Antibiotic prescribing patterns among patients admitted to an academic teaching hospital for COVID-19 during the first wave of the pandemic in Toronto: A retrospective, controlled study
Publication: Official Journal of the Association of Medical Microbiology and Infectious Disease Canada
Volume 7, Number 1
Abstract
Abstract
BACKGROUND: Empirical antibiotics are not recommended for coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, patients admitted to Toronto General Hospital’s general internal medicine from the emergency department for COVID-19 between March 1 and August 31, 2020 were compared with those admitted for community-acquired pneumonia (CAP) in 2020 and 2019 in the same months. The primary outcome was antibiotics use pattern: prevalence and concordance with COVID-19 or CAP guidelines. The secondary outcome was antibiotic consumption in days of therapy (DOT)/100 patient-days. We extracted data from electronic medical records. We used logistic regression to model the association between disease and receipt of antibiotics, linear regression to compare DOT. RESULTS: The COVID-19, CAP 2020, and CAP 2019 groups had 67, 73, and 120 patients, respectively. Median age was 71 years; 58.5% were male. Prevalence of antibiotic use was 70.2%, 97.3%, and 90.8% for COVID-19, CAP 2020, and CAP 2019, respectively. Compared with CAP 2019, the adjusted odds ratio (aOR) for receiving antibiotics was 0.23 (95% CI 0.10 to 0.53, p = 0.001) and 3.42 (95% CI 0.73 to 15.95, p = 0.117) for COVID-19 and CAP 2020, respectively. Among patients receiving antibiotics within 48 hours of admission, compared with CAP 2019, the aOR for guideline-concordant combination regimens was 2.28 (95% CI 1.08 to 4.83, p = 0.031) for COVID-19, and 1.06 (95% CI 0.55 to 2.05, p = 0.856) for CAP 2020. Difference in mean DOT/100 patient-days was –24.29 (p = 0.009) comparing COVID-19 with CAP 2019, and +28.56 (p = 0.003) comparing CAP 2020 with CAP 2019. CONCLUSIONS: There are opportunities for antimicrobial stewardship to address unnecessary antibiotic use.
Résumé
HISTORIQUE : L’antibiothérapie empirique n’est pas recommandée pour le traitement de la maladie à coronavirus 2019 (COVID-19). MÉTHODOLOGIE : Dans cette étude rétrospective, les chercheurs ont comparé les patients atteints de COVID-19 hospitalisés au département de médecine interne générale du Toronto General Hospital entre le 1er mars et le 31 août 2020 après être passés par l’urgence à ceux hospitalisés à cause d’une pneumonie d’origine communautaire (POC) au cours des mêmes mois en 2020 et 2019 (POC-20 et POC-19). Le résultat primaire était le schéma d’utilisation des antibiotiques, c’est-à-dire la prévalence et le respect des lignes directrices sur la COVID-19 ou la POC. Le résultat secondaire correspondait à la consommation d’antibiotiques pendant les jours de traitement (JdT)/100 jours-patients. Les chercheurs ont puisé les données dans les dossiers médicaux électroniques. Ils se sont servi de la régression logistique pour modéliser l’association entre la maladie et la réception des antibiotiques, et de la régression linéaire pour comparer les JdT. RÉSULTATS : Le groupe COVID-19, le groupe POC-20 et le groupe POC-19 étaient composés de 67, 73 et 120 patients, respectivement. Ils avaient un âge médian de 71 ans, et 58,5 % étaient de sexe masculin. La prévalence d’utilisation d’antibiotiques s’élevait à 70,2 %, 97,3 % et 90,8 % dans les groupes COVID-19, POC-20 et POC-19, respectivement. Par rapport au groupe POC-19, le rapport de cotes rajusté (RCr) relatif à la réception d’antibiotiques s’élevait à 0,23 (IC à 95 %, 0,10 à 0,53, p = 0,001) et 3,42 (IC à 95 %, 0,73 à 15,95, p = 0,117) dans les groupes COVID-19 et POC-20, respectivement. Chez les patients qui avaient reçu des antibiotiques dans les 48 heures suivant leur hospitalisation par rapport au POC-19, le RCr relatif à la posologie d’association conforme aux lignes directrices était de 2,28 (IC à 95 %, 1,08 à 4,83, p = 0,031) et de 1,06 (IC à 95 %, 0,55 à 2,05, p = 0,856) dans le groupe POC-20. La différence quant au nombre moyen de JdT/100 jours-patients correspondait à –24,29 (p = 0,009) lorsqu’on comparait le groupe COVID-19 au groupe POC-19, et à +28,56 (p = 0,003) lorsqu’on comparait le groupe POC-20 au groupe POC-19. CONCLUSIONS : L’utilisation inutile d’antibiotiques pourrait très bien être prise en charge par la gérance des antimicrobiens.
