Impact of shortages of amoxicillin and amoxicillin/clavulanate on the outcome of bacterial sinusitis in adults: a French retrospective, single-centre study

Impact of shortages of amoxicillin and amoxicillin/clavulanate on the outcome of bacterial sinusitis in adults: a French retrospective, single-centre study | 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 Research Article Impact of shortages of amoxicillin and amoxicillin/clavulanate on the outcome of bacterial sinusitis in adults: a French retrospective, single-centre study Sandra Devatine, Clara Maubaret, Florian Chatelet, Anne Lise Munier, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6658540/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Nov, 2025 Read the published version in European Journal of Clinical Microbiology & Infectious Diseases → Version 1 posted 9 You are reading this latest preprint version Abstract Objectives. Recent shortages of amoxicillin and amoxicillin/clavulanate in France have raised concerns about a possible impact on the management and outcome of acute sinusitis. We therefore assessed the rates of complicated sinusitis occurring during two time periods, one with and one without antibiotic shortages. Methods. We reviewed cases of sinusitis from two periods: December-February 2018-19 and 2019-20 (no antibiotic shortages) and December-February 2021-22 and 2022-23 (shortages of amoxicillin and amoxicillin/clavulanate). We included all patients over 15 years of age who had been treated in the hospital’s ear, nose and throat department of Lariboisiere hospital for sinusitis. The primary outcome was the rate of complicated sinusitis among the total number of cases of sinusitis treated at Lariboisière hospital during the two study periods. Results. One hundred and forty-two patients were treated for sinusitis during the study periods: 60 during the no-shortage period and 82 during the shortage period. The rate of complicated sinusitis was significantly higher during the shortage period (23/82, 28%) than during the no-shortage period (3/60, 5%) (OR 7.32, CI [2.04-40.15], p=0.0003). The use of alternative antibiotics prior to attendance was independently associated with an increased risk of complications (OR 7.88, CI [1.58-77.87], p=0.004). The presence of oral streptococci was also associated with complications, suggesting a correlation between microbial patterns and antibiotic shortages. Conclusions. Shortages of first-line antibiotics for sinusitis was associated with an increased rate of complications, highlighting the need to explore alternative treatments and reinforce public health actions to anticipate shortages. Community-acquired infections Antibiotic policy ENT infections Sinusitis Antibiotic shortage Figures Figure 1 Figure 2 INTRODUCTION Acute sinusitis is one of the ten most common community-acquired diseases, particularly among adults: between 6,000 and 6,500 patients attend French emergency departments for sinusitis each winter ( 1 ). Among them only 0.5 to 2% are caused by bacteria( 2 ) and need an antibiotic therapy. A subset of cases range from 3.7–14.6% according to previous studies( 3 , 4 ) may progress to complicated disease with the spread of infection beyond the paranasal sinuses and nasal cavity into the surrounding tissues, orbit, or central nervous system ( 5 ). These complications can be related to several factors, including the infected sinus (frontal, sphenoidal and ethmoidal sinuses being more prone to complications), presence of diabetes or immune suppression, young age ( 7 ), and lack of adequate management during the initial disease phase ( 6 – 9 ). The result can be life-threatening, with mortality rates for patients with intracranial empyema (subdural, extradural) or intracerebral abscess reaching 30–40% ( 10 ), and 10% for patients with cerebral thrombophlebitis ( 11 ). In most national guidelines, the first-line antibiotic treatment for acute maxillary sinusitis is amoxicillin, and amoxicillin/clavulanate for other types of acute sinusitis ( 12 – 14 ). French guidelines recommended the use of cefpodoxime, or, in case of allergy to ß-lactam antibiotics, fluoroquinolones or pristinamycin as second-line agents ( 12 ). These recommendations stem from comparative therapeutic studies for acute maxillary and/or paediatric sinusitis ( 15 , 16 ). Medication shortages have become increasingly frequent since the end of 2020, following the COVID pandemic ( 17 ). In France, antibiotics, especially amoxicillin and amoxicillin/clavulanate ( 18 ), are the main drugs affected by such shortages ( 19 ). Lack of access to first-line antimicrobials for humans is a threat to global health and contributes to the emergence and spread of antimicrobial resistance ( 20 ). Given the recent shortages of amoxicillin and amoxicillin/clavulanate in France, alternative agents have been proposed for the treatment of acute sinusitis ( 21 ), but the impact of the shortages on sinusitis outcomes is not known. We therefore performed a retrospective study to investigate the effects of amoxicillin and amoxicillin/clavulanate shortages in sinusitis outcome. Our primary objective was to compare the relative proportions of cases of complicated sinusitis, as a marker of the adequacy of initial antibiotic therapy for sinusitis, occurring during two time periods (with and without antibiotic shortages). MATERIAL AND METHODS Study design, inclusion criteria, and case identification The study centre was Lariboisiere Hospital, a 976-bed teaching hospital in Paris, France. The ear, nose and throat (ENT) department at Lariboisiere Hospital is the only adult emergency ENT department in Paris that has permanent, 24/7, medical and surgical teams. We retrospectively identified all patients aged more than 15 years who attended Lariboisiere Hospital with sinusitis requiring surgery or a sinus swab during two periods, chosen to match the peak months of sinusitis incidence in France (December to February) (1): “No antibiotic shortage” period: December 1, 2018 - February 28, 2019 and December 1, 2019 - February 28, 2020. “Antibiotic shortage” period: December 1, 2021 - February 28, 2022 and December 1, 2022 - February 28, 2023. We did not include the period from March 1, 2020 to February 28, 2021 because of the first wave of the COVID pandemic. Patients were identified by two means. Firstly, we checked for all sinus samples sent to the hospital’s