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AAVS_MH20141201091236-R1_Grema

 

Review Article

 

Methicillin Resistant Staphylococcus aureus (MRSA): A Review

 

Hafsat Ali Grema1, Yaqub Ahmed Geidam1, Galadima Bala Gadzama2, James Agbo Ameh3, Abubakar Suleiman4

1Department of Veterinary Medicine, Faculty of Veterinary Medicine; 2Department of Microbiology, College of Medical Sciences, University of Maiduguri Teaching Hospital; 3Department of Veterinary Microbiology, Faculty of Veterinary Medicine; University of Maiduguri, P. M. B 1069, Maiduguri, Borno State, Nigeria; 4Department of Veterinary Microbiology, Ahmadu Bello University, Zaria, Nigeria.

 

Abstract | Staphylococcus aureus (S. aureus) is a gram positive organism that serves as an opportunistic pathogen and frequent colonizer of the epithelium causing severe diseases in human and animals. The widespread use of antibiotics both in human and Veterinary medicine resulted in the emergence of resistant strains of S. aureus. Methicillin-resistant Staphylococcus aureus (MRSA) is a common bacterial pathogen responsible for a variety of infections. Resistance to methicillin is determined by the mecA gene, which encodes the low-affinity penicillin-binding protein PBP 2. Lately, new methicillin resistance gene, mecC has been discovered from humans, animals and food products. MRSA infection was first considered hospital-associated (HA-MRSA) and community-associated MRSA (CA-MRSA) infections. However, another group emerged known as livestock-associated MRSA (LA-MRSA). The isolation of MRSA from different species, food products and the environment raised concern on the role of animals particularly livestock and wildlife in the epidemiology of MRSA. The spatial distribution of MRSA indicates interspecies transmission and colonization of different populations. This review summarizes the current knowledge, transmission pattern and the epidemiology of MRSA from hospitals, communities, animals and their products.

 

Keywords | HA-MRSA, CA-MRSA, LA-MRSA, Epidemiology, Transmission

 

Editor | Kuldeep Dhama, Indian Veterinary Research Institute, Uttar Pradesh, India.

Received | December 01, 2014; Revised | December 16, 2014; Accepted | December 18, 2014; Published | January 02, 2015

*Correspondence | Hafsat Ali Grema, University of Maiduguri, Maiduguri, Borno State, Nigeria; Email: gremahafsa@yahoo.com

Citation | Grema HA, Geidam YA, Gadzama GB, Ameh JA, Suleiman A (2015). Methicillin resistant Staphyloccus aureus (MRSA): a review. Adv. Anim. Vet. Sci. 3(2): 79-98.

DOI | http://dx.doi.org/10.14737/journal.aavs/2015/3.2.79.98

ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331

Copyright © 2015 Grema et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

 

Introduction

 

Staphylococcus aureus is a bacterium of significant importance because of its ability to cause a wide range of diseases and capacity to adapt to diverse environmental forms (Lowy, 1998; Waldvogel, 2000). The organism colonises skin, skin glands and mucous membrane, causing infections both in human and animals such as rashes, inflammations of bones and the meninges as well as septicaemia (Aklilu et al., 2010). In addition, S. aureus causes inflammation of the mammary gland in bovine and the lower part of the foot in poultry (Quinn et al., 2000). Penicillin and its derivatives, including methicillin have been used for the treatments of infections caused by S. aureus (Rayner and Munckhof, 2005). However, certain strains of S. aureus developed resistance known as methicillin resistant Staphylococcus aureus (MRSA). At present, less than 90% of S. aureus strains are resistant to most penicillin derivatives (Freeman-Cook and Freeman-Cook, 2006) and ordinary antimicrobial agents like drugs from the family of aminoglycosides, macrolides, chloramphenicols, tetracyclines and fluoroquinolones (Lee, 2003).

 

A gene known as mecA gene is responsible for the resistance to methicillin which codes for penicillin-binding protein PBP 2A (Wielders et al., 2002). Lately, a new methicillin resistance mechanism gene, mecC was described in S. aureus (Porrero et al., 2014). García-Álvarez et al. (2011), Paterson et al. (2012), Walther et al. (2012) and Paterson et al. (2014) reported MRSA isolates carrying mecC gene from humans and animals. Harrison et al. (2013) suggested the public health hazard of mecC-positive MRSA isolates as it has been isolated in human case and their livestock.

 

Until recently, MRSA was associated with prior exposure to health care facility, and as such, was considered a nosocomial pathogen (Tiemersma et al., 2004). A number of publications on MRSA infections in populations lacking traditional risk factors (Herold et al., 1998) have been reported. This raised concern for infections originating from the community and veterinary species (Cohn and Middleton, 2010). Reports of MRSA isolation in domestic animals seems to be rising in number (Devriese and Hommez, 1975; Hartmann et al., 1997; Tomlin et al., 1999; Lee, 2003; Goni et al., 2004; Rich and Roberts, 2004). The epidemiology of MRSA isolates from human and animal sources showed that for certain strains, a cross-infection might have happened (Seguin et al., 1999; Strommenger et al., 2006; Weese et al., 2006). Studies conducted by Feirrera et al. (2011) and Verkade and Kluytman (2014) suggested that animals can be a potential source of MRSA infection to humans.

 

Therefore knowledge on the epidemiology of MRSA will underpin effective prevention and control strategies, including the rational use of antibiotics. This review article wishes to highlight the epidemiology and possible source of MRSA transmission in hospitals, community and livestock settings.

 

Historical Background of MRSA

 

Alexander Fleming conducted a research and reported the bactericidal effects of a fungal contaminant that produced penicillin against S. aureus growing on culture plates (Fleming, 1929). A mass production of the drug from vats of cornsteep liquid growing on the mold was preceded due to the high mortalities during World War II (Neushul, 1993). Subsequently, there was a dramatic drop in death rates from bacterial pneumonia and meningitis in World War II compared to World War I. This led to the development of penicillin as the first major driver in selecting for resistant S. aureus. In 1940, an active β- lactam ring enzyme was described in Escherichia coli that are capable of hydrolyzing the penicillin. This enzyme was later named “penicillinase” (Abraham and Chain, 1940) while in 1944; penicillinase production was also discovered in S. aureus (Kirby, 1944). In 1948, it was observed that over 50% of staphylococcal isolates recovered from patients in a United Kingdom hospital were resistant to penicillin (Barber and Rozwadowska-Dowzenko, 1948). Since then to date, 90 to 95% of S. aureus strains worldwide are penicillin resistant, with the plasmid encoded penicillinase readily transferable via transduction or conjugation. A penicillinase-resistant penicillin known as methicillin was introduced in 1959 to combat penicillin-resistant S. aureus, but within a year, late Professor Patricia Jevons reported the first human S. aureus strain to be methicillin resistant in UK hospital (Kim, 2009). In 1962, an epidemic occurred at a hospital called Queen Mary’s Children’s Hospital, Carshalton. These strains became widespread in hospitals and into communities by the 1960’s (Spink, 1978). In 1968, United States recorded the first outbreak of MRSA (Palavecino, 2004) while in the 1970s, S. aureus strains have become resistant to most penicillinase-stable penicillins. It was first assumed to be a disease of human origin until when MRSA was first isolated in 1972 in a mastitic cow (Deveriese et al., 1972). Thereafter, reports of MRSA infection became established in domestic and wild animals (Rich and Roberts, 2004; Wardyn et al., 2012).

 

Epidemiology of MRSA 

 

Epidemiological typing of MRSA strains resulted in the recognition of different lineages that are zoonotic, humanosis and/or host specific. Seventeen epidemic strains of human MRSA have been described in the United Kingdom (Aucken et al., 2002) but the most dorminant are EMRSA-15 and EMRSA-16 (Hardy et al., 2004.). The EMRSA-16 clone represents major cause of human MRSA infections in Europe and America (Holden et al., 2004). In Africa, epidemiological data on the predominant clones responsible for most epidemics is poorly documented. According to Breurec et al. (2011), the most predominant clones of African origin are ST88-IV, ST5-IV and ST239-III which are CA-MRSA. ST88-IV is a clone identified both in hospitals and community infections. The European lineage (EMRSA-16) has been described to originate from sub-saharan Africa (Stegger et al., 2014) and has been reported in hospital and community acquired infections in Algeria (Abdulqader et al., 2014). Other lineages of human origin include CC1, CC5, CC8, CC22, CC30 and CC45 while MRSA lineage predominant in pigs and other food animals is CC398 (Witte et al., 2007; Feßler et al., 2012). Interspecies transmission of the strain CC398 (ST398) is a potential hazard and can be facilitated by frequent contact, environmental contamination and individual’s immunity (Declercq et al., 2008). Three major settings were recognized according to host specification, reservoir and source of transmission (Millar et al., 2007).

 

Healthcare-Associated MRSA (HA-MRSA)

MRSA isolates from hospital settings has been gradually increasing in the United States and other parts of the world (Summary of MRSA prevalence from different countries across the world is presented in (Table 1). However, reports in 2011 surveillance programme in USA suggest the recent decline in MRSA infections specific to hospital settings (Raymund et al., 2013). Depending on the study area and sample size, high rate of MRSA rates (>50%) have been reportd in USA, Asia and Malta, intermediate rate (25-50%) reported in Africa, China and Europe while in some part of Europe, the prevalence rate is relatively lower than 50% (Mejìa et al., 2010). Stafeni et al. (2012) compiled the prevalence rates of HA-MRSA in some European countries like France, Ireland and UK and reported decline in hospital cases. While in Asia particularly South Korea (77.6%), Vietnam (74.1%), Taiwan (65%) and Hong Kong (56.8%) reports on HA-MRSA infections is still high. The major lineage responsible to the hospital spread of MRSA between these continents is CC8 (ST239) (Harris et al., 2010). For MRSA acquired in hospitals, colonisation do increases the chance for infection (Safdar and Bradley, 2008). Anterior nare is the usual site for MRSA colonization, although other anatomical sites such as hands, perineal region, skin wounds, throat, genitourinary tract and the digestive tract may also be colonized (Sanford et al., 1994). High chance of hospital colonization may be from contact with MRSA colonized patient or contaminated objects. Respiratory infection is a predisposing factor for dessimination of MRSA through aerosols (Kucers and Bennett, 1987) which can cause serious infections and complications. Generally, HA-MRSA results in dermatitis, septicemias, heart and lung diseases which are mostly seen in immunocompromised people. Risk factors include hospitalization, surgery, dialysis and previous history of MRSA infection (Umaru et al., 2011).

 

Community-Associated MRSA (CA-MRSA)

MRSA strains acquired in the community were first reported in the late 1990s in patients with no history of exposure to healthcare settings (Umaru et al., 2011). The most common lineage in this case was USA300 (CC8-ST8) in the USA. These strains are mostly responsible to skin and soft tissue infections. In comparism, the most dorminant lineage causing infection in Europe is CC80 (ST80). However the strain USA300 has also been reported in Europe (Tietz et al., 2005). Transboundary transmission of MRSA strain is reported between countries like North America and Middle East, Asia and South America (Stefani et al., 2012). The spread of CA-MRSA has extended to healthcare centres in USA and France (Donnio et al., 2004). Outbreaks of CA-MRSA is mostly seen from populations such as sports teams (Collins and Oconnell, 2012), prisons (Palavecino, 2004), day care centers (Simmonds et al., 2008), military quarters (Marchese et al., 2000) homeless people (Yano et al., 2000), and intravenous drug users (Torres-Tortosa et al., 1994). Risk factors include international travel (Mikael et al., 2010), overcrowding, compromised skin, poor hygiene and sharing of items such as towels, sporting equipment and unsterilized first aid instruments (Kazakova et al., 2005). 

