What is the next appropriate treatment for a male patient with hemiparesis after cerebrovascular accident (CVA) and stage 4 chronic kidney disease (CKD) who has failed Levaquin (levofloxacin) treatment for a urinary tract infection (UTI) caused by Escherichia coli (E. coli) and Klebsiella pneumoniae?

Treatment for Complex UTI in a Male with Hemiparesis, CKD Stage 4, and Levaquin Failure

For a complex UTI caused by E. coli and Klebsiella pneumoniae in a male patient with hemiparesis and stage 4 CKD who failed levofloxacin therapy, ceftazidime-avibactam (2.5g IV q8h with renal dose adjustment) is the recommended treatment option.

Patient Considerations

This case involves several critical factors that influence antibiotic selection:

• Complex UTI: Male gender, neurological impairment (hemiparesis post-CVA), and stage 4 CKD all classify this as a complicated UTI
• Failed fluoroquinolone therapy: Levofloxacin failure suggests possible resistance
• Pathogens: E. coli and Klebsiella pneumoniae, both potentially resistant organisms
• Renal impairment: Stage 4 CKD requires dose adjustment for many antibiotics

Treatment Algorithm

First-line Option:

• Ceftazidime-avibactam (with renal dose adjustment based on creatinine clearance)
  • Highly effective against resistant Enterobacterales including E. coli and Klebsiella 1
  • Recommended for complicated UTIs caused by carbapenem-resistant Enterobacterales (CRE) 1
  • Requires dose adjustment in renal impairment

Alternative Options (in order of preference):

1. Meropenem-vaborbactam (4g IV q8h with renal dose adjustment)

   • Recommended for complicated UTIs caused by resistant gram-negative organisms 1
   • Effective against KPC-producing Enterobacterales

2. Imipenem-cilastatin-relebactam (1.25g IV q6h with renal dose adjustment)

   • Active against most KPC-producing CRE strains 1
   • Requires careful dose adjustment in CKD stage 4

3. Plazomicin (15 mg/kg IV q24-48h with renal dose adjustment)

   • Aminoglycoside with activity against many resistant gram-negative organisms 1
   • Requires therapeutic drug monitoring in renal impairment

Dosing Considerations in CKD Stage 4

• Ceftazidime-avibactam: Reduce dose to 0.94g IV q12h for CrCl 15-30 mL/min
• Meropenem-vaborbactam: Reduce dose to 2g IV q12h for CrCl 15-30 mL/min
• Imipenem-cilastatin-relebactam: Reduce dose to 0.625g IV q12h for CrCl 15-30 mL/min
• Plazomicin: Extend interval to q48h and consider therapeutic drug monitoring

Treatment Duration

• 14-day course is recommended for complicated UTIs in males 2
• Extended therapy may be needed if there is concern for concurrent prostatitis

Additional Management Considerations

• Obtain repeat cultures during and after therapy to ensure clearance
• Remove or change any indwelling catheter if present before collecting cultures 2
• Assess for urinary retention which is common in patients with neurological impairment
• Monitor renal function closely during antibiotic therapy
• Evaluate for anatomical abnormalities that may contribute to infection persistence

Rationale for Recommendation

Ceftazidime-avibactam is preferred because:

1. It has demonstrated efficacy against resistant Enterobacterales including E. coli and Klebsiella pneumoniae 1
2. It can be safely used in patients with renal impairment with appropriate dose adjustment 2
3. It provides coverage for potential extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing organisms that may be present after fluoroquinolone failure 1
4. Recent guidelines recommend it for complicated UTIs caused by resistant gram-negative organisms 1

Cautions and Pitfalls

• Avoid fluoroquinolones as the patient has already failed levofloxacin therapy
• Avoid nitrofurantoin in CKD stage 4 due to reduced efficacy and increased toxicity risk
• Monitor for superinfection with resistant organisms during extended antibiotic therapy
• Be aware of potential drug interactions with the patient's other medications for stroke and CKD
• Consider infectious disease consultation given the complexity of the case and potential for multidrug resistance

Patients with neurological impairment after stroke are at higher risk for UTIs and may have atypical presentations 1. The combination of hemiparesis and CKD increases the risk of treatment failure and recurrent infections 3, necessitating careful antibiotic selection and monitoring.