Is Nitrofurantoin (Macrobid) 100mg for 5 days effective for Proteus mirabilis urinary tract infection (UTI) with greater than 100,000 CFU/mL?

Nitrofurantoin Should NOT Be Used for Proteus mirabilis UTI

Do not prescribe nitrofurantoin 100 mg for 5 days for this Proteus mirabilis UTI—Proteus species are intrinsically resistant to nitrofurantoin, making this treatment ineffective and potentially harmful by delaying appropriate therapy. 1, 2

Why Nitrofurantoin Fails Against Proteus mirabilis

Intrinsic Resistance Pattern

• Proteus mirabilis demonstrates extremely high resistance rates to nitrofurantoin, with only 3.2% susceptibility documented in clinical isolates from UTI patients 1
• The Proteeae group (Proteus species, Morganella morganii, and Providencia species) is generally resistant to nitrofurantoin due to urease production that alkalinizes urine 2
• At alkaline urine pH (which Proteus creates), nitrofurantoin resistance increases dramatically—at pH 8-9, only 66.1% of all bacteriuria is sensitive to nitrofurantoin, dropping to 54.6% at pH ≥9 2

Clinical Implications

• Nitrofurantoin resistance in Proteus is an indicator of extensive drug resistance (XDR) phenotype, with 51% of nitrofurantoin-resistant Enterobacteriaceae exhibiting XDR characteristics 3
• The guidelines supporting nitrofurantoin for uncomplicated UTI (100 mg twice daily for 5 days) 4, 5 apply to susceptible organisms—primarily E. coli—not to Proteus species 4

Recommended Alternative Antibiotics for Proteus mirabilis UTI

First-Line Options (Based on Susceptibility Data)

• Ceftriaxone: 96.8% susceptibility rate—highest among tested antibiotics for Proteus mirabilis 1
• Norfloxacin or Ciprofloxacin: 82.5% and 69.8% susceptibility rates respectively 1
• Gentamicin: 71.4% susceptibility rate 1

Treatment Algorithm

1. Immediately obtain formal antibiotic susceptibility testing from the culture that identified this Proteus mirabilis
2. Empirically treat with ceftriaxone or a fluoroquinolone (if no contraindications) while awaiting susceptibilities 1
3. Avoid nitrofurantoin, ampicillin (36.5% susceptibility), and sulfamethoxazole (39.7% susceptibility) as empiric choices 1
4. Treat for 7 days minimum for uncomplicated UTI with Proteus, as this organism has higher virulence potential than E. coli 1

Critical Pitfalls to Avoid

• Never assume nitrofurantoin will work for Proteus despite it being guideline-recommended for uncomplicated UTI—those guidelines specifically apply to susceptible organisms 4, 5
• Alkaline urine pH (≥8) on urinalysis is a red flag predicting nitrofurantoin resistance and suggesting Proteus infection 2
• Do not use nitrofurantoin for any suspected pyelonephritis, as it achieves inadequate tissue concentrations 5
• Check renal function—nitrofurantoin is contraindicated if creatinine clearance <60 mL/min 6