scholarly journals Baseline Activity of Telavancin against Gram-Positive Clinical Isolates Responsible for Documented Infections in U.S. Hospitals (2011-2012) as Determined by the Revised Susceptibility Testing Method

2014 ◽  
Vol 59 (1) ◽  
pp. 702-706 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
David J. Farrell ◽  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones

ABSTRACTTelavancin had MIC50and MIC90values of 0.03 and 0.06 μg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptibleStaphylococcus aureus. Telavancin was active against vancomycin-susceptibleEnterococcus faecalis(MIC50/90, 0.12/0.12 μg/ml; 100% susceptible) andEnterococcus faecium(MIC50/90, 0.03/0.06 μg/ml), while higher MIC values were obtained against vancomycin-resistantE. faecium(MIC50/90, 1/2 μg/ml) andE. faecalis(MIC50/90, >2/>2 μg/ml). Streptococci showed telavancin modal MIC results of ≤0.015 μg/ml, except againstStreptococcus agalactiae(i.e., 0.03 μg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.

2014 ◽  
Vol 58 (9) ◽  
pp. 5547-5551 ◽  
Author(s):  
David J. Farrell ◽  
Rodrigo E. Mendes ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones

ABSTRACTThe reference broth microdilution (BMD) antimicrobial susceptibility testing method for telavancin was revised to include dimethyl sulfoxide (DMSO) as a solvent and diluent for frozen-form panel preparation, following the CLSI recommendations for water-insoluble agents. Polysorbate 80 (P-80) was also added to the test medium to minimize proven drug losses associated with binding to plastic surfaces. Four hundred sixty-two Gram-positive isolates, including a challenge set of organisms with reduced susceptibilities to comparator agents, were selected and tested using the revised method for telavancin, and the MIC results were compared with those tested by the previously established method and several Sensititre dry-form BMD panel formulations. The revised method provided MIC results 2- to 8-fold lower than the previous method when tested against staphylococci and enterococci, resulting in MIC50values of 0.03 to 0.06 μg/ml for staphylococci and 0.03 and 0.12 μg/ml forEnterococcus faeciumandEnterococcus faecalis, respectively. Less-significant MIC decreases (1 to 2 log2dilution steps) were observed when testing streptococci in broth supplemented with blood, which showed similar MIC50values for both methods. However,Streptococcus pneumoniaehad MIC50results of 0.008 and 0.03 μg/ml when tested by the revised and previous methods, respectively. Highest essential agreement rates (≥94.0%) were noted for one candidate dry-form panel formulation compared to the revised test. The revised BMD method provides lower MIC results for telavancin, especially when tested against staphylococci and enterococci. This is secondary to the use of DMSO for panel production and the presence of P-80, which ensure the proper telavancin testing concentration and result in a more accurate MIC determination. Moreover, earlier studies where the previous method was applied underestimated thein vitrodrug potency.


2017 ◽  
Vol 55 (6) ◽  
pp. 1883-1893 ◽  
Author(s):  
Cheryl Leong ◽  
Antonino Buttafuoco ◽  
Martin Glatz ◽  
Philipp P. Bosshard

ABSTRACTMalasseziais a genus of lipid-dependent yeasts. It is associated with common skin diseases such as pityriasis versicolor and atopic dermatitis and can cause systemic infections in immunocompromised individuals. Owing to the slow growth and lipid requirements of these fastidious yeasts, convenient and reliable antifungal drug susceptibility testing assays forMalasseziaspp. are not widely available. Therefore, we optimized a broth microdilution assay for the testing ofMalasseziathat is based on the CLSI and EUCAST assays forCandidaand other yeasts. The addition of ingredients such as lipids and esculin provided a broth medium formulation that enabled the growth of allMalasseziaspp. and could be read, with the colorimetric indicator resazurin, by visual and fluorescence readings. We tested the susceptibility of 52 strains of 13Malasseziaspecies to 11 commonly used antifungals. MIC values determined by visual readings were in good agreement with MIC values determined by fluorescence readings. The lowest MICs were found for the azoles itraconazole, posaconazole, and voriconazole, with MIC90values of 0.03 to 1.0 μg/ml, 0.06 to 0.5 μg/ml, and 0.03 to 2.0 μg/ml, respectively. AllMalasseziaspp. were resistant to echinocandins and griseofulvin. SomeMalasseziaspp. also showed high MIC values for ketoconazole, which is the most widely recommended topical antifungal to treatMalasseziaskin infections. In summary, our assay enables the fast and reliable susceptibility testing ofMalasseziaspp. with a large panel of different antifungals.


2013 ◽  
Vol 57 (11) ◽  
pp. 5701-5703 ◽  
Author(s):  
María Díez-Aguilar ◽  
María-Isabel Morosini ◽  
Rosa del Campo ◽  
María García-Castillo ◽  
Javier Zamora ◽  
...  