Introduction
In Canada, the first case of coronavirus disease 2019 (COVID-19), the respiratory infection caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported on January 25, 2020, in a traveller returning from Wuhan, China, to Toronto. On March 17, 2020, Ontario declared a state of emergency because of the pandemic.
Although antibiotics have no role in viral illnesses, they can treat bacterial co-infections, which are recognized complications among patients with viral pneumonias, most notably those with influenza (1,2). The estimated prevalence of bacterial co-infection among patients with viral pneumonias varies widely, ranging from 2% to 65% (3). During the 2009 H1N1 influenza A pandemic, the prevalence of bacterial co-infection was estimated to be between 18% and 34% and as high as 55% among fatal cases (1,4). The most common bacterial pathogens are Streptococcus pneumoniae and Staphylococcus aureus, with an estimated prevalence of 35% and 28%, respectively (3). In contrast, bacterial co-infections among patients with coronavirus infections appear to be lower. Among patients with SARS-CoV-1, 11% were estimated to have bacterial infections, with predominantly secondary infections (5), whereas among patients with Middle East respiratory syndrome–related coronavirus, reports of bacterial infections were limited (6). As for COVID-19, the overall prevalence of bacterial co-infection was estimated in two systematic reviews and meta-analyses to be approximately 7% (7,8), and slightly higher (8.1%) among critically ill patients (7). The low prevalence of bacterial co-infections among patients with COVID-19 is incongruent with the high proportion of patients who received antibiotics, which was estimated to be 70% overall (9).
Concerns have been raised regarding emerging bacterial resistance after widespread use of antibiotics during the pandemic, as well as the potential harms from antibiotics, including Clostridioides difficile infections (10–12). Thus, there may be potential opportunities for antimicrobial stewardship programs to address unnecessary antibiotic use among patients hospitalized with COVID-19 (13,14). As a quality improvement initiative, antimicrobial stewardship is usually guided by local data. Therefore, a description of the prevalence of antibiotics prescribed, selection of regimens, and nature of bacterial infections (if identified) among COVID-19 patients will inform local antimicrobial stewardship strategies. The objective of this study was to evaluate the association between hospitalization for COVID-19 and receipt of antibiotics, compared with concurrent non-COVID community-acquired pneumonia (CAP) in 2020 and in 2019 at the Toronto General Hospital.
