Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes and other resistance mechanisms

Castanheira, Mariana; Deshpande, Lalitagauri M.; Woosley, Leah N.; Serio, Alisa W.; Krause, Kevin M.; Flamm, Robert K.

doi:10.1093/jac/dky344

Cited by 39 publications

(54 citation statements)

References 14 publications

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“…In several surveillance studies, plazomicin exhibited MIC 50/90 against Pseudomonas aeruginosa between 4-8 and 8-32 µg/mL. 12,14,18,19,21 This was similar to the amikacin activity in all of these studies. Similarly, in the studies in which these data were published, the plazomicin MIC 50/90 in isolates resistant to amikacin jumped to 64/>64 µg/mL.…”

Section: Chemistry and Mechanism Of Actionsupporting

confidence: 71%

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Clark

Burgess

2020

Therapeutic Advances in Infection

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Objective: To review the mechanism of action, mechanisms of resistance, in vitro activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside. Data sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature. Study selection and data extraction: All English-language studies presenting original research ( in vitro, in vivo, pharmacokinetic, and clinical) were evaluated. Data synthesis: Plazomicin has in vitro activity against several multi-drug-resistant organisms, including carbapenem-resistant Enterobacteriaceae. It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial. Relevance to patient care and clinical practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant Enterobacteriaceae infections. Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant Enterobacteriaceae.

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Section: Chemistry and Mechanism Of Actionsupporting

confidence: 71%

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Clark

Burgess

2020

Therapeutic Advances in Infection

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“…In vitro studies suggest that plazomicin has activity against most CREs including those isolates that produce KPC and VIM enzymes; however, there is concern that some NDM-producing isolates co-expresse16S rRNA methylase which inactivate the aminoglycoside-binding site in the ribosome inactivating nearly all aminoglycosides including plazomicin. 103,104 In addition to the complicated urinary tract infection indication, FDA approval for bloodstream infections caused by documented or presumed CRE was also sought but was denied because the RCT did not meet its predefined enrollment. 105,106 In this study 39 patients underwent randomization with 18 receiving plazomicin and 21 receiving a colistin-based regimen with an overall microbiological modified intention to treat population of 37 patients with confirmed CRE.…”

Section: Enterobacteriaceae (Carbapenem Resistant)mentioning

confidence: 99%

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

Strich

Kadri

2019

Semin Respir Crit Care Med

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Antibiotic resistance among gram-negative pathogens is a world-wide problem that poses a constant threat to patients in the intensive care unit and a therapeutic challenge for the intensivist. Furthermore, the substantial economic burden and increased mortality associated with infections due to highly resistant gram-negative pathogens exacerbate these challenges. Understanding the mechanisms, epidemiology, and risk factors for these infections is paramount to the successful control of outbreaks and for guiding therapy which often entails use of antibiotics with suboptimal efficacy and/or toxicity profiles. In this review we will discuss the global epidemiology, burden, risk factors, and treatment of highly resistant gram-negative infections as they apply to the intensive care population.

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“…Plazomicin consistently retains in vitro activity against Gram-negative bacilli resistant to other antimicrobial classes, including isolates harboring extended-spectrum ␤-lactamase (ESBL) enzymes, carbapenemase enzymes, and acquired colistin resistance genes (e.g., mcr-1) (5)(6)(7)(8)(9). Similar to other aminoglycosides, plazomicin is not active against Gram-negative bacilli that possess acquired 16S rRNA methyltransferase genes, but at present these remain uncommon in many parts of the world (3,4,8,(10)(11)(12)(13)(14). Data from recent clinical trials support a role for plazomicin in the treatment of complicated urinary tract infections, and the United States Food and Drug Administration (FDA) has recently approved the use of plazomicin for this indication (15)(16)(17).…”

mentioning

confidence: 99%

In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

Walkty

Karlowsky

Baxter

et al. 2019

Antimicrob Agents Chemother

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The Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate thein vitroactivities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from 2013 to 2017 from patients in Canadian hospitals as part of the CANWARD Surveillance Study. Plazomicin demonstrated potentin vitroactivity againstEnterobacteriaceae(MIC90≤ 1 µg/ml for all species tested exceptProteus mirabilisandMorganella morganii), including aminoglycoside-nonsusceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates ofStaphylococcus aureus.

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Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes and other resistance mechanisms

Abstract: Plazomicin demonstrated activity against Enterobacteriaceae isolates tested in this study, including isolates carrying AMEs and a high percentage of the carbapenem-non-susceptible isolates. Plazomicin displayed activity against staphylococci.

Cited by 39 publications

References 14 publications

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Difficult-to-Treat Antibiotic-Resistant Gram-Negative Pathogens in the Intensive Care Unit: Epidemiology, Outcomes, and Treatment

In Vitro Activity of Plazomicin against Gram-Negative and Gram-Positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017 as Part of the CANWARD Surveillance Study

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