ABSTRACTThe broth microdilution method for fosfomycin andPseudomonas aeruginosawas assessed and compared with the approved agar dilution method in 206 genetically unrelatedP. aeruginosaclinical isolates. Essential agreement between the two methods was 84%, and categorical agreement was 89.3%. Additionally, Etest and disk diffusion assays were performed. Results validate broth microdilution as a reliable susceptibility testing method for fosfomycin againstP. aeruginosa. Conversely, unacceptable concordance was established between Etest and disk diffusion results with agar dilution results.


2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Helio S. Sader ◽  
Glenn E. Dale ◽  
Paul R. Rhomberg ◽  
Robert K. Flamm

ABSTRACT Murepavadin (formerly POL7080), a 14-amino-acid cyclic peptide, and comparators were tested by the broth microdilution method against 1,219 Pseudomonas aeruginosa isolates from 112 medical centers. Murepavadin (MIC 50/90 , 0.12/0.12 mg/liter) was 4- to 8-fold more active than colistin (MIC 50/90 , 1/1 mg/liter) and polymyxin B (MIC 50/90 , 0.5/1 mg/liter) and inhibited 99.1% of isolates at ≤0.5 mg/liter. Only 4 isolates (0.3%) exhibited murepavadin MICs of >2 mg/liter. Murepavadin was equally active against isolates from Europe, the United States, and China.


2013 ◽  
Vol 58 (2) ◽  
pp. 916-922 ◽  
Author(s):  
M. A. Pfaller ◽  
A. Espinel-Ingroff ◽  
B. Bustamante ◽  
E. Canton ◽  
D. J. Diekema ◽  
...  

ABSTRACTSince epidemiological cutoff values (ECVs) using CLSI MICs from multiple laboratories are not available forCandidaspp. and the echinocandins, we established ECVs for anidulafungin and micafungin on the basis of wild-type (WT) MIC distributions (for organisms in a species-drug combination with no detectable acquired resistance mechanisms) for 8,210Candida albicans, 3,102C. glabrata, 3,976C. parapsilosis, 2,042C. tropicalis, 617C. krusei, 258C. lusitaniae, 234C. guilliermondii, and 131C. dubliniensisisolates. CLSI broth microdilution MIC data gathered from 15 different laboratories in Canada, Europe, Mexico, Peru, and the United States were aggregated to statistically define ECVs. ECVs encompassing 97.5% of the statistically modeled population for anidulafungin and micafungin were, respectively, 0.12 and 0.03 μg/ml forC. albicans, 0.12 and 0.03 μg/ml forC. glabrata, 8 and 4 μg/ml forC. parapsilosis, 0.12 and 0.06 μg/ml forC. tropicalis, 0.25 and 0.25 μg/ml forC. krusei, 1 and 0.5 μg/ml forC. lusitaniae, 8 and 2 μg/ml forC. guilliermondii, and 0.12 and 0.12 μg/ml forC. dubliniensis. Previously reported single and multicenter ECVs defined in the present study were quite similar or within 1 2-fold dilution of each other. For a collection of 230 WT isolates (nofksmutations) and 51 isolates withfksmutations, the species-specific ECVs for anidulafungin and micafungin correctly classified 47 (92.2%) and 51 (100%) of thefksmutants, respectively, as non-WT strains. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin and micafungin due tofksmutations.


2013 ◽  
Vol 57 (8) ◽  
pp. 3823-3828 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
A. Chowdhary ◽  
G. M. Gonzalez ◽  
C. Lass-Flörl ◽  
E. Martin-Mazuelos ◽  
...  

ABSTRACTEpidemiological cutoff values (ECVs) were established for the new triazole isavuconazole andAspergillusspecies wild-type (WT) MIC distributions (organisms in a species-drug combination with no detectable acquired resistance mechanisms) that were defined with 855Aspergillus fumigatus, 444A. flavus, 106A. nidulans, 207A. niger, 384A. terreus, and 75A. versicolorspecies complex isolates; 22AspergillussectionUstiisolates were also included. CLSI broth microdilution MIC data gathered in Europe, India, Mexico, and the United States were aggregated to statistically define ECVs. ECVs were 1 μg/ml for theA. fumigatusspecies complex, 1 μg/ml for theA. flavusspecies complex, 0.25 μg/ml for theA. nidulansspecies complex, 4 μg/ml for theA. nigerspecies complex, 1 μg/ml for theA. terreusspecies complex, and 1 μg/ml for theA. versicolorspecies complex; due to the small number of isolates, an ECV was not proposed forAspergillussectionUsti. These ECVs may aid in detecting non-WT isolates with reduced susceptibility to isavuconazole due tocyp51A(anA. fumigatusspecies complex resistance mechanism among the triazoles) or other mutations.


2020 ◽  
Vol 64 (3) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Dee Shortridge ◽  
Helio S. Sader ◽  
Mariana Castanheira

ABSTRACT Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales isolates causing pneumonia, including VAP, in hospitalized patients in the United States. Susceptibility testing was performed by using the broth microdilution method, and all carbapenem-resistant isolates were submitted for whole-genome sequencing. Meropenem-vaborbactam exhibited almost complete activity against Enterobacterales (>99.9% susceptible), including carbapenem-resistant Enterobacterales (CRE), and was also very active against P. aeruginosa isolates (89.5% susceptible).


