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1.
Emerg Infect Dis ; 26(3): 611-613, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32091370

RESUMO

Bacterial infection is a well-known complication of breast implant surgery. We identified Mycobacterium senegalense, the principal pathogen of bovine farcy of cattle, in a woman after implant-based breast reconstruction. This finding indicates that unusual pathogens should be considered as an etiology of infected breast prostheses.

2.
Antimicrob Agents Chemother ; 64(2)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31767719

RESUMO

Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.

3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31806416

RESUMO

INTRODUCTION: The aim of this study was to evaluate the association between biomass formation and the clinical characteristics and prognosis of Staphylococcus aureus infective endocarditis (IE). METHODS: We prospectively studied 209 S. aureus strains causing IE. Biomass formation was examined using the crystal violet assay and quantified spectrophotometrically. The average (SD) optical density of the biomass was compared for each clinical, microbiological (methicillin-resistance, vancomycin MIC≥1.5µg/ml) and molecular (clonal complex, agr type and agr dysfunction) variable according to their presence or absence. The primary clinical endpoints studied were in-hospital death, severe sepsis, persistent bacteraemia, symptomatic peripheral embolisms and prosthetic valve IE. RESULTS: Mean age was 66.1 years, 61.5% of patients were male and the median age-adjusted Charlson comorbidity index was 5 points (IQR 3-8). In-hospital mortality was 37.3%. Strains belonging to CC5 and CC22 had optical biomass densities [mean (SD) 1.573 (1.14) vs 0.942 (0.98) p<0.001 and 1.720 (0.94) vs 1.028 (1.04) p=0.001, respectively]. Strains belonging to CC5 and CC22 had significantly higher optical biomass densities [1.369 (1.18) vs 0.920 (0.93) p=0.008]. No statistically significant differences were found in the clinical endpoints studied. CONCLUSIONS: High biomass production was associated with CC5 and CC22 but not with higher hospital mortality, septic complications, type of endocarditis, methicillin-resistance, elevated vancomycin MIC or agr dysfunction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31823150

RESUMO

Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical concern. The interplay between antimicrobial resistance and virulence of P. aeruginosa was investigated in in vitro and in vivo studies. Thirty-eight well-characterized (21 MDR and 17 non-MDR) P. aeruginosa strains from patients with bacteraemia were analysed. Resistance phenotype, carbapenemase production, clonal relatedness, type III secretion system genotype, O-antigen serotype, cytotoxicity (ability to lyse cells) on A549 cells, and virulence (lethality in nematodes) in a Caenorhabditis elegans model were investigated. MDR strains showed lower cytotoxicity (35.4 ± 21.30% vs. 45.0 ± 18.78 %; P = 0.044) and virulence (66.7% vs. 100%; P = 0.011) than non-MDR strains. However, the pathogenicity of MDR high-risk clones varied broadly, with ST235 and ST175 clones being the most and least cytotoxic (51.8 ± 10.59% vs. 11.0 ± 1.25%; P < 0.0001) and virulent ([100% vs. 73.1; P = 0.075] and [0% vs. 93.9%; P < 0.0001], respectively). The pathogenicity of the ST235 clone was similar to that of non-MDR strains, and its ability to lyse cells and high virulence were related with the exoU-positive genotype. Furthermore, the O11 serotype was more frequent among the ST235 clone and exoU-positive genotype strains and was also essential for the pathogenicity of P. aeruginosa. Our data suggest that the pathogenicity of MDR high-risk clones is the result not only of the resistance phenotype but also of the virulence genotype. These findings have implications for the clinical management of patients and infection control programmes.

