1. Fishing in Canada may be hazardous to your health: A 55 yo man with nausea Christie Seibert, MD September 27, 2006

2. History of Present Illness 55yo man fishing in Canada, snagged his 3 rd finger on a fishing hook. Initially only painful. 55yo man fishing in Canada, snagged his 3 rd finger on a fishing hook. Initially only painful. One week later, started getting red and swollen. One week later, started getting red and swollen. Returned to Madison, went to ER when it started draining pus and looking “angry”. Returned to Madison, went to ER when it started draining pus and looking “angry”.

3. Other History PMH PMH Diabetes (on glargine and asparte insulin, metformin and rosiglitazone. Last HbA1c was 7.5) Diabetes (on glargine and asparte insulin, metformin and rosiglitazone. Last HbA1c was 7.5) HTN (on lotensin) HTN (on lotensin) Hyperlipidemia (on simvastatin) Hyperlipidemia (on simvastatin) GERD GERD SH: Married, home care worker for Hospice, triathlete, non-smoker, no Etoh SH: Married, home care worker for Hospice, triathlete, non-smoker, no Etoh ROS: No F/C, malaise ROS: No F/C, malaise

4. Emergency Room ER doc incised and drained a small abscess on pt’s 3 rd finger. ER doc incised and drained a small abscess on pt’s 3 rd finger. Gave 2g IV Unasyn and 900mg IV Clinda Gave 2g IV Unasyn and 900mg IV Clinda Wound cx: MRSA, sensitive to Clinda Wound cx: MRSA, sensitive to Clinda Sent home w/ oral Augmentin and Clinda. Sent home w/ oral Augmentin and Clinda.

5. 1 st Followup Visit (4 d after ER) Finger still swollen and very painful. Redness is markedly better. No F/C. Finger still swollen and very painful. Redness is markedly better. No F/C. Blood sugars higher (160-180’s) than usual (120-130’s). Blood sugars higher (160-180’s) than usual (120-130’s). Antibiotics extended from planned 7 days to 10 days. Antibiotics extended from planned 7 days to 10 days.

6. 2 nd Followup Visit (7d after ER) Finger still painful and swollen, esp at PIP joint. Sig loss of ROM at PIP joint. Finger still painful and swollen, esp at PIP joint. Sig loss of ROM at PIP joint. Blood sugars: some > 300. Blood sugars: some > 300. Developing malaise, severe nausea and epigastric pain. Developing malaise, severe nausea and epigastric pain. Xray: Sig DJD of PIP and DIP joints of the 3 rd finger. Possible widening of the joint space at the PIP joint. No erosions or active osteo. Xray: Sig DJD of PIP and DIP joints of the 3 rd finger. Possible widening of the joint space at the PIP joint. No erosions or active osteo.

7. Physical Exam Weight 207 (BMI 29) Weight 207 (BMI 29) BP 112/72 BP 112/72 Sclerae icteric, rest of HEENT WNL Sclerae icteric, rest of HEENT WNL CV, Lungs WNL CV, Lungs WNL Liver edge not palpable, no ascites Liver edge not palpable, no ascites Skin: no spider angiomatas or gynecomastia Skin: no spider angiomatas or gynecomastia

8. Testing MRI: Severe focal osteoarthritis of the third PIP joint. No findings of superimposed septic joint, abscess, osteomyelitis, or foreign body are seen. MRI: Severe focal osteoarthritis of the third PIP joint. No findings of superimposed septic joint, abscess, osteomyelitis, or foreign body are seen. Labs: Labs: Alk Phos: 535 Alk Phos: 535 ALT/AST: 401/110 ALT/AST: 401/110 Total Bili: 5.0 Direct Bili: 3.1 Total Bili: 5.0 Direct Bili: 3.1 Nl CBC, lytes, BUN/Cr Nl CBC, lytes, BUN/Cr

9. Differential Diagnosis?

10. Amoxacillin-Clavulanic Acid Hepatotoxicity Learning Objectives Learning Objectives Recognize the possibility of hepatotoxicity from amox-clav acid Recognize the possibility of hepatotoxicity from amox-clav acid Know who might be at highest risk of this adverse reaction Know who might be at highest risk of this adverse reaction Know how to manage amox-clav acid hepatotoxicity Know how to manage amox-clav acid hepatotoxicity