clinical bacteriology laboratory during the study period. Secondly, we analysed the database of the Medical Information Department of Lariboisière hospital to identify cases of complicated sinusitis based on ICD10 diagnosis codes (diagnosis codes are summarised in the appendix). Patients were not included if they had a fungal sinusitis. Definitions and data collection All data were extracted from the patients’ electronic medical records (EMRs). Epidemiological data, including age, sex, and comorbidities, were collected. Body temperature, blood leukocyte and C-reactive protein concentrations were recorded at presentation. The affected sinus, occurrence of any complication (cerebral thrombophlebitis, abscess, or empyema; orbital abscess or cellulitis), and data regarding prior antibiotic treatment were also noted. When the use of prior antibiotic(s) was not recorded in the medical file, we considered that no antibiotic had been taken before reaching our ENT emergency department. Antibiotics were categorised into two groups: i) amoxicillin and amoxicillin/clavulanate; ii) all other antibiotics. Microbiological data were extracted from sinus culture results in the EMR. Sinus swab and samples in our department were analysed in the bacteriology laboratory by direct examination (Gram staining) and culture. When possible, antibiotic susceptibility testing was performed. Staphylococcus aureus , Pseudomonas aeruginosa, and Haemophilus influenzae were analysed separately; oral streptococci ( Streptococcus mitis , Streptococcus anginosus, Streptococcus salivarius, Streptococcus oralis ) were grouped together, as were all Enterobacterales. Other bacteria were grouped in an "other bacteria" group, details of which can be found in Table S1. We recorded data regarding each patient’s management, including surgical management. Outcomes on Day 7 (a favorable outcome was defined as discharge from hospital or no additional consultation within the 7-day period), and after 3 months (based on data from follow-up consultations) were noted. To estimate long-term outcomes, we collected data on the need for surgery after 12 months. To exclude a possible bias of observing more cases of complicated sinusitis because of changes in department activity across the different periods, we recorded the number of emergency consultations and the number of ethmoidectomies (the most frequently performed surgical activity in the Lariboisière ENT department) during the study periods. Outcomes The primary outcome was the rate of complicated sinusitis among the total number of cases of sinusitis treated at Lariboisière hospital during the two study periods. Secondary outcomes included the species and resistance profile of bacteria identified in the two periods, the type of antibiotic therapy received prior to admission, and the rate of postoperative re-intervention at three months. Statistical analysis Statistical analyses were performed using R software (version 2023.03.0+386, R Foundation for Statistical Computing). Data are described as mean +/- standard deviation or median [interquartile range] for quantitative variables and frequencies (%) for qualitative variables. To test differences between groups, a Fisher's exact test was used for univariate analysis of categorical data. P values less than 0.05 were considered statistically significant. For multivariate analysis, we selected some of the significant variables from the univariate analysis and used a logistic multimodal regression model with stepwise method. We chose variables according to their relevance to the main objectives of the study: “sex”, “period”, “prior β-lactam antibiotic”, “prior other antibiotics”, “fever”, “high CRP”, “oral streptococci”, “ethmoid” and “sphenoid”. An imputation model using a MICE package was conducted after a sensitivity analysis on missing data. Ethics statement All procedures were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments. This study was approved by the Infectious and Tropical Diseases ethics committee (2024-0505) and was registered on the APHP internal data processing register (registration number: 20230821123620). In compliance with French law, a letter of information was sent to all included patients providing written information about the study protocol. As it was a non-interventional cohort, no written informed consent was required from included patients. All data for included patients were collected from their EMRs and anonymised. RESULTS Patient characteristics One hundred and forty-two patients were included: 60 in the no-shortage period and 82 during the shortage period ( Table 1 ). Mean patient age was 53 [15-90] years; there were 72 men and 70 women (sex ratio 1:1). Among the 139 patients (98%, N=139/142) for whom data regarding antibiotic prescription prior to admission were available, 60%(N=83/139), had received antibiotic therapy. Among the 69 patients for whom the class of prior antibiotic therapy was known 57% (N=39/69) had received amoxicillin or amoxicillin/clavulanate. The maxillary sinus was the most frequently affected sinus (68%, N=96/142 ). Sixty two percent (N=88/142) of the cases of sinusitis were polymicrobial, and 44% (N=62/142) of the samples were positive for oropharyngeal flora (Table S1). S. aureus was the most frequently identified pathogen (25% of cases). To explore possible bias in recruitment during the two study periods, we compared patient characteristics between the “shortage” and “no-shortage” periods. There were no statistically significant differences in patient comorbidities or epidemiological variables in the two groups ( Table S2 ). Oral streptococci were isolated more frequently during the antibiotic shortage period (OR 6.42, CI [1.4-60.28], p=0.008) ( Figure 1) . Their resistance profiles were similar between the two periods except for the MLS (macrolides, lincosamides, streptogramins) resistance profile. All resistant strains for Erythromycin and Clindamycin were identified during the shortage period (100%, N=4/4). There were no significant differences among other species or in the profiles of antimicrobial resistance. Factors associated with complicated sinusitis: There were 26 cases of complicated sinusitis (18%, N=26/142): 23 during the shortage period (28%, N=23/82) and 3 during the no-shortage period (5%, N=3/60). Orbital cellulitis was the most frequent complication (46%, N=12/26). Complicated sinusitis