scholarly journals Determination of Disk Diffusion and MIC Quality Control Ranges for Nafithromycin (WCK 4873), a New Lactone-Ketolide

2017 ◽  
Vol 55 (10) ◽  
pp. 3021-3027 ◽  
Author(s):  
Meredith A. Hackel ◽  
James A. Karlowsky ◽  
Dana Dressel ◽  
Daniel F. Sahm
Keyword(s):  
Quality Control ◽  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Tier 2 ◽  
Phase 3 ◽  
Content Type ◽  
Surveillance Studies ◽  
Testing Patient

ABSTRACTDisk diffusion and MIC quality control (QC) ranges were determined for nafithromycin, a new lactone-ketolide, following the completion of a nine-laboratory, Clinical and Laboratory Standards Institute (CLSI) document M23-defined tier 2 study. Five QC strains consistent with the spectrum of activity of nafithromycin were tested:Staphylococcus aureusATCC 25923 (disk only),S. aureusATCC 29213 (broth only),Enterococcus faecalisATCC 29212 (broth only),Streptococcus pneumoniaeATCC 49619 (disk and broth), andHaemophilus influenzaeATCC 49247 (disk and broth). Nafithromycin disk diffusion QC ranges were determined to be 25 to 31 mm forS. aureusATCC 25923, 25 to 31 mm forS. pneumoniaeATCC 49619, and 16 to 20 mm forH. influenzaeATCC 49247. Nafithromycin MIC QC ranges were determined to be 0.06 to 0.25 μg/ml forS. aureusATCC 29213, 0.016 to 0.12 μg/ml forE. faecalisATCC 29212, 0.008 to 0.03 μg/ml forS. pneumoniaeATCC 49619, and 2 to 8 μg/ml forH. influenzaeATCC 49247. All disk diffusion and MIC QC ranges established in this study were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing at their June 2015 meeting and were initially reported in the 2017 M100S document. The QC ranges established in this study should be used for determining thein vitroactivity of nafithromycin in phase 2 and phase 3 human clinical trials and subsequently for testing patient isolates and isolates in phase 4 surveillance studies.

scholarly journals Determination of MIC Quality Control Ranges for the Novel Gyrase Inhibitor Zoliflodacin

2019 ◽  
Vol 57 (9) ◽  
Author(s):  
Alita A. Miller ◽  
Maria M. Traczewski ◽  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
John P. Mueller
Keyword(s):  
Quality Control ◽  
Susceptibility Testing ◽  
The Novel ◽  
Tier 2 ◽  
Phase 3 ◽  
Content Type ◽  
Surveillance Studies ◽  
Agar Dilution

ABSTRACT This report describes the results of two different, multilaboratory quality control (QC) studies that were used to establish QC ranges for the novel gyrase inhibitor zoliflodacin against the ATCC strains recommended by the Clinical and Laboratory Standards Institute (CLSI). Following the completion of an eight-laboratory, CLSI document M23-defined tier 2 study, the agar dilution MIC QC range for zoliflodacin against the Neisseria gonorrhoeae QC strain ATCC 49226 was defined as 0.06 to 0.5 μg/ml and was approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing. This QC range will be used for in vitro susceptibility testing of zoliflodacin during phase 3 human clinical trials and surveillance studies, and eventually it will be implemented in clinical labs. In a separate study, broth microdilution MIC quality control ranges for zoliflodacin against additional QC strains were determined to be 0.12 to 0.5 μg/ml for Staphylococcus aureus ATCC 29213, 0.25 to 2 μg/ml for Enterococcus faecalis ATCC 29212, 1 to 4 μg/ml for Escherichia coli ATCC 25922, 0.12 to 0.5 μg/ml for Streptococcus pneumoniae ATCC 49619, and 0.12 to 1 μg/ml for Haemophilus influenzae ATCC 49247. These MIC QC ranges were also approved by CLSI for use in future in vitro susceptibility testing studies against organisms other than N. gonorrhoeae.

