Should metronidazole be used to treat empyema?

Metronidazole in the Treatment of Empyema

Metronidazole should be included in the antibiotic regimen for treating empyema to provide coverage for anaerobic organisms, but it should not be used as monotherapy. 1

Rationale for Metronidazole Use in Empyema

• Anaerobic organisms are frequently involved in pleural infections, particularly in community-acquired empyema, necessitating coverage with agents like metronidazole 1
• A significant proportion of both aerobes and anaerobes isolated from pleuropulmonary infections may be resistant to penicillin alone, making additional anaerobic coverage important 1
• Metronidazole provides targeted coverage against anaerobic bacteria that are commonly present in mixed pleural infections 2

Recommended Antibiotic Regimens Including Metronidazole

For Community-Acquired Empyema:

• Cefuroxime 1.5g three times daily IV + metronidazole 400mg three times daily orally (or 500mg three times daily IV) 1
• Benzyl penicillin 1.2g four times daily IV + ciprofloxacin 400mg twice daily IV 1
• Meropenem 1g three times daily IV + metronidazole 400mg three times daily orally (or 500mg three times daily IV) 1
• Amoxicillin + clavulanic acid or amoxicillin + metronidazole (for oral therapy when appropriate) 1

For Hospital-Acquired Empyema:

• Piperacillin + tazobactam 4.5g four times daily IV 1
• Ceftazidime 2g three times daily IV 1
• Meropenem 1g three times daily IV ± metronidazole 400mg three times daily orally (or 500mg three times daily IV) 1

Important Clinical Considerations

• Metronidazole should always be combined with other antibiotics that provide coverage for aerobic bacteria, as it lacks activity against aerobes 3
• Aminoglycosides should be avoided in empyema treatment as they have poor penetration into the pleural space and may be inactive in acidic pleural fluid 1
• Beta-lactams (penicillins and cephalosporins) show good penetration into the pleural space and remain the drugs of choice when combined with metronidazole for anaerobic coverage 1
• Clindamycin can be used as a single agent in penicillin-allergic patients as it provides both aerobic and anaerobic coverage 1

Evidence Limitations and Cautions

• Earlier studies showed limited efficacy of metronidazole monotherapy in anaerobic pleuropulmonary infections, with failure rates higher than with other agents 4, 5
• In one study, only 5 out of 13 patients with anaerobic pleuropulmonary infections were cured with metronidazole monotherapy 4
• Another study found metronidazole less effective than clindamycin for treating anaerobic lung abscesses and necrotizing pneumonia 5

Special Populations

• In children with empyema, metronidazole should be considered for older children (mid to late teens) to cover Fusobacterium unless co-amoxiclav or clindamycin are used 1
• For aspiration-related empyema, anaerobic coverage with metronidazole is particularly important 1

Treatment Monitoring

• Antibiotic therapy should be guided by pleural fluid culture results whenever possible 1
• If poor drainage persists despite appropriate antibiotic therapy, imaging should be performed to check chest tube position and look for undrained locules 1
• Surgical consultation should be considered after approximately 7 days in any patient not improving with drainage and antibiotics 1

Emerging Approaches

• In refractory cases, intrapleural metronidazole therapy in conjunction with systemic antibiotics has been reported as a successful salvage therapy 6

In conclusion, metronidazole plays an important role in the treatment of empyema as part of a combination antibiotic regimen providing necessary anaerobic coverage, but should not be used as monotherapy due to its lack of activity against aerobic pathogens.