#Antimicrobial #resistance in #MRSA to newer antimicrobial agents (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Antimicrobial resistance in methicillin-resistant Staphylococcus aureus to newer antimicrobial agents

Richard R. Watkins, Marisa Holubar, Michael Z. David

DOI: 10.1128/AAC.01216-19



Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) result in significant morbidity and mortality for patients in both community and health care settings. This is primarily due to the difficulty in treating MRSA, which is often resistant to multiple classes of antibiotics. Understanding the mechanisms of antimicrobial resistance (AMR) in MRSA provides insight into the optimal use of antimicrobial agents in clinical practice and also underpins critical aspects of antimicrobial stewardship programs. In this review we delineate the mechanisms, prevalence, and clinical importance of resistance to antibiotics licensed in the past 20 years that target MRSA, as well as new drugs in the pipeline which are likely to be licensed soon. Current gaps in scientific knowledge about MRSA resistance mechanisms are discussed, and topics in the epidemiology of AMR in S. aureus that require further investigation are highlighted.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA.



#Evolution of a 72-kb cointegrant, conjugative #multiresistance #plasmid from early CA #MRSA isolates (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Evolution of a 72-kb cointegrant, conjugative multiresistance plasmid from early community-associated methicillin-resistant Staphylococcus aureus isolates

Karina Yui Eto, Neville Firth, Amy M. Davis, Stephen M. Kwong, Marcelina Krysiak, Yung Thin Lee, Frances G. O’Brien, Warren B. Grubb, Geoffrey W. Coombs, Charles S. Bond, Joshua P. Ramsay

DOI: 10.1128/AAC.01560-19



Horizontal transfer of plasmids encoding antimicrobial-resistance and virulence determinants has been instrumental in Staphylococcus aureus evolution, including the emergence of community-associated methicillin-resistant S. aureus (CA-MRSA). In the early 1990s the first CA-MRSA isolated in Western Australia (WA), WA-5, encoded cadmium, tetracycline and penicillin-resistance genes on plasmid pWBG753 (∼30 kb). WA-5 and pWBG753 appeared only briefly in WA, however, fusidic-acid-resistance plasmids related to pWBG753 were also present in the first European CA-MRSA at the time. Here we characterized a 72-kb conjugative plasmid pWBG731 present in multiresistant WA-5-like clones from the same period. pWBG731 was a cointegrant formed from pWBG753 and a pWBG749-family conjugative plasmid. pWBG731 carried mupirocin, trimethoprim, cadmium and penicillin-resistance genes. The stepwise evolution of pWBG731 likely occurred through the combined actions of IS257, IS257-dependent miniature inverted-repeat transposable elements (MITEs) and the BinL resolution system of the β-lactamase transposon Tn552. An evolutionary intermediate ∼42-kb non-conjugative plasmid pWBG715, possessed the same resistance genes as pWBG731 but retained an integrated copy of the small tetracycline-resistance plasmid pT181. IS257 likely facilitated replacement of pT181 with conjugation genes on pWBG731, thus enabling autonomous transfer. Like conjugative plasmid pWBG749, pWBG731 also mobilized non-conjugative plasmids carrying oriT mimics. It seems likely that pWBG731 represents the product of multiple recombination events between the WA-5 pWBG753 plasmid and other mobile genetic elements present in indigenous CA-MSSA. The molecular evolution of pWBG731 saliently illustrates how diverse mobile genetic elements can together facilitate rapid accrual and horizontal dissemination of multiresistance in S. aureus CA-MRSA.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylococcus aureus; Plasmids.


#Toxic #shock #syndrome toxin 1-producing #MRSA of clonal complex 5, the #NY / #Japan #epidemic #clone, causing a high early #mortality rate in patients with #bloodstream infections (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Toxic shock syndrome toxin 1-producing methicillin-resistant Staphylococcus aureus of clonal complex 5, the New York/Japan epidemic clone, causing a high early mortality rate in patients with bloodstream infections

Dokyun Kim, Jun Sung Hong, Eun-Jeong Yoon, Hyukmin Lee, Young Ah Kim, Kyeong Seob Shin, Jeong Hwan Shin, Young Uh, Jong Hee Shin, Yoon Soo Park, Seok Hoon Jeong

DOI: 10.1128/AAC.01362-19




This study was performed to evaluate the clinical impacts of putative risk factors in patients with Staphylococcus aureus bloodstream infections (BSIs) through a prospective, multicenter, observational study.


All 576 patients with S. aureus BSIs that occurred during a one-year period in six general hospitals were included in this study. Host- and pathogsen-related variables were investigated to determine risk factors for the early mortality of patients with S. aureus BSIs.


The all-cause mortality rate was 14.8% (85/576) during the four-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first two weeks. One-quarter (26.8%, 152/567) of the S. aureus blood isolates carried the tst-1 gene, and most (86.2%, 131/152) of them were identified as clonal complex 5-agr type 2-methicillin-resistant S. aureus (MRSA) strains harboring staphylococcal cassette chromosome mec type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that tst-1-positivity of causative S. aureus isolates was associated with an increased two-week mortality rate both in patients with S. aureus BSIs [adjusted odds ratio (aOR), 1.62; 95% confidence interval (CI), 0.90-2.88] and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19-6.03).


