In 1959, methicillin , an antibiotic closely related to penicillin , was introduced to treat staphylococcal and other bacterial infections. Within one to two years, resistance to methicillin was observed in the strains of Staphylococcus aureus ( S. aureus ). These S. aureus bacteria were then termed methicillin-resistant, i.e. MRSA.

MRSA is the aetiologic agent for a wide range of clinical illnesses, ranging from common skin infections such as impetigo and cellulitis to the more serious manifestations of necrotizing fasciitis, abscess, osteomyelitis, pneumonia and sepsis.

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1959
Methicillin, the first beta-lactamase-resistant penicillin, was licensed in England .

1960–1967
Infrequent hospital outbreaks of MRSA in Western Europe and Australia .

1968
First hospital outbreak of MRSA in the U.S. at the Boston City Hospital, Massachusetts.

1968–mid-1990s
MRSA gradually recognized as an endemic pathogen in hospitals, especially in large urban university hospitals.

Percentage of S. aureus infections in hospitalized patients that were caused by MRSA increased slowly but steadily.

1982
Large outbreak of MRSA infections among intravenous drug users in Detroit , Michigan , U.S.

Late 1980s–1990s
Outbreaks of MRSA noted in Australia among the Aboriginal populations who had no exposure to hospitals.

Mid-1990s
Scattered reports of community-acquired MRSA (CA-MRSA) infections in children in the U.S.

1998
* Comparing two periods — 1993–1995 and 1995–1997— among children with no risk factors for healthcare exposure, there was a 25-fold increase in the rate of hospitalizations due to MRSA.

1998–2008: The CA-MRSA Epidemic Decade
While the rates of hospital-acquired MRSA (HA-MRSA) infections remained stable, the rates of CA-MRSA increased.

1999
* First reports of healthy young children dying of severe MRSA infections.

2001
Shift from USA400 to USA300 as the predominant strain of CA-MRSA in the U.S.

2003
* s taphylococcal cassette chromosome, SCC mec IV recognized.
Major groups of MRSA defined by the U.S. Centers for Disease Control and Prevention (USA100, USA200, USA300, up to USA1000).

2003–2004
In large studies, correlations made between different MRSA genotypes and specific clinical syndromes.

2005
CA-MRSA risk factor groups identified to date include athletes, military recruits, incarcerated people, emergency room patients, children in urban areas, HIV patients, men who have sex with men, and indigenous populations.

2009
Hospital admissions due to CA-MRSA became higher

1. CA-MRSA has confusing criteria because the CA-MRSA strains commonly cause infections in healthcare settings.
2. CA-MRSA infections now common in most U.S. cities.
3. CA-MRSA infections and asymptomatic colonization remain less common outside the U.S.

*University of Chicago-led findings

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• Invasive MRSA infections occur in approximately 94,000 people each year and are associated with approximately 19,000 deaths — reportedly more deaths than HIV per year. 2
• Of the MRSA infections that cause death, about 86% are HA-MRSA and 14% are CA-MRSA. 2
• Methicillin resistance in India has been reported to be as high as 80%. 3
• Recent data suggest that MRSA causes about 59% of all skin and soft tissue infections (SSTIs). 2
• There has been a 10-fold increase in annual hospital admissions with MRSA infections since the early ‘90s. 4
• MRSA is emerging as a major pathogen in India . 3,5,6,7,8,9,10

• A genetic element that can be transferred from one bacterium to another causes
  S. aureus to develop resistance to antibiotics.
• At least five types of genetic material (SCC mec genes I–V) have been identified.
• HA-MRSA usually has genes I–III while CA-MRSA has genes IV–V.
• HA-MRSA is resistant to more antibiotics than CA-MRSA.

