Methicillin Resistant Staphylococcus

aureus (MRSA)
Presented by
Nagaraj.s
M.Sc. 3rd year microbiology.
Carbapenems penicillins cephalosporins monobactams

Beta-lactam ring

enzymes altered binding sites efflux pumps

(beta-lactamase) (PBP PBP2a) Erwinia, Neisseria, E.coli
mecA, mecC genes
of staphylococcus
Staphylococcus
Taxonomy

• Domain : Bacteria

• Phylum : Firmicutes

• Class : Bacilli

• Order : Bacillales

• Family : Staphylococcaceae

• Genus : Staphylococcus
Introduction
• Staphylococci are gram positive cocci that occur in grape like clusters. They are
ubiquitous and most common cause of localised suppurative lesions in humans.

• Their ability to develop resistance to penicillin and other antibiotics enhance their
importance as a human pathogen, especially in the hospital environment.

• Staphylococci was first observed in human pyogenic lesions by von Recklinghausen in

1871.

• Sir Alexander Ogston who gave it name Staphylococcus (staphyle= bunch of grapes,
kokkos= berry). He noticed that Non-virulent Staphylococci were also often present on
skin surfaces.
Cultural characteristics
• They grow readily on ordinary media with in a temperature range of 10 to 42c. The optimum being 37c and a pH of 7.4-
7.6.

• They are aerobes and facultative anaerobes.

• On Nutrient agar, it produces circular, opaque, smooth, shiny, and easily emulsifible. Most strains produce golden
yellow pigment. Pigment production is enhanced by 1% glycerol monoacetate or milk is incorporated in the medium.

• On Nutrient agar slope, confluent growth presents a characteristic oil-paint appearance.

• On Blood agar, most strains are haemolytic(beta-haemolytic), especially when incubated under 20-25% of CO2.

• In Mac Conkey agar, they produce lactose fermenting pink coloured colonies.

• In liquid media, uniform turbidity is produced.

• Selective media are Ludlam’s media (LiCl2 and tellurite), Salt milk agar, salt broth.
Antigenic structures
Cell associated polymers
• Polysaccharide peptidoglycan layer
• Teichoic acid
• Capsular polysaccharide

Cell surface proteins

• Protein A
• Clumping factor
Antigenic structures
Extracellular enzymes

• Coagulase

• Lipid hydrolases

• Hyaluronidase

• Heat stable nuclease

• Protein receptors
Toxins
• Cytolytic toxins

I. Alpha haemolysin

II. Beta haemolysin

III. Gamma haemolysin

• Leucocidin (PVL) toxin

• Enterotoxin

• Toxic shock syndrome

• Exfoliative toxin
Confirmatory tests for S.aureus

• Deoxyribose nuclease test

• Thermostable endonuclease test

• Mannitol fermentation test

• AccuProbe staphylococcus aureus test (Gen-probe)

MRSA
(METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS )
Emergence of methicillin-resistant S. aureus
(MRSA)
• Penicillin was the first beta-lactam antibiotic developed for the treatment of S. aureus
infections. Which is usually fatal.1
• The introduction of penicillin to treat infections caused by S. aureus greatly improved the
prognosis of patients with severe staphylococcal infections.12 these strains resistant to
penicillin soon appeared following its clinical use.12
• Penicillin resistance is due to the production, by the bacteria, of penicillinase, which
inactivates the antibiotic. Penicillinase hydrolyses the beta-lactam ring that is central to
the antimicrobial activity of these drugs.
• The emergence of penicillin resistance in S. aureus stimulated the development of new
antibiotics such as streptomycin, tetracycline, erythromycin, and chloramphenicol in the
1950s.12
• These new antibiotics were developed and put into clinical use, resistance to them also appeared. 4 The continuous search for

antibiotics active against penicillin-resistant S. aureus led to the development of methicillin also known as methicillin or

Staphcillin.5

• Methicillin is a semisynthetic derivative of penicillin, developed in the late 1950s, by a modification of the penicillin structure

which conferred resistance to penicillinase. 9 it kills bacteria by inhibiting bacterial cell-wall synthesis, a mechanism of action

similar to that of other penicillins.