scholarly journals Determination of Disk Diffusion and MIC Quality Control Guidelines for Solithromycin, a Novel Fluoroketolide Antibacterial, against Neisseria gonorrhoeae

2015 ◽  
Vol 53 (12) ◽  
pp. 3888-3890 ◽  
Author(s):  
Stefan Riedel ◽  
James E. Ross ◽  
David J. Farrell ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Quality Control ◽  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Control Strain ◽  
Content Type ◽  
Disk Diffusion Testing ◽  
Quality Control Study ◽  
Agar Dilution ◽  
Control Study

This solithromycin quality control study was performed to establish quality control (QC) ranges for theN. gonorrhoeaeATCC 49226 control strain for MIC agar dilution testing (AD) and zones by disk diffusion testing (DD). The following ranges were established: AD, 0.03 to 0.25 μg/ml, and DD, 33 to 43 mm. In January 2015, the CLSI Subcommittee on Antimicrobial Susceptibility Testing approved these ranges, which will be important when evaluating solithromycin against clinical isolates ofN. gonorrhoeae.

scholarly journals DelafloxacinIn VitroBroth Microdilution and Disk Diffusion Antimicrobial Susceptibility Testing Guidelines: Susceptibility Breakpoint Criteria and Quality Control Ranges for an Expanded-Spectrum Anionic Fluoroquinolone

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
M. A. Pfaller ◽  
R. K. Flamm ◽  
S. P. McCurdy ◽  
C. M. Pillar ◽  
D. Shortridge ◽  
...  
Keyword(s):  
Quality Control ◽  
Susceptibility Testing ◽  
Test Methods ◽  
Susceptibility Test ◽  
Disk Diffusion ◽  
Surveillance Program ◽  
Broth Microdilution ◽  
Testing Methods ◽  
Content Type

ABSTRACTDelafloxacin, a recently approved anionic fluoroquinolone, was tested within an international resistance surveillance program. Thein vitrosusceptibilities of 7,914 indicated pathogens causing acute bacterial skin and skin structure infections (ABSSSI) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MIC testing methods. The U.S. Food and Drug Administration (FDA) susceptibility testing breakpoints and quality control ranges for routine broth microdilution and disk diffusion methods were confirmed. The delafloxacin MIC50/90(% susceptibility) results were as follows:Staphylococcus aureus, including methicillin-resistantS. aureus(MRSA), 0.008/0.25 μg/ml (92.8%);Staphylococcus lugdunensis, 0.016/0.03 μg/ml (99.3%);Streptococcus pyogenes, 0.016/0.03 μg/ml (100.0%);Streptococcus anginosusgroup, 0.008/0.016 μg/ml (100.0%);Enterococcus faecalis, 0.12/1 μg/ml (66.2%); andEnterobacteriaceae, 0.12/4 μg/ml (69.5%). The FDA clinical breakpoints were used to assess intermethod test agreement between delafloxacin MIC and disk diffusion methods for the indicated pathogens. The intermethod susceptibility test categorical agreement for delafloxacin was acceptable, with only 0.4% very major, false-susceptible errors amongS. aureusstrains. Across all FDA-indicated species, the selected breakpoints produced only 0.0 to 1.7% rates of serious (very major and major errors) intermethod error. Quality control ranges for these standardized delafloxacin susceptibility test methods were calculated from three multilaboratory (12 total sites) studies for six control organisms. In conclusion, the application of FDA MIC breakpoints for delafloxacin against contemporary (2014 to 2016) isolates of ABSSSI pathogens provides additional support for the use of delafloxacin in the treatment of adults with ABSSSI. Delafloxacin MIC and disk diffusion susceptibility testing methods have been standardized for clinical application, achieving high intermethod categorical agreement.

scholarly journals EUCAST Determination of Olorofim (F901318) Susceptibility of Mold Species, Method Validation, and MICs

