What empiric broad‑spectrum antibiotics should be initiated for postoperative mediastinitis, and what alternatives are recommended for patients with severe beta‑lactam allergy or who cannot receive vancomycin?

Empiric Antibiotic Therapy for Postoperative Mediastinitis

For postoperative mediastinitis, initiate empiric broad-spectrum therapy with vancomycin 30 mg/kg/day IV in 2 divided doses PLUS piperacillin-tazobactam or a carbapenem (meropenem) to cover methicillin-resistant staphylococci, gram-negative organisms including Pseudomonas, and anaerobes. 1, 2

Initial Empiric Regimen

Standard Broad-Spectrum Coverage

• Vancomycin 30 mg/kg/day IV in 2 divided doses is essential for empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci, which together account for approximately 72% of postoperative mediastinitis cases 3, 4
• Target vancomycin trough levels of 15-20 mg/L for optimal efficacy 5, 3
• PLUS piperacillin-tazobactam to provide coverage for gram-negative bacteria (including Pseudomonas aeruginosa), enterococci, and anaerobes 1, 2
• Alternatively, meropenem can be used instead of piperacillin-tazobactam for broader gram-negative coverage, particularly in institutions with high rates of resistant organisms 1

Microbiological Rationale

The empiric regimen must account for the polymicrobial nature of mediastinitis:

• Coagulase-negative staphylococci cause 46% of cases, particularly associated with sternal dehiscence and obesity 4
• Staphylococcus aureus causes 26% of cases, more common with stable sternum and often from perioperative contamination 4
• Gram-negative bacteria cause 18% of cases, especially in patients requiring reoperation before mediastinitis onset 6, 4
• Anaerobes may be present in conducted infections or esophageal perforation-related cases 2

Alternatives for Severe Beta-Lactam Allergy

When Vancomycin Can Be Used

If the patient has a severe beta-lactam allergy but can tolerate vancomycin:

• Vancomycin 30 mg/kg/day IV in 2 divided doses 1, 3
• PLUS aztreonam (for gram-negative coverage including Pseudomonas) 1
• PLUS metronidazole (for anaerobic coverage) 1, 2

This combination provides comprehensive coverage without beta-lactam exposure while maintaining activity against the key pathogens.

When Vancomycin Cannot Be Used

For patients who cannot receive vancomycin (e.g., severe vancomycin allergy or intolerance):

• Linezolid 600 mg IV every 12 hours for gram-positive coverage including MRSA 7
• PLUS a fluoroquinolone (levofloxacin or moxifloxacin) for gram-negative and some gram-positive coverage 1
• PLUS metronidazole for anaerobic coverage 1, 2

Note that linezolid at 50 mg/kg dosing (approximately 600 mg every 12 hours in adults) has demonstrated efficacy in experimental MRSA mediastinitis, though clinical data are limited 7

Critical Management Principles

Obtain Cultures Before Antibiotics

• Collect tissue samples from sternum and mediastinal swabs for culture and susceptibility testing before initiating antibiotics whenever possible 1, 2, 4
• Blood cultures should be obtained in all patients, as 57% of mediastinitis cases are bacteremic 6

De-escalation Strategy

• Reassess antibiotic therapy daily once culture results are available 1
• Narrow spectrum based on identified organisms and susceptibility patterns, typically within 48-72 hours 1
• If methicillin-susceptible S. aureus (MSSA) is identified, switch vancomycin to nafcillin or oxacillin 1-2 g IV every 4 hours 1, 5
• If gram-negative organisms are not isolated, discontinue gram-negative coverage 1

Duration of Therapy

• Treat for 4-6 weeks for complicated mediastinitis with persistent infection or osteomyelitis 3, 2
• Shorter courses of 10-14 days may be appropriate for uncomplicated cases with prompt clinical response and adequate source control 3, 8

Common Pitfalls to Avoid

• Do not use gentamicin as part of the empiric regimen for mediastinitis, as aminoglycosides are not recommended for staphylococcal infections 1
• Avoid rifampin as monotherapy or routine adjunctive therapy due to rapid resistance development 1, 5, 2
• Do not rely on cefazolin alone for empiric therapy, as many coagulase-negative staphylococci and MRSA are resistant to perioperative prophylactic agents 6, 4
• Recognize that gram-negative infections appear earlier (median 7 days) and are more likely to be bacteremic (70%) compared to gram-positive infections 6

Surgical Management

Antibiotic therapy alone is insufficient—surgical debridement and drainage are mandatory for successful treatment of mediastinitis 2, 8. Vacuum-assisted closure (VAC) therapy is more effective than conventional open packing 8.