1. METHICILLIN-RESISTANT
Staphylococcus aureus IN
ORTHOPAEDIC SURGERY

2. Staphylococcus
Gram Positive cocci
Grow in clusters
1884 Rosenbach
1. Staph. aureus - yellow colony,
coagulase +ve
2. Staph albus - white colonies, do not
clot blod

3. Penicillin
Bacterial cell walls contain peptidoglycans
Penicillin prevents cross linking of small peptide chains
Thus newly produced cells lack rigidity and undergo lysis
(existing cells unaffected)

4. Resistance to Penicillin
Within 10 yrs
Prodn. of B lactamase
Enzyme cleaves the B lactam ring of penicillin

5. 1960
Semisynthetic penicillin (Methicillin)
Additional acyl group in B lactam ring
Wider antibacterial spectrum
Resistant to penicillinase

6. Resistance to Methicillin was slower to appear
Alternative penicillin binding protein PBP2a
Conferred resistance to the entire antibiotic class
Encoded on the methicillin resistance gene mec A component
of Staphylococcal cassette chromosome (SCC)

7. 4 types of SCC
Type 1, 2 and 3 a/w healthcare associated MRSA – encode
resistance to other antibiotics
Type 4 in community acquired MRSA – does not confer
resistance to other antibiotics.

8. Years to Years until 25%
Yr drug report Years until 25% rate in
Drug introduced resistance rate in hospitals community
Penic 1941 1 to 2 6 15 to 20
illin
Vanc 1956 40 unknown unknown
omyc
in
Methi 1961 <1 25 to 30 40 to 50
cillin (projected)
Published with permission from Emerg Infect Dis, 20013

9. MRSA- New Sub classification
CA MRSA HA MRSA
1. More susceptible to B 1. Multiple drug Resistance
lactams, Erythromycin &
Quinolones 2. Recently hospitalised
2. Young healthy patients-hemodialysis,
individuals- athletes HIV patients, Elderly
3. Varies
3. Skin and lungs 4. SCC 1 to 3
4. PVL gene, SCC 4

10. Community Acquired MRSA
Defn: Staph aureus isolated from an outpatient or inpatient within 48
hrs of admission.
Results from transfer of mec A to Staph in the the community.
Genetic characteristic: mec A on SCC 4
Usually resistant only to methicillin
Carries the PVL locus
PVL causes neutrophil lysis severe soft tissue infection & necrotising
pneumonia
PVL in only 2% HA MRSA

11.  Meta analysis of 6000 people 1.3% of community members tested
+ve for CA MRSA
 30% MRSA isolates in hospitals were CA MRSA
 Community members without risk factors for MRSA- 0.2%
prevalence
 Risk factors:
1. Hospitalization within the last yr
2. Antimicrobial use within last 3 months
3. HIV Infection
4. admission from group housing settings

12. Infection common in the soft tissues
1647 pts in a CDC study
77% skin infection- abscess / cellulitis
6% were invasive infections
in athletes- team sports

13. RECOMMENDED FOR Rx OF SKIN
INFN IN SPORT
 Aggressive evaluation of any skin infection
 Incision & Drainage
 Culture of Exudate
 For Documented CA MRSA nasal mupirocin is indicated for the
entire team and staff
PREVENTION:
1. Aggressive monitoring of wounds
2. Shower before use of whirlpools
3. Limit sharing of equipment
4. Frequent cleaning of equipment

14. Hospital Acquired MRSA
Acutely / chronically ill patients requiring in dwelling devices
(catheters & central lines)
Nares are the most consistent site from which MRSA have been
isolated
REASON: Relative lack of local host defenses
Elimination of MRSA from nares reflects that from other areas of the
body.
Nasal carriers of MRSA have an increased risk of MRSA bacteremia.

15. Peri operative colonisation with MRSA after admission to
and ICU greatly increases the risk of post op infection.
Intubation traumatizes the colonised airway allowing access
of MRSA to the blood stream
Air in the operating room is contaminated with MRSA which
then seeds the wound.

