Perioperative Antibiotic Prophylaxis

Timing: The Most Critical Factor

Optimal window: 30-60 minutes before incision

Evidence for timing:

• 30 minutes pre-incision: Peak tissue levels at incision (optimal)
• 60 minutes pre-incision: Still therapeutic levels, acceptable
• Greater than 120 minutes pre-incision: Levels drop, increased infection risk
• After incision: Bacteria already attached, prophylaxis fails (becomes treatment)

Special considerations for vancomycin:

• Vancomycin requires 1-2 hour IV infusion (rapid infusion causes red man syndrome)
• Start vancomycin 120 minutes (2 hours) before incision to complete infusion by incision
• If started too late, may not achieve therapeutic levels until after incision (failure)

Timing within 30-60 minutes pre-incision is THE most important factor for prophylaxis efficacy.

Weight-Based Dosing

Cefazolin dosing:

• Standard dose: 2g IV if weight less than 120kg
• High dose: 3g IV if weight greater than or equal to 120kg
• Pediatric: 30 mg/kg IV (maximum 2g)

Why weight matters:

• Volume of distribution increases with body weight
• Obese patients have greater tissue volume requiring antibiotic penetration
• Standard 1g dose (historical) is insufficient for modern patients (average weight increased)
• 2g dose achieves adequate tissue levels in 70-90kg patients
• 3g dose necessary for adequate levels in greater than 120kg patients

Evidence for higher dosing:

• Studies show standard 1g cefazolin inadequate tissue levels in many patients
• 2g dose achieves MIC90 for S. aureus in bone/tissue in 95% of patients
• Obesity epidemic necessitates higher doses (average patient weight increased)
• Underdosing associated with increased SSI risk

Other antibiotics dosing:

• Vancomycin: 15 mg/kg IV (maximum 2g per dose), infuse over 1-2 hours
• Gentamicin: 5 mg/kg IV (single dose, maximum 320mg)
• Clindamycin: 900mg IV (beta-lactam allergy alternative)

Adequate dosing essential - underdosing as bad as wrong timing.

Intraoperative Redosing

Redosing indications:

1. Surgery duration exceeds 2 drug half-lives
2. Blood loss exceeds 1500mL

Cefazolin redosing:

• Half-life: 1.8-2 hours (renal function normal)
• Redose at 4 hours if surgery ongoing (2 × half-life = 4 hours)
• Redose with same dose (2g or 3g based on weight)
• Continue redosing every 4 hours until wound closure

Other antibiotics redosing intervals:

• Vancomycin: Half-life 6 hours, redose at 12 hours (rarely needed)
• Gentamicin: Single dose only, do NOT redose (toxicity)
• Clindamycin: Half-life 3 hours, redose at 6 hours

Blood loss indication:

• Greater than 1500mL blood loss: Redose regardless of time
• Mechanism: Dilutional effect reduces serum and tissue concentrations
• Applies to all antibiotics
• Estimate blood loss intraoperatively (suction, sponges, field)

Practical redosing:

• Communicate with anesthesia to track time and blood loss
• Set timer for 4 hours from initial dose (cefazolin)
• Notify surgeon when redosing given (some surgeons want to know timing)
• Document each dose in anesthesia record

Maintain therapeutic levels throughout surgery - redosing as important as initial dose.

Postoperative Duration: When to STOP

Evidence-based recommendation: Stop within 24 hours post-op

Most procedures: Single dose sufficient

• Clean orthopaedic surgery (THA, TKA, arthroscopy): Single preoperative dose
• No benefit to additional postoperative doses
• Multiple RCTs show single dose = multiple doses for SSI prevention

If continued: 24 hours maximum

• Some surgeons continue for 24 hours (tradition, medicolegal)
• Acceptable but NOT more effective than single dose
• Never exceed 24 hours for routine prophylaxis

Evidence AGAINST prolonged prophylaxis (greater than 24 hours):

• Does NOT reduce SSI further (plateau effect after 24 hours)
• Increases antimicrobial resistance (selects resistant S. aureus, Enterobacteriaceae)
• Increases C. difficile infection risk
• Increases antibiotic adverse effects (allergy, renal toxicity, drug interactions)
• Increases cost without benefit

Exceptions (continue beyond 24 hours):

• Open fractures: Continue until wound definitively closed (Type I: 24h, Type II: 48h, Type III: 72h maximum)
• Contaminated surgery: Gross contamination (e.g., fecal, pus) may warrant 24-48h treatment (NOT prophylaxis)
• Established infection: Treatment regimen, not prophylaxis

Documentation and stewardship:

• Document planned duration at surgery (e.g., "cefazolin 2g pre-op, stop at 24h")
• Automatic stop orders at 24 hours (default)
• Antimicrobial stewardship teams review prolonged courses
• Educate surgeons on evidence against prolonged prophylaxis

Single dose or 24 hours maximum - more is not better, it is worse.

