Antimicrobial activity of a novel aminoglycoside, ACHN-490, against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City

Landman, David; Kelly, Paul; Bäcker, Martín; Babu, Elizabeth; Shah, Neha; Bratu, Simona; Quale, John

doi:10.1093/jac/dkq459

Cited by 83 publications

(66 citation statements)

References 9 publications

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“…The in vitro activity of plazomicin versus P. aeruginosa was similar to that for amikacin, an aminoglycoside for which the AUC appears to be more comparable (13). The data presented here are in agreement with results published by Landman et al (26). These investigators evaluated plazomicin in comparison with amikacin versus 679 P. aeruginosa isolates.…”

Section: Discussionsupporting

confidence: 90%

“…These investigators evaluated plazomicin in comparison with amikacin versus 679 P. aeruginosa isolates. The MIC 50 and MIC 90 values of plazomicin were 8 g/ml and 32 g/ ml, respectively, and for amikacin, 8 g/ml and 16 g/ml, respectively (26). In the present study, the activity of plazomicin versus MDR P. aeruginosa was similar to that of amikacin.…”

Section: Discussionsupporting

confidence: 65%

See 1 more Smart Citation

In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012

Walkty

Adam

Baxter

et al. 2014

Antimicrob Agents Chemother

110

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Plazomicin is a next-generation aminoglycoside that is not affected by most clinically relevant aminoglycoside-modifying enzymes. The in vitro activities of plazomicin and comparator antimicrobials were evaluated against a collection of 5,015 bacterial isolates obtained from patients in Canadian hospitals between January 2011 and October 2012. Susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, with MICs interpreted according to CLSI breakpoints, when available. Plazomicin demonstrated potent in vitro activity against members of the family Enterobacteriaceae, with all species except Proteus mirabilis having an MIC 90 of <1 g/ml. Plazomicin was active against aminoglycoside-nonsusceptible Escherichia coli, with MIC 50 and MIC 90 values identical to those for aminoglycoside-susceptible isolates. Furthermore, plazomicin demonstrated equivalent activities versus extended-spectrum ␤-lactamase (ESBL)-producing and non-ESBL-producing E. coli and Klebsiella pneumoniae, with 90% of the isolates inhibited by an MIC of <1 g/ml. The MIC 50 and MIC 90 values for plazomicin against Pseudomonas aeruginosa were 4 g/ml and 16 g/ml, respectively, compared with 4 g/ml and 8 g/ml, respectively, for amikacin. Plazomicin had an MIC 50 of 8 g/ml and an MIC 90 of 32 g/ml versus 64 multidrug-resistant P. aeruginosa isolates. Plazomicin was active against methicillin-susceptible and methicillin-resistant Staphylococcus aureus, with both having MIC 50 and MIC 90 values of 0.5 g/ml and 1 g/ml, respectively. In summary, plazomicin demonstrated potent in vitro activity against a diverse collection of Gram-negative bacilli and Gram-positive cocci obtained over a large geographic area. These data support further evaluation of plazomicin in the clinical setting.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 65%

In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012

Walkty

Adam

Baxter

et al. 2014

Antimicrob Agents Chemother

110

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“…These infections are most worrisome because there are no approved or efficacious antimicrobial agents available in many nosocomial settings (11,254). Among the agents that play a role in addressing this issue are plazomicin and eravacycline, protein synthesis inhibitors that have a broad Gram-negative spectrum of activity, including at least some nonfermentative bacteria (10,55). Perhaps the agents with the greatest potential, however, are the ␤-lactamase inhibitor combinations in which potent inhibitors of novel structural classes, such as avibactam, MK-7655, and RPX7009, are combined with safe and efficacious ␤-lactams for the treatment of serious nosocomial infections.…”

Section: Discussionmentioning

confidence: 99%

“…All known transferable aminoglycoside-modifying enzymes were unable to inactive plazomicin, although plasmid-carried armA and rmtC encoding ribosomal methyltransferases, such as those found in NDM-1 metallo-␤-lactamase (MBL)-producing pathogens, conferred resistance to plazomicin with MICs ranging from 64 to Ͼ256 g/ml (53). Plazomicin had modest activity against P. aeruginosa, with MIC 50 values of 8 g/ml, but was more potent than other aminoglycosides against A. baumannii (55).…”

Section: Aminoglycosidesmentioning

confidence: 95%

Investigational Antimicrobial Agents of 2013

Pucci

Bush

2013

Clin Microbiol Rev

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SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting.

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“…Similarly, the broad-spectrum agent eravacycline (a new fluorocycline) also lacks activity against A. baumannii, B. cenocepacia, and P. aeruginosa (949,952). Plazomicin is a new aminoglycoside derivative of sisomicin with significant activity against a range of Gram-positive and Gram-negative bacteria (including multidrug-resistant isolates) (953,954). However, its activity is adversely affected by increased efflux in A. baumannii and P. aeruginosa (955).…”

Section: Multidrug Efflux Pumps As a Challenge In Drug Developmentmentioning

confidence: 99%

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

2015

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SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

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Antimicrobial activity of a novel aminoglycoside, ACHN-490, against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City

Abstract: For A. baumannii, the MICs of ACHN-490 were lower than those of traditional aminoglycosides. For P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin.

Cited by 83 publications

References 9 publications

In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012

In Vitro Activity of Plazomicin against 5,015 Gram-Negative and Gram-Positive Clinical Isolates Obtained from Patients in Canadian Hospitals as Part of the CANWARD Study, 2011-2012

Investigational Antimicrobial Agents of 2013

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

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