 

Livestock-Associated MRSA (LA-MRSA)

The scope of MRSA infection is not limited to human medicine only but also in Veterinary Medicine (Lee, 2003; Baptise et al. 2005; Voss et al., 2005; Khanna et al., 2008; Smith et al., 2008). MRSA was first considered a human infection until when it was isolated in a dairy cow with mastitis (Devriese et al, 1972) and in pigs (Stefani et al., 2012). The most predominant lineage in livestock is CC398 which has been reported in Europe, USA and Asia (Monecke et al., 2011). However, the prevalence of LA-MRSA CC398 in these countries is still very low (Stefani et al., 2012). But in countries like Denmark, Netherland and Belgium, the report of MRSA CC398 in livestock is high (Köck et al., 2009a; Köck et al., 2009b). Epidemiological studies in UK indicate the spread of LA-MRSA into hospitals particularly in individuals with frequent animal contact (Paterson et al., 2012). Recently, there is evidence of MRSA transmission between human-to-animals and animals-to-humans (Umaru et al., 2011). Voss et al. (2005) reported 23% of pig farmers colonized MRSA from a pig farm in the Netherlands with while VanRijen et al., 2008 found 32% of farm workers colonized with MRSA.

 

Table 1: Prevalence of MRSA carriage in some countries across the world

Country

Sample size

Prevalence %

Source

References

Argentina

591

16

Hospital

Egea et al., 2014

Bangladesh

49

53.1

Hospital specimens

Afroz et al., 2008

Bolivia

585

0.5

community

Batoloni et al 2013

Cameroon

295

34.6

Hospital staff/patients

Gonsu et al., 2013

Chile

246

80

Hospital

Guzman-Blanco, 2009

Columbia

538

92.4,65.1,43.6

Hospital record

Jiménez  et al., 2012

Congo

60

patients

Iyamba et al., 2014

Costa Rica

674

58

Hospital

Guzman-Blanco, 2009

Cuba

80

6

Hospital

Guzman-Blanco, 2009

Equator

1363

25

Hospital

Guzman-Blanco, 2009

Ethiopia

118

44.1

Hospital

Shibabaw et al., 2013

Guatemala

1483

64

Hospital

Guzman-Blanco, 2009

Hongkong

NK

75

NK

Diekema et al., 2000

Hounduras

393

12

Hospital

Guzman-Blanco, 2009

Indonesia

1502

4.3

Hospital

Santosaningsih et al., 2014

Japan

90

44.4

Environmental surfaces

Asoh et al., 2005

Kenya

950

7.0

Hospital

Aiken et al., 2014

Malaysia

26

Hospital

Norazah, 2008

Mexico

497

52

Hospital

Guzman-Blanco, 2009

Nepal

750

26.14

Hospital

Kumari et al., 2008

Netherland

9859

0.03

Hospital

Wertheim et al., 2004

Nicaragua

296

20

Hospital

Guzman-Blanco, 2009

Nigeria

208

19.2

Hospital

Olowe et al., 2013

North India

6743

46

Hospital

Arora et al., 2010

Paraguay

980

44

Hospital

Guzman-Blanco, 2009

Peru

1431

80

Hospital

Guzman-Blanco, 2009

Singapore

35

Hospital

Hsu et al., 2007

Sudan

426

69.4

Hospital

Elimam et al., 2014

Thailand

41.5

Hospital

Trakulsomboom and Thamlikitkul, 2008

Uganda

188

31.5

Hospital

Ojulong et al., 2008

Uraguay

2114

59

Hospital

Guzman-Blanco, 2009

NK: Not known

 

 

Table 2: Prevalence of MRSA infection and carriage rates in different animals

Year

Country

Species

Sample

Prevalence (%)

Detection Methods

MRSA Characterization

References

2010/2012

Germany

Dogs, cats, horses

Wound specimen

62.7,46.4, 41.3

Spa, MLST

CC22, CC5, CC398

Vincze et al., 2014

2003/2004

Germany

Cats

Clincal

10

BA/ChromAgar

ST22/SCCmecIV

Walther et al., 2008

2007

Belgium

Horses

Clinical

10.9

Phenotypic, PCR

ST398, t011& t1451

Van den Eede et al., 2009

2007/2008

Netherland

Calves

Nasal sample

88,28

Phenotypic and PCR

ST398

Graveland et al., 2010

2010

Germany

Pigs

Healthy swabs

52

PCR, MLST

CC398

Alt et al., 2011

2006/2008

Czech Republic

Goat Farm

Goats milk

1.1

PCR

SCCmec IV, spa type t064

Stastkova et al., 2009

2009/2011

Belgium

Cows/ Broilers

Nasal, cloaca

5.0,5.0

PCR, MLST

CC599, CC130, CC398

Vandendriessche et al., 2013

2years

Malaysia Egypt

Tilapia Tilapia

Brain, eyes,kidney swabs

50

MSA/PCR

NK

Atyah et al., 2010, Soliman et al., 2014

2009

Elephant

Clinical

100

PFGE

USA300

Leggiadro, 2009

2006

Canada

Dolphin, Walrus

Necropsy

Nasal swab

33.3, 16.7

PFGE

USA100

Faires et al., 2009

 

BA: Blood Agar; MSA: Mannitol salt agar; PCR: Polymerase Chain Reaction, NK: Not Known; PFGE: Pulse Field Gel Electrophoresis

 

 

Table 3: Prevalence of MRSA isolates from major food/meat product

Food Product

Samples collected

Prevalence (%)

Source

References

Beef

395

42 (10.6)

Farm

De Boer et al., 2009

Milk

894

265 (29.6)

Farm

Lee, 2003

Pork

395

26 (6.6)

Retail

O'Brien et al., 2012

Chicken

25

11 (44.0)

Retailer

Karmi, 2013

Turkey

116

41 (35.3)

Retail Trade

De Boer et al., 2009

Guinea fowl

118

4 (3.4)

Retail Trade

De Boer et al., 2009

Lamb/mutton

324

20 (6.2)

Retail Trade

De Boer et al., 2009

Tilapia Fish

559

198 (50)

Fish pond

Atyah et al., 2010

Game birds

178

4 (2.2)

Retail Trade

De Boer et al., 2009

Veal

119

20 (16.8)

Retail

Anonymous, 2007

 

 

Likewise, Stein (2009) conducted a study among pig farmers in North America and found colonization rates of 20%. These results backup other findings that revealed the chances of animals becoming reservoirs of human MRSA infections regardless of location (Feingold et al 2012). In addition, human-to-human transmission can occur following one’s exposure to colonized or infected animals due to isolation of MRSA strains from people with no animal contact (Huijsdens et al., 2006). High risk groups are the veterinary clinic personnel and the animals care givers (O’Mahony et al., 2005; Moodley et al., 2005; Wulf et al., 2006; Hanselman et al., 2006).

 

MRSA in companion Animals

Animals such as dogs, cats and horses have become an important part of most families particularly in developed countries like USA and UK (chomel and sun 2011). Therefore, there are high chances of human colonization or infection with MRSA from these animals (Mustapha et al., 2014). In the UK, 1.5% of MRSA were recovered from samples of infected companion animals (Rich and Roberts, 2004) and dogs are more infected/colonized with MRSA in comparism to cats (Morgan, 2008). Skin and soft tissue infections are the main form of disease manifestation. MRSA strains isolated in most UK hospitals are identified as EMRSA-15 (ST22) and EMRSA-16 (ST36) (Ellington et al., 2010) while the strains isolated in USA pets are the USA100 (ST5) which has been documented in HA-MRSA infections in humans (McDougal et al., 2003). In addition, a study in UK recovered MRSA clone (ST398) in dogs and horses that were characteristic of livestock animals (Loeffler et al., 2009).

 

Reports of MRSA colonization in horses with a percentage rate of 0 to 11% has been published (Loeffler et al., 2011). Most cases and outbreak of MRSA infections were reported in large stables and post-operative complications (Weese et al., 2005; Morgan, 2008). In horses, MRSA lineages isolated were distinct from the strains isolated in humans (Loeffler and Lloyd, 2010).

 

MRSA in Wildlife

Although the role of wildlife as reservoir for MRSA colonisation and/or infection has not yet been established, there are several studies that revealed the isolation of MRSA in many captive wildlife animals (Loncaric et al., 2014). A study by Wardyn et al. (2012) revealed the isolation of MRSA from cottontail rabbit and a lesser yellow migratory shore bird. Other studies include isolation of MRSA from Wild rat, (Himsworth et al., 2014), wood mice (Gómez et al., 2014) red deer, Iberian ibex, vulture, wild boar (Porrero et al., 2012). In some of the studies, the homologue of mecA gene known as mecC strain (ST398 and ST1) were isolated and suspected to be of livestock and human origin (Porrero et al., 2012). Although the mecC homologue is currently uncommon in human infections globally, it has been identified recently in human and animal infections in the UK, Denmark and Ireland (Paterson et al., 2014b). The most common animal lineage that causes disease in wild life is CC130 and ST425 (Paterson et al., 2014a).

 

As the menance of MRSA colonization is extending into the wild life, control of the disease in human and domesticated animals will become a new challenge. This is due to the fact that wild animals can serve as source of animal and human colonization (particularly park rangers and zoo keepers) as well as contamination of the environment (Guideline for management of zoonoses, 2011; Chethan Kumar et al., 2013). Summary of MRSA prevalence in animals (both wild and domesticated) is presented in Table 2 according to some reports published.

 

MRSA in abattoirs, food processing units and animal products

The environment of abattoirs and food production units are contaminated with MRSA (EFSA, 2009). The sources of contamination can either be the animals moving into the abattoir for slaughter or the workers involved in processing the end product (Gilbert et al., 2012). Contaminated skin, feces, infected organs and water used in processing are the vital sources of contamination in abattoirs and food processing units (Soonthornchaikul et al., 2006). Some studies suggest that S. aureus from food handlers can be part of normal body flora that subsequently contaminates carcasses. Broens et al. (2011) conducted a study and found 12 out of 117 pigs tested MRSA positive in a slaughterhouse after being tested negative during and after transportation.

 

Animal food products such as meat, meat products and milk may become contaminated with MRSA through slaughter or milking of colonized/ infected animal, thus, contaminating the product and environment. MRSA strains have been discovered from foods such as bovine milk and cheese, pork and beef as well as raw chicken meat (Kwon et al., 2006; Normanno et al., 2007; Van Loo et al., 2007; O’Brien et al., 2012). The strains of MRSA isolated in most food samples include ST398, ST125 and ST217 (Faccioli-Martins and de Souza da Cunha, 2012) while the recent mecC homologue of mecA gene has been isolated in bovine milk in England (Paterson et al., 2014b). The presence of these strains on food products could suggest possible human or animal contamination. An important link in food borne infections connecting humans and food producing animals is the meat and milk or their products (Mayrhofer et al., 2004). Although food products may serve as vehicle for MRSA transmission, consumption of such meat carry only small risk as S. aureus found on meat surfaces and can be killed by high temperature. However, there is high risk of transmission from live animal or raw meat to people working directly with animals or their products. The prevalence of MRSA isolation from food/meat products is presented in table 3.

 

MRSA Transmission in hospital settings

For hospital infection, the hands and nostrils of colonized individuals are the major sources of MRSA transmission. MRSA is released into the hospital environment either through aerosol, skin cells or stools of infected patient (Klotz et al., 2005). Areas contaminated in the hospital include medical instrument, beddings, clothing, furnitures, toiletries and the atmosphere (Dancer, 2008). Gehanno et al. (2009) found similar strain of MRSA in patients of a hospital and the room atmosphere. While Loeffler et al. (2005) and Weese et al. (2004) reported MRSA in environmental samples collected from small animal veterinary hospital and equine veterinary hospital, respectively. Although, hospital cleaning reduces MRSA contamination of the environment, in some cases it does not eliminate it.