Total Hip/Knee Arthroplasty and Clean Spine

Target pathogens:

• S. aureus (30-40% of SSI)
• Coagulase-negative Staphylococci (S. epidermidis 30-40%)
• Streptococcus species (10-15%)

First-line: Cefazolin

• Dose: 2g IV (3g if greater than 120kg)
• Timing: 30-60 minutes pre-incision
• Duration: Single dose (or 24 hours if surgeon preference)
• Redosing: Every 4 hours if surgery prolonged

Alternative agents:

• Beta-lactam allergy: Vancomycin 15 mg/kg IV OR clindamycin 900mg IV
• MRSA colonized: Vancomycin 15 mg/kg IV (start 120 min pre-incision for infusion)
• MRSA high-risk: Some add vancomycin to cefazolin (controversial, no strong evidence)

Antibiotic cement:

• PMMA bone cement loaded with gentamicin or vancomycin
• Provides local high-concentration antibiotic release
• Does NOT replace systemic prophylaxis (still give IV cefazolin)
• May reduce infection in high-risk patients (revision, immunosuppressed)
• Joint registries (e.g. AOANJRR, Swedish/Norwegian) report benefit of antibiotic-loaded cement particularly in revision and high-risk arthroplasty

Open Fracture Antibiotic Prophylaxis

Gustilo-Anderson classification guides prophylaxis:

Type I (clean wound, less than 1cm):

• Antibiotics: Cefazolin 2g IV
• Duration: 24 hours (stop after wound closure)
• Pathogens: S. aureus, Streptococcus

Type II (moderate contamination, 1-10cm):

• Antibiotics: Cefazolin 2g IV + gentamicin 5 mg/kg IV
• Duration: 48 hours or until wound closed
• Pathogens: S. aureus, Streptococcus, gram-negatives

Type III (severe contamination, greater than 10cm, high-energy, farm/soil)**:

• Antibiotics: Cefazolin 2g IV + gentamicin 5 mg/kg IV + metronidazole 500mg IV
• Duration: 72 hours maximum or until wound definitively closed
• Pathogens: S. aureus, gram-negatives (Pseudomonas), anaerobes (Clostridium, Bacteroides)

Special considerations:

• Farm/fecal contamination: Add metronidazole for anaerobes (Clostridium, Bacteroides)
• Aquatic/marine contamination: Add doxycycline or fluoroquinolone (Aeromonas, Vibrio)
• Duration: Continue until wound definitively closed (primary closure or flap coverage)
• Maximum: 72 hours even if wound not closed (becomes treatment if longer)

Gentamicin considerations:

• Single daily dose (5 mg/kg, max 320mg) for prophylaxis
• Monitor renal function if continued beyond 48 hours
• Do NOT redose intraoperatively (nephrotoxic, single dose provides coverage)

Extended duration prophylaxis for open fractures is evidence-based, but must be balanced against emergence of resistant organisms and C. difficile risk.

MRSA Colonized or High-Risk Patients

MRSA risk factors:

• Known MRSA colonization (nasal swab positive)
• Recent hospitalization (within 6 months)
• Nursing home resident
• Chronic wounds, indwelling catheters
• Previous MRSA infection
• High local MRSA prevalence (greater than 20%)

Prophylaxis options:

Option 1: Vancomycin alone

• Dose: 15 mg/kg IV (max 2g per dose)
• Timing: Start 120 minutes (2 hours) pre-incision (requires slow infusion)
• Infusion: Over 1-2 hours (red man syndrome if too rapid)
• Covers MRSA and MSSA, but weaker against MSSA than cefazolin

Option 2: Vancomycin + cefazolin (dual prophylaxis)

• Vancomycin 15 mg/kg IV (for MRSA)
• Cefazolin 2g IV (better MSSA and Streptococcus coverage)
• Rationale: Cefazolin superior to vancomycin for MSSA
• No strong evidence for benefit vs vancomycin alone
• Some institutions use for high-risk (obesity, diabetes, revision)

MRSA decolonization (preoperative):

• Nasal mupirocin: 2% ointment, twice daily × 5 days pre-op
• Chlorhexidine baths: 2-4% solution, daily × 5 days pre-op
• Reduces MRSA carriage and SSI in colonized patients
• Screen with nasal swab if high-risk patient

Beta-Lactam Allergy Alternatives

Type of allergy matters:

• True IgE-mediated (anaphylaxis, angioedema, bronchospasm): Absolute contraindication to cephalosporins
• Non-IgE (rash, GI upset): May tolerate cephalosporins (low cross-reactivity)
• Many reported "penicillin allergies" are not true IgE reactions (70-80%)

Cross-reactivity:

• Penicillin to cephalosporin: 1-3% cross-reactivity overall (historically over-quoted as 10%, now known to be much lower)
• Penicillin to carbapenem: about 1% cross-reactivity
• Cross-reactivity is driven by R1 side-chain similarity, NOT the shared beta-lactam ring - and cefazolin has a unique R1 side chain shared with no penicillin, so its true cross-reactivity is negligible (see pearl below)
• If non-severe reaction to penicillin, cefazolin is generally safe (discuss with patient)

Alternative agents for true beta-lactam allergy:

Vancomycin 15 mg/kg IV:

• Covers S. aureus (MSSA and MRSA), S. epidermidis
• Less effective than cefazolin for MSSA (but acceptable)
• Does NOT cover gram-negatives or anaerobes
• Start 2 hours pre-incision (infusion time)

Clindamycin 900mg IV:

• Covers S. aureus (MSSA, some MRSA resistance), Streptococcus, anaerobes
• Good bone penetration
• Does NOT cover gram-negatives
• Resistance increasing in some S. aureus strains

Vancomycin + gentamicin:

• If gram-negative coverage needed (open fracture, contaminated case)
• Vancomycin 15 mg/kg IV + gentamicin 5 mg/kg IV
• Broad coverage but nephrotoxic combination

Aztreonam (monobactam):

• NO cross-reactivity with penicillins (safe in beta-lactam allergy)
• Covers gram-negatives only (NOT gram-positives)
• Rarely used for prophylaxis (no Staph coverage)
• Can combine with vancomycin for broad coverage