What is the recommended treatment for bacterial infections caused by bacteria with beta-lactamase (beta-lactamase) genes?

Treatment of Bacterial Infections with Beta-Lactamase Genes

For bacteria producing beta-lactamases, use beta-lactam/beta-lactamase inhibitor combinations or carbapenems as first-line therapy, with specific agent selection based on the type of beta-lactamase enzyme present.

Identify the Beta-Lactamase Type First

Rapid identification of the specific beta-lactamase mechanism is essential for optimal treatment selection 1. The three major classes of carbapenemases require different therapeutic approaches:

• Class A (KPC-type): Most common carbapenemase, accounting for 47.4% of meropenem-resistant Enterobacterales 1
• Class B (Metallo-beta-lactamases/MBLs): Including NDM, VIM, IMP - these hydrolyze all beta-lactams except aztreonam 1
• Class D (OXA-48-like): Accounts for 19% of carbapenem-resistant isolates 1

Treatment Algorithm by Beta-Lactamase Type

For KPC-Producing Organisms (Class A)

First-line agents: ceftazidime/avibactam or meropenem/vaborbactam 1, 2

• These novel beta-lactam/beta-lactamase inhibitor combinations demonstrate superior clinical outcomes compared to traditional antibiotic regimens 1
• Imipenem/relebactam and cefiderocol are acceptable alternatives 1
• Historical regimens with colistin showed approximately one-third mortality and less than 70% clinical response rates 1

For MBL-Producing Organisms (Class B)

Strongly recommended: ceftazidime/avibactam plus aztreonam 1, 2

• MBLs hydrolyze all beta-lactams except monobactams (aztreonam), making this combination uniquely effective 1
• Cefiderocol may be considered as an alternative 1, 2
• Classic serine beta-lactamase inhibitors cannot inhibit MBLs 1

For ESBL-Producing Organisms (Non-Carbapenemase)

Severity-based approach:

Critically ill patients or septic shock:

• Group 2 carbapenems (meropenem, imipenem/cilastatin, or doripenem) as immediate first-line therapy 2
• Meropenem 1g IV every 6 hours by extended infusion 2

Stable patients with adequate source control:

• Piperacillin/tazobactam: 6g/0.75g loading dose, then 4g/0.5g IV every 6 hours or 16g/2g continuous infusion 2, 3
• Ceftazidime/avibactam plus metronidazole for intra-abdominal infections 2
• Ertapenem 1g IV every 24 hours for community-acquired ESBL infections 2

Pharmacokinetic/Pharmacodynamic Optimization

Target free plasma beta-lactam concentration at 4-8 times the MIC for 100% of the dosing interval 1

• A minimum target of 100% fT ≥ MIC is required for clinical efficacy in ICU patients 1
• Higher targets (fCmin/MIC ratio above 7.6) achieve 100% bacterial eradication versus 33% with lower ratios 1
• Extended or continuous infusions optimize time above MIC 1

Critical Pitfalls to Avoid

Do not use first-generation cephalosporins - they lack activity against ESBL-producing organisms 2

Avoid fluoroquinolones in areas with >20% resistance rates among E. coli isolates 2

Do not use third- or fourth-generation cephalosporins alone for ESBL producers - even when appearing susceptible in vitro, clinical outcomes are poor 1

Delayed source control leads to treatment failure - particularly critical in intra-abdominal infections 2

Overuse of carbapenems drives resistance - use carbapenem-sparing regimens when appropriate for stable patients 2

Special Considerations

For nosocomial pneumonia caused by Pseudomonas aeruginosa: Add an aminoglycoside to piperacillin/tazobactam therapy 3

For beta-lactam allergies: Eravacycline 1 mg/kg IV every 12 hours is an alternative 2

Tigecycline considerations: Viable for complicated intra-abdominal infections with ESBL producers, but lacks activity against P. aeruginosa and should be used cautiously in bacteremia 2

Monitor local epidemiology: Resistance patterns vary significantly by region and institution, requiring adjustment of empiric therapy 2

Renal dosing adjustments: Required for piperacillin/tazobactam when creatinine clearance ≤40 mL/min 3