Phase 1: Systematic Literature Review

Antimicrobial stewardship implementation before and during the COVID-19 pandemic in the acute care settings: a systematic review

This study has been published in the PMC Public Health Journal: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-15072-5

The systematic literature search was conducted from the 9th to the 13th of March 2021 using predefined search terms and updated on the 20th of March 2023 and the 24th of November 2023. This search yielded 8,763 articles, with the screening process outlined in the PRISMA flow diagram (Figure 3.1.) and the included articles summarised in Table 3.4. The initial search produced 8,763 abstracts potentially eligible for inclusion: MEDLINE (n=3,640), all OVID journals (n=44), CINHAL PLUS (n=4,708), PsycINFO (n=10), SCOPUS (n=101), Web of Science (n=12), Cochrane (n=75), and an additional 173 from Google Scholar. After duplicates were removed, 4,566 articles proceeded to title and abstract screening. Of the 101 articles eligible for full-text screening, 79 met the inclusion criteria (Figure 3.1.). Sixty-six articles were excluded for not meeting the inclusion criteria due to lack of AMS intervention (n=36), inappropriate study settings (n=22), or irrelevant outcomes such as infection control precautions (n=8). Ultimately, 13 studies were included in the final analysis (Figure 1). For details from this link: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-15072-5

Figure 1. Systematic literature review results and screening process according to PRISMA guidelines.

Table 2. Summary of findings about antimicrobial stewardship implementation prior to and during the COVID-19 pandemic.

Prior to the COVID-19 pandemic, DDD was noticed in five studies (Trivedi et al., 2013; Kallen et al., 2021; Surat et al., 2021; Panditrao et al., 2021; and Ababneh et al., 2020). Additionally, the Days of Therapy (DOT) was found in eight studies (Trivedi et al., 2013; Surat et al., 2021; Mehta et al., 2014; Thakkar et al., 2021; and Ababneh et al., 2020). The Length of Stay (LOS) was found in three studies (Kallen et al., 2021; Surat et al., 2021; and Mehta et al., 2014), and Cost was found in three studies (Trivedi et al., 2013; Mehta et al., 2014; Moriyama et al., 2021). Furthermore, the Clostridioides Difficile Infection (CDI) was found in two studies (Trivedi et al., 2013; Tamma et al., 2021). However, Indicators of Quality Improvement were found in eight studies (Trivedi et al., 2013; Mehta et al., 2014; Panditrao et al., 2021; Ababneh et al., 2020). Appendix 11 provides examples of measures used to evaluate the efficacy of Antimicrobial Stewardship implementation.

During the COVID-19 pandemic, DDD was found in only one study (Williams et al., 2021), CDI was found in two studies (Ashiru-Oredope et al., 2021; Williams et al., 2021), and Procalcitonin (PCT) was found in one study (Williams et al., 2021). Indicators or Quality Improvement were found in two studies (Ashiru-Oredope et al., 2021 and Williams et al., 2021) (Table 3.6) (Figure 2). For details from this link: https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-023-15072-5

Figure 2. AMS before and during the COVID-19 pandemic in acute care settings (Total studies 13).

Phase 2: Retrospective Medical Records Review

Start Smart, Then Focus: Antimicrobial Stewardship Before and During the COVID-19 Pandemic at a Secondary Care

Clinical and Demographic Characteristics: A retrospective analysis was performed on 640 patient medical records from the Trust. The demographics of these patients are presented in Table 3. The comprehensive analysis of various variables did not reveal any statistically significant differences between the years 2019 and 2020. Patients admitted for RTIs during these years ranged in age from 25 to 99 years. A slight variation was observed in gender distribution: in 2019, females accounted for 49.4% (158) of the cases, increasing slightly to 49.7% (159) in 2020. Regarding patient outcomes, the data indicated that the mortality rate, the proportion of patients who passed away or died, remained steady at 15% during the two-year study period, as shown in Table 3.

Table 3. Characteristics of the patient demographics admitted prior to the COVID-19 pandemic (n=320)  and during the pandemic (n=320) (in 2019 and 2020).

The Five Rights of Antibiotic Safety

The Five Rights of Antibiotic Safety are essential for ensuring proper antibiotic use in acute care settings before and during the COVID-19 pandemic (Institute for Safe Medication Practices, 2007). These rights encompass the correct patient, drug, dose, time, and duration (Appendix 22). This study evaluated adherence to the 'Five Rights of Antibiotics' for the years 2019 and 2020.  As illustrated in Figure 3. below, there were significant shifts in the proportions of inappropriate antibiotic prescribing during this period. The inappropriate route of antibiotic administration saw a slight increase from 33% in 2019 to 36% in 2020. Similarly, instances of inappropriate dosing rose from 13% in 2019 to 18% in 2020. However, the proportion of inappropriate duration prescriptions showed improvement, decreasing from 70% in 2019 to 66% in 2020. However, prescriptions made without clear indications increased from 16% in 2019 to 20% in 2020. Interestingly, the selection of the antibiotic, in accordance with antimicrobial guidelines, remained relatively stable, levitating at 63-64% across both years. These findings highlight a concerning rise in inappropriate antibiotic prescribing patterns, especially during the 2020 COVID-19 pandemic. It has been published in the Journal of Global Antimicrobial Resistance: https://www.sciencedirect.com/science/article/pii/S2213716523002369?via%3Dihub

Figure 3. Five Rights of Antibiotic Safety: A Comparison of 2019 and 2020 During the COVID-19 Pandemic. 

