What is the recommended treatment for ESBL (Extended-Spectrum Beta-Lactamase)-positive infections?

Treatment of ESBL-Positive Infections

Carbapenems remain the first-line treatment for serious ESBL-producing bacterial infections, particularly in critically ill patients, while carbapenem-sparing alternatives like ceftazidime/avibactam or ceftolozane/tazobactam should be considered for less severe infections to preserve carbapenem activity. 1

Severity-Based Treatment Algorithm

Critically Ill Patients or Septic Shock

• Initiate Group 2 carbapenems immediately as first-line therapy: 1
  • Meropenem 1g IV every 6 hours by extended infusion 1
  • Imipenem/cilastatin 500mg IV every 6 hours by extended infusion 1
  • Doripenem 500mg IV every 8 hours by extended infusion 1
• These agents have superior activity against non-fermentative gram-negative bacilli and are most appropriate for high bacterial loads 1
• For beta-lactam allergies, use eravacycline 1 mg/kg IV every 12 hours 1

Moderate to Severe Infections (Non-Critical)

• Ceftazidime/avibactam 2.5g (ceftazidime 2g + avibactam 0.5g) IV every 8 hours plus metronidazole demonstrates excellent activity against ESBL-producers and some KPC-producing organisms 1, 2
• Ceftolozane/tazobactam plus metronidazole is effective for ESBL-producing Enterobacteriaceae and preserves carbapenems 3
• Ertapenem 1g IV every 24 hours is suitable for patients with inadequate source control or high risk of community-acquired ESBL infections 1

Uncomplicated Urinary Tract Infections

• Fosfomycin shows >95% susceptibility for uncomplicated lower UTIs caused by ESBL-producing organisms 4
• Nitrofurantoin is effective against ESBL-producing E. coli (>90% susceptibility) but not for other Enterobacteriaceae or upper UTIs 4
• Aminoglycosides (amikacin) may be effective for short-duration therapy if susceptibility is confirmed 4

Site-Specific Considerations

Intra-Abdominal Infections

• Non-critically ill, immunocompetent patients with adequate source control: Amoxicillin/clavulanate 2g/0.2g IV every 8 hours 1
• Critically ill or immunocompromised patients: Piperacillin/tazobactam 6g/0.75g loading dose, then 4g/0.5g IV every 6 hours or 16g/2g by continuous infusion 1
• Treatment duration: 5-7 days after adequate source control 4

Bacteremia

• Treatment duration: 10-14 days depending on source control and clinical response 4
• Follow-up blood cultures to document clearance 4

Pyelonephritis

• Treatment duration: 7-14 days 4

Special Resistance Mechanisms

Metallo-β-Lactamase (MBL)-Producing Organisms

• Ceftazidime/avibactam plus aztreonam is strongly recommended as MBLs hydrolyze all β-lactams except monobactams 1
• Cefiderocol may be considered as an alternative 1

Carbapenem-Resistant Enterobacteriaceae

• Tigecycline at high doses plus carbapenem in continuous infusion 3
• Addition of IV colistin may be necessary in severe infections 3
• Polymyxins (colistin) and fosfomycin have been revived but should be used judiciously 3, 1

Critical Pitfalls to Avoid

• Never use cephalosporins (including cefepime) or cephamycins for ESBL infections despite possible in vitro susceptibility 4, 5
• Avoid fluoroquinolones in regions with >20% resistance rates among E. coli isolates 1
• Piperacillin-tazobactam and cefepime cannot be widely recommended for ESBL-producing Enterobacteriaceae based on available data 6
• Delayed source control leads to treatment failure in intra-abdominal infections 1
• Overuse of carbapenems creates selection pressure for carbapenem-resistant organisms 1

Carbapenem-Sparing Strategy

In settings with high carbapenem-resistant Klebsiella pneumoniae incidence, carbapenem-sparing regimens are strongly recommended 1

• Reserve newer agents (ceftolozane/tazobactam, ceftazidime/avibactam) for multidrug-resistant infections to preserve their activity 1
• Extended use of cephalosporins should be discouraged and limited to pathogen-directed therapy due to selective pressure 3
• Extended use of fluoroquinolones should be discouraged due to selective pressure for ESBLs and MRSA 3

Monitoring Requirements

• Monitor clinical response within 48-72 hours of initiating therapy 4
• For bacteremic infections, obtain follow-up blood cultures to document clearance 4
• For UTIs, consider repeat urine cultures 1-2 weeks after treatment completion 4
• Serum levels of aminoglycosides and vancomycin must be monitored closely to decrease risk of renal failure 3

Local Epidemiology Considerations

Local antimicrobial resistance patterns and bacterial ecology must guide empiric therapy choices 1, 4

• Rapid identification of the specific resistance mechanism is crucial for optimizing therapy 1
• In areas with high ESBL prevalence in community-acquired infections, anti-ESBL coverage may be warranted even for community-acquired IAIs 3