ant(6)-I Genes encoding aminoglycoside O-nucleotidyltransferases are widely spread among Streptomycin resistant strains of Campylobacter jejuni and Campylobacter coli

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Genome comparison of erythromycin resistant campylobacter from Turkeys identifies hosts and pathways for horizontal spread of erm(B) genes

Los patógenos en el género Campylobacter son la causa más común de gastroenteritis bacteriana transmitida por los alimentos. La campilobacteriosis, causada principalmente por Campylobacter jejuni y Campylobacter coli, se transmite a los humanos mediante alimentos de origen animal, especialmente aves de corral. En cuanto a muchos patógenos, la resistencia antimicrobiana en Campylobacter está aumentando a un ritmo alarmante. La prescripción de eritromicina es el tratamiento de elección para los casos clínicos que requieren terapia antimicrobiana, pero esto se ve comprometido por la movilidad del gen de resistencia a la eritromicina erm (B) entre las cepas. Aquí, evaluamos la resistencia a seis antimicrobianos en 170 aislados de Campylobacter (133 C. coli y 37 C. jejuni) de pavos. Los aislados resistentes a la eritromicina (n = 85; 81 C. coli y 4 C. jejuni) se examinaron en busca de la presencia del gen erm (B), que no se ha identificado previamente en aislamientos de pavos. Se secuenciaron los genomas de dos aislamientos positivos de C. coli y en ambos aislamientos el gen erm (B) se agrupó con determinantes de resistencia contra aminoglucósidos más tetraciclina, incluidos aad9, aadE, aph (2 ") - IIIa, aph (3 ') - IIIa , y genes tet (O). El análisis genómico comparativo identificó secuencias erm (B) idénticas entre Campylobacter de pavos, Streptococcus suis de cerdos y Enterococcus faecium y Clostridium difficile de humanos. Esto es consistente con múltiples eventos de transferencia horizontal entre diferentes especies de bacterias que colonizan pavos. Este ejemplo destaca el potencial de diseminación de la resistencia antimicrobiana a través de los límites de las especies bacterianas que pueden comprometer su efectividad en la terapia antimicrobiana.Pathogens in the genus Campylobacter are the most common cause of food-borne bacterial gastro-enteritis. Campylobacteriosis, caused principally by Campylobacter jejuni and Campylobacter coli, is transmitted to humans by food of animal origin, especially poultry. As for many pathogens, antimicrobial resistance in Campylobacter is increasing at an alarming rate. Erythromycin prescription is the treatment of choice for clinical cases requiring antimicrobial therapy but this is compromised by mobility of the erythromycin resistance gene erm(B) between strains. Here, we evaluate resistance to six antimicrobials in 170 Campylobacter isolates (133 C. coli and 37 C. jejuni) from turkeys. Erythromycin resistant isolates (n = 85; 81 C. coli and 4 C. jejuni) were screened for the presence of the erm(B) gene, that has not previously been identified in isolates from turkeys. The genomes of two positive C. coli isolates were sequenced and in both isolates the erm(B) gene clustered with resistance determinants against aminoglycosides plus tetracycline, including aad9, aadE, aph(2″)-IIIa, aph(3′)-IIIa, and tet(O) genes. Comparative genomic analysis identified identical erm(B) sequences among Campylobacter from turkeys, Streptococcus suis from pigs and Enterococcus faecium and Clostridium difficile from humans. This is consistent with multiple horizontal transfer events among different bacterial species colonizing turkeys. This example highlights the potential for dissemination of antimicrobial resistance across bacterial species boundaries which may compromise their effectiveness in antimicrobial therapy.• Ministerio de Ciencia e Innovación. Ayudas AGL2009-07550, AGL2012-39028 • Ministerio de Agricultura, Alimentación y Medio Ambiente. Ayuda 2014/000223 • Comunidad Autónoma de Madrid. Ayudas S2009 / AGR-1489; S2013 / ABI-2747 • Ministerio de Economía y Competitividad de España. Ayuda AGL2012-39028 • Ministerio de Economía y Competitividad. Beca BES-2013-065003, para Diego Flórez Cuadrado • Consejo de Investigación Médica. Ayuda MR / L015080 / 1, para Samuel K. SheppardpeerReviewe