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Karin Meinike Jørgensen ◽  
Karen M. T. Astvad ◽  
Rasmus Krøger Hare ◽  
Maiken Cavling Arendrup
Keyword(s):  
Fusarium Solani ◽  
Susceptibility Testing ◽  
Wild Type ◽  
Preparation Methods ◽  
Content Type ◽  
Microtiter Plates ◽  
Upper Limits ◽  
Limited Variation

ABSTRACT Olorofim is a novel antifungal agent with in vitro activity against Aspergillus and some other molds. Here, we addressed technical aspects for EUCAST olorofim testing and generated contemporary MIC data. EUCAST E.Def 9.3.1 testing was performed comparing two plate preparation methods (serial dilution in medium [serial plates] versus predilution in DMSO [ISO plates]), two lots of olorofim, visual (visual-MIC) versus spectrophotometer (spec-MIC) reading, and four polystyrene plates using 34 to 53 Aspergillus isolates from five genera. Subsequently, olorofim MICs were compared to itraconazole, voriconazole, posaconazole, and amphotericin B MICs for 298 clinical mold isolates (2016 to 2017). Wild-type upper limits (WT-UL) were determined following EUCAST principles for epidemiologic cutoff value (ECOFF) setting. Olorofim median MICs comparing serial plates and ISO plates were identical (25/36 [69%]) or one dilution apart (11/36 [31%]). Interperson agreement for visual-MICs was 92% to 94%/100% for ≤1/≤2 dilutions, respectively. The visual-MIC values across tested microtiter plates and olorofim lots revealed only discrete differences (≤1 dilution lower for treated plates). No single spec-MIC criterion was applicable to all species. Olorofim MICs were low against 275 Aspergillus species isolates (modal MIC, 0.06 mg/liter; MIC range, < 0.004 to 0.25 mg/liter) and three dermatophytes (MICs 0.03 to 0.06 mg/liter). MICs against Fusarium were diverse, with full inhibition of F. proliferatum (MIC, 0.016), 50% growth inhibition of Fusarium solani at 1 to 2 mg/liter, and no inhibition of F. dimerum. Olorofim displayed potent in vitro activity against most mold isolates and was associated with limited variation in EUCAST susceptibility testing.

scholarly journals In Vitro Antimicrobial Activity of a New Cephalosporin, Ceftaroline, and Determination of Quality Control Ranges for MIC Testing

2008 ◽  
Vol 53 (3) ◽  
pp. 1271-1274 ◽  
Author(s):  
Steven D. Brown ◽  
Maria M. Traczewski
Keyword(s):  
Antimicrobial Activity ◽  
Quality Control ◽  
Disk Diffusion ◽  
Bacterial Isolates ◽  
In Vitro Antimicrobial Activity ◽  
Reference Strains ◽  
Phenotypic Groups

ABSTRACT The spectrum of activity of ceftaroline was evaluated against 1,247 bacterial isolates representing 44 different species or phenotypic groups. For the majority of species, the activity of ceftaroline was comparable or superior to that of ceftriaxone. MIC and/or disk diffusion quality control ranges of ceftaroline were determined for five standard ATCC reference strains.

scholarly journals Effects of KPC Variant and Porin Genotype on the In Vitro Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
William R. Wilson ◽  
Ellen G. Kline ◽  
Chelsea E. Jones ◽  
Kristin T. Morder ◽  
Roberta T. Mettus ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Disk Diffusion ◽  
Broth Microdilution ◽  
Wild Type ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Strip Testing ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We describe the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered Escherichia coli isolates harboring mutant blaKPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam MICs were 1 and 0.03 µg/ml, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MICs ≤ 4 µg/ml). Against Klebsiella pneumoniae isolates harboring mutant blaKPC, the addition of vaborbactam lowered the meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates with mutant ompK36 porin genes (n = 26) than against those with wild-type ompK36 porin genes (n = 54) (0.25 versus 0.03 µg/ml; P < 0.0001). Against E. coli TOP10 isolates with plasmid constructs containing wild-type blaKPC or mutant blaKPC, the addition of vaborbactam at 8 µg/ml lowered the meropenem MICs 2- to 512-fold, resulting in meropenem-vaborbactam MICs of 0.03 µg/ml. The rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged from 90 to 95%. Essential agreement rates were higher for research-use-only (RUO) gradient strips manufactured by bioMérieux (82%) than for those manufactured by Liofilchem (48%) (P < 0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae isolates with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. The results of susceptibility testing with RUO bioMérieux gradient strips most closely aligned with those of broth microdilution methods.

