Antimicrobial Strategies for Extended-Spectrum β-Lactamase Infections

The global proliferation of extended-spectrum β-lactamase (ESBL)-producing bacteria has escalated antimicrobial resistance, challenging treatment of common infections such as urinary tract infections, bloodstream infections and pneumonia. These enzymes hydrolyse penicillins and cephalosporins, undermining first-line therapies and driving reliance on carbapenems. However, overuse of carbapenems fosters further resistance, prompting development of carbapenem-sparing strategies. These include optimisation of β-lactam/β-lactamase inhibitor combinations, guided by pharmacokinetic/pharmacodynamic (PK/PD) principles and therapeutic drug monitoring (TDM), to ensure adequate drug exposure while minimising toxicity. Continuous-infusion dosing regimens and real-time TDM enable precise attainment of PK/PD targets, improving microbiological eradication and clinical outcomes. Novel agents such as ceftazidime–avibactam, temocillin and cefepime–zidebactam, alongside non-β-lactam alternatives like aminoglycosides, tigecycline and fosfomycin, offer additional options, particularly in severe or refractory cases. Combination therapy, dosing adjustments for renal function and de-escalation protocols further refine treatment. Integration of antimicrobial stewardship, rapid diagnostics and infection control measures underpins these strategies, ensuring that therapeutic advances translate into reduced morbidity, mortality and the spread of resistance on a global scale.

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Antimicrobial Strategies for Extended-Spectrum β-Lactamase Infections publication trend

The graph below shows the total number of articles in antimicrobial strategies for extended-spectrum β-lactamase infections across all publications each year (not limited to Nature Index journals).

Technical terms

Extended-spectrum β-lactamase (ESBL): Enzymes produced by certain Gram-negative bacteria that inactivate a wide range of β-lactam antibiotics, leading to resistance.

Carbapenems: A class of broad-spectrum β-lactam antibiotics often reserved as last-line agents against multidrug-resistant Gram-negative pathogens.

Piperacillin–tazobactam: A combination antibiotic pairing a penicillin derivative with a β-lactamase inhibitor to overcome resistance in Enterobacterales.

Pharmacokinetic/pharmacodynamic (PK/PD) target attainment: Achievement of drug concentration and exposure metrics that correlate with optimal antimicrobial effect.

Therapeutic drug monitoring (TDM): Measurement of drug levels in patient samples to adjust dosing and ensure therapeutic efficacy while minimising toxicity.

References

1. Predictors of mortality from extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia. Emerging Microbes & Infections (2023).
2. Efficacy of carbapenem vs non carbapenem β-lactam therapy as empiric antimicrobial therapy in patients with extended-spectrum β-lactamase-producing Enterobacterales urinary septic shock: a propensity-weighted multicenter cohort study. Annals of Intensive Care (2023).
3. Real-Time TDM-Guided Optimal Joint PK/PD Target Attainment of Continuous Infusion Piperacillin–Tazobactam Monotherapy Is an Effective Carbapenem-Sparing Strategy for Treating Non-Severe ESBL-Producing Enterobacterales Secondary Bloodstream Infections: Findings from a Prospective Pilot Study. Microorganisms (2024).
4. Carbapenem-Sparing Strategies for ESBL Producers: When and How. Antibiotics (2020).