In vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline against carbapenemase-producing Enterobacteriaceae strains

Rodríguez-Avial, Iciar; Peña, Irene; Picazo, Juan J.; Rodríguez-Avial, Carmen; Culebras, Esther

doi:10.1016/j.ijantimicag.2015.07.021

Cited by 55 publications

(19 citation statements)

References 21 publications

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“…The in vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline was tested against carbapenemase-producing Enterobacteriaceae (CPE) strains. When plazomicin was combined with meropenem, colistin or fosfomycin, synergy was observed against CPE isolates ( Rodriguez-Avial et al, 2015 ).…”

Section: The Epidemiology Genetic Context Treatment Options and Dementioning

confidence: 99%

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

et al. 2016

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The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-β-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most β-lactam antibiotics and many other non-β-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed.

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Section: The Epidemiology Genetic Context Treatment Options and Dementioning

confidence: 99%

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

et al. 2016

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“…The next generation aminoglycoside, plazomicin, had an MIC90 value of 1 μg/ml against 164 Enterobacteriaceae isolates expressing Class A ( bla KPC-2 , n =34), Class B ( bla VIM-1 , n=125; bla IMP-22 , n=1), or Class D ( bla OXA-48 , n=4) carbapenemases compared to MIC 90 of 256, 64, and 16 μg/ml for gentamicin, tobramycin, and amikacin respectively [Rodriguez-Avial 2015]. …”

Section: Treatment Optionsmentioning

confidence: 99%

The rapid spread of carbapenem-resistant Enterobacteriaceae

Potter

D’Souza

Dantas

2016

Drug Resistance Updates

318

211

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Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments.

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“…As a consequence, numerous new generation aminoglycosides, also known as neoglycosides, started to be synthesized [ 19 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. Of the several neoglycosides existing in the pipeline, plazomicin (ACHN-490) ( Figure 2 ), which has been granted Breakthrough Therapy designation by the FDA in May 2017, is the one closest to be approved for human use [ 59 , 60 , 61 , 62 ]. A New Drug Application for plazomicin was submitted in October 2017 to the U.S. Food and Drug Administration [ 63 ].…”

Section: A Brief History Of Aminoglycoside Antibioticsmentioning

confidence: 99%

Amikacin: Uses, Resistance, and Prospects for Inhibition

2017

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Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.

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In vitro activity of the next-generation aminoglycoside plazomicin alone and in combination with colistin, meropenem, fosfomycin or tigecycline against carbapenemase-producing Enterobacteriaceae strains

Cited by 55 publications

References 21 publications

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

Global Dissemination of Carbapenemase-Producing Klebsiella pneumoniae: Epidemiology, Genetic Context, Treatment Options, and Detection Methods

The rapid spread of carbapenem-resistant Enterobacteriaceae

Amikacin: Uses, Resistance, and Prospects for Inhibition

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