Characteristic	HA-MRSA	CA-MRSA
Epidemiological Characteristics
Population affected	•  Hospital/healthcare/nursing home patients/residents •  Elderly population •  Pre-term neonates •  Immunocompromised patients	•  Usually, young healthy individuals in the community •  Those who have no risk factors for acquisition of HA-MRSA •  Individuals in prisons, military personnel, athletes, male homosexuals, ethnic populations (native American Indians, Hawaiian islanders, Alaskan native people)
Clinical Characteristics
Site of infection	•  Bacteraemia •  Wound infections. •  Symptomatic infections of the respiratory and urinary tracts.	•  Mainly skin (abscesses and cellulitis furunculosis, severe SSTIs) •  In severe cases, septic shock and bacteraemia. •  Necrotizing pneumonia.
Risk factors	Indwelling devices, catheter lines, haemodialysis, prolonged hospitalization, long-term antibiotic use.	Close physical contact, abrasion injuries, activities associated with poor communal hygiene (e.g. sharing towels).
Transmission	•  Person-to-person spread: h ealthcare staff (e.g. nurses, doctors, surgeons, physiotherapists), visitors, patients. •  Environment-to-patient spread, e.g. hospital equipment.	•  Person-to-person spread, shared facilities. •  Environment-to-person spread, e.g. shared sports equipment.
Microbiological Characteristics
Susceptibility to methicillin	No	No
Susceptibility to other antibiotic agents (fluoroquinolones, aminoglycosides, erythromycin, clindamycin)	No	Yes (in majority of the cases)
Presence of PVL gene	Low (<5%)	High (>95%)
SCC mecA type	Predominantly, subclasses I, II or III	Mainly IV # and V
agr genotype	Predominantly II	Predominantly I and III
Virulence	Less virulent than CA-MRSA	More virulent. Evades the host's innate immune system by neutrophil lysis following phagocytosis at a more rapid rate than HA-MRSA strains.
PVL: Pantone Valentine Leukocidin; agr: a ccessory gene regulator; SCC mec A: s taphylococcal cassette chromosome # Note: SCC mec A type IV accounts for the transformation of normal staphylococcal flora into MRSA

Clinical manifestations of HA MRSA & CA MRSA in India 14

BSI: Blood stream infection ; UTI: Urinary tract infection; SSTI: Skin and soft tissue infection; RTI: Respiratory tract infection

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Laboratory determination of MRSA susceptibility is important to establish an effective antibiotic treatment.

The earlier the appropriate diagnosis is made and therapy is instituted for MRSA, the better the prognosis .

* Not approved for paediatric use

CNS: Central nervous system; GISA: Glycopeptide-intermediate S.aureus ; GRSA: Glycopeptide-resistant S.aureus

• Any infection that continues to hold on and is not adequately treated by antibiotic therapy should be considered for surgical intervention .
  
• Drainage of pus is the main surgical treatment in MRSA infections, followed by appropriate antibiotic therapy.
  
• Foreign bodies like artificial grafts or pacemakers need to be removed if appropriate antibiotic therapy is unsuccessful.

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• Avoid direct contact with the skin, clothing or any items of either MRSA patients or those who have been exposed to MRSA.
• Follow excellent hygiene practices.
• Treat and cover any skin breaks.
• Although MRSA is not transmitted to infants by breast feeding , there have been a few reports that infants can be infected by their MRSA-positive mothers.

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Method	Comment
Screening  •  Patients •  Staff	Effective if followed by isolation, cost-effective for threshold values Low screening rates, expensive
Handwashing	Effective but poor compliance
Antimicrobials •  Topical agents •  Systemic	Mupirocin widely used and effective, but resistance occurs Using commonly used agents may increase resistance
Body cleansing	Certain agents like povidone iodine, chlorohexidine and triclosan are effective
Cohorting of patients •  Complete separation/ward closure •  Single room isolation	Nurses are required to take care of a variety of patients — effective but disruptive method Variable effectiveness; blocks of room may be helpful.
Pre-identification of carriers and previously infected •  Patients •  Gowns •  Gloves	Effective with total isolation No proved value Effective if changed between patients
Environmental cleaning	Not effective in slowing outbreaks

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S. aureus continues to be one of the most prominent human bacterial pathogens and the emergence of CA-MRSA further escalates the need for improved diagnostic, preventative and therapeutic modalities. Hence, prompt recognition of MRSA infection, appropriate antibiotic use and the institution of consistent prevention measures are essential.

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1. http://mrsa-research-center.bsd.uchicago.edu/timeline.html a ccessed on 12 August 2010
2. http:// www.emedicinehealth.com /mrsa-infections Accessed on 18 September 2009
3. Indian J Med Sci 2000; 54:535–540
4. http://www.aaos.org/news/aaosnow/may08/research1.asp a ccessed on 18 September 2009
5. Tambekar et al. Afr. J. Infect. Dis.1:52–56, Amravati ( India )
6. Ind J Med Microbiol 2001; 19(2):13–16
7. Ind J Med Microbiol 2003; 21:1;49–51
8. Int J Medicine and Med Sci 2010; 2;4:116–120
9. Ind J Med Res 1996; 103:212–215
10. Tropical Doctor 2010; 40:108–110
11. J Global Infect Dis 2010;2;3:275-283
12. Journal of Hospital Infection 2007; 67,109–113
13. Curr Opin Pharmacol 2009, 9:1–7
14. J Clin Diagnostic Research 2010 Feb; 4:2111–2115
15. Journal of Antimicrobial Chemotherapy 2006; 1–20
16. Journal of Hospital Infection 2006;63S: S1-S44

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