In a 31‑year‑old woman who completed a 7‑ to 10‑day course of cephalexin (Keflex) for acute uncomplicated cystitis with a prior positive Escherichia coli urine culture and now presents with recurrent dysuria, urinary frequency, and suprapubic pain, which laboratory tests and antibiotic regimen should be ordered?

Recurrent UTI After Cephalexin: Laboratory Testing and Antibiotic Selection

Immediate Laboratory Testing Required

Order a urine culture with antimicrobial susceptibility testing immediately before starting any antibiotics. 1 This is critical because her symptoms are recurring after completing cephalexin, suggesting either treatment failure due to resistant E. coli or reinfection with a different organism. 1

• Do not treat empirically without culture in this scenario – the European Association of Urology guidelines specifically recommend urine culture when "symptoms do not resolve or recur within 4 weeks after completion of treatment." 1
• A urinalysis (dipstick) can be performed concurrently but adds minimal diagnostic value when symptoms are classic for cystitis. 1
• Do not order imaging or cystoscopy – extensive workup is not indicated in women under 40 without risk factors for complicated UTI. 1

Antibiotic Selection: First-Line Empiric Therapy

Start nitrofurantoin 100 mg twice daily for 5 days as empiric therapy while awaiting culture results. 1, 2 This is the optimal choice for several reasons:

Why Nitrofurantoin is Preferred Over Repeating Cephalexin:

• Cephalexin has inferior efficacy compared to other UTI antimicrobials and should be used with caution for uncomplicated cystitis. 1 The fact that her symptoms recurred after cephalexin suggests either inadequate treatment or resistant organism.
• β-lactams like cephalexin are considered alternative rather than first-line agents by IDSA guidelines. 1
• Nitrofurantoin maintains 96% susceptibility against E. coli in recent studies, compared to only 59% for trimethoprim-sulfamethoxazole. 3
• Nitrofurantoin produces minimal collateral damage to normal flora, preserving broader-spectrum antibiotics for serious infections. 2

Alternative First-Line Options (in order of preference):

1. Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days – only if local E. coli resistance rates are below 20% (check your institution's antibiogram). 1
2. Fosfomycin trometamol 3 g single dose – appropriate choice with minimal resistance, though may have slightly inferior efficacy. 1

When to Avoid Nitrofurantoin:

• Creatinine clearance <60 mL/min – nitrofurantoin does not achieve adequate concentrations in renal insufficiency. 2
• Suspected pyelonephritis (fever, flank pain, systemic symptoms) – nitrofurantoin does not achieve adequate tissue concentrations for upper UTI. 2

Fluoroquinolones: Reserve as Last Resort

Do not use ciprofloxacin or levofloxacin empirically for uncomplicated cystitis. 1 While fluoroquinolones are highly efficacious in 3-day regimens, they should be reserved for:

• Documented resistance to first-line agents based on culture results 2
• Pyelonephritis (upper UTI) where tissue penetration is required 2
• The FDA has issued warnings about serious adverse effects affecting tendons, muscles, joints, nerves, and CNS. 2

Clinical Decision Algorithm

Step 1: Obtain urine culture with susceptibilities before starting antibiotics 1

Step 2: Start empiric nitrofurantoin 100 mg twice daily for 5 days 1, 2

Step 3: Reassess in 48-72 hours:

• If symptoms improve, complete the 5-day course 2
• If no improvement or worsening, consider pyelonephritis and switch to fluoroquinolone (ciprofloxacin 500 mg twice daily for 7 days) 1

Step 4: When culture results return:

• If organism is susceptible to nitrofurantoin, continue current therapy 1
• If resistant, switch to an agent based on susceptibilities for a 7-day course (assuming the original organism was not eradicated) 1

Common Pitfalls to Avoid

• Do not repeat cephalexin – her recurrence after completing this agent suggests it was inadequate. 1
• Do not treat without culture – this is a treatment failure scenario requiring susceptibility data. 1
• Do not use amoxicillin or ampicillin – very high worldwide resistance rates make these inappropriate for empiric therapy. 1
• Do not order post-treatment cultures if asymptomatic – routine follow-up cultures are not indicated. 1

Duration of Therapy

• Nitrofurantoin: 5 days 1, 2
• If switching to alternative agent based on culture: 7 days (longer duration for presumed treatment failure) 1
• Do not exceed 7 days for acute cystitis – this increases adverse effects without improving outcomes. 1, 2