• Methicillin resistance occurs due to the acquisition of mecA or mecC gene by previously susceptible strains.6 The mecA gene

codes for an altered penicillin-binding protein called penicillin-binding protein-2a (PBP2a) with reduced affinity to the entire

beta-lactam class of antibiotics including penicillin, cephalosporin and carbapenems 11 except the recently approved beta-

lactams, ceftaroline and ceftobiprole.7

• mecC carrying MRSA was identified in 2007, a retrospective search of archived
collections found mecC in isolates collected as early as 1975. indicating that these strains
have been around for a long time possibly as long as the mecA-MRSA strains.6

• MecC gene is a homolog of mecA. It was initially designated mecALGA251. It shares 69%
nucleotide homology with mecA.6 MRSA isolates carrying mecC have been isolated from
human as well as animal hosts.8

• the mecA PCR or PBP2a latex agglutination test fails to detect mecC. In sensitivity
testing, using both cefoxitin and oxacillin, mecA-MRSA show resistance to both antibiotics
whereas the majority of mecC MRSA will express resistance only to cefoxitin.8 This
discrepancy is explained by the observation that PBP2a produced by mecC strains have
higher affinity to oxacillin than cefoxitin.8
Types of MRSA
Types of MRSA

• When MRSA strains first occurred, they were usually confined to elderly patients admitted
to healthcare facilities especially those with previous antibiotic use. The MRSA strains
were also isolated from apparently healthy individuals in the communities of no previous
contact with healthcare facilities.

• MRSA strains circulating in the healthcare settings and the community were classified as
either nosocomial or healthcare associated MRSA (HA-MRSA) and community-
associated MRSA (CA-MRSA).10

• This was followed by a new type of MRSA that arose from animals, designated Livestock-
associated MRSA (LA-MRSA) has recently been described.10
Healthcare-associated MRSA
• Healthcare-associated MRSA (HA-MRSA) were isolated from patients admitted to
healthcare facilities such as nursing homes and long-term care facilities.

• the infections caused by HA-MRSA include bloodstream infections, urinary tract

infections, respiratory tract infections, surgical-wounds and device-associated infections.2

• Risk factors for acquiring HA-MRSA include previous admission to healthcare facilities,
impaired immune system, use of multiple antibiotics, use of invasive medical devices and
old age.11

• Genetically, the HA-MRSA carried SCC mec types I, II and III, are usually multi resistant
to antibiotics, and tend to multiply slowly in culture.11
Community-associated MRSA (CA-MRSA)
• Community-associated MRSA (CA-MRA) strains were initially reported in the late 1980s among individuals living in
remote communities in Western Australia with no previous history of hospitalization. 9

• CA-MRSA were mostly associated with skin and soft tissue infections such as impetigo, cellulitis, folliculitis and boils
and those at risk were the young patients.10

• some CA-MRSA strains have been reported to cause severe infections including necrotizing fasciitis, post-influenza
pneumonia, septic thrombophlebitis, septic arthritis, and bacteremia .10

• CA-MRSA are usually susceptible to non-beta lactam antibiotics carry smaller-sized SCC mec types IV, V and VI.10

• CA-MRSA strains often express lower levels of resistance to oxacillin (MIC; 8–32 mg/L) and multiply faster than HA-
MRSA strains with significantly shorter doubling times which may help CA-MRSA achieve successful colonization by
enabling it to out compete commensal bacterial flora. 10
Livestock-associated MRSA
• Staphylococcus aureus is also an important cause of infections in live stock resulting in economic losses in the food
industry.11

• Livestock-associated MRSA (LA-MRSA) strains were initially identified because they were non-typeable by pulsed-field
gel electrophoresis following digestion with SmaI restriction enzyme.12

• The molecular typing revealed that LA-MRSA defined to a new lineage of MRSA that belonged to clonal complex 398
(CC398).16 the LA-MRSA ST398 was initially reported among livestock, 11,12

• it has also appeared in the community among human patients in contact with infected or colonized animals which is
considered the major risk factor for LA-MRSA colonization.12

• Other LA-MRSA lineages reported in humans include ST9, ST97 and ST433. 18 LA-MRSA has also caused invasive
infections including endocarditis, osteomyelitis, and ventilator-associated pneumonia in humans.13,14
• By applying epidemiological typing methods such as multilocus-sequence typing (MLST),
classification of the mobile genetic element Staphylococcal cassette chromosome mec(SCCmec),
spa typing, and DNA microarray for detection of resistance and virulence genes, a number of
important clones have been identified.15

