What oral antibiotics provide ESBL (Extended-Spectrum Beta-Lactamase) coverage?

Oral Antibiotics for ESBL-Producing Bacteria

For ESBL-producing bacteria, the most effective oral antibiotics are fosfomycin, nitrofurantoin, and pivmecillinam, with carbapenems remaining the gold standard for severe infections requiring intravenous therapy. 1

First-Line Oral Options for ESBL Infections

Urinary Tract Infections

• Fosfomycin tromethamine: Single 3g dose for uncomplicated UTIs; shows 98% effectiveness against ESBL-producing E. coli 2
• Nitrofurantoin: 100mg four times daily for 5-7 days; 93% effective against ESBL E. coli but less effective (42%) against ESBL Klebsiella 2
• Pivmecillinam: 400mg three times daily for 5-7 days; demonstrates 96% effectiveness against ESBL E. coli and 83% against ESBL Klebsiella 2

Oral Options for Non-UTI ESBL Infections

• Cefixime + amoxicillin/clavulanate combination: This combination has shown synergistic activity against ESBL-producing organisms, with in vitro studies demonstrating increased susceptibility from 8.6% with cefixime alone to 86.3% when combined with amoxicillin/clavulanate 3

Second-Line Options

• Newer cephalosporin/beta-lactamase inhibitor combinations: Ceftazidime/avibactam and ceftolozane/tazobactam are primarily available as IV formulations but may be considered for step-down therapy in select cases 1
• Fluoroquinolones: Should only be used if susceptibility is confirmed by testing due to high rates of co-resistance (60-93%) in ESBL-producing organisms 1, 4

Treatment Algorithm Based on Infection Type

1. Uncomplicated UTI with ESBL-producing E. coli:

   • First choice: Fosfomycin 3g single dose
   • Alternative: Nitrofurantoin 100mg QID for 5 days or pivmecillinam 400mg TID for 5 days

2. UTI with ESBL-producing Klebsiella:

   • First choice: Pivmecillinam 400mg TID for 7 days
   • Alternative: Fosfomycin 3g every 48 hours for 3 doses (off-label)

3. Complicated UTI requiring oral therapy:

   • Consider cefixime + amoxicillin/clavulanate combination
   • Duration: 7-14 days depending on severity

4. Non-UTI ESBL infections requiring oral therapy:

   • Limited options available
   • Consider IV-to-oral switch with carbapenems followed by cefixime + amoxicillin/clavulanate if susceptible

Important Considerations

• Always obtain cultures before initiating therapy to confirm ESBL production and determine susceptibility patterns 1
• Local resistance patterns should guide empiric therapy choices 5
• Avoid fluoroquinolones for empiric therapy of suspected ESBL infections due to high resistance rates (only 14.7-32.7% susceptibility) 4
• Carbapenems remain the gold standard for severe ESBL infections requiring IV therapy 6, 1
• Amoxicillin-clavulanate alone is not recommended due to high resistance rates (only 20% susceptibility) 4

Emerging Options

• Ceftazidime/avibactam and ceftolozane/tazobactam show promise for treating ESBL infections but are currently available primarily as IV formulations 6
• Combination therapy with cefixime and amoxicillin/clavulanate has shown clinical success in 18 out of 20 patients with ESBL E. coli UTIs in recent studies 3

For optimal outcomes, treatment selection should be guided by susceptibility testing whenever possible, with consideration of infection site, severity, and local resistance patterns.