METHICILLIN-RESISTANTStaphylococcus aureus INORTHOPAEDIC SURGERY
StaphylococcusGram Positive cocciGrow in clusters1884 Rosenbach     1. Staph. aureus - yellow colony,           coagula...
PenicillinBacterial cell walls contain peptidoglycansPenicillin prevents cross linking of small peptide chainsThus newl...
Resistance to PenicillinWithin 10 yrsProdn. of B lactamaseEnzyme cleaves the B lactam ring of penicillin
1960Semisynthetic penicillin (Methicillin)Additional acyl group in B lactam ringWider antibacterial spectrumResistant...
Resistance to Methicillin was slower to appearAlternative penicillin binding protein PBP2aConferred resistance to the e...
4 types of SCCType 1, 2 and 3 a/w healthcare associated MRSA – encode  resistance to other antibioticsType 4 in communi...
Years to                            Years until 25%     Yr drug     report           Years until 25%       rate inDrug int...
MRSA- New Sub classification     CA MRSA                        HA MRSA1. More susceptible to B     1.   Multiple drug Res...
Community Acquired MRSADefn: Staph aureus isolated from an outpatient or inpatient within 48  hrs of admission.Results f...
 Meta analysis of 6000 people 1.3% of community members tested   +ve for CA MRSA 30% MRSA isolates in hospitals were CA ...
Infection common in the soft tissues1647 pts in a CDC study  77% skin infection- abscess / cellulitis  6% were invasive ...
RECOMMENDED FOR Rx OF SKIN      INFN IN SPORT  Aggressive evaluation of any skin infection Incision & Drainage Culture ...
Hospital Acquired MRSAAcutely / chronically ill patients requiring in dwelling devices  (catheters & central lines)Nares...
Peri operative colonisation with MRSA after admission to  and ICU greatly increases the risk of post op infection.Intuba...
MUPIROCINAntibiotic from Pseudomonas fluorescensReversibly binds to bacterial isoleucyl tRNA synthetasePromotes convers...
MRSA infections are clinically and financially more costly than Non MRSAEngeman et al. study of 479 pts. With deep surgi...
Previous MRSA infection at any site is a risk factor for persistant colonisation and further infn.Huang and Platt identi...
MRSA & Orthopaedic SurgeryIncreasing number of elderly and trauma pts. Requiring orthopaedic  surgerymore infnInfection...
 Bacteria adhere to the implant, become sessile, reduce metabolic rate, secrete a glycalyx  layer which protects them fro...
MRSA & AntibioticsKalmeijer et al examined 272 patients admitted for elective orthopaedic procedures.Characterised by ag...
In a similar study by the same group patients requiring internal fixation or metal prostheses received prophylaxis with n...
 In 2004, Merrer et al examined MRSA carriage rate in pts admitted with # of the  femoral neck. Those admitted from home...
Recommendations for pre-operative use of vancomycin1.   patients who have a life-threatening allergy to cephalosporins2.  ...
Newly Approved DrugsDaptomycin :Cyclic lipopeptide- conc. Dependent bactericidal activityBroad spectrum activity against ...
LinezolidOral oxazolidindione antibioticInterferes with bacterial ribosomesExcellent bio-activity and is bacteriostatic a...
Trimethoprim-sulphamethoxazole,Tetracyclines,RifampicinClindamycinhave activity against certain strains of MRSA
REMOVAL OF HARDWARE IS ESSENTIAL   FOR CLEARANCE OF MRSA
Alternative Antibiotic Delivery                       MechanismTo combat local infectionAntibiotic-impregnated cement l...
Antibiotic Characteristics for    Incorporation into Cementwater solubilityHeat stabilityFavourable elution properties...
Vancomycin elution can be significantly augmented with the  addition of tobramycin to the cement.Recommended combination...
Preparations having deleterious effects on                cement mantle:1.     Lyophilised Vancomycin2.     Liquid antibio...
For prophylactic purposes:Low-dose antibiotic cement (1 g to 2 g of antibiotic/40 g of cement).For therapeutic PurposesH...
Once the antibiotics have eluted from the cement,the cement surface becomes available for formation of the biofilm.Alterna...
Rx Of MRSA Implant InfectionsAIM:Successful eradication of infectionOptimal outcome for the patientMETHODS:Surgical debrid...
For infected fracture:Goals:1. Healing of the fracture2. Optimal rehabilitation3. Prevention of chronic osteomyelitis.Impl...
Infection Control Effectiveness  Finland, Denmark low prevalence rate <1% Reason:1. National policy for screening patien...
Conclusions Community- and healthcare-acquired MRSA are different organisms. Affects different patient populations, prod...
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Methicillin resistant staphylococcus aureus in orthopaedic surgery