5.
Genes (Basel) ; 10(12)2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766738

RESUMO

Gene Networks (GN), have emerged as an useful tool in recent years for the analysis of different diseases in the field of biomedicine. In particular, GNs have been widely applied for the study and analysis of different types of cancer. In this context, Lung carcinoma is among the most common cancer types and its short life expectancy is partly due to late diagnosis. For this reason, lung cancer biomarkers that can be easily measured are highly demanded in biomedical research. In this work, we present an application of gene co-expression networks in the modelling of lung cancer gene regulatory networks, which ultimately served to the discovery of new biomarkers. For this, a robust GN inference was performed from microarray data concomitantly using three different co-expression measures. Results identified a major cluster of genes involved in SRP-dependent co-translational protein target to membrane, as well as a set of 28 genes that were exclusively found in networks generated from cancer samples. Amongst potential biomarkers, genes N C K A P 1 L and D M D are highlighted due to their implications in a considerable portion of lung and bronchus primary carcinomas. These findings demonstrate the potential of GN reconstruction in the rational prediction of biomarkers.

6.
Future Cardiol ; 15(5): 329-331, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502878

RESUMO

Biography Dr Fernando Chaves is a board-certified hematopathologist with over 15 years of experience in the diagnostic industry, where he has focused on studying, evaluating and bringing to market new laboratory tests for multiple medical conditions. He has worked with innovative researchers in multiple countries and across medical specialties, not only with new assays but also focusing on how to deploy multiparametric algorithms to improve the diagnostic performance of currently available tests. Dr Chaves serves as Global Head of Clinical and Scientific Affairs at Ortho Clinical Diagnostics.

7.
Diabetol Metab Syndr ; 11: 62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384310

RESUMO

Background: Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. Method and results: ADDENDA-BHS2 is a prospective, single-center, active-controlled, open, randomized trial. Ninety-eight participants (40-70 years old) with HbA1c 7-9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. Conclusion: The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations.Trial registration Clinical trial registration: NCT02919345 (September, 2016).

8.
Artigo em Inglês | MEDLINE | ID: mdl-31413826

RESUMO

Background: Nosocomial sepsis is the main problem that preterms have to face during their stay at neonatal intensive care units (NICU). Serratia marcescens is an emerging cause of preterm sepsis but its epidemiology is still largely unknown. Consequently, the aims of this study were to know the rate of preterms colonized by S. marcescens during their stay at the NICU and the characteristics and evolution of the S. marcescens population, including the susceptibility to clinically relevant antibiotics. Methods: Twenty-six preterm infants born with a gestational age ≤ 32 weeks and/or weigh ≤1500 g were included in the study. Samples of meconium and feces (n = 92) were collected during their first month of life of the infants, together with feeding samples after their pass through enteral feeding tubes (n = 37). Samples were inoculated on MacConkey agar plates. The isolates identified as S. marcescens were genotyped using RAPD and PFGE; and antibiotics susceptibility was performed in a Vitek 2 system. Results: A total of 179 S. marcescens isolates were obtained from the samples. PFGE profiling and cluster analysis allowed the classification of the isolates into 7 different S. marcescens clones. PFGE patterns 1 and 3 were the dominant strains in the fecal samples colonizing 31 and 35% of the infants, respectively. Those isolates causing bacteremia in two infants clustered in PFGE pattern 3. Conclusion: S. marcescens is a bacterial species closely associated to the NICU environment. It can be frequently isolated from preterm's feces although only some genetic lineages seem to be associated to sepsis. Enteral feeding tubes act as important reservoirs to keep the S. marcescens population in the NICU. Trial registration: The local ethic committee approved this trial with the reference 09/157.

