What are the treatment options for a urinary tract infection caused by Proteus mirabilis with resistance to Macrobid (Nitrofurantoin), Cipro (Ciprofloxacin), and Levaquin (Levofloxacin)?

Treatment Options for Proteus mirabilis UTI with Resistance to Macrobid, Cipro, and Levaquin

For a urinary tract infection caused by Proteus mirabilis with resistance to nitrofurantoin, ciprofloxacin, and levofloxacin, aminoglycosides (gentamicin or amikacin) are the recommended first-line treatment options. 1

First-Line Treatment Options

• Aminoglycosides are recommended as effective treatment for complicated UTIs caused by multidrug-resistant organisms, including resistant Proteus mirabilis 1

  • Gentamicin: 5-7 mg/kg/day IV once daily 1
  • Amikacin: 15 mg/kg/day IV once daily 1
  • Single-dose aminoglycoside therapy can be effective for simple cystitis due to resistant organisms 1

• Cephalosporins (if susceptible):

  • Ceftriaxone: 1-2 g IV once daily 1
  • Cefotaxime: 2 g IV three times daily 1
  • Cefepime: 1-2 g IV twice daily 1

Alternative Treatment Options

• For complicated UTIs with multidrug resistance, consider newer beta-lactam/beta-lactamase inhibitor combinations: 1

  • Ceftazidime-avibactam: 2.5 g IV every 8 hours 1
  • Meropenem-vaborbactam: 4 g IV every 8 hours 1
  • Imipenem-cilastatin-relebactam: 1.25 g IV every 6 hours 1

• For severe infections or when other options are limited: 1

  • Piperacillin-tazobactam: 2.5-4.5 g IV three times daily 1
  • Plazomicin: 15 mg/kg IV every 12 hours 1

Treatment Duration

• Uncomplicated lower UTI: 3-7 days 1
• Complicated UTI: 5-7 days (may be extended based on clinical response) 1
• Pyelonephritis: 7-14 days 1

Important Clinical Considerations

• Proteus mirabilis has intrinsic resistance to nitrofurantoin (Macrobid), which explains the resistance observed 2, 3
• Infectious disease consultation is highly recommended for management of infections caused by multidrug-resistant organisms 1
• Urine culture and susceptibility testing are essential to guide definitive therapy 1
• Proteus mirabilis can form urinary stones due to its urease activity, which may complicate treatment and require longer therapy 4
• Consider imaging studies to rule out urinary obstruction or anatomical abnormalities if clinical response is inadequate 1

Monitoring and Follow-up

• Monitor renal function when using aminoglycosides 1
• Follow-up urine culture may be necessary to confirm eradication, especially in complicated cases 1
• Assess for symptom resolution within 48-72 hours of initiating therapy 1
• Consider alternative diagnoses or complications if fever persists beyond 72 hours of appropriate therapy 1

Antibiotic Resistance Patterns

• Proteus mirabilis commonly develops plasmid-mediated resistance to multiple antibiotics 5
• Resistance rates to fluoroquinolones (ciprofloxacin, levofloxacin) have been increasing globally 3, 6
• Carbapenems generally maintain good activity against Proteus mirabilis, with low resistance rates reported 6