Oral Cephalosporin for UTI in End-Stage Renal Disease
For an adult with ESRD on hemodialysis and uncomplicated UTI, cefixime 200 mg once daily is the preferred oral cephalosporin, given after each dialysis session if the patient dialyzes three times weekly. 1
Rationale for Cefixime Selection
Cefixime is the only oral third-generation cephalosporin with proven efficacy in UTI and favorable pharmacokinetics for ESRD patients. 2, 3 The drug achieves urinary concentrations exceeding 1000 mg/L even with renal dysfunction, making it suitable for UTI treatment despite minimal kidney function. 4
The FDA-approved dosing for renal impairment specifies 200 mg daily (10 mL of 200 mg/5 mL suspension) for creatinine clearance ≤20 mL/min or patients on continuous peritoneal dialysis. 1 This same dose applies to hemodialysis patients, as neither hemodialysis nor peritoneal dialysis removes significant amounts of cefixime from the body. 1
Cefixime's 3-hour elimination half-life in normal renal function extends significantly in ESRD, allowing once-daily dosing without accumulation. 2, 3 This contrasts with other cephalosporins like cefpirome, which has an interdialytic half-life of 9.35 hours and requires post-dialysis dosing adjustments. 5
Dosing Regimen
Administer 200 mg (10 mL of 200 mg/5 mL suspension or half of a 400 mg capsule if available) once daily. 1 The suspension is preferred over capsules for precise dose measurement in renal impairment. 1
For patients on thrice-weekly hemodialysis, give the dose after each dialysis session to maintain therapeutic levels while avoiding accumulation during the interdialytic period. 1
Treatment duration should be 7 days for uncomplicated lower UTI, or 10-14 days if upper tract involvement cannot be excluded. 6 In male patients with ESRD, always use the 14-day duration because UTI in males is categorically complicated and prostatitis cannot be reliably excluded. 6
Alternative Oral Cephalosporins (Less Preferred)
Cephalexin 500 mg twice daily is an alternative first-generation option if cefixime is unavailable, though it has narrower spectrum coverage. 7 Recent evidence demonstrates that twice-daily dosing is as effective as four-times-daily dosing for uncomplicated UTI. 7
In ESRD, reduce cephalexin to 250 mg twice daily or 500 mg once daily to prevent accumulation, as first-generation cephalosporins are primarily renally eliminated. 4
Cefuroxime axetil and cefaclor have been used historically for UTI but lack specific ESRD dosing guidance in current guidelines and are inferior to cefixime for complicated infections. 4
Critical Pitfalls to Avoid
Never use the standard 400 mg daily dose of cefixime in ESRD patients, as this exceeds the FDA-recommended dose for creatinine clearance ≤20 mL/min and risks drug accumulation. 1
Do not substitute cefixime capsules for suspension in otitis media, but for UTI either formulation is acceptable as long as the dose is correct. 1
Avoid oral cephalosporins entirely if the patient has risk factors for ESBL-producing organisms (recent hospitalization, recent antibiotic use, healthcare-associated infection), as these require parenteral carbapenems or newer β-lactam/β-lactamase inhibitor combinations. 6
Do not use cefoperazone or ceftriaxone for UTI in ESRD, as these drugs exhibit significant biliary excretion and achieve minimal urinary concentrations in renal dysfunction. 4
Always obtain urine culture before initiating therapy to guide targeted treatment, as complicated UTIs in ESRD patients have higher rates of antimicrobial resistance. 6, 8
When Oral Cephalosporins Are Inappropriate
If the patient has fever, flank pain, or systemic signs suggesting pyelonephritis or urosepsis, initiate parenteral therapy with ceftriaxone 1-2 g IV once daily (no dose adjustment needed in ESRD due to dual renal-biliary elimination). 6, 8
If local fluoroquinolone resistance is <10% and the organism is susceptible, ciprofloxacin 250 mg twice daily or levofloxacin 250 mg once daily (both renally adjusted) are superior to oral cephalosporins for complicated UTI. 6
Trimethoprim-sulfamethoxazole 160/800 mg once daily (half the standard dose) is preferred over oral cephalosporins if the organism is susceptible, as β-lactams demonstrate inferior efficacy compared to fluoroquinolones and TMP-SMX for complicated UTI. 6
Monitoring and Follow-Up
Reassess at 72 hours if symptoms persist despite therapy, as this suggests treatment failure requiring culture-directed adjustment or imaging to exclude obstruction. 6
Monitor for diarrhea and stool changes, the most common adverse effects of cefixime, which are usually mild and transient. 2
Ensure the reconstituted suspension is discarded after 14 days and stored either refrigerated or at room temperature. 1