was more common in men (OR = 2.56 CI [0.97-7.39], p = 0.05) and in patients ≤ 25 years old (OR 3.77, CI [0.92-15.1], p = 0.03) (Table 1). Complicated sinusitis occurred more frequently during the period of antibiotic shortages than during the no-shortage period (OR 7.32, CI [2.04-40.15], p = 0.0003). Patients who had received treatment other than amoxicillin or amoxicillin/clavulanate prior to admission were more likely to develop complications (OR = 7.88; CI [1.58-77.87]; p=0.004), as were patients with oral streptococci (OR = 9.5; CI [2.82-34.1]; p<0.0001) ( Table 1) . There were no significant differences in the odds ratios for other bacterial species, including P. aeruginosa ( Table S1 ). In multivariate analysis ( Table 2 ), the antibiotic shortage period was independently associated with a risk of complicated sinusitis (aOR = 7.32; CI [2.04 -40.15]; p=0.003). The use of prior antibiotics other than amoxicillin or amoxicillin/clavulanate (aOR=7.88; CI [1.58-77.87]; p = 0.0007), the presence of oral streptococci (aOR = 9.5; CI [2.82-34.1]; p = 0.0002), and sphenoid sinus involvement (aOR= 2; CI [0.74-5.26]; p = 0.01) were risk factors for developing complicated sinusitis. To exclude a possible bias of observing more cases of complicated sinusitis because of changes in our department’s activity across the different periods, we recorded the total numbers of emergency ENT consultations in the two periods: there were no significant differences in the numbers of cases overall ( Figure 2 ). To exclude differences in surgical activity, we recorded the total numbers of ethmoidectomies in the two periods; there were no significant differences ( Table S3 ). Outcome and management A total of 104 patients (78%, N=104/142) had sinus drainage for complications of sinusitis or for bacteriological analysis during the initial admission (Table 3). Two percents (N=3/142) had a neurosurgical intervention. By day 7, 80% (N=106/133) of patients for whom the data were available had a favorable outcome. Surgical revision was required for 6 patients on day 7, all of whom had complicated sinusitis. There were no significant differences in the numbers of patients with a favorable outcome at 3 months between the groups (p = 1). DISCUSSION In this retrospective, monocentre study, the rate of complicated sinusitis was higher during the “antibiotic shortage” period than during the “no shortage” period with a 7-fold higher risk (OR 7.32, CI [2.04–40.15], p = 0.0003). The rate of complicated sinusitis increased with the use of antibiotics other than amoxicillin or amoxicillin/clavulanate, suggesting a direct correlation between the clinical outcome and antibiotic shortage. This result did not appear to be influenced by the activity of our ENT department; moreover, the study populations were epidemiologically comparable in the two periods. These findings support our hypothesis that choice of initial antibiotic therapy may influence outcomes in sinusitis. Increased medication shortages in recent years have been highlighted by global health authorities such as the WHO, the US Senate, and the French Senate ( 1 , 22 , 23 ). According to data from the ANSM (French national agency for medication safety), the winters of 21–22 and 22–23 were particularly marked by antibiotic shortages, with decreased consumption and pharmacy purchases of amoxicillin and amoxicillin/clavulanate ( 24 ). Some of the key reasons for antibiotic shortages are: i) a decline in local production and reliance on Asian suppliers, causing increased supply vulnerability; ii) an increased focus on high-profit, innovative drugs over older, essential ones like amoxicillin; iii) poor anticipation of increased demand due to COVID-19, influenza, and bronchiolitis epidemics; and iv) repercussions of the COVID pandemic on the global economy ( 18 , 22 , 25 ). We observed that reduced use of amoxicillin or amoxicillin/clavulanate for acute sinusitis was associated with the occurrence of complications, reinforcing their position as first-line antibiotics in sinusitis management guidelines. Of note, there was a significant increase in oral streptococci during the periods of antibiotic shortage. This bacteria is considered highly pyogenic ( 26 ). In France, the resistance profile of these bacteria is evolving: in 2021, the French National Reference Center for Streptococcus estimated that around 30% of oral streptococci strains were resistant to MLS antibiotic groups ( 27 ). In our study, resistance to MLS antibiotics was present in around 30% of our oral streptococci strains (for erythromycin and clindamycin; no strain was resistant to pristinamycin). This finding may in part explain the increase in these streptococci during the antibiotic shortage period, when MLS antibiotics were used instead of amoxicillin or amoxicillin/clavulanate before admission to the ENT emergency unit. Our study has several limitations. Firstly, as a monocentre study, results may not be applicable to other centres. However, the ENT department at Lariboisière Hospital is the only adult ENT emergency department in Paris, and therefore accounts for a large proportion of acute ENT activity so we considered it representative of the region. Secondly, we observed 26 cases of complicated sinusitis, representing 18% of the total cases of sinusitis over the study periods. This value is considerably higher than national data, reporting 0.10 to 0.16 cases of complicated sinusitis per 10,000 cases of acute sinusitis ( 6 , 28 ). Previous european studies focusing on bacterial sinusitis have found rate of complicated sinusitis under 15% of cases ( 3 , 4 ). This high proportion is likely related to recruitment bias due to the study design and to factors associated with our periods of interest. This period represents the pre- and post-COVID period. Indeed, after the periods of confinement changes in patients nasal function and innate immunity have appeared leading to some fragility ( 29 , 30 ). Thirdly, because of the retrospective nature of the study, there were numerous missing data. However, to compensate for these missing data, we performed data imputation (multiple imputation, MICE Package) after sensitivity analyses of the missing data. In addition, multivariate analysis was used to control for potential confounding effects of multiple variables simultaneously and to better understand the independent associations between predictors