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Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research

Nature Reviews Microbiology volume 17, pages 203–218 (2019)Cite this article

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Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses a formidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. In this Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.

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Fig. 1: Major genomic elements in methicillin-resistant Staphylococcus aureus.
Fig. 2: Global distribution and diversity of methicillin-resistant Staphylococcus aureus.
Fig. 3: Methicillin-resistant Staphylococcus aureus colonization.

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Acknowledgements

N.A.T. and T.L.H. were supported, in part, by an Antibacterial Resistance Leadership Group fellowship (National Institute of Allergy and Infectious Diseases, UM1AI104681, from the National Institutes of Health). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.A.M. was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (1KL2TR002554). V.G.F. was supported by U01 AI-124319-01, 2R01-AI068804 and K24-AI093969, from the National Institutes of Health.

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Nature Reviews Microbiology thanks M. Otto and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Duke University Medical Center, Durham, NC, USA

    Nicholas A. Turner, Batu K. Sharma-Kuinkel, Stacey A. Maskarinec, Emily M. Eichenberger, Pratik P. Shah, Manuela Carugati, Thomas L. Holland & Vance G. Fowler Jr

  2. Division of Infectious Diseases, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Manuela Carugati

  3. Duke Clinical Research Institute, Durham, NC, USA

    Vance G. Fowler Jr

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  2. Batu K. Sharma-Kuinkel
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  3. Stacey A. Maskarinec
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The authors contributed equally to all aspects of the article.

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Correspondence to Vance G. Fowler Jr.

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Competing interests

T.L.H. has been a consultant for Basilea Pharmaceutica, Genentech, The Medicines Company, Motif Biosciences and Theravance Biopharma and has received grant support from Basilea Pharmaceutica and Achaogen. V.G.F. served as Chair of the V710 Scientific Advisory Committee (Merck); has received grant support from Cerexa/Actavis/Allergan, Pfizer, Advanced Liquid Logics, National Institutes of Health (NIH), MedImmune, Basilea Pharmaceutica, Karius, ContraFect, Regeneron Pharmaceuticals and Genentech; has NIH STTR/SBIR grants pending with Affinergy, Locus and Medical Surface; has been a consultant for Achaogen, AmpliPhi Biosciences, Astellas Pharma, Arsanis, Affinergy, Basilea Pharmaceutica, Bayer, Cerexa, ContraFect, Cubist, Debiopharm, Destiny Pharmaceuticals, Durata Therapeutics, Grifols, Genentech, MedImmune, Merck, The Medicines Company, Pfizer, Novartis, NovaDigm Therapeutics, Theravance Biopharma, XBiotech and Integrated BioTherapeutics; has received honoraria from Theravance Biopharma and Green Cross; and has a patent pending in sepsis diagnostics.

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Glossary

Endocarditis

An infection of the interior heart structures or valves.

Osteomyelitis

An infection involving bone.

Methicillin

An anti-staphylococcal penicillin.

Fomite

An object or material capable of carrying or transmitting infection.

Echocardiography

A diagnostic imaging technique in which ultrasound is used to construct images of heart chambers, valves and associated structures.

Mobile genetic elements

Segments of DNA-encoding enzymes that mediate transfer of DNA within and between bacterial genomes.

Clindamycin

An antibiotic in the lincosamide family.

Methicillin-susceptible Staphylococcus aureus

(MSSA). Staphylococcus aureus strains that are susceptible to methicillin, oxacillin and cefoxitin.

Minimum inhibitory concentrations

(MICs). The lowest concentration of a chemical at which bacterial growth is prevented.

Competent

Refers to bacteria capable of taking up DNA from their environment for recombination.

Hyaluronidase

An enzyme that catalyses the degradation of hyaluronic acid; it may play a role in pathogenesis by facilitating the breakdown of host intercellular matrix.

Arginine-catabolic mobile element

(ACME). A mobile genetic element that accompanies staphylococcal cassette chromosome mec (SCCmec) and is believed to have a role in the regulation of growth and survival in Staphylococcus aureus and strain fitness.

Panton–Valentine leukocidin

(PVL). A cytotoxin produced by some strains of Staphylococcus aureus that induces pore formation in the membranes of white blood cells, resulting in cell lysis.

att s sites

Sites targeted by the staphylococcal cassette recombinases.

Gene nurseries

Regions of the genome from which other genes are believed to have originated.

Phenol-soluble modulin

(PSM). A peptide toxin that attracts and lyses white blood cells.

One Health approach

An integrative approach to medicine that recognizes connections between animal, environmental and human health.

Mupirocin

A topical antibiotic with activity against S. aureus.

Transoesophageal

A technique for echocardiography in which the echo probe is positioned within the oesophagus, providing much higher resolution imaging of select heart structures.

Transthoracic

The standard, non-invasive method for echocardiographic imaging of the heart by applying the echo probe to the external chest wall.

Non-inferior

In the specific context of clinical trials, a statistical definition by which an intervention is determined to be no worse than its comparator within a pre-specified range.

Pulmonary surfactant

A lipoprotein substance secreted by the lungs that reduces surface tension and thus prevents collapse of alveoli.

Modified intention-to-treat analysis

A variation on the traditional analysis of clinical trial results in which some subset of patients are excluded after randomization; there is no single definition for how this exclusion occurs, and there is some risk of introduction of bias.

Embolization

The occlusion of a blood vessel by a material travelling within the bloodstream; this may be caused by clot (that is, thrombus) or infectious material.

Pharmacokinetics

The study of the movement and distribution of medications within the body.

Myelosuppression

The inhibition of bone marrow activity resulting in decreased red blood cells, white blood cells and platelets.

Neuropathy

The dysfunction or disease of the peripheral nerves.

Two-stage exchange arthroplasty

A method of joint replacement in which the original infected artificial joint is removed in one operation, antibiotic treatment is given and re-implantation of a new artificial joint is performed at a later date.

Parenteral

Administered by a route other than the gastrointestinal tract; in general, refers to intravenous or injection therapies.

Haematogenous

Blood-borne or carried within the bloodstream.

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Turner, N.A., Sharma-Kuinkel, B.K., Maskarinec, S.A. et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat Rev Microbiol 17, 203–218 (2019). https://doi.org/10.1038/s41579-018-0147-4

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