• Most of the epidemic MRSA isolates belong to eight major clonal complexes (CCs) including CC1,
CC5, CC8, CC22, CC30, CC45, CC59 and CC80.15

• In addition, strains belonging to sporadically distributed clonal complexes such as CC6, CC7, CC9,
CC12, CC15, CC20, CC75, CC88, CC93, CC96/ST154, CC97, CC130, CC121, CC152, CC188,
CC361, CC395/ST426, CC398, CC509, CC779 and CC913 have been reported.15,16
• By inserting the smaller mobile SCC mec type IV into PVL-positive MSSA, the
community-associated MRSA would possess resistance determinants and
enhanced toxins, potentially gaining a fitness advantage.

• Resulting characteristics of community-associated MRSA infections include a lack

of hospital-associated risk factors, susceptibility to many non–β-lactam
antibiotics, distinct genotypes, and distinct genetic determinants of virulence
(e.g., PVL toxin).

• Gordon and Lowy discuss the molecular epidemiology and virulence associated
with community-associated MRSA in this supplement.
Changes in the epidemiology of MRSA isolates
• Beginning in the late 1980s, the MRSA population expanded with the emergence of community
isolates.9,10

• clones that have been isolated widely include the HA-MRSA clones ST239/ST241-III-MRSA, ST22-
IV-MRSA and the CA- MRSA clones ST80-IV-MRSA, ST30-IV-MRSA, ST772-V-MRSA. On the
other hand, clones such as ST59-IV, ST93-IV and ST8-IV (USA300) have restricted geographical
spread.15

• The USA300 is the dominant CA-MRSA clone causing infections in North America.26,27 USA300
have been reported sporadically in some European countries and Australia.15

• It is commonly associated with skin and soft tissue infections, necrotizing pneumonia and
endocarditis.17,18
Virulence determinants in MRSA
Panton Valentine-leukocidin

• Panton Valentine leukocidin (PVL) is a toxin composed of two components, LukS-PV and LukF-PV.

• These two components act together to form pores on the polymorpho- nuclear cells membranes
leading to neutrophil lysis.19

• PVL has been reported in HA-MRSA as well as MSSA strains belonging to diverse genetic
backgrounds.20 The toxin is encoded by bacteriophages which explains its carriage in strains
belonging to diverse genetic backgrounds.20

• The most PVL- positive S. aureus strains are associated with skin and soft tissue and
musculoskeletal infections, some PVL-positive strains also cause invasive infections such as
bacteraemia, and necrotizing pneumonia in diverse patient populations.19,21
Arginine catabolic mobile element
• The arginine catabolic mobile element (ACME) is a novel class of virulence determinants
carried on a genomic island which varies in size from 31-kb to 46-kb in staphylococcus.17

• ACME encodes a putative virulence determinant which provides for several immune
modulating functions, including resistance to polyamines which serve as a non-specific
immune response both on intact skin, and following the inflammatory response in wound
healing.

• It is thought to aid bacterial growth, provide a competitive survival advantage, and

enhance the fitness of S. aureus possibly by facilitating colonization and/or
hematogenous spread to target organs.22,23
Transmission
Transmission
• MRSA is transmitted from person to person by contaminated hands. Lack of access to hand
hygiene products can increase the risk of transmission.

• Additional risk factors includes, sharing personal products such as shampoo or nail clippers,
infrequent showers and hand washing.

• Another mode of transmission noted within the federal prison system is illicit, unsanitary tattoo
practices.

• In other settings close physical contact, body shaving, turf burns and sharing athletic equipment
have been associated with MRSA transmission.

• Persons with asymptomatic MRSA nasal carriage can shed MRSA resulting in transmission to other
persons or contamination of food that may cause toxin mediated acute gastroenteritis.
• Some MRSA strains, CC398 are readily transmitted with in the
host species to which they are adopted.

• Inhalation of contaminated dust, which can contain large no.of

organisms, is thought to be a major route of spread in
confinement operations.
Identification of MRSA
Phenotypic detection methods
• All isolates of S. aureus are tested by oxacillin disc diffusion,
cefoxitin disc diffusion, oxacillin screen agar and latex agglutination
tests, and growth on CHROM agar.

