2. Staphylococcus
● GramPositive 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 wallscontain peptidoglycans
● Penicillin prevents cross linking of small peptide chains
● Thusnewly produced cells lack rigidity and undergo lysis
(existing cells unaffected)
4. Resistance to Penicillin
● Within 10 yrs
● Prodn. of Blactamase
● Enzymecleavesthe Blactam ring of penicillin
5. ● 1960
● Semisynthetic penicillin (Methicillin)
● Additional acyl group in Blactamring
● Wider antibacterial spectrum
● Resistant to penicillinase
6. ● Resistance to Methicillin wasslower to appear
● Alternative penicillin binding protein PBP2a
● Conferred resistance to the entire antibiotic class
● Encoded on the methicillin resistance gene mecAcomponent
of Staphylococcal cassette chromosome (SCC)
7. ● 4 typesof 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. Drug
Yr drug
introduced
Years to
report
resistance
Years until 25%
rate in hospitals
Years until 25%
rate in
community
Penic
illin
1941 1 to 2 6 15 to 20
Vanc
omyc
in
1956 40 unknown unknown
Methi
cillin
1961 < 1 25 to 30 40 to 50
(projected)
Published with permission from Emerg Infect Dis, 20013
9. MRSA- New Sub classification
CA MRSA
1. More susceptible to B
lactams, Erythromycin
& Quinolones
2. Younghealthy
individuals- athletes
3. Skin and lungs
4. PVLgene, SCC 4
HA MRSA
1. Multiple drugResistance
2. Recentlyhospitalised
patients-hemodialysis,
HIVpatients, Elderly
3. Varies
4. SCC 1 to 3
10. Community Acquired MRSA
● Defn: Staph aureus isolated from an outpatient or inpatient within 48
hrsof admission.
● Results from transfer of mecAto Staph in the the community.
● Genetic characteristic: mecAon SCC4
● Usuallyresistant onlyto methicillin
● Carriesthe PVLlocus
severe soft tissue infection &necrotising
● PVLcauses neutrophil lysis
pneumonia
● PVLin only2% HAMRSA
11. ● Meta analysis of 6000 people 1.3% of community members tested
+ve for CAMRSA
● 30%MRSAisolatesin hospitals were CAMRSA
● Community members without risk factors for MRSA-0.2%
prevalence
● Riskfactors:
1. Hospitalization within the last yr
2. Antimicrobial use within last 3 months
3. HIVInfection
4. admission from group housingsettings
12. ● Infection common in the soft tissues
● 1647 pts in aCDC 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 anyskin infection
Incision &Drainage
Culture ofExudate
For Documented CAMRSAnasal mupirocin is indicated for the
entire teamand staff
PREVENTION:
1. Aggressive monitoring of wounds
2. Shower before use of whirlpools
3. Limit sharingof equipment
4. Frequent cleaningof equipment
14. Hospital Acquired MRSA
● Acutely / chronically ill patients requiring in dwelling devices
(catheters ¢ral lines)
● Naresare the most consistent site from which MRSAhave been
isolated
REASON: Relative lack oflocal host defenses
● Elimination of MRSAfrom nares reflects that from other areas of the
body.
● Nasal carriers of MRSAhavean increased risk of MRSAbacteremia.
15. ● Peri operative colonisation with MRSAafter admission to
and ICU greatlyincreases the riskof post op infection.
● Intubation traumatizes the colonised airway allowing access
of MRSAto the blood stream
● Air in the operating room is contaminated with MRSAwhich
then seedsthe wound.
16. MUPIROCIN
● Antibiotic from Pseudomonasfluorescens
● Reversibly binds to bacterial isoleucyl tRNAsynthetase
● Promotes conversion ofIsoleucine tRNAto Isoleucyl tRNA
inhibition of bacterial RNA&protein synthesis
RECOMMENDATION:
Murirocin Ointment twice aday x 5 dayseliminates MRSAin 91%
carriers
Kluytmans et al. found that nasal elimination of MRSApre op reduced post
op infection by60%
17. ● MRSAinfections 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 MRSAhad alonger
and more costlystay in the hospital.
