METHICILLIN-RESISTANT Staphylococcus aureus IN ORTHOPAEDIC SURGERY

Staphylococcus Gram 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 peptidoglycans

Penicillin prevents cross linking of small peptide chains

Thus newly produced cells lack rigidity and undergo lysis (existing cells unaffected)

Resistance to PenicillinWithin 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 to penicillinase

Resistance to Methicillin was slower to appear

Alternative 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 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.

DrugYr drug introduced

Years to report resistance

Years until 25% rate in hospitals

Years until 25% rate in community

Penicillin

1941 1 to 2 6 15 to 20

Vancomycin

1956 40 unknown unknown

Methicillin

1961 < 1 25 to 30 40 to 50 (projected)

Published with permission from Emerg Infect Dis, 20013

MRSA- New Sub classification CA MRSA1. More susceptible

to B lactams, Erythromycin & Quinolones

2. Young healthy individuals- athletes

3. Skin and lungs4. PVL gene, SCC 4

HA MRSA1. Multiple drug

Resistance

2. Recently hospitalised patients-hemodialysis, HIV patients, Elderly

3. Varies4. SCC 1 to 3

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 yr 2. Antimicrobial use within last 3 months 3. HIV Infection 4. 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 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.

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.

MUPIROCINAntibiotic from Pseudomonas fluorescensReversibly binds to bacterial isoleucyl tRNA

synthetasePromotes 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% 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 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 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 infn

Infection 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 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.

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 antibiotic Interferes 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,

Rifampicin

Clindamycin

have 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 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.

Antibiotic Characteristics for Incorporation into Cement

water 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 cement Produces serum levels lower than 3 ml/l

Preparations having deleterious effects on cement mantle:

1. Lyophilised Vancomycin

2. 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 of cement weakens the bone cement and should not

be used 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 patient

METHODS:Surgical debridementAntibioticsFor joints: Two-stage exchange of the

implant with concurrent antibiotic therapy For 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 has healed.

At that point, the implanted hardware is generally removed 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 nursing

Segregation 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.