Facilitating antibiotic stewardship in the laboratory

According to the Centers for Disease Control and Prevention (CDC) 30% of all antibiotics prescribed in the United States’ acute care hospitals are either unnecessary or suboptimal.¹ Misuse or overuse of antibiotics can cause unintended adverse reactions in patients and lead to emergence of antimicrobial resistant strains. The Centers for Disease Control and Prevention (CDC) estimates that annually, more than 2.8 million patients are infected by antibiotic-resistant (AR) organisms and more than 35,000 of these patients die in the United States.² Additionally, antibiotic misuse is also responsible for causing deadly diarrhea in more than 500,000 patients and 15,000 deaths annually due to Clostridium difficile, a bacterium that is not typically resistant.² Antibiotic resistance (AR) or antimicrobial resistance (AMR) also makes an antibiotic useless in delivering life-saving medical care to surgery or cancer patients.²

The estimated national cost is more than $4.6 billion annually to treat infections caused by a few commonly encountered antimicrobial-resistant organisms in healthcare settings, e.g., multidrug resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococci (VRE); carbapenem-resistant Enterobacteriaceae (CRE),  Carbapenem-resistant Acitenobacter baumannii (CRAB), Multidrug resistant Pseudomonas aeruginosa;  and extended-spectrum beta-lactamases (ESBLs).³ According to the World Health Organization (WHO), antibiotic resistance was directly responsible for 1.27 million global deaths in 2019 and was a contributing factor to an estimated 4.95 million deaths.⁴ If corrective measures are not taken, this could rise to 10 million deaths by 2050 and be the leading cause of deaths.⁵

Following antimicrobial stewardship (AMS) programs is essential to fighting the growing crisis posed by antimicrobial resistance (AMR). The term “antimicrobial stewardship (AMS)” was first used by John McGowan and Dale Gerding in an article in New Horizon in 1996 where they commented on the causal association between antimicrobial use and increasing emergence of antimicrobial resistance (AMR) in hospitals.⁶ According to the authors, efforts to educate and follow quality management or clinical guidelines are not sufficient to control AMR, a series of additional measures are needed to be taken urgently to control this menace. They suggested conducting large-scale, well-controlled trials of antimicrobial-use regulation using sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis to determine the best methods to prevent and control AMR problems and thereby ensure the optimal antimicrobial use, e.g.,  "stewardship." Additionally, consideration of the long-term effects of antimicrobial selection, dosage, and duration of treatment on resistance development for every antimicrobial treatment decision should be a part of AMS.⁷

Goals and guidelines

The goals of AMS programs are as follows:⁸

• To prevent overuse, misuse, and abuse of antibiotics when prescribing antimicrobial therapy, prescribing doctors should follow the following guidelines: 

§  Right drug: Is the drug effective against the present organism?

§  Correct dose: Is the recommended dose within the correct range?

§  Right drug-route: Is the route by which the drug is given appropriate for the patient?

§  Suitable duration: Is the recommended duration of therapy appropriate?

§ Timely de-escalation: From broad spectrum to pathogen directed therapy or higher to lower dose.

•      To prevent antimicrobial overuse, misuse, and abuse in inpatient, outpatient, and community settings, including the agriculture industry.
•         To reduce antibiotic-related adverse effects, for example, C.difficile.
•         To minimize antimicrobial resistance.
•          To reduce healthcare-associated costs.

In 1997, the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA) first published guidelines for the prevention of antimicrobial resistance in hospitals.⁹ The guidelines set out for the first time the criteria for applied infection control programs in hospitals. The recommended criteria were as follows:

1)     Having a system for monitoring bacterial resistance and antibiotic usage;

2)     Developing practice guidelines for the control and use of antibiotics;

3)     Adopting the Centers for Disease Control and Prevention (CDC) Guidelines for Isolation Precautions in Hospitals;

4)     Utilizing hospital committees to develop local policies;

5)    Making hospital administration accountable for the implementation and enforcement of policies adopted by the hospital committees; and

6)     Measuring outcomes to evaluate the effectiveness of policies put in place.

