Introduction

Antibiotics have been a source of increasing concern and subsequent regulation among providers, especially those within wound care. Antimicrobial stewardship has been emphasized within the medical system in recent years as antibiotic-resistant organisms have increased globally and among at-risk patient populations. Antibiotic time-outs have been a recent and successful approach to tackling this concern. They have resulted in better patient outcomes and lower incidences of antimicrobial resistance (AMR) infection in the health care setting.

How Does AMR Develop?

AMR develops naturally within microbial populations through selective evolution. However, the potential for mutations resulting in AMR increases when the environment creates a particular advantage for resistant traits.¹ If only a percentage of bacteria die when treated by a certain antimicrobial, the remaining bacteria that are more resistant to that antimicrobial have more opportunities to colonize. Specifically, AMR can present within bacteria as one or a combination of the following:^1,2

• Limiting uptake of a medication
• Modifying a medication's target
• Inactivation of a medication entirely
• Active efflux of a medication

Antimicrobial Time-Outs

An antimicrobial time-out is a structured, continuous reevaluation of a patient’s antimicrobial regimen. This reevaluation allows a medical provider to determine the presence of any specific patient factors and if a change in treatment is needed to have the most responsible antibiotic stewardship possible. Adjustments are considered in reference to a patient's response to the current treatment and any recent blood or lab work and cultures, usually within the first 36-72 hours after initiating an antimicrobial regimen.³ Such adjustments can present as a change to:³

• Drug duration
• Drug route
• Drug dosage
• Drug type

Cultures are a helpful tool during a time-out, as they show what specific organism is causing an infection. A pharmacist can then pick a specific antibiotic with a high success rate against this particular organism.³ The selected antimicrobial might be better administered intravenously, orally, or need a different dose than the current medication. This approach is preferred today instead of broad-spectrum antibiotic use because of the high risk of AMR development with such broad-spectrum antibiotics. These small changes can result in better patient care and fewer instances of patients developing AMR.³ Antimicrobial stewardship program (ASP) implementation can be challenging in settings with limited resources and growing needs.⁴ When these practices are centralized, teams and departments can experience difficulty implementing an effective ASP. Antibiotic time-outs aid systems in decentralizing ASP demand, improving adherence, and encouraging effective utilization.⁴ In particular, outpatient settings may benefit from antibiotic time-out implementation. Unfortunately, this setting has the most barriers to adopting a formal time-out process.⁴ Time and resources are significantly limited, and patients can potentially have low re-engagement.⁴ Preparation will be the key to success in implementing a more formal ASP in an outpatient setting, with particular emphasis on patient and public education.⁴

Incorporation of Antibiotic Time-Outs in Health Care

The Centers for Disease Control and Prevention (CDC) has pushed for greater antimicrobial stewardship in health care settings, in and out of the hospital.3 As the CDC emphasizes antibiotic time-outs, the prevalence of infections from antimicrobial-resistant pathogens has decreased.^3,5 Unfortunately, the COVID-19 pandemic has also slowed progress on this front, and reintegration is imperative.⁵ In 2020, a series of pilot programs first introduced antibiotic time-outs in the inpatient setting.3 Since the implementation of this practice among health care providers was high despite the amount of effort associated with it, a global strategy to ensure time-out adherence will likely be necessary.³ Currently, there is no standardized protocol to ensure antibiotic time-outs. However, an inherently high adherence rate is a core tenet of good antimicrobial stewardship.³ Hopefully, soon electronic health care record systems will help track antibiotic time-outs. An example of this system would be an automated digital template within a patient's chart. A health care provider must complete this aspect of the record within a certain number of calendar days when starting antimicrobial treatment.⁶ Educational campaigns have started and will likely continue to raise awareness of AMR and help the public understand why antibiotics are not as widely administered for certain illnesses as they used to be.⁶ These can present in public service announcements, social media posts, local health department campaigns, or even flyers in health care providers' offices.

Multi-Disciplinary Involvement

Team leaders and interdisciplinary teams are also responsible for adherence to good antibiotic stewardship. In the inpatient setting, an infectious disease team will often be consulted if certain criteria are flagged within an antimicrobial time-out to provide further guidance and recommendations.⁶

Conclusion

In sum, antimicrobial resistance is an inherently natural process, all organisms evolve to best succeed in their environment, and certain traits are favored over others that then get passed down to future generations. Misuse and overuse of antimicrobial agents have led to an environment that favors antimicrobial-resistant bacteria and now poses a great threat to public health and safety. Antibiotic time-outs are imperative to reduce the incidence of acquiring or developing an AMR infection and are necessary to promote the best outcomes. References

1. How antibiotic resistance happens. Centers for Disease Control and Prevention. November 9, 2021. Accessed August 26, 2022. https://www.cdc.gov/drugresistance/about/how-resistance-happens.html.
2. Reygaert WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol. 2018;4(3):482-501. doi:10.3934/microbiol.2018.3.482.
3. Carolina Antimicrobial Stewardship Program. Antibiotic time-outs expand stewardship’s reach. UNC School of Medicine. October 5, 2020. Accessed August 26, 2022. https://www.med.unc.edu/casp/2020/10/antibiotic-time-outs-expand-stewar…
4. Kinn P, Postelnick M, Schroeder S, et al. A time-out on the antimicrobial time-out: Where does it stand and what is it’s future?. Curr Treat Options Infect Dis. 2018;10:281-290. doi: 10.1007/s40506-018-0146-z
5. Graber CJ, Jones MM, Glassman PA, et al. Taking an antibiotic time-out: utilization and usability of a self-stewardship time-out program for renewal of vancomycin and piperacillin-tazobactam. Hosp Pharm. 2015;50(11):1011-1024. doi:10.1310/hpj5011-1011
6. CDC. COVID-19: U.S. impact on antimicrobial resistance, special report 2022. U.S. Department of Health and Human Services, CDC; 2022. Accessed August 26, 2022. https://www.cdc.gov/drugresistance/covid19.html