9.
Int J Antimicrob Agents ; 54(3): 356-360, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254616

RESUMO

BACKGROUND: Staphylococcus aureus may invade and persist intracellularly in prosthetic joint infections (PJIs). Despite optimized treatments with levofloxacin plus rifampin, the intracellular reservoir may lead to infection relapse. This study assessed the intracellular activity of levofloxacin and rifampin in an in-vitro model of human osteoblastic infection. METHODS: Ten meticillin-susceptible S. aureus strains were used to infect osteoblastic MG63 cells. Osteoblasts were challenged with rifampin and levofloxacin at cortical and cancellous bone concentrations. Efficacy was measured as the intracellular counts of colony-forming units (log10CFU) compared with untreated controls. The emergence of small colony variants (SCVs) was determined, and the results were stratified according to the patient's prognosis (six cured and four with persistence/relapse). RESULTS: All regimes led to a significant decrease in CFU count compared with controls (1-2 log10CFU). Levofloxacin was the most effective treatment at both cortical and cancellous bone concentrations (-2.4 to -1.9 log10CFU, respectively). The addition of rifampin to levofloxacin did not improve performance (-1.9 log10CFU for cortical concentration and -1.8 log10 CFU for cancellous concentration). An increase in SCVs was observed in the presence of rifampin. The efficacy of antimicrobials was higher and the formation of SCVs was lower against strains belonging to PJIs with a favourable outcome. CONCLUSIONS: Levofloxacin plus rifampin had good intracellular activity against S. aureus. However, from the intracellular perspective, the addition of rifampin to levofloxacin showed no benefit but could account for an increased number of SCVs.


Assuntos
Antibacterianos/farmacologia , Levofloxacino/farmacologia , Osteoartrite/microbiologia , Osteoblastos/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Rifampina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Linhagem Celular , Contagem de Colônia Microbiana , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Modelos Teóricos
11.
J Cataract Refract Surg ; 45(3): 343-350, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30691922

RESUMO

PURPOSE: To evaluate the safety and efficacy of intracameral (IC) 0.5% moxifloxacin in the prevention of post-cataract endophthalmitis. SETTING: University of Campinas, São Paulo, Brazil. DESIGN: Prospective randomized partially masked single-site clinical trial. METHODS: Patients who had phacoemulsification were randomized into two groups in block sizes of 4. Group A (moxifloxacin group) consisted of patients who received an IC injection of 0.03 mL (150 µg) of undiluted 0.5% moxifloxacin at the end of surgery. Group B (control group) consisted of patients who received no IC medication. The postoperative prescription for both groups consisted of 0.5% moxifloxacin and 0.1% dexamethasone. Patients were monitored for 6 weeks after surgery. The primary outcome was the incidence of acute endophthalmitis in each group. Secondary outcomes were corrected distance visual acuity (CDVA), endothelial cell density (ECD), intraocular pressure (IOP), and central corneal thickness (CCT). RESULTS: The study comprised 3640 eyes from 3640 patients. There were 1818 patients in Group A and 1822 patients in Group B. The incidence of endophthalmitis within 6 weeks of follow-up was 1 (0.05%) of 1818 eyes in the moxifloxacin group and 7 (0.38%) of 1822 eyes in the control group (P = .035). There was no significant difference in CDVA (P = .202), ECD (P = .482), IOP (P = .105), or CCT (P = .558). No ocular or systemic study-related adverse events were observed. CONCLUSIONS: The IC injection of undiluted 0.5% moxifloxacin can be safely applied as the last step of phacoemulsification. It was found to be effective in reducing the risk for endophthalmitis. This study represents the first controlled randomized clinical trial to evaluate the safety and efficacy of IC moxifloxacin in the prevention of post-cataract endophthalmitis.

13.
Database (Oxford) ; 20182018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30295725

RESUMO

Over the past years, herbarium collections worldwide have started to digitize millions of specimens on an industrial scale. Although the imaging costs are steadily falling, capturing the accompanying label information is still predominantly done manually and develops into the principal cost factor. In order to streamline the process of capturing herbarium specimen metadata, we specified a formal extensible workflow integrating a wide range of automated specimen image analysis services. We implemented the workflow on the basis of OpenRefine together with a plugin for handling service calls and responses. The evolving system presently covers the generation of optical character recognition (OCR) from specimen images, the identification of regions of interest in images and the extraction of meaningful information items from OCR. These implementations were developed as part of the Deutsche Forschungsgemeinschaft-funded a standardised and optimised process for data acquisition from digital images of herbarium specimens (StanDAP-Herb) Project.