Methods
Study design
This was a retrospective cohort study with concurrent and historical controls. It was conducted at the Toronto General Hospital of University Health Network, an academic research hospital system affiliated with the University of Toronto. Patients were identified by Decision Support at the University Health Network from electronic hospital records as individuals with a primary discharge diagnosis of COVID-19 or CAP, as coded using the International Classification of Diseases and Related Health Problems 10th Revision (ICD-10) with standardized methods and according to the following pre-specified criteria (15). Patients were included if they were admitted directly from the emergency department to the general internal medicine (GIM) service. The target group was patients admitted for COVID-19 between March 1 and August 31, 2020 (the COVID group). Concurrent controls were patients admitted for CAP in the same time frame (the CAP 2020 group). Historical controls were patients admitted for CAP during the same months in 2019 (the CAP 2019 group). Diagnosis of COVID-19 was confirmed by standardized method using real-time polymerase chain reaction with the Seegene AllplexTM 2019-nCoV Assay by the University Health Network/Sinai Health microbiology laboratory. Investigations for co-infections were conducted at the discretion of the treating clinician. Patients subsequently transferred to the intensive care unit were censored, but data collected until then were included in the analyses. Patients with pre-existing cancer diagnoses undergoing treatment, uncontrolled HIV infection, or receipt of solid organ or stem cell transplantation, and patients transferred from a non-GIM unit within the hospital or from another facility were excluded.
Outcome definitions and data sources
The primary outcome was patterns of antibiotic use, reported as the overall prevalence of antibiotic prescribing during hospitalization and the empirical antibiotic’s concordance with institutional clinical guidelines for COVID-19 or CAP, as applicable. The COVID-19 and CAP guidelines are available through the publicly accessible website of the Sinai Health–University Health Network Antimicrobial Stewardship Program. The first version of the COVID-19 guideline was available in February 2020. This so-called living guideline was later transformed into the Ontario COVID-19 guideline, which was and continues to be actively implemented at the University Health Network. Empirical regimens were defined as antibiotics administered within 48 hours of admission. Guideline-concordant empirical antibiotic regimens for both COVID-19 and CAP were ceftriaxone or amoxicillin–clavulanate, with or without azithromycin. However, specific to COVID-19 patients, antibiotic therapy was only recommended for patients with suspected or documented bacterial co-infections, given the viral etiology of COVID-19 and available literature (5,7,8,16). Antimicrobial stewardship efforts during the study period were primarily focused on informing clinicians about available COVID-19 resources, including the clinical guideline. Secondary outcomes were the overall quantity of antibiotic use, expressed as days of therapy (DOT)/100 patient-days, and number of hospital-acquired C. difficile infections/1,000 patient-days. DOT normalized to specific patient-days is a standardized metric recommended for reporting antibiotic consumption (17,18), and C. difficile infections are adverse events associated with antibiotic exposure (19). Each administered dose of antibiotic had a date–time stamp in the electronic medication administration record. The study dataset was created by linking each medication administration event to the patient’s medical record number and visit identification. DOT for each antibiotic was calculated by adding the number of days it was administered to the patient. If a patient received more than one antibiotic, the total DOT for the patient was aggregated as per current standards (18).
Patient’s age, sex, Charlson Comorbidity Index score, key chronic illnesses, date and time of admission and discharge, disposition from hospitalization, and length of stay were extracted from electronic health records. The Forward Sortation Area (FSA), which is the first three letters of the patient’s postal code, was used as a proxy for factors associated with the social determinants of health, specifically the patient’s neighbourhood-level household income and COVID-19 infection rate. FSA-level income data were referenced from the 2016 Canadian census. Each patient was categorized as residing in an FSA that was at or above versus below the Toronto median income ($78,373). Cumulative FSA-level COVID-19 infection rates by the week of August 30, 2020 were obtained from Public Health Ontario, and divided into quartiles. Each patient in the COVID group was categorized as residing in an FSA with a low, medium, high, or very high COVID-19 infection rate.
Statistical analysis
A chi-square test was used to compare the overall prevalence of antibiotic use between groups. Logistic regression was used to model the association between study group and receipt of at least one dose of antibiotics during hospitalization (ever versus never) and receipt of guideline-based regimens among patients who received empirical antibiotics within 48 hours of admission, with the CAP 2019 group as the reference. We conducted crude and multivariable analyses adjusting for age, sex, Charlson Comorbidity Index score, and neighbourhood income level. Model goodness-of-fit was assessed with the Akaike information criterion and likelihood ratio test. The Kruskal–Wallis test was used to compare duration of antibiotic therapy at the patient level. Linear regression was used to compare the aggregate monthly DOT/100 patient-days and C. difficile rates between groups. Statistical significance was defined as p < 0.05. Descriptive statistics were reported for patient characteristics. For other categorical variables, a chi-square test was used, and for other continuous variables, the Kruskal–Wallis test was used for between-group comparisons. All statistical analyses were conducted with Stata version 16.1 (College Station, Texas, USA).