 

MRSA in the Community

Some studies investigated environmental contamination of MRSA outside hospital settings (EFSA, 2007). Reports include continous colonization of a medical staff which was related to contamination of home environment (Allen et al., 1997; de Boer et al., 2006). Again, contamination of animal housing revealed the possibility of human and animal colonization. Van Den Broek et al. (2008) isolated MRSA from pig house dust and humans working in MRSA positive pig farms.

 

Airborne MRSA in livestock settings are mostly seen in dust particles that are derived from the animals. MRSA was isolated in dust from infected herds which may be subsequently inhaled by workers in the farm (EFSA, 2007; Schulz et al., 2012). Transmission of disease through water may occur in aquatic animals such as fish. Transmission from fish to humans could be through injury from cleaning aquarium with bare hands (Alinovi et al., 1993) and exposure to fish tank water (Kern et al., 1989).

 

MRSA Detection in Humans and Animals

In an effort to control MRSA in major settings (hospital, community, animals) colonized and infected humans, animals and environmental surfaces must be identified. The menance of MRSA colonization and infection has extended from human, companion and food animals into wildlife animals. The screening of human carriers in hospitals and communities is necessary for the successful diagnosis and control of MRSA. In addition, companion animals with skin and soft tissue infections should be screened for MRSA. Sites for screening of MRSA colonized animals include nose, skin, perineum and rectal or cloacal swabs (de Neeling et al., 2007; Khanna et al., 2008) and nostril for humans (Peacock et al., 2001). Nasal screening alone identifies 80% of carriers, and addition of sampling from throat, may increase this to 92% (Grundmann et al., 2006). For environmental samples, swabs are taken from dust samples (EFSA, 2007; Broens et al., 2008), tables, containers, feed material or feces and bedding material (Lee, 2003). Other samples like milk and meat from animals and cloacal swab from poultry should be cultured for detection of MRSA.

 

Various methods are applied for the detection of MRSA through phenotypic and genotypic characterization of samples from infected sites such as skin lesions, abscesses or blood. Both has advantages and disadvantages such as speed, reliability and acessibility. Phenotypic methods involves standard microbiological technique of S. aureus detection which include Gram staining, colonial morphorlogy, catalase and coagulase tests, pigment production and anaerobic growth (Karthy et al., 2009). Additional methods include Minimum Inhibitory Concentrations, methods that detect mecA gene or PBP20 protein and media containing oxacillin (Louie et al., 2001). Selective enrichment media have been developed to achieve isolation and identification of MRSA in a single step, thus by-passing the conventional procedures (Stoakes et al., 2006). Ideal enrichment media contains indicators, inhibitory agents and antibiotics usually oxacillin or cefoxitin. Examples are Oxacillin Resistant Screening Agar Base (ORSAB) which result in intense blue colonies (Becker et al., 2002), CHROM agar which give rise to a rose to mauve color and MRSA ID which forms distinctive green colonies.

 

In addition to culture media, antimicrobial susceptibility tests (AST) such as agar disc diffusion technique or minimum inhibitory concentration are used in diagnostic laboratories to isolate MRSA (Aklilu et al., 2010). Detection of the mecA gene is considered as the reference method for determining methicillin resistance (Chambers, 1997). Resistance of S. aureus to oxacillin and/or cefoxitin provides a clue for MRSA suspicion (van Enk and Thompson, 1992). Oxacillin and cefoxitin test are the preferred method for testing mecA resistant gene of S. aureus (CLSI, 2006). In order to report isolates as resistant or susceptible should be based on the result obtained on the cefoxitin test. Cefoxitin disc diffusion is the most sensitive methods for detecting MRSA isolates showing negative and positive predictive values of 100% and 98%, respectively (Valesco et al., 2005).

 

A more advanced technique usually accompanies the phenotypic methods in order to enhance specificity and time. Molecular methods such as PCR are used to detect S. aureus specific DNA sequences encoding for protein synthesis and the mec genes. Other molecular typing methods include pulsed-field gel electrophoresis (PGFE) and multilocus sequence typing (MLST), Staphylococcal Protein A Gene (spa) locus typing and Staphylococcal Cassette Chromosme (SCCmec) typing. The strength and weaknesses of the above genotypic methods are presented in table 4.

 

Treatment and Control of MRSA

 

The indiscriminate exposure of humans and animals to antibiotics created problem through acquisition and dessimination of MRSA which limit the choice of treatment. Most antibiotics used for treatment of MRSA infection has been reported to have developed resistance (Ayliffe, 1997). In order to manage the risk of antibiotic resistance in humans and animals, decolonization of carriers and monitoring of resistant strains through susceptibility test will surely help. The use of antibiotic to treat infection should depend on the result of antimicrobial susceptibility testing, although most strains appear ineffective during treatment even when sensitive in routine susceptibility test. Antibiotics such as trimethoprim-sulphamethoxazole, clindamycin and doxycycline are reported to be effective in the treatment of CA-MRSA infection (Ernst, 2012). Newer drugs such as oritavancin, telavancin omadacycline, tedizolid and dalbavancin have a promising impact on the treatment of MRSA. Other existing agents such as fosfomycin and fusidic acid are under investigation for potential used in the treatment of MRSA infection (Burke and Warren, 2014).

 

Table 4: Summary of the comparative strength and weaknesses of current genotypic methods used for MRSA typing

Methods

Principle

Strengths

Weaknesses

References

Pulsed-field gel electrophoresis (PFGE)

S. aureus DNA fragments are move down the gel, creating unique band patterns that are then compared with those of other isolates to identify related strains

High discriminatory power

Technically demanding

Slow

Limited inter laboratory portability

Multiple nomenclature

Tenover et al., 1995

Multilocus sequence typing

(MLST)

Uses sequence analysis of ~500-bp internal fragments of seven housekeeping genes: arcC, aroE, glpF, gmk, pta, tpi, and yqiL. The DNAsequences are compared to those of previously identified alleles at each locus on the MLST online database

Phylogenic structure of core genome

Inter laboratory portability

Standard nomenclature

Limited discriminatory power

Low throughput

Expensive

Enright et al., 2000

S. aureus protein A (spa)

Typing of a single locus zone in the polymorphic region X of S. aureus A which involves duplication and mutation in the variable repeats of 24bp

Rapid

High throughput

Inter laboratory portability

Standard nomenclature

Attribution of MLSTS STs by BURP algorithm

Moderate discriminatory power

Misclassification of particular STs due to recombination/homoplasy

Szabó (2014)

SCCmec typing

Used to define the 7 major mec and ccr gene of 7 major SCCmec types and subtypes ranging from 20 to 67kb

High discriminatory power

No universally used assay

No nomenclature used but a combination of SCCmec typing and MLST has been proposed

Chongtrakool et al., 2006

Rep- PCR typing

Polymorphism in chromosomal inter-repeat element spacers

Rapid

High throughput

Limited discriminatory power

No validated interpretation criteria

No standard nomenclature

Struelens et al., 2009

Multilocus VNTR analysis (MLVA)

Polymorphism in number of chromosomal VNTR elements

Rapid

High throughput

Limited discriminatory power

No validated interpretation criteria

No standard nomenclature

Struelens et al., 2009

 

 

As the MRSA epidemic becomes life threatening and beyond antibiotic therapy, development of vaccine to combat the disease became important (Cimolai, 2006). The first attempt to develop S. aureus vaccine was by the use of Streptococcus pneumonia and hemophilus influenza vaccine model. The formula was called Staphvax developed by biopharmaceuticals in 1990s though unsuccessful (Mckenna, 2014). Continous attempts were made by different institutions like University of Chicago and the Absynth biologics which uses clotting factors to produce abscess and membrane protein, respectively (Cheng et al., 2010). However, trial on mice did not produce the desired result of abscess development and antibody production (Hu et al., 2013). Recently, Russell (2012) suggested the role of polyvalent pneumococcal vaccine to develop vaccine for staphylococcal infections. Therefore based on published data, researches are still been conducted on MRSA vaccine development but no established vaccine is available. In the absence of preventive measures such as vaccination, basic control options that will reduce MRSA colonisation or infection in humans and animals are necessary.

 

Basic hygiene, good husbandry and biosecurity measures on farms, abattoirs and food processing units have a tendency to reduce the spread of MRSA in animal population. Individuals with frequent animal contact should be educated on the risk of MRSA transmission in animals or their environment. In hospitals, hygienic measures particularly hand washing before and after contact with contaminated surfaces and the avoidance of close contact with discharges from nose, mouth and wounds of infected human and animals will surely reduce the chances of transmission. Decolonization of MRSA positive carriers’ either through the use of antibiotic therapy (chlorhexidene or murocidin) or culling of affected animals or product will reduce the spread in the environment. Medical practitioners should be encouraged to choose antibiotic based on susceptibility test and to wear protective equipment during surgery and handling of patients to reduce contamination and spread.

 

Conclusion

 

In conclusion, the prevalence of MRSA isolation from hospitals, community, animals and their products has increased in different geographical locations. The continous vigilance of MRSA through monitoring of newer strains, their characteristic, host specificity and transmission routes in each of the settings (HA-MRSA, CA-MRSA, LA-MRSA) will help in effective control of MRSA. MRSA is no longer infection acquired in the hospital alone, but rather in communities through contact with domesticated and wild animals as well as food products and the environment. Therefore, there is need for effective control of MRSA in all the settings and the avoidance of indiscriminate use of antibiotics to prevent further selection of resistance by microorganisms.

 

References

 

  • Abdulqader SMA, Shittu A, Nicol PM, Kaba W (2014). Molecular epidemiology of Methicillin Resistant Staphylococcus aureus in Africa: A systemic review of the published literature. Int. J. Infect. Dis. 21(1): 1-484.

  • Abraham EP, Chain E (1940). An enzyme from bacteria able to destroy penicillin. Nature. 146: 837-842.

  • Afroz S, Kobayashi N, Nagashima, S, Alam MM, Hussain ABMB, Rahaman MA, Islam MR, Luifor AB, Muazzam NMAH, Paul SK, Shamsuzzaman AKM., Mahmud MC, Musa A KM, Hossain MM (2008). Genetic Characterization of S. aureus isolates carrying Panton-valine leukocidin genes in Bangledesh. J. infect. Dis. 61(5): 393-396.

  • Aiken AM, Mutuku IM, Sabat AJ, Akkerboom V, Mwangi J, Scott JA, Morpeth SC, Friedrich AW, Grundmann H.(2014). Carriage of Staphylococcus aureus in Thika Level 5 Hospital, Kenya: a cross-sectional study. Antimicrob. Resist. Infect. Control. 15(3): 22. http://dx.doi.org/10.1186/2047-2994-3-22

  • Aklilu E, Zunita Z, Hassan L, Chen HC (2010). Phenotypic and genotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolated from dogs and cats at University Veterinary Hospital, Universiti Putra Malaysia. Trop. Biomed. 27(3): 483-492.

  • Alinovi A, Vecchini F, Bassissi P (1993). Sporothricoid mycobacterial infection – a case-report. Acta Dermato- Venereologica. 73(2): 146-147.