11. Pharmacology 101 Bacteria can produce penicillinases (like B-lactamase) to inhibit penicillin Bacteria can produce penicillinases (like B-lactamase) to inhibit penicillin To combat this, clavulanic acid is added. To combat this, clavulanic acid is added. Produced from Streptomyces organism Produced from Streptomyces organism Has a B-lactam ring like penicillin Has a B-lactam ring like penicillin Acts as “suicide” non-competitive inhibitor, forms inactive complex with B-lactamase Acts as “suicide” non-competitive inhibitor, forms inactive complex with B-lactamase

12. Pharmacology 102 In vivo spectrum of activity: Staph epi, Enterococci, Bacteroides, other anaerobes In vivo spectrum of activity: Staph epi, Enterococci, Bacteroides, other anaerobes Used in bite wounds, otitis media, sinusitis, lower resp tract and cutaneous infections Used in bite wounds, otitis media, sinusitis, lower resp tract and cutaneous infections Clavulanic Acid (clavulanate) is combined Clavulanic Acid (clavulanate) is combined With Amox (Augmentin) With Amox (Augmentin) With Ticarcillin (Timentin) With Ticarcillin (Timentin)

13. Amoxacillin-Clavulanic Acid Hepatotoxicity Rare adverse reaction (1-100/100,000) Rare adverse reaction (1-100/100,000) Clavulanic acid thought to be culprit Clavulanic acid thought to be culprit Usually cholestatic picture Usually cholestatic picture Idiosyncratic/not dose-dependent Idiosyncratic/not dose-dependent Time to onset: average 25 days Time to onset: average 25 days Prognosis good, usually reversible Prognosis good, usually reversible Resolution of jaundice by 1-8 weeks, complete recovery in 4-16 weeks Resolution of jaundice by 1-8 weeks, complete recovery in 4-16 weeks

14. Possible Risk Factors ? Risk in men (2:1 ratio) ? Risk in men (2:1 ratio) ? Risk over age 60 ? Risk over age 60 ? Risk in longer treatment (>10 days) ? Risk in longer treatment (>10 days) ? Risk if previous drug hepatotoxicity ? Risk if previous drug hepatotoxicity Probably not related Probably not related Underlying liver disease Underlying liver disease Co-medication with other hepatotoxic drugs Co-medication with other hepatotoxic drugs

15. Resolution of Case Resolution of Case Possible hepatotoxic meds were stopped Possible hepatotoxic meds were stopped Amox-clav acid Amox-clav acid Rosiglitizone Rosiglitizone Metformin Metformin Simvistatin Simvistatin Hep A, B, C testing negative Hep A, B, C testing negative Abd ultrasound negative Abd ultrasound negative LFTs peaked with TB at 6-7 range, then resolved over 3 weeks. LFTs peaked with TB at 6-7 range, then resolved over 3 weeks.

16. Bibliography Zaidi SA. Hepatitis associated with Amoxacillin/Clavulanic Acid and/or Ciprofloxacin. Amer J Med Sci 2003; 325(1): 31-3. Zaidi SA. Hepatitis associated with Amoxacillin/Clavulanic Acid and/or Ciprofloxacin. Amer J Med Sci 2003; 325(1): 31-3. Dowsett JF et al. Amoxicillin/Clavulanic Acid Induced Intrahepatic Cholestatis. Dig Dis Sci 1989;34(8):1290-3. Dowsett JF et al. Amoxicillin/Clavulanic Acid Induced Intrahepatic Cholestatis. Dig Dis Sci 1989;34(8):1290-3. Gresser U. Amoxacillin-clavulanic acid therapy may be associated with severe side effects—a review of the literature. Eur J Med Res 2001; 6(4): 139-49. Gresser U. Amoxacillin-clavulanic acid therapy may be associated with severe side effects—a review of the literature. Eur J Med Res 2001; 6(4): 139-49.