16. MUPIROCIN
Antibiotic from Pseudomonas fluorescens
Reversibly binds to bacterial isoleucyl tRNA synthetase
Promotes conversion of Isoleucine tRNA to Isoleucyl tRNA 
inhibition of bacterial RNA & protein synthesis
RECOMMENDATION:
Murirocin Ointment twice a day x 5 days eliminates MRSA in 91%
carriers
Kluytmans et al. found that nasal elimination of MRSA pre op reduced post
op infection by 60%

17. MRSA infections are clinically and financially more costly than
Non MRSA
Engeman et al. study of 479 pts. With deep surgical site
infection with staph. showed that pts. With MRSA had a longer
and more costly stay in the hospital.
MRSA was independently a/w higher mortality
Roche et al. 318 pts. Hospital stay trebled in pts with MRSA
post Orthopaedic procedure.

18. Previous MRSA infection at any site is a risk factor for persistant
colonisation and further infn.
Huang and Platt identified 209 pts with colonisn or infection with
MRSA in the last 6 months.
Over a F/U of 18 months 30% of colonised pts. Developed infn,
with bone and jt. Infn having the highest rates of recurrence.
Pts. With atopic dermatitis/ hemodialysis had higher rate of
colonisation

19. MRSA & Orthopaedic Surgery
Increasing number of elderly and trauma pts. Requiring orthopaedic
surgerymore infn
Infection rates following Internal Fixation is 5% Open #’s being
affected more.
MRSA produces a biofilm  cause infections in implants.

20.  Bacteria adhere to the implant, become sessile, reduce metabolic rate, secrete a glycalyx
layer which protects them from antibiotics, phagocytosis & opsonisation.
 Biofilm-associated bacteria are up to 100 times more resistant to antibiotics, including
vancomycin (marked increases in the MIC)
 MRSA has a large number of surface proteins which facilitate adhesion to foreign bodies.
Within a colony, cell-to-cell interactions are mediated by polysaccharide adhesion
molecules which confer a quorum-sensing ability, inhibiting further bacterial
reproduction once an ideal colony number has been reached
 These biofilm-covered colonies then act as a reservoir for MRSA increasing difficulty in
eradication, hence the rationale for removing orthopaedic hardware in cases of chronic
infection with MRSA.

21. MRSA & Antibiotics
Kalmeijer et al examined 272 patients admitted for elective
orthopaedic procedures.
Characterised by age, gender, date of surgery, date of discharge,
length of hospitalisation, operating time & the diag of diabetes.
Findings in nasal swabs & swabs taken from surgeons were recorded.
MRSA carriage rate was 27%, with an overall infection rate of 6.6%.
The only variable predictive of post-operative infection was nasal
colonisation with MRSA.

22. In a similar study by the same group patients requiring
internal fixation or metal prostheses received prophylaxis
with nasal mupirocin for 4 days.
There was a significant reduction in surgical-site infection
rates of MRSA in the treatment group.

23.  In 2004, Merrer et al examined MRSA carriage rate in pts admitted with # of the
femoral neck.
 Those admitted from home had an MRSA colonisation rate of 2%
 Those admitted from an assisted-care facility had a rate at 16%.
 Recommendation:
Use of pre-operative intravenous vancomycin and mupirocin in patients admitted from
chronic-care facilities.
 Sanderson proposed that a combination of vancomycin and mupirocin in patients with a
h/o colonisation or infection, as well as in those who were current carriers.

24. Recommendations for pre-operative use of vancomycin
1. patients who have a life-threatening allergy to cephalosporins
2. Residents of institutions in which there is a high rate of MRSA
infection
Prophylactic intravenous dose of vancomycin:
15 mg/kg must be given 60 minutes before the skin
incision in order to obtain detectable levels in the skin.

25. Newly Approved Drugs
Daptomycin :
Cyclic lipopeptide- conc. Dependent bactericidal activity
Broad spectrum activity against Gram +ve organisms including MRSA
Efficacy of this drug in treating MRSA soft-tissue infections and MRSA
osteomyelitis demonstrated.
Little data regarding use of daptomycin in orthopaedic surgical infections,
and no randomised controlled trials have been published.