scholarly journals In Vitro Activity of Iclaprim against Isolates in Two Phase 3 Clinical Trials (REVIVE-1 and -2) for Acute Bacterial Skin and Skin Structure Infections

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Stephanie Noviello ◽  
Sophie Magnet ◽  
Stephen Hawser ◽  
David B. Huang
Keyword(s):  
Susceptibility Testing ◽  
In Vitro Activity ◽  
Phase 3 ◽  
Gram Positive ◽  
Two Phase ◽  
Content Type ◽  
Skin Structure ◽  
Streptococcus Anginosus ◽  
Antibacterial Susceptibility

ABSTRACT Iclaprim, a selective bacterial dihydrofolate reductase inhibitor, and other antibiotics were tested against Gram-positive isolates from two phase 3 studies of acute bacterial skin and skin structure infections (ABSSSIs) (REVIVE-1 and -2). Seven hundred ninety baseline isolates, including Staphylococcus aureus, β-hemolytic streptococci, and Streptococcus anginosus group, underwent antibacterial susceptibility testing. Iclaprim had an MIC90 of 0.12 μg/ml for S. aureus (0.12 μg/ml for methicillin susceptible, 0.25 μg/ml for methicillin resistant), 0.25 μg/ml for β-hemolytic streptococci, and 0.008 μg/ml for S. anginosus group. Iclaprim demonstrated potent activity against these Gram-positive ABSSSI isolates.

scholarly journals Cefiderocol Antimicrobial Susceptibility Testing Considerations: the Achilles' Heel of the Trojan Horse?

2020 ◽  
Vol 59 (1) ◽  
pp. e00951-20 ◽  
Author(s):  
Patricia J. Simner ◽  
Robin Patel
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Antimicrobial Susceptibility Testing ◽  
Disk Diffusion ◽  
Research Use ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton

ABSTRACTCefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death. Iron concentrations need to be taken into consideration when in vitro antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine in vitro activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of in vivo activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other Acinetobacter species (non-baumannii complex) and Stenotrophomonas maltophilia at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.

scholarly journals Determination of Disk Diffusion and MIC Quality Control Guidelines for High-Dose Cefepime-Tazobactam (WCK 4282), a Novel Antibacterial Combination Consisting of a β-Lactamase Inhibitor and a Fourth-Generation Cephalosporin

2017 ◽  
Vol 55 (10) ◽  
pp. 3130-3134 ◽  
Author(s):  
Stefan Riedel ◽  
Michael D. Huband ◽  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Quality Control ◽  
Generation Cephalosporin ◽  
Test Methods ◽  
Disk Diffusion ◽  
Fourth Generation ◽  
High Dose ◽  
Gram Negative ◽  
Lactamase Inhibitor

ABSTRACTHigh-dose cefepime-tazobactam (1:1; WCK 4282), a novel antibacterial combination consisting of the β-lactamase inhibitor tazobactam and a fourth-generation cephalosporin, is under clinical development for the treatment of serious Gram-negative infections. A quality control (QC) study was performed to establish disk diffusion and MIC ranges for cefepime-tazobactam for multiple QC reference strains. The cefepime-tazobactam QC ranges for a fixed tazobactam MIC of 8 μg/ml and disk diffusion (30/20-μg disk) test methods were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing in January 2015 and January 2016. These QC ranges will be important for accuratein vitroactivity evaluations of cefepime-tazobactam when tested against clinical Gram-negative bacteria during clinical studies and routine patient care.

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