Assuntos
Armazenamento e Recuperação da Informação , Plantas , Fluxo de Trabalho , Automação , Internet , Software
14.
Infect Dis (Lond) ; 50(11-12): 837-846, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30325676

RESUMO

BACKGROUND: Recent studies have demonstrated improved survival when the management of Staphylococcus aureus bloodstream infection (BSI) is compliant with evidence-based therapeutic interventions. Whether this effect extends to low-risk sources, such as catheter-related BSI, remains unclear. METHODS: We retrospectively included 225 episodes of methicillin-sensitive S. aureus catheter-related BSI diagnosed in our centre during two non-consecutive periods: 2002-2004 (first period (101 episodes)) and 2009-2013 (second period (124 episodes)). We evaluated the adherence (percentage of compliance = (no. of interventions performed/no. of interventions recommended) × 100) to the following bundle: early catheter removal (≤72 hours), early initiation of appropriate antibiotic therapy, adequate sampling of follow-up blood cultures, transthoracic echocardiography (TTE) during hospitalization and adequate duration of therapy. RESULTS: Patients in the second period had a higher burden of comorbidities and more severe underlying conditions. All-cause 30-day mortality was 9.3%, with a significant difference between the first and second periods (13.9% versus 5.6%; p value = .035). Bundle adherence was significantly higher in the second period, particularly for follow-up blood cultures (26.7% versus 48.4%; p value = .001), performance of TTE (45.5% versus 84.7%; p value < .001) and appropriate duration of therapy (34.7% versus 50.0%; p value = .022). Bundle adherence ≥ 55% was associated with lower 30-day mortality (hazard ratio: 0.31; 95% confidence interval: 0.13-0.76). This effect remained significant across propensity score-based models adjusted for septic shock, study period and underlying conditions. CONCLUSIONS: There was a survival benefit in adhering to a bundle of evidence-based interventions in the specific setting of catheter-related BSI due to methicillin-sensitive S. aureus.


Assuntos
Bacteriemia/mortalidade , Infecções Relacionadas a Cateter/mortalidade , Medicina Baseada em Evidências , Qualidade da Assistência à Saúde , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/terapia , Hemocultura , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/terapia , Estudos de Coortes , Feminino , Humanos , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/terapia , Cooperação e Adesão ao Tratamento
15.
Front Microbiol ; 9: 2210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319561

RESUMO

Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality, which varies depending on the source of infection. Nevertheless, the global molecular epidemiology of SAB and its possible association with specific virulence factors remains unclear. Using DNA microarrays, a total of 833 S. aureus strains (785 SAB and 48 colonizing strains) collected in Spain over a period of 15 years (2002-2017) were characterized to determine clonal complex (CC), agr type and repertoire of resistance and virulence genes in order to provide an epidemiological overview of CCs causing bloodstream infection, and to analyze possible associations between virulence genes and the most common sources of bacteremia. The results were also analyzed by acquisition (healthcare-associated [HA] and community-acquired [CA]), methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains, and patient age (adults vs. children). Our results revealed high clonal diversity among SAB strains with up to 28 different CCs. The most prevalent CCs were CC5 (30.8%), CC30 (20.3%), CC45 (8.3%), CC8 (8.4%), CC15 (7.5%), and CC22 (5.9%), which together accounted for 80% of all cases. A higher proportion of CC5 was found among HA strains than CA strains (35.6 vs. 20.2%, p < 0.001). CC5 was associated with methicillin resistance (14.7 vs. 79.4%, p < 0.001), whereas CC30, CC45, and CC15 were correlated with MSSA strains (p < 0.001). Pathogen-related molecular markers significantly associated with a specific source of bacteremia included the presence of sea, undisrupted hlb and isaB genes with catheter-related bacteremia; sed, splE, and fib genes with endocarditis; undisrupted hlb with skin and soft tissue infections; and finally, CC5, msrA resistance gene and hla gene with osteoarticular source. Our study suggests an association between S. aureus genotype and place of acquisition, methicillin resistance and sources of bloodstream infection, and provides a valuable starting point for further research insights into intrinsic pathogenic mechanisms involved in the development of SAB.

