The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic

The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic Ailiana Santosa, Julius Collin, Elin Dahlén, Anders Lignell, Maria Furberg, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5903243/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Apr, 2026 Read the published version in Communications Medicine → Version 1 posted You are reading this latest preprint version Abstract This study explored trends in antibiotic use and the risk of complications for pharyngotonsillitis in Swedish primary care before, during and after the pandemic. Using register-based data from 295,972 cases (2018–2023) of patients aged 12 + in the Stockholm and Västra Götaland regions with a 180-day washout period, logistic regression models assessed 30-day complication risks for patients who received antibiotics versus those who did not. Antibiotic prescriptions decreased during the pandemic, followed by a partial rebound, with penicillin remaining the preferred antibiotic. Complications, particularly peritonsillar abscess, were more frequent in patients receiving antibiotics (1.75%) than in untreated individuals (0.43%). Patients prescribed penicillin had fewer complications (1.62%) compared to other antibiotics (2.87%). Adjusted analyses showed the risk for complications was lower for untreated patients (aOR 0.24, 95% CI 0.22–0.26). The pandemic significantly impacted prescribing patterns, supporting penicillin’s continued use as a first-line therapy supported by its association with lower complication risks. Health sciences/Health care Health sciences/Diseases/Respiratory tract diseases Pharyngotonsillitis Antibiotic Treatment Complications COVID-19 pandemic Sweden Background Pharyngotonsillitis, an inflammation of the pharynx and tonsils, is commonly caused by viral or bacterial infections, with Streptococcus pyogenes (group A streptococci, GAS) being the most significant bacterial pathogen. Treatment guidelines ( 1 – 5 ) generally recommend antibiotics only for GAS-related infections. Since 2001, the Swedish Medical Products Agency and Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) ( 3 , 6 ) have recommended using the Centor scoring system to identify patients at higher risk of GAS infection. For patients with a Centor score of 3–4 and a positive GAS rapid antigen test, penicillin V is the recommended treatment ( 1 ). During the COVID-19 pandemic, viral infections such as influenza and respiratory syncytial virus, as well as bacterial respiratory infections like otitis media, declined notably across Europe ( 7 – 9 ) and the US ( 10 ). In the UK, a significant reduction in pharyngotonsillitis episodes was observed among children with recurrent pharyngotonsillitis during lockdown ( 11 ). Similarly, a retrospective study in the US (2019–2021) reported a sharp decline in tonsil-related diagnoses in April 2020, though these later rebounded to exceed those seen pre-pandemic ( 12 ). Reduced healthcare visits during the pandemic also resulted in less antibiotics being prescribed and dispensed across Europe ( 13 ). A systematic review of 81 studies ( 14 ) found a 37% decline in healthcare visits early in the pandemic, with a greater reduction among individuals with less severe illness. In Sweden, primary care consultations decreased by around 12%, particularly among patients over 65, with no observed gender differences ( 15 ). In the US, outpatient antibiotic prescriptions dropped by 40% between January and May 2020 compared to 2017–2019 ( 16 ). Conversely, in the UK, primary care antibiotic prescriptions increased during the pandemic despite fewer appointments from April to August 2020 compared to 2019 ( 17 ). In Sweden, the decline in antibiotic prescription in 2020 marked the largest reduction in 20 years ( 18 ). The impact of antibiotic treatment on complications from upper respiratory tract infections (URTIs) and urinary tract infections (UTIs) has been well-documented ( 19 , 20 ). Antibiotic prescriptions reduced return visits for patients with a positive Rapid Antigen Detection Test (RADT) for GAS, while those with a negative RADT tend to have more return visits ( 21 ). In Sweden, the incidence of uncomplicated bacterial infections, including otitis media, acute rhinosinusitis, and acute pharyngotonsillitis dropped by 40% in 2020 compared to 2019, particularly among patients aged 0–19, alongside declines in antibiotic prescriptions and complications from URTIs, such as acute mastoiditis and peritonsillitis ( 22 ). However, it remains unclear whether this trend persisted during the continued pandemic or after the pandemic. Pre-pandemic studies from Sweden ( 23 ) and the UK ( 24 ) found that URTIs rarely cause complications, and antibiotic mainly shortens the time with symptoms and help prevent the spread of infection. Nevertheless, there have been anecdotal reports of an increasing proportion of complications following pharyngotonsillitis during and after the COVID-19 pandemic, alongside a major upsurge of invasive group A streptococci across Europe ( 25 ) and other regions post-pandemic ( 26 , 27 ). This study therefore investigated trends in antibiotic use among pharyngotonsillitis patients and the associated risk of complications before, during and after the pandemic. RESULTS Characteristics of study participants The study includes 295,972 pharyngotonsillitis patients identified from the Stockholm and Västra Götaland regions between 1 January 2018 and 31 December 2023 (Table 1 ). Of these, 37.6% were male, with the predominant age group being 25–39 years (39.2%). Most patients had tertiary education (63.7%), were not married (70.1%), were Nordic-born (78.5%), had received a COVID-19 booster (51.6%), and had only one primary care visit (74.1%), with only 6.1% of patients with ≥ 3 visits. The Charlson Comorbidity Index showed that 81.2% had no comorbidities. In addition, 8.4% had autoimmune disease, and 9.4% had glucocorticoid treatment. Table 1 Characteristics, including sociodemographics, Charlson comorbidity index, primary care visits, COVID-19 vaccination and immunosuppression status, among pharyngotonsillitis patients living in Stockholm and Västra Götaland regions in Sweden between 1 January 2018 and 31 December 2023, overall and by antibiotic treatment (yes/no) Characteristics Overall n = 295,972 Antibiotic treatment Yes (n = 154,021) No (n = 141,951) Sex, male, n (%) 111,407 (37.6%) 57,544 (37.4%) 53,863 (37.9%) Age, n (%) 12–24 87,133 (29.4%) 45,161 (29.3%) 41,972 (29.6%) 25–39 116,019 (39.2%) 64,827 (42.1%) 51,192 (36.1%) 40–69 83,318 (28.2%) 40,780 (26.5%) 42,538 (30.0%) >=70 9,502 (3.2%) 3,253 (2.1%) 6,249 (4.4%) Education level, n (%) Primary school 75,904 (25.6%) 38,911 (25.3%) 36,993 (26.1%) Secondary school 31,788 (10.7%) 16,014 (10.4%) 15,774 (11.1%) Tertiary school = 3 years 108,509 (36.7%) 56,343 (36.6%) 52,166 (36.7%) Marital status, n (%) Not married 207,405 (70.1%) 105,564 (68.5%) 101,841 (71.7%) Married/register partner 88,567 (29.9%) 48,457 (31.5%) 40,110 (28.3%) Country of birth, n (%) Nordic countries 232,387 (78.5%) 118,989 (77.3%) 113,398 (79.9%) Other countries 63,585 (21.5%) 35,032 (22.7%) 28,553 (20.1%) Vaccination status, n (%) None 44,178 (14.9%) 24,047 (15.6%) 20,131 (14.2%) 1 dose 8,482 (2.9%) 4,570 (3.0%) 3,912 (2.8%) 2 doses 90,635 (30.6%) 48,067 (31.2%) 42,568 (30.0%) Booster (3rd) dose 152,677 (51.6%) 77,337 (50.2%) 75,340 (53.1%) Number of primary care visits, n (%) One visit 219,273 (74.1%) 112,090 (72.8%) 107,183 (75.5%) Two visits 58,640 (19.8%) 31,822 (20.7%) 26,818 (18.9%) Three visits 14,247 (4.8%) 7,929 (5.1%) 6,318 (4.5%) Four or more visits 3,812 (1.3%) 2,180 (1.4%) 1,632 (1.1%) Charlson comorbidity index, n (%) 0 240,435 (81.2%) 128,128 (83.2%) 112,307 (79.1%) 1 25,970 (8.8%) 12,909 (8.4%) 13,061 (9.2%) 2–3 8,914 (3.0%) 3,939 (2.6%) 4,975 (3.5%) 4–5 912 (0.3%) 360 (0.2%) 552 (0.4%) >=6 19,741 (6.7%) 8,685 (5.6%) 11,056 (7.8%) Autoimmune disease, n(%) 24,873 (8.4%) 12,683 (8.2%) 12,190 (8.6%) Immunosuppressive treatments , n(%) Selective immunosuppressants 402 (0.1%) 193 (0.1%) 209 (0.1%) TNF-alfa inhibitors 2,521 (0.9%) 1,412 (0.9%) 1,109 (0.8%) Interleukin inhibitors 599 (0.2%) 302 (0.2%) 297 (0.2%) Other immunosuppressants 3,314 (1.1%) 1,657 (1.1%) 1,657 (1.2%) Glucocorticoids 26,975 (9.1%) 13,241 (8.6%) 13,734 (9.7%) Cytostatic 721 (0.2%) 316 (0.2%) 405 (0.3%) Trend in antibiotic treatments Table 2 shows trends in antibiotic treatment and types of antibiotics used among pharyngotonsillitis patients across three periods. The proportion of patients receiving antibiotics decreased significantly during the pandemic (39.9%) compared to pre-pandemic levels (53.4%), then increased post-pandemic (51.3%) to a level similar to pre-pandemic. Despite these changes in overall prescribing, penicillin-V remained the most prescribed antibiotics, with consistently high usage across all periods. Patients with and without antibiotic treatment showed similar characteristics (Table 1 ), but with fewer treated patients aged 70 or older (2.1%), compared to untreated patients (4.4%). Additionally, a high CCI score (over 6) was less common among treated patients (5.6%) than untreated patients (7.8%). Table 2 Trends of antibiotic treatment (yes/no) and type of antibiotics (penicillin/other) among patients with pharyngotonsillitis who lived in Stockholm and Västra Götaland regions in Sweden and visited primary healthcare between 1 January 2018-31 December 2023 Period Antibiotic treatment, n (%) Type of antibiotics a , n (%) Yes (n = 154,021) No (n = 141,951) Penicillin (n = 137,836) Other antibiotic (n = 16,185) Pre-pandemic 81,504 (53.4) 58,109 (41.6) 72,739 89.3) 8,765 (10.8) Pandemic 26,791 (39.9) 40,369 (60.1) 23,851 (89) 2,940 ( 11 ) Post pandemic 45,726 (51.3) 43,473 (48.7) 41,246 (90.2) 4,480 (9.8) Footnote: Pre-pandemic: 1 Jan 2018-31 Jan 2020; Pandemic: 1 Feb 2020-28 Feb 2022; Post pandemic: 1 Mar 2022-31 Jan 2024 a only for those received antibiotic treatment Characteristics of pharyngotonsillitis patients who received antibiotic treatment across periods highlight that, post-pandemic, a higher proportion of patients aged 25–39 received antibiotics, while the proportion of younger patients (12–24 years) receiving antibiotics decreased compared to pre-pandemic levels ( Suppl Table 5 ). Additionally, there was an increase in antibiotic treatment among patients with autoimmune diseases and those on glucocorticoid therapy across periods. Complications in pharyngotonsillitis patients Complications occurred in 1.75% of patients who received antibiotics, compared to 0.43% of those who did not receive antibiotics (Table 3 ). The overwhelmingly most common complication was peritonsillar abscess, occurring in 1.72% of patients receiving antibiotics and 0.41% of untreated patients. Other types of complications were very rare across all groups. In terms of antibiotic type, 1.62% of patients treated with penicillin-V experienced complications, compared to 2.87% of those who received other antibiotics. Peritonsillar abscess was the overwhelmingly most frequent complication in both groups. Rare complications, like retropharyngeal and parapharyngeal abscesses, occurred slightly more often with other antibiotics, while necrotizing fasciitis and bacteremia were exceedingly rare. Table 3 Proportion of complications observed within 30 days among patients with pharyngotonsillitis who lived in Stockholm and Västra Götaland regions in Sweden between1 January 2018 and 31 Jan 2024, stratified by antibiotic treatment (yes/no) and by type of antibiotic treatment (penicillin/other antibiotics) Complications Antibiotics treatment n (%) Type of antibiotics a n (%) Yes (n = 154,021) No (n = 141,951) Penicillin (n = 137,836) Other antibiotic (n = 16,185) Total 2,695 (1.75%) 612 (0.43%) 2,230 (1.62%) 465 (2.87%) Type of complications Peritonsillar abscess 2,647 (1.72%) 577 (0.41%) 2,193 (1.59%) 454 (2.81%) Retropharyngeal & parapharyngeal abscess 62 (0.04) 38 (0.03) 42 (0.03) 20 (0.12%) Rheumatic fever 0 0 0 0 Necrotizing fasciitis < 5 (0.0) < 5 (0.0) < 5 (0.0) 0 (0.0) Bacteremia 17 (0.01) 9 (0.006) 15 (0.01) < 5 (0.0) Footnote: a analysis only including those who received antibiotic treatment Complication among patients receiving antibiotics varied across periods, with the highest proportion observed during the pandemic at 2.58%, predominantly due to peritonsillar abscesses ( Suppl Table 6 ). Pre-pandemic and post-pandemic rates were lower, at 1.38% and 1.92%, respectively, with peritonsillar abscesses also being the predominant