• A standard strain of MSSA (ATCC 29213) and a PCR-positive control

strain [ATCC 43300 (mecA positive)] are used as controls for all
methods.
Oxacillin disc diffusion method
• All strains were tested with 1 ug oxacillin discs (Hi-Media) on
Mueller–Hinton agar plates.
• For each strain, a bacterial suspension adjusted to 0.5 McFarland
was used. The zone of inhibition was determined after 24 h
incubation at 35C. Zone size was interpreted according to CLSI
(2008) criteria: susceptible, >13 mm; intermediate, 11–12 mm; and
resistant >10 mm.
Cefoxitin disc diffusion method
• All strains are tested with 30 ug cefoxitin discs (Hi-Media) on Mueller–
Hinton agar plates.
• For each strain, a bacterial suspension adjusted to 0.5 McFarland was
used.
• The zone of inhibition was determined after 16–18 h incubation at 35C.
• Zone size was interpreted according to CLSI (2008) criteria: susceptible,
>22 mm; resistant, <21 mm.
Oxacillin screen agar test

• A bacterial inoculum of each strain was made and turbidity was adjusted to
0.5 McFarland.

• One drop of this suspension was inoculated on Mueller–Hinton agar

containing 4 % NaCl and 6 ug oxacillin (Hi-Media).

• Plates are incubated at 35 C for 24 h. Any strains showing growth on the

plate containing oxacillin are considered to be resistant to methicillin.
CHROM agar
• CHROM agar (Hi-Media) is a new chromogenic medium for the identification of MRSA.

• For each strain, a bacterial suspension adjusted to 0.5 McFarland was used.
Subsequently, a swab was dipped in the suspension and streaked onto a CHROM agar
plate.

• The growth of any green colony was considered to be positive, indicating MRSA

Latex agglutination test for detection of PBP2a

A latex agglutination MRSA screen test (Denka Seiken) was carried out for all strains
according to the manufacturer’s instructions.
• For MRSA, cotrimoxazole (25 mg), erythromycin (15 mg), clindamycin (10 mg),
ciprofloxacin (30 mg), netilmicin (30 mg), amikacin (10 mg), linezolid (30 mg), vancomycin
(30 mg) and dalfopristin/quinpristin (15 mg) are tested.

• For MSSA, the same antibiotics as for MRSA are used, as well as ampicillin (10 mg),
cephalexin (30 mg) and amoxicillin/ clavulanic acid (30 mg).

• The Kirby Bauer disc diffusion method is used routinely to detect the sensitivity of all S.
aureus isolates and interpretations are made according to CLSI (2008) guidelines.
Differences between oxacillin and cefoxitin
Oxacillin Cefoxitin
Sensitivity is 73.1% Sensitivity is 96.2%

Specificity is 96.2% Specificity is 96.2%

PPV is 95.0% PPV is 95.0% PPV is 96.2%

NPV is 73.8 % NPV is 73.8NPV is 96.2%

• The superiority of cefoxitin on MRSA detection is because, cefoxitin acts
as a strong inducer on mec A gene regulatory system.

• Cefoxitin is easier to interpret and to read.

• Oxacillin, which is also the same antibiotic group with methicillin, is

cheaper and accessible.

• Oxacillin replace methicillin which is no longer available commercially in

the US and oxacillin is more possible to detect hetero resistant strains.
Molecular detection methods
• MRSA lineages and strains can be identified with molecular tests such
as :
i. PFGE (Pulse Field Gel Electrophoresis)
ii. MLST (Multi Locus Sequence Typing)
iii. MLVA (Multiple Loci VNTR Analysis)
iv. SCC (Staphylococcal cassette chromosome) mec typing
v. spa typing.
Rapid detection of MRSA
• Cycling probe amplification or fluorescence technology (crystal MRSA-ID
system).

• Vologene assay using fluorescein conjugated probes.

• Latex agglutination test.

• Immunochromatographic strip methods for detection of PBP2a which contains

Clear View Exact PBP2a and Binax Now 2a methods for rapid, qualitative
detection of PBP2a.

• Oxoid latex agglutination test for PBP2a.

MRSA genes

• virulence genes including: sea (102 bp), seb (164 bp) , sed(278
bp), tst (326 bp), eta (93 bp), etb (226 bp), LuKS/F-PV (443 bp)
, hla (209 bp) and hld (11 bp) and mec A (147 bp) in methicillin-
resistant S. aureus.

