What are alternative treatments to Keflex (Cephalexin) 500mg for cystitis?

Alternatives to Keflex (Cephalexin) 500mg for Cystitis

Nitrofurantoin monohydrate/macrocrystals (100 mg twice daily for 5 days) is the preferred first-line alternative to cephalexin for uncomplicated cystitis due to its minimal resistance patterns, limited collateral damage, and efficacy comparable to other standard regimens. 1

First-Line Treatment Options (in order of preference)

• Nitrofurantoin monohydrate/macrocrystals: 100 mg twice daily for 5 days - highest recommendation due to minimal resistance and comparable efficacy to other agents 1

• Trimethoprim-sulfamethoxazole: 160/800 mg (1 double-strength tablet) twice daily for 3 days - appropriate only if local resistance rates are <20% or if the infecting strain is known to be susceptible 1

• Fosfomycin trometamol: 3 g single dose - convenient dosing but may have slightly inferior efficacy compared to multi-day regimens 1

• Pivmecillinam: 400 mg three times daily for 3-5 days - good option where available (primarily in European countries) 1

Alternative Options When First-Line Agents Cannot Be Used

• Fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin): Highly efficacious in 3-day regimens but should be reserved for more serious infections due to concerns about collateral damage and increasing resistance 1, 2

• Other β-lactams: Including amoxicillin-clavulanate, cefdinir, cefaclor, and cefpodoxime-proxetil (3-7 day regimens) 1, 3

Treatment Selection Algorithm

1. Assess patient allergies and contraindications:

   • If allergic to cephalexin or other β-lactams, choose nitrofurantoin or fosfomycin 1
   • If renal impairment (CrCl <30 mL/min), avoid nitrofurantoin 2

2. Consider local resistance patterns:

   • If local E. coli resistance to TMP-SMX >20%, choose nitrofurantoin or fosfomycin 1, 2
   • If fluoroquinolone resistance >10%, avoid these agents 1

3. Consider patient-specific factors:

   • For patients needing single-dose therapy: fosfomycin is the only option 1
   • For pregnant women: nitrofurantoin (avoid in 3rd trimester) or fosfomycin 1

Important Considerations and Caveats

• β-lactams (including cephalexin) generally have inferior efficacy and more adverse effects compared to other UTI antimicrobials and should be used with caution 1, 3

• Amoxicillin or ampicillin should not be used for empirical treatment due to poor efficacy and high prevalence of antimicrobial resistance 1

• Fluoroquinolones should be reserved for more serious infections due to their propensity for collateral damage (e.g., C. difficile infection, tendinopathy) despite high efficacy 1

• Nitrofurantoin should not be used for suspected pyelonephritis as it does not achieve adequate tissue concentrations 2

• Recent evidence suggests that short-course therapy with twice-daily cephalexin may be effective for uncomplicated UTIs with clinical success rates of approximately 81%, making it a reasonable option when first-line agents cannot be used 3