How should a patient with an intra-abdominal infection of unknown origin, increasing International Normalized Ratio (INR) and adenocarcinoma of the appendix be treated after 3 days of intravenous (IV) Tigecycline (generic name), without Warfarin for 7 days?

Management of Intra-Abdominal Infection with Increasing INR and Appendiceal Adenocarcinoma

For a patient with intra-abdominal infection of unknown origin, increasing INR despite no Warfarin for 7 days, and adenocarcinoma of the appendix who has received 3 days of IV Tigecycline, treatment should be switched to ceftazidime/avibactam 2.5g IV q8h plus metronidazole 500mg IV q6h with urgent source control.

Assessment of Current Situation

The patient presents with several concerning features:

• Intra-abdominal infection of unknown origin
• 3 days of IV Tigecycline therapy already administered
• Increasing INR despite no Warfarin for 7 days (suggesting liver dysfunction or coagulopathy)
• Underlying adenocarcinoma of the appendix

Evaluation of Current Therapy

Tigecycline has been used for 3 days with apparent treatment failure as evidenced by:

• Persistent infection
• Worsening coagulopathy (increasing INR)

Tigecycline can be effective for complicated intra-abdominal infections (cIAI) 1, but the increasing INR is concerning as it may be related to:

1. Progression of infection despite antibiotic therapy
2. Possible liver dysfunction (which can be exacerbated by Tigecycline)
3. Underlying malignancy causing coagulopathy

Recommended Treatment Plan

1. Antimicrobial Therapy

First-line recommendation:

• Switch to ceftazidime/avibactam 2.5g IV q8h plus metronidazole 500mg IV q6h 2

Alternative options (if first-line unavailable):

• Imipenem/cilastatin/relebactam 1.25g IV q6h 2
• Meropenem 1g IV q8h by extended infusion 2

The rationale for this change:

• The World Society of Emergency Surgery guidelines recommend ceftazidime/avibactam plus metronidazole for complicated intra-abdominal infections 2
• These regimens provide broader coverage against potential resistant organisms that may be causing treatment failure 2
• The increasing INR despite no Warfarin suggests possible liver dysfunction, which may be worsened by Tigecycline

2. Source Control

Urgent surgical intervention is essential and should include:

• Diagnostic laparoscopy/laparotomy to identify and control the source of infection
• Drainage of any collections/abscesses
• Debridement of necrotic tissue
• Possible resection of involved bowel segments

Source control is the cornerstone of treatment for intra-abdominal infections and should not be delayed 2.

3. Management of Coagulopathy

• Administer vitamin K 10mg IV once daily
• Consider fresh frozen plasma (FFP) if INR >1.5 and patient requires urgent surgical intervention
• Monitor INR daily

4. Duration of Therapy

• 5-7 days of antimicrobial therapy after adequate source control 2
• Treatment duration should be individualized based on:
  • Adequacy of source control
  • Clinical response
  • Underlying comorbidities (including malignancy)

Special Considerations

Malignancy

The presence of appendiceal adenocarcinoma complicates management:

• Higher risk of treatment failure
• Possible immunosuppression
• Increased risk of resistant organisms
• Potential for malignancy-related coagulopathy

Potential Pathogens

Consider coverage for:

• Enterobacteriaceae (including potential ESBL-producers)
• Anaerobes
• Enterococci (in this high-risk patient with malignancy)
• Potential drug-resistant organisms due to prior antibiotic exposure

Monitoring and Follow-up

• Daily clinical assessment
• Daily INR monitoring
• Regular inflammatory markers (CRP, WBC)
• Repeat imaging if clinical improvement is not observed within 48-72 hours

Common Pitfalls to Avoid

1. Inadequate source control - This is the most common reason for treatment failure in intra-abdominal infections 2
2. Insufficient spectrum of antimicrobial coverage - Consider resistant organisms in a patient with malignancy and prior antibiotic exposure
3. Prolonged antibiotic therapy without source control - Antibiotics alone are unlikely to resolve the infection without adequate drainage/debridement
4. Failure to investigate worsening coagulopathy - The increasing INR may indicate liver dysfunction, DIC, or other serious complications requiring specific management

By implementing this comprehensive approach with appropriate antimicrobial therapy and urgent source control, the patient's intra-abdominal infection can be effectively managed while addressing the concerning coagulopathy and underlying malignancy.