What's the next step for a patient who completed a 7-day course of Keflex (Cephalexin) 2 days ago and still experiences symptoms of a urinary tract infection?

Management of Persistent UTI Symptoms After Completing Cephalexin

Obtain a urine culture with antimicrobial susceptibility testing immediately and retreat with a 7-day course of a different antibiotic class, assuming the original organism is not susceptible to cephalexin. 1

Immediate Diagnostic Steps

• Perform urine culture and susceptibility testing for any patient whose symptoms do not resolve by the end of treatment or whose symptoms recur within 2-4 weeks after completing antibiotics 1
• The diagnosis of treatment failure is clinical—persistent dysuria, frequency, urgency, or systemic symptoms 2 days after completing therapy indicates the need for culture 1

Key Clinical Decision Point: Was This Cystitis or Pyelonephritis?

This distinction is critical because β-lactams like cephalexin have insufficient data to support their use for pyelonephritis 1:

If Lower UTI (Cystitis) Was Suspected:

• Cephalexin is considered an alternative agent with inferior efficacy compared to first-line options for uncomplicated cystitis 1
• The 7-day course completed was appropriate duration for cephalexin in cystitis 1
• Treatment failure suggests either resistant organism or inadequate drug choice 1

If Upper UTI (Pyelonephritis) Was Suspected:

• Cephalexin should not have been used—data are insufficient to recommend oral β-lactams for pyelonephritis 1
• Fluoroquinolones (7 days) or TMP-SMX (14 days) are guideline-recommended for pyelonephritis 1

Empiric Retreatment Strategy (While Awaiting Culture)

Select an antibiotic from a different class than cephalexin 1:

First-Line Options for Retreatment:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days (if lower UTI only) 1
• Fosfomycin trometamol 3 g single dose (if lower UTI only) 1
• TMP-SMX 160/800 mg twice daily for 3 days (if local E. coli resistance <20% and lower UTI) 1

If Pyelonephritis Cannot Be Excluded:

• Ciprofloxacin 500 mg twice daily for 7 days (if local fluoroquinolone resistance <10%) 1, 2
• Levofloxacin 750 mg daily for 5 days (alternative fluoroquinolone option) 1
• Consider initial one-time IV dose of ceftriaxone 1 g if patient appears ill 1

Critical Pitfalls to Avoid

• Do not simply extend cephalexin therapy—assume the organism is not susceptible to the original agent when symptoms persist 1
• Do not use cephalexin for empiric pyelonephritis treatment—it lacks supporting evidence for upper tract infections 1
• Do not retreat without obtaining culture—this is a mandatory step for treatment failures 1
• Do not use fluoroquinolones empirically if local resistance exceeds 10% without culture confirmation 1, 2

Why Cephalexin May Have Failed

• Cephalexin has inferior efficacy compared to first-line agents for uncomplicated cystitis, with higher rates of adverse effects 1
• Recent data show clinical success rates of only 81% with short-course twice-daily cephalexin for uncomplicated UTI 3
• β-lactams are explicitly not recommended for pyelonephritis due to insufficient efficacy data 1
• Local E. coli resistance patterns may favor non-β-lactam agents 1

Follow-Up Considerations

• Adjust therapy based on culture results when available 1
• If symptoms persist despite appropriate antibiotic therapy based on susceptibilities, consider imaging to evaluate for complications (abscess, obstruction) 1
• Routine post-treatment cultures are not indicated if symptoms resolve 1