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

The use of antimicrobials in human and veterinary medicine has coincided with a rise in antimicrobial resistance (AMR) in the food-borne pathogens Campylobacter jejuni and Campylobacter coli. Faecal contamination from the main reservoir hosts (livestock, especially poultry) is the principal route of human infection but little is known about the spread of AMR among source and sink populations. In particular, questions remain about how Campylobacter resistomes interact between species and hosts, and the potential role of sewage as a conduit for the spread of AMR. Here, we investigate the genomic variation associated with AMR in 168 C. jejuni and 92 C. coli strains isolated from humans, livestock and urban effluents in Spain. AMR was tested in vitro and isolate genomes were sequenced and screened for putative AMR genes and alleles. Genes associated with resistance to multiple drug classes were observed in both species and were commonly present in multidrug-resistant genomic islands (GIs), often located on plasmids or mobile elements. In many cases, these loci had alleles that were shared among C. jejuni and C. coli consistent with horizontal transfer. Our results suggest that specific antibiotic resistance genes have spread among Campylobacter isolated from humans, animals and the environment.S.K.S., B.P. and S.C.B. were supported by grants from the Medical Research Council (MR/L015080/1), the Wellcome Trust (088786/C/09/Z), the Food Standards Agency (FS246004) and the Biotechnology and Biological Sciences Research Council (BB/I02464X/1). E.M. received a University of Bath Faculty of Science URSA studentship. D.F.C. is supported by the FPI program (BES-2013-065003) from the Spanish Ministry of Economy and Competitiveness. J.K.C. is supported by a BBSRC KTN PhD studentship (BB/P504750/1)

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Method Comparison for Enhanced Recovery, Isolation and Qualitative Detection of C. jejuni and C. coli from Wastewater Effluent Samples

Seeking a sensitive protocol, culture-dependent methods were compared to detect thermophilic Campylobacter species in untreated urban effluents. We evaluated various combinations of selective media, with and without an enrichment steps, as well as an extra filtration step. Culture-independent real-time quantitative PCR was also included and all detected isolates underwent antimicrobial susceptibility testing. All tested water samples contained Campylobacter DNA, but only 64% were positive after culture. Although enrichment using Preston broth resulted in better recovery of potentially stressed Campylobacter than Bolton or Campyfood broth (CFB), there was no significant increase in efficiency compared to direct plating. The type of selective agar media used, on the other hand, had a significant effect, with CASA plates performing better than mCCDA or CFA ones. Inclusion of an enrichment step increased the ratio of C. coli vs. C. jejuni being isolated. Resistances against all antimicrobials tested were observed in C. coli, but fewer instances of resistance were found in C. jejuni isolates

Effect of seafood peptones on biomass and metabolic activity by Enterococcus faecalis DM19

Eight seafood protein hydrolysates (SPHs) obtained from squid, shrimp and fish gelatin were incorporated as substitutes of peptones in culture media in order to evaluate its effect on survival and metabolic activity (lactic acid, acetic acid and bacteriocins production) of Enterococcus faecalis DM19. The substitution of commercial peptones in culture media by either a shrimp hydrolysate prepared with Protamex, or by squid protein hydrolysates prepared with Esperase or Alkaline protease, stimulated E. faecalis DM19 growth up to 16%. The incorporation of SPHs, mainly from shrimp, in the culture media significantly increased production of lactic and acetic acids in more than 60%. Furthermore, the media containing SPHs stimulated antimicrobial activity by E. faecalis DM19. The inhibitory activity was observed against both Gram-positive and Gram-negative microorganisms, but it was remarkably observed against Listeria monocytogenes. SPHs incorporated in culture media render properties of bio-technological interest, which, together with their low price, make them suitable for industrial use.This research was financed by the Spanish Ministry of Economy and Competitiveness (projects AGL2011-27607, AGL2014-52825-R). Author M. Djellouli is funded by The National Centre of Biotechnology Research (CHER-Stage 06-2013) (CNRBt) of Algeria and ENP (Exceptional National Program) Scholarship provided by the Ministry of Higher Education and Scientific Research of Algeria (099/PNE/ENS./ESPAGNE/2015-2016). Author M. Arancibia is funded by a SENESCYT Scholarship (20100338) provided by the Ecuadorian government.Peer Reviewe

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events