Both host-related factors, increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of tst-1 by causative MRSA isolates, were risk factors for two-week mortality in patients with BSIs, and careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; MRSA; Bacteremia; Staphylococcus aureus.


#MRSA in #swine, #farmers and #abattoir #workers in Southern #Italy (Food Microbiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Food Microbiol. 2019 Sep;82:287-293. doi: 10.1016/j.fm.2019.03.003. Epub 2019 Mar 6.

MRSA in swine, farmers and abattoir workers in Southern Italy.

Parisi A1, Caruso M1, Normanno G2, Latorre L1, Miccolupo A1, Fraccalvieri R1, Intini F3, Manginelli T3, Santagada G1.

Author information: 1 Experimental Zooprophylactic Institute of Apulia and Basilicata, Via Manfredonia 20, 71121, Foggia, Italy. 2 Department of Science of Agriculture, Food and the Environment (SAFE), Via Napoli 25, University of Foggia, 7121, Foggia, Italy. Electronic address: giovanni.normanno@unifg.it. 3 Azienda Sanitaria Locale Bari, Lungomare Starita 6, 70123, Bari, Italy.



Methicillin-resistant Staphylococcus aureus (MRSA) is an important medical issue, since it causes serious and sometimes fatal infections in humans. Intensively reared swine may serve as reservoirs for MRSA that can infect swine workers, and also consumers (via contaminated meat). In this study, MRSA strains were isolated from 55 of the 85 (64.7%) intensive pig farms surveyed, and prevalence was greater on pig fattening farms than on breeding farms. In addition, we included in the study 63 foreign pigs imported for slaughter. Overall, the prevalence of MRSA in the 418 sampled swine was 59.1%; 12 genotypes were identified among the isolates; ST398 (96.4%) was most prevalent, followed by ST97 (2%), ST9 (0.8%) and ST1 (0.8%). MRSA isolates were also detected in 26 (17.3%) of the 150 operators included in the study; the genotypes detected were ST398 (85%), ST9 (7.6%), ST5 (3.8%) and ST1 (3.8%). All the strains were pvl negative and pia positive. Both swine and human strains displayed a multi-resistance pattern, and almost all were resistant to tetracycline. The results obtained in this study confirm the high prevalence of MRSA in swine reared and slaughtered in Italy, and underline the public health risk linked to the spread of antimicrobial-resistant Staphylococcus aureus among intensively reared pigs.

Copyright © 2019 Elsevier Ltd. All rights reserved.

KEYWORDS: Antimicrobial resistance; Food safety; MRSA; Professional risk; Public health; Swine

PMID: 31027785 DOI: 10.1016/j.fm.2019.03.003 [Indexed for MEDLINE]

Keywords: Antibiotics; Drugs Resistance; Tetracycline; MRSA; Staphylococcus aureus; Italy; Apulia; Pigs; Human.


#Staphylococcus aureus from #hospital-acquired #pneumonia from an #Italian nationwide #survey: activity of #ceftobiprole …, & molecular epidemiology of methicillin-resistant isolates (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Staphylococcus aureus from hospital-acquired pneumonia from an Italian nationwide survey: activity of ceftobiprole and other anti-staphylococcal agents, and molecular epidemiology of methicillin-resistant isolates

Alberto Antonelli, Tommaso Giani, Marco Coppi, Vincenzo Di Pilato, Fabio Arena, Olga Lorenza Colavecchio, Viola Conte, Anne Santerre Henriksen, Gian Maria Rossolini, MRSA-HAP Study Group

Journal of Antimicrobial Chemotherapy, dkz371, https://doi.org/10.1093/jac/dkz371

Published: 06 September 2019




To determine the prevalence of Staphylococcus aureus from hospital-acquired pneumonia (HAP) in Italy and the susceptibility to ceftobiprole and comparators of MSSA and MRSA isolates. A secondary objective was to characterize the clonality and acquired resistance and virulence genes of MRSA.


Consecutive non-replicate isolates from HAP were collected from 13 laboratories distributed across Italy, from January to May 2016. Antimicrobial susceptibility testing was performed by broth microdilution, and results were interpreted according to the EUCAST breakpoints. All MRSA isolates were subjected to WGS using an Illumina platform. Clonality and resistance and virulence gene content were investigated with bioinformatics tools.


Among 333 isolates from HAP, S. aureus was the third most common pathogen (18.6%). The proportion of MRSA was 40.3%. Susceptibility to ceftobiprole was 100% for MSSA and 95.5% for MRSA. Lower susceptibility rates of 78.4% and 94.6% in MSSA and 36.4% and 12.1% in MRSA isolates were observed for erythromycin and levofloxacin, respectively. The MRSA from HAP mostly belonged to clonal complex (CC) 22 (47.0%), CC5 (25.8%) and CC8 (15.2%), with a minority of other lineages (ST1, ST6, ST7, ST30, ST152 and ST398). Acquired resistance and virulence genes in most cases exhibited a clonal distribution. The three ceftobiprole-resistant isolates exhibited an MIC of 4 mg/L and belonged to ST228-MRSA-I of CC5.