and the outcome of interest. This approach enables adjustment for various covariates, thus providing a more accurate estimation of the true effect sizes. Fourthly, we did not consider important criteria related to antibiotic usage, such as the delay between the onset of symptoms and access to primary care, or the delay in taking antibiotics due to supply difficulties during periods of shortage ( 31 , 32 ). Finally, for two reasons, we included patients for whom no antibiotic prescription had been recorded: i) to reduce the risk of selection bias; and ii) because we suspected that a significant proportion of these patients may have received antibiotics before reaching the ENT emergency, but did not mention it to the ENT physician. In conclusion, our results suggest that shortages of amoxicillin and amoxicillin/clavulanate are associated with a higher likelihood of complicated sinusitis. To mitigate this effect, therapeutic alternatives to these first-line treatments, adapted to local recent bacterial epidemiology, need to be identified and public health actions to anticipate antibiotic shortages reinforced. Declarations ACKNOWLEDGMENTS The authors would like to thank Dr. Karen Pickett for her editorial suggestions. CONFLICT OF INTEREST The authors declare that no funds, grants, or other support were received during the preparation of this manuscript FUNDING The authors have no relevant financial or non-financial interests to disclose . AUTHORSHIP CONTRIBUTION All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sandra Devatine, Sarah Atallah, David Lebeaux, Clara Maubaret and Noémie Leclerc Du Sablon. The first draft of the manuscript was written by Sandra Devatine and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. DATA AVAILABILITY The datasets generated during and analysed during the current study are not publicly available due to patient confidentiality agreement but are available from the corresponding author on reasonable request. ETHICS APPROVAL All procedures were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments. This study was approved by the Infectious and Tropical Diseases ethics committee (2024-0505) and was registered on the APHP internal data processing register (registration number: 20230821123620) CONSENT TO PARTICIPATE Informed consent was obtained from all individual participants included in the study References HUIART L, Santé Publique France. Surveillance syndromique SurSaUD® Bulletin du réseau OSCOUR® / Santé publique France Point hebdomadaire numéro 935 du 14/03/2023. 2023. Thomas M, Yawn BP, Price D, Lund V, Mullol J, Fokkens W, et al. EPOS Primary Care Guidelines: European Position Paper on the Primary Care Diagnosis and Management of Rhinosinusitis and Nasal Polyps 2007 - a summary. Prim Care Respir J J Gen Pract Airw Group. juin 2008;17(2):79‑89. 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Rhinology. 1 oct 2023;61(5):412‑20. Millien C, Chaput H, Cavillon M. La moitié des rendez-vous sont obtenus en 2 jours chez le généraliste, en 52 jours chez l’ophtalmologiste [Internet]. DRESS; 2018 oct. Disponible sur: https://drees.solidarites-sante.gouv.fr/publications/etudes-et-resultats/la-moitie-des-rendez-vous-sont-obtenus-en-2-jours-chez-le Le quotiden du médecin [Internet]. Consultations : face au casse-tête des délais d’attente qui s’allongent, les Français renoncent. Disponible sur: https://www.lequotidiendumedecin.fr/archives/consultations-face-au-casse-tete-des-delais-dattente-qui-sallongent-les-francais-renoncent Tables Table 1. Comparison of baseline characteristics in patients with non-complicated and complicated sinusitis. Variables N=142 (100%) Non complicated sinusitis (n=116) Complicated sinusitis (n=26) Univariate model Odds ratio (OR) CI 95% p value Age (years) 26 - 65 93 (65%) 76 17 ≤ 25 13 (9%) 7 6 3.77 [0.92-15.1] 0.03 > 65 36 (25%) 33 3 0.4 [0.07-1.56] 0.19 Men 72 (51%) 54 18 2.56 [0.97-7.39] 0.05 Antibiotic shortage period 82 (58%) 59 23 7.32 [2.04-40.15] 0.0003 Body mass index, kg/m 2 (n=101) 30 21 (21%) 19 2 0.38 [0.04-2.08] 0.31 Prior antibiotic prescription (n=139) 83 (60%) 64 19 2.46 [0.86-8.1] 0.08 Prior Amox-Amox/ac clav antibiotic prescription (n=69) 39 (57%) 35 4 0.15 [0.03-0.59] 0.002 Prior other antibiotic* (n=69) 40 (58%) 25 15 7.88 [1.58-77.87] 0.004 Prior prescription of both Amox-Amox/ac clav and other antibiotic (n=69) 10 (14%) 8 2 0.74 [0.07-4.3] 1 Fever** (n=53) 7 (13%) 3 4 5.26 [0.75-42.64] 0.05 High C-Reactive protein (CRP)*** (n=58) 48 (83%) 28 20 inf [1.38-inf] 0.01 High blood leukocyte**** (n=79) 26 (33%) 14 12 2.89 [0.95-8.97] 0.04 Affected sinus Maxillary 96 (68%) 82 14 0.49 [0.19-1.28] 0.11 Ethmoid 69 (49%) 51 18 2.85 [1.07-8.21] 0.03 Frontal 46 (32%) 34 12 2.06 [0.78-5.36] 0.11 Sphenoid 42 (30%) 31 11 2 [0.74-5.26] 0.15 Complication Orbital cellulitis or abscess 12 (8%) 0 12 inf [19.5-inf] <0.0001 Empyema 8 (6%) 0 8 inf [9.69-inf] <0.0001 Cerebral venous thrombosis 6 (4%) 0 6 inf [6.12-inf] <0.0001 Brain abscess 6 (4%) 0 6 inf [6.12-inf] <0.0001 Microbiological data S. aureus 36 (25%) 32 4 0.48 [0.11-1.57] 0.22 H. influenzae 20 (14%) 17 3 0.76 [0.13-2.97] 1 P. aeruginosa 15 (11%) 15 0 inf [inf-1.78] 0.07 Oral streptococci 17 (12%) 7 10 9.5 [2.82-34.1] <0.0001 NOTE . Data are presented as No. (%) unless otherwise indicated. n=number of data analysed (when <142); univariate analysis, Fisher's exact test, probability values lower than 0.05 were considered statistically significant and depicted in bold). *Other antibiotic included: oral cephalosporins, pristinamycin, clindamycin, fluoroquinolone, macrolides ** Fever was defined as T° > 38°C; ***High CRP was defined as > 5 mg/L; **** High blood leukocyte was defined as > 10 G/L Table 2. Factors associated with complicated sinusitis in multivariate model Variables N=142 (100%) Non complicated sinusitis (N= 116) Complicated sinusitis (N=26) P value Men 72 (51%) 54 18 0.36 Shortage period 82 (82%) 59 23 0.003 Prior Amox-Amox/ac clav antibiotic 39 (57%) 35 4 0.14 Prior other antibiotic 40 (58%) 25 15 0.0007 Fever 7 (13%) 3 4 0.03 High C-reactive protein (CRP)** (n=58) 48 (83%) 28 20 0.0007 Affected sinus Ethmoid 69 (49%) 51 18 0.36 Sphenoid 42 (30%) 31 11 0.01 Oral streptococci 17 (12%) 7 10 0.0002 Logistic multimodal regression model and stepwise method, probability values 38°C ; **High CRP was defined as > 5 mg/L Table 3 . Comparison of outcomes and surgical management of patients