16.
J. Health Biol. Sci. (Online) ; 6(4): 463-466, out.-dez. 2018. ilus
Artigo em Português | LILACS | ID: biblio-964448

RESUMO

Introdução: As lesões de esôfago são consideradas graves. Avanços técnicos permitiram aplicar técnicas de cirurgia minimamente invasiva nesse tipo de lesão. Relato de caso: mulher, 22 anos, vítima de perfuração por projétil de arma de fogo transfixante. Após avaliação inicial, foi submetida à toracostomia à direita por hemopneumotórax. No segundo dia de internamento, após o início da dieta por via oral, foi flagrada uma saída de secreção mucoide pelo dreno. A paciente foi submetida à videotoracoscopia à direita, sendo realizada sutura da lesão esofágica associada a patch de pleura parietal e músculo intercostal. Conclusão: a abordagem por videotoracoscopia mostra-se segura e eficaz.(AU)


Introduction: Esophageal injuries are considered serious. Technical advances allowed the application of minimally invasive surgery techniques in this type of lesion. Case report: Woman, 22 years old, victim of transfixing gunfire wound. After initial evaluation, patient was submitted to right thoracostomy due to hemopneumothorax. On the second day of hospitalization, after starting oral diet, the elimination of mucoid secretion from the chest drain was detected. Pacient underwent right-sided videothoracoscopy, in which suturing of an esophageal lesion was performed in association with a parietal pleura and intercostal muscle patch placement. Conclusion: Thoracoscopy approach is safe and effective.(AU)


Assuntos
Doenças do Esôfago , Traumatismos Torácicos , Toracoscopia
17.
Vet Microbiol ; 219: 80-86, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29778209

RESUMO

This study investigated the genetic characteristics of 121 ovine Mannheimia haemolytica isolates from lungs with (n = 75) and without pneumonic lesions (n = 46) using multilocus sequence typing (MLST), virulence-associated gene typing and pulsed-field gel electrophoresis (PFGE). Twelve STs were identified with most isolates (81%) belonged to ST16, ST28 and ST8. Analysis of the M. haemolytica MLST Database indicate a wide distribution of these genotypes in small ruminants, never reported in bovine isolates. This could suggest the adaptation of certain genetic lineages of M. haemolytica to small ruminants. e-BURST analysis grouped most STs into three clonal complexes (CC2, CC8 and CC28), consistent with a clonal population structure of M. haemolytica. Virulence-associated gene typing identified five virulence profiles in 64% and 65.1% of the M. haemolytica isolates from lungs with and without pneumonic lesions, respectively. These data suggest that M. haemolytica isolates from the lungs with and without pneumonic lesions are genetically homogeneous. By PGFE analysis a high level of genetic diversity was observed not only within isolates from lungs without pneumonic lesions but also among isolates from pneumonic lesions (GD 0.69 and GD 0.66, respectively; P > 0.05). These results indicate that multiple strains of M. haemolytica may be associated with individual cases of pneumonia in sheep.


Assuntos
Genótipo , Pulmão/microbiologia , Mannheimia haemolytica/genética , Mannheimia haemolytica/isolamento & purificação , Pasteurelose Pneumônica/microbiologia , Animais , Variação Genética , Pulmão/patologia , Mannheimia haemolytica/classificação , Mannheimia haemolytica/patogenicidade , Tipagem de Sequências Multilocus , Ovinos/microbiologia , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia , Especificidade da Espécie , Virulência/genética
18.
BMC Infect Dis ; 18(1): 177, 2018 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-29661157

