MRSA: The Clinician's Challenge

9 Jul, 14

MRSA: The Clinician'S Challenge

MRSA (Methicillin-Resistant Staphylococcus Aureus)

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 wasobserved 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.

MRSA Statistics

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.¹
Of the MRSA infections that cause death, about 86% are hospital-acquired (HA-MRSA) and 14% are community-acquired (CA-MRSA).¹
Methicillin resistance in India has been reported to be as high as 80%.²
Recent data suggest that MRSA causes about 59% of all skin and soft tissue infections (SSTIs).¹
There has been a ten fold increase in annual hospital admissions with MRSA infections since early 90's.³
MRSA is emerging as a major pathogen in India.^{2,4,5,6,7,8,9}

Figure 1: MRSA incidence across India

MRSA History Timeline: The First Half-Century, 1959-2009.10

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 2003
Outbreaks of MRSA noted in Australia among the Aboriginal populations who had no exposure to hospitals.

Mid-1990s
Scattered reports of 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 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
* Staphylococcal 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
Hospitals admission due to CA MRSA became higher

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

* University of Chicago-led findings

Transformation of S.Aureus to MRSA

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.

Comparison of Epidemiological, Clinical and Microbiological Characteristics of HA-MRSA and CA-MRSA 11

Epidemiological Characteristics

Clinical Characteristic

Microbiological Characteristics

PVL: Pantone Valentine Leukocidin; agr: Accessory gene regulator; SCCmecA: Staphylococcal cassette chromosome

*Note:
SCC mecA type IV accounts for the transformation of normal staphylococcal flora into MRSA

Treatment12

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

Special features of antibiotics used in the treatment of MRSA infections

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.

MRSA Infection Prevention

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

MRSA Infection Control Practices 2

Table 2. Infection control methods for MRSA

Conclusion

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, preventive and therapeutic modalities. Hence, prompt recognition of MRSA infection, appropriate antibiotic use and the institution of consistent prevention measures are essential.

Reference

1. http://www.emedicinehealth.com/mrsa-infections. Accessed on 18 September 2009
2. Indian J Med Sci 2000; 54:535-540
3. http://www.aaos.org/news/aaosnow/may08/research1.asp Accessed on 18 September 2009
4. Tambekar et al. Afr. J. Infect. Dis.1(1):52-56, Amravati (India)
5. Ind J Med Microbiol 2001; 19(2):13-16
6. Ind J Med Microbiol 2003; 21(1):49-51
7. Int J Medicine and Med Sci 2010; 2(4):116-120
8. Ind J Med Res 1996; 103:212-215
9. Tropical Doctor 2010; 40:108-110
10. http://mrsa-researchcenter.bsd.uchicago.edu/timeline.html Accessed on 12 August 2010
11. Journal of hospital infection 2007; 67,109-1134
12. Journal of Antimicrobial Chemotherapy 2006, 1-20M