They emphasized having a multidisciplinary team approach and the role of pharmacists and administrators in the development of an optimal “antibiotic control program.” The stewardship guidelines were based on a two-pronged approach: preventing transmission of infection through infection prevention and control (IP&C) and the optimization of antibiotic use. From then on, antibiotic stewardship was increasingly used, which included education and training, decision support systems, restriction, and audit and feedback, which were incorporated into the strategic agenda of organizations seeking to optimize antibiotic use. The effectiveness of these interventions was assessed through peer-reviewed publications and several systematic reviews.^10-12

In 2014, the CDC released the “Core Elements of Hospital Antibiotic Stewardship Programs” to set guidelines on antimicrobial stewardship for hospitals.¹ In 2015, the United States National Action Plan for Combating Antibiotic Resistant Bacteria (CARB) received federal funding for this purpose. Since 2014, the CDC has used the National Healthcare Safety Network (NHSN) annual hospital survey to determine the extent to which hospitals have implemented the core elements. In 2015, more than 50% of hospitals with more than 50 beds reported meeting all seven core elements compared to 26% of hospitals with 25 or fewer beds.¹

In November 2019, the CDC released an updated version of “The Core Elements of Hospital Antibiotic Stewardship Programs.”¹³ The seven core elements of hospital antibiotic stewardship are listed in Figure 1. Along with “The Core Elements of Antibiotic Stewardship,” the CDC also developed the antibiotic stewardship program assessment tool¹⁴ that provides examples of ways to implement the Core Elements. The Core Elements and the tool are an adaptable framework to guide hospitals in their efforts to

optimize antibiotic prescribing. The assessment tool can be used on a periodic basis (e.g., annually) to document the current program infrastructure and activities and to help identify items that could improve the effectiveness of the stewardship program. In addition, the CDC in collaboration with the American Hospital Association, Federal Office of Rural Health Policy, and Pew Charitable Trusts prepared a document, “Implementation of Antibiotic Stewardship Core Elements Hospitals Small and Critical Access Hospitals” to provide small and critical access hospitals implementation strategies based on the seven elements of an antibiotic stewardship program.¹⁵

Role of clinical laboratories in AMS

The clinical microbiology and molecular biology laboratories play a critical role in the success of antimicrobial stewardship programs both for individual patients as well as the whole population in the following ways: 

• Identification and drug susceptibility testing for patients — labs provide diagnostic testing results to identify the infectious agent, determine its antibiotic susceptibility, and help prescribing doctors in choosing the appropriate drug for treatment.
• Surveillance and outbreak investigation reporting — labs can monitor local trends in antimicrobial resistance among pathogens, create antibiograms, and share reports regarding susceptibility with prescribing physicians. Labs can also detect and report outbreaks of hospital-acquired infections to concerned authorities.
• Educating clinicians about the various tests and technologies that facilitate antibiotic stewardship. 

Role of rapid diagnostic testing (RDT) in facilitating antimicrobial stewardship

A successful antimicrobial stewardship program needs rapid and accurate identification of pathogens, antimicrobial susceptibility testing (AST), and resistance detection. The traditional method of microbiology is slow and takes 24 to 48 hours for culture and identification and another 24 to 48 hours to generate antibiotic susceptibility results. Because of that, physicians managing patients with suspected infectious diseases started empirical treatment with broad spectrum antibiotics without waiting for laboratory results. Now, rapid diagnostic tests (RDT) are available and can provide rapid and accurate results in a matter of hours and are playing a significant role in diagnostic and antimicrobial stewardship.¹⁶

RDTs use different techniques, such as polymerase chain reaction (PCR), magnetic resonance, mass spectrometry, microarray technology, next-generation sequencing, and can rapidly identify different kinds of microorganisms — bacterial, fungi, and viral. RDTs are available for identifying respiratory tract infections and blood stream infections, antimicrobial resistance genes for determining antimicrobial resistance in organisms, and surveillance screening for MRSA.

Use of information technology in facilitating antimicrobial stewardship

Since antimicrobial stewardship requires a collaboration and flow of information among different teams in the healthcare organization, including the laboratory, information technology plays an important role in implementing a successful antimicrobial stewardship program. Table 1 lists a sample of software solutions that facilitate antimicrobial stewardship.

Conclusion

Even though antimicrobial stewardship was introduced in 1996, antimicrobial resistance still remains a global crisis. However, during the COVID-19 pandemic, antibiotic stewardship program efforts slowed tremendously due to the changes in patient care, testing, treatment, and staff availability. As a result, there was an increase in combined antimicrobial resistance by 20%.²³ Antimicrobial stewardship is necessary for better patient outcomes and reduced healthcare costs. So, actions mentioned in the guidance documents for antimicrobial stewardship need to be made a habitual practice in every healthcare setting so that even if there are pandemic situations in the future there is no rise in antimicrobial resistance.

The emergence of newer technologies enabling rapid accurate diagnosis, and the increased incorporation of big data, artificial intelligence (AI), and internet of things (IoT) in healthcare is making personalized medicine possible. Personalized medicine will make antimicrobial stewardship programs a success.

References

1. CDC. Core elements of Hospital Antibiotic Stewardship Programs. Antibiotic Prescribing and Use. Published May 20, 2024. Accessed July 26, 2024. https://www.cdc.gov/antibiotic-use/hcp/core-elements/hospital.html?.  