2011 ◽  
Vol 55 (11) ◽  
pp. 5150-5154 ◽  
Author(s):  
A. Espinel-Ingroff ◽  
M. Cuenca-Estrella ◽  
A. Fothergill ◽  
J. Fuller ◽  
M. Ghannoum ◽  
...  

ABSTRACTAlthough clinical breakpoints have not been established for mold testing, epidemiological cutoff values (ECVs) are available forAspergillusspp. versus the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a species-drug combination with no acquired resistance mechanisms) were defined in order to establish ECVs for sixAspergillusspp. and amphotericin B. Two sets (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those forA. fumigatus(3,988/833),A. flavus(793/194),A. nidulans(184/69),A. niger(673/140),A. terreus(545/266), andA. versicolor(135/22). Three sets of data were analyzed: (i) CLSI data gathered in eight independent laboratories in Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory; and (iii) the combined CLSI and EUCAST data. ECVs, expressed in μg/ml, that captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and combined data) were as follows: forA. fumigatus, 2, 2, and 4; forA. flavus, 2, 4, and 4; forA. nidulans, 4, 4, and 4; forA. niger, 2, 2, and 2; forA. terreus, 4, 4, and 8; and forA. versicolor, 2, 2, and 2. Similar to the case for the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of strains with acquired mechanisms of resistance to this agent.


Author(s):  
Maria M. Traczewski ◽  
Jane E. Ambler ◽  
Raymond Schuch

Exebacase (CF-301), a novel, anti-staphylococcal lysin (cell-wall hydrolase) is the first agent of this class to enter late-stage clinical development (Phase 3, NCT04160468) for the treatment of Staphylococcus aureus bacteremia including right-sided endocarditis. A multi-laboratory Clinical and Laboratory Standards Institute (CLSI) M23-defined tier 2 quality control (QC) study was conducted to establish exebacase QC ranges for a new reference broth microdilution method. Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 were selected as reference QC strains. Broth microdilution MIC QC ranges for exebacase spanned 4 log2 dilutions and contained 99.2% of the MIC results generated for the two reference strains. The QC ranges for exebacase were defined as 0.25–2 μg/ml and 8–64 μg/ml against S. aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, respectively and were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing. These QC ranges established for use with the reference broth microdilution method developed for exebacase susceptibility testing will ensure the test performance and accuracy of results generated during clinical development.


2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Mariana Castanheira ◽  
Andrew P. Davis ◽  
Rodrigo E. Mendes ◽  
Alisa W. Serio ◽  
Kevin M. Krause ◽  
...  

ABSTRACTPlazomicin and comparator agents were tested by using the CLSI reference broth microdilution method against 4,825 clinical isolates collected during 2014 and 2015 in 70 U.S. hospitals as part of the ALERT (Antimicrobial Longitudinal Evaluation and Resistance Trends) program. Plazomicin (MIC50/MIC90, 0.5/2 μg/ml) inhibited 99.2% of 4,362Enterobacteriaceaeat ≤4 μg/ml. Amikacin, gentamicin, and tobramycin inhibited 98.9%, 90.3%, and 90.3% of these isolates, respectively, by applying CLSI breakpoints. The activities of plazomicin were similar amongEnterobacteriaceaespecies, with MIC50values ranging from 0.25 to 1 μg/ml, with the exception ofProteus mirabilisand indole-positiveProteeaethat displayed MIC50values of 2 μg/ml. For 97 carbapenem-resistantEnterobacteriaceae(CRE), which included 87 isolates carryingblaKPC, plazomicin inhibited all but 1 isolate at ≤2 μg/ml (99.0% and 98.9%, respectively). Amikacin and gentamicin inhibited 64.9% and 56.7% of the CRE isolates at the respective CLSI breakpoints. Plazomicin inhibited 96.5 and 95.5% of the gentamicin-resistant isolates, 96.9 and 96.5% of the tobramycin-resistant isolates, and 64.3 and 90.0% of the amikacin-resistant isolates according to CLSI and EUCAST breakpoints, respectively. The activities of plazomicin againstPseudomonas aeruginosa(MIC50/MIC90, 4/16 μg/ml) andAcinetobacterspecies (MIC50/MIC90, 2/16 μg/ml) isolates were similar. Plazomicin was active against coagulase-negative staphylococci (MIC50/MIC90, 0.12/0.5 μg/ml) andStaphylococcus aureus(MIC50/MIC90, 0.5/0.5 μg/ml) but had limited activity againstEnterococcusspp. (MIC50/MIC90, 16/64 μg/ml) andStreptococcus pneumoniae(MIC50/MIC90, 32/64 μg/ml). Plazomicin activity against theEnterobacteriaceaetested, including CRE and isolates carryingblaKPCfrom U.S. hospitals, supports the development plan for plazomicin to treat serious infections caused by resistantEnterobacteriaceaein patients with limited treatment options.


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