Activity of Plazomicin (ACHN-490) against MDR clinical isolates of<i>Klebsiella pneumoniae, Escherichia coli</i>, and<i>Enterobacter</i>spp. from Athens, Greece

Galani, Irene; Souli, María; Daikos, George L.; Chrysouli, Zoi; Poulakou, Garyphalia; Psichogiou, Mina; Panagea, Theofano; Argyropoulou, Athina; Stefanou, Ioanna; Plakias, George; Giamarellou, Helen; Petrikkos, George

doi:10.1179/1973947812y.0000000015

Cited by 94 publications

(66 citation statements)

References 14 publications

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“…Plazomicin demonstrated potent in vitro activity versus members of the family Enterobacteriaceae, including aminoglycoside-nonsusceptible E. coli and ESBL-producing E. coli and K. pneumoniae. Similar results have been reported by other investigators (13,16,17,(20)(21)(22)(23)(24). Furthermore, many of these studies also specifically evaluated the activity of plazomicin against collections of antimicrobial-resistant isolates (20)(21)(22).…”

Section: Discussionsupporting

confidence: 82%

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: 82%

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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“…No significant differences were found between agar dilution MICs and microdilution MICs (MIC 50 , 0.5 mg/liter; MIC 90 , 1 mg/liter; MIC range, 0.125 to 4 mg/liter). Our findings are consistent with previous studies that showed plazomicin to be highly active against MDR clinical isolates of Enterobacteriaceae, including ESBL-producing E. coli isolates (15,16).…”

supporting

confidence: 83%

Plazomicin Activity against 346 Extended-Spectrum-β-Lactamase/AmpC-Producing Escherichia coli Urinary Isolates in Relation to Aminoglycoside-Modifying Enzymes

Lopez-Diaz

Culebras

Rodríguez-Avial

et al. 2017

Antimicrob Agents Chemother

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The activity of plazomicin and clinically relevant aminoglycosides was tested against 346 extended-spectrum-␤-lactamase/AmpC-producing Escherichia coli urinary isolates, and the results were correlated with the presence of aminoglycoside-modifying enzymes (AMEs). Data showed that plazomicin was very active against all ESBL/AmpCproducing E. coli urinary isolates. Its activity was not related to the AME genes studied.KEYWORDS AMEs, ESBL, Escherichia coli, plazomicin, aminoglycosides E scherichia coli strains producing extended-spectrum ␤-lactamases (ESBLs) have emerged as major global pathogens, primarily associated with urinary tract infections (1). These strains possess plasmids that carry genes conferring resistance to multiple antibiotic classes (2). As a result, therapeutic options against these ␤-lactamresistant E. coli infections are extremely limited.Aminoglycoside resistance in Gram-negatives is mainly conferred by production of aminoglycoside-modifying enzymes (AMEs) (3). Genes encoding AMEs are located on mobile genetic elements along with other resistance determinants, resulting in multidrug-resistant (MDR) isolates (3). Plazomicin is a next-generation aminoglycoside modified to evade AMEs. The compound is currently under clinical development for the treatment of complicated urinary tract infections (cUTIs) and acute pyelonephritis as a single agent (4,5).In this study, we evaluated the activity of plazomicin and clinically relevant aminoglycosides against 346 ESBL/AmpC-producing E. coli urinary isolates. The presence of four AME genes was also investigated, and the relationship between the AME genes detected and the resistance phenotype found was determined.The isolates were obtained prospectively during 2013 at the Hospital Clínico San Carlos (Madrid, Spain). Only one isolate per patient was included. PCR characterization (6, 7) showed 302 ESBL producers and 44 AmpC producers.MICs of gentamicin, tobramycin, amikacin, and plazomicin were determined by the agar dilution method. MICs of plazomicin were also determined by the broth microdilution method (8). Antimicrobial agents were obtained from their respective manufacturers. Plazomicin was supplied from Achaogen (South San Francisco, CA). The results were interpreted according the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (9).All isolates resistant to at least one of the aminoglycosides studied were tested by PCR for the presence of AME genes. Sets of primers for the following genes were

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“…It is not affected by the aminoglycoside-modifying enzymes except for AAC(2')-Ia, -Ib, and -Ic. Plazomicin has shown in vitro activity against multidrug-resistant enterobacteria, including isolates producing ESBLs, KPCs, and MLBs, except NDM-1 producers which may be resistant due to the production of 16S rRNA methylase [Endimiani et al 2009;Livermore et al 2011b;Galani et al 2012] and has shown to be efficacious in animal models [Reyes et al 2011].…”

Section: New Antimicrobial Agentsmentioning

confidence: 99%

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

Delgado-Valverde

Sojo-Dorado

Pascual

2013

Therapeutic Advances in Infection

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Enterobacteriaceae showing resistance to cephalosporins due to extended-spectrum b-lactamases (ESBLs) or plasmid-mediated AmpC enzymes, and those producing carbapenemases have spread worldwide during the last decades. Many of these isolates are also resistant to other first-line agents such as fluoroquinolones or aminoglycosides, leaving few available options for therapy. Thus, older drugs such as colistin and fosfomycin are being increasingly used. Infections caused by these bacteria are associated with increased morbidity and mortality compared with those caused by their susceptible counterparts. Most of the evidence supporting the present recommendations is from in vitro data, animal studies, and observational studies. While carbapenems are considered the drugs of choice for ESBL and AmpC producers, recent data suggest that certain alternatives may be suitable for some types of infections. Combined therapy seems superior to monotherapy in the treatment of invasive infections caused by carbapenemase-producing Enterobacteriaceae. Optimization of dosage according to pharmacokinetics/pharmacodynamics data is important for the treatment of infections caused by isolates with borderline minimum inhibitory concentration due to lowlevel resistance mechanisms. The increasing frequency and the rapid spread of multidrug resistance among the Enterobacteriaceae is a true and complex public health problem. IntroductionThe traditional first-line available options for treating serious infections caused by enterobacteria include penicillins, cephalosporins, monobactams, carbapenems, fluorquinolones, and in certain situations, aminoglycosides. The frequency of resistance to these first-line agents has been rising worldwide during the last decades [Paterson 2006;Rhomberg and Jones 2009;Houghton et al. 2010;Nordmann, et al. 2011] and now reach high proportions in many areas of the world.

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Activity of Plazomicin (ACHN-490) against MDR clinical isolates ofKlebsiella pneumoniae, Escherichia coli, andEnterobacterspp. from Athens, Greece

Cited by 94 publications

References 14 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

Plazomicin Activity against 346 Extended-Spectrum-β-Lactamase/AmpC-Producing Escherichia coli Urinary Isolates in Relation to Aminoglycoside-Modifying Enzymes

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

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