Ceftazidime-avibactam: are we safe from class A carbapenemase producers' infections?
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
34505209
DOI
10.1007/s12223-021-00918-5
PII: 10.1007/s12223-021-00918-5
Knihovny.cz E-zdroje
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- azabicyklické sloučeniny MeSH
- bakteriální proteiny genetika MeSH
- beta-laktamasy genetika MeSH
- ceftazidim farmakologie MeSH
- fixní kombinace léků MeSH
- infekce bakteriemi rodu Klebsiella * farmakoterapie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antibakteriální látky MeSH
- avibactam, ceftazidime drug combination MeSH Prohlížeč
- azabicyklické sloučeniny MeSH
- bakteriální proteiny MeSH
- beta-laktamasy MeSH
- carbapenemase MeSH Prohlížeč
- ceftazidim MeSH
- fixní kombinace léků MeSH
Recently, new combinations of β-lactams and β-lactamase inhibitors became available, including ceftazidime-avibactam, and increased the ability to treat infections caused by carbapenem-resistant Enterobacterales (CRE). Despite the reduced time of clinical use, isolates expressing resistance to ceftazidime-avibactam have been reported, even during treatment or in patients with no previous contact with this drug. Here, we detailed review data on global ceftazidime-avibactam susceptibility, the mechanisms involved in resistance, and the molecular epidemiology of resistant isolates. Ceftazidime-avibactam susceptibility remains high (≥ 98.4%) among Enterobacterales worldwide, being lower among extended-spectrum β-lactamase (ESBL) producers and CRE. Alterations in class A β-lactamases are the major mechanism involved in ceftazidime-avibactam resistance, and mutations are mainly, but not exclusively, located in the Ω loop of these enzymes. Modifications in Klebsiella pneumoniae carbapenemase (KPC) 3 and KPC-2 have been observed by many authors, generating variants with different mutations, insertions, and/or deletions. Among these, the most commonly described is Asp179Tyr, both in KPC-3 (KPC-31 variant) and in KPC-2 (KPC-33 variant). Changes in membrane permeability and overexpression of efflux systems may also be associated with ceftazidime-avibactam resistance. Although several clones have been reported, ST258 with Asp179Tyr deserves special attention. Surveillance studies and rationale use are essential to retaining the activity of this and other antimicrobials against class A CRE.
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