complication. Untreated patients consistently had a lower proportion of complications across all periods, with an increase observed from 0.38% pre-pandemic to 0.51% post-pandemic, primarily due to peritonsillar abscesses. Associations between antibiotic treatments and complications within 30 days Table 4 presents the unadjusted and adjusted odds ratios of complication within 30 days across the study period. The adjusted odds ratio (aOR) of experiencing any complication within 30 days was lower in untreated patients compared to antibiotic-treated patients, with an aOR of 0.24 (95% CI 0.22–0.27). This trend was consistent across all pandemic periods, with the lowest odds ratios observed during the pandemic (aOR 0.16, 95%CI 0.13–0.19). For specific complications (Table 5 ), the odds ratio of developing a peritonsillar abscess, the most common complication, was 0.23 (95% CI 0.21–0.26) for untreated patients compared to antibiotic-treated patients. Table 4 Crude and adjusted odds ratio for the association between antibiotic treatment (No vs Yes) and type of antibiotic treatment (other antibiotics vs penicillin) with complications occurring within 30 days among pharyngotonsillitis patients in Stockholm and Västra Götaland regions in Sweden, overall and across different pandemic periods. Period Antibiotic treatment (No vs Yes) Type of antibiotic ,a (Other vs Penicillin) Crude OR(95%CI) aOR b (95%CI) Crude OR(95%CI) aOR b (95%CI) Overall 0.24 (0.22–0.27) 0.24 (0.22–0.26) 1.80(1.63–1.99) 1.84 (1.66–2.04) Pre-pandemic 0.27 (0.24–0.32) 0.27 (0.24–0.31) 2.03(1.75–2.36) 2.05 (1.75–2.39) Pandemic 0.16 (0.13–0.19) 0.16 (0.13–0.19) 1.66(1.35–2.03) 1.71 (1.39–2.09) Post pandemic 0.26 (0.22–0.30) 0.26 (0.22–0.30) 1.62(1.34–1.95) 1.70 (1.40–2.06) Footnote: aOR: adjusted odds ratio; CI: confidence interval a analysis only including those who received antibiotic treatment b - adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments Table 5 Association between antibiotic treatment (No vs Yes) and type of antibiotic (other antibiotics vs penicillin) with specific complications within 30 days among pharyngotonsillitis patients in Stockholm and Västra Götaland regions in Sweden. Type of complications Antibiotic treatment c (No vs Yes) Type of antibiotic ,a, (Other vs Penicillin) Crude OR, 95% CI aOR b , 95% CI Crude OR, 95% CI aOR b , 95% CI Peritonsillar abscess 0.23(0.21–0.26) 0.23 (0.21–0.26) 1.79(1.61–1.98) 1.83(1.65–2.03) Retropharyngeal & parapharyngeal abscess 0.66(0.44–0.99) 0.60 (0.40–0.90) 4.06(2.38–6.92) 3.98(2.32–6.82) Rheumatic fever - - - - Necrotizing fasciitis 1.09(0.22–5.38) 0.85(0.17–4.30) - - Bacteremia 0.57(0.26–1.29) 0.60 (0.26–1.35) 1.13(0.26–4.97) 1.00(0.22–4.52) Footnote: aOR: adjusted odds ratio; CI: confidence interval a analysis only including those who received antibiotic treatment b adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments Among antibiotic-treated patients, those prescribed other antibiotics had higher odds of complications within 30 days compared to patients treated with penicillin-V (aOR 1.84, 95% CI 1.66–2.04) (Table 4 ). For specific complication, such as retropharyngeal or parapharyngeal abscess, the aOR was even higher (3.98, 95% CI 2.32.-6.82). Patients without antibiotic treatment had a significantly reduced risk of complications among pharyngotonsillitis patients that was consistent across all age groups, with the lowest odds ratio observed in the oldest age group 70+ (aOR 0.17, 95% CI 0.10–0.29) (Table 6 ). Similarly, the reduced risks were observed in both males and females. Among patients treated with antibiotics, those receiving with other antibiotic had a higher odds ratio of complications compared to those treated with penicillin-V, and this was also regardless of age or sex. Table 6 Associations between antibiotic treatment (No vs Yes) and type of antibiotic (other antibiotics vs /penicillin) with complications occurring within 30 days among patients with pharyngotonsillitis in Stockholm and Västra Götaland regions in Sweden, stratified by sex and age Antibiotic treatment (no vs yes) c Type of antibiotic (other vs penicillin) a Crude OR (95% CI) aOR b (95% CI) Crude OR (95% CI) aOR b (95% CI) Age group (years) 12–24 0.29(0.25–0.33) 0.29(0.25–0.34) 2.11(1.75–2.55) 2.10(1.71–2.50) 25–39 0.25(0.22–0.29) 0.25(0.21–0.28) 1.81(1.54–2.13) 1.83(1.56–2.16) 40–69 0.19(0.16–0.23) 0.19(0.15–0.23) 1.56(1.29–1.88) 1.65(1.37-2.00) 70+ 0.17(0.10–0.28) 0.17(0.10–0.29) 1.95(1.13–3.38) 2.00(1.14–3.50) Sex Female 0.25(0.22–0.28) 0.25(0.22–0.29) 1.76(1.54–2.02) 1.76(1.54–2.2) Males 0.23(0.20–0.26) 0.23(0.20–0.26) 1.97(1.69–2.29) 1.96(1.68–2.29) Footnote: aOR = adjusted odd ratio, CI = confidence interval a only for those received antibiotic treatment c adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments. Discussions This study provides a comprehensive analysis of antibiotic prescribing trends and the occurrence of complications among pharyngotonsillitis patients living in Stockholm and Västra Götaland regions across different periods (pre-pandemic, pandemic, and post-pandemic). These two populous regions in Sweden represent approximately 40% of the national population. The main findings indicate: ( 1 ) a temporary decrease in antibiotic prescriptions during the pandemic, followed by a partial rebound afterward, with penicillin-V consistently being the preferred antibiotics, ( 2 ) complications were more frequent in patients receiving antibiotics (1.75%) compared to those not treated (0.43%), and patients treated with penicillin-V had fewer complications (1.62%) than those treated with other antibiotics (2.97%), and ( 3 ) after adjusting for sociodemographics, comorbidities, primary care visits, and vaccination status, the odds ratio of experiencing complications within 30 days was lower (aOR 0.24, 95%CI 0.22–0.26) for those who did not receive antibiotic treatment. Effectiveness of Antibiotic Treatment The COVID-19 pandemic significantly impacted antibiotic prescribing patterns for common infections ( 17 ), including pharyngotonsillitis, in primary care settings. This study observed a marked decline in antibiotic prescriptions during the COVID-19 pandemic, with a rebound afterward, consistent with prior research ( 29 – 31 ). Despite these fluctuations, penicillin-V remained the first-choice antibiotic for treating pharyngotonsillitis throughout study period, with only 10% of patients being prescribed other antibiotics. Penicillin-V continues to be the first-choice antibiotic for treating group A beta-hemolytic streptococcal (GABHS) pharyngotonsillitis due to its effectiveness, narrow spectrum, and low cost ( 32 ), as recommended by the Swedish guidelines ( 3 , 6 ). In a randomized controlled inferiority study, Skoog et al ( 33 ) compared relapses and complication rates of two intervention groups treated with penicillin-V. The findings revealed no significant differences, suggesting the continued use of penicillin-V as a primary treatment for uncomplicated pharyngotonsillitis, with potential for shorter treatment durations. Furthermore, our study highlights that Sweden’s restrictive approach to antibiotic use has demonstrated that limiting prescriptions does not increase complications, such as peritonsillar abscesses or rheumatic fever. This reinforces the safety and efficacy of penicillin-V as the preferred treatment. Additionally, the study found that complications were more frequent in patients receiving antibiotics compared those untreated, in line with previous studies ( 23 , 24 ). Notably, however, patients treated with penicillin-V experienced fewer complications (1.6%) than those on other antibiotics (2.9%), echoing findings from a large retrospective study conducted in Israel ( 34 ). Although antibiotics overall were associated with increased risk of complications within 30 days in pharyngotonsillitis patients (likely due to selection of high-risk patients for treatment), this study found that other antibiotics (broad-spectrum antibiotics) were associated with higher odds of complications compared to penicillin-V, across all age groups and sexes. The findings suggest that penicillin-V is effective and a safe option to use to prevent complications compared to broader spectrum antibiotics. Broad-spectrum antibiotics, typically used when penicillin fails, may disrupt a broader range of bacteria, potentially increasing the risk of adverse effects and complications. These findings underscore the benefits of selecting narrow-spectrum antibiotics like penicillin-V when appropriate to reduce risk. Strengths and limitation of the study One of the primary strengths of this study is its large sample size, which includes data spanning five years from two major Swedish regions, illustrating different periods for evaluating trend in antibiotic prescription for pharyngotonsillitis patients and complications. This extensive dataset enhances the generalizability of the findings to broader populations. Additionally, this study accounts for various confounding factors such as sociodemographics, comorbidities (Charlson Comorbidity Index and immunosuppressive conditions), COVID-19 vaccination status, and healthcare utilization, enabling a more precise assessment of the association between antibiotic use and the occurrence of complication in pharyngotonsillitis patients. Another strength is its temporal analysis, covering pre-pandemic, pandemic and post-pandemic periods, which shed light on healthcare practices, particularly in antibiotic treatment in pharyngotonsillitis patients. The consistent use of penicillin-V as the primary treatment across all periods underscores its effectiveness and low risk of complications in managing pharyngotonsillitis, even within a challenging healthcare environment. Despite its strengths, the study has several limitations. First, as an observational study, there is a risk of confounding by indication. This occurs when the decision to prescribe antibiotics is influenced by factors such as the severity of illness or underlying health conditions, which are also related to the risk of complications. As a result, patients who receive antibiotics inherently are likely to have a higher baseline risk of developing complications compared to those who do not, irrespective of the treatment itself. Although we adjusted for sociodemographic characteristics, comorbidities, primary care visits, and vaccination status, residual confounding in this situation is likely, and should be considered when interpreting the causal relationship between antibiotic treatment (vs. no treatment) and complication risk. By design, this study cannot establish causality; it only demonstrates an association between antibiotic use and complications in actual use, with the indications in clinical practice, without confirming that antibiotics directly prevent complications or vice versa. Another limitation is the lack of detailed information on patient adherence to prescribed antibiotic regimens. Non-adherence, such as patients not completing their full course of antibiotics or improperly timing doses, could have influences the study outcomes ( 35 ). This factor is particularly relevant for those who received antibiotics yet still developed complications, as inadequate adherence may reduce the effectiveness of the medication, potentially leading to unresolved infections or the development of complications. Lastly, reliance on healthcare records may result in missing or misclassified data. For instance, complications could be underreported if patients sought care outside the documented healthcare system or if minor complications were not thoroughly recorded, potentially underestimating the true complication rates. This study highlights penicillin-V’s continued role as the preferred treatment option for pharyngotonsillitis, primarily due to its association with lower complication rates compared to other antibiotics. The results provide valuable evidence to guide clinicians, especially when faced with uncertainty between opting for penicillin-V or alternative treatments. Additionally, the notable decline in antibiotic prescriptions observed during the pandemic, followed by a rebound in the post-pandemic period, indicates a substantial shift in healthcare delivery and patient behavior. This pattern suggests that factors such as reduced healthcare access, heightened infection control measures, or a more cautious approach to prescribing during the pandemic likely influenced antibiotic use. The subsequent return to pre-pandemic prescribing levels highlights the