1. Presenter: Zipporah Machuki
Methicillin-resistant Staphylococcus Aureus - (MRSA): not just a health-care associated multi-drug resistant pathogen anymore
Presenter: Zipporah Machuki

2. Background gram-positive coccal bacterium.
S. aureus :
Facultative anaerobic
gram-positive coccal bacterium.
forms large, round, golden-yellow colonies on BA often with hemolysis.
Reproduces asexually by binary fission
cells are arranged in cluster.
catalase-positive,
coagulase test was used to differentiate S. aureus from other staphylococci epidermidis. However it is now known that not all S. aureus are coagulase-positive.

3. S.aureus commonly colonizes
Survives for a long time on skin or environment.
Mortality 80% prior to introduction of Penicillin.
Resistance to penicillin usually mediated by beta-lactamase,

4. Methicillin
A penicillinase-resistant penicillin
First used in 1959 and
2 years later S.aureus developed methicillin-resistance.
Due to acquisition of the mecA gene.
Traditionally recognized as a nosocomial pathogen
Epidemiology has radically changed

5. Mode of action of methicillin
Bind to the native PBPs that are present in the S. aureus cell wall
Leads to the disruption of the synthesis of the peptidoglycan layer and therefore lysis of the S.aureus.

6. Methicillin Resistant S.aureus(MRSA)
Has a mecA gene which is 2.1kb in length
mecA gene codes for the 78-kDa penicillin binding protein (PBP) 2a (or PBP2’),
PBP2 has decreased affinity for most beta-lactam antibiotics.

7. Mechanism of resistance
When PBP2a is produced,
the binding of the b-lactam antibiotics is hindered and
PBP2A (a transpeptidase), assisted by the transglycosylase domain of the native PBP2 of S aureus, takes over the function of biosynthesis of cell-walls
Result in the growth of MRSA

8. staphylococcal cassette chromosome mec (SCCmec)
A mobile genomic island where mecA gene is located.
Carries chromosome recombinances genes called ccrA/ccrB and ccrC that enable excision and intergration into the host chromosome.
seven types main of SCCmec (SCCmec I to VII)

9. Epidemiology of MRSA MRSA first identified in 1960
became a common nosocomial infection in 1980.
Previously known to be only a nosocomial pathogen.
Risk factors associated with development of MRSA infections:
surgery, dialysis, hospitalization or residence in a long-term care facility within the prior year;
indwelling percutaneous devices such as central venous catheters or feeding tubes;
an MRSA infection identified more than 48 hours after hospital admission; or
Had previously hadMRSA cultured

10. MRSA cultured from patients with these risk factors are known as HA-MRSA.
major clones that disseminated internationally:Iberian,
Brazilian,
Hungarian,
New York/Japan, and
Paediatric clones
CA-MRSA is cultured from healthy and young individuals without any of these clinical risk factors.

12. Control of HA-MRSA Screening of staff
Health-care workers who are nasal carriers can serve as sources of MRSA transmission,
Isolation and barrier nursing
Patients colonised or infected with MRSA
Hand hygiene
Transient contamination of health-care workers’ hands
Environmental cleaning
How important are contaminated environmental surfacesas a reservoir for MRSA?

13. Treatment of HA-MRSA Laptomycin, Linezolid, Tigecycline and Vancomycin
Zhanel et al. 2013

14. Differences between HA-MRSA and CA-MRSA
Bassetti M et al 2009

15. Transmission of CA-MRSA
colonize the nose and nares (Reservoir)- risk of developing a subsequent infection is 10.7% (Ellis MW 2et al 200)
Transmission between individuals is likely to be facilitated by:
crowded living conditions,
activities that involve skin-to-skin contact,
poor hygiene practices and
sharing of contaminated household items (towels, combs etc.).

16. Groups at risk of CA-MRSA
Zetola N et al 2005

17. CA-MRSA causes:
skin and soft tissue infections and
invasive disease such as
sepsis and
necrotizing pneumonia

18. Skin and Soft Tissue Infection
Most common manifestation of CA-MRSA, -particularly abscess or furunculosis
Necrotising pneumonia
Caused by PVL gene-positive CA-MRSA strains
Osteoarticular Infections
Common in children
Other Infections
Infective endocarditis
Sepsis is a complication of CA-MRSA disease

19. Treatment of CA-MRSA Infections
There is no defined optimum management of CA-MRSA infections.
Current strategies include a combination of pharmacological and non-pharmacological intervention eg In patients with recurrent infections, attempts to decolonize CA-MRSA

20. Commonly used antibiotic
Agent
comment
Ceflobiprole
Not yet widely availabel
Clindamycin
iMLSβ resistance my reduce activity
Daptomycin
6mg/kg IV indicated for bacteraemia; do not use to treat pneumonia
Linezolid
Not recommended to treat bacteraemia
Quinupristin/dalfopristin
Tigecycline
Tlow serum concentration so not recommended for bacteraemia treatment
Cotrimoxazole
Activity against GAS is unknown;
Not for use in infants aged <2 mo or during 3rd trimester of pregnance.
Vanomycin
Requires monitoring concentration when treating serious infections

21. Thank you