  • Allen KD, Anson JJ, Parsons LA, Frost NG (1997). Staff carriage of methicillin resistant Staphylococcus aureus (EMRSA 15) and the home environment: a case report. J. Hosp. Infect. 35(4): 307-311. http://dx.doi.org/10.1016/S0195-6701(97)90225-5

  • Alt K, Fetsch A, Schroeter A, Guerra B, Hammerl JA, Hertwig S, Senkov N, Geinets A, Mueller-Graf C, Braeunig J, Kaesbohrer A, Appel B, Hensel A, Tenhagen BA (2011). Factors associated with the occurrence of MRSA CC398 in herds of fattening pigs in Germany. BMC Vet. Res. 7: 69. http://dx.doi.org/10.1186/1746-6148-7-69 PMid: 22074403 PMCid:PMC3260235
  •  

  • Anonymous (2007). Prevalence of MRSA in meat, (2007). FACTSHEET MRSA op vlees ENG 20080304 OSdef www2.vwa.nl/cdlpub/servlet/CDLServlet?p_file_id=25742. Acessed on 17 Nov 2014.
  •  

  • Arora S, Devi P, Devi B (2010). Prevalence of Methicillin-resistantStaphylococcus aureus (MRSA) in a Tertiary Care Hospital in Northern India. J. lab. Physicians. 2(2): 78-81. http://dx.doi.org/10.4103/0974-2727.72154 PMid:21346901 PMCid:PMC3040078
  •  

  • Asoh N, Masaki H, Watanabe H, Watanabe K, Mitsusima H, Matsumoto K, Oishi K, Nagatake T (2005). Molecular characterization of the transmission between the colonization of methicillin-resistant Staphylococcus aureus to human and environmental contamination in geriatric long-term care wards. Intern. Med. 44(1): 41-45. http://dx.doi.org/10.2169/internalmedicine.44.41 PMid:15704661
  •  

  • Atyah MAS, Zamri-Saad M, Siti-Zahrah A (2010). First report of methicillin-resistant Staphylococcus aureus from cage-cultured tilapia (Oreochromis niloticus). Vet. Microbiol. 144(3-4): 502-504. http://dx.doi.org/10.1016/j.vetmic.2010.02.004 PMid:20189324
  •  

  • Aucken HM, Ganner M, Murchan S, Cookson B, Johnson AP (2002). A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics. J. Antimicrob. Chemother. 50(2): 171-175.
  •  

  • Ayliffe G (1997). The progressive intercontinental spread of methicillin-resistant Staphylococcus aureus. Clin. Infec. Dis. 24 (1): 74-79. http://dx.doi.org/10.1093/clinids/24.Supplement_1.S74
  •  

  • Baptiste KE, Williams K, Willams NJ, Wattret A, Clegg PD, Dawson S, Corkill J E, O’Neill T, Hart CA (2005). Methicillin-resistant staphylococci in companion animals. Emerg. Infect. Dis. 11(12): 1942-1944.
  •  

  • Barber M, Rozwadowska-Dowzenko M (1948). Infection by penicillin resistant staphylococci. Lancet. 252(6532): 641-644.
  •  

  • Bartoloni A, Pallecchi L, Fernandez C, Mantella A, Riccobono E, Magnelli D, Mannini D, Strohmeyer M, Bartalesi F, Segundo H, Monasterio J, Rodriguez H, Cabezas C, Gotuzzo E, Rossolini GM (2013). Low prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in urban and rural community settings in Bolivia and Peru. Int. J. Infect. Dis. 17(5): 339-342. http://dx.doi.org/10.1016/j.ijid.2012.11.017
  •  

  • Becker A, Forster DH, Kniehl E (2002). Oxacillin resistance screening agar base for detection of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 40(11): 4400-4401.
  •  

  • Breurec S, Zriouil SB, Fall C, Boisier P, Brisse S, Djibo S, Etienne J, Fonkoua MC, Perrier-Gros-Claude JD, Pouillot R, Ramarokoto CE, Randrianirina F, Tall A, Thiberge JM; Working Group on Staphylococcus aureus infections, Laurent F, Garin B (2011). Epidemiology of methicillin-resistant Staphylococcus aureus lineages in five major African towns: emergence and spread of atypical clones. Clin Microbiol Infect. 17(2): 160-165. http://dx.doi.org/10.1111/j.1469-0691.2010.03219.x PMid:20298267
  •  

  • Broens EM, Graat EA, van der Wolf PJ, van der Broek IV, Tiemersma EW, Van de Giessen AW, de Jong MC (2008). Prevalence study and risk factor analysis of NTMRSA in pigs in the Netherlands. American Society for Microbiology meeting on: Antimicrobial resistance in zoonotic bacteria and foodborne pathogens, Copenhagen, Denmark.
  •  

  • Broens EM, Graat EA, Van der Wolf PJ, Van de Giessen AW, De Jong M (2011). Transmission of methicillin resistant Staphylococcus aureus among pigs during transportation from farm to abattoir. Vet. J. 189(3): 302-305. http://dx.doi.org/10.1016/j.tvjl.2010.08.003
  •  

  • Burke ST and Warren ER (2014). New pharmacological treatments for methicillin-resistant Staphylococcus aureus infections. Expert opinion on pharmacotherapy. 15 (4): 483-491. http://dx.doi.org/10.1517/14656566.2014.876991
  •  

  • Cefai C, Ashurst S, Owens C (1994). Human carriage of methicillin-resistant Staphylococcus aureus linked with pet dog. Lancet. 344(8921): 539-540. http://dx.doi.org/10.1016/S0140-6736(94)91926-7
  •  

  • Chambers HF (1997). Methicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin. Microbiol. Rev. 10(4): 781–791. PMid:9336672 PMCid:PMC172944
  •  

  • Cheng AG, McAdow M, Kim HK, Bae T, Missiakas DM, Schneewin (2010). Contribution of Coagulases towards Staphylococcus aureus Disease and Protective Immunity. PLoS Pathog. 6(8): e1001036. http://dx.doi.org/10.1371/journal.ppat.1001036
  •  

  • Chethan Kumar HB, Lokesha KM, Madhavaprasad CB, Shilpa VT, Karabasanavar NS, Kumar A (2013). Occupational zoonoses in zoo and wildlife veterinarians in India. Vet. World 6(9): 605-613. http://dx.doi.org/10.5455/vetworld.2013.605-613
  •  

  • Chomel BB, Sun B (2011). Zoonoses in the Bedroom, Emerg. Infect. Dis. 17(2): 167-172. http://dx.doi.org/10.3201/eid1702.101070 PMid:21291584 PMCid:PMC3298380
  •  

  • Chongtrakool P, Ito T, Ma XX, Kondo Y, Trakulsomboon S, Tiensasitorn C, Jamklang M, Chavalit T, Song J, Hiramatsu K (2006). Staphylococcal cassette chromosome mec (SCCmec) typing of methicillin-resistant Staphylococcus aureus strains isolated in 11 Asian countries: a proposal for a new nomenclature for SCCmec elements. Antimicrob. Agents Chemother. 50(3): 1001-1012. http://dx.doi.org/10.1128/AAC.50.3.1001-1012.2006 PMid:16495263 PMCid:PMC1426434
  •  

  • Cimolai N (2006). Community-acquired MRSA infection: An emerging trend. BCMJ. 48(3): 116-120.
  •  

  • Clements A, Halton K, Graves N, Pettitt A, Morton A, Looke D & Whitby M (2008). Overcrowding and understaffing in modern health-care systems: key determinants in meticillin-resistant Staphylococcus aureus transmission. Lancet Infect. Dis. 8 (7): 427-434. http://dx.doi.org/10.1016/S1473-3099(08)70151-8
  •  

  • CLSI (2006). Performance Standards for Antimicrobial Disk Susceptibility Tests, Approved Standards, 9th ed. Approved Standard (M2-A9). PMid:16447401
  •  

  • Collins CJ, O’Connell B (2012). Infectious disease outbreaks in competitive sports, 2005-2010. J. Athl. Train. 47(5):516-8. PMid:23068588 PMCid:PMC3465031
  •  

  • Cohn LAMiddleton JR (2010). A veterinary perspective on methicillin-resistant staphylococci. J Vet Emerg Crit Care, 20(1):31-45. doi: 10.1111/j.1476-4431.2009.00497.x
  •  

  • Dancer SJ (2008). Importance of the environment in meticillin-resistant Staphylococcus aureus acquisition: the case for hospital cleaning. Lancet Infect. Dis. 8(2): 101-113. http://dx.doi.org/10.1016/S1473-3099(07)70241-4
  •  

  • de Boer E, Zwartkruis-Nahuis JTM, Wit B, Huijsdens XW, de Neeling AJ, Bosch T, van Oosterom RAA, Vila A, Heuvelink AE (2009). Prevalence of methicillin-resistant Staphylococcus aureus in meat. Int. J. Food Microbiol. 134(1-2): 52-56. http://dx.doi.org/10.1016/j.ijfoodmicro.2008.12.007 PMid:19144432
  •  

  • de Boer HEL, van Elzelingen-Dekker CM, van Rheenen-Verberg CMF, Spanjaard L (2006). Use of Gaseous Ozone for eradication of Methicillin resistant Staphylococcus aureus from the home environment of a colonized hospital employee. Infect. Control Hosp. Epidemiol. 27(10): 1120-1122. http://dx.doi.org/10.1086/507966 PMid:17006820
  •  

  • de Neeling AJ, van den Broek MJ, Spalburg EC, van Santen- Verheuvel MG, Dam-Deisz WD, Boshuizen HC, van de Giessen AWvan Duijkeren EHuijsdens XW (2007). High prevalenceof methicillin-resistant Staphylococcus aureus in pigs. Vet Microbiol 122(3-4): 366-72. http://dx.doi.org/10.1016/j.vetmic.2007.01.027 PMid:17367960
  •  

  • Declercq P, Petré D, Gordts B, Voss A (2008). Complicated community-Acquired soft tissue infection by MRSA from porcine origin. Infection. 36(6): 590-592. http://dx.doi.org/10.1007/s15010-007-7029-4 PMid:17973077
  •  

  • Devriese LA, Hommez J (1975). Epidemiology of methicillin-resistant Staphylococcus aureus in dairy herds. Res. Vet. Sci. 19(1): 23-27. PMid:125447
  •  

  • Devriese LA, Van Damme LR, Fameree L (1972). Methicillin (cloxacillin)-resistant Staphylococcus aureus strains isolated from bovine mastitis cases. Zentralbl. Veterinarmed. B. 19(7): 598-605. http://dx.doi.org/10.1111/j.1439-0450.1972.tb00439.x PMid:4486473
  •  

  • Diekema DJ, Pfaller MA., Schmitz FJ, Smayevsky J, Bell J, Jones RN, Beach M (2001). Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin. Infect. Dis. 32(2): 114-132. http://dx.doi.org/10.1086/320184 PMid:11320452
  •  

  • Donnio PY, Preney L, Gautier-Lerestif AL, Avril JL, Lafforgue N. (2004). Changes in staphylococcal cassette chromosome type and antibiotic resistance profile in methicillin-resistant Staphylococcus aureus isolates from a French hospital over an 11 year period. J. Antimicrob. Chemother. 53(5): 808-813. http://dx.doi.org/10.1093/jac/dkh185 PMid:15073162
  •  

  • EFSA (2007). Report of the task force on zoonoses data collection including a porposal for technical specifications for a baseline survey on the prevalence of methicillin resistant Staphylococcus aureus (MRSA) in breeding pigs. EFSA J. 129: 1-14
  •  