importance of continued efforts in antibiotic management to prevent overuse and ensure optimal patient outcomes. Conclusion This study demonstrates that the COVID-19 pandemic impacted antibiotic prescribing practices for pharyngotonsillitis in Swedish primary care, leading to a notable decline in overall antibiotic use during this period. Penicillin-V’s continued use as a first-line therapy appears well-justified due to its association with a lower risk of complications. Additionally, the consistently lower complication rates observed among patients who did not receive antibiotics highlight the importance of careful antibiotic prescribing. These findings emphasize the necessity of appropriate antibiotic use, as well as the continued monitoring of prescribing trends, particularly during the periods of healthcare disruption, such as the COVID-19 pandemic. Method Data sources This cohort study is part of the RECOVAC study (Register-based large-scale national population study to monitor COVID-19 vaccination effectiveness and safety) within the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights – a Population Epidemiology Approach using Register Linkage) project, described in detail elsewhere ( 28 ), and expanded to cover the entire Swedish population. We linked individual data from multiple Swedish national and regional registers. Diagnoses from outpatient specialist visits and inpatient care came from the National Patient Register, while primary care diagnoses were obtained from regional primary healthcare registers for Stockholm Region and Västra Götaland Region (the two largest regions in Sweden, approximately 40% of the population). A comprehensive medical history from 2015 was accessed through the National Patient Register, and prescription drug histories from 2018 onward were obtained from the National Prescribed Drug Register. Sociodemographic data, including education, marital status, and country-of-birth, were acquired from Statistics Sweden (covering 2015–2019), and COVID-19 vaccination data were retrieved from the national vaccination register. Study population and index infection episodes The study included individuals aged 12 and older residing in Stockholm Region and Västra Götaland Region who had at least one primary care visit between 1 January 2018 and 30 December 2023. To identify unique episodes of pharyngotonsillitis for the same patient and exclude recurrent or chronic cases, a 180-day washout period was applied prior to each primary care visit. Thus, for an episode to be counted as a new episode, at least 180 days prior to that primary care visit had to be free of any records of pharyngotonsillitis in primary, specialist outpatient or inpatient care. Study period, exposures and follow-up risk window The study period spanned from 1 January 2018 to 31 January 2024, covering both the initial diagnosis of pharyngotonsillitis and the occurrence of any complications within one month of the pharyngotonsillitis diagnosis. Antibiotic treatment exposure was defined as a dispensed prescription for an antibiotic used for upper respiratory infection prescribed within 2 days of each index date of a pharyngotonsillitis episode. Complications were assessed for a follow-up of 30 days after the pharyngotonsillitis diagnosis. The study period from 1 January 2018 to 31 January 2020 was classified as pre-pandemic, 1 February 2020 to 28 February 2022 as pandemic, and 1 March 2022 to 30 January 2024 as post-pandemic period. Outcome Infectious complications were identified in primary care, outpatient specialist care and hospital inpatient care. They included peritonsillar abscess, retro-parapharyngeal abscess, necrotizing fasciitis, invasive Group A streptococcal disease, and rheumatic fever (for ICD-10 code definitions, see Suppl Table 1 ). Exposures Antibiotic treatment for pharyngotonsillitis was identified using ATC codes for dispensed prescriptions (see Suppl Table 2 ) and coded as “yes” or “no”, with the reference group being those who received antibiotic treatment. Further, antibiotic treatment was dichotomised into those receiving phenoximethylpenicillin (penicillin-V) and those receiving other antibiotics, with penicillin-V serving as the reference group. Covariates The following covariates were used for adjustment and stratification: age (12–24, 25–39, 40–69, 70+), sex, country of birth (Nordic/other countries), marital status (married/not married), education (primary, secondary, tertiary less than three years, tertiary three years or longer), number of primary care visits from the index date to outcome occurrence (one, two, three, four or more), vaccination status (none, one dose, two doses, booster), the Charlson Comorbidity Index (CCI) based on diagnoses in the three years preceding the index date (categorized 0,1,2–3,4–5 and ≥6) ( Suppl Table 3 ) as well as immunosuppression status (autoimmune disease and immunosuppressive treatment) ( Suppl Table 4 ). Statistical analysis Descriptive analyses were conducted to examine trends in antibiotic treatment and type of antibiotic use over the pandemic period. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for complications within 30 days, comparing those who did not received antibiotics to those who did (reference group) among pharyngotonsillitis patients. Apart from the crude unadjusted model, an adjusted model included adjustment for sex, age, sociodemographic factors, number of primary care visits, CCI, and immunosuppression status. Similar regressions were done only among antibiotic-treated patients, comparing those prescribed other antibiotics to patients treated with penicillin-V (reference group). Subgroup analyses were conducted by sex and age. Results are presented as crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CI). Statistical analyses were performed in SAS 9.4 and STATA 18. Declarations Acknowledgement: Author Contributions: AS-conception, design, analysis, writing, revisions; JC, ED, AL, MF, AT, RL, FN-conception, design, revisions. All authors reviewed and approved the final version. Funding support: The SCIFI-PEARL study has basic funding based on grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (grants ALFGBG-938453, ALFGBG-971130, and ALFGBG-978954) and previously from a joint grant from Forte (Swedish Research Council for Health, Working Life and Welfare) and Formas (Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning), grant 2020-02828. AL, ED, MF, RL are employed at the Swedish Medical Products Agency, SE-751 03 Uppsala, Sweden. JC and AT are employed at the Public Health Agency of Sweden, SE-171 82 Solna, Sweden. The views expressed in this paper do not necessarily represent the views of the Agency. Conflicts of interest: All none References Läkemedelsverket [Swedish Medical Products Agency]. Läkemedelsbehandling vid faryngotonsillit – behandlings-rekommendation [Drug treatment of pharyngotonsillitis - treatment recommendation]. Inf Läkemedelsverket; 2024 [Available from: https://www.lakemedelsverket.se/sv/behandling-och-forskrivning/behandlingsrekommendationer/sok-behandlingsrekommendationer/lakemedelsbehandling-vid-faryngotonsillit--behandlingsrekommendation#hmainbody1. National Institute for Health and Care Excellence. Sore throat (acute): antimicrobial prescribing 2018 [Available from: www.nice.org.uk/guidance/ng84. Läkemedelsverket [Swedish Medical Products Agency]. Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance Annual Report (STRAMA). Läkemedelsverket; 2024. Scottish Intercollegiate Guidelines Network (SIGN). SIGN Guideline – management of sore throat and indications for tonsillectomy. A national clinical guideline. 2010 [Available from: https://www.nice.org.uk/guidance/ng84. Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, et al. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012;18 Suppl 1:1-28. Folkhalsomyndigheten [Public Health Agency of Sweden]. Behandlingsrekommendationer för vanliga infektioner i öppenvård [Treatment recommendations for common outpatient infections]: Folkhalsomyndigheten [Public Health Agency of Sweden]; 2023 [Available from: https://www.folkhalsomyndigheten.se/contentassets/246aa17721b44c5380a0117f6d0aba40/behandlingsrekommendationer-oppenvard.pdf. (EDCC) ECfDPaC. Seasonal Influenza 2020-2021 - annual report 2020 Stockholm: EDCC; 2021 [Available from: https://www.ecdc.europa.eu/sites/default/files/documents/AER-seasonal-influenza-2020-final.pdf. Folkhälsomyndigheten [Public Health Agency of Sweden]. RSV-säsongen 2021–2022. Stockholm: Folkhälsomyndigheten [Public Health Agency of Sweden],; 2022. Hullegie S, Schilder AGM, Marchisio P, de Sevaux JLH, van der Velden AW, van de Pol AC, et al. A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands. Front Cell Infect Microbiol. 2021;11:768377. Kaur R, Schulz S, Fuji N, Pichichero M. COVID-19 Pandemic Impact on Respiratory Infectious Diseases in Primary Care Practice in Children. Front Pediatr. 2021;9:722483. Heward E, Rocke J, Kumar N, Izzat S. Recurrent tonsillitis and parental perceptions of tonsillectomy during the COVID-19 pandemic. Int J Pediatr Otorhinolaryngol. 2020;139:110463. Allen DZ, Challapalli S, Lee KH, Bell CS, Roy S, Bowe S, et al. Impact of COVID-19 on nationwide pediatric otolaryngology practice: Adenotonsillectomies (TA) and tonsil-related diagnoses trends. Am J Otolaryngol. 2022;43(5):103526. Control ECfDPa. Antimicrobial consumption in the EU/EEA (ESAC-Net) - Annual Epidemiological Report for 2022 Stockholm: EDCC; 2022 [Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-consumption-europe-2022. Moynihan R, Sanders S, Michaleff ZA, Scott AM, Clark J, To EJ, et al. Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review. BMJ Open. 2021;11(3):e045343. Ekman B, Arvidsson E, Thulesius H, Wilkens J, Cronberg O. Impact of the Covid-19 pandemic on primary care utilization: evidence from Sweden using national register data. BMC Res Notes. 2021;14(1):424. King LM, Lovegrove MC, Shehab N, Tsay S, Budnitz DS, Geller AI, et al. Trends in US Outpatient Antibiotic Prescriptions During the Coronavirus Disease 2019 Pandemic. Clin Infect Dis. 2021;73(3):e652-e60. Armitage R, Nellums LB. Antibiotic prescribing in general practice during COVID-19. Lancet Infect Dis. 2021;21(6):e144. Norman C, Svensson M, Schmidt I, Bergfeldt VS, Obeid R, Ternhag A, et al. Reduced dispensing of prescribed antibiotics during the Covid-19 pandemic has not increased severe complications from common infections. BMC Public Health. 2022;22(1):252. Dahlén E, Collin J, Hellman J, Norman C, Nauclér P, Ternhag A. The effect of absent or deferred antibiotic treatment on complications of common infections in primary care. Int J Infect Dis. 2022;124:181-6. Petersen I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. Bmj. 2007;335(7627):982. Pallon J, Sundqvist M, Rööst M, Hedin K. Association between bacterial finding, antibiotic treatment and clinical course in patients with pharyngotonsillitis: a registry-based study in primary healthcare in Sweden. BMC Infectious Diseases. 2021;21(1):779. Gisselsson-Solen M, Hermansson A. Trends in upper respiratory tract infections and antibiotic prescriptions during the COVID-19 pandemic - a national observational study. Acta Otolaryngol. 2022;142(7-8):549-52. Cars T, Eriksson I, Granath A, Wettermark B, Hellman J, Norman C, et al. Antibiotic use and bacterial complications following upper respiratory tract infections: a population-based study. BMJ Open. 2017;7(11):e016221. Gulliford MC, Moore MV, Little P, Hay AD, Fox R, Prevost AT, et al. Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. Bmj. 2016;354:i3410. Goldberg-Bockhorn E, Hagemann B, Furitsch M, Hoffmann TK. Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic. Dtsch Arztebl Int. 2024(Forthcoming). Schweon SJ. Group A Streptococcal infections on the rise. Nursing. 2023;53(7):41-4. Vieira A, Wan Y, Ryan Y, Li HK, Guy RL, Papangeli M, et al. Rapid expansion and international spread of M1(UK) in the post-pandemic UK upsurge of Streptococcus pyogenes. Nat Commun. 2024;15(1):3916. Nyberg F, Franzen S, Lindh M, Vanfleteren L, Hammar N, Wettermark B, et al. Swedish Covid-19 Investigation for Future Insights - A Population Epidemiology Approach Using Register Linkage (SCIFI-PEARL). Clin Epidemiol. 2021;13:649-59. Li C, Ong C, Morris A, Woollons I, Ashfaq A, Jagatia R. Evaluating the Appropriateness of Antibiotic Treatment of Tonsillitis during COVID-19 in the North Wale Primary Healthcare Setting. J Prim Care Community Health. 2021;12:21501327211003687. Zhu N, Aylin P, Rawson T, Gilchrist M, Majeed A, Holmes A. Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves. Clinical Microbiology and Infection. 2021;27(5):762-8. Shah M, Fleming A, Barbosa TM, van der Velden AW, Parveen S, Vellinga A. Point prevalence audit surveys of respiratory tract infection consultations and antibiotic prescribing in primary care before and during the COVID-19 pandemic in Ireland. Journal of Antimicrobial Chemotherapy. 2023;78(5):1270-7. van Driel ML, De Sutter AIM, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database of Systematic Reviews. 2010(10). Skoog Ståhlgren G, Tyrstrup M, Edlund C, Giske CG, Mölstad S, Norman C, et al. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. BMJ. 2019;367:l5337. Bar-Yishay M, Yehoshua I, Bilitzky A, Press Y. Treatment outcomes of acute streptococcal tonsillitis according to antibiotic treatment. A retrospective analysis of 242,366 cases treated in the community. European Journal of General Practice. 2022;28(1):142-9. Baryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nature Reviews Drug Discovery. 2023;22(5):387-409 Additional Declarations There is NO Competing Interest. Supplementary Files SupplAntibioticsonPharyngotonsillitisComplications.docx Supplementary material for The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic Cite Share Download PDF Status: Published Journal Publication published 01 Apr, 2026 Read the published version in Communications Medicine → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Gothenburg","correspondingAuthor":false,"prefix":"","firstName":"Fredrik","middleName":"","lastName":"Nyberg","suffix":""}],"badges":[],"createdAt":"2025-01-25 18:25:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5903243/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5903243/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s43856-026-01564-z","type":"published","date":"2026-04-01T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":106074185,"identity":"52f876a8-5d13-46c4-815c-d84d1505f022","added_by":"auto","created_at":"2026-04-03 07:11:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1089375,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5903243/v1/43a9276d-8448-43be-803f-8903d2cbefc1.pdf"},{"id":80827286,"identity":"42aa337f-00bd-4ad6-ae7d-037c033a935b","added_by":"auto","created_at":"2025-04-17 13:25:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40129,"visible":true,"origin":"","legend":"Supplementary material for The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic","description":"","filename":"SupplAntibioticsonPharyngotonsillitisComplications.docx","url":"https://assets-eu.researchsquare.com/files/rs-5903243/v1/206b81a68ab0b842eb58e0e6.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic","fulltext":[{"header":"Background","content":"\u003cp\u003ePharyngotonsillitis, an inflammation of the pharynx and tonsils, is commonly caused by viral or bacterial infections, with \u003cem\u003eStreptococcus pyogenes\u003c/em\u003e (group A streptococci, GAS) being the most significant bacterial pathogen. Treatment guidelines (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) generally recommend antibiotics only for GAS-related infections. Since 2001, the Swedish Medical Products Agency and Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) have recommended using the Centor scoring system to identify patients at higher risk of GAS infection. For patients with a Centor score of 3\u0026ndash;4 and a positive GAS rapid antigen test, penicillin V is the recommended treatment (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring the COVID-19 pandemic, viral infections such as influenza and respiratory syncytial virus, as well as bacterial respiratory infections like otitis media, declined notably across Europe (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) and the US (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In the UK, a significant reduction in pharyngotonsillitis episodes was observed among children with recurrent pharyngotonsillitis during lockdown (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Similarly, a retrospective study in the US (2019\u0026ndash;2021) reported a sharp decline in tonsil-related diagnoses in April 2020, though these later rebounded to exceed those seen pre-pandemic (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Reduced healthcare visits during the pandemic also resulted in less antibiotics being prescribed and dispensed across Europe (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A systematic review of 81 studies (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) found a 37% decline in healthcare visits early in the pandemic, with a greater reduction among individuals with less severe illness. In Sweden, primary care consultations decreased by around 12%, particularly among patients over 65, with no observed gender differences (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In the US, outpatient antibiotic prescriptions dropped by 40% between January and May 2020 compared to 2017\u0026ndash;2019 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Conversely, in the UK, primary care antibiotic prescriptions increased during the pandemic despite fewer appointments from April to August 2020 compared to 2019 (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In Sweden, the decline in antibiotic prescription in 2020 marked the largest reduction in 20 years (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe impact of antibiotic treatment on complications from upper respiratory tract infections (URTIs) and urinary tract infections (UTIs) has been well-documented (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Antibiotic prescriptions reduced return visits for patients with a positive Rapid Antigen Detection Test (RADT) for GAS, while those with a negative RADT tend to have more return visits (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In Sweden, the incidence of uncomplicated bacterial infections, including otitis media, acute rhinosinusitis, and acute pharyngotonsillitis dropped by 40% in 2020 compared to 2019, particularly among patients aged 0\u0026ndash;19, alongside declines in antibiotic prescriptions and complications from URTIs, such as acute mastoiditis and peritonsillitis (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). However, it remains unclear whether this trend persisted during the continued pandemic or after the pandemic. Pre-pandemic studies from Sweden (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and the UK (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) found that URTIs rarely cause complications, and antibiotic mainly shortens the time with symptoms and help prevent the spread of infection. Nevertheless, there have been anecdotal reports of an increasing proportion of complications following pharyngotonsillitis during and after the COVID-19 pandemic, alongside a major upsurge of invasive group A streptococci across Europe (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) and other regions post-pandemic (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). This study therefore investigated trends in antibiotic use among pharyngotonsillitis patients and the associated risk of complications before, during and after the pandemic.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of study participants\u003c/h2\u003e \u003cp\u003eThe study includes 295,972 pharyngotonsillitis patients identified from the Stockholm and V\u0026auml;stra G\u0026ouml;taland regions between 1 January 2018 and 31 December 2023 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 37.6% were male, with the predominant age group being 25\u0026ndash;39 years (39.2%). Most patients had tertiary education (63.7%), were not married (70.1%), were Nordic-born (78.5%), had received a COVID-19 booster (51.6%), and had only one primary care visit (74.1%), with only 6.1% of patients with \u0026ge;\u0026thinsp;3 visits. The Charlson Comorbidity Index showed that 81.2% had no comorbidities. In addition, 8.4% had autoimmune disease, and 9.4% had glucocorticoid treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics, including sociodemographics, Charlson comorbidity index, primary care visits, COVID-19 vaccination and immunosuppression status, among pharyngotonsillitis patients living in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden between 1 January 2018 and 31 December 2023, overall and by antibiotic treatment (yes/no)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;295,972\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eAntibiotic treatment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;154,021)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;141,951)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSex, male, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111,407 (37.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57,544 (37.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e53,863 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e87,133 (29.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45,161 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41,972 (29.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e116,019 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64,827 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51,192 (36.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e83,318 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40,780 (26.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42,538 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;=70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9,502 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3,253 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,249 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEducation level, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75,904 (25.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e38,911 (25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36,993 (26.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31,788 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16,014 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15,774 (11.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTertiary school\u0026thinsp;\u0026lt;\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79,771 (27.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42,753 (27.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37,018 (26.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTertiary school\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108,509 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56,343 (36.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52,166 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMarital status, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNot married\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e207,405 (70.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e105,564 (68.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e101,841 (71.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried/register partner\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e88,567 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48,457 (31.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40,110 (28.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCountry of birth, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNordic countries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e232,387 (78.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e118,989 (77.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e113,398 (79.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther countries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e63,585 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35,032 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28,553 (20.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVaccination status, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44,178 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24,047 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20,131 (14.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8,482 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4,570 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3,912 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 doses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90,635 (30.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48,067 (31.