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Ann Pharmacother. 2015 Jan;49(1):86-98. doi: 10.1177/1060028014556652. Epub 2014 Oct 31.

β-lactam/β-lactamase inhibitor combinations: from then to now.

Author information

1
Temple University School of Pharmacy, Philadelphia, PA, USA toussaka@temple.edu.
2
Temple University School of Pharmacy, Philadelphia, PA, USA.

Abstract

OBJECTIVE:

To review the available evidence regarding the utility of the currently available β-lactam/β-lactamase inhibitor combinations (BLICs) as well as the emerging body of data for the novel agents in the pipeline.

DATA SOURCES:

A MEDLINE literature search (1960-August 2014) was performed using the search terms β-lactamase, β-lactamase inhibitor, clavulanate, sulbactam, tazobactam, avibactam, NXL104, MK-7655, and RPX7009. Current studies focusing on new agents were obtained from clinicaltrials.gov. Additional references were identified from a review of literature citations and meeting abstracts.

STUDY SELECTION AND DATA EXTRACTION:

All English-language studies pertaining to BLICs were evaluated.

DATA SYNTHESIS:

Historical clinical and in vitro data focusing on the characteristics of the conventional BLICs are reviewed. Avibactam, relebactam (formerly MK-7655), and RPX7009 are new β-lactamase inhibitors that are being studied in combination with β-lactams. Clinical and in vitro data that provide support for their use for multidrug-resistant organisms are reviewed. β-Lactam antibiotics are a mainstay for the treatment of many infections. The addition of β-lactamase inhibitors enhances their activity against organisms that produce β-lactamases; however, organisms that produce extended-spectrum β-lactamases, AmpC β-lactamases, and carbapenemases are proliferating. The BLICs (amoxicillin/clavulanate, ticarcillin/clavulanate, ampicillin/sulbactam, and piperacillin/tazobactam) lack activity against some of these enzymes, presenting a critical need for new antibiotics.

CONCLUSIONS:

The historical BLICs are useful for many infections; however, evolving resistance limits their use. The new BLICs (combinations with avibactam, relebactam, and RPX7009) may be valuable options for patients infected with multidrug-resistant organisms.

KEYWORDS:

MK-7655; RPX7009; avibactam; bacterial resistance; carbapenemase; clavulanate; relebactam; sulbactam; tazobactam; β-lactamase; β-lactamase inhibitor

PMID:
25361682
DOI:
10.1177/1060028014556652
[Indexed for MEDLINE]

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