What oral cephalosporin (a type of antibiotic) can be used to treat urinary tract infections (UTIs)?

Oral Cephalosporins for UTI Treatment

For uncomplicated UTIs, cefixime 400 mg daily or cephalexin 50-100 mg/kg/day (divided into 2-4 doses) are the primary oral cephalosporin options, though they are considered second-line alternatives to fluoroquinolones, nitrofurantoin, or fosfomycin. 1, 2

First-Generation Cephalosporins

Cephalexin is the most commonly used first-generation oral cephalosporin for UTIs:

• Dosing: 50-100 mg/kg per day divided into 4 doses (or 500 mg twice daily in adults) 3, 4
• Duration: 7-14 days for most UTIs 3
• Important limitation: Cephalexin should NOT be used for pyelonephritis or febrile UTIs because it does not achieve adequate serum and tissue concentrations—it is primarily excreted in urine only 1
• Resistance considerations: Local resistance rates should be <20% for empiric use, and cephalexin is inactive against Pseudomonas, Enterococcus, MRSA, most Enterobacter species, and ESBL-producing organisms 1
• Recent evidence suggests twice-daily dosing (500 mg BID) may be as effective as four-times-daily dosing for uncomplicated UTIs, improving adherence 4

Third-Generation Oral Cephalosporins

For uncomplicated pyelonephritis or when broader coverage is needed, third-generation oral cephalosporins are preferred over first-generation agents:

Cefixime

• FDA-approved indication: Uncomplicated UTIs caused by E. coli and Proteus mirabilis 2
• Dosing: 400 mg daily (can be given as single daily dose or 200 mg twice daily) 3, 2
• Duration: 10 days for pyelonephritis 3
• Clinical efficacy: 96.2% efficacy rate in uncomplicated cystitis and 80% in complicated UTIs in clinical trials 5, 6
• Advantage: Once-daily dosing improves adherence, though twice-daily dosing (200 mg BID) reduces gastrointestinal side effects 7

Cefpodoxime

• Dosing: 200 mg twice daily for 10 days 3, 8
• Indication: Recommended for uncomplicated pyelonephritis and as oral step-down therapy for complicated UTIs 3, 8
• Important: Should be preceded by an initial IV dose of long-acting cephalosporin (e.g., ceftriaxone) when used empirically for pyelonephritis 3

Ceftibuten

• Dosing: 400 mg once daily for 10 days 3, 8
• Indication: Alternative to cefpodoxime for pyelonephritis 3

Other Options

• Cefprozil: 30 mg/kg per day in 2 doses 3
• Cefuroxime axetil: 20-30 mg/kg per day in 2 doses (or 500 mg twice daily for 10-14 days in adults) 3, 8

Clinical Algorithm for Selection

For uncomplicated cystitis (lower UTI):

• Cephalosporins are second-line; prefer nitrofurantoin, fosfomycin, or trimethoprim-sulfamethoxazole first 1, 8
• If cephalosporin needed: Use cephalexin 500 mg twice daily for 7 days 3, 4

For uncomplicated pyelonephritis (upper UTI):

• First choice: Fluoroquinolone (if local resistance <10%) 3, 8
• If fluoroquinolone contraindicated: Give IV ceftriaxone 1-2 g once, then switch to oral cefpodoxime 200 mg BID or ceftibuten 400 mg daily for 10 days 3, 8
• Never use cephalexin alone for pyelonephritis 1

For complicated UTIs:

• Obtain urine culture before initiating therapy 8
• Use second-generation cephalosporin plus aminoglycoside for systemic symptoms 3
• For oral step-down: Cefpodoxime 200 mg BID or ceftibuten 400 mg daily for 7-14 days 8
• Duration: 14 days for men when prostatitis cannot be excluded 3

Critical Pitfalls to Avoid

• Do not use cephalexin for febrile UTIs or suspected kidney involvement—it lacks adequate tissue penetration 1
• β-lactams including cephalosporins have inferior efficacy compared to fluoroquinolones for UTIs 8
• Always consider local resistance patterns; cephalosporins should not be used empirically if local resistance exceeds 20% 1
• For pyelonephritis treated with oral cephalosporins, always give an initial parenteral dose (e.g., ceftriaxone) to ensure adequate initial tissue levels 3
• Reassess at 72 hours if no clinical improvement with defervescence 8