Research ethics
The study was approved by the Research Ethics Board of the University Health Network.
Results
Patient characteristics
The study included 260 patients, with 67 (25.8%) in the COVID group, 73 (28.1%) in the CAP 2020 group, and 120 (46.1%) in the CAP 2019 group. Their baseline characteristics and clinical course are presented in Table 1. Compared with the control groups, the COVID group had a higher proportion of men (p = 0.509) and was younger (p = 0.203), but the differences were not statistically significant. The COVID group had a longer median length of stay (p < 0.001) and a higher proportion of patients who died or required admission to the intensive care unit (p = 0.005). Most patients in the COVID group resided in an FSA with a high COVID infection rate. The proportion of patients residing in an FSA with a median household income below that of the Toronto median was higher in the COVID group than in the control groups, but the differences were not statistically significant (p = 0.388).
| Variable | No. (%)* | ||
|---|---|---|---|
| COVID; n = 67 | CAP 2020; n = 73 | CAP 2019; n = 120 | |
| Median age (IQR), y | 69 (32.0) | 70 (28.0) | 71 (24.5) |
| Male | 43 (64.2) | 40 (54.8) | 69 (57.5) |
| Pre-existing comorbid illness | |||
| Charlson Comorbidity Index score < 3 (low risk of mortality) | 59 (88.1) | 68 (93.2) | 108 (90.0) |
| Diabetes | 17 (25.4) | 24 (32.9) | 19 (15.8) |
| Cardiovascular disease | 35 (52.2) | 45 (61.6) | 85 (70.8) |
| Chronic lung disease | 8 (11.9) | 19 (26.0) | 28 (23.3) |
| Social determinants of health | |||
| No address on record | 5 (7.5) | 7 (9.6) | 4 (3.3) |
| Residing in a neighbourhood (FSA) with median income below Toronto regional median | 50 (74.6) | 50 (68.5) | 85 (70.8) |
| Distribution of patients’ neighbourhood (FSA) level COVID-19 infection rate by regional quartiles† | n/a | n/a | |
| Low | 16 (25.8) | ||
| Medium | 11 (17.7) | ||
| High | 33 (53.2) | ||
| Very high | 2 (3.2) | ||
| Microbiological workup | |||
| Nasopharyngeal swab for viral infections collected | 67 (100.0) | 73 (100.0) | 98 (81.7) |
| Respiratory culture collected | 3 (4.5) | 12 (16.4) | 41 (34.2) |
| Urine Legionella antigen test | 9 (13.4) | 9 (12.3) | 23 (19.2) |
| Blood culture collected | 60 (90.0) | 62 (84.9) | 93 (77.5) |
| Disposition status | |||
| Median length of stay (IQR), days | 10 (18) | 4 (5) | 5 (6) |
| Discharged alive | 48 (71.6) | 64 (87.7) | 110 (91.7) |
| Transferred to ICU | 11 (16.4) | 4 (5.5) | 6 (5.0) |
| Readmitted to hospital ≥3 mo after discharge | 1 (1.5) | 1 (1.4) | 2 (1.7) |
*
* Unless otherwise indicated
†
† Distribution of FSA was calculated based on 62 patients, as FSA data were not available for 5 patients.
