Cephalexin for Uncomplicated Cystitis
Cephalexin 500 mg twice daily for 7 days is an appropriate and effective treatment for uncomplicated cystitis in adults without penicillin/cephalosporin allergy or severe renal impairment, offering a convenient fluoroquinolone-sparing alternative with comparable efficacy to traditional first-line agents. 1, 2
Dosing Regimen
The FDA-approved dose for uncomplicated cystitis is 500 mg every 12 hours (twice daily) for 7–14 days in patients over 15 years of age. 1
Recent high-quality evidence demonstrates that cephalexin 500 mg twice daily is as effective as 500 mg four times daily for uncomplicated UTI treatment, with no difference in treatment failure rates (12.7% vs 17%, P = 0.343). 3
Twice-daily dosing improves patient adherence while maintaining equivalent efficacy, making it the preferred regimen over the traditional four-times-daily schedule. 3, 4
A 7-day course is sufficient for uncomplicated cystitis, though the FDA label permits extension to 14 days if clinically indicated. 1
Clinical Efficacy
Cephalexin achieves excellent urinary penetration and bioavailability, with bacteriological cure rates of 67% overall and up to 87% in younger patients (<25 years) with uncomplicated lower UTI. 5
Against non-ESBL-producing Escherichia coli (the most common uropathogen, isolated in 85.4% of cases), cephalexin demonstrates early bacteriological and clinical cure rates comparable to traditional first-line agents including trimethoprim-sulfamethoxazole and nitrofurantoin. 3, 2
Modern cefazolin-cephalexin surrogate testing (recommended by CLSI and USCAST) has reclassified many previously "resistant" isolates as susceptible, expanding cephalexin's utility. 2
Position in Treatment Algorithm
Cephalexin is classified as an alternative rather than first-line agent by IDSA guidelines for uncomplicated UTI, but serves as an excellent fluoroquinolone-sparing option in the current era of antimicrobial resistance. 3, 2
Use cephalexin when:
Critical Limitations and Contraindications
Do not use cephalexin for complicated UTIs, pyelonephritis, or upper tract involvement, as oral β-lactams demonstrate inferior efficacy compared to fluoroquinolones or parenteral agents for these conditions. 6
Avoid in patients with ESBL-producing organisms, as cephalexin lacks activity against extended-spectrum β-lactamase producers. 2
Cephalexin is ineffective for Pseudomonas aeruginosa, Enterococcus species, and methicillin-resistant Staphylococcus aureus, limiting its use to susceptible Gram-negative uropathogens. 2
Do not use for sexually transmitted urethritis (Chlamydia, Ureaplasma), as cephalexin lacks activity against these pathogens. 7
Practical Prescribing Details
Standard adult dose: 500 mg orally every 12 hours for 7 days 1, 3
No renal dose adjustment is required for patients with normal or mildly impaired renal function (eGFR >30 mL/min). 1
Obtain urine culture before initiating therapy when treating recurrent UTIs or in populations at higher risk for resistance, though empiric treatment without culture is acceptable for straightforward uncomplicated cystitis. 7
Common Pitfalls to Avoid
Do not prescribe four-times-daily dosing when twice-daily achieves equivalent outcomes with better adherence. 3, 4
Do not extend therapy beyond 7 days for uncomplicated cystitis unless there is documented delayed clinical response or complicating factors. 1
Do not use cephalexin for asymptomatic bacteriuria, as treatment is not indicated and promotes resistance. 7
Recognize that cure rates are lower in older patients (>40 years: 46%) compared to younger patients (<25 years: 87%), suggesting that alternative agents may be preferable in elderly populations. 5