  • Egea AL, Gagetti P, Lamberghini R, Faccone D, Lucero C, Vindel A, Tosoroni D, Garnero A, Saka HA, Galas M, Bocco JL, Corso A, Sola C, S. aureus Study Group-Argentina (2014). New patterns of methicillin-resistant Staphylococcus aureus (MRSA) clones, community-associated MRSA genotypes behave like healthcare-associated MRSA genotypes within hospitals, Argentina. Int. J. Med. Microbiol. 1438-4221(14): 101-105. http://dx.doi.org/10.1016/j.ijmm.2014.08.002
  •  

  • Elimam MAE, Rehan S, Elmekki MA, Elhassan MM. (2014). Emergence of Vancomycin Resistant and Methcillin Resistant StaphylococuS aureus in Patients with Different Clinical Manifestations in Khartoum State, Sudan. J. Am. Sci. 10(6): 106-110
  •  

  • Ellington MJ, Hope R, Livermore DM, Kearns AM, Henderson K, Cookson BD, Pearson A, Johnson AP (2010). Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007. J. Antimicrob. Chemother. 65(3): 446-448. http://dx.doi.org/10.1093/jac/dkp448 PMid:20035019
  •  

  • Enright, MC, Day, NP, Davies, CE, Peacock, SJ, Spratt, BG (2000). Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J. Clin. Microbiol. 38(3): 1008-1015. PMid:10698988 PMCid:PMC86325
  •  

  • Ernst J (2012). Managing CA-MRSA. Dermatol. 20 (3). http://www.the-dermatologist.com/content/managing-ca-mrsa, accessed in 10 December 2014.
  •  

  • European Food Safety Authority (EFSA) (2007). Report of the task force on zoonoses data collection including a porposal for technical specifications for a baseline survey on the prevalence of methicillin resistant Staphylococcus aureus (MRSA) in breeding pigs. EFSA J. 129: 1-14.
  •  

  • European Food Safety Authority (EFSA) (2009). Assessment of the Public Health significance of meticillin resistant Staphylococcus aureus (MRSA) in animals and foods. EFSA J. 993: 20-73.
  •  

  • Faccioli-Martins YP and de Souza da Cunha MR (2012). MRSA Epidemiology in Animals, Epidemiology Insights, Dr. Maria De Lourdes Ribeiro De Souza Da Cunha (Ed.), ISBN: 978-953-51-0565-7, InTech, Available from: http://www.intechopen.com/books/epidemiologyinsights/mrsa-epidemiology-in-animals, Pp 80-95.
  •  

  • Faires MC, Gehring E, Mergl J, Weese JS (2009).Methicillin-resistant Staphylococcus aureus in marine mammals. Emerg. Infect. Dis. 15(12): 09-0220. http://dx.doi.org/10.3201/eid1512.090220
  •  

  • Feingold BJ, Silbergeld EK, Curriero FC, van Cleef BA, Heck ME, Kluytmans JA (2012). Livestock density as risk factor for livestock-associated methicillin-resistant Staphylococcus aureus, the Netherlands. Emerg. Infect. Dis. 18(11): 1841-9. http://dx.doi.org/10.3201/eid1811.111850 PMid:23092646 PMCid:PMC3559158
  •  

  • Ferreira JP, Anderson KL, Correa MT, Lyman R, Ruffin F, (2011). Transmission of MRSA between Companion Animals and Infected Human Patients Presenting to Outpatient Medical Care Facilities. PLoS ONE 6(11): e26978. http://dx.doi.org/10.1371/journal.pone.0026978
  •  

  • Feßler AT, Richard GM, Olde R, Rothkamp A, Kadlec K, Otlis C, Sampimon T, Lam JGM, Stefan S (2012). Characterization of methicillin-resistant Staphylococcus aureusCC398 obtained from humans and animals on dairy farms, Vet. Microbiol. 160 (1–2): 77-84. http://dx.doi.org/10.1016/j.vetmic.2012.05.005 PMid:22655975
  •  

  • Fleming A (1929). On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae. Br. J. Exp. Pathol. 10(3): 226-236. PMCid:PMC204800
  •  

  • Freeman-Cook L, Freeman-Cook K (2006). Staphylococcus aureus infections. Chelsea house publishers, USA.
  •  

  • García-Álvarez L, Holden MT, Lindsay H, Webb CR, Brown DF, Curran MD(2011). Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect. Dis. 11(8): 595-603. http://dx.doi.org/10.1016/S1473-3099(11)70126-8
  •  

  • Gehanno J, Louvel A, Nouvellon M, Caillard JF, Pestel-Caron M (2009). Aerial dispersal of meticillin-resistant Staphylococcus aureus in hospital rooms by infected or colonised patients. J. Hosp. Infect. 71 (3): 256-262. http://dx.doi.org/10.1016/j.jhin.2008.11.015 PMid:19162372
  •  

  • Gilbert MJ, Bos ME, Duim B, Urlings BA, Heres L, Wagenaar JA, Heederik DJ (2012). Livestock-associated MRSA ST398 carriage in pig slaughterhouse workers related to quantitative environmental exposure. Occup. Environ. Med. 69(7): 472-8. http://dx.doi.org/10.1136/oemed-2011-100069
  •  

  • Gómez P, González-Barrio D, Benito D, García JTViñuela JZarazaga MRuiz-Fons FTorres C (2014). Detection of methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene in wild small mammals in Spain. J. Antimicrob. Chemother. 69(8): 2061-2064. http://dx.doi.org/10.1093/jac/dku100 PMid:24710026
  •  

  • Goni P, Vergara Y, Ruiz J, Albizu I, Vila J, Gomez-Lus R (2004). Antibiotic resistance and epidemiological typing of Staphylococcus aureus strains from ovine and rabbit mastitis. Int. J. Antimicrob. Agents. 23(3): 268-272. http://dx.doi.org/10.1016/j.ijantimicag.2003.07.016 PMid:15164968
  •  

  • Gonsu KH, Kouemo SL, Toukam M, Ndze VN, Koulla SS (2013). Nasal carriage of methicillin resistant Staphylococcus aureus and its antibiotic susceptibility pattern in adult hospitalized patients and medical staff in some hospitals in Cameroon. J. Microbiol. Antimicrob. 5(3):29-33. http://dx.doi.org/10.5897/JMA2012.0232
  •  

  • Graveland H, Wagenaar JA, Heesterbeek H, Mevius D, van Duijkeren E, Heederik D (2010). Methicillin Resistant Staphylococcus aureus ST398 in Veal Calf Farming: Human MRSA Carriage Related with Animal Antimicrobial Usage and Farm Hygiene. PLoS ONE 5(6): e10990. http://dx.doi.org/10.1371/journal.pone.0010990
  •  

  • Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E (2006). Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet. 368(9538): 874-885. http://dx.doi.org/10.1016/S0140-6736(06)68853-3
  •  

  • Guidance on Management of Zoonoses in zoos, Managing Zoonotic Risk in Zoos and Wildlife Parks (2011). http://www.salford.gov.uk/d/zoonotic_risk.pdf, pp 1-20.
  •  

  • Guzmán-Blancoa M., Carlos M, Raul I, Carlos A, Luis B, Eduardo G, Jaime L, Carlos ML, Eduardo R, Mauro JCS, Jeannete Z, Carlos S (2009). Review Epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in Latin America. Int. J. Antimicrob. Agents. 34(4): 304-308. http://dx.doi.org/10.1016/j.ijantimicag.2009.06.005 PMid:19625169
  •  

  • Hamed DM, Youssef AI (2013). Clinical Features of Methicillin-Resistant Staphylococcus aureus (MRSA) Infection in Rabbits and its Zoonotic Potentials. Pak. J. Nutr. 12(3): 244-249. http://dx.doi.org/10.3923/pjn.2013.244.249
  •  

  • Hanselman BA, Kruth SA, Rousseau J, Low DE, Willey BM, McGeer A, Weese JS (2006). Methicillin-resistant Staphylococcus aureus colonization in veterinary personnel. Emerg. Infect. Dis. 12(12):1933-1938.
  •  

  • Hardy KJ, Hawkey PM, Gao F, Oppenheim BA (2004). Methicillin resistant Staphylococcus aureus in the critically ill. Br. J. Anaesth. 92(1): 121-130. http://dx.doi.org/10.1093/bja/aeh008
  •  

  • Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete STavares ADay NLindsay JAEdgeworth JDde Lencastre HParkhill JPeacock SJBentley SD (2010). Evolution of MRSA during hospital transmission and intercontinental spread. Science. 327(5964): 469-474. http://dx.doi.org/10.1126/science.1182395 PMid:20093474 PMCid:PMC2821690
  •  

  • Harrison EM, Paterson GK, Holden MTG, Morgan FJE, Larsen AR, Petersen A,  Leroy S, De Vliegher S,  Perreten V,  Fox LK,  Lam TJGM, Sampimon OC, Zadoks RS, Peacock SJ, Parkhill J, Holmes MA (2013). A Staphylococcus xylosus Isolate with a New mecC Allotype. Antimicrob. Agents Chemother. 57(3): 1524-1528. http://dx.doi.org/10.1128/AAC.01882-12
  •  

  • Hartmann FA, Trostle SS, Klohnen AA (1997). Isolation of methicillin-resistant Staphylococcus aureus from a postoperative wound infection in a horse. J. Am. Vet. Med. Assoc. 211(5): 590-592. PMid:9290826
  •  

  • Herold BC, Immergluck LC, Maranan MC, Lauderdale DS, Gaskin RE, Boyle- Vavra S, Leitch CD, Daum RS (1998). Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. J. Am. Med. Assoc. 279(8): 593-598. http://dx.doi.org/10.1001/jama.279.8.593 PMid:9486753
  •  

  • Himsworth CG, Miller RR, Montoya V, Hoang L, Romney MG, Al-Rawahi GN, Kerr T, Jardine CM, Patrick DM, Tang P, Weese SJ (2013). Carriage of Methicillin-Resistant Staphylococcus aureus by Wild Urban Norway Rats (Rattus norvegicus) PLoS ONE 9(2): e87983. http://dx.doi.org/10.1371/journal.pone.0087983
  • Holden MTG, Feil EJ, Lindsay JA, Peacock SJ, Day NPJ, Enright MC, Foster TJ, Moore CE, Hurst L, Atkin R, Barron A, Bason N, Bentley SD, Chillingworth C, Chillingworth T, Churcher C, Clark L, Corton C, Cronin A, Doggett J, Dowd L, Feltwell T, Hance Z, Harris B, Hauser H, Holroyd S, Jagels K, James KD, Lennard N, Line A, Mayes R, Moule S, Mungall K, Ormond D, Quail MA, Rabbinowitsch E, Rutherford K, Sanders M, Sharp S, Simmonds M, Stevens K, Whitehead S, Barrell BG, Spratt BG, Parkhill J (2004). Complete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc. Natl. Acad. Sci. USA. 101(26): 9786-9791. http://dx.doi.org/10.1073/pnas.0402521101 PMid:15213324 PMCid:PMC470752
  •  

  • Hsu ST, Breukink E, Bierbaum G, Sahl HG, de Kruijff B, Kaptein R, van Nuland NA, Bonvin AM (2003). NMR study of mersacidin and lipid II interaction in dodecylphosphocholine micelles. Conformational changes are a key to antimicrobial activity. J. Biol. Chem. 278(15): 13110-13117. http://dx.doi.org/10.1074/jbc.M211144200 PMid:12562773
  •  

  • Hu CJ, Fang RH, Luk BT, Zhang L (2013). Nanoparticle-detained toxins for safe and effective vaccination Nat. Nanotechnol. 8(12): 933-938. http://dx.doi.org/10.1038/nnano.2013.254
  •  

