In a 62-year-old male with chronic kidney disease stage 4 and hypertension who had a Klebsiella urinary infection (sensitive to cefepime, cefoxitin, trimethoprim‑sulfamethoxazole, and ceftriaxone) and received a 1‑gram loading dose of cefepime in the emergency department, what renal‑adjusted antibiotic should be started for definitive therapy?

Antibiotic Selection for Klebsiella UTI with Complicated Urinary Tract Infection in CKD Stage 4

Continue cefepime with renal dose adjustment to 1 gram IV every 24 hours, as the organism is susceptible and this provides definitive therapy for your patient's complicated UTI with bacteremia. 1, 2

Rationale for Cefepime Continuation

Your patient received an appropriate loading dose of 1 gram cefepime in the ED, and since the Klebsiella is susceptible to cefepime, continuing this agent with proper renal adjustment is the most direct path to cure. 1, 2 The 2022 ESCMID guidelines explicitly suggest against routine use of cefepime for third-generation cephalosporin-resistant Enterobacterales (3GCephRE), but your organism is susceptible to cefepime, making this recommendation inapplicable to your case. 1

• For CKD Stage 4 (GFR 15-29 mL/min), cefepime requires dose reduction to 1 gram every 24 hours to prevent neurotoxicity, which is particularly concerning given the elevated pro-convulsive activity of cefepime (relative activity 160 compared to penicillin G = 100). 1, 3

• The loading dose of 1 gram was appropriate regardless of renal function, as critically ill patients with sepsis have expanded volume of distribution from fluid resuscitation, and full loading doses are essential to achieve therapeutic concentrations rapidly. 1

Alternative Regimens Based on Susceptibility

Since your culture shows susceptibility to multiple agents, here is the hierarchy of options:

First Alternative: Ceftriaxone

• Ceftriaxone 1-2 grams IV once daily requires no dose adjustment in CKD Stage 4 and provides excellent urinary concentrations for complicated UTI. 2, 4, 5
• Ceftriaxone's half-life increases only modestly in renal failure (12 hours versus 8 hours in normal function), and no major drug accumulation occurs even in anephric patients with preserved hepatic function. 4, 5
• This is the most practical alternative if you wish to switch from cefepime, as it maintains once-daily dosing and avoids neurotoxicity concerns. 2

Second Alternative: Trimethoprim-Sulfamethoxazole (Step-Down)

• Once the patient is clinically stable (afebrile ≥48 hours, hemodynamically stable), step down to oral trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) once daily (half the standard dose for CrCl 15-30 mL/min). 1, 2, 6
• The ESCMID guidelines explicitly endorse trimethoprim-sulfamethoxazole for non-severe complicated UTI as good clinical practice under antibiotic stewardship considerations. 1, 2
• Total treatment duration should be 7-14 days, with 7 days appropriate if prompt clinical response and 14 days if delayed response or inability to exclude prostatitis in males. 2

Third Alternative: Fluoroquinolones (If Susceptible)

• Ciprofloxacin 500 mg every 18-24 hours or levofloxacin 500 mg loading dose followed by 250 mg every 48 hours for CKD Stage 4. 6
• Fluoroquinolones should only be used if local resistance is <10% and the patient has no recent fluoroquinolone exposure. 2
• Interval extension rather than dose reduction is critical for fluoroquinolones to maintain their concentration-dependent bactericidal activity. 6

Agents to Avoid in This Patient

• Do not use aminoglycosides (gentamicin, amikacin) for definitive therapy in CKD Stage 4 due to nephrotoxicity risk, though a single dose for initial empiric coverage was reasonable. 6

• Do not use carbapenems (meropenem, imipenem, ertapenem) for this susceptible Klebsiella, as the ESCMID guidelines emphasize antibiotic stewardship and reserving carbapenems for resistant organisms. 1, 2

• Do not use nitrofurantoin, fosfomycin, or pivmecillinam for complicated UTI with upper tract involvement and bacteremia, as these agents have insufficient tissue penetration. 2

Critical Monitoring for Cefepime Neurotoxicity

If you continue cefepime, monitor closely for neurotoxicity (confusion, tremor, seizures, agitation), as CKD Stage 4 dramatically increases risk even with appropriate dose adjustment. 1, 3

• Cefepime trough concentrations >20 mg/L are associated with neurotoxicity in 50% of patients, and therapeutic drug monitoring should be considered in this critically ill patient with fluctuating renal function. 1

• If any neurologic changes develop, discontinue cefepime immediately and switch to ceftriaxone, as neurotoxicity typically resolves with drug discontinuation alone. 3

Management of Concurrent Issues

Your patient's severe anemia (Hgb 4.6) and hematuria require urgent GI and urology consultation as planned, but do not delay antibiotic therapy while awaiting these consultations. 2

The presence of yeast in urine does not require antifungal therapy in this non-critically ill patient, as empiric antifungal therapy for candiduria in ICU patients with positive yeast cultures has been associated with increased mortality (OR 3.24,95% CI 1.48-7.11). 2

Blood pressure control with hydralazine and labetalol is appropriate, but avoid concurrent use of loop diuretics (furosemide) if aminoglycosides are used, as this combination increases ototoxicity risk. 6

Treatment Duration and Follow-Up

Total treatment duration should be 14 days for this male patient with complicated UTI and bacteremia, as shorter courses are associated with higher failure rates when prostatitis cannot be excluded. 2

Obtain repeat blood cultures if fever persists beyond 72 hours to assess for treatment failure or endovascular source. 2

Replace any indwelling catheter that has been in place ≥2 weeks at the onset of treatment to hasten symptom resolution and reduce recurrence risk. 2