What are the management steps for an adult patient with a history of rhinosinusitis and elevated Serum Glutamic-Pyruvic Transaminase (SGPT) while on antibiotics, such as amoxicillin-clavulanate?

Evaluation of Elevated SGPT in a Patient on Amoxicillin-Clavulanate for Rhinosinusitis

Immediate Action: Stop Amoxicillin-Clavulanate

Stop amoxicillin-clavulanate immediately if SGPT (ALT) elevation is detected, as this antibiotic combination is a well-recognized hepatotoxin that can cause drug-induced liver injury. 1

The clavulanate component is particularly hepatotoxic and can cause cholestatic hepatitis, typically presenting 1-6 weeks after initiation of therapy. 1

Assess the Severity of Liver Injury

Obtain Complete Hepatic Panel

• Measure ALT, AST, alkaline phosphatase, total and direct bilirubin, and INR/PT 2
• If ALT is >3 times the upper limit of normal, discontinue all potentially hepatotoxic medications immediately 2
• Check for signs of hepatic synthetic dysfunction (prolonged INR, hypoalbuminemia) that would indicate more severe injury 2

Determine the Pattern of Injury

• Hepatocellular pattern: ALT/AST elevation predominates (>5x upper limit of normal with alkaline phosphatase <2x upper limit) 2
• Cholestatic pattern: Alkaline phosphatase elevation predominates with modest transaminase elevation—this is the typical pattern for amoxicillin-clavulanate hepatotoxicity 1
• Mixed pattern: Both transaminases and alkaline phosphatase elevated 2

Rule Out Alternative Causes of Elevated Transaminases

Before attributing liver injury solely to amoxicillin-clavulanate, exclude:

• Viral hepatitis (check hepatitis A, B, C serologies) 2
• Autoimmune hepatitis (ANA, anti-smooth muscle antibody) 2
• Alcohol use (obtain detailed history) 2
• Other medications or supplements the patient may be taking 2
• Biliary obstruction (right upper quadrant ultrasound if cholestatic pattern) 2

Management Based on Severity

Mild Elevation (ALT 1-3x Upper Limit of Normal)

• Discontinue amoxicillin-clavulanate 1, 2
• Monitor liver enzymes weekly until normalization 2
• Do not rechallenge with amoxicillin-clavulanate, as recurrence of hepatotoxicity is common and can be more severe 1

Moderate to Severe Elevation (ALT >3x Upper Limit of Normal)

• Discontinue amoxicillin-clavulanate immediately 2
• Monitor liver enzymes twice weekly initially, then weekly until normalization 2
• Consider hepatology consultation if ALT >5x upper limit of normal or if bilirubin is elevated 2
• Never rechallenge with amoxicillin-clavulanate 1, 2

Fulminant Hepatic Failure (INR >1.5, Encephalopathy, or Rapidly Rising Bilirubin)

• Immediate hospitalization and hepatology consultation 2
• Consider transfer to a liver transplant center 2

Alternative Antibiotic Selection for Ongoing Rhinosinusitis

Since amoxicillin-clavulanate must be discontinued, select an alternative based on the clinical scenario:

For Mild to Moderate Rhinosinusitis Without Recent Antibiotic Exposure

• Amoxicillin alone 500 mg three times daily or 875 mg twice daily for 5-7 days 3, 4, 5
• Amoxicillin lacks the hepatotoxic clavulanate component and provides adequate coverage for Streptococcus pneumoniae 3, 5

For Patients with Risk Factors for Resistant Organisms

Risk factors include: recent antibiotic use (past 4-6 weeks), age >65, moderate-to-severe disease, immunocompromised state, or high local resistance rates 3, 4

Use a respiratory fluoroquinolone:

• Levofloxacin 500 mg once daily for 5-7 days 3, 4, 6
• Moxifloxacin 400 mg once daily for 5-7 days 3, 4, 6
• These provide 90-92% predicted clinical efficacy without hepatotoxic risk comparable to amoxicillin-clavulanate 3, 4

For Penicillin-Allergic Patients

• Doxycycline 100 mg once daily for 10 days (acceptable alternative with 20-25% failure rate) 3, 6
• Respiratory fluoroquinolones (levofloxacin or moxifloxacin) as above 3, 6
• Avoid azithromycin and clarithromycin due to 20-25% resistance rates 3, 6

Monitoring After Antibiotic Switch

• Recheck liver enzymes 1 week after discontinuing amoxicillin-clavulanate 2
• Continue monitoring every 1-2 weeks until complete normalization 2
• Most drug-induced liver injury from amoxicillin-clavulanate resolves within 2-8 weeks after discontinuation 1

Adjunctive Therapies to Continue

Regardless of antibiotic choice, optimize symptomatic management:

• Intranasal corticosteroids (mometasone, fluticasone, or budesonide twice daily) to reduce mucosal inflammation 3, 6
• Saline nasal irrigation for symptomatic relief 3, 6
• Analgesics (acetaminophen or NSAIDs) for pain—use acetaminophen cautiously if significant hepatic impairment 6

Critical Pitfalls to Avoid

• Never rechallenge with amoxicillin-clavulanate after documented hepatotoxicity, as recurrence is common and can be more severe 1, 2
• Do not continue amoxicillin-clavulanate while "monitoring" liver enzymes if ALT is already elevated—stop immediately 2
• Do not assume all penicillins are contraindicated; amoxicillin alone (without clavulanate) does not carry the same hepatotoxic risk 3, 5
• Avoid using first-generation cephalosporins (cephalexin) as alternatives, as they provide inadequate coverage for Haemophilus influenzae 6

Documentation and Future Prevention

• Document amoxicillin-clavulanate as causing drug-induced liver injury in the patient's medical record 1
• Add amoxicillin-clavulanate to the patient's allergy list with the specific reaction noted as "hepatotoxicity" 1
• Counsel the patient to avoid amoxicillin-clavulanate in the future and inform all healthcare providers of this adverse reaction 1