Staphylococcus aureus

Staphylococcus aureus (Greek staphyle = bunch of grapes, Latin coccus = spherical bacterium, aureus = golden), or golden staph (pronounced ’staff’), is the most common staphylococcus species causing infections in human.

Lab Tests for Staph
Staph Epidemiology

Staph Infections

S. aureus lives as the part of the normal skin flora in the nose or on the skin in 20-30% of healthy people (staph carriers), (1). However, in even slightly injured skin or mucosa, staph may cause styes, pimples, folliculitis, furuncles, boils (picture 1), swimmer’s ear, sinusitis, epiglotitis, whitlow, breast infection, impetigo, cellulitis, genital infection, or scalded skin syndrome. Infections of internal organs include urinary tract infections, arthritis, pneumonia, infection of veins (thrombophlebitis), lymph nodes (lymphadenitis) or lymph vessels (lymphangitis), bone infection (osteomyelitis) (picture 2), or life threatening  sepsis (staph blood invasion), infection of heart valves (endocarditis),  meningitis, “flesh eating bacteria” infection (necrotizing fasciitis), and toxic shock syndrome. S. aureus enterotoxins may cause food poisoning.

S. aureus and S. epidermidis are among the most common causes of hospital-acquired infections like bloodstream infections, infections of surgical wounds, or pneumonia (2). Staph may also appear in vascular and urinary catheters, prosthetic joints, and heart valves.

Staph skin infection usually appears as a red, warm, painful swelling with a blister, ulcer, or crust, and a drainage (picture 1). Infection may spread into deeper tissues, like bones (picture 2).

Staph Boil Staph Osteomyelitis

Picture 1.
A boil on the upper arm

Picture 2.
X-ray of child’s legs:
osteomyelitis in shin bones (grey patches)

How Widespread and How Dangerous is Staph?

Staph does not just float around in the air. A close skin contact, sharing towels, sport equipment and such with an infected person or staph carrier, is needed to catch the infection. In an otherwise healthy persons staph usually causes only localized skin infections, which heal on their own within a few weeks (3). In heavily ill or immunodeficient patients, staph may cause deadly sepsis.   

Staph Antibiotic Resistance

In 1942, only two years after introducing penicillin into infection treatment, staph resistance to penicillin was recognized in hospitals (4). In 1960, methicillin (later replaced by oxacillin) was used to treat penicillin resistant staph. Over 90% of staphylococci now contain enzyme penicillaze (which breaks down penicillin), so they have to be treated with penicillase-resistant penicillins, cephalosporins or other antibiotics (5). 

MRSA 

Methicillin Resistant S. aureus (MRSA) is resistant to most antibiotics derived from penicillin, including methicillin, so it’s got a nickname ’superbug’. MRSA was first detected in Britain in 1961 and is now increasingly recognized in the community worldwide (4). MRSA still mainly occurs in hospitals and nursing homes, but has lately spread to general community (Community Associated MRSA or CA-MRSA). It is impossible to distinguish MRSA from the “common” S. aureus (MSSA = Methicillin Susceptible S. aureus) clinically (6). MRSA itself is not more “powerful” than MSSA, but it can be dangerous when it is not recognised as MRSA and not treated with appropriate antibiotics.

VISA and VRSA

In 1996, in Japan, S. aureus which didn’t respond to usual dose of vancomycin, was recognized. The terms Vancomycin Intermediate S. aureus (VISA) and Vancomycin Resistant S. aureus (VRSA) are now used, when 8-16 µg/ml or > 32 µg/ml of vancomycin respectively, is needed to inhibit staph growth during antibiotic susceptibility test (7). VISA and VRSA again are not more powerful than other staphylococci, but they should be recognised as such, otherwise the treatment may not be successful. At present VISA may be treated with larger doses of vancomycin and VRSA by some other antibiotics. VRSA is still rare: only seven cases were identified in United States between y. 2002-2006 (8).

Taxonomy of Staphylococcus aureus

Taxonomy (Greek taxis = arrangement, -nomia = method) is classification of organisms in groups, according to their presumed natural relationships. In the “Bergey’s Manual of Systematic Bacteriology” Staphylococcus aureus is placed into:

Kingdom Bacteriae,
Phylum (Division) XIII. ‘Firmicutes‘ (Latin: firmus = strong, cutis= skin, referring to the cell wall),
Class I. ‘Bacilli‘,
Order I. ‘Bacillales‘,
Family.VIII ‘Staphylococcaceae‘,
Genus I. ‘Staphylococcus‘
Species ‘Staphylococcus aureus’ (9).

