ISSN 2398-2977      

Methicillin-resistant Staphylococcus aureus

pequis
Contributor(s):

Sarah Binns

Scott Weese

Synonym(s): MRSA, meticillin-resistant Staphylococcus aureus


Introduction

  • Cause:Staphylococcus aureus  Staphylococcus aureus  resistant to the beta-lactam antibiotic methicillin, and all other beta-lactam antibiotics (penicillins, cephalosporins, carbapenems).
  • Methicillin, also called meticillin (oxacillin), has been used to treat human infections since the 1950s. Resistance to the antibiotic was first reported in staphylococci isolated from humans in the UK in 1961.
  • Methicillin-resistantStaphylococcus aureus(MRSA) was first reported to be a major problem in human hospitals in the USA in the 1970s, and in the 1990s it became recognized as an important cause of nosocomial (hospital-associated) infection   Hospital-associated infections   in human hospitals all over the world. Recently, MRSA has become an important cause of infection in people in the general population (community-associated MRSA).
  • The first isolates of MRSA from domestic animals were obtained from milk from cows with mastitis.
  • MRSA is becoming an increasingly recognized problem in small animal and equine medicine. It can occur as sporadic cases or outbreaks in veterinary hospitals   Hospital-associated infections   but is likely more common in horses in the general population.
  • Methicillin resistance is also found in other species of staphylococci   Staphylococcus spp  isolated from animals.
  • Signs: may be colonization, especially of nasal passages, with no clinical signs; clinical infections range from mild skin infections to life-threatening infections of various body sites. 
  • Diagnosis: samples for bacteriological culture.
  • Treatment: antimicrobial therapy based on sensitivity testing.

Pathogenesis

Etiology

  • S. aureus  Staphylococcus aureus   resistant to the beta-lactam antibiotic methicillin (meticillin, oxacillin).
  • Gram-positive cocci, catalase-, mannitol- and maltose-positive.
  • Equine MRSA strains may be only weakly coagulase-positive.

Predisposing factors

General
  • Risk factors for hospital-associated MRSA in humans include proximity to other patients with MRSA, long-term antibiotic treatment, long-term hospitalization, intensive care, immunosuppression and surgery.
  • Most reports of MRSA infection in horses and dogs describe infections of open wounds, post-operative sepsis, invasive techniques involving needles, or infections associated with implants (orthopedic implants or suture material).
  • Risk factors in horses include larger size of premises, earlier identification of MRSA in horses on the same premises, previous antibiotic therapy, especially with aminoglycosides   Therapeutics: aminoglycosides  or ceftiofur   Ceftiofur  , and previous residence at a veterinary hospital.
  • Horses colonized with MRSA on admission to a clinic have been found to be more likely to develop clinical MRSA infection.
  • Hospitalization and prophylactic use of penicillin have been shown to select for multiple drug resistance in commensal staphylococci. One study compared the percentage ofStaphylococcusisolates taken from hospitalized horses at admission and 3 days later. The percentage of isolates showing antimicrobial resistance increased only slightly in horses that did not receive surgery or penicillin treatment, but increased greatly in horses that had received colic surgery and penicillins. The number of antibiotic resistance genes harboured by each isolate also increased.
  • Infections may be seen in healthy individuals in the absence of recognized predisposing factors.

Specific

  • Penicillinases (often beta-lactamase)   Therapeutics: beta-lactam antibacterials  are synthesized by at least 80% of isolates ofS. aureus. These can confer resistance to some beta-lactam antibiotics but are not associated with methicillin-resistance.
  • Infections withS. aureushave therefore often been treated with antibiotics that are able to resist penicillinase action, such as methicillin.
  • Most strains of MRSA are multi-resistant; ie they are resistant to many other classes of antimicrobial agents.
  • Resistance to methicillin and other beta-lactam antimicrobials is caused by possession of the mecA gene, which codes for a penicillin-binding protein in the bacterial cell wall, PBP2a, that does not allow beta-lactam antibiotics to bind effectively.
  • This gene is part of the larger staphylococcal chromosomal cassette (SCC) mec, and may have been acquired from other species of coagulase-negative staphylococci.

Pathophysiology

  • MRSA colonizes the nasal passages of healthy individuals. It can also be found in the intestinal tract and on the skin and oral mucous membranes.
  • Infections generally often associated with exposure to one or more of the predisposing factors listed above but many infections occur in the absence of any identifiable risk factors.
  • Colonized horses may be a source of infection for themselves or others.

Timecourse

  • Clinical infection has been reported to occur days to weeks after colonization in young horses.

