What is the best first‑line antibiotic for a 75‑year‑old woman with an uncomplicated urinary tract infection, assuming an estimated glomerular filtration rate ≥30 mL/min and no sulfa allergy, severe hepatic disease, or contraindicating drug interactions?

First-Line Antibiotic for Uncomplicated UTI in Women Over 75

Nitrofurantoin 100 mg orally twice daily for 5 days is the preferred first-line antibiotic for a 75-year-old woman with uncomplicated cystitis and normal renal function (eGFR ≥30 mL/min). 1, 2

Rationale for Nitrofurantoin as First Choice

• Nitrofurantoin achieves 93% clinical cure and 88% microbiological eradication rates in women with uncomplicated cystitis, matching or exceeding other first-line agents. 3, 2
• Despite over 60 years of use, nitrofurantoin retains excellent activity against E. coli (the causative organism in 75-95% of uncomplicated UTIs) with resistance rates remaining <1% worldwide. 1, 4, 5
• The drug causes minimal disruption to intestinal flora compared to fluoroquinolones or broad-spectrum agents, reducing the risk of C. difficile infection and other collateral damage. 1, 2
• The 5-day regimen represents the shortest effective duration that balances efficacy with minimizing antibiotic exposure and adverse effects. 2, 6

Alternative First-Line Options

Fosfomycin

• Fosfomycin 3 g as a single oral dose provides approximately 91% clinical cure rates with the convenience of single-dose administration. 1, 7
• Therapeutic urinary concentrations persist for 24-48 hours after the single dose, sufficient to eradicate most uropathogens. 1
• Resistance rates remain low at only 2.6% for initial E. coli infections. 1
• Critical limitation: Fosfomycin should not be used for suspected pyelonephritis or upper-tract infections due to insufficient tissue penetration. 1, 7

Trimethoprim-Sulfamethoxazole (TMP-SMX)

• TMP-SMX 160/800 mg orally twice daily for 3 days achieves 93% clinical cure and 94% microbiological eradication when the organism is susceptible. 3, 1
• Use only when local E. coli resistance is <20% and the patient has not received TMP-SMX in the prior 3 months. 3, 1, 6
• Many regions now report TMP-SMX resistance >20%, making verification of current local antibiogram data mandatory before selection. 1, 8

Critical Contraindications for Nitrofurantoin

• Avoid if eGFR <30 mL/min/1.73 m² due to reduced efficacy and increased risk of peripheral neuropathy. 1, 2, 9
• Do not use for suspected pyelonephritis (fever >38°C, flank pain, costovertebral angle tenderness, nausea/vomiting) because nitrofurantoin does not achieve adequate renal tissue concentrations. 1, 2, 6
• Contraindicated in the last three months of pregnancy. 4

Agents to Reserve or Avoid

Fluoroquinolones (Ciprofloxacin, Levofloxacin)

• Should be reserved for pyelonephritis or culture-proven resistant organisms only. 1, 6, 8
• Community resistance rates now approach 24% in many areas, and serious adverse effects include tendon rupture, peripheral neuropathy, and aortic dissection. 1
• Empiric use for uncomplicated cystitis accelerates resistance and causes unnecessary collateral damage. 1, 8

Beta-Lactams (Amoxicillin-Clavulanate, Cephalosporins)

• Demonstrate inferior efficacy with approximately 89% clinical cure and 82% microbiological cure, significantly lower than first-line agents. 1
• Should be used only when first-line agents are unsuitable. 1, 8
• Amoxicillin or ampicillin alone should never be used due to global resistance rates exceeding 55-67%. 1

Diagnostic Considerations

• Routine urine culture is not required for otherwise healthy women presenting with typical cystitis symptoms (dysuria, frequency, urgency, suprapubic pain) without vaginal discharge. 1, 6
• Obtain urine culture and susceptibility testing if:
  • Symptoms persist after completing therapy
  • Symptoms recur within 2 weeks
  • Atypical presentation or presence of vaginal discharge
  • Fever, flank pain, or systemic signs suggesting pyelonephritis 1, 6

Management of Treatment Failure

• If symptoms do not resolve by the end of therapy or recur within 2 weeks, obtain urine culture immediately and switch to a different antibiotic class for a 7-day course (not the original short regimen). 1, 2
• Assume the original pathogen is resistant to the previously used agent. 1

Common Clinical Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in non-pregnant elderly women; treatment offers no benefit and promotes resistance. 1, 6
• Do not prescribe nitrofurantoin for "borderline" upper-tract symptoms; any flank pain or low-grade fever warrants a fluoroquinolone or cephalosporin. 1, 2
• Always verify renal function before prescribing nitrofurantoin; efficacy drops markedly when eGFR falls below 30 mL/min. 1, 9
• Do not use empiric TMP-SMX without knowing local resistance rates; treatment failure rates are unacceptably high when resistance exceeds 20%. 3, 1

Safety Profile in Elderly Patients

• Common adverse events (nausea, headache) occur in 5.6-34% of patients but are generally mild. 2
• Serious pulmonary and hepatic toxicity are extremely rare (0.001% and 0.0003% respectively) and mainly occur with long-term use. 2, 4
• Short-term nitrofurantoin therapy (5 days) demonstrates good tolerability comparable to other standard regimens. 4, 5