COVID-19 = Coronavirus disease 2019; CAP = Community-acquired pneumonia; IQR = Inter-quartile range; FSA = Forward sortation area, which is the first three letters of the patient’s postal code; n/a = Not applicable; ICU = Intensive care unit
Microbiological workup and results
All patients in 2020 and most in 2019 had nasopharyngeal swab for viral infections (Table 1). In the COVID group, no other viral infections were detected. In the CAP 2020 group, 1 patient had respiratory syncytial virus (RSV). In the CAP 2019 group, 4 had RSV and 3 had influenza A. Only 4% of COVID patients had sputum collected for bacterial or fungal cultures, compared with 16% and 34% in the CAP 2020 and CAP 2019 groups, respectively. In the COVID group, 3 patients had positive sputum cultures, growing Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus aureus (MSSA), and Candida albicans. In the CAP 2020 group, 4 patients had positive cultures, identified as Escherichia coli, P. aeruginosa, and MSSA (2 patients). In the CAP 2019 group, 5 patients had positive cultures, growing P. aeruginosa, Streptococcus intermedius, Mycobacterium avium complex, Mycobacterium xenopi, and Aspergillus fumigatus. In the COVID group, 1 patient had S. aureus bacteremia. In the CAP 2020 group, 3 had bacteremia (2 Streptococcus pneumoniae, 1 Streptococcus constellatus). In the CAP 2019 group, 6 patients had bacteremias: 2 cases each of S. pneumoniae and viridans group streptococci, 1 case of E. coli, and 1 case of S. intermedius. Of the 41 (15.8%) patients in the entire cohort tested for Legionella urinary antigen, none had a positive result.
Primary outcome
Prevalence of antibiotic use during hospitalization was 70.2% (47/67), 97.3% (71/73), and 90.8% (109/120) for the COVID, CAP 2020, and CAP 2019 groups, respectively (p < 0.001). Compared with the CAP 2019 group, the adjusted odds ratio (aOR) of receiving at least one dose of antibiotic was 0.23 (95% CI 0.10 to 0.53, p = 0.001) for the COVID group and 3.42 (95% CI 0.73 to 15.59, p = 0.117) for the CAP 2020 group (Table 2). Among the 227 patients who received at least one dose of antibiotics, 211 (93.0%) were prescribed empirical antibiotics within 48 hours of admission (40 in the COVID group, 63 in the CAP 2020 group, and 108 in the CAP 2019 group). Compared with the CAP 2019 group, the aOR for receiving guideline-concordant combination empirical antibiotics was 2.28 (95% CI 1.08 to 4.83, p = 0.031) for the COVID group and 1.06 (95% CI 0.55 to 2.05, p = 0.856) for the CAP 2020 group. The aOR for receiving guideline-concordant empirical monotherapy was 0.54 (95% CI 0.24 to 1.24, p = 0.147) for the COVID group and 0.93 (95% CI 0.49 to 1.79, p = 0.838) for the CAP 2020 group. The aOR for receiving antibiotics not endorsed by guideline was 0.70 (95% CI 0.29 to 1.66, p = 0.413) for the COVID group and 1.01 (95% CI 0.50 to 2.03, p = 0.975) for the CAP 2020 group.