2. Antimicrobial resistance facts and stats. Antimicrobial Resistance. Published July 16, 2024. Accessed July 26, 2024. https://www.cdc.gov/antimicrobial-resistance/data-research/facts-stats/index.html.

3. Nelson RE, Hatfield KM, Wolford H, et al. National estimates of healthcare costs associated with multidrug-resistant bacterial infections among hospitalized patients in the United States. Clin Infect Dis. 2021;72(Supplement_1):S17-S26. doi:10.1093/cid/ciaa1581.
4. Antimicrobial resistance. Who.int. Accessed July 26, 2024. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance.
5. O’Neill J. Review on Antimicrobial Resistance. Tackling Drug-Resistant Infections Globally (2016). Available from: https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf. Accessed July 26, 2024.
6. McGowan J.E., Jr., Gerding D.N. Does antibiotic restriction prevent resistance? New Horiz. 1996;4:370–376. 
7. Shlaes D.M., Gerding D.N., John J.J.F., et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: Guidelines for the prevention of antimicrobial resistance in hospitals. Clin. Infect. Dis. 1997;25:584–599. doi:10.1086/513766.
8. Shrestha J, Zahra F, Cannady P Jr. Antimicrobial Stewardship in Non-Traditional Settings: A Practical Guide. 1st ed. (Doron S, Campion M, eds.). Springer International Publishing; 2023.
9. Shlaes DM, Gerding DN, John JF Jr, et al. Society for healthcare epidemiology of America and infectious diseases society of America joint committee on the prevention of antimicrobial resistance guidelines for the prevention of antimicrobial resistance in hospitals. Infect Control Hosp Epidemiol. 1997;18(4):275-291. doi:10.1086/647610.
10. Davey P, Brown E, Hartman G. Interventions to improve antibiotic prescribing practices for hospital inpatients. In: The Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2002. 
11. Davey P, Brown E, Fenelon L, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2005;(4):CD003543. doi:10.1002/14651858.CD003543.pub2. 
12. Davey P, Peden C, Charani E, Marwick C, Michie S. Time for action—Improving the design and reporting of behaviour change interventions for antimicrobial stewardship in hospitals: Early findings from a systematic review. Int J Antimicrob Agents. 2015;45(3):203-212. doi:10.1016/j.ijantimicag.2014.11.014.
13. CDC. U.S. actions & events to combat. Antimicrobial Resistance. Published May 20, 2024. Accessed July 26, 2024. https://www.cdc.gov/antimicrobial-resistance/programs/AR-actions-events.html. 
14. Centers for Disease Control and Prevention. The Core Elements of Hospital Antibiotic Stewardship Program Tools. Accessed July 26, 2024. https://www.cdc.gov/antibiotic-use/media/pdfs/assessment-tool-P.pdf. 
15. CDC. Implementation of antibiotic stewardship Core Elements at Small and Critical Access Hospitals. Antibiotic Prescribing and Use. Published May 20, 2024. Accessed July 26, 2024. https://www.cdc.gov/antibiotic-use/hcp/core-elements/small-and-critical-access-hospitals.html.  
16. Althubyani A, Holger D. Rapid Diagnostic Testing: Changing the Game for Antimicrobial Stewardship. IDSE Infectious Disease Special Edition. Published October 20, 2023. Accessed July 26, 2024. https://www.idse.net/Review-Articles/Article/10-23/Rapid-Diagnostic-Testing-Changing-the-Game-for-Antimicrobial-Stewardship/71647. 
17. Data-driven infectious disease management. Biomerieux-usa.com. Accessed August 1, 2024. https://microsite.biomerieux-usa.com/clarion/.
18. Wolters Kluwer. Antimicrobial Stewardship. Sentri7 Clinical Surveillance. Accessed July 26, 2024. https://www.wolterskluwer.com/en/solutions/sentri7-clinical-surveillance/medication-management/antimicrobial-stewardship.  
19. Antibiokos-Software for antimicrobial stewardship. Nosotech. Published March 1, 2022. Accessed July 26, 2024. https://nosotech.com/en/solutions/antibiokos/. 
20. Antimicrobial stewardship. MEG. Accessed July 26, 2024. https://megit.com/antimicrobial-stewardship. 
21. Firstline. Firstline - clinical decision support platform. Firstline.org. Accessed July 26, 2024. https://firstline.org/.  
22. APSS - antimicrobial stewardship software & resistance surveillance. Lumed.ca. Accessed July 26, 2024. https://lumed.ca/en/apss/. 
23. CDC. COVID-19 &. Antimicrobial Resistance. Published July 16, 2024. Accessed July 26, 2024. https://www.cdc.gov/antimicrobial-resistance/data-research/threats/COVID-19.html.