Staphylococcus aureus Characteristics

S. aureus is a spherical (coccus) Gram-positive bacterium, about 1 micrometer in size, with the thick cell wall and thin capsule. It doesn’t form spores, but it can still survive outside the body, e.g. on bed lining or computer keyboards from few days to several weeks (10). It is a facultative anaerobe - it grows in the air, but can also thrive in anaerobic conditions. It is opportunistic pathogen - it may be present in the body without causing any harm, but in lowered immunity or injury, it may cause a disease. Staph bacteria have no flagella, so they are immobile. They grow in pairs, short chains or clusters (picture 3).

Staphylococcus aureus

Picture 3. Grape-like clusters of S. aureus, el. micrograph, Magn. ~ 5000x;
Src: phil.cdc.gov

S. aureus has ability to clot plasma - it is coagulase positive. Bacteria are resistant to temperatures as high as 50°C, to high salt concentrations (<10%), and to drying (11). Colonies are usually 6-8 mm in diameter, rounded and smooth, golden yellow, or pale yellow to orange (picture 6).  

Staphylococcus aureus Cell Wall Structure

S. aureus wall consists from three layers: outer polysaccharide capsule, peptidoglycan (murein) layer, and inner cytoplasmic membrane. Into this structure, proteins and teichoic acid are embedded and protrude from the cell wall on its outer side, forming a “fuzzy coat” (picture 4), (12). Capsule is thin and may be seen only under the electron microscope. Sometimes more bacteria share one capsule and form a slime layer or biofilm, mostly found on the inner wall of venous and urinary catheters (13).

S. aureus Cell Wall Structure

Picture 4. S. aureus cell wall structure  

Virulence Factors of Staphylococcus aureus

The term ‘virulence’ refers to microbe’s “ability to invade the tissues of the host”, or ”the potential to cause a disease”. Virulence factors of S. aureus:

  1. surface proteins that promote attachment of staphylococci to the damaged host tissues;
  2. inhibitors of phagocytosis: capsule, Protein A - binds IgG molecules the wrong way and thus disrupt phagocytosis (14); polysaccharides secreted by staph aureus may form a biofilm or slime layer on indwelling medical devices (13); yellow pigment from carotenoids protect bacteria against free radicals, and catalase breaks down peroxide (phagocytes use free radicals and peroxide to kill bacteria) (15);
  3. bound coagulase - “clumping factor” which causes coagulation of plasma and bacteria clumping, and free coagulase, which again triggers plasma coagulation (14);
  4. invasins that promote bacterial spread in tissues: kinases, hyaluronidases (destroy hyaluronic acid in connective tissue), and fatty acid modifying enzyme (FAME);
  5. cytotoxins that lyse cell membranes: hemolysins (lysis of erythrocites), leukotoxin and Panton-Valentine leukocidin - PVL (lysis of leukocytes);
  6. Exfoliatin Toxin - ET (in scalded skin syndrome), and superantigen toxins, which may trigger massive non-specific T-cell response: enterotoxins SEA-G (in food poisoning), and TSST-1 (in Toxic Shock Syndrome) (14);
  7. antibiotic resistance - inherited and acquired. More details about S. aureus virulence factors.

NOTE: Amount of virulence factors may differ among individual S. aureus bacteria considerably.

Prevention of Staphylococcus aureus Infections

Staph infection may be prevented on many levels:

  1. Hands washing and regular bathing.
  2. Skin wounds should be cleaned and covered.
  3. Food workers should be tested for staphylococci, and being treated, even if they have no active infection. Staph carriers should not work in food preparation.
  4. Surfaces in hospitals may be cleaned with alcohol, quaternary ammonium or iodine compounds, which are effective to both MSSA and MRSA (20). Effective sprays for air disinfection also exist (16).
  5. Cows should be regularly checked for mastitis, and milk tested for S. aureus or its toxins. Only pasteurized or cooked milk should be used.
  6. Human and bovine vaccines against S. aureus have been developing.

What is NOT NEEDED to prevent staph infections: antibacterial soaps, wearing masks, washing linens of staph infected persons separately from others, using disposal dishes, disinfecting surfaces with hypochlorite, denying patients from using whirlpools or foot baths, work restrict staff members who are MRSA carriers, unless they have skin lesions or active nasal infection (20).

Treatment of Staphylococcus aureus Infections

Staph colonization may be treated with mupirocin (Bactroban) nasal gel, and daily Hibiclens skin cleanser baths (17). 

Local skin infections are treated with antibacterial ointments. In more extensive infections, S. aureus has to be tested for antibiotic sensitivity, and then usually oral antibiotics are used. Skin abscesses often have to be drained, and deep abscesses, may require surgical drainage. In systemic infection, hospitalization and intravenous antibiotics are needed. Artificial heart valves and vein catheters often need to be removed/replaced.