RESUMO

BACKGROUND: The ability of Staphylococcus aureus to invade tissues and cause an infectious disease is the result of a multi-factorial process supported by the huge number of virulence factors inherent to this microorganism tightly regulated by the accessory gene regulator (agr). During antimicrobial therapy bacteria may be exposed to sub-inhibitory concentrations (subMICs) of antibiotics that may trigger transcriptional changes that may have an impact on the pathogenesis of infection. The objective of this study was to investigate the effect of oxacillin sub-MICs on agr system expression as the key component in the regulation of virulence in methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA) strains. Furthermore, we studied the genetic basis of the agr locus and their potential association with the expression levels. METHODS: We have examined the expression of RNAIII and agrA mRNA as biomarkers for agr expression in the presence and absence of oxacillin subMICs in 10 MSSA and 4 MRSA clinical strains belonging to 5 clonal complexes (CC45-agrI, CC8-agrI, CC5-agrII, CC15-agrII and CC30-agrIII) causing endovascular complications. The DNA sequences of agr locus were obtained by whole genome sequencing. RESULTS: Our results revealed that exposure to subMICs of oxacillin had an impact on agr locus expression modifying the relative levels of expression with increases in 11 strains and with decreases in 3 strains. Thereby, the exposure to subMICs of oxacillin resulted in higher levels of expression of agr in CC15 and CC45 and lower levels in CC30. We also observed the presence of mutations in agrC and agrA in 13/14 strains with similar mutation profiles among strains within individual CCs except for strains of CC5. Although, agr expression levels differed among strains within CCs, the presence of these mutations was associated with differences in agr expression levels in most cases. CONCLUSIONS: Changes in agr expression induced by exposure to oxacillin subMICs should be considered because they could lead to changes in the virulence modulation and have an adverse effect on the course of infection, especially in certain clonal complexes.


Assuntos
Proteínas de Bactérias/genética , Oxacilina/administração & dosagem , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Transativadores/genética , Antibacterianos/uso terapêutico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Mutação , Óperon/efeitos dos fármacos , Oxacilina/farmacologia , Proteínas Quinases/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Virulência/genética , Fatores de Virulência/genética
19.
Int J Antimicrob Agents ; 52(2): 172-179, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29621591

RESUMO

Predictors of mortality and the impact of multidrug resistance and virulence on patients with Pseudomonas aeruginosa (PA) bacteraemia were evaluated. Patients with PA bacteraemia in a 12-month period were retrospectively analysed. Carbapenemase production, molecular typing and identification of virulence factor ExoU were carried out. The activity of ceftolozane-tazobactam and ceftazidime-avibactam was also investigated. The primary endpoint was 30-day crude mortality. Of 64 patients with bacteraemia, 24 (37.5%) were caused by extensively drug-resistant PA (XDR-PA): 10 (41.7%) cases involved the VIM-2 carbapenemase-producing ST175 clone, 11 (45.8%) the GES-5 carbapenemase-producing ST235 clone, and 3 (12.5%) were non-carbapenemase producers. The exoU genotype was detected in all ST235 strains and in 6 (15%) of the non-XDR isolates. Ceftazidime-avibactam (58.3%) showed greater activity than ceftolozane-tazobactam (12.5%) against XDR-PA isolates, particularly in GES-5 producers (100%). The 30-day crude mortality rate in patients with XDR-PA bacteraemia was higher than in cases caused by susceptible strains (62.5% vs. 30%; P=0.02). Multivariate analysis showed that independent risk factors associated with 30-day crude mortality were Pitt score ≥2 (OR, 42.31; 95% CI, 4.88-366.7; P=0.001) and respiratory source of bacteraemia (OR, 49.13; 95% CI 3.89-620.5; P=0.003). Stratified analysis adjusting for respiratory source revealed a non-significant trend towards higher mortality in patients with bacteraemia caused by the ST235 clone and exoU-producing isolates. These data support the notion that the XDR phenotype associated with the GES-5 carbapenemase-producing ST235 clone and the exoU-positive genotype adversely affects the outcome of patients with PA bacteraemia, particularly those with respiratory tract infections and a severe clinical presentation.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Infecções Respiratórias/microbiologia , beta-Lactamases/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Azabicíclicos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Bacteriemia/patologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/biossíntese , Técnicas de Tipagem Bacteriana , Ceftazidima/farmacologia , Cefalosporinas/farmacologia , Células Clonais , Combinação de Medicamentos , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/mortalidade , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/mortalidade , Infecções Respiratórias/patologia , Estudos Retrospectivos , Análise de Sobrevida , Tazobactam , beta-Lactamases/metabolismo
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