| Study group | Unadjusted model, OR (95% CI), p-value | Multivariable* model, aOR (95% CI), p-value | ||||
| Receipt of ≥1 dose of antibiotic during hospitalization | ||||||
| COVID-19 | 0.24 (0.11 to 0.54), 0.001 | 0.23 (0.10 to 0.53), 0.001 | ||||
| CAP 2020 | 3.58 (0.77 to 16.65), 0.103 | 3.42 (0.73 to 15.95), 0.117 | ||||
| CAP 2019 (Ref.) | 1.00 | |||||
| Receipt of guideline-concordant empiric regimen within 48 h of admission | ||||||
| Ceftriaxone + azithromycin or amoxicillin-clavulanate + azithromycin | Ceftriaxone or amoxicillin-clavulanate | Others | Ceftriaxone + azithromycin or amoxicillin-clavulanate + azithromycin | Ceftriaxone or amoxicillin-clavulanate | Others | |
| COVID-19 | 2.21 (1.06 to 4.63), 0.035 | 0.52 (0.23 to 1.18), 0.119 | 0.75 (0.32 to 1.77), 0.518 | 2.28 (1.08 to 4.83), 0.031 | 0.54 (0.24 to 1.24), 0.147 | 0.70 (0.29 to 1.66), 0.413 |
| CAP 2020 | 1.07 (0.56 to 2.06), 0.56 | 0.90 (0.48 to 1.72), 0.757 | 1.04 (0.52 to 2.07), 0.911 | 1.06 (0.55 to 2.05), 0.856 | 0.93 (0.49 to 1.79), 0.838 | 1.01 (0.50 to 2.03), 0.975 |
| CAP 2019 (Ref.) | 1.00 | |||||
*
*Multivariable model was adjusted for age, sex, and Charlson Comorbidity Index
OR = Odds ratio; aOR = Adjusted odds ratio; COVID-19 = Coronavirus disease 2019; CAP = Community-acquired pneumonia; Ref. = Reference
Secondary outcomes
Among patients who received at least one dose of antibiotic, the median duration of therapy was 7 days (inter-quartile range [IQR] 8) in the COVID group, 4 days (IQR 5) in the CAP 2020 group, and 5 days (IQR 7) in the CAP 2019 group (p = 0.17). At the aggregate level, the mean monthly DOT/100 patient-days was 41.6 (SD 13.0) for the COVID group, 94.4 (SD 15.0) for the CAP 2020 group, and 65.9 (SD 13.7) for the CAP 2019 group (Figure 1). The between-groups difference in mean monthly DOT/100 patients was –24.29 DOT/100 patient-days for the COVID group versus the CAP 2019 group (p = 0.009) and 28.56 DOT/100 patient-days for the CAP 2020 group versus the CAP 2019 group (p = 0.003). There were 3 cases of C. difficile infection in the COVID group (3.02 cases/1,000 patient-days), 1 case in the CAP 2020 group (2.46 cases/1,000 patient-days), and none in the CAP 2019 group.
Figure 1: Quantity of antibiotic consumption by study group
COVID-19 = Coronavirus disease 2019; CAP = Community- acquired pneumonia
Discussion
In this retrospective study of patients admitted to the GIM service at Toronto General Hospital, the odds of receiving antibiotics were significantly lower in the COVID group than in the CAP 2019 group. Although consistent with the literature, with a prevalence of use of 70.2%, local COVID-19 patients were prescribed more antibiotics than necessary given the low risk of bacterial co-infections reported worldwide (5,8,9).
Clinical guidance for managing COVID-19 patients, such as the Ontario COVID-19 guidelines and the UK National Institute for Health and Care Excellence COVID-19 guidelines (20), emphasizes that the role of antibiotics should be limited to those with suspected or confirmed bacterial co-infections. If prescribed, a review within 24–48 hours based on microbiological investigations is encouraged, and the antibiotics should be promptly discontinued when no longer required (20). However, in the initial months of the pandemic, there was substantial diagnostic uncertainty in identifying bacterial co-infections among patients with suspected or confirmed SARS-CoV-2 infections because limited microbiological investigations were performed (9). In the current study, only 4% of patients in the COVID group had respiratory specimens collected for cultures. When the true prevalence of bacterial co-infections was unclear, clinicians may have opted to give antibiotics if they considered the possible benefits to outweigh the potential harms, including C. difficile infections, despite the viral etiology of COVID-19.
Among patients who received empirical antibiotics for pneumonia, the COVID group was more than twice as likely to be prescribed guideline-concordant empirical combination therapy than the CAP 2019 group. There are several possible explanations. First, because SARS-CoV-2 was a novel entity, clinicians may prefer to follow available guidelines, however preliminary, given the learning curve of managing a new disease. Second, the study period overlapped with seasonal Legionella infections, for which azithromycin is indicated. Third, early in the pandemic, azithromycin was purported to be a potential treatment for COVID, although that hypothesis was later refuted in large clinical trials (20–23).
