Introduction

The coronavirus disease 2019 (COVID-19) pandemic has had a devastating global impact, with 6,287,771 reported cases and 379,941 deaths as of June 3, 2020 [1••]. The number of hospitalized COVID-19 patients has overwhelmed the health system infrastructure in many parts of the world [2]. Antimicrobial stewardship programs (ASPs) have not traditionally been involved in disaster relief planning or pandemic response efforts [3•]. ASPs represent an enormous potential resource, as these programs are ubiquitous, often include physicians and pharmacists with specialized infectious disease training, and often are already integrated and closely collaborated with infection prevention departments. Leveraging the knowledge and skills of ASP personnel is critical in the setting of the current COVID-19 pandemic.

Patients with COVID-19 may develop secondary nosocomial infections with bacteria and fungi as a result of critical illness and prolonged hospitalizations. There is high concern that antimicrobials may be overused, a fact that may be driven by the difficulty in diagnosing actual concurrent or secondary bacterial or fungal infections. Patients may receive both empiric and pathogen-directed broad-spectrum antimicrobials. Given the potential for significant antimicrobial use, ASPs play a crucial role in monitoring antibiotic use to prevent the emergence of drug resistance during the pandemic [4].

Methods

A PubMed search using the search terms “antimicrobial stewardship and COVID-19,” “antimicrobial stewardship and coronavirus disease 2019,” and “antimicrobial stewardship and SARS-CoV-2” was performed on April 21, 2020, resulting in only two relevant articles. In this article, we summarize the limited existing literature on this topic and discuss potential ways that ASPs can be utilized in COVID-19 response efforts. Additionally, we discuss possible adverse consequences of ASP attention diversion on COVID-19 response efforts and the overall implications for future pandemic planning.

Results

ASP core activities can be refocused on COVID-19 (Table 1).

Table 1 Selected core antimicrobial stewardship program activities and the COVID-19 pandemic
Full size table

Prospective Audit with Intervention and Feedback

ASP resources can be utilized to identify patients with COVID-19-like illness in the health system [5•]. Stevens et al. showed that they can quickly revise their existing ASP platform to identify patients with positive or pending SARS-CoV-2 polymerase chain reaction (PCR) test results [5•]. Once patients with positive SARS-CoV-2 PCR test results are identified, their medication orders and treatment plans may be audited to ensure concordance with treatment guidelines. In addition, patients with COVID-19 often receive antibiotics for suspected bacterial pneumonia [3•]. ASPs can play a critical role in the assessment of appropriateness of therapy.

A potential ramification may be diversion of focus away from non-COVID-19 patients; this may lead to subpar antimicrobial use and negative clinical consequences including the emergence of antimicrobial resistance.

In the setting of the current pandemic, ASPs have an opportunity to expand and improve upon their existing technology infrastructure. Additionally, the COVID-19 pandemic presents an opportunity for ASPs to formally integrate with infection prevention programs and enhance relationships with microbiology laboratories and information technology departments. Electronic Medical Records (EMRs) and Clinical Decision Support Systems (CDSSs) are technologies that ASPs can enhance to optimize antimicrobial stewardship work. EMR enhancements can allow ASPs to review and intervene in the care of a higher number of patients more efficiently, while CDSSs can send real-time alerts and aid in the rapid identification of patients with positive PCR test results [8]. EMR stewardship modules can be upgraded to include audit functions for COVID19-specific medications in addition to usual antimicrobials. This may include alerts for medications requiring authorization, regimens needing dose adjustment, or flagging patients with medication contraindications.

Formulary Restriction and Preauthorization

ASPs have a critical potential role as the primary gatekeeper for the appropriate use of COVID-19 treatment medications in order to optimize patient selection and to minimize misuse. ASPs can be actively involved in the development of therapy protocols for COVID-19 and implement these through restrictions. With hydroxychloroquine being under investigation as a potential treatment of SARS-CoV-2 [9], there has been fear of medication shortage among patients with rheumatological disorders [10]. ASPs can monitor drug shortages and ensure proper allocation of medications for patients with rheumatologic conditions using formulary restrictions and preauthorization.

Early in the pandemic, other medications, many with significant potential toxicity (such as lopinavir/ritonavir), were being considered as possible COVID-19 therapies. As new data became available, the use of many of these drugs for COVID-19 has fallen out of favor. ASPs can play a key role in restricting drugs to control their optimal use and avoid toxicity.

Importantly, expanding the number of restricted drugs in the setting of the COVID-19 pandemic may cause delays in responding to antimicrobial approvals for traditional antimicrobials. In addition, relaxing some antimicrobial restriction protocols to relieve the burden of the increasing volume of COVID-19 restriction calls may lead to the suboptimal use of antimicrobials and to the emergence of antimicrobial-resistant organisms.

The COVID-19 pandemic presents an opportunity for ASPs to evolve and enhance their infrastructure for addressing antimicrobial shortages.

Streamlining/De-escalating Therapy and Antibiotic “Time Outs”

Patients may be started on therapy for COVID-19, while they wait for PCR test results, especially when there are delays in testing [5•], In this setting, it is critical that therapy be reassessed and de-escalated for patients whose test results come back negative [5•]. In addition, empirical antimicrobial therapy for secondary/concomitant bacterial pneumonia should be de-escalated based on diagnostic test results and clinical reassessment.

A focus on patients with COVID-19 may pull time away from traditional ASP activities.

