Is Keflex (Cephalexin) effective against E. coli in an adult patient with an uncomplicated urinary tract infection (UTI)?

Cephalexin (Keflex) for E. coli UTI

Cephalexin is FDA-approved and effective for uncomplicated urinary tract infections caused by E. coli, but it is not recommended as first-line empiric therapy for complicated UTIs due to increasing resistance patterns and inferior efficacy compared to fluoroquinolones and trimethoprim-sulfamethoxazole. 1, 2

FDA-Approved Indications

• Cephalexin is specifically FDA-approved for genitourinary tract infections caused by E. coli, Proteus mirabilis, and Klebsiella pneumoniae. 1
• The FDA label explicitly states that culture and susceptibility tests should be initiated prior to and during therapy to confirm susceptibility. 1

Uncomplicated UTI in Women

For uncomplicated cystitis in non-pregnant women, cephalexin can be used as an alternative agent when first-line options are contraindicated or unavailable, but it is not preferred empirically. 2, 3

• The 2024 European Association of Urology guidelines do not list cephalexin among the recommended first-line agents for uncomplicated cystitis, which include fosfomycin, nitrofurantoin, pivmecillinam, and trimethoprim-sulfamethoxazole. 2
• Beta-lactams, including cephalexin, demonstrate lower efficacy than trimethoprim-sulfamethoxazole regardless of treatment duration. 3, 4
• When cephalexin is used, the recommended dosing is 500 mg twice daily for 5-7 days, which has been shown to be as effective as four-times-daily dosing with improved adherence. 5, 6

Complicated UTI Considerations

Cephalexin should not be used for complicated UTIs, pyelonephritis, or catheter-associated UTIs due to inadequate tissue penetration and inferior outcomes. 2

• The 2024 European Association of Urology guidelines recommend fluoroquinolones, trimethoprim-sulfamethoxazole, or parenteral agents (ceftriaxone, carbapenems, aminoglycosides) for complicated UTIs, with no mention of oral cephalexin. 2, 7
• For pyelonephritis, antimicrobials that attain high renal tissue levels—such as fluoroquinolones, trimethoprim-sulfamethoxazole, or aminoglycosides—are strongly preferred over beta-lactams. 3, 4

Resistance Patterns and Clinical Efficacy

• E. coli remains the most common uropathogen (85.4% of cases), and most strains retain susceptibility to cephalexin when tested. 5
• Recent retrospective data show clinical success rates of 81.1% with twice-daily cephalexin for uncomplicated UTIs in emergency department settings. 6
• However, increasing resistance to commonly used agents, including beta-lactams, has been documented, making culture-guided therapy essential. 3, 8

Critical Pitfalls to Avoid

• Never use cephalexin empirically when local fluoroquinolone or trimethoprim-sulfamethoxazole resistance exceeds 10%, or when the patient has risk factors for multidrug-resistant organisms. 2, 7
• Do not use cephalexin for upper tract infections (pyelonephritis) or when systemic symptoms are present, as tissue penetration is inadequate. 3, 4
• Avoid cephalexin in men with UTI unless prostatitis has been definitively excluded, as treatment duration and agent selection differ significantly. 2, 8
• Always obtain urine culture before initiating therapy for complicated UTIs to guide targeted treatment, as the microbial spectrum is broader and resistance more likely. 2, 7

When Cephalexin Is Appropriate

Use cephalexin for uncomplicated cystitis in non-pregnant women when:

• The patient has contraindications to first-line agents (allergy, intolerance, or recent exposure). 2
• Culture results confirm E. coli susceptibility to cefazolin (a surrogate marker for cephalexin). 5
• The infection is limited to lower urinary tract symptoms (dysuria, frequency, urgency) without fever, flank pain, or systemic symptoms. 2

Dosing: 500 mg orally twice daily for 5-7 days. 5, 6