  • Huijsdens XW, van Dijke BJ, Spalburg E, van Santen-Verheuvel MG, Heck ME, Pluister GN, Voss AWannet WJde Neeling AJ (2006). Community-acquired MRSA and pig-farming. Ann. Clin. Microbiol. Antimicrob. 10(5):26-29.
  •  

  • Iyamba JML, Wambale JM, Lukukula CM, Takaisi-Kikuni NB (2014). High prevalence of methicillin resistant staphylococci strains isolated from surgical site infections in Kinshasa. Pan Afr. Med. J. 18:322. http://dx.doi.org/10.11604/pamj.2014.18.322.4440
  •  

  • Jiménez JN, Ocampo AM, Vanegas JM, Rodriguez EA, Mediavilla JR, Chen L, Muskus CE, Vélez LA, Rojas C, Restrepo AV, Ospina S, Garcés C, Franco L, Bifani P, Kreiswirth BN, Correa MM (2012). CC8 MRSA Strains Harboring SCCmec Type IVc are Predominant in Colombian Hospitals. PLoS ONE. 7(6): 38576. http://dx.doi.org/10.1371/journal.pone.0038576 PMid:22745670 PMCid:PMC3380008
  •  

  • Karmi M (2013). Prevalence of methicillin-resistant Staphylococcus aureus in poultry meat in Qena, Egypt. Vet. World. 6(10): 711-715. http://dx.doi.org/10.14202/vetworld.2013.711-715
  •  

  • Karthy ES, Ranjitha P, MohankUmaru A (2009). Performance of CHROM Agar and Oxacillin ResistantScreening Agar Base Media for Detection of Methicillin Resistant Staphylococcus aureus (MRSA) from Chronic Wound. Mod. Appl. sci. 3(5): 51-56. http://dx.doi.org/10.5539/mas.v3n5p51
  •  

  • Kazakova SV, Hageman JC, Matava M, Srinivasan APhelan LGarfinkel BBoo TMcAllister SAnderson JJensen BDodson D,Lonsway DMcDougal LKArduino MFraser VJKillgore GTenover FCCody SJernigan DB (2005). A clone of methicillin-resistant Staphylococcus aureus among professional football players. N. Engl. J. Med. 352(5): 468-475. http://dx.doi.org/10.1056/NEJMoa042859 PMid:15689585
  •  

  • Kern W, Vanek E, Jungbluth H (1989). Fish breeder granuloma: infection caused by Mycobacterium marinum and other atypical mycobacteria in the human. Analysis of 8 cases and review of the literature (in German). Medizinische Klinik. 84(12): 578-583.
  •  

  • Khanna T, Friendship R, Dewey C, Weese JS (2008). Methicillin-resistant Staphylococcus aureus colonization in pigs and pig farmers. Vet. Microbiol. 128(3-4): 298-303.
  •  

  • Kim JY (2009). Understanding the Evolution of Methicillin-Resistant, Clin. Microbiol. Newsl. 31(3): 17-23. http://dx.doi.org/10.1016/j.clinmicnews.2009.01.002
  •  

  • Kirby WMM (1944). Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science. 99(2579): 452-453. http://dx.doi.org/10.1126/science.99.2579.452 PMid:17798398
  •  

  • Klotz M, Zimmermann S, Opper S, Heeg K, Mutters R (2005). Possible risk for recolonization with methicillin-resistant Staphylococcus aureus (MRSA) by faecal transmission. Int. J. Hyg. Environ. Health 208 (5): 401-405. http://dx.doi.org/10.1016/j.ijheh.2005.05.004 PMid:16217924
  •  

  • Köck R, Brakensiek L, Mellmann A, Kipp F, Henderikx M, Harmsen D, Daniels-Haardt I, von Eiff C, Becker K, Hendrix MG, Friedrich AW (2009a). Cross-border comparison of the admission prevalence and clonal structure of meticillin-resistant Staphylococcus aureus. J. Hosp. Infect. 71(4):320-326. http://dx.doi.org/10.1016/j.jhin.2008.12.001 PMid:19201056
  •  

  • Köck R, Harlizius J, Bressan N, Laerberg R, Wieler LH, Witte W, Deurenberg RHVoss ABecker KFriedrich AW (2009b). Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German farms and import of livestock-related MRSA into hospitals. Eur. J. Clin. Microbiol. Infect. Dis. 28(11): 1375-82. http://dx.doi.org/10.1007/s10096-009-0795-4 PMid:19701815 PMCid:PMC2772956
  •  

  • Kucers A, Bennett NMcK (1987). The use of antibiotics, 4th ed. London: William Heinemann.
  •  

  • Kumari N, Mohapatra TM, Singh Y (2008). Prevalence of methicillin resistant Staphylococcus aureus isolated in a tertiary- care hospital in Eastern Nepal. J. Nepal. Med. assoc. 47(170): 53-56 PMid:18709031
  •  

  • Kwon NH, Kun TP, Woo KJ, Hwa YY, Yeonhee L, So HK, Wonki B, Ji YL, Ji YK, Jun MK, Soon KH, Yong HP (2006). Characteristics of methicillin resistant Staphylococcus aureus isolated from chicken meat and hospitalized dogs in Korea and their epidemiological relatedness. Vet. Microbiol. 117(2-4): 304-312.
  •  

  • Lee JH (2003). Methicillin (Oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans. Appl. Environ. Microbiol. 69(11): 6489-6494. http://dx.doi.org/10.1128/AEM.69.11.6489-6494.2003 PMid:14602604 PMCid:PMC262320
  •  

  • Leggiadro, RJ (2009). Methicillin-Resistant Staphylococcus aureus Skin Infections From an Elephant Calf–San Diego, California, 2008. Pediatr. Infect. Dis. J. 28(5): 454. http://dx.doi.org/10.1097/INF.0b013e3181a6ba71
  •  

  • Loeffler A, Boag AK, Sung J, Lindsay JA, Guardabassi L, Dalsgaard A, Smith H, Stevens KB, Lloyd DH (2005). Prevalence of methicillin-resistant Staphylococcus aureus among staff and pets in a small animal referral hospital in the UK. J. Antimicrob. Chemother. 56 (4):692-697. http://dx.doi.org/10.1093/jac/dki312 PMid:16141276
  •  

  • Loeffler A, Kearns AM, Ellington MJ, Smith LJ, Unt VE, Lindsay JA, Pfeiffer DU, Lloyd DH (2009). First isolation of MRSA ST398 from UK animals: a new challenge for infection control team? J. Hosp. infect. 72(3): 269-271. http://dx.doi.org/10.1016/j.jhin.2009.04.002 PMid:19481297
  •  

  • Loeffler A, Lloyd DH (2010). Companion animals: a reservoir for methicillin-resistant Staphylococcus aureus in the community? Epidemiol. Infect. 138(5): 595–605. http://dx.doi.org/10.1017/S0950268809991476
  •  

  • Loeffler A, Pfeiffer DU, Lindsay JA, Magalhaes RJ, Lloyd DH (2011). Prevalence of and risk factors for MRSA carriage in companion animals: a survey of dogs, cats and horses. Epidemiol. Infect. 139(7): 1091-1028. http://dx.doi.org/10.1017/S095026881000227X PMid:20943000
  •  

  • Loncaric, I, Kübber-Heiss A, Posautz A, Stalder GL, Hoffmann D, Rosengarten R, Walzer C (2014). mecC and mecA-positive methicillin-resistant Staphylococcus aureus (MRSA) isolated from livestock sharing habitat with wildlife previously tested positive for mecC-positive MRSA. Vet. Dermatol. 25(2): 147–148. http://dx.doi.org/10.1111/vde.12116
  •  

  • Louie L, Majury A, Goodfekllow J, Louie M, Simor AE (2001). Evaluation of a latex agglutination test (MRSA-Screen) for detection of oxacillin resistance in coagulase-negative staphylococci. J. Clin. Microbiol. 39: 4149–4151. http://dx.doi.org/10.1128/JCM.39.11.4149-4151.2001 PMid:11682545 PMCid:PMC88502
  •  

  • Lowy FD (1998). Staphylococcus aureus infections. New Engl J Med 339(8): 520-532. http://dx.doi.org/10.1056/NEJM199808203390806 PMid:9709046
  •  

  • Marchese A, Balistreri G, Tonoli E, Debbia EA, Schito GC (2000). Heterogeneous vancomycin resistance in methicillin-resistant Staphylococcus aureus strains isolated in a large Italian hospital. J. Clin. Microbiol. 38(2): 866-869. PMid:10655401 PMCid:PMC86227
  •  

  • Mayrhofer S, Paulsen P, Smulders FJM, Hilbert F (2004). Antimicrobial resistance profile of five major food-borne pathogens isolated from beef, pork and poultry. Int. J. Food Microbiol. 97(1): 23-29. http://dx.doi.org/10.1016/j.ijfoodmicro.2004.04.006 PMid:15527915
  •  

  • McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC (2003). Pulse-field gel electrophoresis of oxacillin-resistant Staphylococcus aureus from the United States: Establishing anationaldatabase. J. Clin. Microbiol. 41(11): 5113-5120. http://dx.doi.org/10.1128/JCM.41.11.5113-5120.2003 PMid:14605147 PMCid:PMC262524
  •  

  • McKenna M (2014). Man Vs MRSA, Nature, Int. wkly J Sci. 482(7383): 23-25. http://www.nature.com/polopoly_fs/1.9940!/menu/main/topColumns/topLeftColumn/pdf/482023a.pdf, Macmillan publishers limited. Accessed in 8 Dec., 2014
  •  

  • Mejía C, Zurita J, Guzmán-Blanco M. (2010). Epidemiology and surveillance of methicillin-resistant Staphylococcus aureus in Latin America. Braz. J. Infect. Dis. 14(2):79-86. http://dx.doi.org/10.1590/S1413-86702010000800003
  •  

  • Merrer J, Santoli F, Appere de Vecchi C, Tran B, De Jonghe B, Outin H (2000). “Colonization pressure” and risk of acquisition of methicillin-resistant Staphylococcus aureus in a medical intensive care unit. Infect. Control Hosp. Epidemiol. 21(11): 718-723. http://dx.doi.org/10.1086/501721 PMid:11089656
  •  

  • Mikael S, Örtqvist Å, Ringberg H, Larsson L, Olsson-Liljequist B, Hæggman S, Kalin M, Ekdahl K (2010). Emerg. Infect. Dis. 16(2): 189-196. http://dx.doi.org/10.3201/eid1602.081655
  •  

  • Millar BC, Loughrey A, Elborn JS, Moore JE (2007). Proposed definitions of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). J. Hosp. Infect. 67(2): 109-113. http://dx.doi.org/10.1016/j.jhin.2007.06.003 PMid:17669546
  •  

  • Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, Borg M, Chow H, Ip M, Jatzwauk Jonas D, Kadlec K, Kearns A, Laurent F, O’Brien FG, Pearson J, Ruppelt A, Schwarz S, Scicluna E, Peter Slickers, Tan H, Weber S, Ehricht R (2011). A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One 6:e17936. http://dx.doi.org/10.1371/journal.pone.0017936 PMid:21494333 PMCid:PMC3071808
  •  

  • Moodley A, Nightingale EC, Stegger M, Nielsen SS, Skov RL, Guardabassi L (2008). High risk for nasal carriage of methicillin-resistant Staphylococcus aureus among Danish veterinary practitioners. Scan. J. Work, Environ. Health 34(2): 151-7. http://dx.doi.org/10.5271/sjweh.1219
  •  

  • Morgan M (2008). Methicillin resistant Staphylococcus aureus and animals: zoonosis or humanosis? J. Antimicrob. Chemother. 62(6):1181-1187. http://dx.doi.org/10.1093/jac/dkn405 PMid:18819971
  •  