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42,568 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBooster (3rd) dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152,677 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77,337 (50.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75,340 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of primary care visits, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOne visit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e219,273 (74.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e112,090 (72.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e107,183 (75.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTwo visits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58,640 (19.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31,822 (20.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26,818 (18.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThree visits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14,247 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7,929 (5.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6,318 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFour or more visits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,812 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2,180 (1.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,632 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharlson comorbidity index, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e240,435 (81.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128,128 (83.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e112,307 (79.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25,970 (8.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12,909 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13,061 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8,914 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3,939 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,975 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e912 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e360 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e552 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;=6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19,741 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8,685 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11,056 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAutoimmune disease, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24,873 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12,683 (8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12,190 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImmunosuppressive treatments\u003c/b\u003e, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSelective immunosuppressants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e402 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e193 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e209 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTNF-alfa inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2,521 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1,412 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,109 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInterleukin inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e599 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e302 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e297 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther immunosuppressants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,314 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1,657 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,657 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlucocorticoids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26,975 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13,241 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13,734 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCytostatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e721 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e316 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e405 (0.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTrend in antibiotic treatments\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows trends in antibiotic treatment and types of antibiotics used among pharyngotonsillitis patients across three periods. The proportion of patients receiving antibiotics decreased significantly during the pandemic (39.9%) compared to pre-pandemic levels (53.4%), then increased post-pandemic (51.3%) to a level similar to pre-pandemic. Despite these changes in overall prescribing, penicillin-V remained the most prescribed antibiotics, with consistently high usage across all periods. Patients with and without antibiotic treatment showed similar characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), but with fewer treated patients aged 70 or older (2.1%), compared to untreated patients (4.4%). Additionally, a high CCI score (over 6) was less common among treated patients (5.6%) than untreated patients (7.8%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTrends of antibiotic treatment (yes/no) and type of antibiotics (penicillin/other) among patients with pharyngotonsillitis who lived in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden and visited primary healthcare between 1 January 2018-31 December 2023\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAntibiotic treatment, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eType of antibiotics \u003csup\u003ea\u003c/sup\u003e, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;154,021)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;141,951)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePenicillin\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;137,836)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther antibiotic\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16,185)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81,504 (53.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58,109 (41.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72,739 89.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8,765 (10.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26,791 (39.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40,369 (60.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23,851 (89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2,940 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost pandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45,726 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43,473 (48.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41,246 (90.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4,480 (9.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eFootnote: Pre-pandemic: 1 Jan 2018-31 Jan 2020; Pandemic: 1 Feb 2020-28 Feb 2022; Post\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003epandemic: 1 Mar 2022-31 Jan 2024\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e only for those received antibiotic treatment\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCharacteristics of pharyngotonsillitis patients who received antibiotic treatment across periods highlight that, post-pandemic, a higher proportion of patients aged 25\u0026ndash;39 received antibiotics, while the proportion of younger patients (12\u0026ndash;24 years) receiving antibiotics decreased compared to pre-pandemic levels (\u003cb\u003eSuppl Table\u0026nbsp;5\u003c/b\u003e). Additionally, there was an increase in antibiotic treatment among patients with autoimmune diseases and those on glucocorticoid therapy across periods.\u003c/p\u003e\n\u003ch3\u003eComplications in pharyngotonsillitis patients\u003c/h3\u003e\n\u003cp\u003eComplications occurred in 1.75% of patients who received antibiotics, compared to 0.43% of those who did not receive antibiotics (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The overwhelmingly most common complication was peritonsillar abscess, occurring in 1.72% of patients receiving antibiotics and 0.41% of untreated patients. Other types of complications were \u003cem\u003every\u003c/em\u003e rare across all groups. In terms of antibiotic type, 1.62% of patients treated with penicillin-V experienced complications, compared to 2.87% of those who received other antibiotics. Peritonsillar abscess was the overwhelmingly most frequent complication in both groups. Rare complications, like retropharyngeal and parapharyngeal abscesses, occurred slightly more often with other antibiotics, while necrotizing fasciitis and bacteremia were exceedingly rare.\u003c/p\u003e \u003ctable id=\"Tab3\" border=\"1\" style=\"margin-right: calc(21%); width: 79%;\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eProportion of complications observed within 30 days among patients with pharyngotonsillitis who lived in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden between1 January 2018 and 31 Jan 2024, stratified by \u003cem\u003eantibiotic treatment\u003c/em\u003e (yes/no) and by \u003cem\u003etype of antibiotic treatment (penicillin/other antibiotics)\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eComplications\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\" style=\"width: 24.4774%;\"\u003e\n \u003cp\u003eAntibiotics treatment\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 12.203%;\"\u003e\n \u003cp\u003eType of antibiotics \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;154,021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;141,951)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003ePenicillin\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;137,836)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003eOther antibiotic\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16,185)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e2,695 (1.75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e612 (0.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e2,230 (1.62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e465 (2.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eType of complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003ePeritonsillar abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e2,647 (1.72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e577 (0.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e2,193 (1.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e454 (2.81%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eRetropharyngeal \u0026amp;\u003c/p\u003e\n \u003cp\u003eparapharyngeal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e62 (0.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e38 (0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e42 (0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e20 (0.12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eRheumatic fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eNecrotizing fasciitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;5 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;5 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;5 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 16.1782%;\"\u003e\n \u003cp\u003eBacteremia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e17 (0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.4548%;\"\u003e\n \u003cp\u003e9 (0.006)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" style=\"width: 9.98%;\"\u003e\n \u003cp\u003e15 (0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.9255%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;5 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 57.464%;\"\u003eFootnote: \u003csup\u003ea\u003c/sup\u003e analysis only including those who received antibiotic treatment\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e \u003cp\u003eComplication among patients receiving antibiotics varied across periods, with the highest proportion observed during the pandemic at 2.58%, predominantly due to peritonsillar abscesses (\u003cb\u003eSuppl Table\u0026nbsp;6\u003c/b\u003e). Pre-pandemic and post-pandemic rates were lower, at 1.38% and 1.92%, respectively, with peritonsillar abscesses also being the predominant complication. Untreated patients consistently had a lower proportion of complications across all periods, with an increase observed from 0.38% pre-pandemic to 0.51% post-pandemic, primarily due to peritonsillar abscesses.