• These genes are isolated by using the polymerase chain

reaction (PCR) technique.
Resistant gene Antimicrobial agent Mechanism of resistance
Ars B Arsinite/antimony Active export
Bla Z Penicillin Inactivation by a beta-lactamases
Cad A Cadmium/zinc Active export
Cat Chloramphenicol Inactivation by a chloramphenicol
acetyltransferase
Erm A MLS Methylation of RNA
Fus A Fusidic acid Target alteration in EF-G
Fus B Fusidic acid Decreased permeability
Mec A Methicillin Production of an altered PBP2
Str Streptomycin Modification by a 6 adenyl transferase
Str A Streptomycin Ribosomal alteration
Tet A(K) Tetracycline Active export
Tet A(M) Tetracycline Ribosomal protection
Vat sgA Modification by an acetyl tranferase
Vgb sgB Modification by a hydrolase enzyme
Epidemiology
• The frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections continues to grow
in hospital-associated settings and more recently, in community settings in the United States and
globally.

• The increase in the incidence of infections due to S. aureus is partially advances in patient care and
also the pathogen ability to adapt a changing environment.

• The first appearance of methicillin resistance S. aureus strains in 1960, has become widespread in
hospitals and intensive care units (ICUs).

• National Nosocomial Infection Surveillance (NNIS) System data demonstrates that, increase in the
incidence of nosocomial infections caused by methicillin-resistant S. aureus (MRSA) among ICU
patients over time.

• The MRSA now accounts for >60% of S. aureus isolates in US hospital ICUs.
Hospital associated MRSA
• The increase in MRSA infections most likely reflects the growing impact of medical
interventions, devices, older age of patients.

• Antibiotic use and overuse probably also contribute to the emergence of resistance.

• Recent studies demonstrate a continuing increase in MRSA infections in hospitals (CDC

investigations). an estimated 1,25,969 hospitalizations annually for S. aureus infections in
1999–2000, including bloodstream infections and pneumonia. of the isolates 43.2% were
methicillin resistant.

• Some of the therapies suggesting that β-lactam antibiotics are superior for treatment of
these infections.
• Risk factors for HA-MRSA
• Being hospitalized. MRSA remains a concern in hospitals, where it
can attack those most vulnerable — older adults and people with
weakened immune systems.
• Having an invasive medical device. Medical tubing — such as
intravenous lines or urinary catheters — can provide a pathway for
MRSA to travel into your body.
• Residing in a long-term care facility. MRSA is prevalent in nursing
homes. Carriers of MRSA have the ability to spread it, even if they're
not sick themselves.
Community Acquired MRSA
• The causative bacteria of MW2 strain of community-associated MRSA, which appears to
have acquired staphylococcal cassette chromosome (SCC) mec type IV, the S.
aureus pathogenicity island (SaPI3), and the bacteriophage Sa2 in its evolution from
MSSA476.

• in France from 1986 to 1998, children's with pneumonia caused by S. aureus strains
positive for Panton-Valentine leucocidin (PVL). of 16 children, 12 (75%) presented with an
influenza-like illness, and 37.5% died within 48 h after hospital admission.

• In this series, MRSA isolates were susceptible to non–β-lactam antibiotics and caused
clinical disease. Most children presented with skin infections, including cellulitis or
abscess.
Treatment
Daptomycin

• It is more active against MRSA/MSSA.

• MSSA/MRSA MIC’s = 0.5 mcg/ml.

• Daptomycin is inactivated by calcium in alveolar surfactant fluid and not be

used for pneumonia, but useful for septic pulmonary emboli or lung
abscess.

• An initial dose of gentamycin, which increases the intracellular entry or

effectiveness of daptomycin when treating with MSSA/MRSA infections.
TMP- SMX (same spectrum of ceftriaxone)

• It is inactivate against most streptococci, it is an excellent antibiotic against

MSSA.

• TMP- SMX is active against CA-MRSA, but it is suboptimal against HA-

MRSA.

Linezolid

• Highly effective against major G+ve pathogens. Including, MSSA,MRSA .

Tetracyclines

• MRSA is sensitive to doxycycline invitro. But, it is delayed or incomplete response in in

vivo.

• Clinically, minocycline IV for treatment of MRSA/MSSA is more effective than doxycycline.

