What is the best course of action for a patient with a persistent urinary tract infection due to an extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, who is currently taking cephalexin and has an allergy to sulfa drugs?

Management of ESBL-Producing E. coli Urinary Tract Infection

Stop cephalexin, and start fosfomycin 3 g orally one time with instructions to call the clinic if symptoms persist.

Rationale for Treatment Decision

The patient has a confirmed urinary tract infection with ESBL-producing E. coli that is resistant to cephalexin (the current treatment), which explains why her symptoms have persisted despite therapy. The culture results show the organism is susceptible to several antibiotics, including fosfomycin, trimethoprim/sulfamethoxazole (TMP-SMX), tobramycin, meropenem, and ertapenem.

Key Considerations:

1. Antibiotic Susceptibility: The ESBL-producing E. coli is resistant to:

   • Amoxicillin
   • Cephalexin (current treatment)
   • Ceftriaxone
   • Piperacillin/tazobactam
   • Ciprofloxacin
   • Nitrofurantoin

2. Patient Allergies: The patient has a documented sulfa allergy (hives), which eliminates TMP-SMX as an option despite its in vitro susceptibility.

3. Severity Assessment:

   • The patient has persistent symptoms but no signs of systemic infection or sepsis
   • She is hemodynamically stable and able to take oral medications
   • This represents an uncomplicated UTI despite the resistant organism

Treatment Options Analysis

Fosfomycin (Recommended Option)

• Advantages:
  • Single-dose oral therapy with excellent urinary concentrations
  • Active against the ESBL-producing organism
  • No cross-allergy with sulfa drugs
  • Convenient for out-of-town patient
  • Preserves carbapenems for more severe infections (antibiotic stewardship)

TMP-SMX

• Contraindicated due to the patient's sulfa allergy (hives represent a true allergic reaction)

Carbapenems (Ertapenem/Meropenem)

• Reserved for more severe infections
• Requires parenteral administration
• Not necessary for uncomplicated UTI in a stable patient
• Should be preserved for more severe infections per antibiotic stewardship principles 1

Why Not Other Options?

1. Continuing cephalexin or increasing the dose would be inappropriate as the organism is confirmed resistant to cephalexin, explaining the lack of clinical response.

2. Hospitalization for IV carbapenem therapy is excessive for a patient with an uncomplicated UTI without signs of sepsis. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines recommend that "for patients with non-severe infections due to CRE, under the consideration of antibiotic stewardship, we consider the use of an old antibiotic, chosen from among the in vitro active on an individual basis and according to the source of infection, as good clinical practice" 1.

3. TMP-SMX would be an effective option based on susceptibility but is contraindicated due to the patient's sulfa allergy.

Follow-up Recommendations

• Instruct the patient to call if symptoms persist beyond 48-72 hours after fosfomycin administration
• Consider urine culture follow-up only if symptoms persist (not routinely recommended)
• If symptoms persist, reevaluate for:
  • Treatment failure
  • Anatomical abnormalities
  • Potential need for parenteral therapy with a carbapenem

Key Clinical Pearls

1. ESBL-producing organisms are increasingly common in community-acquired UTIs, not just healthcare-associated infections.

2. Single-dose fosfomycin is effective for uncomplicated lower UTIs, even those caused by resistant organisms, due to its high urinary concentrations.

3. Carbapenems should be preserved when possible for more severe infections to prevent further antimicrobial resistance 1.

4. Always check susceptibility results when patients fail to respond to empiric therapy, as was appropriately done in this case.

5. Consider patient-specific factors such as allergies, location, and severity when selecting antimicrobial therapy.