Which common urinary‑tract infection bacterial species are resistant to nitrofurantoin (Macrobid)?

Bacterial Strains Commonly Resistant to Nitrofurantoin (Macrobid)

Nitrofurantoin maintains excellent activity against most common UTI pathogens, but Proteus species, Pseudomonas aeruginosa, Klebsiella species, Serratia species, and Enterobacter species demonstrate intrinsic or high rates of resistance and should not be treated with this agent.

Organisms with Intrinsic or High Resistance

Proteus Species

• Proteus mirabilis is intrinsically resistant to nitrofurantoin and should never be treated with this agent, despite being a common uropathogen accounting for 4-5% of uncomplicated UTIs 1, 2.
• Proteus species lack the bacterial nitroreductases necessary to activate nitrofurantoin, making resistance a class effect 3.

Pseudomonas aeruginosa

• Pseudomonas aeruginosa demonstrates intrinsic resistance to nitrofurantoin with MIC90 values consistently >16 mg/L, well above susceptibility breakpoints 3.
• P. aeruginosa accounts for 2.9-10.2% of UTI isolates, particularly in complicated and healthcare-associated infections 1, 2.

Klebsiella Species

• Klebsiella pneumoniae shows variable but concerning resistance rates to nitrofurantoin, with 14.3% overall resistance in North American outpatient isolates 2.
• K. pneumoniae is the second most common uropathogen (12.4-32.2% of UTIs) and frequently produces ESBL enzymes 1, 4.
• ESBL-producing Klebsiella demonstrates two-fold higher MIC90 values for nitrofurantoin compared to non-ESBL strains 3.

Serratia and Enterobacter Species

• Serratia species and Enterobacter species are commonly resistant to nitrofurantoin and are specifically mentioned as problematic organisms in complicated UTIs 1.
• These organisms represent 1.9-2.7% of UTI isolates but are more prevalent in healthcare-associated and catheter-associated infections 1, 2.

Organisms with Excellent Susceptibility

Escherichia coli

• E. coli maintains exceptional susceptibility to nitrofurantoin with only 1.1% resistance in the largest North American surveillance study 2.
• This holds true even for ESBL-producing E. coli strains, making nitrofurantoin a preferred agent 1, 4.
• E. coli accounts for 57.5-87% of all UTIs, making nitrofurantoin highly effective for empiric therapy 1, 5.

Staphylococcus saprophyticus

• S. saprophyticus remains highly susceptible to nitrofurantoin with MIC90 values ≤16 mg/L 3.
• This organism causes 1.2% of UTIs, primarily in young women 2.

Enterococcus Species

• Enterococcus faecalis demonstrates good susceptibility to nitrofurantoin and is specifically recommended for uncomplicated VRE UTIs at 100 mg PO every 6 hours 1.
• Enterococcus species account for 4.7-6.6% of UTI isolates 1, 2.

Clinical Decision Algorithm

When considering nitrofurantoin for UTI treatment:

1. Obtain urine culture before initiating therapy to identify resistant organisms 6.

2. Avoid nitrofurantoin empirically if:

   • Male patient (higher risk of Proteus species) 1
   • Complicated UTI with structural abnormalities (increased Pseudomonas, Serratia risk) 1
   • Healthcare-associated or catheter-associated UTI (broader resistant spectrum) 1
   • Known ESBL-producing Klebsiella colonization 6

3. Nitrofurantoin is appropriate for:

   • Uncomplicated cystitis in women 1
   • E. coli UTI (confirmed or suspected) 1, 2
   • VRE uncomplicated cystitis 1

4. Switch from nitrofurantoin if culture grows:

   • Any Proteus species 1, 3
   • Pseudomonas aeruginosa 1, 3
   • Serratia or Enterobacter species 1
   • Klebsiella with documented nitrofurantoin resistance 2

Critical Pitfalls to Avoid

• Never use nitrofurantoin for pyelonephritis or upper tract infections, as it does not achieve adequate tissue concentrations despite urinary activity 1.
• Do not use nitrofurantoin for complicated UTIs where Proteus, Pseudomonas, or resistant Klebsiella are more prevalent 1.
• Avoid in patients with creatinine clearance <30 mL/min, as inadequate urinary concentrations result in treatment failure 1.
• Geographic resistance patterns matter less for nitrofurantoin than other agents, as it maintains activity even in high-resistance areas 1.