Is Augmentin (amoxicillin/clavulanate) suitable for a patient with E. coli pyelonephritis refractory to Keflex (cephalexin) who has Chronic Kidney Disease (CKD) and Polycystic Kidney Disease (PKD) and is on Jynarque (tolvaptan)?

Augmentin for E. coli Pyelonephritis in CKD with Polycystic Kidney Disease

Augmentin (amoxicillin-clavulanate) is an appropriate choice for E. coli pyelonephritis refractory to Keflex in a patient with CKD and polycystic kidney disease on Jynarque, provided susceptibility is confirmed. 1

Rationale for Augmentin Use

Augmentin offers several advantages in this clinical scenario:

1. Efficacy against resistant organisms: Amoxicillin-clavulanate is effective against many beta-lactamase-producing E. coli strains that may be resistant to first-line agents like Keflex (cephalexin) 2

2. Appropriate for non-severe infections: For patients with low-risk, non-severe infections due to third-generation cephalosporin-resistant Enterobacterales (which includes many E. coli strains), guidelines suggest amoxicillin-clavulanate as a suitable option 3

3. Standard dosing in moderate CKD: Amoxicillin-clavulanate 500mg/125mg twice daily is suitable for UTI treatment in CKD stage II when susceptibility is confirmed 1

Considerations for This Patient Population

CKD and Polycystic Kidney Disease Factors:

• Patients with CKD require careful antibiotic selection and potentially dose adjustment based on creatinine clearance
• Standard dosing of amoxicillin-clavulanate is appropriate for creatinine clearance ≥50 mL/min 1
• For lower creatinine clearance, dose adjustment may be necessary:
  • CrCl 10-30 mL/min: 500/125 mg every 12 hours
  • CrCl <10 mL/min: 500/125 mg every 24 hours

Jynarque (Tolvaptan) Considerations:

• Tolvaptan is a vasopressin V2 receptor antagonist used to slow ADPKD progression 4
• No significant drug interactions between tolvaptan and amoxicillin-clavulanate have been reported
• Both medications can be hepatotoxic, so liver function should be monitored 4, 5

Treatment Algorithm

1. Confirm susceptibility: Ensure E. coli is susceptible to amoxicillin-clavulanate before initiating therapy

2. Assess infection severity:

   • If severe infection/sepsis: Consider carbapenem (imipenem or meropenem) 3
   • If non-severe infection: Proceed with amoxicillin-clavulanate 3, 1

3. Determine appropriate dosing based on renal function:

   • CrCl ≥50 mL/min: Standard dosing (500/125 mg twice daily)
   • CrCl 10-30 mL/min: 500/125 mg every 12 hours
   • CrCl <10 mL/min: 500/125 mg every 24 hours

4. Duration of therapy:

   • 7-14 days for complicated UTI/pyelonephritis 1

5. Monitoring:

   • Assess clinical response within 48-72 hours 1
   • Monitor renal function
   • Monitor liver function due to potential hepatotoxicity risk with both medications

Alternative Options

If Augmentin is not appropriate or the patient fails to respond:

1. Carbapenems: For severe infections, a carbapenem (imipenem or meropenem) is recommended as targeted therapy 3

2. Fosfomycin: IV fosfomycin is recommended for complicated UTIs in patients without septic shock 3, 1

3. Aminoglycosides: For complicated UTIs without septic shock, aminoglycosides can be used for short durations when active in vitro 3, 1

Pitfalls and Caveats

1. Hepatotoxicity risk: Both amoxicillin-clavulanate and tolvaptan can cause liver injury. Monitor liver function tests regularly.

2. Resistance patterns: Local resistance patterns should be considered when selecting empiric therapy.

3. Avoid fluoroquinolones: Despite their efficacy, fluoroquinolones should be avoided as first-line therapy in elderly patients with CKD due to adverse effects and increasing resistance rates 1, 6

4. Avoid tigecycline: Guidelines strongly recommend against using tigecycline for infections caused by third-generation cephalosporin-resistant Enterobacterales 3

5. Adjust therapy based on culture: Always adjust therapy based on culture and sensitivity results when available 1