\u003c/p\u003e\n\u003ch3\u003eAssociations between antibiotic treatments and complications within 30 days\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents the unadjusted and adjusted odds ratios of complication within 30 days across the study period. The adjusted odds ratio (aOR) of experiencing any complication within 30 days was lower in untreated patients compared to antibiotic-treated patients, with an aOR of 0.24 (95% CI 0.22\u0026ndash;0.27). This trend was consistent across all pandemic periods, with the lowest odds ratios observed during the pandemic (aOR 0.16, 95%CI 0.13\u0026ndash;0.19). For specific complications (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), the odds ratio of developing a peritonsillar abscess, the most common complication, was 0.23 (95% CI 0.21\u0026ndash;0.26) for untreated patients compared to antibiotic-treated patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCrude and adjusted odds ratio for the association between antibiotic treatment (No vs Yes) and type of antibiotic treatment (other antibiotics vs penicillin) with complications occurring within 30 days among pharyngotonsillitis patients in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden, overall and across different pandemic periods.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAntibiotic treatment\u003c/p\u003e \u003cp\u003e(No vs Yes)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eType of antibiotic\u003csup\u003e,a\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(Other vs Penicillin)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude OR(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e (95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCrude OR(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e (95%CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.24 (0.22\u0026ndash;0.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.24 (0.22\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.80(1.63\u0026ndash;1.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.84 (1.66\u0026ndash;2.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.27 (0.24\u0026ndash;0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.27 (0.24\u0026ndash;0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.03(1.75\u0026ndash;2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.05 (1.75\u0026ndash;2.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.16 (0.13\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16 (0.13\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.66(1.35\u0026ndash;2.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.71 (1.39\u0026ndash;2.09)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost pandemic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.26 (0.22\u0026ndash;0.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.26 (0.22\u0026ndash;0.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.62(1.34\u0026ndash;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.70 (1.40\u0026ndash;2.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eFootnote: aOR: adjusted odds ratio; CI: confidence interval\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e analysis only including those who received antibiotic treatment\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e - adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between antibiotic treatment (No vs Yes) and type of antibiotic (other antibiotics vs penicillin) with specific complications within 30 days among pharyngotonsillitis patients in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eType of complications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eAntibiotic treatment \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(No vs Yes)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eType of antibiotic\u003csup\u003e,a,\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e(Other vs Penicillin)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude OR, 95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e,\u003c/p\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCrude OR, 95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e,\u003c/p\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeritonsillar abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.23(0.21\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23 (0.21\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.79(1.61\u0026ndash;1.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.83(1.65\u0026ndash;2.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetropharyngeal \u0026amp; parapharyngeal abscess\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.66(0.44\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60 (0.40\u0026ndash;0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.06(2.38\u0026ndash;6.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.98(2.32\u0026ndash;6.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatic fever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNecrotizing fasciitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09(0.22\u0026ndash;5.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.85(0.17\u0026ndash;4.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.57(0.26\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60 (0.26\u0026ndash;1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.13(0.26\u0026ndash;4.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00(0.22\u0026ndash;4.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eFootnote: aOR: adjusted odds ratio; CI: confidence interval\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e analysis only including those who received antibiotic treatment\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong antibiotic-treated patients, those prescribed other antibiotics had higher odds of complications within 30 days compared to patients treated with penicillin-V (aOR 1.84, 95% CI 1.66\u0026ndash;2.04) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). For specific complication, such as retropharyngeal or parapharyngeal abscess, the aOR was even higher (3.98, 95% CI 2.32.-6.82).\u003c/p\u003e \u003cp\u003ePatients without antibiotic treatment had a significantly reduced risk of complications among pharyngotonsillitis patients that was consistent across all age groups, with the lowest odds ratio observed in the oldest age group 70+ (aOR 0.17, 95% CI 0.10\u0026ndash;0.29) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Similarly, the reduced risks were observed in both males and females. Among patients treated with antibiotics, those receiving with other antibiotic had a higher odds ratio of complications compared to those treated with penicillin-V, and this was also regardless of age or sex.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations between antibiotic treatment (No vs Yes) and type of antibiotic (other antibiotics vs /penicillin) with complications occurring within 30 days among patients with pharyngotonsillitis in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions in Sweden, stratified by sex and age\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eAntibiotic treatment\u003c/p\u003e \u003cp\u003e(no vs yes) \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eType of antibiotic\u003c/p\u003e \u003cp\u003e(other vs penicillin) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCrude OR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCrude OR\u003c/p\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eaOR\u003csup\u003eb\u003c/sup\u003e (95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAge group (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29(0.25\u0026ndash;0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29(0.25\u0026ndash;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.11(1.75\u0026ndash;2.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.10(1.71\u0026ndash;2.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u0026ndash;39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25(0.22\u0026ndash;0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25(0.21\u0026ndash;0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.81(1.54\u0026ndash;2.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.83(1.56\u0026ndash;2.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.19(0.16\u0026ndash;0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.19(0.15\u0026ndash;0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.56(1.29\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.65(1.37-2.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.17(0.10\u0026ndash;0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17(0.10\u0026ndash;0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.95(1.13\u0026ndash;3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00(1.14\u0026ndash;3.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.25(0.22\u0026ndash;0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25(0.22\u0026ndash;0.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.76(1.54\u0026ndash;2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.76(1.54\u0026ndash;2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMales\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23(0.20\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23(0.20\u0026ndash;0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.97(1.69\u0026ndash;2.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.96(1.68\u0026ndash;2.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eFootnote: aOR\u0026thinsp;=\u0026thinsp;adjusted odd ratio, CI\u0026thinsp;=\u0026thinsp;confidence interval\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e only for those received antibiotic treatment\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ec\u003c/sup\u003e adjusted for age, sex, sociodemographics, Charlson comorbidity index, vaccination status, primary care visits, and immunosuppressive treatments.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussions","content":"\u003cp\u003eThis study provides a comprehensive analysis of antibiotic prescribing trends and the occurrence of complications among pharyngotonsillitis patients living in Stockholm and V\u0026auml;stra G\u0026ouml;taland regions across different periods (pre-pandemic, pandemic, and post-pandemic). These two populous regions in Sweden represent approximately 40% of the national population. The main findings indicate: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) a temporary decrease in antibiotic prescriptions during the pandemic, followed by a partial rebound afterward, with penicillin-V consistently being the preferred antibiotics, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) complications were more frequent in patients receiving antibiotics (1.75%) compared to those not treated (0.43%), and patients treated with penicillin-V had fewer complications (1.62%) than those treated with other antibiotics (2.97%), and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) after adjusting for sociodemographics, comorbidities, primary care visits, and vaccination status, the odds ratio of experiencing complications within 30 days was lower (aOR 0.24, 95%CI 0.22\u0026ndash;0.26) for those who did not receive antibiotic treatment.