Although the odds of receiving an antibiotic among patients in the CAP 2020 group was not significantly different from the odds in the CAP 2019 group, the more refined antibiotic consumption metric of DOT/100 patient-days indicated that CAP 2020 patients received a significantly higher quantity of antibiotics. Some patients may have delayed or avoided seeking medical care as a result of concerns about contracting COVID-19 in medical facilities (24) because during the first wave, virtual health care had not been well established in Ontario (25,26). Therefore, it was possible that CAP 2020 patients were more severely ill than CAP 2019 patients. In addition, with enhanced public health measures and provincewide restrictions on gathering and commerce, rates of communicable respiratory viral infections in the 2020 season were lower than in 2019 (27). For example, in April 2020, the average influenza A positivity rate in Ontario was 0.1%, compared with 10.3% in April 2019. Similar patterns were observed for parainfluenza and RSV locally and elsewhere (28). With few microbiological tests being conducted in March–August 2020, clinicians may have assumed bacteria to be the primary etiologies of CAP in non-COVID patients admitted to GIM. Thus, more antibiotics were prescribed at the aggregate level, potentially signalling a spillover effect of COVID-19 on clinical decision making.
Staub et al evaluated changes in antimicrobial use after implementing a COVID-19 antimicrobial stewardship team at an academic, tertiary acute-care hospital (29). The study period was divided into three parts: (1) pre-COVID-19 (12 wk), (2) during COVID but pre-stewardship team (3 wk), and (3) during COVID and with stewardship team (8 wk). In GIM, average weekly antibiotic consumption increased by 14.53 DOT/100 patient-days (95% CI 3.51 to 25.55) between periods 1 and 2, compared with non-COVID patients. After implementation of the stewardship team, antibiotic use was reduced significantly by 36.23 DOT/100 patient-days between periods 2 and 3. In that study, 65.6% (86/131) of COVID-19 patients received antibiotics. This single-centre study of hospitalized COVID-19 patients was limited by a short interval (11 wk).
Seaton et al conducted a point-prevalence survey in 15 Scottish hospitals on a single day between April 20 and 30, 2020, and compared antibiotic use among patients who tested positive for SARS-CoV-2 (n = 531) with use among those who tested negative (n = 289) (30). Among patients in the general medical and elderly wards, empirical antibiotics were active on the day of survey for 86.9% (133/153) of patients with COVID-19, compared with 92.5% (148/160) of patients admitted for non-COVID reasons. In the entire study population, the prevalence of antibiotic prescription was 45.0%, of which 73.9% was prescribed for suspected respiratory tract infections. Amoxicillin, amoxicillin–clavulanate, and doxycycline accounted for more than half of the antibiotics used in the general medical wards.
More comprehensively, Russell et al conducted a prospective cohort study of 260 hospitals in the United Kingdom and analyzed data from more than 48,000 patients admitted between February 6 and June 8, 2020 (31). Overall, 85.2% of patients received antibiotics during hospitalization, and the proportion was highest in March and April 2020 for both medical ward and critically ill patients. Microbiological investigations were conducted for 8,649 patients (17.7%), of whom 1,107 (12.8%) had documented infections (respiratory tract infections or bacteremia). Notably, 70.6% (762/1,080) of the infections were secondary, occurring more than 2 days after admission. The authors commented on the need to set stewardship targets to address the high frequency of antibiotic use, despite rare bacterial infections.
Our study has several strengths. First, it is the first Canadian report on antibiotic use among patients hospitalized for COVID-19 in a well-defined population. Second, through this study, we have established a reliable procedure to extract analyzable variables from electronic health records in the existing data infrastructure, as well as from unstructured sources such as microbiology results, thereby improving the efficiency in examining antibiotic use in subsequent waves of the pandemic. Third, we included neighbourhood (FSA) income level as a proxy of social determinants of health to enhance our understanding of their impact on the epidemiology of COVID-19 and CAP in GIM patients.