Education

Education is a core activity of ASPs [11]. A combination of passive education and active intervention can impact provider prescribing behavior and improve compliance with guidelines [11]. In the setting of the current pandemic, ASPs can be actively involved in educating providers on local COVID-19 treatment protocols, especially if ASPs are involved in developing these guidelines. Taking part in guideline development also equips ASPs to educate providers about potential medication toxicities (such as QTc prolongation with the combination of hydroxychloroquine and azithromycin). A unique feature of the COVID-19 pandemic is the enormous amount of new literature being released that includes non-peer-reviewed article preprints and sometimes news reports without formal data release. ASPs can take the lead on interpreting and communicating these data to providers treating patients on the frontlines.

Monitoring new data is labor intensive and requires a near daily commitment, and this time can divert traditional ASP attention on activities focused on patients without COVID-19.

While ASPs have relied on face-to-face educational engagement since their inception, ASPs must now adapt to new platforms to deliver educational content, such as video conferencing technology and online tools to maintain learners’ connection with topics such as antibiotic spectrum and resistance mechanisms. Additionally, targeted, real-time education via other mechanisms such as email for things like updates to internal guidelines has a critical role in the setting of the current pandemic. Finally, programs that utilize electronic treatment guideline platforms (such as those using mobile “apps”) can educate providers about new information via these tools, as well.

IV to PO Therapy

Conversion from intravenous (IV) to oral antimicrobial therapy in eligible patients has multiple potential advantages, including shortened duration of hospitalization, decreased hospital-acquired infections (HAIs), and decreased IV-site infections [6, 7]. This is especially important in the setting of the COVID-19 pandemic where there is concern about a rise in HAIs [12]. Shortening the duration of hospital stay is highly valuable when many hospitals, especially those in outbreak epicenters, are facing a shortage of ICU beds.

A computerized system may be placed to identify patients who meet certain criteria and can safely undergo conversion from IV to oral therapy [6]. Nursing staff can support IV to PO conversion through optimizing documentation in the EMR, identifying patients who may qualify, and alerting pharmacy. Pharmacy staff can assess patient’s eligibility and make recommendations to physicians [6]. Automatic IV to PO conversion protocols can be adopted that reduce the burden on physicians and enhance patient care. New processes that are put into place during the current pandemic may continue to be deployed after the pandemic ends.

Engagement with Microbiology Laboratories and Infection Prevention Programs

ASPs and infection prevention programs have great potential for synergy, and formal integration has multiple potential advantages [13, 14]. ASPs can also collaborate with microbiology laboratories to act on diagnostic test results in real time. ASPs have established similar workflows with a variety of rapid diagnostic tests, including upper respiratory PCR panels [15]. ASPs can apply these workflows to SARS-CoV-2 PCR results for the timely de-escalation of isolation precautions when patients do not otherwise have a clinical syndrome consistent with COVID-19. Likewise, ASPs can assist with developing indications for SARS-CoV-2 serologic testing in hospitalized patients. Diagnostic stewardship presents an opportunity for ASPs to strengthen collaborative relationships with both microbiology laboratories and infection prevention programs. However, real-time assessment and response to COVID-19 diagnostic testing is labor intensive and might draw attention away from traditional ASP activities.

ASP relationships with Microbiology departments focused on diagnostic stewardship can continue in the post-pandemic period. Mechanisms for responding to test results in real-time can be applied to other molecular diagnostics, e.g. respiratory direct pathogen PCR panels, interpretation of Clostridiodes difficile testing, et cetera.

Guidelines and Clinical Pathways

ASPs can play a pivotal role in summarizing and updating the treatment recommendations for the evolving COVID-19 pandemic, serving as an institution’s center for guidance on treatment. ASPs are frequently involved in the development of local treatment guidelines and their dissemination. This puts ASPs in an ideal position to develop local treatment protocols for COVID-19 and relay them to providers on the frontlines. Anecdotally, the three stewardship programs represented here were all directly involved in developing COVID-19 treatment protocols at our individual institutions. In addition, ASPs can modify current treatment plans to better serve patients with concomitant and secondary bacterial infections such as community-acquired pneumonia. The COVID-19 pandemic highlights opportunities to enhance guidelines dissemination to providers. ASPs can adopt creative solutions for guidelines dissemination such as the use of mobile/electronic software. Furthermore, ASPs can enhance their infrastructure to monitor and assess usage of guidelines and communicate this information back to providers on the frontlines as well as health system leadership.

ASPs can play a critical role in screening patients for COVID-19-focused clinical trials. Additionally, ASPs can assist in obtaining medications via expanded access programs through pharmaceutical companies. ASPs can also play a key role in placing clinical trial options in context via clinical guidelines development, thereby providing key information and context for frontline providers and helping to cross-coordinate direct clinical and research efforts.

Guidelines creation, upkeep and dissemination, as well as eligibility screening for experimental agents and obtaining medications via expanded access programs are time-consuming activities and may divert attention away from traditional ASP efforts.

New mechanisms for guidelines development and dissemination can continue in the post-pandemic period. Additionally, heightened provider awareness and adoption of guidelines may enhance their utilization in the post-pandemic period.

Conclusion

ASPs are uniquely positioned to support hospital COVID-19 response efforts. Potential ASP activities can include identifying patients with disease, developing diagnostic and treatment protocols and disseminating these to providers, and optimizing guideline concordant treatment. The COVID-19 pandemic provides opportunities for ASPs to strengthen and enhance relationships with specialized groups within health systems, as well. However, the diversion of time away from traditional ASP efforts may have negative consequences, and these should be balanced with pandemic responsibilities as much as possible. New ASP processes and infrastructure adopted during the pandemic should continue to be utilized in the post-pandemic period.