Treatment of extended-spectrum β-lactamases infections: what is the current role of new β-lactams/β-lactamase inhibitors?

Abstract

PURPOSE OF REVIEW:

The widespread diffusion of extended-spectrum β-lactamases (ESBLs)-producing Enterobacteriales currently represents a major threat for public health worldwide. Carbapenems are currently considered the first-line choice for serious ESBL infections. However, the dramatic global increase in ESBL prevalence has led to a significant overuse of carbapenems that has promoted the selection and spread of carbapenemases, which might further prejudicated our ability to treat infections due to multidrug-resistant pathogens. Therefore, strategies to limit the use of carbapenems should be implemented.

RECENT FINDINGS:

Although piperacillin-tazobactam should no longer be considered an alternative to carbapenems for definitive treatment of bloodstream infections due to ESBL-producing strains, it might still represent an alternative for step-down therapy or for low-to-moderate severity infection originating from urinary or biliary sources and when piperacillin-tazobactam minimum inhibitory concentration of 4 mg/l or less. Ceftazidime-avibactam and ceftolozane-tazobactam are both carbapenem sparing agents that appear interesting alternatives for treatment of serious ESBL infections. New β-lactams/β-lactamase inhibitors (BL/BLI), including cefepime-enmetazobactam, ceftaroline fosamil-avibactam, aztreonam-avibactam and cefepime-zidebactam, are also promising agents for treatment of ESBL infections, but further clinical data are needed to establish their efficacy relative to carbapenems. The role of carbapenems/β-lactamase inhibitors remain to be clarified.

SUMMARY:

New BL/BLI have distinctive specificities and limitations that require further investigations. Future randomized clinical trials are required to define the best strategy for their administering for ESBL infections.

• Authors: Matteo Bassetti, Daniele R Giacobbe, Chiara Robba, Paolo Pelosi, Antonio Vena
• Journal: Current opinion in infectious diseases (Curr Opin Infect Dis) Vol. 33 Issue 6 Pg. 474-481 (12 2020) ISSN: 1473-6527 [Electronic] United States
• PMID: 33060469 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Bacterial Agents
• Azabicyclo Compounds
• Bacterial Proteins
• Carbapenems
• Cephalosporins
• Cyclooctanes
• Drug Combinations
• WCK 5222
• avibactam, ceftazidime drug combination
• beta-Lactamase Inhibitors
• beta-Lactams
• ceftolozane, tazobactam drug combination
• Piperacillin, Tazobactam Drug Combination
• Ceftazidime
• beta-Lactamases
• carbapenemase
• Tazobactam

Topics

• Anti-Bacterial Agents (therapeutic use)
• Azabicyclo Compounds (therapeutic use)
• Bacterial Proteins (metabolism)
• Carbapenems (therapeutic use)
• Ceftazidime (therapeutic use)
• Cephalosporins (therapeutic use)
• Cyclooctanes (therapeutic use)
• Drug Combinations
• Drug Resistance, Multiple, Bacterial
• Enterobacteriaceae (isolation & purification)
• Enterobacteriaceae Infections (drug therapy, epidemiology)
• Humans
• Microbial Sensitivity Tests
• Piperacillin, Tazobactam Drug Combination (therapeutic use)
• Public Health
• Sepsis (drug therapy)
• Tazobactam (therapeutic use)
• beta-Lactamase Inhibitors (therapeutic use)
• beta-Lactamases (metabolism)
• beta-Lactams (therapeutic use)
• Ceftaroline