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEffectiveness of Antibiotic Treatment\u003c/h2\u003e \u003cp\u003eThe COVID-19 pandemic significantly impacted antibiotic prescribing patterns for common infections (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), including pharyngotonsillitis, in primary care settings. This study observed a marked decline in antibiotic prescriptions during the COVID-19 pandemic, with a rebound afterward, consistent with prior research (\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Despite these fluctuations, penicillin-V remained the first-choice antibiotic for treating pharyngotonsillitis throughout study period, with only 10% of patients being prescribed other antibiotics. Penicillin-V continues to be the first-choice antibiotic for treating group A beta-hemolytic streptococcal (GABHS) pharyngotonsillitis due to its effectiveness, narrow spectrum, and low cost (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), as recommended by the Swedish guidelines (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In a randomized controlled inferiority study, Skoog et al (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) compared relapses and complication rates of two intervention groups treated with penicillin-V. The findings revealed no significant differences, suggesting the continued use of penicillin-V as a primary treatment for uncomplicated pharyngotonsillitis, with potential for shorter treatment durations. Furthermore, our study highlights that Sweden\u0026rsquo;s restrictive approach to antibiotic use has demonstrated that limiting prescriptions does not increase complications, such as peritonsillar abscesses or rheumatic fever. This reinforces the safety and efficacy of penicillin-V as the preferred treatment. Additionally, the study found that complications were more frequent in patients receiving antibiotics compared those untreated, in line with previous studies (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Notably, however, patients treated with penicillin-V experienced fewer complications (1.6%) than those on other antibiotics (2.9%), echoing findings from a large retrospective study conducted in Israel (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough antibiotics overall were associated with increased risk of complications within 30 days in pharyngotonsillitis patients (likely due to selection of high-risk patients for treatment), this study found that other antibiotics (broad-spectrum antibiotics) were associated with higher odds of complications compared to penicillin-V, across all age groups and sexes. The findings suggest that penicillin-V is effective and a safe option to use to prevent complications compared to broader spectrum antibiotics. Broad-spectrum antibiotics, typically used when penicillin fails, may disrupt a broader range of bacteria, potentially increasing the risk of adverse effects and complications. These findings underscore the benefits of selecting narrow-spectrum antibiotics like penicillin-V when appropriate to reduce risk.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStrengths and limitation of the study\u003c/h3\u003e\n\u003cp\u003eOne of the primary strengths of this study is its large sample size, which includes data spanning five years from two major Swedish regions, illustrating different periods for evaluating trend in antibiotic prescription for pharyngotonsillitis patients and complications. This extensive dataset enhances the generalizability of the findings to broader populations. Additionally, this study accounts for various confounding factors such as sociodemographics, comorbidities (Charlson Comorbidity Index and immunosuppressive conditions), COVID-19 vaccination status, and healthcare utilization, enabling a more precise assessment of the association between antibiotic use and the occurrence of complication in pharyngotonsillitis patients. Another strength is its temporal analysis, covering pre-pandemic, pandemic and post-pandemic periods, which shed light on healthcare practices, particularly in antibiotic treatment in pharyngotonsillitis patients. The consistent use of penicillin-V as the primary treatment across all periods underscores its effectiveness and low risk of complications in managing pharyngotonsillitis, even within a challenging healthcare environment.\u003c/p\u003e \u003cp\u003eDespite its strengths, the study has several limitations. First, as an observational study, there is a risk of confounding by indication. This occurs when the decision to prescribe antibiotics is influenced by factors such as the severity of illness or underlying health conditions, which are also related to the risk of complications. As a result, patients who receive antibiotics inherently are likely to have a higher baseline risk of developing complications compared to those who do not, irrespective of the treatment itself. Although we adjusted for sociodemographic characteristics, comorbidities, primary care visits, and vaccination status, residual confounding in this situation is likely, and should be considered when interpreting the causal relationship between antibiotic treatment (vs. no treatment) and complication risk. By design, this study cannot establish causality; it only demonstrates an association between antibiotic use and complications in actual use, with the indications in clinical practice, without confirming that antibiotics directly prevent complications or vice versa. Another limitation is the lack of detailed information on patient adherence to prescribed antibiotic regimens. Non-adherence, such as patients not completing their full course of antibiotics or improperly timing doses, could have influences the study outcomes (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). This factor is particularly relevant for those who received antibiotics yet still developed complications, as inadequate adherence may reduce the effectiveness of the medication, potentially leading to unresolved infections or the development of complications. Lastly, reliance on healthcare records may result in missing or misclassified data. For instance, complications could be underreported if patients sought care outside the documented healthcare system or if minor complications were not thoroughly recorded, potentially underestimating the true complication rates.\u003c/p\u003e \u003cp\u003eThis study highlights penicillin-V\u0026rsquo;s continued role as the preferred treatment option for pharyngotonsillitis, primarily due to its association with lower complication rates compared to other antibiotics. The results provide valuable evidence to guide clinicians, especially when faced with uncertainty between opting for penicillin-V or alternative treatments. Additionally, the notable decline in antibiotic prescriptions observed during the pandemic, followed by a rebound in the post-pandemic period, indicates a substantial shift in healthcare delivery and patient behavior. This pattern suggests that factors such as reduced healthcare access, heightened infection control measures, or a more cautious approach to prescribing during the pandemic likely influenced antibiotic use. The subsequent return to pre-pandemic prescribing levels highlights the importance of continued efforts in antibiotic management to prevent overuse and ensure optimal patient outcomes.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrates that the COVID-19 pandemic impacted antibiotic prescribing practices for pharyngotonsillitis in Swedish primary care, leading to a notable decline in overall antibiotic use during this period. Penicillin-V’s continued use as a first-line therapy appears well-justified due to its association with a lower risk of complications. Additionally, the consistently lower complication rates observed among patients who did not receive antibiotics highlight the importance of careful antibiotic prescribing. These findings emphasize the necessity of appropriate antibiotic use, as well as the continued monitoring of prescribing trends, particularly during the periods of healthcare disruption, such as the COVID-19 pandemic.\u003c/p\u003e"},{"header":"Method","content":"\u003ch2\u003eData sources\u003c/h2\u003e\u003cp\u003eThis cohort study is part of the RECOVAC study (Register-based large-scale national population study to monitor COVID-19 vaccination effectiveness and safety) within the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights – a Population Epidemiology Approach using Register Linkage) project, described in detail elsewhere (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), and expanded to cover the entire Swedish population. We linked individual data from multiple Swedish national and regional registers. Diagnoses from outpatient specialist visits and inpatient care came from the National Patient Register, while primary care diagnoses were obtained from regional primary healthcare registers for Stockholm Region and Västra Götaland Region (the two largest regions in Sweden, approximately 40% of the population). A comprehensive medical history from 2015 was accessed through the National Patient Register, and prescription drug histories from 2018 onward were obtained from the National Prescribed Drug Register. Sociodemographic data, including education, marital status, and country-of-birth, were acquired from Statistics Sweden (covering 2015–2019), and COVID-19 vaccination data were retrieved from the national vaccination register.\u003c/p\u003e\u003ch2\u003eStudy population and index infection episodes\u003c/h2\u003e\u003cp\u003eThe study included individuals aged 12 and older residing in Stockholm Region and Västra Götaland Region who had at least one primary care visit between 1 January 2018 and 30 December 2023. To identify unique episodes of pharyngotonsillitis for the same patient and exclude recurrent or chronic cases, a 180-day washout period was applied prior to each primary care visit. Thus, for an episode to be counted as a new episode, at least 180 days prior to that primary care visit had to be free of any records of pharyngotonsillitis in primary, specialist outpatient or inpatient care.\u003c/p\u003e\u003ch2\u003eStudy period, exposures and follow-up risk window\u003c/h2\u003e\u003cp\u003eThe study period spanned from 1 January 2018 to 31 January 2024, covering both the initial diagnosis of pharyngotonsillitis and the occurrence of any complications within one month of the pharyngotonsillitis diagnosis. Antibiotic treatment exposure was defined as a dispensed prescription for an antibiotic used for upper respiratory infection prescribed within 2 days of each index date of a pharyngotonsillitis episode. Complications were assessed for a follow-up of 30 days after the pharyngotonsillitis diagnosis. The study period from 1 January 2018 to 31 January 2020 was classified as pre-pandemic, 1 February 2020 to 28 February 2022 as pandemic, and 1 March 2022 to 30 January 2024 as post-pandemic period.\u003c/p\u003e\u003ch2\u003eOutcome\u003c/h2\u003e\u003cp\u003eInfectious complications were identified in primary care, outpatient specialist care and hospital inpatient care. They included peritonsillar abscess, retro-parapharyngeal abscess, necrotizing fasciitis, invasive Group A streptococcal disease, and rheumatic fever (for ICD-10 code definitions, see \u003cb\u003eSuppl Table\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e\u003ch2\u003eExposures\u003c/h2\u003e\u003cp\u003eAntibiotic treatment for pharyngotonsillitis was identified using ATC codes for dispensed prescriptions (see \u003cb\u003eSuppl Table\u0026nbsp;2\u003c/b\u003e) and coded as “yes” or “no”, with the reference group being those who \u003cem\u003ereceived\u003c/em\u003e antibiotic treatment. Further, antibiotic treatment was dichotomised into those receiving phenoximethylpenicillin (penicillin-V) and those receiving other antibiotics, with penicillin-V serving as the reference group.\u003c/p\u003e\u003ch2\u003eCovariates\u003c/h2\u003e\u003cp\u003eThe following covariates were used for adjustment and stratification: age (12–24, 25–39, 40–69, 70+), sex, country of birth (Nordic/other countries), marital status (married/not married), education (primary, secondary, tertiary less than three years, tertiary three years or longer), number of primary care visits from the index date to outcome occurrence (one, two, three, four or more), vaccination status (none, one dose, two doses, booster), the Charlson Comorbidity Index (CCI) based on diagnoses in the three years preceding the index date (categorized 0,1,2–3,4–5 and ≥6) (\u003cb\u003eSuppl Table\u0026nbsp;3\u003c/b\u003e) as well as immunosuppression status (autoimmune disease and immunosuppressive treatment) (\u003cb\u003eSuppl Table\u0026nbsp;4\u003c/b\u003e).\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDescriptive analyses were conducted to examine trends in antibiotic treatment and type of antibiotic use over the pandemic period. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for complications within 30 days, comparing those who did not received antibiotics to those who did (reference group) among pharyngotonsillitis patients. Apart from the crude unadjusted model, an adjusted model included adjustment for sex, age, sociodemographic factors, number of primary care visits, CCI, and immunosuppression status. Similar regressions were done only among antibiotic-treated patients, comparing those prescribed other antibiotics to patients treated with penicillin-V (reference group). Subgroup analyses were conducted by sex and age. Results are presented as crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CI). Statistical analyses were performed in SAS 9.4 and STATA 18.