• oral Minocycline to treat serious systemic infections due to MRSA/MSSA. i.e.

Osteomyelitis, meningitis.

• Minocycline is the most cost effective oral anti-MRSA antibiotic.

Quinupristin/ dalfopristin

• Highly effective against MRSA/MSSA.

Clindamycin
• It is one of the few antibiotics, able to penetrate or dissolve staphylococcal
biofilms.
• It is effective against CA-MRSA but not HA-MRSA.
• With CA-MRSA, inducible clindamycin resistance should be suspected. if
erythromycin is resistant and clindamycin is sensitive.
• The D test will conform the clindamycin resistant.
Cephalosporins
• ceftaroline is the only cephalosporin active in vivo against MRSA.
• Vancomycin
• vancomycin is one of the major antibiotic for MRSA use.

• The MRSA is sensitive to vancomycin with MIC being 1 ug/ml.

• MIC values of vancomycin against MRSA has been increasing worldwide, leading to the emergence
of VISA.

• The combination therapy mainly included the combined regimen of vancomycin and carbapenems
with other aminoglycoside drugs, which increase the risk of developing nephrotoxicity and
ototoxicity.

• If combined therapy is needed for MRSA infection, the third generation cephalosporins should be
administrated.
Combination therapy
• Combination with vancomycin

• The Synergetic interactions between the vancomycin and wide variety of beta-lactams are there, but the mechanism is
still not clear.

• The see-saw effect

(if decreased vancomycin susceptibility, which results, decreased transcription of mecA gene and increase the
susceptibility of beta-lactams).

• Combination with daptomycin

• Daptomycin with beta-lactams, which kills the daptomycin susceptible and daptomycin non-susceptible MRSA.

• Increases the daptomycin binding to the bacterial cell membrane.

• Prevents the development of daptomycin resistant strains.

• It is proved in rabbit model of endocarditis.

Prevention
Preventing HA-MRSA

Preventing HA-MRSA
• In the hospital, people who are infected or colonized with MRSA often are
placed in contact precautions as a measure to prevent the spread of
MRSA.

• Visitors and health care workers caring for people in isolation may be
required to wear protective garments and must follow strict hand hygiene
procedures.

• Contaminated surfaces and laundry items should be properly disinfected.

 Preventing CA-MRSA
• Wash your hands. Careful hand washing remains your best defence against germs. Carry a small bottle of hand sanitizer
containing at least 62 percent alcohol for times when you don't have access to soap and water.

• Keep wounds covered. Keep cuts and abrasions clean and covered with sterile, dry bandages until they heal. The pus from
infected sores may contain MRSA, and keeping wounds covered will help prevent the bacteria from spreading.

• Keep personal items personal. Avoid sharing personal items such as towels, sheets, razors, clothing and athletic equipment.
MRSA spreads on contaminated objects as well as through direct contact.

• Shower after athletic games or practices. Shower immediately after each game or practice. Use soap and water. Don't share
towels.

• Sanitize linens. If you have a cut or sore, wash towels and bed linens in a washing machine set to the hottest water setting
(with added bleach, if possible) and dry them in a hot dryer. Wash gym and athletic clothes after each wearing.
 Antibiotic stewardship
• Antimicrobial stewardship is defined as “the optimal selection, dosage, and duration of antimicrobial
treatment that results in the best clinical outcome for the treatment or prevention of infection, with
minimal toxicity to the patient and minimal impact on subsequent resistance”. 24

• The goals of antibiotic stewardship are to work with health care practitioners to help each patient
receive the most appropriate antimicrobial with the correct dose and duration, to prevent
antimicrobial overuse, misuse, abuse and minimize the development of resistance.24

• An added benefit of programs that aim to optimize antibiotic use is that they generally experience
cost savings. Because, fewer doses of antibiotic are used and less expensive antibiotics are
chosen.
• Both at the individual patient level and at the community level, antibiotic use changes
susceptibility patterns.

• Patients exposed to antibiotics are at higher risk of becoming colonized or infected by

resistant organisms.

• As hospitalized patients become more complex to treat, the increasing prevalence of

antimicrobial resistance in both healthcare and community settings represents a daunting
challenge.

• Antimicrobial stewardship can provide all practitioners with tools to prevent the overuse of
valuable resources and help to control the increase in antimicrobial resistance.24,25
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