with non-complicated and with complicated sinusitis Variable Non-complicated sinusitis (N=116) Complicated sinusitis (N=26 Odds Ratio CI 95% P value Neurosurgery (n=141) 3 (2%) 0 3 inf [1.91-inf] 0.006* Orbital drainage (n=141) 9 (6%) 0 9 inf [11.65-inf] <0.0001* Sinus drainage (n=141) 104 (74%) 78 26 inf [inf-2.88] 0.0002* External sinus approach (n=141) 11 (8%) 2 9 19.3 [3.56-199.1] <0.0001* Endonasal approach (n=141) 104 (74%) 78 26 Inf [inf-2.88] 0.0002* Favorable outcome D7 (n=133) 106 (80%) 90 16 0.3 [0.11-0.89] 0.02* Surgical revision D7 (n=138) 6 (4%) 0 6 inf [5.91-inf] <0.0001* Favorable outcome M3 (n=126) 93 (74%) 76 17 1 [0.33-3.45] 1 Surgical revision M12 (=128) 6 (5%) 4 2 2.38 [0.2-17.9] 0.29 Number of surgery 0 36 (25%) 36 0 1 93 (65%) 76 17 inf [1.8-inf] 0.003* ≥ 2 13 (9%) 4 9 inf [11.24-inf] <0.0001* NOTE . Data are presented as No. (%) unless otherwise indicated. n=number of data analysed (when <142); univariate analysis, Fisher's exact test, probability values < 0.05 were considered statistically significant and are marked with an * Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6658540","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":495671833,"identity":"d3c37799-aecd-4a99-a835-b560e9bfe0e1","order_by":0,"name":"Sandra Devatine","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIiWNgGAWjYJACCSBmbACxEhgY5ED0gQdEamFsAGoxBmtJIFoLkJEIsw4nkG8/e/B2RQ2DbL9E8vMHD3fYpM8PO/wQaIudnG4Ddi0GZ/KSLc8cYzCeOSPNsCHxTFruxttpBkAtycZmB3BoYcgxk2xgY0jccOYAUEvb4dyNsxNAWg4kbsOhRb7/DVDLP4bE/WeOfwRq+Z9uODv9A14tDDeAtjS2AW1h7wHZciBBXjoHvy0GN94YWzb2SRjPON5TOCOxLdlwg3ROwYEEA9x+ke/PMbzZ8M1Gtr+ZfcPHn2128vKz0zd/+FBhJ4dLCxRIINl7ABIsJAD5BlJUj4JRMApGwUgAACtYZtjzUtXWAAAAAElFTkSuQmCC","orcid":"","institution":"AP-HP, Hôpital Saint-Louis","correspondingAuthor":true,"prefix":"","firstName":"Sandra","middleName":"","lastName":"Devatine","suffix":""},{"id":495671835,"identity":"8d59677a-d4ef-4c96-9830-5a8797ad9747","order_by":1,"name":"Clara Maubaret","email":"","orcid":"","institution":"AP-HP, Groupe hospitalier Saint Louis-Lariboisière-Fernand-Widal, Université Paris Cité","correspondingAuthor":false,"prefix":"","firstName":"Clara","middleName":"","lastName":"Maubaret","suffix":""},{"id":495671837,"identity":"5dcfe4a5-e065-4799-a816-6481fa1c30ad","order_by":2,"name":"Florian Chatelet","email":"","orcid":"","institution":"Paris city University, Lariboisière Hospital","correspondingAuthor":false,"prefix":"","firstName":"Florian","middleName":"","lastName":"Chatelet","suffix":""},{"id":495671839,"identity":"cf4739be-890f-41ae-be01-dfebc19dbfe8","order_by":3,"name":"Anne Lise Munier","email":"","orcid":"","institution":"AP-HP, Hôpital Saint-Louis","correspondingAuthor":false,"prefix":"","firstName":"Anne","middleName":"Lise","lastName":"Munier","suffix":""},{"id":495671840,"identity":"db9c7696-26e5-4d4f-a45c-26f64ee57087","order_by":4,"name":"Benjamin Verillaud","email":"","orcid":"","institution":"Paris city University, Lariboisière Hospital","correspondingAuthor":false,"prefix":"","firstName":"Benjamin","middleName":"","lastName":"Verillaud","suffix":""},{"id":495671842,"identity":"78915df6-fa5d-4dd9-9e66-9e665cac8029","order_by":5,"name":"Noémie Leclerc Du Sablon","email":"","orcid":"","institution":"AP-HP, Groupe hospitalier Saint Louis-Lariboisière-Fernand-Widal, Université Paris Cité","correspondingAuthor":false,"prefix":"","firstName":"Noémie","middleName":"Leclerc","lastName":"Du Sablon","suffix":""},{"id":495671843,"identity":"4f587fb2-4196-4ab0-a325-8da09d03bef5","order_by":6,"name":"David Lebeaux","email":"","orcid":"","institution":"AP-HP, Hôpital Saint-Louis","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Lebeaux","suffix":""},{"id":495671844,"identity":"00020ea6-decc-4dbc-a25d-c3b0fedbd45a","order_by":7,"name":"Sarah Atallah","email":"","orcid":"","institution":"Paris city University, Lariboisière Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Atallah","suffix":""}],"badges":[],"createdAt":"2025-05-13 20:23:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6658540/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6658540/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10096-025-05305-3","type":"published","date":"2025-11-15T15:58:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88643604,"identity":"96199358-19a8-4e60-85e2-72befa5122ac","added_by":"auto","created_at":"2025-08-08 16:16:52","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":248614,"visible":true,"origin":"","legend":"\u003cp\u003eBacterial species in the two study periods. The proportions of each bacterial species in the shortage and no shortage periods were compared using Fisher's exact test . (There were no significant differences between the groups except for oral streptococci).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6658540/v1/27131f927911f9416a4f84c1.jpeg"},{"id":88643605,"identity":"6bbb3dd6-1463-462a-8809-e37bf468f73e","added_by":"auto","created_at":"2025-08-08 16:16:52","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":202157,"visible":true,"origin":"","legend":"\u003cp\u003eENT consultations and the proportion of cases of complicated sinusitis in the two study periods. ENT consultations are shown as an absolute number; cases of complicated sinusitis are shown as a proportion of all cases of sinusitis included during this period.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6658540/v1/a7b220d88f887f441561ae14.jpeg"},{"id":96105078,"identity":"b1ebeb77-a784-460f-afeb-f3340fc4b93f","added_by":"auto","created_at":"2025-11-17 16:08:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1772143,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6658540/v1/4dc46f20-01ff-4c4d-aded-6554e2a00e71.pdf"},{"id":88643603,"identity":"766b525f-e560-47c0-b7ef-3ca1fa317fb8","added_by":"auto","created_at":"2025-08-08 16:16:52","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":52216,"visible":true,"origin":"","legend":"","description":"","filename":"finalSupplementaryDataShortageatbAndSinusitisEJCMID.docx","url":"https://assets-eu.researchsquare.com/files/rs-6658540/v1/a2c9e5e8332db865ddacd39e.