Prophylactic antibiotics

Introduction

Definition

·      surgical antibiotic prophylaxis is the administration of antibiotics to patients undergoing surgery without clinical evidence of infection in the operative field

Objectives

·      prevent naturally occurring organisms in one site from proliferating in a normally sterile site

·      prevent organisms contaminating a normally sterile site from producing disease

·      prevent infection by exogenous organisms

Indications

·      unacceptably high incidence of infection

·      low incidence of infection where infection would be devastating or lethal

Useage

·      prophylactic antibiotic use widespread

·      30-50% of antibiotics used in surgical services for prophylaxis

·      esp. common in orthopaedics in implant surgery

·      infection uncommon but devastating when it occurs

Drawbacks

·      expense

·      drug-related side-effects

·      masking of signs of unrelated infections

·      unfavourable influence on local and hospital microflora

Antibiotic considerations

·      choice influenced by

·      type of surgery

·      current hospital antibiotograms

·      risk of adverse reactions

·      expense

·      should choose according to efficacy against most likely organisms

Susceptibility

·      1st generation cephalosporins

·      effective against gram-positive organisms (Staph. aureus and Staph. epidermidis)

·      as effective as flucloxacillin

·      some effect against gram-negative organisms

·      not effective against Pseudomonas

·      aminoglycosides

·      more effective against gram-negatives (incl. effective against Pseudomonas)

·      less effective against gram-positives

Body fluid concentrations

·      1st generation cephalosporins have high concentrations in synovial fluid and moderate concentration in bone

·      gentamicin and clindamycin have better bone concentrations

Toxicity

·      advantage to have high therapeutic index

·      cephalosporins and penicillins have high therapeutic index and side-effects usually are hypersensitivity

·      aminoglycosides have low therapeutic index and side-effects include nephrotoxicity and ototoxicity

Conclusion

·      cephalosporins are drug of choice

·      broad spectrum of activity against common pathogens

·      low toxicity

·      hight concentrations achieved in bone and soft tissue

Use of antibiotics

Systemic
Drug

·      cephalosporins are drugs of choice

·      inexpensive

·      non-toxic

·      effective against most of potential pathogens

·      good bone antibiotic concentrations achieved

·      comparative data among cephalosporins inadequate

·      cefazolin theoretically advantageous because of

·      longer half-life (allows 8-hour doses)

·      higher bone concentrations

Timing

·      should be given immediately preoperatively

·      avoids problems with on call dosage

·      if anaphylactic reaction occurs, is in controlled environment

·      shown that peak levels reached 20-40 min after bolus IV dose

·      must be given before tourniquet inflated

·      should give another dose if surgery prolonged

·      adequate levels maintained for 2 hrs for cephalothin and 4 hrs for cefazolin

Duration

·      duration of administration varies

·      probably sufficient to give for 24 hrs postoperatively only

·      study showed 24 hrs effective

·      Nelson showed no difference between 1 day and 7 days

·      Wymenga showed no difference between 1 dose and 3 doses

·      probably no need to wait for removal of drains

·      24 hrs of administration gives adequate antibiotic concentrations in joint for several days postoperatively

·      shorter duration means

·      less expensive

·      lower incidence of side-effects

·      less resistant organisms

Dose

·      2g preoperatively gives significantly higher bone and serum levels when important

·      Williams et al (CORR 1983)

·      bone and serum concentrations of 5 cephalosporins

·      1g postoperatively is probably sufficient

Efficacy

·      incidence of infection in implant surgery reduced from 4% to <1%

 Topical

·      in form of local irrigation

·      one study showed it to be effective

·      Riska (Ann Chir Gyneacol 1980)

·      more effective than systemic penicillin

·      do not achieve tissue penetration or concentration

·      may be useful against certain types of infection

·      where toxic antibiotics are necessary

·      eg. aminoglycosides for Pseudomonas

Cement
Physical properties

·      antibiotics in powder form mixed with powdered polymer before mixing with liquid monomer

·      gentamicin-impregnated cement available commercially (Palacos R)

·      0.5 g gentamicin in 40 g powdered polymer

·      composition allows higher rate of elution over longer period

·      mechanical properties altered

·      breaking strength, modulus of elasticity and fatigue strength tested

·      variable results

·      probably insignificant cf. cementing techniques in  Palacos R

·      > 3 g gives more significant alteration

·      antibiotic elution

·      most rapid elution in first few days

·      antibiotic continues to leach out for a prolonged period

·      rates vary with type of cement

·      local concentrations in first few days far in excess of that available from systemic administration

·      no side-effects

·      no hypersensitivities

·      no resistant bacteria

·      no toxic manifestation (include. ototoxicity or nephrotoxicity)

Results

·      no well constructed prospective trials

·      appears to be at least as effective as systemic antibiotics

·      Josefsson et al (CORR 1981)

·      gentamicin cement in THR more effective than sinlge dose of systemic antibiotics (deep infection of 0.4% vs 1.2%)

·      determined infection by ESR and x-ray changes

·      appears to significantly reduces infection rate when used alone

·      Bucholz et al (CORR 1984)

·      infection rate in primary THR 1% with Palacos R as sole prophylaxis cf 5% with plain cement

·      not a prospective randomised trial

Specific uses
Prosthetic joints

·      use best validated in prosthetic joints, as most of research done in this regard

·      number of trials show reduction in infection from 4% with placebo to <1% with prophylactic antibiotics

Femoral fractures

·      shown to be effective

·      Boyd et al (JBJS, 1973)

·      reduction in infection from 5% to 1% in hips treated by pinning

·      should use prophylactic antibiotics as for prosthetic surgery

Clean orthopaedic surgery

·      no adequate trials

·      resultant controversy

·      often used in

·      laminectomy

·      surgery lasting > 2 hrs

·      some use routinely

·      probably not routinely justified

 

References

1.   Mader, J & Cierny, G III, “The Principles of Use of Preventive Antibiotics”, CORR 190:Nov 1984, 75-82

2.   Williams, N & Gustilo, R, “The Use of Preventive Antibiotics in Orthopaedic Surgery”, CORR 190:Nov 1984, 84-88

3.   Bucholz, H et al “Antibiotic-loaded Acrylic Cement: Current Concepts”, CORR190:Nov 1984, 96-108