Systems Approach to Improving Antimicrobial Susceptibility Testing in Clinical Laboratories in the United States

Antimicrobial resistance is a serious threat to animal and human health worldwide, requiring a collaborative, holistic approach. The U.S. Government has developed a national strategy to address antimicrobial resistance, with one component being to monitor antimicrobial resistance in agricultural settings. We developed a survey to collect information about antimicrobial susceptibility testing (AST) from the veterinary diagnostic laboratory community in the United States, assessing current practices and technologies and determining how AST information is shared. Of the 132 surveys administered, 52 (39%) were returned. Overall, responding laboratories conducted susceptibility tests on 98,788 bacterial isolates in 2014, with Escherichia coli being the most common pathogen tested across all animal species. The 2 most common AST methods employed were the disk diffusion method (71%) and the Sensititre platform broth microdilution system (59%). Laboratories primarily used the Clinical Laboratory Standards Institute (CLSI) VET-01 standard (69%) and the automatically calculated interpretations provided by the commercial AST systems (61%) for interpreting their AST data. Only 22% of laboratories published AST data on a periodic basis, usually via annual reports published on the laboratory’s website or through peer-reviewed journals for specific pathogens. Our results confirm that disk diffusion and broth microdilution remain the standard AST methods employed by U.S. veterinary diagnostic laboratories, and that CLSI standards are commonly used for interpreting AST results. This information will help determine the most efficient standardized methodology for future surveillance. Furthermore, the current infrastructure within laboratories, once harmonized, will help provide a mechanism for conducting national surveillance programs.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02945-15 ◽

2016 ◽

Vol 60 (10) ◽

pp. 6418-6421 ◽

Cited By ~ 9

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.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01495-19 ◽

2019 ◽

Vol 64 (2) ◽

Cited By ~ 3

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.

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CIM City: the Game Continues for a Better Carbapenemase Test

Journal of Clinical Microbiology ◽

10.1128/jcm.00353-19 ◽

2019 ◽

Vol 57 (7) ◽

Cited By ~ 6

Author(s):

Romney M. Humphries

Keyword(s):

Antimicrobial Susceptibility ◽

Clinical Microbiology ◽

Susceptibility Testing ◽

Clinical Care ◽

Antimicrobial Susceptibility Testing ◽

European Committee ◽

Link Type ◽

Clinical Laboratories ◽

The Right

ABSTRACT The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing agree that carbapenemase testing is not necessary for clinical care, provided that the laboratory is up to date with current breakpoints. Nonetheless, publication on the development and modification of carbapenemase tests continues, as is the case in this issue of the Journal of Clinical Microbiology (R. W. Beresford and M. Maley, J Clin Microbiol 57:e01852-18, 2019, https://doi.org/10.1128/JCM.01852-18). This commentary explores modifications to the carbapenem inactivation method—but is this the right focus for clinical laboratories?

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Point-Counterpoint: Differences between the European Committee on Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute Recommendations for Reporting Antimicrobial Susceptibility Results

Journal of Clinical Microbiology ◽

10.1128/jcm.01129-19 ◽

2019 ◽

Vol 57 (9) ◽

Cited By ~ 16

Author(s):

Gunnar Kahlmeter ◽

Christian G. Giske ◽

Thomas J. Kirn ◽

Susan E. Sharp

Keyword(s):

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Antimicrobial Susceptibility Testing ◽

Test Results ◽

Diffusion Test ◽

Disk Diffusion Test ◽

Technical Variability ◽

European Committee ◽

Clinical Laboratories ◽

Antibiotic Susceptibility Test

INTRODUCTION Antibiotic susceptibility test results are among the most important results issued by clinical microbiology laboratories because they routinely guide critical treatment decisions. Interpretations of MIC or disk diffusion test results, such as “susceptible” or “resistant,” are easily understood. Clinical laboratories also need to determine whether and how their reports will reflect more complex situations. Such situations include, first, whether there is need to administer higher or more frequent doses of antibiotic than usual for clinical efficacy; second, whether an antimicrobial is likely to be effective at a body site where it concentrates; and third, whether there is some uncertainty in the test results due to technical variability that cannot be eliminated. Two leading organizations that set standards for antimicrobial susceptibility testing, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical and Laboratory Standards Institute (CLSI), have taken different strategies to deal with these challenges. In this Point-Counterpoint, Gunnar Kahlmeter and Christian Giske discuss how EUCAST is addressing these issues, and Thomas Kirn and Susan Sharp discuss the CLSI approach.

