scholarly journals Analysis of Potential β-Lactam Surrogates To Predict In Vitro Susceptibility and Resistance to Ceftaroline for Clinical Isolates of Enterobacteriaceae

2018 ◽  
Vol 56 (4) ◽  
pp. e01892-17
Author(s):  
Meredith A. Hackel ◽  
Joseph P. Iaconis ◽  
James A. Karlowsky ◽  
Daniel F. Sahm
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
The United States ◽  
Antimicrobial Susceptibility Testing ◽  
Clinical Isolates ◽  
Content Type ◽  
United States Food ◽  
States Food ◽  
Susceptibility And Resistance

ABSTRACT Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibility testing device offered a Gram-negative panel that included ceftaroline. This circumstance is unfortunate, as many clinical microbiology laboratories rely solely on commercial devices to generate in vitro antimicrobial susceptibility testing results for common bacterial pathogens. In lieu of device-based testing of clinical isolates of Enterobacteriaceae, laboratories wishing to test ceftaroline must either opt for disk diffusion testing or use a gradient strip; however, both alternatives interrupt laboratory workflow and require additional labor and expense. Identification of a reliable surrogate β-lactam to predict in vitro susceptibility to ceftaroline may offer another interim solution as laboratories await availability of ceftaroline for testing on their commercial devices. We tested six β-lactams (aztreonam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, and cefpodoxime) as potential surrogates for ceftaroline against a collection of 543 clinical isolates of Enterobacteriaceae selected to approximate the distribution of ceftaroline MICs observed in AWARE global surveillance studies conducted in 2013. All six potential surrogates generated very major error rates of 16.3% to 56.6%, far exceeding the accepted limit of 1.5% set by the Clinical and Laboratory Standards Institute (CLSI) and the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health. Failure to identify a reliable surrogate to predict in vitro susceptibility and resistance to ceftaroline for clinical isolates of Enterobacteriaceae underscores the need for expedited addition of newer antimicrobial agents to commercial antimicrobial susceptibility testing devices.

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 Antimicrobial susceptibility testing of Neisseria gonorrhoeae and implications for epidemiology and therapy.

1993 ◽  
Vol 6 (1) ◽  
pp. 22-33 ◽  
Author(s):  
T Fekete
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
The United States ◽  
Primary Treatment ◽  
Antimicrobial Susceptibility Testing ◽  
Response To Therapy ◽  
In Vitro Tests

Antimicrobial susceptibility testing (AST) of Neisseria gonorrhoeae has been under development since the early days of antimicrobial agents. However, it is rarely applied to clinical isolates today. The history of the various in vitro tests to determine the susceptibility of N. gonorrhoeae to antibiotics is rich with evidence that these results predict response to therapy for almost all agents tested. Further, AST is a useful and important aspect of strain characterization and disease epidemiology in conjunction with the more specific but laborious techniques of auxotyping, serotyping, and plasmid analysis. Current technology has overcome many of the objections to AST for N. gonorrhoeae with standardization of test media and the development of an accurate disk diffusion AST method that is suited to most clinical laboratories regardless of volume or level of technical expertise. Ironically, the very low level of resistance to the current primary treatment strategy in the United States, ceftriaxone or another potent cephalosporin, makes the use of AST somewhat superfluous.

scholarly journals Feasibility and potential significance of rapid in vitro qualitative phenotypic antimicrobial susceptibility testing of gram-negative bacilli with the ProMax system

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249203
Author(s):  
Jade Chen ◽  
Michael Tomasek ◽  
Amorina Cruz ◽  
Matthew L. Faron ◽  
Dakai Liu ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Pathogenic Bacteria ◽  
Susceptibility Testing ◽  
Klebsiella Oxytoca ◽  
Antimicrobial Susceptibility Testing ◽  
Clinical Isolates ◽  
Clinical Samples ◽  
Automation System ◽  
Gram Negative

The emergence and evolution of antibiotic resistance has been accelerated due to the widespread use of antibiotics and a lack of timely diagnostic tests that guide therapeutic treatment with adequate sensitivity, specificity, and antimicrobial susceptibility testing (AST) accuracy. Automated AST instruments are extensively used in clinical microbiology labs and provide a streamlined workflow, simplifying susceptibility testing for pathogenic bacteria isolated from clinical samples. Although currently used commercial systems such as the Vitek2 and BD Phoenix can deliver results in substantially less time than conventional methods, their dependence on traditional AST inoculum concentrations and optical detection limit their speed somewhat. Herein, we describe the GeneFluidics ProMax lab automation system intended for a rapid 3.5-hour molecular AST from clinical isolates. The detection method described utilizes a higher starting inoculum concentration and automated molecular quantification of species-specific 16S rRNA through the use of an electrochemical sensor to assess microbiological responses to antibiotic exposure. A panel of clinical isolates consisting of species of gram-negative rods from the CDC AR bank and two hospitals, New York-Presbyterian Queens and Medical College of Wisconsin, were evaluated against ciprofloxacin, gentamicin, and meropenem in a series of reproducibility and clinical studies. The categorical agreement and reproducibility for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, and Pseudomonas aeruginosa were 100% and 100% for ciprofloxacin, 98.7% and 100% for gentamicin and 98.5% and 98.5% for meropenem, respectively.