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of shortages of amoxicillin and amoxicillin/clavulanate on the outcome of bacterial sinusitis in adults: a French retrospective, single-centre study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute sinusitis is one of the ten most common community-acquired diseases, particularly among adults: between 6,000 and 6,500 patients attend French emergency departments for sinusitis each winter (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Among them only 0.5 to 2% are caused by bacteria(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and need an antibiotic therapy. A subset of cases range from 3.7\u0026ndash;14.6% according to previous studies(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) may progress to complicated disease with the spread of infection beyond the paranasal sinuses and nasal cavity into the surrounding tissues, orbit, or central nervous system (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). These complications can be related to several factors, including the infected sinus (frontal, sphenoidal and ethmoidal sinuses being more prone to complications), presence of diabetes or immune suppression, young age (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), and lack of adequate management during the initial disease phase (\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The result can be life-threatening, with mortality rates for patients with intracranial empyema (subdural, extradural) or intracerebral abscess reaching 30\u0026ndash;40% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), and 10% for patients with cerebral thrombophlebitis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn most national guidelines, the first-line antibiotic treatment for acute maxillary sinusitis is amoxicillin, and amoxicillin/clavulanate for other types of acute sinusitis (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). French guidelines recommended the use of cefpodoxime, or, in case of allergy to \u0026szlig;-lactam antibiotics, fluoroquinolones or pristinamycin as second-line agents (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). These recommendations stem from comparative therapeutic studies for acute maxillary and/or paediatric sinusitis (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMedication shortages have become increasingly frequent since the end of 2020, following the COVID pandemic (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In France, antibiotics, especially amoxicillin and amoxicillin/clavulanate (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), are the main drugs affected by such shortages (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Lack of access to first-line antimicrobials for humans is a threat to global health and contributes to the emergence and spread of antimicrobial resistance (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Given the recent shortages of amoxicillin and amoxicillin/clavulanate in France, alternative agents have been proposed for the treatment of acute sinusitis (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), but the impact of the shortages on sinusitis outcomes is not known. We therefore performed a retrospective study to investigate the effects of amoxicillin and amoxicillin/clavulanate shortages in sinusitis outcome. Our primary objective was to compare the relative proportions of cases of complicated sinusitis, as a marker of the adequacy of initial antibiotic therapy for sinusitis, occurring during two time periods (with and without antibiotic shortages).\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy design, inclusion criteria, and case identification\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study centre was Lariboisiere Hospital, a 976-bed teaching hospital in Paris, France. The ear, nose and throat (ENT) department at Lariboisiere Hospital is the only adult emergency ENT department in Paris that has permanent, 24/7, medical and surgical teams.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe retrospectively identified all patients aged more than 15 years who attended Lariboisiere Hospital with sinusitis requiring surgery or a sinus swab during two periods, chosen to match the peak months of sinusitis incidence in France (December to February) (1):\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u0026nbsp;\u0026ldquo;No antibiotic shortage\u0026rdquo; period: December 1, 2018 - February 28, 2019 and December 1, 2019 - February 28, 2020.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp; \u0026ldquo;Antibiotic shortage\u0026rdquo; period: December 1, 2021 - February 28, 2022 and December 1, 2022 - February 28, 2023.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe did not include the period from March 1, 2020 to February 28, 2021 because of the first wave of the COVID pandemic.\u003c/p\u003e\n\u003cp\u003ePatients were identified by two means. Firstly, we checked for all sinus samples sent to the hospital\u0026rsquo;s clinical bacteriology laboratory during the study period. Secondly, we analysed the database of the Medical Information Department of Lariboisi\u0026egrave;re hospital to identify cases of complicated sinusitis based on ICD10 diagnosis codes (diagnosis codes are summarised in the appendix). Patients were not included if they had a fungal sinusitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions and data collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data were extracted from the patients\u0026rsquo; electronic medical records (EMRs). Epidemiological data, including age, sex, and comorbidities, were collected. Body temperature, blood leukocyte and C-reactive protein concentrations were recorded at presentation. The affected sinus, occurrence of any complication (cerebral thrombophlebitis, abscess, or empyema; orbital abscess or cellulitis), and data regarding prior antibiotic treatment were also noted. When the use of prior antibiotic(s) was not recorded in the medical file, we considered that no antibiotic had been taken before reaching our ENT emergency department. Antibiotics were categorised into two groups: \u003cem\u003e\u003cu\u003ei)\u003c/u\u003e\u003c/em\u003e amoxicillin and amoxicillin/clavulanate; \u003cem\u003eii)\u003c/em\u003e all other antibiotics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMicrobiological data were extracted from sinus culture results in the EMR. Sinus swab and samples in our department were analysed in the bacteriology laboratory by direct examination (Gram staining) and culture. When possible, antibiotic susceptibility testing was performed. \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa,\u003c/em\u003e and \u003cem\u003eHaemophilus influenzae\u003c/em\u003e were analysed separately; oral streptococci (\u003cem\u003eStreptococcus mitis\u003c/em\u003e, \u003cem\u003eStreptococcus anginosus, Streptococcus salivarius, Streptococcus oralis\u003c/em\u003e) were grouped together, as were all \u003cem\u003eEnterobacterales.