9 results on '"Arhin, Francis"'
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2. Characterization of the in vitro activity of novel lipoglycopeptide antibiotics.
- Author
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Arhin FF, Belley A, McKay GA, and Moeck G
- Subjects
- Anti-Bacterial Agents chemistry, Biofilms drug effects, Glycopeptides chemistry, Lipopeptides chemistry, Membrane Potentials drug effects, Microbial Viability drug effects, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Glycopeptides pharmacology, Lipopeptides pharmacology, Microbial Sensitivity Tests methods
- Abstract
The increasing incidence of antibiotic resistance in human pathogens is of significant concern. Resistance to the widely-used and highly effective glycopeptide antibacterial agent vancomycin, which has been in clinical use for over half a century, has emerged in staphylococci and enterococci. This has spurred the development of newer glycopeptide agents, some of which show activity against vancomycin-resistant organisms. The newer agents currently being developed contain lipophilic side-chains, which distinguish them from vancomycin; as such, they are categorized as lipoglycopeptides. Oritavancin, telavancin, and dalbavancin are lipoglycopeptides in late-stage development to combat Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. This unit describes methods that may be used to assess the in vitro activities of lipoglycopeptides. The methods include susceptibility assays, time-kill and time-kill-synergy assays, inhibition of synthesis of macromolecules, membrane perturbation assays, and measurement of activity against biofilms.
- Published
- 2010
- Full Text
- View/download PDF
3. Newly defined in vitro quality control ranges for oritavancin broth microdilution testing and impact of variation in testing parameters.
- Author
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Arhin FF, Tomfohrde K, Draghi DC, Aranza M, Parr TR Jr, Sahm DF, and Moeck G
- Subjects
- Humans, Lipoglycopeptides, Microbial Sensitivity Tests methods, Polysorbates, Quality Control, Reference Standards, Anti-Bacterial Agents pharmacology, Enterococcus faecalis drug effects, Glycopeptides pharmacology, Microbial Sensitivity Tests standards, Staphylococcus aureus drug effects, Streptococcus pneumoniae drug effects
- Abstract
A 9-laboratory M23-A2 quality control (QC) study was performed to evaluate reproducibility of oritavancin MICs against reference strains of Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae using broth microdilution assays in the presence of polysorbate 80. Polysorbate 80 has previously been shown to be required for accurate measurement of oritavancin broth microdilution MICs. Greater than 95% of replicate results (n = 270/organism) fell within the following QC ranges (in micrograms per milliliter): S. aureus ATCC 29213, 0.015 to 0.12; E. faecalis ATCC 29212, 0.008 to 0.03; and S. pneumoniae ATCC 49619, 0.001 to 0.004. Oritavancin MIC QC ranges were, thus, narrow and reproducible. Parameters affecting testing results in the presence of polysorbate 80 were also evaluated. Oritavancin MICs were equivalent to or within 1 doubling dilution of those obtained under standard Clinical and Laboratory Standards Institute testing conditions, regardless of incubation time (18, 24, or 48 h), Ca(2+) concentration, pH, or frozen panel storage time (up to 6 months).
- Published
- 2008
- Full Text
- View/download PDF
4. Effect of polysorbate 80 on oritavancin binding to plastic surfaces: implications for susceptibility testing.
- Author
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Arhin FF, Sarmiento I, Belley A, McKay GA, Draghi DC, Grover P, Sahm DF, Parr TR Jr, and Moeck G
- Subjects
- Adsorption drug effects, Animals, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents metabolism, Anti-Bacterial Agents pharmacology, Bacterial Infections microbiology, Carbon Radioisotopes, Culture Media, Conditioned metabolism, Enterococcus drug effects, Glycopeptides chemistry, Glycopeptides metabolism, Horses, Humans, Lipoglycopeptides, Radioligand Assay, Staphylococcus drug effects, Streptococcus drug effects, Surface Properties, Teicoplanin analogs & derivatives, Teicoplanin chemistry, Teicoplanin metabolism, Teicoplanin pharmacology, Glycopeptides pharmacology, Microbial Sensitivity Tests methods, Polysorbates pharmacology
- Abstract
Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition of cell wall synthesis and the perturbation of the membrane potential. Approved guidelines for broth microdilution MIC assays with dalbavancin, another lipoglycopeptide, require inclusion of 0.002% polysorbate 80. To investigate the potential impact of polysorbate 80 on oritavancin susceptibility assays, we quantified the recovery of [(14)C]oritavancin from susceptibility assay plates with and without polysorbate 80 and examined the effect of the presence of polysorbate 80 on the oritavancin MICs for 301 clinical isolates from the genera Staphylococcus, Enterococcus, and Streptococcus. In the absence of polysorbate 80, [(14)C]oritavancin was rapidly lost from solution in susceptibility assay test plates: 9% of the input drug was recovered in broth at 1 h when [(14)C]oritavancin was tested at 1 mug/ml. Furthermore, proportionately greater losses were observed at lower oritavancin concentrations, suggesting saturable binding of oritavancin to surfaces. The inclusion of 0.002% polysorbate 80 or 2% lysed horse blood permitted the recovery of 80 to 100% [(14)C]oritavancin at 24 h for all drug concentrations tested. Concordantly, oritavancin MIC(90)s for streptococcal isolates, as determined in medium containing 2% lysed horse blood, were identical with and without polysorbate 80. In stark contrast, polysorbate 80 reduced the oritavancin MIC(90)s by 16- to 32-fold for clinical isolates of enterococci and staphylococci, which are typically cultured without blood. The results presented here provide evidence that the MIC data for oritavancin in the current literature significantly underestimate the potency of oritavancin in vitro. Moreover, the combination of data from MIC and [(14)C]oritavancin recovery studies supports the revision of the oritavancin broth microdilution method to include polysorbate 80 throughout the assay.