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Methicillin resistant staphylococcus aureus in orthopaedic surgery

  1. 1. METHICILLIN-RESISTANTStaphylococcus aureus INORTHOPAEDIC SURGERY
  2. 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. 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. 4. Resistance to PenicillinWithin 10 yrsProdn. of B lactamaseEnzyme cleaves the B lactam ring of penicillin
  5. 5. 1960Semisynthetic penicillin (Methicillin)Additional acyl group in B lactam ringWider antibacterial spectrumResistant to penicillinase
  6. 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. 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. 8. Years to Years until 25% Yr drug report Years until 25% rate inDrug introduced resistance rate in hospitals communityPenic 1941 1 to 2 6 15 to 20illinVanc 1956 40 unknown unknownomycinMethi 1961 <1 25 to 30 40 to 50cillin (projected)Published with permission from Emerg Infect Dis, 20013
  9. 9. MRSA- New Sub classification CA MRSA HA MRSA1. More susceptible to B 1. Multiple drug Resistance lactams, Erythromycin & Quinolones 2. Recently hospitalised2. Young healthy patients-hemodialysis, individuals- athletes HIV patients, Elderly 3. Varies3. Skin and lungs 4. SCC 1 to 34. PVL gene, SCC 4
  10. 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. 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 yr2. Antimicrobial use within last 3 months3. HIV Infection4. admission from group housing settings
  12. 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. 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 staffPREVENTION:1. Aggressive monitoring of wounds2. Shower before use of whirlpools3. Limit sharing of equipment4. Frequent cleaning of equipment
  14. 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 isolatedREASON: 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. 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. 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 synthesisRECOMMENDATION:Murirocin Ointment twice a day x 5 days eliminates MRSA in 91% carriersKluytmans et al. found that nasal elimination of MRSA pre op reduced post op infection by 60%
  17. 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. 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. 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. 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. 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. 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. 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. 24. Recommendations for pre-operative use of vancomycin1. patients who have a life-threatening allergy to cephalosporins2. 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. 25. Newly Approved DrugsDaptomycin :Cyclic lipopeptide- conc. Dependent bactericidal activityBroad spectrum activity against Gram +ve organisms including MRSAEfficacy 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. 26. LinezolidOral oxazolidindione antibioticInterferes with bacterial ribosomesExcellent bio-activity and is bacteriostatic against MRSA.Favourable outcomes with the use of linezolid in treating MRSA orthopaedic infectionsNo randomised controlled trials have been performed
  27. 27. Trimethoprim-sulphamethoxazole,Tetracyclines,RifampicinClindamycinhave activity against certain strains of MRSA
  28. 28. REMOVAL OF HARDWARE IS ESSENTIAL FOR CLEARANCE OF MRSA
  29. 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. 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. 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 cementProduces serum levels lower than 3 ml/l
  32. 32. Preparations having deleterious effects on cement mantle:1. Lyophilised Vancomycin2. Liquid antibiotics
  33. 33. For prophylactic purposes:Low-dose antibiotic cement (1 g to 2 g of antibiotic/40 g of cement).For therapeutic PurposesHigher doses (> 2 g/40 g) such as in beads and spacers.The addition of over 4.5g of antibiotic per 40 g ofcement weakens the bone cement and should not beused for the fixation of prostheses.
  34. 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. 35. Rx Of MRSA Implant InfectionsAIM:Successful eradication of infectionOptimal outcome for the patientMETHODS:Surgical debridementAntibioticsFor joints: Two-stage exchange of the implant withconcurrent antibiotic therapyFor pts. Who refuse Sx:Lifelong suppressive antibiotic therapy
  36. 36. For infected fracture:Goals:1. Healing of the fracture2. Optimal rehabilitation3. Prevention of chronic osteomyelitis.Implants may have to remain in place whileantibiotics suppress infection, until the fracture hashealed.At that point, the implanted hardware is generallyremoved to allow systemic antibiotics to eradicate theinfection effectively.
  37. 37. Infection Control Effectiveness Finland, Denmark low prevalence rate <1% Reason:1. National policy for screening patients to detect colonistion2. Strict barrier precautions3. Cohort nursingSegregation of Patients
  38. 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.

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