Methicillin resistant staphylococcus aureus in orthopaedic surgery
METHICILLIN-RESISTANTStaphylococcus aureus INORTHOPAEDIC SURGERY
StaphylococcusGram Positive cocciGrow in clusters1884 Rosenbach 1. Staph. aureus - yellow colony, coagulase +ve 2. Staph albus - white colonies, do not clot blod
PenicillinBacterial cell walls contain peptidoglycansPenicillin prevents cross linking of small peptide chainsThus newly produced cells lack rigidity and undergo lysis (existing cells unaffected)
Resistance to PenicillinWithin 10 yrsProdn. of B lactamaseEnzyme cleaves the B lactam ring of penicillin
1960Semisynthetic penicillin (Methicillin)Additional acyl group in B lactam ringWider antibacterial spectrumResistant to penicillinase
Resistance to Methicillin was slower to appearAlternative penicillin binding protein PBP2aConferred resistance to the entire antibiotic classEncoded on the methicillin resistance gene mec A component of Staphylococcal cassette chromosome (SCC)
4 types of SCCType 1, 2 and 3 a/w healthcare associated MRSA – encode resistance to other antibioticsType 4 in community acquired MRSA – does not confer resistance to other antibiotics.
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
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
Community Acquired MRSADefn: 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 4Usually resistant only to methicillinCarries the PVL locusPVL causes neutrophil lysis severe soft tissue infection & necrotising pneumoniaPVL in only 2% HA MRSA
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
Infection common in the soft tissues1647 pts in a CDC study 77% skin infection- abscess / cellulitis 6% were invasive infections in athletes- team sports
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
Hospital Acquired MRSAAcutely / 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 defensesElimination of MRSA from nares reflects that from other areas of the body.Nasal carriers of MRSA have an increased risk of MRSA bacteremia.
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 streamAir in the operating room is contaminated with MRSA which then seeds the wound.
MUPIROCINAntibiotic from Pseudomonas fluorescensReversibly binds to bacterial isoleucyl tRNA synthetasePromotes 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%
MRSA infections are clinically and financially more costly than Non MRSAEngeman 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 mortalityRoche et al. 318 pts. Hospital stay trebled in pts with MRSA post Orthopaedic procedure.
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
MRSA & Orthopaedic SurgeryIncreasing number of elderly and trauma pts. Requiring orthopaedic surgerymore infnInfection rates following Internal Fixation is 5% Open #’s being affected more.MRSA produces a biofilm cause infections in implants.
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.
MRSA & AntibioticsKalmeijer 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.
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.
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.
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.
Newly Approved DrugsDaptomycin :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.
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
Trimethoprim-sulphamethoxazole,Tetracyclines,RifampicinClindamycinhave activity against certain strains of MRSA
REMOVAL OF HARDWARE IS ESSENTIAL FOR CLEARANCE OF MRSA
Alternative Antibiotic Delivery MechanismTo combat local infectionAntibiotic-impregnated cement local delivery without systemic complications.Allows elution of the antibiotic through a cost-effective mediumMarks, 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.
Antibiotic Characteristics for Incorporation into Cementwater solubilityHeat stabilityFavourable elution propertiesAntimicrobial activity against common pathogensMaintenance of the mechanical integrity of the cement
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
Preparations having deleterious effects on cement mantle:1. Lyophilised Vancomycin2. Liquid antibiotics
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.
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
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
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.
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
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.