/farmacologia , Sequência de Bases , Carbapenêmicos/farmacologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Dados de Sequência Molecular , New York , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , beta-Lactamases/metabolismoRESUMO
Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) is a rapid and accurate method of identifying microorganisms. Throughout Europe, it is already in routine use but has not yet been widely implemented in the United States, pending FDA approval. Here, we describe two medically complex patients at a large tertiary-care academic medical center with recurring bacteremias caused by distinct but related species. Bacterial identifications were initially obtained using the Vitek-2 system with the GPI card for Enterococcus and the API system for staphylococci. Initial results misled clinicians as to the source and proper management of these patients. Retrospective investigation with MALDI-TOF MS clarified the diagnosis by identifying a single microorganism as the pathogen in each case. To our knowledge, this is one of the first reports in the United States demonstrating the use of MALDI-TOF MS to facilitate the clinical diagnosis in patients with recurrent bacteremias of unclear source.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Técnicas Bacteriológicas/métodos , Enterococcus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Feminino , Humanos , Masculino , Recidiva , Centros de Atenção Terciária , Estados Unidos , Adulto JovemRESUMO
We describe a novel Tn4401 variant (Tn4401d) in epidemic Klebsiella pneumoniae clone ST258, from which a partial bla(KPC) fragment has been excised along with ISKpn7 and a partial tnpA fragment. Nested-PCR experiments confirmed that this region can be removed from distinct Tn4401 isoforms in both K. pneumoniae and Escherichia coli. This study highlights that the region surrounding bla(KPC) is undergoing recombination and that Tn4401 itself is heterogeneous and highly plastic.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Sequência de Bases/genética , Carbapenêmicos/farmacologia , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Elementos de DNA Transponíveis , Escherichia coli/genética , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Deleção de SequênciaRESUMO
We describe a multiplex real-time PCR assay capable of identifying both the epidemic Klebsiella pneumoniae ST258 clone and bla(KPC) carbapenemase genes in a single reaction. The assay displayed excellent sensitivity (100%) and specificity (100%) for identification of ST258 clone and bla(KPC) in a collection of 75 K. pneumoniae isolates comprising 41 sequence types. Our results suggest that this assay is an effective tool for surveillance of this clone among carbapenem-resistant K. pneumoniae clinical isolates.
Assuntos
Proteínas de Bactérias/genética , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , beta-Lactamases/genética , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Klebsiella pneumoniae/efeitos dos fármacosRESUMO
OBJECTIVE: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD: Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.
Assuntos
Selênio , Oligoelementos , Animais , Cálcio , Cobre , Estudos Transversais , Feminino , Humanos , Ferro , Magnésio , Gravidez , Gestantes , Vitaminas , ZincoRESUMO
We report the results of the 3M rapid detection respiratory syncytial virus (RSV) assay. This study includes pediatric patient results from nasopharyngeal swabs submitted from October to December 2009. There was a sensitivity of 74% and specificity approaching 100% compared to the PCR-based xTAG respiratory viral panel.