Which antibiotics are appropriate for treating an otherwise healthy adult with uncomplicated cystitis caused by extended‑spectrum β‑lactamase‑producing Enterobacteriaceae?

Antibiotics Effective for ESBL in Urine

For an otherwise healthy adult with uncomplicated cystitis caused by ESBL-producing Enterobacteriaceae, fosfomycin 3g single dose or nitrofurantoin 100mg twice daily for 5-7 days are the preferred first-line oral treatments, with pivmecillinam (where available) as an alternative. 1, 2, 3

First-Line Oral Options for Uncomplicated ESBL Cystitis

Fosfomycin

• Fosfomycin trometamol 3g as a single oral dose is highly effective, with >95% susceptibility rates against ESBL-producing E. coli and minimal collateral damage to normal flora 1, 4
• Achieves cure rates of 93% in community-acquired ESBL cystitis 5
• The European Association of Urology supports its use for uncomplicated UTIs 1

Nitrofurantoin

• Nitrofurantoin 100mg twice daily for 5-7 days shows >90% susceptibility against ESBL-producing E. coli 3, 4
• Effective only for lower urinary tract infections (cystitis), not for pyelonephritis or systemic infections 2, 3
• More than 95% of ESBL-producing Enterobacteriaceae remain sensitive 4

Pivmecillinam (Limited Availability)

• Pivmecillinam 400mg twice daily for 3-7 days demonstrates >95% susceptibility against ESBL producers 1, 4
• Available in some European countries but not licensed in North America 1
• Shows 98% sensitivity for E. coli and 83% for Klebsiella species 4

Important Caveats and Pitfalls

Avoid These Common Mistakes

• Do NOT use fluoroquinolones (ciprofloxacin, levofloxacin) empirically for ESBL infections, as resistance rates frequently exceed 20% and they should be reserved for other indications 1, 3
• Do NOT use trimethoprim-sulfamethoxazole, as ESBL-producing organisms typically exhibit co-resistance 3, 4
• Do NOT use standard cephalosporins or amoxicillin alone, as these are ineffective against ESBL producers 1, 6

When Oral Options Are Insufficient

• If the patient has upper UTI symptoms (fever, flank pain, systemic illness), oral agents are inadequate and parenteral therapy is required 1, 7
• For complicated cystitis with risk factors (diabetes, recurrent UTIs, recent instrumentation), consider initial parenteral therapy 1, 5

Parenteral Options When Needed

For Complicated or Severe ESBL UTIs

• Carbapenems (ertapenem 1g IV daily, meropenem, or imipenem-cilastatin) are first-line for severe infections 2, 8, 3
• Ertapenem is preferred for once-daily dosing in stable patients 2
• Treatment duration: 7-14 days depending on severity (14 days for males when prostatitis cannot be excluded) 1

Carbapenem-Sparing Alternatives

• For mild-moderate infections with documented susceptibility, consider piperacillin-tazobactam or ceftazidime-avibactam to preserve carbapenem activity 2, 3
• Aminoglycosides (amikacin) may be used for short-duration therapy if susceptibility confirmed, but require monitoring 7, 3
• Avoid piperacillin-tazobactam for bacteremia despite possible in vitro susceptibility 2

Treatment Algorithm

1. Confirm uncomplicated cystitis: No fever, no flank pain, no systemic symptoms, otherwise healthy adult 1

2. Obtain urine culture before treatment if ESBL suspected (prior ESBL infection, recent antibiotics, healthcare exposure) 7, 2

3. Initiate empiric oral therapy:

   • First choice: Fosfomycin 3g single dose 1, 4
   • Alternative: Nitrofurantoin 100mg BID for 5-7 days 1, 4
   • Where available: Pivmecillinam 400mg BID for 3-7 days 1, 4

4. Escalate to parenteral therapy if:

   • Fever or systemic symptoms develop 1
   • No clinical improvement within 48-72 hours 2
   • Upper tract involvement suspected 1

5. Adjust based on culture results and clinical response 1, 2

Critical Clinical Considerations

• Local resistance patterns matter: If your institution has >10% ESBL prevalence in community UTIs, obtain cultures routinely 1, 6
• Recent research challenges dogma: A 2022 study showed non-carbapenem β-lactams achieved similar outcomes to carbapenems for ESBL UTIs, with higher microbiologic cure rates (98% vs 92%) and shorter therapy durations 9
• Amoxicillin-clavulanate may work for susceptible isolates (MIC ≤8 μg/mL) with 93% cure rates, but only 56% for resistant strains 5