Epidemiology

  • Human hospital-associated MRSA is usually associated with dissemination of an epidemic clonal lineage ofS. aureus, eg MLST ST254, EMRSA-15 (CC22) in the UK, CMRSA-2/USA100 in Canada and the US. Community-associated MRSA infections in North America are largely caused by USA300/CMRSA10.
  • Most reports of MRSA in horses have involved ST8 strains, including CMRSA5/USA500 in North America. These strains, which are uncommon in people, have been reported to be more common in people with horse contact. 
  • Recently, there have been reports of MRSA infection and colonization in horses caused by ST398, the strain that is associated with MRSA in pigs and cattle. 
  • Carriage ofS. aureusis less common in most animals than in humans. Colonization rates of ~10% have been reported in healthy horses.S. pseudintermediusis the most common coagulase-positive staphylococcus found in dogs, and has itself been found to be transmitted between dogs and their owners. 
  • MRSA isolates have been obtained from cattle, horses, cats, dogs, chickens, sheep, and pigs, described in reports published from 1972-2005.
  • A survey of university veterinary clinics found that 14% of patients withS. aureushad MRSA, and this was most common in dogs and horses. Reported MRSA infection rates in equine hospitals vary from 4.712%. 
  • In one study, approximately 50% of horses kept on one premises were found to be colonized.
  • Colonization in adult horses tends to be transient, and is naturally eliminated in a period of weeks. A few horses may be persistently colonized, or at least for several months.
  • Environmental contamination is thought to be a significant source of MRSA infections in veterinary hospitals, but transmission is thought mainly to occur via human hands. MRSA can also exist in airborne bioaerosols but the relevance of this for transmission is unclear. 
  • Increasing numbers of veterinary personnel have been found to carry MRSA strains that have also been isolated from animals.
  • There is accumulating evidence that strains of MRSA can be transmitted in both directions between humans and companion animals. It is probable that domestic pets become colonized with human MRSA strains, and then become a reservoir for re-infection of in-contact humans.
  • Equine MRSA infections have occurred in clusters in veterinary hospitals in the USA, and also in the UK, Ireland and Austria.
  • Although isolates from horses are different from those that commonly cause infections in human hospitals, they are similar to those that colonize healthy people who work with horses.
  • Isolates of MRSA from horses in different countries appear to be of different (but typically related) types, according to molecular epidemiological studies.
  • It is thought that equine MRSA strains may have originated in humans but are now being transmitted within the equine population.
  • It is difficult to discern whether the increase in reports of MRSA in domestic animals is due to increased awareness or a true increase in prevalence, however it is likely that MRSA rates are truly increasing. 
  • There has, as yet, been no research carried out to provide definitive information on the prevalence and persistence of MRSA in different species of animal, the ease of transmission, or the effectiveness of control procedures in these species.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Heller J & Hughes K (2013) MRSA in horses. In Pract 35 (1), 30-35 VetMedResource.
  • Maddox T W et al (2012) Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 1: Prevalence of antimicrobial-resistant Escherichia coli and methicillin-resistant Staphylococcus aureusEquine Vet J 44(3), 289-296 PubMed.
  • Weese J S (2011) Methicillin-resistant staphylococcal infections in pets. European J Comp Anim Pract 21 (1), 101-110 VetMedResource.
  • Abbott Y et al (2010) Isolation rates of meticillin-resistant Staphylococcus aureus in dogs, cats and horses in Ireland. Vet Rec 166 (15), 451-455 PubMed.
  • Maddox T W et al (2010) A review of the characteristics and treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the horse and a case series of MRSA infection in four horses. Equine Vet Educ 22 (1), 91-102 Wiley Online Library.
  • Anderson M E C et al (2009) Retrospective multicentre study of methicillin-resistantStaphylococcus aureusinfections in 115 horses. Equine Vet J 41 (4), 401-405 PubMed.
  • Leonard F C & Markey B K (2008) Meticillin-resistant Staphylococcus aureus in animals. Vet J 175, 27-36 PubMed.
