A patient with an uncomplicated urinary tract infection developed a rash after starting nitrofurantoin (Macrobid); what alternative antibiotic should be prescribed?

Alternative Antibiotic for Uncomplicated UTI After Nitrofurantoin Rash

Switch to fosfomycin 3 g as a single oral dose, which is the preferred alternative first-line agent when nitrofurantoin cannot be used due to allergy or adverse reaction. 1

First-Line Alternative: Fosfomycin

• Fosfomycin trometamol 3 g single dose is recommended by the IDSA and ESCMID as an alternative first-line option when nitrofurantoin is contraindicated, with a clinical cure rate of approximately 63-74% 1
• This agent is classified as an "Access" antibiotic by the WHO AWaRe framework, reflecting its favorable resistance profile and minimal collateral damage to normal flora 1
• Fosfomycin may be taken with or without food and should always be mixed with water before ingesting—never taken in dry form 2
• The single-dose regimen offers excellent compliance and avoids the need for multi-day therapy in a patient who has already experienced an adverse reaction 1

Second-Line Alternative: Trimethoprim-Sulfamethoxazole (Bactrim)

• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is an acceptable alternative only if local E. coli resistance rates are <20% and the patient has not received this agent in the previous 3 months 3, 1
• Clinical cure rates with Bactrim are approximately 90% when resistance patterns permit its use 1
• Critical pitfall to avoid: Do not prescribe Bactrim empirically without knowing your local antibiogram; treatment failure rates become unacceptably high when community resistance exceeds 20% 1

Agents to Reserve or Avoid

• Fluoroquinolones (ciprofloxacin, levofloxacin) should be reserved for pyelonephritis or complicated UTIs due to FDA safety warnings (tendon rupture, peripheral neuropathy, aortic dissection) and rising community resistance rates of approximately 24% 1
• The IDSA explicitly states that fluoroquinolones "should be reserved for important uses other than acute cystitis" because of collateral damage to normal flora and acceleration of antimicrobial resistance 1
• Beta-lactam agents (cephalosporins, amoxicillin-clavulanate) demonstrate inferior efficacy compared to nitrofurantoin and fosfomycin for uncomplicated cystitis and should be used only when first-line agents are unsuitable 1
• Amoxicillin or ampicillin alone should never be used empirically due to globally high resistance prevalence 1

Clinical Decision Algorithm

1. Confirm uncomplicated lower UTI: Symptoms limited to dysuria, urgency, frequency, or suprapubic discomfort without fever >38°C, flank pain, nausea/vomiting, or costovertebral angle tenderness 1
2. Document nitrofurantoin allergy/reaction in the patient's chart to prevent future exposure 4
3. Prescribe fosfomycin 3 g single dose as the preferred alternative 1
4. If fosfomycin is unavailable or unsuitable: Use Bactrim 160/800 mg twice daily for 3 days only if local resistance <20% and no recent use 3, 1
5. Obtain urine culture with susceptibility testing if symptoms persist after therapy or recur within 2 weeks 1

Important Contraindications to Verify

• Do not use fosfomycin or any oral agent if upper-tract infection is suspected (fever, flank pain, systemic symptoms); these patients require fluoroquinolones or parenteral cephalosporins 1
• Verify renal function before prescribing any alternative; some agents have renal dosing adjustments 1
• Avoid treating asymptomatic bacteriuria—antibiotics should not be prescribed for positive urine cultures in asymptomatic patients 3, 1

Common Pitfalls

• Do not reflexively prescribe ciprofloxacin for simple cystitis just because the patient cannot take nitrofurantoin; this contributes to rising resistance and exposes the patient to serious adverse effects 1
• Do not extend antibiotic duration beyond what is recommended; fosfomycin is a single dose, and Bactrim should not exceed 3 days for uncomplicated cystitis 3, 1
• Routine post-treatment urine cultures are unnecessary for asymptomatic patients; obtain cultures only if symptoms persist or recur 1