  • Mustapha M, Bukar-Kolo YM, Geidam YA and Gulani IA. (2014). Review on Methicillin-resistant Staphylococcus aureus (MRSA) in Dogs and Cats. Int. J. Anim. Vet. Adv. 6(2): 61-73.
  •  

  • Neushul P (1993). Science, government, and the mass production of penicillin. J. His. Med. Allied Sci. 48(4): 371-395. http://dx.doi.org/10.1093/jhmas/48.4.371 PMid:8283024
  •  

  • Norazah A (2008). National surveillance on Antibiotic resistance report for 2007. Institue for medical research ministry of health, Malaysia. Available at: http://www.imr.gov.my/report/nsar.html
  •  

  • Normanno G, Corrente M, La Salandra G, Dambrosio A, Quaglia NC, Parisi A, Greco G, Bellacicco AL, Virgilio S, Celano GV (2007). Methicillin-resistant Staphylococcus aureus (MRSA) in foods of animal origin product in Italy, Int. J. Food Microbiol. 117(2): 219-222. http://dx.doi.org/10.1016/j.ijfoodmicro.2007.04.006 PMid:17533002
  •  

  • O’Mahony R, Abbott Y, Leonard FC, Markey BK, Quinn PJ, Pollock PJ, Fanning SRossney AS (2005). Methicillin-resistant Staphylococcus aureus (MRSA) isolated from animals and veterinary personnel in Ireland. Vet. Microbiol. 109(3-4): 285-296. http://dx.doi.org/10.1016/j.vetmic.2005.06.003 PMid:16026939
  •  

  • O’Brien AM, Hanson BM, Farina SA, Wu JY, Simmering JE, Brett MF, Kurlick ME, Wallinga DB, Smith TC. (2012). MRSA in Conventional and Alternative Retail Pork Products. PLoS ONE 7(1): 1-6, e30092. http://dx.doi.org/10.1371/journal.pone.0030092
  •  

  • Ojulong J, Mwambu T, Jolobo M, Agwu E, Bwanga F, Najjuka C, Kaddu-Mulindwa C (2008). Prevalence of Methicillin resistant Staphylococcus aureus (MRSA) among isolates from surgical site infections in Mulago hospital- Kampala, Uganda. Intern. J. Infect. Diss. 7 (2): 10326.
  •  

  • Olowe OA, Kukoyi OO, Taiwo SS, Ojurongbe O, Opaleye OO, Bolaji OS, Adegoke AA, Makanjuola OB, Ogbolu DO, Alli OT (2013). Phenotypic and molecular characteristics of methicillin-resistant Staphylococcus aureus isolates from Ekiti State, Nigeria. Infect. Drug Resis. 2013(6): 87-9. http://dx.doi.org/10.2147/IDR.S48809
  •  

  • Palavecino E (2004). Community-acquired methicillin-resistant Staphylococcus aureus infections. Clin Lab Med 24(2): 403-418. http://dx.doi.org/10.1016/j.cll.2004.03.007 PMid:15177847
  •  

  • Paterson GK, Harrison EM, Holmes MA (2014a). The emergence of mecC MRSA. Trends microbial. 22(1): 42-46/
  •  

  • Paterson GK, Morgan FJE, Harrison EM, Peacock SJ, Parkhill J, Zadoks RN, Holmes MA (2014b). Prevalence and properties of mecC methicillin-resistant Staphylococcus aureus (MRSA) in bovine bulk tank milk in Great Britain. J. Antimicrob. Chemother. 69(3): 598-602. http://dx.doi.org/10.1093/jac/dkt417 PMid:24155057 PMCid:PMC3922150
  •  

  • Paterson GK, Larsen AR, Robb A, Edwards GE, Pennycott TW, Foster G (2012). The newly described mecA homologue, mecALGA251, is present in methicillin-resistant Staphylococcus aureus isolates from a diverse range of host species. J. Antimicrob. Chemother. 67(12): 2809-2813. DOIPubMed http://dx.doi.org/10.1093/jac/dks329 PMid:22941897 PMCid:PMC3494845
  •  

  • Peacock, SJ, de Silva I, Lowy FD (2001). What determines nasal carriage of Staphylococcus aureus? Trends Microbiol. 9(12): 605-610. http://dx.doi.org/10.1016/S0966-842X(01)02254-5
  •  

  • Porrero CM , Mentaberre G, Sánchez S, Fernández-Llario P, Gómez-Barrero S, Navarro-Gonzalez N, Serrano E, Casas-Díaz E, Marco I, Fernández-Garayzabal J, Mateos A, Vidal D, Lavín S, Domínguez L. (2013). Methicillin resistant Staphylococcus aureus (MRSA) carriage in different free-living wild animal species in Spain. Vet. J. 198(1): 127-130. http://dx.doi.org/10.1016/j.tvjl.2013.06.004 PMid:23846031
  •  

  • Porrero MC, Valverde A, Fernández-Llario P, Díez-Guerrier A, Mateos A, Lavín S, Canton R, Fernandez Garayzabel J, Domenguez L (2014). Staphylococcus aureus carrying mecC gene in animals and urban wastewater, Spain. Emerg. Infect. Dis. 20(5): 899-901. http://dx.doi.org/10.3201/eid2005.130426
  •  

  • Quinn PJ, Carter ME, Markey BK, Carter GR (2000). Staphylococcus species In: Clinical veterinary microbiology, Mosby, Edinburgh, pp. 118-126.
  •  

  • Raymund D, Yi M, Belflower R, Aragon D, Dumyati G, Harrison LH, Lessa FC, Lynfield R, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, Fridkin S, the Emerging Infections Program (2013). J. Am. Med. Assoc., Intern. Med. 173(21): 1970-1978. http://dx.doi.org/10.1001/jamainternmed.2013.10423
  •  

  • Rayner C, Munckhof WJ (2005). Antibiotics currently used in the treatment of infections caused by Staphylococcus aureus. Intern. Med. J. 35 (2): 3-16. http://dx.doi.org/10.1111/j.1444-0903.2005.00976.x PMid:16271060
  •  

  • Rich M, Roberts L (2004). Methicillin-resistant Staphylococcus aureus isolates from companion animals. Vet. Rec. 154(10): 310. PMid:15053141
  •  

  • Roberson JR (1999). The epidemiology of Staphylococcus aureus on dairy farms. National Mastitis Council 38th Annual Meeting. USA.
  •  

  • Russel CD (2012). Staphylococcus Vaccination and MRSA. Lancet Infect. Dis. 12 (8): 586. http://dx.doi.org/10.1016/S1473-3099(12)70167-6
  •  

  • Safdar N, Bradley EA (2008). The risk of infection after nasal colonization with Staphylococcus aureus. Am. J. Med. 121 (4): 310-315. http://dx.doi.org/10.1016/j.amjmed.2007.07.034 PMid:18374690
  •  

  • Sanford MD, Widmer AF, Bale MJ, Jones RN, Wenzel RP (1994). Efficient detection and long-term persistence of the carriage of methicillin-resistant Staphylococcus aureus. Clin. Infect. Dis. 19(6): 1123-1128. http://dx.doi.org/10.1093/clinids/19.6.1123 PMid:7888543
  •  

  • Santosaningsih D, Santoso S, Budayanti NS, Kuntaman K, Lestari ES, Farida H, Hapsari R, Hadi P, Winarto W, Milheiriço C, Maquelin K, Willemse-Erix D, van Belkum A, Severin JA, Verbrugh HA (2014). Epidemiology of Staphylococcus aureus harboring the mecA or Panton-Valentine leukocidin genes in hospitals in Java and Bali, Indonesia. Am. J. Trop. Med. Hyg. 90(4): 728-34. http://dx.doi.org/10.4269/ajtmh.13-0734
  •  

  • Scalcini MC, Sanders CV (1980). Endocarditis from human-to-human transmission of Staphylococcus aureus. Arch. Intern. Med. 140 (1): 111-112. http://dx.doi.org/10.1001/archinte.1980.00330130113027 PMid:7352786
  •  

  • Schulz J, Friese A, Klees S, Tenhagen BA, Fetsch A, Rösler U, Hartung J (2012). Longitudinal Study of the Contamination of Air and of Soil Surfaces in the Vicinity of Pig Barns by Livestock-Associated Methicillin ResistantStaphylococcus aureus 2012. Appl. Environ. Microbiol. 78(16): 5666-5671.http://dx.doi.org/10.1128/AEM.00550-12 PMid:22685139 PMCid:PMC3406131
  •  

  • Seguin JC, Walker RD, Caron JP, Kloos WE, George CG, Hollis RJ, Jones RN, Pfaller MA (1999). Methicillin-resistant Staphylococcus aureus outbreak in a veterinary teaching hospital: potential humanto- animal transmission. J. Clin. Microbiol. 37 (5):1459–1463
  •  

  • Shibabaw A, Abebe T, Mihret A. (2013). Nasal carriage rate of methicillin resistant Staphylococcus aureus among Dessie Referral Hospital Health Care Workers; Dessie, Northeast Ethiopia. Antimicrob. Resist. Infect. Control. 2(1): 25. http://dx.doi.org/10.1186/2047-2994-2-25 PMid:24088259 PMCid:PMC3851550
  •  

  • Simmonds KA, Dover DC, Louie M, Keays G (2008). Epidemiology of community associated methicillin-resistant Staphylococcus aureus, Canada communicable disease report, monthly report, public health agency of Canada. 34(08). www.publichealth.gc.ca
  •  

  • Smith TC, Male MJ, Harper AL, Kroeger JS, Tinkler GP, Moritz ED, Capuano AW, Herwaldt LA, Diekema DJ (2008). Methicillin-resistant Staphylococcus aureus (MRSA) strain ST398 is present in Midwestern U.S. swine and swine workers. PLoS ONE 4 (1): e4258. http://dx.doi.org/10.1371/journal.pone.0004258 PMid:19145257 PMCid:PMC2626282
  •  

  • Soliman MK, Ellakany HF, Gaafar AY, Elbialy AK, Zaki MS, Younes AM (2014). Epidemiology and antimicrobial activity of methicillin-resistant Staphylococcus aureus (MRSA) isolated from Nile tilapia (Oreochromis niloticus) during an outbreak in Egypt. Life Sci. J. 11(10): 1245-1252.
  •  

  • Soonthornchaikul N, Garelick H, Jones H, Jacobs J, Ball D, Choudhury M (2006). Resistance to three antimicrobial agents of Campylobacter isolated from organically- and intensively-reared chickens purchased from retail outlets. Int. J. Antimicrob. Agents. 27(2): 125-130. http://dx.doi.org/10.1016/j.ijantimicag.2005.09.020 PMid:16417991
  •  

  • Spink WW (1978). Infectious Diseases: Prevention and Treatment in the Nineteenth and Twentieth Centuries. Minneapolis: University of Minnesota Press, 1978.
  •  

  • Stastkova Z, Karpiskova S, Karpiskova S (2009). Occurrence of methicillin-resistant strains of Staphylococcus aureus at a goat breeding farm. Vet. Med. 54 (9): 419-426
  •  

  • Stegger M, Wirth T, Andersen PS, Skov RL, De Grassi A, Simões PM, Tristan A, Petersen A, Aziz M, Kiil K, Cirkovic´ I, Udo EE, del Campo R, Vuopio-Varkila J, Ahmad N, Tokajian S, Peters G, Schaumburg F, Olsson-Liljequist B, Givskov M, Driebe EE, Vigh HE, Shittu A, Ramdani-Bougessa N, Rasigade J, Price LB, Vandenesch F, Larsen AR, Laurent F. ( 2014). Origin and evolution of European community-acquired methicillin-resistant Staphylococcus aureus. mBio 5(5):e01044-14. http://dx.doi.org/10.1128/mBio.01044-14
  •  

