How to manage a patient with a urinary tract infection (UTI) who is clinically improving on nitrofurantoin but has a culture indicating the presence of Proteus?

Management of UTI with Proteus Species While on Nitrofurantoin

For a patient with a urinary tract infection who is clinically improving on nitrofurantoin but has a urine culture showing Proteus species, the antibiotic should be changed to a more appropriate agent such as trimethoprim-sulfamethoxazole or ciprofloxacin, as Proteus species are intrinsically resistant to nitrofurantoin. 1, 2

Why Nitrofurantoin Is Ineffective Against Proteus

• Proteus species are intrinsically resistant to nitrofurantoin, making it an inappropriate choice regardless of clinical improvement 1
• Proteus produces urease, which alkalinizes the urine (pH ≥8), further reducing nitrofurantoin's effectiveness 2, 3
• Studies show that at urine pH 8-9, only 66.1% of urinary isolates remain sensitive to nitrofurantoin, dropping to 54.6% at pH 9 2
• Alkaline urine in the emergency department is a predictor of nitrofurantoin resistance 2

Recommended Alternative Treatment Options

First-line options:

• Trimethoprim-sulfamethoxazole: 160/800 mg twice daily for 3 days (uncomplicated cystitis) or 14 days (pyelonephritis) 4, 5
• Ciprofloxacin: 500 mg twice daily for 7 days 4, 6

Alternative options:

• Cephalosporins (e.g., cefpodoxime 200 mg twice daily for 10 days) 4
• Aminoglycosides (e.g., gentamicin) for more severe infections 4, 7

Clinical Decision Algorithm

1. Confirm Proteus infection: Verify that Proteus is the causative organism from culture results 4
2. Assess clinical status:
   • If improving but still symptomatic: Change to appropriate antibiotic immediately 4, 1
   • If completely asymptomatic: Still change antibiotic to prevent relapse, as clinical improvement may be temporary despite inappropriate therapy 1
3. Check for complications:
   • Assess for urinary pH (alkaline urine suggests Proteus) 2
   • Consider imaging if there are risk factors for stone formation, as Proteus can promote struvite stones 4, 3
4. Select appropriate antibiotic based on susceptibility testing 4
5. Complete appropriate duration of therapy based on infection severity 4

Important Considerations

• Proteus species (including P. mirabilis and P. vulgaris) account for approximately 18% of UTIs, with higher prevalence in catheterized patients 7
• Proteus UTIs are associated with a higher risk of stone formation due to urease production and urine alkalinization 3
• Gentamicin and nalidixic acid show >92% sensitivity against Proteus isolates in some studies 7
• Fluoroquinolones and cephalosporins are the only antimicrobials recommended for oral empiric treatment of upper UTIs, while nitrofurantoin should be avoided due to insufficient efficacy data 4

Pitfalls to Avoid

• Don't continue nitrofurantoin despite clinical improvement: Clinical improvement may be temporary or incomplete, and continuing an ineffective antibiotic can lead to treatment failure or recurrence 1, 2
• Don't ignore alkaline urine: pH ≥8 strongly suggests Proteus infection and predicts nitrofurantoin resistance 2
• Don't overlook the risk of stone formation: Proteus infections can lead to struvite stones due to urease activity 3
• Don't forget to assess for complicated UTI: Proteus infections are more common in patients with structural abnormalities or indwelling catheters 4, 7

By promptly changing to an appropriate antibiotic based on culture results, you can ensure complete eradication of the infection and prevent complications associated with Proteus UTIs.