What is the appropriate treatment for a patient with impaired renal function and a Proteus mirabilis infection, on Keflex (Cephalexin) with a Foley catheter?

Keflex 500mg BID is INAPPROPRIATE for this patient—dose reduction is mandatory with GFR 29, and the catheter-associated infection may require alternative therapy.

Critical Dosing Error

With a GFR of 29 mL/min, standard Keflex 500mg BID dosing will cause dangerous drug accumulation. The FDA label explicitly states "cephalexin should be administered with caution in the presence of markedly impaired renal function" and "safe dosage may be lower than that usually recommended" 1.

Required Dose Adjustment

• Reduce the dose to 250mg every 8-12 hours for GFR 10-50 mL/min based on established pharmacokinetic data showing prolonged serum concentrations in renal impairment 2
• Cephalosporins require dose adjustment (not interval extension) as time-dependent antibiotics to maintain bactericidal activity 3
• Monitor closely for drug accumulation and adverse effects given the severe renal impairment 1, 4

Proteus mirabilis Susceptibility Considerations

Cephalexin has marginal activity against Proteus mirabilis, which is a critical limitation:

• Only 56% of P. mirabilis strains are inhibited by 12.5 mcg/mL cephalexin, and 90% require 25 mcg/mL 5
• P. mirabilis is naturally sensitive to most beta-lactams except penicillin G and oxacillin, but cephalexin is among the weaker options 6
• Even with dose adjustment, urinary concentrations remain adequate for most P. mirabilis strains in renal impairment 2

Foley Catheter Complication

The presence of a Foley catheter fundamentally changes the clinical scenario:

• This represents catheter-associated bacteriuria, which may require catheter removal for cure 7
• P. mirabilis produces urease that alkalinizes urine and promotes struvite stone formation, particularly problematic with indwelling catheters 7
• Consider whether this is asymptomatic bacteriuria (which may not require treatment) versus symptomatic catheter-associated UTI

Superior Alternative Regimens for GFR 29

Fluoroquinolones offer better P. mirabilis coverage with simpler renal dosing:

• Ciprofloxacin 250mg every 12 hours (50% dose reduction for CrCl <50 mL/min) provides excellent P. mirabilis coverage 3, 8
• Levofloxacin 250mg every 48 hours is another option for CrCl <50 mL/min 3

If beta-lactam preferred:

• Ceftriaxone 1-2g every 24 hours requires no adjustment until severe renal impairment and provides superior gram-negative coverage 3
• Piperacillin/tazobactam with appropriate dose reduction for CrCl <90 mL/min 3

Critical Pitfalls to Avoid

• Never use standard dosing of renally-cleared antibiotics in GFR <30 mL/min without adjustment—this causes toxicity 3, 4
• Do not assume cephalexin adequately covers all P. mirabilis—susceptibility testing is essential given only 56-90% susceptibility 5, 6
• Avoid nitrofurantoin completely—it is contraindicated at CrCl <30 mL/min due to toxic metabolite accumulation causing peripheral neuritis 3
• Do not combine with NSAIDs or other nephrotoxic agents as this worsens renal function 8
• Consider catheter removal if feasible, as antibiotics alone may not eradicate catheter-associated P. mirabilis infection 7

Monitoring Requirements

• Check renal function periodically during the 5-day course 3
• Monitor for signs of drug toxicity given narrow therapeutic window in renal impairment 3
• Assess clinical response at 48-72 hours; if no improvement, obtain urine culture and consider alternative antibiotics 1