The WHO Access, Watch, Reserve (AWaRe) classification: A heatmap was generated to visually display the antibiotics prescribed for RTIs before and during the COVID-19 pandemic. The WHO Access, Watch, Reserve (AWaRe) classification was employed as the gold standard for antibiotic classification. Table 4.7. shows the heatmap for antibiotic consumption in 2019 and 2020 based on AWaRe criteria, indicating a significant increase in antibiotic consumption in 2020 compared to 2019. Among Access Classification antibiotics, Amoxicillin/Clavulanic Acid was the most frequently prescribed in both 2019 and 2020. However, for Watch Classification antibiotics, Azithromycin showed a significant increase in 2020 (13 in March 2020, 19 in June 2020, 3 in September 2020, and 11 in December 2020) compared to 2019. Clarithromycin also significantly increased to 33 in December 2019 and 32 in March 2020. In contrast, Quinolones, such as Ciprofloxacin and Levofloxacin, were more frequently prescribed in 2020 (26 and 64, respectively) than in 2019 (15 and 40, respectively). Broad-spectrum antibiotics were also increasingly used before and during the pandemic. Furthermore, Linezolid, a Reserve Classification antibiotic, was more commonly used before the pandemic (7 in 2019) compared to during the pandemic (2 in 2020). It has been published in Frontiers Microbiology Journal: https://www.frontiersin.org/articles/10.3389/fmicb.2023.1298858/full

Table 7. The heatmap for antibiotic use in 2019 and 2020 is based on AWaRe criteria.

The Top Seven Prescribed Antibiotics Prior to and During the COVID-19 Pandemic

The seven most commonly prescribed antibiotics in both PP and DP, further detailed in Supplement 1. In 2019, amoxicillin/clavulanic acid was the most frequently prescribed antibiotic, accounting for 247 instances. This trend persisted in 2020 with 260 instances, maintaining its top position. In 2020, compared to 2019, there was an increase in prescriptions for most of the other antibiotics. For instance, clarithromycin saw an increase from 94 prescriptions in 2019 to 100 in 2020. Piperacillin/tazobactam also witnessed a slight rise, from 90 instances in 2019 to 97 in 2020. Additionally, 2020 saw increased prescriptions of levofloxacin, azithromycin, and ciprofloxacin compared to 2019. Levofloxacin prescriptions grew from 40 in 2019 to 64 in 2020. Azithromycin had a surge, jumping from 12 in 2019 to 46 in 2020. Ciprofloxacin also displayed a rising trend, going from 15 in 2019 to 26 in 2020, while meropenem's usage modestly increased in 2020, from 10 to 18 instances.

Phase 3: Prospective Survey Study

Healthcare professionals’ knowledge, attitudes and perceptions regarding antibiotic prescribing, antibiotic resistance and stewardship during the COVID-19 pandemic: A descriptive study at a secondary care setting in the UK

A total of 240 HCPs responded to the survey, with results recorded online and subsequently analysed. Data was exported to an Excel sheet from the secure online platform, ‘Qualtrics’ (Qualtrics.com, 2023). The researcher organised and cleaned the data, providing codes for the 5-point Likert scale responses as follows: 0 for Strongly Disagree; 1 for Disagree; 2 for Neutral; 3 for Agree; and 4 for Strongly Agree.

Healthcare professionals’ demographic characteristics

Most survey respondents were pharmacists (n=125, 52%), doctors (n=72, 30%), and nurses (n=43, 18%). Table 5.2 illustrates the breakdown of participants’ age characteristics: most respondents (n=96, 40.0%) were between 32 and 41 years old. In regard to education, most participants held a postgraduate master’s degree (n=163, 68.0%) or a postgraduate doctorate degree (n=43, 18.0%), while only a small percentage had an undergraduate degree (n=24, 10%). Regarding years of experience, those with 6-20 years were most represented among respondents (n=132, 55%). Table 5.2 provides a detailed breakdown of theHCPs’ demographic characteristics. Most respondents were female (56%), and the predominant qualification was a pharmacist (52%). Concerning educational achievements, the majority of respondents held a postgraduate master's degree (68%). Regarding job banding, the majority were in band 7 (27%). Descriptive statistics and logistic regression analysed healthcare professionals' views on antibiotic use and antimicrobial stewardship during COVID-19.