In an otherwise healthy adult with an uncomplicated urinary tract infection, can cephalexin (Keflex) be used as treatment?

Cephalexin (Keflex) for Uncomplicated UTI in Healthy Adults

Cephalexin is an acceptable alternative agent for uncomplicated urinary tract infections in otherwise healthy adults, but it is not a first-line choice and should be reserved for situations where recommended first-line agents (nitrofurantoin, fosfomycin, or trimethoprim-sulfamethoxazole) cannot be used. 1

First-Line Agents to Consider Before Cephalexin

Before prescribing cephalexin, the following first-line options should be evaluated:

• Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5 days achieves clinical cure rates of 88-93% and bacterial cure rates of 81-92%, with minimal resistance and collateral damage 1
• Fosfomycin trometamol 3 g as a single oral dose provides clinical cure rates of 90-91%, though microbiologic cure rates are slightly lower at 78-80% 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days is appropriate only when local E. coli resistance is documented to be <20% 1

When Cephalexin Is Appropriate

Cephalexin should be used only when first-line agents are contraindicated or unavailable, such as:

• Nitrofurantoin cannot be used (eGFR <30 mL/min) 1
• Patient has sulfa allergy (excluding trimethoprim-sulfamethoxazole) 1
• Local resistance patterns make first-line agents unsuitable 1
• Patient has documented allergy or intolerance to first-line agents 1

Evidence-Based Cephalexin Dosing

The optimal regimen is cephalexin 500 mg twice daily for 5-7 days, which has been shown to be as effective as four-times-daily dosing while improving adherence 2, 3:

• A retrospective study of 261 patients demonstrated no difference in treatment failure between twice-daily (12.7%) and four-times-daily (17%) dosing (P = 0.343) 2
• In a separate cohort of 264 patients treated with twice-daily cephalexin, 81.1% achieved clinical success at 30 days 3
• The twice-daily regimen offers comparable efficacy to traditional four-times-daily dosing with improved patient adherence 2

Efficacy Considerations and Limitations

β-lactam agents including cephalexin generally have inferior efficacy compared to first-line agents and are associated with more adverse effects 1:

• Oral β-lactams demonstrate 15-30% higher failure rates than fluoroquinolones or trimethoprim-sulfamethoxazole for complicated UTIs 4
• Clinical cure rates for cephalexin in uncomplicated UTI are good (81.1% in recent studies) but still lower than nitrofurantoin (88-93%) 1, 3
• Cephalexin provides excellent urinary penetration and bioavailability against non-ESBL-producing Enterobacteriaceae 5

Modern Susceptibility Testing

Recent updates to susceptibility testing have improved cephalexin's utility:

• CLSI and USCAST now recommend cefazolin-cephalexin surrogate testing, which has recategorized many isolates from resistant to susceptible 5
• Cephalexin demonstrates very good early bacteriological and clinical cures in uLUTIs caused by non-ESBL-producing Enterobacteriaceae, comparable to many first-line agents 5

Critical Pitfalls to Avoid

• Do not use cephalexin as first-line empiric therapy when nitrofurantoin, fosfomycin, or trimethoprim-sulfamethoxazole (with appropriate resistance data) are available 1
• Do not prescribe cephalexin for less than 5 days—shorter courses have not been adequately studied and β-lactams require 3-7 days minimum 1
• Do not use amoxicillin or ampicillin alone for uncomplicated UTI due to poor efficacy and worldwide resistance rates exceeding 30% 1
• Avoid using cephalexin when early pyelonephritis is suspected—upper tract infections require agents with better tissue penetration such as fluoroquinolones 6

Follow-Up and Treatment Failure

• Obtain urine culture with susceptibility testing if symptoms persist or recur within 2-4 weeks after completing cephalexin therapy 1
• If treatment fails, retreat with a 7-day course of a different appropriate agent based on culture results 1
• Routine follow-up or repeat culture is unnecessary in asymptomatic patients after completing therapy 1