What is the treatment for Extended-Spectrum Beta-Lactamase (ESBL)-producing bacterial infections?

Treatment of ESBL-Producing Bacterial Infections

Carbapenems are the first-line treatment for serious infections caused by ESBL-producing bacteria, particularly in critically ill patients, while carbapenem-sparing alternatives should be considered for less severe infections to reduce selection pressure for carbapenem resistance. 1

First-Line Treatment Options Based on Infection Severity

Critical Illness/Septic Shock

• Group 2 carbapenems (imipenem/cilastatin, meropenem, doripenem) are preferred for critically ill patients with high bacterial loads or when treating serious infections 2, 1
• These carbapenems have activity against non-fermentative gram-negative bacilli and are more appropriate for severe infections 2

Moderate to Severe Infections

• Ceftolozane/tazobactam plus metronidazole is effective against ESBL-producing Enterobacteriaceae and can preserve carbapenems 1, 3
• Ceftazidime/avibactam plus metronidazole has demonstrated activity against ESBL-producers and some KPC-producing organisms 1, 2
• Group 1 carbapenems like ertapenem have activity against ESBL-producing pathogens but are not active against Pseudomonas aeruginosa 2, 4

Mild to Moderate Infections

• Piperacillin/tazobactam may be considered for stable patients with mild to moderate infections, particularly those with urinary or biliary sources 1, 5
• For urinary tract infections, aminoglycosides may be effective when the source is urinary 2, 1

Special Considerations for Specific ESBL Types

MBL-Producing Enterobacterales

• Ceftazidime/avibactam plus aztreonam is strongly recommended for infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales 2
• Cefiderocol may also be considered as an alternative option for MBL-producing organisms 2

Carbapenem-Sparing Strategies

• Newer β-lactam/β-lactamase inhibitor combinations should be used to preserve carbapenems 5, 6
• Ceftolozane/tazobactam has excellent in vitro activity against ESBL-producing Enterobacteriaceae and MDR P. aeruginosa 2, 3
• Ceftazidime/avibactam has activity against ESBL and KPC-producing organisms 7
• For outpatient treatment of less severe infections (like UTIs), oral options may include fluoroquinolones if susceptibility is confirmed 1, 8

Important Considerations for Treatment Selection

• Local epidemiology and resistance patterns should guide empiric therapy choices 1, 7
• Rapid identification of the specific resistance mechanism is crucial for optimizing therapy 7
• In areas with high carbapenem-resistant Klebsiella pneumoniae, carbapenem-sparing regimens are strongly recommended 1, 7
• For KPC-producing organisms, combination therapy with carbapenems and aminoglycosides may provide synergistic activity 9

Common Pitfalls to Avoid

• Overuse of carbapenems leads to selection pressure and emergence of carbapenem-resistant organisms 1, 6
• First-generation cephalosporins lack activity against ESBL-producing organisms and should not be used 7
• Fluoroquinolones should be avoided in regions with fluoroquinolone resistance rates >20% among E. coli isolates 1
• Delayed source control can lead to inadequate treatment of intra-abdominal infections 2

Emerging Treatment Options

• Newer agents like ceftolozane/tazobactam and ceftazidime/avibactam should be reserved for multidrug-resistant infections to preserve their activity 1, 5
• "Old" antibiotics such as polymyxins (colistin) and fosfomycin have been revived for treating carbapenem-resistant infections but should be used judiciously 2, 1
• Tigecycline is a viable treatment option for complicated intra-abdominal infections due to its favorable activity against anaerobic organisms and several ESBL-producing Enterobacteriaceae 2