  • Stein RA (2009). Methicillin-resistant Staphylococcus aureus–the new zoonosis. Int. J. Infect. Dis. 13(3): 299-301 http://dx.doi.org/10.1016/j.ijid.2008.09.008 PMid:19042144
  •  

  • Stefani S, Chung DR, Lindsay JA, Friedrich AW, Kearns AM, Westh H, MacKenzie FM (2012). Meticillin-resistant Staphylococcus aureus (MRSA): global epidemiology and harmonisation of typing methods, Int J Antimicrob Agents 39 (4):273–282.
  •  

  • Stoakes L, Reyes R, Daniel J, Lennox G, John M A, Lannigan R, Hussain Z (2006). Prospective comparison of a new chromogenic medium, MRSASelect to CHROMagar, MRSA and mannitol salt medium supplemented with oxacillin or cefoxitin for detection of methicillinresistant Staphylococcus aureus. J. Clin. Microbiol. 44: 637-639. http://dx.doi.org/10.1128/JCM.44.2.637-639.2006 PMid:16455933 PMCid:PMC1392665
  •  

  • Strommenger B, Kettlitz C, Weniger T, Harmsen D, Friedrich AW, Witte W (2006). Assignment of Staphylococcus isolates to groups by spa typing, SmaI macrorestriction analysis, and multilocus sequence typing. J. Clin. Microbiol. 44 (7): 2533–2540.
  •  

  • Struelens, MJ, Hawkey, PM, French, G.L, Witte, W, Tacconelli, E (2009). Laboratory tools and strategies for methicillin-resistant Staphylococcus aureus screening, surveillance and typing: state of the art and unmet needs. Clin. Microbiol. Infect. 15(2):112-119. http://dx.doi.org/10.1111/j.1469-0691.2009.02698.x PMid:19291142
  •  

  • Szabó J (2014). Molecular Methods in Epidemiology of Methicillin Resistant Staphylococcus aureus (MRSA): Advantages, Disadvantages of Different Techniques. J. Med. Microb. Diagn. 3 (3): 147. http://dx.doi.org/10.4172/2161-0703.1000147
  •  

  • Tiemersma EW, Bronzwaer S, Lyytikainen O, Degener JE, Schrijnemakers P, Bruinsma N, Monen J, Witte W, Grundmann H, Participants U K E A R S S (2004). Methicillin-resistant Staphylococcus aureus in Europe, 1999–2002. Emerg. Infect. Dis. 10(9): 1627-1634. http://dx.doi.org/10.3201/eid1009.040069 PMid:15498166 PMCid:PMC3320277
  •  

  • Tietz A, Frei R, Widmer AF (2005). Transatlantic spread of the USA300 clone of MRSA. New Engl. J. Med. 353(5): 532-533. http://dx.doi.org/10.1056/NEJM200508043530522 PMid:16079385
  •  

  • Tomlin J, Pead MJ, Lloyd D H, Howell S, Hartmann F, Jackson HA, Muir P (1999). Methicillin-resistant Staphylococcus aureus infections in 11 dogs. Vet. Rec. 144(3): 60-64. http://dx.doi.org/10.1136/vr.144.3.60 PMid:10070689
  •  

  • Torres-Tortosa M, de Cueto M, Vergara A, Sanchez-Porto A, Perez-Guzman E, Gonzalez-Serrano M, Canneto J, Grupo de Estudio de Enfermedades Infecciosas de la Provincia de Cadiz. (1994). Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Eur. J. Clin. Microbiol. Infect. Dis. 13(7): 559-564. http://dx.doi.org/10.1007/BF01971306 PMid:7805683
  •  

  • Trakulsomboom S, Thamlikitkul V (2008). In Vitro activity of daptomycin against MRSA and vancomycin hetero-resistant MRSA (h-MRSA) isolated from patients at Siraj hospital. J. Infect. Dis. Antimicrob. Agents. 25(1): 57-61.
  •  

  • Umaru GA, Kabiru J, Adamu NB, Umar YA (2011). A review of emerging Methicillin-resistant Staphylococcus aureus (MRSA): A growing threat to Veterinarians. Nig. Vet. J. 32(3): 174-186.
  •  

  • Van den Broek IV, van Cleef BA, Haenen A, Broens EM, van der Wolf PJ, van den Broek MJ, Huijsdens XW, Kluytmans JA, van de Giessen AW, Tiemersma EW (2008). Methicillin-resistant Staphylococcus aureus in people living and working in pig farms. Epidemiol. Infect. 24: 1-9.
  •  

  • Van den Eede A, Martens A, Lipinska U, Struelens M, Deplano A, Denis O, Haesebrouck F, Gasthuys F, Hermans K (2009). High occurrence of methicillinresistant Staphylococcus aureus ST398 in equine nasal samples. Vet. Microbiol. 133 (1-2):138-144. http://dx.doi.org/10.1016/j.vetmic.2008.06.021 PMid:18701224
  •  

  • Van Enk R A, Thompson K D (1992). Use of a primary isolation medium for recovery of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 30(3): 504-505. PMid:1537925 PMCid:PMC265087
  •  

  • van Loo I, Huisdens, Tiemersma E, de Neeling A, van de Sande-Bruinsma N, Bearijlan D, Voss, Kluytmans J (2007). Emergence of methicillin-resistant Staphylococcus aureus of animal origin in humans. Emerg. Infect. Dis. 13(12): 1834-1839. http://dx.doi.org/10.3201/eid1311.070358 PMid:18258032 PMCid:PMC2876750
  •  

  • van Rijen MM, Van Keulen PH, Kluytmans JA (2008). Increase in a Dutch hospital of methicillin-resistant Staphylococcus aureus related to animal farming. Clin. Infect. Dis. 46(2): 261-263. http://dx.doi.org/10.1086/524672 PMid:18171259
  •  

  • Vandendriessche S, Vanderhaeghen W, Valente Soares F, Hallin M, Catry B, Hermans B, Butaye P, Haesebrouck F, Struelens MJ, Denis O (2013). Prevalence, risk factors and genetic diversity of methicillin-resistant Staphylococcus aureus carried by humans and animals across livestock production sectors. J. Antimicrob. Chemother. 68(7): 1510-1516. http://dx.doi.org/10.1093/jac/dkt047
  •  

  • Valesco D, del Mar Tomas M, Cartelle M, Beceiro A, Perez A, Molina F, Moure R, Villanueva R, Bou G (2005). Evaluation of different methods for detecting methicillin (oxacillin) resistance in Staphylococcus aureus J. Antimicrob. Chemother. 55(3): 379-382. http://dx.doi.org/10.1093/jac/dki017 PMid:15722394
  •  

  • Verkade E, Kluytmans J. (2014). Livestock-associated Staphylococcus aureus CC398: animal reservoirs and human infections. Infect. Genet. Evol. 21: 523-530. http://dx.doi.org/10.1016/j.meegid.2013.02.013
  •  

  • Vincze S, Stamm I, Kopp PA, Hermes J, Adlhoch C, Semmler T, Wieler LH, Lübke-Becker A, Walther B (2014). Alarming Proportions of Methicillin-Resistant Staphylococcus aureus (MRSA) in Wound Samples from Companion Animals, Germany 2010–2012 PLoS ONE. 9(1): e85656. http://dx.doi.org/10.1371/journal.pone.0085656
  •  

  • Voss A, Loeffen F, Bakker J, Klaassen C, Wulf M (2005). Methicillinresistant Staphylococcus aureus in pig farming. Emerg. Infect. Dis. 11(12): 1965-1966. http://dx.doi.org/10.3201/eid1112.050428 PMid:16485492 PMCid:PMC3367632
  •  

  • Waldvogel FA (2000). Staphylococcus aureus. In: GL Mandell, RG Douglas & JE Bennett (ed.), Principles and practices of infectious disease, 3rd ed. Churchill Livingstone, Philadelphia, Pennsylvania, USA. p. 1754-1777.
  •  

  • Walther B, Wieler LH, Friedrich AW, Hanssen AM, Kohn B, Brunnberg L, Lubke-Becker A (2008). Methicillin-resistant Staphylococcus aureus (MRSA) isolated from small and exotic animals at a university hospital during routine microbiological examinations. Vet. Microbiol. 127(1-2): 171-178. http://dx.doi.org/10.1016/j.vetmic.2007.07.018 PMid:17804179
  •  

  • Walther B, Wieler LH, Vincze S, Antao EM, Brandenburg A, Stamm I (2012). MRSA variant in companion animals. Emerg. Infect. Dis. 18(12): 2017-2020. http://dx.doi.org/10.3201/eid1812.120238 PMid:23171478 PMCid:PMC3557870
  •  

  • Wardyn SE, Kauffman LK, Smith TC (2012). Methicillin-resistant Staphylococcus aureus in Central Iowa Wildlife. J Wildl Dis: 48(4): 1069-1073. http://dx.doi.org/10.7589/2011-10-295 PMid:23060511
  •  

  • Weese JS, Archambault M, Willey BM, Dick H, Hearn P, Kreiswirth BN, Said-Salim B, McGeer A, Likhoshvay Y, Prescott JF (2005). Methicillin-Resistant Staphylococcus aureus in horses and horse personnel, 2000–2002. Emerg. Infect. Dis. 11(3): 430-435. http://dx.doi.org/10.3201/eid1103.040481 PMid:15757559 PMCid:PMC3298236
  •  

  • Weese JS, Caldwell F, Willey BM, Kreiswirth BN, McGeer A, Rousseau J, Low DE (2006). An outbreak of methicillin-resistant Staphylococcus aureus skin infections resulting from horse to human transmission in a veterinary hospital. Vet. Microbiol. 114(1-2): 160-4. http://dx.doi.org/10.1016/j.vetmic.2005.11.054 PMid:16384660
  •  

  • Wertheim H F, Vos MC, Boelens HA, Voss A, Vandenbroucke-Grauls CM, Meester MH, Kluytmans JA, van Keulen PH, Verbrugh HA (2004). Low prevalence of methicillin resistant Staphylococcus aureus (MRSA) at hospital admission in the Netherlands: the value of search and destroy and restrictive antibiotic use. J. Hosp. Infect. 56(4): 321-325. http://dx.doi.org/10.1016/j.jhin.2004.01.026 PMid:15066745
  •  

  • Wielders, C. L. C. A. C. Fluit, S. Brisse, J. Verhoef, and F. J. Schmitz (2002). mecA Gene Is Widely Disseminated in Staphylococcus aureus Population. J. Clin. Microbiol. 40(11): 3970-3975. http://dx.doi.org/10.1128/JCM.40.11.3970-3975.2002
  •  

  • Witte W, Strommenger B, Stanek C, Cuny C (2007). Methicillin-resistant Staphylococcus aureus ST398 in Humans and Animals. Cent. Eur. 13(2): 255–258.
  •  

  • Wulf M, van Nes A, Eikelenboom-Boskamp A, de Vries J, Melchers W, Klaassen C, Voss A (2006). Methicillin-resistant Staphylococcus aureus in veterinary doctors and students, the Netherlands. Emerg. Infect. Dis. 12(12): 1939-41. http://dx.doi.org/10.3201/eid1212.060355 PMid:17326948 PMCid:PMC3291345
  •  

  • Yano M, Doki Y, Inoue M, Tsujinaka T, Shiozaki H, Monden M (2000). Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery. Surg. Today 30(1): 16-22. http://dx.doi.org/10.1007/PL00010040 PMid:10648077
  •