In vitro activity of Plazomicin against Enterobacteriaceae isolates carrying genes encoding aminoglycoside-modifying enzymes most common in US Census divisions

Castanheira, Mariana; Davis, Andrew P; Serio, Alisa W.; Krause, Kevin M.; Mendes, Rodrigo E.

doi:10.1016/j.diagmicrobio.2018.10.023

Cited by 25 publications

(16 citation statements)

References 14 publications

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“…Plazomicin, like other aminoglycosides, was not effective against Enterococcus, Streptococcus, and Stenotrophomonas species. 12,13,18,19 Aminoglycoside resistance Aminoglycoside resistance can be mediated by three types of mechanisms: enzymatic modification, target site modification, and porin channel/efflux pump expression changes. The most common mechanism in Enterobacteriaceae species is enzymatic modification mostly via three AME classes: n-acetyltransferases (AACs), o-adenyltransferases (ANTs), and o-phosphotransferases (APHs).…”

Section: Chemistry and Mechanism Of Actionmentioning

confidence: 99%

“…All other aminoglycosides demonstrated significantly lower activity against these isolates with the exception of Enterobacteriaceae expressing 16S rRNA methyltransferases, which conferred resistance to all aminoglycosides as discussed. 12 – 15 These MDR isolates are known to carry numerous determinants of resistance against aminoglycosides, namely AMEs, which explain this sharp decline in activity.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…Plazomicin, like other aminoglycosides, was not effective against Enterococcus, Streptococcus , and Stenotrophomonas species. 12 , 13 , 18 , 19 …”

Section: In Vitro Studiesmentioning

confidence: 99%

“…ArmA and RmtB are the most commonly expressed of these enzymes; 7 however, they are rarely expressed in clinical isolates, with only 0.14%, 1.28%, and 0.05% isolates identified from the U.S., Europe and parts of Asia, and Canada in recent surveillance studies. 12 , 13 , 22 Recent concern has been raised around these enzymes due to their increasing co-expression with New Delhi metallo-beta-lactamase producing isolates. 16 , 23 , 24 …”

Section: Aminoglycoside Resistancementioning

confidence: 99%

“…Two recent publications from the Antimicrobial Longitudinal Evaluation and Resistance Trends global surveillance program identified AAC(6′)-Ib and AAC(3)-IIa as the enzymes most responsible for aminoglycoside resistance in the U.S., Europe, and select countries in Asia. 12,13 While uncommon in Enterobacteriaceae , down-regulation of porin channels and/or increase in efflux pump expression can be seen in P. aeruginosa , and Acinetobacter baumannii in addition to AME expression, which explains the higher MICs often seen in these organisms. 6 Target site modification is carried out by 16S rRNA methyltransferases and completely nullifies the activity of all 4, 6 disubstituted aminoglycosides, which includes gentamicin, tobramycin, and amikacin.…”

Section: Aminoglycoside Resistancementioning

confidence: 99%

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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 Actionmentioning

confidence: 99%

Section: In Vitro Studiesmentioning

confidence: 99%

“…Plazomicin, like other aminoglycosides, was not effective against Enterococcus, Streptococcus , and Stenotrophomonas species. 12 , 13 , 18 , 19 …”

Section: In Vitro Studiesmentioning

confidence: 99%

Section: Aminoglycoside Resistancementioning

confidence: 99%

Section: Aminoglycoside Resistancementioning

confidence: 99%

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Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance

Clark

Burgess

2020

Therapeutic Advances in Infection

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Mechanisms of Resistance to Antibacterial Agents

Bradford,

Castanheira

2023

ClinMicroNow

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Bacterial pathogens have developed resistance to antibacterial agents via multiple routes. The emergence of antimicrobial resistance phenotypes is directly linked to the use of any given anti microbial agent. Resistance to aminoglycosides occurs by several different mechanisms that can coexist in the same bacterial cell. β‐Lactam antibiotics act by inhibiting penicillin‐binding proteins, which are transpeptidases and transglycosylases that synthesize the peptidogly can that composes the bacterial cell wall. The main bacterial resistance mechanism against fluoroquinolonesis is the alteration of their target in the deoxyribonucleic acid synthesis process. Tetracyclines are bacteriostatic antibiotics that inhibit bacterial growth by binding to the ribosome, thereby preventing protein synthesis. Nitrofurantoin is a synthetic antibacterial agent that is only used in the treatment of urinary tract infections. Rifampin is particularly active against Gram‐positive bacteria and mycobacteria. Daptomycin is a cyclic lipopeptide antibiotic with activity exclusively against Gram‐positive bacteria.

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