S. aureus is an important cause of HAP in Italy. Ceftobiprole exhibited good in vitro activity against S. aureus isolated from HAP, including MRSA. A trend to replacement of ST228 with ST22 was noticed compared with previous studies.


© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Pneumonia; Nosocomial outbreaks; Italy.


Efficacy of Active #Immunization with Attenuated Alpha-Hemolysin and PVL in a Rabbit Model of #Staphylococcus aureus Necrotizing #Pneumonia (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Efficacy of Active Immunization with Attenuated Alpha-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia

Vuvi G Tran, Arundhathi Venkatasubramaniam, Rajan P Adhikari,Subramaniam Krishnan, Xing Wang, Vien T M Le, Hoan N Le, Trang T T Vu,Erika Schneider-Smith, M Javad Aman, Binh An Diep

The Journal of Infectious Diseases, jiz437, https://doi.org/10.1093/infdis/jiz437

Published: 26 August 2019



Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all three toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus. Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all three toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only alpha-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

MRSA, pneumonia, alpha-toxin, PVL, antibodies, vaccine

Topic: staphylococcus aureus – immunization, active – human leukocyte antigens – clone cells – hemolysin – methicillin – pneumonia – staphylococcal pneumonia – oryctolagus cuniculus – toxins – toxoids – vaccination – vaccines – infection – antibodies – polyclonal antibody – pathogenic organism – pneumonia, necrotizing – epidemics – methicillin-resistant staphylococcus aureus – pathogenicity – alpha-toxin – panton-valentine leukocidin – community – methicillin-resistant staphylococcal aureus pneumonia – attenuation

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Staphylococcus aureus; MRSA; Pneumonia; Vaccines; Animal models.


#Urban brown #rats (Rattus norvegicus) as possible #source of #MDR #Enterobacteriaceae and #MRSA, Vienna, #Austria, 2016 and 2017 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017

Amélie Desvars-Larrive1, Werner Ruppitsch2, Sarah Lepuschitz2, Michael P Szostak1, Joachim Spergser1, Andrea T Feßler3, Stefan Schwarz3, Stefan Monecke4,5,6, Ralf Ehricht4,6, Chris Walzer1,7, Igor Loncaric1

Affiliations: 1 University of Veterinary Medicine, Vienna, Austria; 2 Austrian Agency for Health and Food Safety, Vienna, Austria; 3 Freie Universität, Berlin, Germany; 4 Leibniz Institute of Photonic Technology (IPHT), Jena, Germany; 5 Technische Universität, Dresden, Germany; 6 InfectoGnostics Research Campus, Jena, Germany; 7 Wildlife Conservation Society, Bronx, New York, United States

Correspondence: Amélie Desvars-Larrive amelie.desvarsvetmeduni.ac.at

Citation style for this article: Desvars-Larrive Amélie, Ruppitsch Werner, Lepuschitz Sarah, Szostak Michael P, Spergser Joachim, Feßler Andrea T, Schwarz Stefan, Monecke Stefan, Ehricht Ralf, Walzer Chris, Loncaric Igor. Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017. Euro Surveill. 2019;24(32):pii=1900149. https://doi.org/10.2807/1560-7917.ES.2019.24.32.1900149

Received: 25 Feb 2019;   Accepted: 03 Jun 2019




Brown rats (Rattus norvegicus) are an important wildlife species in cities, where they live in close proximity to humans. However, few studies have investigated their role as reservoir of antimicrobial-resistant bacteria.


We intended to determine whether urban rats at two highly frequented sites in Vienna, Austria, carry extended-spectrum β-lactamase-producing Enterobacteriaceae, fluoroquinolone-resistant Enterobacteriaceae and meticillin-resistant (MR) Staphylococcus spp. (MRS).


We surveyed the presence of antimicrobial resistance in 62 urban brown rats captured in 2016 and 2017 in Vienna, Austria. Intestinal and nasopharyngeal samples were cultured on selective media. We characterised the isolates and their antimicrobial properties using microbiological and genetic methods including disk diffusion, microarray analysis, sequencing, and detection and characterisation of plasmids.


Eight multidrug-resistant Escherichia coli and two extensively drug-resistant New Delhi metallo-β-lactamases-1 (NDM-1)-producing Enterobacter xiangfangensis ST114 (En. cloacae complex) were isolated from nine of 62 rats. Nine Enterobacteriaceae isolates harboured the blaCTX-M gene and one carried a plasmid-encoded ampC gene (blaCMY-2). Forty-four MRS were isolated from 37 rats; they belonged to seven different staphylococcal species: S. fleurettii, S. sciuri, S. aureus, S. pseudintermedius, S. epidermidis, S. haemolyticus (all mecA-positive) and mecC-positive S. xylosus.


Our findings suggest that brown rats in cities are a potential source of multidrug-resistant bacteria, including carbapenem-resistant En. xiangfangensis ST114. Considering the increasing worldwide urbanisation, rodent control remains an important priority for health in modern cities.

© This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Antibiotics; Drugs Resistance; MRSA; Enterobacteriaceae; Wildlife; Austria.