scholarly journals IMP-27, a Unique Metallo-β-Lactamase Identified in Geographically Distinct Isolates of Proteus mirabilis

2016 ◽  
Vol 60 (10) ◽  
pp. 6418-6421 ◽  
Author(s):  
Nyssa Dixon ◽  
Randal C. Fowler ◽  
A. Yoshizumi ◽  
Tsukasa Horiyama ◽  
Y. Ishii ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Susceptibility ◽  
Proteus Mirabilis ◽  
Susceptibility Testing ◽  
Gene Cassette ◽  
The United States ◽  
Antimicrobial Susceptibility Testing ◽  
Content Type ◽  
Lactamase Gene

ABSTRACTA novel metallo-β-lactamase gene,blaIMP-27, was identified in unrelatedProteus mirabilisisolates from two geographically distinct locations in the United States. Both isolates harborblaIMP-27as part of the first gene cassette in a class 2 integron. Antimicrobial susceptibility testing indicated susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime was a substrate for IMP-27.

scholarly journals In Vitro Activity of OPT-80 Tested against Clinical Isolates of Toxin-Producing Clostridium difficile

2008 ◽  
Vol 52 (11) ◽  
pp. 4163-4165 ◽  
Author(s):  
James A. Karlowsky ◽  
Nancy M. Laing ◽  
George G. Zhanel
Keyword(s):  
Clostridium Difficile ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Susceptibility Testing ◽  
Antimicrobial Susceptibility Testing ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Agar Dilution

ABSTRACT Agar dilution antimicrobial susceptibility testing (CLSI, M11-A7, 2007) performed for 208 toxin-producing clinical isolates of Clostridium difficile resulted in OPT-80 MICs ranging from 0.06 to 1 μg/ml, with 90% of the isolates inhibited by a concentration of 0.5 μg/ml. The in vitro activity of OPT-80 was independent of the susceptibilities of isolates to nine other antimicrobial agents.

scholarly journals Polymyxin Susceptibility Testing and Interpretive Breakpoints: Recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST)

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Jason M. Pogue ◽  
Ronald N. Jones ◽  
John S. Bradley ◽  
David R. Andes ◽  
Sujata M. Bhavnani ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Polymyxin B ◽  
The United States ◽  
Antimicrobial Susceptibility Testing ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Testing Strategies ◽  
Tract Infections

ABSTRACT The polymyxins are important agents for carbapenem-resistant Gram-negative bacilli. The United States Committee on Antimicrobial Susceptibility Testing breakpoint recommendations for colistin and polymyxin B are that isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae are considered susceptible at MIC values of ≤2 mg/liter. These recommendations are contingent upon dosing and testing strategies that are described in this commentary. Importantly, these recommendations are not applicable to lower respiratory tract infections, for which we recommend no breakpoints. Furthermore, there is no breakpoint recommendation for polymyxin B for lower urinary tract infections.

scholarly journals Gentamicin susceptibility among a sample of multi-drug resistantNeisseria gonorrhoeaeisolates in India

2016 ◽  
pp. AAC.01907-16 ◽  
Author(s):  
Manju Bala ◽  
Vikram Singh ◽  
Aradhana Bhargava ◽  
Monika Kakran ◽  
Naveen Chandra Joshi ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Treatment Outcomes ◽  
Treatment Option ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Dual Therapy ◽  
Clinical Treatment ◽  
Antimicrobial Susceptibility Testing ◽  
Effective Treatment Option

Antimicrobial susceptibility testing of 258N. gonorrhoeaeisolates by Etest determined that 60.1% were MDR while 5% strains had decreased susceptibility to currently recommended extended-spectrum cephalosporins (ESCs). Among these, 84.5% MDR and 76.9% strains having decreased susceptibility to ESCs were susceptible to gentamicin. No MDR isolate was resistant to gentamicin. Thesein vitroresults suggest that gentamicin might be an effective treatment option for the MDR strains and in dual therapy for gonorrhea. However, further research regarding the clinical treatment outcomes is essential.

Sign in / Sign up

Export Citation Format

Share Document