\u0026nbsp;\u003c/em\u003eOther bacteria were grouped in an \u0026quot;other bacteria\u0026quot; group, details of which can be found in Table S1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe recorded data regarding each patient\u0026rsquo;s management, including surgical management. Outcomes on Day 7 (a favorable outcome was defined as discharge from hospital or no additional consultation within the 7-day period), and after 3 months (based on data from follow-up consultations) were noted. To estimate long-term outcomes, we collected data on the need for surgery after 12 months.\u003c/p\u003e\n\u003cp\u003eTo exclude a possible bias of observing more cases of complicated sinusitis because of changes in department activity across the different periods, we recorded the number of emergency consultations and the number of ethmoidectomies (the most frequently performed surgical activity in the Lariboisi\u0026egrave;re ENT department) during the study periods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the rate of complicated sinusitis among the total number of cases of sinusitis treated at Lariboisi\u0026egrave;re hospital during the two study periods. Secondary outcomes included the species and resistance profile of bacteria identified in the two periods, the type of antibiotic therapy received prior to admission, and the rate of postoperative re-intervention at three months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using R software (version 2023.03.0+386, R Foundation for Statistical Computing). Data are described as mean +/- standard deviation or median [interquartile range] for quantitative variables and frequencies (%) for qualitative variables. To test differences between groups, a Fisher\u0026apos;s exact test was used for univariate analysis of categorical data. P values less than 0.05 were considered statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor multivariate analysis, we selected some of the significant variables from the univariate analysis and used a logistic multimodal regression model with stepwise method. We chose variables according to their relevance to the main objectives of the study: \u0026ldquo;sex\u0026rdquo;, \u0026ldquo;period\u0026rdquo;, \u0026ldquo;prior \u0026beta;-lactam antibiotic\u0026rdquo;, \u0026ldquo;prior other antibiotics\u0026rdquo;, \u0026ldquo;fever\u0026rdquo;, \u0026ldquo;high CRP\u0026rdquo;, \u0026ldquo;oral streptococci\u0026rdquo;, \u0026ldquo;ethmoid\u0026rdquo; and \u0026ldquo;sphenoid\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;An imputation model using a MICE package was conducted after a sensitivity analysis on missing data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments. This study was approved by the Infectious and Tropical Diseases ethics committee (2024-0505) and was registered on the APHP internal data processing register (registration number: 20230821123620). In compliance with French law, a letter of information was sent to all included patients providing written information about the study protocol. As it was a non-interventional cohort, no written informed consent was required from included patients. All data for included patients were collected from their EMRs and anonymised.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOne hundred and forty-two patients were included: 60 in the no-shortage period and 82 during the shortage period (\u003cstrong\u003eTable 1\u003c/strong\u003e). Mean patient age was 53 [15-90] years; there were 72 men and 70 women (sex ratio 1:1). Among the 139 patients (98%, N=139/142) for whom data regarding antibiotic prescription prior to admission were available, 60%(N=83/139), had received antibiotic therapy. Among the 69 patients for whom the class of prior antibiotic therapy was known 57% (N=39/69) had received amoxicillin or amoxicillin/clavulanate.\u003c/p\u003e\n\u003cp\u003eThe maxillary sinus was the most frequently affected sinus (68%, N=96/142 ). Sixty two percent (N=88/142) of the cases of sinusitis were polymicrobial, and 44% (N=62/142) of the samples were positive for oropharyngeal flora (Table S1). \u003cem\u003eS. aureus\u003c/em\u003e was the most frequently identified pathogen (25% of cases). To explore possible bias in recruitment during the two study periods, we compared patient characteristics between the \u0026ldquo;shortage\u0026rdquo; and \u0026ldquo;no-shortage\u0026rdquo; periods. There were no statistically significant differences in patient comorbidities or epidemiological variables in the two groups (\u003cstrong\u003eTable S2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eOral streptococci were isolated more frequently during the antibiotic shortage period (OR 6.42, CI\u0026nbsp;[1.4-60.28], p=0.008) (\u003cstrong\u003eFigure 1)\u003c/strong\u003e. Their\u0026nbsp;resistance profiles were similar between the two periods except for the MLS (macrolides, lincosamides, streptogramins) resistance profile. All resistant strains for Erythromycin and Clindamycin were identified during the shortage period (100%, N=4/4). There were no significant differences among other species or in the profiles of antimicrobial resistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFactors associated with complicated sinusitis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were 26 cases of complicated sinusitis (18%, N=26/142): 23 during the shortage period (28%, N=23/82) and 3 during the no-shortage period (5%, N=3/60). Orbital cellulitis was the most frequent complication (46%, N=12/26). Complicated sinusitis was more common in men (OR = 2.56 CI\u0026nbsp;[0.97-7.39], p = 0.05) and in patients \u0026le; 25 years old (OR 3.77, CI\u0026nbsp;[0.92-15.1],\u0026nbsp;p = 0.03) (Table 1). Complicated sinusitis occurred more frequently during the period of antibiotic shortages than during the no-shortage period (OR 7.32, CI [2.04-40.15], p = 0.0003). Patients who had received treatment other than amoxicillin or amoxicillin/clavulanate prior to admission were more likely to develop complications (OR = 7.88; CI [1.58-77.87]; p=0.004),\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eas were patients with oral streptococci (OR = 9.5; CI\u0026nbsp;[2.82-34.1];\u0026nbsp;p\u0026lt;0.0001) (\u003cstrong\u003eTable 1)\u003c/strong\u003e. There were no significant differences in the odds ratios for other bacterial species, including \u003cem\u003eP. aeruginosa\u0026nbsp;\u003c/em\u003e(\u003cstrong\u003eTable S1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eIn multivariate analysis (\u003cstrong\u003eTable 2\u003c/strong\u003e), the antibiotic shortage period was independently associated with a risk of complicated sinusitis (aOR = 7.32; CI [2.04 -40.15]; p=0.003). The use of prior antibiotics other than amoxicillin or amoxicillin/clavulanate (aOR=7.88; CI [1.58-77.87]; p = 0.0007), the presence of oral streptococci (aOR = 9.5; CI [2.82-34.1]; p = 0.0002), and sphenoid sinus involvement (aOR= 2; CI [0.74-5.26]; p = 0.01) were risk factors for developing complicated sinusitis.