This study also has limitations. First, we did not validate the CAP diagnoses with clinical criteria such as radiographical abnormalities, or correlate signs and symptoms with severity of illness for individual patients. However, adjudicating diagnostic accuracy was beyond the scope of the study objectives. Rather, patients were selected by their primary discharge diagnoses as reported by their physicians, and these diagnoses were subsequently coded as per standardized hospital reports submitted to the Canadian Institute for Health Information. Second, we could not assess appropriateness of antibiotics prescribed because of the limited extent of microbiology investigations other than nasopharyngeal swabs. Instead, we focused on benchmarking antibiotic selection against local guidelines. Third, we did not account for other social determinants of health, such as race–ethnicity, occupation, and measures of social marginalization. However, public health officials have frequently used FSA as a proxy during the pandemic. Last, given the retrospective design of the study, accuracy of the data was limited by the quality of clinical documentation and data extraction procedures, which was a pitfall of health services research with electronic records. To optimize the accuracy of the primary outcome, we validated the data extraction pathways for antibiotic administration records. Despite those limitations, our findings were consistent with the two large studies previously mentioned (30,31).
Future work will include evaluation of antibiotic and antifungal use in subsequent months of the pandemic, because data on secondary bacterial and fungal infections among COVID-19 patients are emerging after widespread implementation of COVID-specific interventions. In conclusion, in this first Canadian retrospective cohort study with concurrent and historical controls, 70.2% of COVID-19 patients admitted to GIM received antibiotics, despite low rates of bacterial co-infection. Antimicrobial stewardship interventions should focus on addressing the spillover effects of the pandemic on clinical decision making, such as encouraging a diagnostic-driven approach to reduce unnecessary therapy among both COVID-19 and non-COVID patients.
Acknowledgement:
This work was conducted at the Toronto General Hospital, University Health Network, as part of the MPH in Epidemiology degree program practicum undertaken by Miranda So at the Harvard T.H. Chan School of Public Health. Miranda So thanks Dr. Heather J. Baer, ScD, Faculty Director of the MPH in Epidemiology program at the Harvard T.H. Chan School of Public Health, for her kindness, continuous support, and generous advice.
Registry and the Registration No. of the Study/Trial:
N/A
Funding:
No funding was received for this work.
Peer Review:
This manuscript has been peer reviewed.
Animal Studies:
N/A
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Information & Authors
Information
Published In
Official Journal of the Association of Medical Microbiology and Infectious Disease Canada
Volume 7 • Number 1 • March 2022
Pages: 14 - 22
Copyright
2022 AMMI Canada.
History
Received: 12 July 2021
Submitted: 15 October 2021
Revision received: 15 October 2021
Accepted: 22 October 2021
Published online: 10 December 2021
Published in print: March 2022
Keywords:
Mots-clés :
Authors
Contributors:
Conceptualization, M So, AM Morris, AM Walker; Methodology, M So, AM Morris, AM Walker; Software, M So; Validation, M So; Formal Analysis, M So, AM Walker; Investigation, M So; Resources, M So, AM Morris, AM Walker; Data Curation, M So; Writing – Original Draft, M So; Writing – Review & Editing, M So, AM Morris, AM Walker; Visualization, M So; Supervision, AM Morris, AM Walker; Project Administration, M So, AM Walker.
Disclosures:
M So is the Chair of the Canadian Society of Hospital Pharmacists Foundation Education Grant Review Committee.
Ethics Approval:
The Research Ethics Review board of the University Health Network approved this study.
Informed Consent:
N/A
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Journal of the Association of Medical Microbiology and Infectious Disease Canada 2022 7:1, 14-22
Journal of the Association of Medical Microbiology and Infectious Disease Canada 2022 7:1, 14-22