  • Bagcigil F A, Moodley A, Baptiste K E et al (2007) Occurrence, species distribution, antimicrobial resistance and clonality of methicillin- and erythromycin-resistant staphylococci in the nasal cavity of domestic animals. Vet Microbiol 121, 307-315 PubMed.
  • Maeda Y, Millar B C, Loughrey A et al (2007)Community-associated MRSA SCCmec type IVd in Irish equids.Vet Rec161(1), 35-36 PubMed.
  • Weese J S (2007) MRSA infection in horses. Vet Rec 161 (10), 359-360 PubMed.
  • Weese J S, Lefebvre S L (2007) Risk factors for methicillin-resistant Staphylococcus aureus colonization in horses admitted to a veterinary teaching hospital. Can Vet J 48 (9), 921-926 PubMed.
  • Cuny C, Kuemmerle J, Stanek C et al (2006) Emergence of MRSA infections in horses in a veterinary hospital: strain characterisation and comparison with MRSA from humans. Eurosurveillance 11 (1), 595 PubMed.
  • Moodley A, Stegger M, Bagcigil A F et al (2006) Spa typing of methicillin-resistant Staphylococcus aureus isolates from domestic animals and veterinary staff in the UK and Ireland. J Antimicrob Chemother 58, 1118-1123 PubMed.
  • Schnellmann C, Gerber V, Rossano A et al (2006) Presence of new mecA and mph(C) variants conferring antibiotic resistance in Staphylococcus spp. isolated from the skin of horses before and after clinic admission. J Clin Microbiol 44 (12), 4444-4454 PubMed.
  • Weese J S, Rousseau J, Willey B M et al (2006) Methicillin-resistant Staphylococcus aureus in horses at a veterinary teaching hospital: frequency, characterization and association with clinical disease. J Vet Intern Med 20 (1), 182-186 PubMed.
  • Baptiste K E, Williams K, Williams N J et al (2005) Methicillin-resistant staphylococci in companion animals. Emerg Infect Dis 11 (12), 1942-1944 PubMed.
  • Middleton J R, Fales W H, Luby C D et al (2005) Surveillance of Staphylococcus aureus in veterinary teaching hospitals. J Clin Microbiol 43 (6), 2916-2919 PubMed.
  • Slater J (2005) MRSA: an emerging equine problem? Equine Vet J 37 (6), 490-492 PubMed.
  • Weese J S & Rousseau J (2005) Attempted eradication of methicillin-resistant Staphylococcus aureus colonisation in horses on two farms. Equine Vet J 37 (6), 510514 PubMed.
  • Weese J S, Rousseau J, Traub-Dargatz J L et al (2005) Community-associated methicillin-resistantStaphylococcus aureusin horses and humans who work with horses. JAVMA 226 (4), 580-583 PubMed.
  • Guardabassi L, Loeber M E & Jacobson A (2004) Transmission of multiple antimicrobial-resistant Staphylococcus intermedius between dogs affected by deep pyoderma and their owners. Vet Microbiol 98, 23-27 PubMed.
  • Weese J S (2004) Methicillin-resistant Staphylococcus aureus in horses and horse personnel. Vet Clin Equine 20, 601-613 PubMed
  • Weese J S, DaCosta T, Button L et al (2004) Isolation of methicillin-resistant Staphylococcus aureus from the environment in a veterinary teaching hospital. J Vet Intern Med 18 (4), 468-470 PubMed.
  • ORourke K (2003) Methicillin-resistant Staphylococcus aureus: an emerging problem in horses? JAVMA 223 (10), 1399-1400 PubMed.
  • Yasuda R, Kawano J, Matsuo E et al (2000) Distribution of mecA-harboring staphylococci in healthy mares. J Vet Med Sci 64 (9), 821-827 PubMed.
  • Yasuda R, Kawano J, Onda H et al (2002) Methicillin-resistant coagulase-negative Staphylococci isolated from healthy horses in Japan. Am J Vet Res 61 (11), 1451-1455 PubMed.
  • Shiomori T, Miyamoto H & Makishima K (2001) Significance of airborne transmission of methicillin-resistant Staphylococcus aureus in an otolaryngologyhead and neck surgery unit. Arch Otolaryngology 127, 644-648 PubMed.
  • Seguin J C, Walker R D, Caron J P et al (1999)Methicillin-resistant Staphylococcus aureus outbreak in a veterinary teaching hospital: potential human-to-animal transmission. J Clin Microbiol 37 (5), 1459-1463 PubMed.
  • Shimizu A, Kawano J, Yamamoto C et al (1997) Genetic analysis of equine methicillin-resistantStaphylococcus aureusby pulsed-field gel electrophoresis. J Vet Med Sci 59 (10), 935-937 PubMed.
  • Hartmann F A, Trostle S S & Klohnen A A (1997) Isolation of methicillin-resistant Staphylococcus aureus from a postoperative wound infection in a horse. JAVMA 211 (5), 590-592 PubMed.

Other sources of information

  • American Veterinary Medical Association (1998, amended 2004, 2007) Judicious use of antimicrobials. Available at: www.avma.org/products/scientific/jtua.pdf (last accessed 27 June 2008).
  • Rich M & Roberts L (2006) Methicillin-resistant Staphylococcus aureus isolates from companion animals. (Letter) Vet Rec 154, 310.
  • Boag A, Loeffler A & Lloyd D H (2004) Methicillin-resistant Staphylococcus aureus isolates from companion animals. (Letter) Vet Rec 154, 411. 

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