26. Linezolid
Oral oxazolidindione antibiotic
Interferes with bacterial ribosomes
Excellent bio-activity and is bacteriostatic against MRSA.
Favourable outcomes with the use of linezolid in treating MRSA
orthopaedic infections
No randomised controlled trials have been performed

27. Trimethoprim-sulphamethoxazole,
Tetracyclines,
Rifampicin
Clindamycin
have activity against certain strains of MRSA

28. REMOVAL OF HARDWARE IS ESSENTIAL
FOR CLEARANCE OF MRSA

29. Alternative Antibiotic Delivery
Mechanism
To combat local infection
Antibiotic-impregnated cement local delivery without systemic
complications.
Allows elution of the antibiotic through a cost-effective medium
Marks, Nelson and Lautenschlager published the first elution studies
 oxacillin, cefazolin and gentamicin were released in biologically
active forms from the cement.
Demonstrated that Palacos cement (Zimmer, Warsaw, Indiana)
eluted larger amounts of antibiotics for longer periods than Simplex
cement (Stryker, Kalamazoo, Michigan) due to the increased pore
size.

30. Antibiotic Characteristics for
Incorporation into Cement
water solubility
Heat stability
Favourable elution properties
Antimicrobial activity against common pathogens
Maintenance of the mechanical integrity of the cement

31. Vancomycin elution can be significantly augmented with the
addition of tobramycin to the cement.
Recommended combination
3.6 g of tobramycin
1 g of vancomycin
40 g of cement
Produces serum levels lower than 3 ml/l

32. Preparations having deleterious effects on
cement mantle:
1. Lyophilised Vancomycin
2. Liquid antibiotics

33. For prophylactic purposes:
Low-dose antibiotic cement (1 g to 2 g of antibiotic/40 g of cement).
For therapeutic Purposes
Higher doses (> 2 g/40 g) such as in beads and spacers.
The addition of over 4.5g of antibiotic per 40 g of
cement weakens the bone cement and should not be
used for the fixation of prostheses.

34. Once the antibiotics have eluted from the cement,
the cement surface becomes available for formation of the biofilm.
Alternative to this problem:
1. Use of biodegradable protein-derived materials such as gelatin,
albumin, and antibiotic-laden type-1 collagen sponges.
2. The use of calcium sulphate is another alternative however, it releases 58% of its
antibiotic within the first 24 hours and can lead to the formation of a seroma during its
absorption.
3. Use of morsellised bone graft is also an option since it can effectively absorb both
vancomycin and tobramycin and continues to elute these substances for over 3 weeks

35. Rx Of MRSA Implant Infections
AIM:
Successful eradication of infection
Optimal outcome for the patient
METHODS:
Surgical debridement
Antibiotics
For joints: Two-stage exchange of the implant with
concurrent antibiotic therapy
For pts. Who refuse Sx:
Lifelong suppressive antibiotic therapy

36. For infected fracture:
Goals:
1. Healing of the fracture
2. Optimal rehabilitation
3. Prevention of chronic osteomyelitis.
Implants may have to remain in place while
antibiotics suppress infection, until the fracture has
healed.
At that point, the implanted hardware is generally
removed to allow systemic antibiotics to eradicate the
infection effectively.

37. Infection Control Effectiveness
 Finland, Denmark low prevalence rate <1%
 Reason:
1. National policy for screening patients to detect colonistion
2. Strict barrier precautions
3. Cohort nursing
Segregation of Patients

38. Conclusions
 Community- and healthcare-acquired MRSA are different organisms.
 Affects different patient populations, produces distinct infections and requires unique
treatment.
 MRSA colonisation correlates with a higher rate of MRSA infection.
 Colonisation elimination strategies are effective and may lower post-operative
infections when coupled with targeted peri-operative antibiotic prophylaxis.
 Separation of patients who are potential carriers from those who are at a lower risk of
carriage is an effective strategy of prevention of infection.
 Antibiotic-laden cement may be used in both the prophylaxis against infection as well
as in its treatment.
 Additional studies are needed to determine the best strategies for the prevention of
infection and the treatment of MRSA in sports medicine and in orthopaedic settings.