Severe staph infections require treatment with parenteral penicillinase-resistant penicillin like nafcillin and oxacillin, or cephalosporins of 1st or 2nd generation (e.g. cephalexin, cefuroxime) plus clindamycin. Vancomycin is reserved for MRSA and clindamycin resistant strains, or for life-threatening infections. Staph food poisoning usually heals on its own. List of antibiotics which my be used in Staph aureus infections (5, 11):

  • Amoxycillin;
  • Cefazolin, Cephalexin, Cephalotin;
  • Ciprofloxacin;
  • Clindamycin;
  • Cloxacillin;
  • Daptomycin;
  • Dicloxacillin;
  • Erythromycin (only for minor skin infections, since it is only bacteriostatic)
  • Flucloxacillin (adv. effect: hepatic cholestasis);
  • Linezolid (C);
  • Methycillin (common adv. effects: hypersensitivity, interstitial nephritis);
  • Minocycline (D);
  • Mupirocin;
  • Nafcillin;
  • Oxacillin;
  • Quinupristin/dalfopristin (Synercid) (C);
  • Penicillin G (Benzylpenicillin), Penicilin V (Phenoxymethylpenicillin);
  • Retapamulin;
  • Rifampin (C);
  • Tigecycline (D);
  • Trimethoprim-sulfamethoxazole (C);
  • Vancomycin.

NOTE: Safety of group C antibiotics in pregnancy is not confirmed; group D antibiotics are unsafe in pregnancy.

Detailed intravenous and oral antibiotic treatment regimes in staph infections

Literature about Staphylococcus aureus:

Books:

  • Staphylococcus: Molecular Genetics
    Publisher: Caister Academic Press
    Edited by: Jodi Lindsay Department of Cellular and Molecular Medicine, St George’s, University of London, UK
    Publication date: May 2008
    ISBN: 978-1-904455-29-5
  • Staphylococcus aureus Infections
    Author: Lisa Freeman-Cook and Kevin D. Freeman-Cook
    Publisher: Facts on File (September 01, 2005)
    ISBN: 9780791085080
  • Methicillin-Resistant Staphylococcus Aureus (MRSA) Protocols
    Author: Yinduo Ji
    Publisher: Humana Pr Inc (December 30, 2007)
    ISBN: 9781588296559
  • Bergey’s Manual of Determinative Bacteriology, 9th ed.,
    Author: Williams & Wilkins.
    ISBN 0-683-00603-7

Research papers:

Online Literature about Staphylococcus aureus:

  1. Bergey’s Taxonomic Outline
  2. Staphylococcus aureus Articles
  3. List of Microbiology Links (by Louis B. Caruana, Ph.D., professor of clinical laboratory science)

Lab Tests for Staph
Staph Epidemiology

References:

  1. STAPH INFECTIONS
    http://www.merck.com/mmhe/sec17/ch190/ch190r.html 
  2. HOSPITAL ACQUIRED INFECTIONS
    http://www.emedicine.com/ped/topic1619.htm  
  3. HOW LONG STAPH INFECTION LASTS
    http://kidshealth.org/college/infections/bacterial_viral/staph.html
  4. S. AUREUS ANTIBIOTIC RESISTANCE
    http://www.emedicine.com/MRSAmanagement/presentations/pdf/eMedicine_id_cme_BuggingTheBugs.pdf
  5. ANTIBIOTICS IN STAPH INFECTION
    http://www.antimicrobe.org/sample_staphylococcus.asp
  6. MSSA and MRSA CAN’T BE DISTINGUISHED CLINICALLY
    http://www.garretthealth.org/pdfs/NewsletterMRSAtreat.pdf 
  7. VRSA
    http://health.utah.gov/epi/diseases/VRSA/gpvisa-vrsa.htm
  8. VRSA INCIDENCE
    http://www.ncbi.nlm.nih.gov/pubmed/18257700?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
  9. TAXONOMY OF S. AUREUS, BERGEY’S MANUAL
    http://www.bergeys.org/outlines/Bergeys_Vol_3_Outline.pdf 
  10. MRSA SURVIVAL TIME ON SURFACES
    http://www.livescience.com/health/050606_staph_survival.html
  11. STAPH SALT AND TEMPERATURE RESISTANCE, ANTIBIOTICS IN STAPH
    http://www.emedicine.com/ped/topic2704.htm 
  12. S. AUREUS - CELL WALL STRUCTURE
    http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=212097&blobtype=pdf 
  13. STAPH BIOFILM
    http://www.cdc.gov/ncidod/EiD/vol7no2/donlan.htm
  14. STAPH VIRULENCE FACTORS, SUPERANTIGEN TOXINS
    http://gsbs.utmb.edu/microbook/ch012.htm
  15. YELLOW PIGMENT AS VIRULENCE FACTOR
    http://www.newscientist.com/channel/life/mg18725085.000 
  16. SPRAYS FOR SA AIR DISINFECTION
    http://news.bbc.co.uk/2/hi/uk_news/england/manchester/6471475.stm 
  17. STAPH COLONISATION TREATMENT
    http://www.bastrop.isd.tenet.edu/news/show/39