- Published
- 2008
- Full Text
- View/download PDF
5. In vitro Activity of Ceftaroline Against Isolates of Gram-Positive Bacteria from Patients with Bloodstream Infections Collected as a Part of ATLAS Between 2017 and 2020.
- Author
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Kempf, Marie, Arhin, Francis F, Kuraieva, Alona, and Utt, Eric
- Subjects
GRAM-positive bacteria ,CEFTAROLINE ,STREPTOCOCCUS pneumoniae ,METHICILLIN-resistant staphylococcus aureus ,ANTI-infective agents ,MICROBIAL sensitivity tests ,STAPHYLOCOCCUS aureus - Abstract
Purpose: To assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, and coagulase-negative staphylococci (CoNS) from blood collected in Africa and Middle East (AfME), Asia Pacific (APAC), Europe, Latin America (LATAM), and North America from 2017 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program.Methods: Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.Results: Ceftaroline showed good activity (susceptibility ≥ 89.8%, MIC
90 0.008– 2 mg/L) against all Gram-positive isolates tested. All isolates of methicillin-susceptible S. aureus, penicillin-susceptible S. pneumoniae, S. agalactiae, S. dysgalactiae, and S. pyogenes were susceptible to ceftaroline (MIC90 0.008– 0.25 mg/L). Ceftaroline susceptibility for MRSA isolates was 89.8% globally (MIC90 2 mg/L). Among the comparator agents, all isolates were susceptible to vancomycin, except S. epidermis (susceptibility, 99.9%). Among other agents, daptomycin, linezolid, and tigecycline showed potent activity (susceptibility ≥ 97.9%, MIC90 0.03– 2 mg/L) against all isolates tested.Conclusion: Ceftaroline showed potent in vitro activity against global bloodstream isolates of Gram-positive bacteria collected between 2017 and 2020. Monitoring and surveillance of global as well as regional longitudinal trends of resistance rates among Gram-positive isolates causing bloodstream infections are important to limit the spread of AMR, establish stewardship measures, and manage and appropriately treat infections. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
6. Antimicrobial Activities of Aztreonam-Avibactam and Comparator Agents against Enterobacterales Analyzed by ICU and Non-ICU Wards, Infection Sources, and Geographic Regions: ATLAS Program 2016–2020.
- Author
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Piérard, Denis, Hermsen, Elizabeth D., Kantecki, Michal, and Arhin, Francis F.
- Subjects
ANTI-infective agents ,MICROBIAL sensitivity tests ,COMPARATOR circuits ,DRUG resistance in microorganisms ,INFECTION - Abstract
Increasing antimicrobial resistance among multidrug-resistant (MDR), extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Enterobacterales (CPE), in particular metallo-β-lactamase (MBL)-positive strains, has led to limited treatment options in these isolates. This study evaluated the activity of aztreonam-avibactam (ATM-AVI) and comparator antimicrobials against Enterobacterales isolates and key resistance phenotypes stratified by wards, infection sources and geographic regions as part of the ATLAS program between 2016 and 2020. Minimum inhibitory concentrations (MICs) were determined per Clinical and Laboratory Standards Institute (CLSI) guidelines. The susceptibility of antimicrobials were interpreted using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. A tentative pharmacokinetic/pharmacodynamic breakpoint of 8 µg/mL was considered for ATM-AVI activity. ATM-AVI inhibited ≥99.2% of Enterobacterales isolates across wards and ≥99.7% isolates across infection sources globally and in all regions at ≤8 µg/mL. For resistance phenotypes, ATM-AVI demonstrated sustained activity across wards and infection sources by inhibiting ≥98.5% and ≥99.1% of multidrug-resistant (MDR) isolates, ≥98.6% and ≥99.1% of ESBL-positive isolates, ≥96.8% and ≥90.9% of carbapenem-resistant (CR) isolates, and ≥96.8% and ≥97.4% of MBL-positive isolates, respectively, at ≤8 µg/mL globally and across regions. Overall, our study demonstrated that ATM-AVI represents an important therapeutic option for infections caused by Enterobacterales, including key resistance phenotypes across different wards and infection sources. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Investigation of mechanisms responsible for decreased susceptibility of aztreonam/avibactam activity in clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019.
