Defining, Screening, and Analyzing: A Tri-Pillar Laboratory’s Approach for Improving Antimicrobial Resistance Workflow

Antimicrobial resistance (AMR) has surged into the spotlight as one of the most serious global health threats. The rise of multidrug-resistant (MDR) strains presents a daunting challenge to global health networks. However, several initiatives are underway to curb this growing menace, with the laboratory-side practices taking precedence in the effort. As a Medical Microbiologist, my team and I continue the work of prioritizing rapid identification and reporting of AMR for epidemiological and therapeutic purposes. Additionally, rapid reporting of anti-MDR susceptibility results may optimize and improve treatment options in a case-by-case scenario, directly impacting patient care. Our lab initiative pivots on a tri-pillar approach: Define, Screen, and Analyze (DSA).

The first pillar and the most important, 'Define', focuses on understanding the specific mechanism of resistance and establishing the antimicrobial susceptibility pattern. In the face of AMR, it is crucial that we understand how the mechanisms of resistance impact different antimicrobial classes. Understanding these mechanisms can shed light on identifying patterns that may offer identification of “suspected” MDR directly from the initial antimicrobial susceptibility testing (AST) results. Also, this strategy may offer opportunities for deciding additional antimicrobial testing, especially anti-MDR, for targeted therapeutic interventions. ‘Define’, also includes understanding intrinsic resistance mechanisms that may obscure or make difficult the identification of acquired resistance patterns. This is why this pillar must include the correlating organism for what a specific mechanism may be applicable, best examples are the presence of mecA that is clinically significant correlated to Staphylococcus aureus or vanA/B with Enterococcus faecalis or Enterococcus faecium.

This first pillar also includes the clinical and epidemiological significance of the specific organism/resistance defined. In theory, every bacterium can be defined as MDR, but the core of the AMR classification goes beyond a simple naming convention. The resistance against a key antimicrobial or an entire class, such as resistance against methicillin that indicate resistance against the entire beta-lactam class in S. aureus, or the presence of an Extended-Spectrum Beta-lactamase (ESBL) in an E. coli that refers to the potential hydrolysis of penicillins, cephalosporins and monobactam by an acquired mechanism, must guide a revised therapeutic approach and infection prevention actions. The MDR definition should also be specific as possible, it should be able to rapidly indicate the affected antimicrobials, mechanism present and the following steps on testing.

By understanding the resistance mechanism, establishing the antimicrobial susceptibility pattern and the correlating carrying organism, we can delineate the specific antimicrobials for a rapid screening and further confirmation. This step forms the groundwork for our efforts, setting the stage for subsequent steps.

The second pillar, 'Screen', involves the use of the defined antimicrobial susceptibility patterns and applicable organisms to evaluate the correlation between the AST results and the presence of an acquired resistance mechanism by confirmatory testing, if applicable. Screening also allows us to understand the magnitude, prevalence, and distribution of MDR organisms. This surveillance step is critical in tracking the spread of AMR and enables healthcare providers to promptly respond to potential clusters or outbreaks and in a case-by-case, provide precision treatment to individual patients. In addition, it facilitates the formulation of tailored infection control measures and aids in the strategic allocation of healthcare resources.

The final pillar, 'Analyze', incorporates an in-depth assessment of the gathered data. Analysis, in this context, extends beyond simple observation of prevalence and trends; it delves into minute aspects such as minimum inhibitory concentration (MIC) distribution, multifaceted analysis incorporating multiple variables such as combination of antimicrobials, and infection sites. The analysis of MIC distributions can help ascertain the potency of antimicrobials against resistant strains and inform decisions regarding therapeutic dosages and reinforce an Expert System for more accurate pattern identification. Moreover, conducting multivariable analyses allows for a more comprehensive understanding of the prevalence and distribution of AMR, considering the interplay between various factors such as patient demographics, infection type and site. ?In addition, the 'Analyze' phase also focuses on additional anti-MDR agents. Evaluating their potency and if possible, their effectiveness provides not only alternative treatment options but also may provide additional confirmatory data regarding specific resistance mechanisms, as example Enterobacterales with a carbapenemase producing patter that are non-susceptible to ceftazidime/avibactam or meropenem/vaborbactam, this initial AST results may indicate the presence of a metallo-β-lactamase producing strain.

The tri-pillar DSA approach to AMR aims to encapsulate the entire spectrum of the threat, starting from defining the resistance to analyzing the data for inferences that could be instrumental in managing in developing local or global policies to manage this threat. The amalgamation of defining the antimicrobial resistance mechanisms, screening for the presence of AMR, and deeply analyzing the gathered data paves the way for a comprehensive understanding of the problem and allows for the development of effective local and global countermeasures.

The tri-pillar DSA approach underscores the importance of laboratory initiatives in the fight against AMR. It harmonizes the components of defining, screening, and analyzing, providing a comprehensive strategy for dealing with antimicrobial resistance. This approach may well provide a blueprint for other labs across the globe, offering a solid platform for global collaboration in our shared battle against the AMR threat.