What is the role of ampicillin (Ampicillin)-sulbactam (Unasyn) for surgical prophylaxis?

Ampicillin-Sulbactam for Surgical Prophylaxis

Ampicillin-sulbactam is an acceptable option for surgical prophylaxis in select urologic procedures and in patients colonized with extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E), but it is not a first-line agent for most surgical prophylaxis indications. 1

Primary Role in Urologic Surgery

Ampicillin-sulbactam serves as an alternative prophylactic agent in urologic procedures, particularly when standard first-generation cephalosporins are not suitable:

• Dosing for urologic prophylaxis: 1.5-3 g IV every 6 hours 1
• The drug achieves adequate tissue concentrations in scrotal organs (mean 38.5 ± 15.9 mg/kg ampicillin and 19.8 ± 5.2 mg/kg sulbactam), exceeding MIC values for common pathogens like Staphylococcus aureus 2
• It is listed as an option for procedures involving urinary tract manipulation, stone procedures, and transrectal prostate biopsy 1

Specific Urologic Indications

For patients with orthopedic prostheses undergoing high-risk urologic procedures, ampicillin 2 g IV (or vancomycin 1 g IV if penicillin-allergic) plus gentamicin 1.5 mg/kg IV should be given 30-60 minutes preoperatively 1

Role in Multidrug-Resistant Colonization

Ampicillin-sulbactam 3 g IV is recommended as a first-line targeted prophylaxis option for patients colonized with ESCR-E undergoing surgery, with redosing every 2-4 hours intraoperatively. 1

Evidence in High-Risk Surgery

• In liver transplant recipients colonized with carbapenem-resistant Klebsiella pneumoniae (CRKP), ampicillin-sulbactam prophylaxis was associated with CRKP infections in 30-37% of carriers versus 0-2% of non-carriers 1
• Multiple observational studies in liver transplantation demonstrate its use as standard prophylaxis, though breakthrough infections still occur in colonized patients 1
• The 2023 ESCMID guidelines classify ampicillin-sulbactam as a WHO AWaRe "Access" category antibiotic, making it preferable from an antimicrobial stewardship perspective 1

Important Caveats for MDR Colonization

• Use alternatives in penicillin-allergic patients (gentamicin or ciprofloxacin) 1
• Postoperative dosing should continue every 6-8 hours when indicated 1
• Amoxicillin-clavulanate IV is an acceptable alternative with similar spectrum 1
• The evidence supporting ampicillin-sulbactam for ESCR-E treatment is insufficient, unlike amoxicillin-clavulanate which has conditional recommendations 1

Limitations in General Surgical Prophylaxis

Ampicillin-sulbactam is not a preferred first-line agent for most clean and clean-contaminated surgeries:

• First-generation cephalosporins (cefazolin) remain the standard for most surgical prophylaxis 1
• In colorectal surgery, ampicillin-sulbactam showed 20% wound infection rates versus 13.3% with penicillin-gentamicin-metronidazole (not statistically significant), indicating it is comparable but not superior 3
• For cardiovascular surgery with cardiopulmonary bypass, dosing every 6 hours is required to maintain adequate free drug concentrations above 2 µg/mL 4

Pharmacokinetic Considerations

Critical timing for redosing: The elimination half-life of ampicillin is approximately 1.5 hours, requiring frequent redosing during prolonged procedures 4

• For procedures longer than 2-4 hours, redose with 1-1.5 g ampicillin-sulbactam 1, 4
• Bone penetration occurs rapidly (within 15 minutes), achieving mean concentrations of 21.8 ± 10.5 mg/kg ampicillin, making it suitable for orthopedic prophylaxis 5
• Tissue concentrations in skin, fat, muscle, and bone remain above MIC for at least 2 hours after administration 5

Spectrum of Activity

The combination provides broad coverage due to sulbactam's beta-lactamase inhibition:

• Gram-positive: S. aureus, S. epidermidis (beta-lactamase producing and non-producing), Streptococcus species 6
• Gram-negative: E. coli, Klebsiella species, Proteus species, H. influenzae, M. catarrhalis (beta-lactamase producing strains) 6
• Anaerobes: Bacteroides fragilis, Clostridium species, Peptostreptococcus species 6

Common Pitfalls to Avoid

• Do not use as monotherapy for procedures requiring anaerobic coverage unless the surgical site naturally harbors anaerobes covered by the drug's spectrum 1
• Avoid in patients with documented immediate hypersensitivity to beta-lactams 1
• Do not assume single-dose prophylaxis is adequate for prolonged procedures—redosing is essential given the short half-life 4, 5
• Consider nephrotoxicity risk when combining with aminoglycosides in patients with renal dysfunction 1