- Author
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Mendes, Rodrigo E, Doyle, Timothy B, Streit, Jennifer M, Arhin, Francis F, Sader, Helio S, and Castanheira, Mariana
- Subjects
AZTREONAM ,PENICILLIN-binding proteins ,ENTEROBACTER cloacae ,GRAM-negative bacteria ,KLEBSIELLA pneumoniae ,SEQUENCE analysis ,ANTIBIOTICS ,ESCHERICHIA coli ,KLEBSIELLA ,CEFTAZIDIME ,RESEARCH ,COMBINATION drug therapy ,RESEARCH methodology ,ORGANIC compounds ,MEDICAL cooperation ,EVALUATION research ,HYDROLASES ,COMPARATIVE studies ,RESEARCH funding ,MICROBIAL sensitivity tests ,PHARMACODYNAMICS - Abstract
Background: The combination aztreonam/avibactam is currently under Phase 3 trials for the treatment of serious infections caused by Gram-negative bacteria including those with MBLs.Objectives: To investigate the resistance mechanisms in Enterobacterales exhibiting aztreonam/avibactam MICs of ≥4 mg/L.Methods: Among 8787 Enterobacterales, 17 (0.2%) isolates exhibited an aztreonam/avibactam MIC of ≥4 mg/L. Isolates were sequenced and screened for β-lactamases. Sequences of porins, penicillin-binding protein 3 (PBP3) and expression levels of AmpC and AcrA were evaluated.Results: Eleven (11/4154 isolates; 0.26%) Escherichia coli, three (3/1981; 0.15%) Klebsiella pneumoniae and three (3/628; 0.5%) Enterobacter cloacae were identified. All E. coli showed either an 'YRIK' or 'YRIN' insertion in PBP3. In general, these isolates carried blaCMY and/or blaCTX-M variants, except for one isolate from Korea that also produced NDM-5 and one isolate from Turkey that produced OXA-48. Two DHA-1-producing K. pneumoniae overexpressed acrA and had a premature stop codon in either OmpK35 or OmpK36, whereas a third K. pneumoniae carried blaPER-2 and had a premature stop codon in OmpK35. All three E. cloacae expressed AmpC at levels ≥570-fold, but sequence analysis did not reveal known amino acid alterations associated with decreased avibactam binding or increased hydrolysis of β-lactams. Minor amino acid polymorphisms within OmpC, OmpF and PBP3 were noted among the E. cloacae.Conclusions: A small number of isolates (0.2%) met the inclusion criteria. E. coli showed altered PBP3 as the most relevant resistance mechanism, whereas K. pneumoniae had multiple resistance mechanisms. Further investigations are needed to clarify resistance in E. cloacae. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
8. In vitro stepwise selection of reduced susceptibility to lipoglycopeptides in enterococci.
- Author
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Arhin, Francis F., Seguin, David Lalonde, Belley, Adam, and Moeck, Gregory
- Subjects
- *
ENTEROCOCCUS , *MICROBIAL sensitivity tests , *GLYCOPEPTIDES , *DRUG resistance in bacteria , *IN vitro studies - Abstract
The propensity of oritavancin to select for stably elevated oritavancin minimum inhibitory concentrations (MICs) was studied by serial passaging of strains in broth containing oritavancin for 20 days. Seven clinical strains of Enterococcus faecalis and E. faecium were studied; they included vancomycin-susceptible and both VanA and VanB vancomycin-resistant isolates. Stepwise oritavancin selection yielded stably elevated oritavancin MICs in six of the seven strains, with MIC increases ranging from 4–32-fold. By comparison, stepwise selection with comparator agents dalbavancin (4- to >128-fold MIC increases), telavancin (4–8-fold MIC increases) and daptomycin (4–32-fold MIC increases) also yielded selectants with elevated MICs of the respective agents. Oritavancin selectants retained parental MICs of vancomycin, daptomycin, linezolid and rifampicin. Some, but not all of the oritavancin selectants also showed MIC increases to the lipoglycopeptides telavancin, dalbavancin and teicoplanin, suggesting that within the lipoglycopeptide class, different mechanisms of action may be elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
9. Comparative in vitro activity of oritavancin and other agents against vancomycin-susceptible and -resistant enterococci.
- Author
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Sweeney, Debora, Stoneburner, Audrey, Shinabarge, Dean L., Arhin, Francis F., Belley, Adam, Moeck, Greg, Pillar, Chris M., and Shinabarger, Dean L
- Subjects
GLYCOPEPTIDES ,VANCOMYCIN resistance ,ENTEROCOCCUS faecalis ,ANTIBIOTICS ,COMPARATIVE studies ,CROSS infection ,ENTEROCOCCUS ,RESEARCH methodology ,MEDICAL cooperation ,MICROBIAL sensitivity tests ,PEPTIDES ,RESEARCH ,VANCOMYCIN ,GRAM-positive bacterial infections ,EVALUATION research ,PHARMACODYNAMICS - Abstract
A letter to the editor is presented which discusses the in vitro activity of oritavancin and other lipoglycopeptides against vancomycin-susceptible and -resistant Enterococcus faecalis.
- Published
- 2017
- Full Text
- View/download PDF
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