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u0026nbsp;\u003c/strong\u003eAuthor Contributions: AS-conception, design, analysis, writing, revisions; JC, ED, AL, MF, AT, RL, FN-conception, design, revisions. All authors reviewed and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding support:\u0026nbsp;\u003c/strong\u003eThe SCIFI-PEARL study has basic\u0026nbsp;funding\u0026nbsp;based on grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF agreement (grants ALFGBG-938453, ALFGBG-971130, and ALFGBG-978954) and previously from a joint grant from Forte (Swedish Research Council for Health, Working Life and Welfare) and Formas (Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning), grant 2020-02828.\u003c/p\u003e\n\u003cp\u003eAL, ED, MF, RL are employed at the Swedish Medical Products Agency, SE-751 03 Uppsala, Sweden. JC and AT are employed at the Public Health Agency of Sweden, SE-171 82 Solna, Sweden. The views expressed in this paper do not necessarily represent the views of the Agency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003eAll none\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eL\u0026auml;kemedelsverket [Swedish Medical Products Agency]. L\u0026auml;kemedelsbehandling vid faryngotonsillit \u0026ndash; behandlings-rekommendation [Drug treatment of pharyngotonsillitis - treatment recommendation]. Inf L\u0026auml;kemedelsverket; 2024 [Available from: https://www.lakemedelsverket.se/sv/behandling-och-forskrivning/behandlingsrekommendationer/sok-behandlingsrekommendationer/lakemedelsbehandling-vid-faryngotonsillit--behandlingsrekommendation#hmainbody1.\u003c/li\u003e\n\u003cli\u003eNational Institute for Health and Care Excellence. Sore throat (acute): antimicrobial prescribing 2018 [Available from: www.nice.org.uk/guidance/ng84.\u003c/li\u003e\n\u003cli\u003eL\u0026auml;kemedelsverket [Swedish Medical Products Agency]. Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance Annual Report (STRAMA). L\u0026auml;kemedelsverket; 2024.\u003c/li\u003e\n\u003cli\u003eScottish Intercollegiate Guidelines Network (SIGN). SIGN Guideline \u0026ndash; management of sore throat and indications for tonsillectomy. A national clinical guideline. 2010 [Available from: https://www.nice.org.uk/guidance/ng84.\u003c/li\u003e\n\u003cli\u003ePelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, et al. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012;18 Suppl 1:1-28.\u003c/li\u003e\n\u003cli\u003eFolkhalsomyndigheten [Public Health Agency of Sweden]. Behandlingsrekommendationer f\u0026ouml;r vanliga infektioner i \u0026ouml;ppenv\u0026aring;rd [Treatment recommendations for common outpatient infections]: Folkhalsomyndigheten [Public Health Agency of Sweden]; 2023 [Available from: https://www.folkhalsomyndigheten.se/contentassets/246aa17721b44c5380a0117f6d0aba40/behandlingsrekommendationer-oppenvard.pdf.\u003c/li\u003e\n\u003cli\u003e(EDCC) ECfDPaC. Seasonal Influenza 2020-2021 - annual report 2020 Stockholm: EDCC; 2021 [Available from: https://www.ecdc.europa.eu/sites/default/files/documents/AER-seasonal-influenza-2020-final.pdf.\u003c/li\u003e\n\u003cli\u003eFolkh\u0026auml;lsomyndigheten [Public Health Agency of Sweden]. RSV-s\u0026auml;songen 2021\u0026ndash;2022. Stockholm: Folkh\u0026auml;lsomyndigheten [Public Health Agency of Sweden],; 2022.\u003c/li\u003e\n\u003cli\u003eHullegie S, Schilder AGM, Marchisio P, de Sevaux JLH, van der Velden AW, van de Pol AC, et al. A Strong Decline in the Incidence of Childhood Otitis Media During the COVID-19 Pandemic in the Netherlands. Front Cell Infect Microbiol. 2021;11:768377.\u003c/li\u003e\n\u003cli\u003eKaur R, Schulz S, Fuji N, Pichichero M. COVID-19 Pandemic Impact on Respiratory Infectious Diseases in Primary Care Practice in Children. Front Pediatr. 2021;9:722483.\u003c/li\u003e\n\u003cli\u003eHeward E, Rocke J, Kumar N, Izzat S. Recurrent tonsillitis and parental perceptions of tonsillectomy during the COVID-19 pandemic. Int J Pediatr Otorhinolaryngol. 2020;139:110463.\u003c/li\u003e\n\u003cli\u003eAllen DZ, Challapalli S, Lee KH, Bell CS, Roy S, Bowe S, et al. Impact of COVID-19 on nationwide pediatric otolaryngology practice: Adenotonsillectomies (TA) and tonsil-related diagnoses trends. Am J Otolaryngol. 2022;43(5):103526.\u003c/li\u003e\n\u003cli\u003eControl ECfDPa. Antimicrobial consumption in the EU/EEA (ESAC-Net) - Annual Epidemiological Report for 2022 Stockholm: EDCC; 2022 [Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-consumption-europe-2022.\u003c/li\u003e\n\u003cli\u003eMoynihan R, Sanders S, Michaleff ZA, Scott AM, Clark J, To EJ, et al. Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review. BMJ Open. 2021;11(3):e045343.\u003c/li\u003e\n\u003cli\u003eEkman B, Arvidsson E, Thulesius H, Wilkens J, Cronberg O. Impact of the Covid-19 pandemic on primary care utilization: evidence from Sweden using national register data. BMC Res Notes. 2021;14(1):424.\u003c/li\u003e\n\u003cli\u003eKing LM, Lovegrove MC, Shehab N, Tsay S, Budnitz DS, Geller AI, et al. Trends in US Outpatient Antibiotic Prescriptions During the Coronavirus Disease 2019 Pandemic. Clin Infect Dis. 2021;73(3):e652-e60.\u003c/li\u003e\n\u003cli\u003eArmitage R, Nellums LB. Antibiotic prescribing in general practice during COVID-19. Lancet Infect Dis. 2021;21(6):e144.\u003c/li\u003e\n\u003cli\u003eNorman C, Svensson M, Schmidt I, Bergfeldt VS, Obeid R, Ternhag A, et al. Reduced dispensing of prescribed antibiotics during the Covid-19 pandemic has not increased severe complications from common infections. BMC Public Health. 2022;22(1):252.\u003c/li\u003e\n\u003cli\u003eDahl\u0026eacute;n E, Collin J, Hellman J, Norman C, Naucl\u0026eacute;r P, Ternhag A. The effect of absent or deferred antibiotic treatment on complications of common infections in primary care. Int J Infect Dis. 2022;124:181-6.\u003c/li\u003e\n\u003cli\u003ePetersen I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. Bmj. 2007;335(7627):982.\u003c/li\u003e\n\u003cli\u003ePallon J, Sundqvist M, R\u0026ouml;\u0026ouml;st M, Hedin K. Association between bacterial finding, antibiotic treatment and clinical course in patients with pharyngotonsillitis: a registry-based study in primary healthcare in Sweden. BMC Infectious Diseases. 2021;21(1):779.\u003c/li\u003e\n\u003cli\u003eGisselsson-Solen M, Hermansson A. Trends in upper respiratory tract infections and antibiotic prescriptions during the COVID-19 pandemic - a national observational study. Acta Otolaryngol. 2022;142(7-8):549-52.\u003c/li\u003e\n\u003cli\u003eCars T, Eriksson I, Granath A, Wettermark B, Hellman J, Norman C, et al. Antibiotic use and bacterial complications following upper respiratory tract infections: a population-based study. BMJ Open. 2017;7(11):e016221.\u003c/li\u003e\n\u003cli\u003eGulliford MC, Moore MV, Little P, Hay AD, Fox R, Prevost AT, et al. Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. Bmj. 2016;354:i3410.\u003c/li\u003e\n\u003cli\u003eGoldberg-Bockhorn E, Hagemann B, Furitsch M, Hoffmann TK. Invasive Group A Streptococcal Infections in Europe After the COVID-19 Pandemic. Dtsch Arztebl Int. 2024(Forthcoming).\u003c/li\u003e\n\u003cli\u003eSchweon SJ. Group A Streptococcal infections on the rise. Nursing. 2023;53(7):41-4.\u003c/li\u003e\n\u003cli\u003eVieira A, Wan Y, Ryan Y, Li HK, Guy RL, Papangeli M, et al. Rapid expansion and international spread of M1(UK) in the post-pandemic UK upsurge of Streptococcus pyogenes. Nat Commun. 2024;15(1):3916.\u003c/li\u003e\n\u003cli\u003eNyberg F, Franzen S, Lindh M, Vanfleteren L, Hammar N, Wettermark B, et al. Swedish Covid-19 Investigation for Future Insights - A Population Epidemiology Approach Using Register Linkage (SCIFI-PEARL). Clin Epidemiol. 2021;13:649-59.\u003c/li\u003e\n\u003cli\u003eLi C, Ong C, Morris A, Woollons I, Ashfaq A, Jagatia R. Evaluating the Appropriateness of Antibiotic Treatment of Tonsillitis during COVID-19 in the North Wale Primary Healthcare Setting. J Prim Care Community Health. 2021;12:21501327211003687.\u003c/li\u003e\n\u003cli\u003eZhu N, Aylin P, Rawson T, Gilchrist M, Majeed A, Holmes A. Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves. Clinical Microbiology and Infection. 2021;27(5):762-8.\u003c/li\u003e\n\u003cli\u003eShah M, Fleming A, Barbosa TM, van der Velden AW, Parveen S, Vellinga A. Point prevalence audit surveys of respiratory tract infection consultations and antibiotic prescribing in primary care before and during the COVID-19 pandemic in Ireland. Journal of Antimicrobial Chemotherapy. 2023;78(5):1270-7.\u003c/li\u003e\n\u003cli\u003evan Driel ML, De Sutter AIM, Keber N, Habraken H, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database of Systematic Reviews. 2010(10).\u003c/li\u003e\n\u003cli\u003eSkoog St\u0026aring;hlgren G, Tyrstrup M, Edlund C, Giske CG, M\u0026ouml;lstad S, Norman C, et al. Penicillin V four times daily for five days versus three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci: randomised controlled, open label, non-inferiority study. BMJ. 2019;367:l5337.\u003c/li\u003e\n\u003cli\u003eBar-Yishay M, Yehoshua I, Bilitzky A, Press Y. Treatment outcomes of acute streptococcal tonsillitis according to antibiotic treatment. A retrospective analysis of 242,366 cases treated in the community. European Journal of General Practice. 2022;28(1):142-9.\u003c/li\u003e\n\u003cli\u003eBaryakova TH, Pogostin BH, Langer R, McHugh KJ. Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nature Reviews Drug Discovery. 2023;22(5):387-409\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pharyngotonsillitis, Antibiotic Treatment, Complications, COVID-19 pandemic, Sweden","lastPublishedDoi":"10.21203/rs.3.rs-5903243/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5903243/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study explored trends in antibiotic use and the risk of complications for pharyngotonsillitis in Swedish primary care before, during and after the pandemic. Using register-based data from 295,972 cases (2018\u0026ndash;2023) of patients aged 12\u0026thinsp;+\u0026thinsp;in the Stockholm and V\u0026auml;stra G\u0026ouml;taland regions with a 180-day washout period, logistic regression models assessed 30-day complication risks for patients who received antibiotics versus those who did not. Antibiotic prescriptions decreased during the pandemic, followed by a partial rebound, with penicillin remaining the preferred antibiotic. Complications, particularly peritonsillar abscess, were more frequent in patients receiving antibiotics (1.75%) than in untreated individuals (0.43%). Patients prescribed penicillin had fewer complications (1.62%) compared to other antibiotics (2.87%). Adjusted analyses showed the risk for complications was lower for untreated patients (aOR 0.24, 95% CI 0.22\u0026ndash;0.26). The pandemic significantly impacted prescribing patterns, supporting penicillin\u0026rsquo;s continued use as a first-line therapy supported by its association with lower complication risks.\u003c/p\u003e","manuscriptTitle":"The Effect of Absent or Deferred Antibiotic Treatment on Pharyngotonsillitis Complications in Primary Care Before, During, and After the COVID-19 pandemic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 13:17:21","doi":"10.21203/rs.3.rs-5903243/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"communications-medicine","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"commsmed","sideBox":"Learn more about [Communications Medicine](http://www.nature.com/commsmed)","snPcode":"43856","submissionUrl":"https://mts-commsmed.nature.com/cgi-bin/main.plex","title":"Communications Medicine","twitterHandle":"@commsmedicine","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Communications Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f084b02-95f2-4342-ac36-e7298ffdc8d5","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":43634858,"name":"Health sciences/Health care"},{"id":43634859,"name":"Health sciences/Diseases/Respiratory tract diseases"}],"tags":[],"updatedAt":"2026-04-03T07:11:29+00:00","versionOfRecord":{"articleIdentity":"rs-5903243","link":"https://doi.org/10.1038/s43856-026-01564-z","journal":{"identity":"communications-medicine","isVorOnly":false,"title":"Communications Medicine"},"publishedOn":"2026-04-01 04:00:00","publishedOnDateReadable":"April 1st, 2026"},"versionCreatedAt":"2025-04-17 13:17:21","video":"","vorDoi":"10.1038/s43856-026-01564-z","vorDoiUrl":"https://doi.org/10.1038/s43856-026-01564-z","workflowStages":[]},"version":"v1","identity":"rs-5903243","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5903243","identity":"rs-5903243","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}