● MRSAwasindependently a/w higher mortality
● Roche et al. 318 pts. Hospital stay trebled in pts with MRSA
post Orthopaedic procedure.
18. ● Previous MRSAinfection at any site is arisk factor for persistant
colonisation and further infn.
● Huang and Platt identified 209 pts with colonisn or infection with
MRSAin the last 6 months.
● Over aF/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.
● MRSAproduces abiofilm cause infections in implants.
20. ● Bacteria adhere to the implant, become sessile, reduce metabolic rate, secrete aglycalyx
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)
● MRSAhasalarge number ofsurface proteins which facilitate adhesionto foreign bodies.
Within a colony, cell-to-cell interactions are mediated by polysaccharide adhesion
molecules which confer aquorum-sensing ability, inhibiting further bacterial
reproduction once an ideal colony number hasbeen reached
● These biofilm-covered colonies then act as a reservoir for MRSAincreasing 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 byage, gender, date of surgery, date of discharge,
length of hospitalisation, operating time &the diag of diabetes.
● Findingsin nasalswabs &swabs taken from surgeons were recorded.
● MRSAcarriage rate was27%, with an overall infection rate of 6.6%.
● The only variable predictive of post-operative infection was nasal
colonisation with MRSA.
22. ● In asimilar study by the same group patients requiring
internal fixation or metal prosthesesreceived prophylaxis
with nasal mupirocin for 4 days.
● There wasasignificant reduction in surgical-site infection
ratesof MRSAin the treatment group.
23. ● In2004, Merrer et alexaminedMRSAcarriage rate in pts admitted with # ofthe
femoral neck.
● Those admitted from home had an MRSAcolonisation rate of 2%
● Those admitted from an assisted-care facility had arate 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, aswell asin those who were current carriers.
24. Recommendationsfor pre-operative use of vancomycin
1. patients who havealife-threatening allergy to cephalosporins
2. Residents of institutions in which there is ahigh rate of MRSA
infection
Prophylactic intravenous dose of vancomycin:
15 mg/kg must be given60 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
Efficacyof this drug in treating MRSAsoft-tissue infections and MRSA
osteomyelitis demonstrated.
Little data regarding use of daptomycin in orthopaedic surgical infections,
and no randomised controlled trials havebeen published.
26. ● Linezolid
Oral oxazolidindione antibiotic
Interfereswith 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
29. Alternative Antibiotic Delivery
Mechanism
● To combat local infection
● Antibiotic-impregnated cement local delivery without systemic
complications.
● Allows elution of the antibiotic through acost-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. ● V
ancomycin elution can be significantlyaugmented with the
addition of tobramycin to the cement.
● Recommended combination
3.6 gof tobramycin
1 gofvancomycin
40 gof cement
Producesserum levelslower than 3 ml/ l
33. ● For prophylactic purposes:
Low-dose antibiotic cement (1 gto 2 gof antibiotic/40 gof cement).
● For therapeutic Purposes
Higher doses(> 2 g/40 g) such asin beads and spacers.
The addition of over 4.5gof antibiotic per 40 gof
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 thisproblem:
1. Use of biodegradable protein-derived materials such asgelatin,
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:
Lifelongsuppressive antibiotic therapy
36. For infected fracture:
Goals:
1. Healingof the fracture
2. Optimal rehabilitation
3. Prevention ofchronic 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, Denmarklow 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 MRSAare different organisms.
● Affects different patient populations, produces distinct infections and requires unique
treatment.
● MRSAcolonisation correlates with ahigher rate of MRSAinfection.
● 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 isan effective strategyofprevention ofinfection.
● Antibiotic-laden cement maybe usedin both the prophylaxisagainstinfection aswell
asin its treatment.
● Additional studies are needed to determine the best strategies for the prevention of
infection and the treatment of MRSAin sports medicine and in orthopaedic settings.
