Is Proteus mirabilis susceptible to nitrofurantoin, and what are the safety considerations for using nitrofurantoin in pregnancy?

Proteus mirabilis Susceptibility to Nitrofurantoin and Pregnancy Considerations

Nitrofurantoin should NOT be used to treat Proteus mirabilis infections, as this organism has intrinsic resistance to nitrofurantoin; however, nitrofurantoin remains safe and effective for treating E. coli UTIs during pregnancy, including the first trimester, with a recommended 7-day course. 1, 2

Proteus mirabilis and Nitrofurantoin Susceptibility

Proteus mirabilis is intrinsically resistant to nitrofurantoin and should never be treated with this agent. The organism accounts for a small percentage of uncomplicated UTIs (typically <10% of cases, with E. coli causing 75-95%), but when present, alternative antibiotics must be selected. 1

Key Microbiologic Considerations:

• Nitrofurantoin does NOT achieve therapeutic concentrations against Proteus species and should be avoided for any suspected or confirmed Proteus infection 2

• The microbial spectrum of uncomplicated UTIs consists mainly of E. coli (75-95%), with occasional Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus 1

• Proteus mirabilis is a urease-producing organism, and persistent growth requires exclusion of stone formation in the urinary tract 1

Nitrofurantoin Use in Pregnancy

First-Line Status for E. coli UTIs:

Nitrofurantoin is recommended as first-line therapy for uncomplicated cystitis caused by susceptible organisms (primarily E. coli) throughout pregnancy, including the first trimester. 1, 2

Dosing and Duration:

• Nitrofurantoin macrocrystals: 50-100 mg four times daily for 7 days (not 5 days as sometimes cited for non-pregnant patients) 1, 2

• Nitrofurantoin monohydrate/macrocrystals: 100 mg twice daily for 7 days 1

• A 7-day regimen is significantly more effective than shorter courses; one randomized trial showed cure rates of 86.2% for 7-day versus 75.7% for 1-day regimens, with lower birth weights and earlier gestational age at delivery in the 1-day group 3

Safety Profile:

• The American College of Obstetricians and Gynecologists (ACOG) explicitly states that nitrofurantoin may be used in the first trimester when appropriate, and should not be withheld when it is the most suitable antibiotic 4, 5

• A retrospective analysis of 91 pregnancies treated with nitrofurantoin macrocrystals showed no evidence of fetal toxicity, with no drug-related abnormal events 6

• During second and third trimesters, nitrofurantoin continues as a first-line agent for UTI treatment and prevention 4, 5

Critical Limitations in Pregnancy:

Nitrofurantoin should NEVER be used for pyelonephritis or upper tract infections during pregnancy, as it does not achieve therapeutic concentrations in the bloodstream. 2

For suspected pyelonephritis in pregnancy:

• Initial parenteral therapy with ceftriaxone (1-2g daily) or cefepime (1-2g twice daily) is recommended 2
• Transition to oral cephalosporin after clinical improvement for completion of 7-14 day course 2

Alternative Antibiotics When Proteus mirabilis is Suspected or Confirmed

First-Line Alternatives for Pregnancy:

• Cephalexin: 500 mg four times daily for 7-14 days - achieves adequate blood and urinary concentrations with excellent safety profile 2

• Cefpodoxime or cefuroxime - appropriate cephalosporin options with 7-14 day courses 2

• Fosfomycin trometamol: 3g single dose - acceptable for uncomplicated lower UTIs, though clinical data for Proteus coverage is more limited 1, 2

• Amoxicillin-clavulanate: 20-40 mg/kg per day in 3 doses - if pathogen is susceptible 2

Antibiotics to AVOID in Pregnancy:

• Trimethoprim/trimethoprim-sulfamethoxazole: contraindicated in first trimester due to teratogenic effects; also contraindicated in last trimester 1, 2

• Fluoroquinolones (ciprofloxacin, levofloxacin): avoid throughout pregnancy due to potential adverse effects on fetal cartilage development 2

Essential Management Algorithm for UTI in Pregnancy

Step 1: Obtain Urine Culture BEFORE Treatment

• Always obtain urine culture before initiating antibiotics to guide therapy 1, 2
• Dipstick testing has only 50% sensitivity for bacteriuria in pregnancy and is unreliable 2
• Optimal screening timing: 12-16 weeks gestation 2

Step 2: Initiate Empiric Therapy Immediately

• Do not wait for culture results if patient is symptomatic 2
• For uncomplicated cystitis with typical E. coli presentation: nitrofurantoin 100 mg twice daily for 7 days 1, 2
• If Proteus suspected (alkaline urine, history of stones, catheter use): use cephalexin instead 2

Step 3: Adjust Based on Culture Results

• If Proteus mirabilis identified, switch from nitrofurantoin to cephalosporin based on susceptibility testing 1, 2
• Continue treatment for full 7-14 day course 2

Step 4: Confirm Cure

• Follow-up urine culture 1-2 weeks after completing treatment to confirm eradication 2
• If symptoms persist or recur within 2 weeks, obtain repeat culture and assume organism is not susceptible to original agent 2

Common Pitfalls to Avoid

• Never use nitrofurantoin for suspected pyelonephritis - it does not achieve adequate blood levels 2

• Do not assume all UTIs in pregnancy are E. coli - obtain culture to identify Proteus and other organisms requiring different antibiotics 1, 2

• Do not use shorter courses (3-5 days) in pregnancy - 7-day minimum is required for adequate cure rates 3

• Do not rely on negative dipstick to rule out UTI in pregnancy - culture is mandatory 2

• Do not repeatedly treat asymptomatic bacteriuria after initial screen-and-treat - this fosters antimicrobial resistance 2