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Don't Get Wound Up: Revised Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa

Journal of Clinical Microbiology ◽

10.1128/jcm.02072-18 ◽

2019 ◽

Vol 57 (7) ◽

Cited By ~ 9

Author(s):

Tam T. Van ◽

Emi Minejima ◽

Chiao An Chiu ◽

Susan M. Butler-Wu

Keyword(s):

United States ◽

Pseudomonas Aeruginosa ◽

Side Effects ◽

Antimicrobial Agents ◽

Susceptibility Testing ◽

The United States ◽

Published Data ◽

Content Type ◽

Clinical Laboratories ◽

Level Resistance

ABSTRACT Fluoroquinolones remain some of the more commonly prescribed antimicrobial agents in the United States, despite the wide array of reported side effects that are associated with their use. In 2019, the Clinical and Laboratory Standards Institute revised the fluoroquinolone antimicrobial susceptibility testing breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa. This breakpoint revision was deemed necessary on the basis of pharmacokinetic and pharmacodynamic analyses suggesting that the previous breakpoints were too high, in addition to the inability of the previous breakpoints to detect low-level resistance to this antibiotic class. In this minireview, we review the published data in support of this revision, as well as the potential challenges that these breakpoint revisions are likely to pose for clinical laboratories.

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Multicenter Evaluation of Colistin Broth Disk Elution and Colistin Agar Test: a Report from the Clinical and Laboratory Standards Institute

Journal of Clinical Microbiology ◽

10.1128/jcm.01269-19 ◽

2019 ◽

Vol 57 (11) ◽

Cited By ~ 11

Author(s):

Romney M. Humphries ◽

Daniel A. Green ◽

Audrey N. Schuetz ◽

Yehudit Bergman ◽

Shawna Lewis ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Polymyxin B ◽

Antimicrobial Susceptibility Testing ◽

Broth Microdilution ◽

Content Type ◽

Clinical Laboratories

ABSTRACT Susceptibility testing of the polymyxins (colistin and polymyxin B) is challenging for clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) Antimicrobial Susceptibility Testing Subcommittee evaluated two methods to enable accurate testing of these agents. These methods were a colistin broth disk elution (CBDE) and a colistin agar test (CAT), the latter of which was evaluated using two inoculum volumes, 1 μl (CAT-1) and 10 μl (CAT-10). The methods were evaluated using a collection of 270 isolates of Enterobacterales, 122 Pseudomonas aeruginosa isolates, and 106 Acinetobacter spp. isolates. Overall, 94.4% of CBDE results were in essential agreement and 97.9% in categorical agreement (CA) with reference broth microdilution MICs. Nine very major errors (VME; 3.2%) and 3 major errors (ME; 0.9%) were observed. With the CBDE, 98.6% CA was observed for Enterobacterales (2.5% VME, 0% ME), 99.3% CA was observed for P. aeruginosa (0% VME, 0.7% ME), and 93.1% CA was observed for Acinetobacter spp. (5.6% VME, 3.3% ME). Overall, CA was 94.9% with 6.8% VME using CAT-1 and improved to 98.3% with 3.9% VME using CAT-10. No ME were observed using either CAT-1 or CAT-10. Using the CAT-1/CAT-10, the CA observed was 99.4%/99.7% for Enterobacterales (1%/0.5% VME), 98.7%/100% for P. aeruginosa (8.3%/0% VME), and 88.5%/92.3% for Acinetobacter spp. (21.4%/14.3% VME). Based on these data, the CLSI antimicrobial susceptibility testing (AST) subcommittee endorsed the CBDE and CAT-10 methods for colistin testing of Enterobacterales and P. aeruginosa.

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

Clinical Microbiology Reviews ◽

10.1128/cmr.6.1.22 ◽

1993 ◽

Vol 6 (1) ◽

pp. 22-33 ◽

Cited By ~ 14

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.

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The Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing: Background, Organization, Functions, and Processes

Journal of Clinical Microbiology ◽

10.1128/jcm.01864-19 ◽

2020 ◽

Vol 58 (3) ◽

Cited By ~ 8

Author(s):

Melvin P. Weinstein ◽

James S. Lewis

Keyword(s):

Infectious Disease ◽

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Performance Standards ◽

The United States ◽

Antimicrobial Susceptibility Testing ◽

Face To Face ◽

Standards And Guidelines ◽

Financial Dependency ◽

Operational Processes

ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST SC) is a volunteer-led, multidisciplinary consensus body that develops and publishes standards and guidelines (among other products) for antimicrobial susceptibility testing (AST) methods and results interpretation in the United States and internationally. The Subcommittee (SC) meets face-to-face twice yearly, and its working groups (WGs) are active throughout the year via teleconferences. All meetings are open to the public. Participants include clinical microbiologists, infectious disease (ID) pharmacists, and infectious disease physicians representing the health care professions, government, and industry. Individuals who work for a company with a primary financial dependency on drug sales cannot serve as voting members, and well-defined conflict of interest polices are in place. In addition to developing and updating susceptibility breakpoints, the SC develops and validates new testing methods, provides guidance on how results should be interpreted and applied, sets quality control ranges, and educates users through seminars, symposia, and webinars. Based on its work, the SC publishes print and electronic standards and guidelines, including an annual update, the Performance Standards for Antimicrobial Susceptibility Testing (M100). This commentary will describe the background, organization, functions, and operational processes of the AST SC.

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