\u003c/p\u003e\n\u003cp\u003eTo exclude a possible bias of observing more cases of complicated sinusitis because of changes in our department\u0026rsquo;s activity across the different periods, we recorded the total numbers of emergency ENT consultations in the two periods: there were no significant differences in the numbers of cases overall (\u003cstrong\u003eFigure 2\u003c/strong\u003e). To exclude differences in surgical activity, we recorded the total numbers of ethmoidectomies in the two periods; there were no significant differences (\u003cstrong\u003eTable S3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome and management\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 104 patients (78%, N=104/142) had sinus drainage for complications of sinusitis or for bacteriological analysis during the initial admission (Table 3). Two percents (N=3/142) had a neurosurgical intervention. By day 7, 80% (N=106/133) of patients for whom the data were available had a favorable outcome. Surgical revision was required for 6 patients on day 7, all of whom had complicated sinusitis. There were no significant differences in the numbers of patients with a favorable outcome at 3 months between the groups (p = 1).\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this retrospective, monocentre study, the rate of complicated sinusitis was higher during the \u0026ldquo;antibiotic shortage\u0026rdquo; period than during the \u0026ldquo;no shortage\u0026rdquo; period with a 7-fold higher risk (OR 7.32, CI [2.04\u0026ndash;40.15], p\u0026thinsp;=\u0026thinsp;0.0003). The rate of complicated sinusitis increased with the use of antibiotics other than amoxicillin or amoxicillin/clavulanate, suggesting a direct correlation between the clinical outcome and antibiotic shortage. This result did not appear to be influenced by the activity of our ENT department; moreover, the study populations were epidemiologically comparable in the two periods. These findings support our hypothesis that choice of initial antibiotic therapy may influence outcomes in sinusitis.\u003c/p\u003e\u003cp\u003eIncreased medication shortages in recent years have been highlighted by global health authorities such as the WHO, the US Senate, and the French Senate (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). According to data from the ANSM (French national agency for medication safety), the winters of 21\u0026ndash;22 and 22\u0026ndash;23 were particularly marked by antibiotic shortages, with decreased consumption and pharmacy purchases of amoxicillin and amoxicillin/clavulanate (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Some of the key reasons for antibiotic shortages are: \u003cem\u003ei)\u003c/em\u003e a decline in local production and reliance on Asian suppliers, causing increased supply vulnerability; \u003cem\u003eii)\u003c/em\u003e an increased focus on high-profit, innovative drugs over older, essential ones like amoxicillin; \u003cem\u003eiii)\u003c/em\u003e poor anticipation of increased demand due to COVID-19, influenza, and bronchiolitis epidemics; and iv) repercussions of the COVID pandemic on the global economy (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e We observed that reduced use of amoxicillin or amoxicillin/clavulanate for acute sinusitis was associated with the occurrence of complications, reinforcing their position as first-line antibiotics in sinusitis management guidelines. Of note, there was a significant increase in oral streptococci during the periods of antibiotic shortage. This bacteria is considered highly pyogenic (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In France, the resistance profile of these bacteria is evolving: in 2021, the French National Reference Center for \u003cem\u003eStreptococcus\u003c/em\u003e estimated that around 30% of oral streptococci strains were resistant to MLS antibiotic groups (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In our study, resistance to MLS antibiotics was present in around 30% of our oral streptococci strains (for erythromycin and clindamycin; no strain was resistant to pristinamycin). This finding may in part explain the increase in these streptococci during the antibiotic shortage period, when MLS antibiotics were used instead of amoxicillin or amoxicillin/clavulanate before admission to the ENT emergency unit.\u003c/p\u003e\u003cp\u003eOur study has several limitations. Firstly, as a monocentre study, results may not be applicable to other centres. However, the ENT department at Lariboisi\u0026egrave;re Hospital is the only adult ENT emergency department in Paris, and therefore accounts for a large proportion of acute ENT activity so we considered it representative of the region. Secondly, we observed 26 cases of complicated sinusitis, representing 18% of the total cases of sinusitis over the study periods. This value is considerably higher than national data, reporting 0.10 to 0.16 cases of complicated sinusitis per 10,000 cases of acute sinusitis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Previous european studies focusing on bacterial sinusitis have found rate of complicated sinusitis under 15% of cases (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This high proportion is likely related to recruitment bias due to the study design and to factors associated with our periods of interest. This period represents the pre- and post-COVID period. Indeed, after the periods of confinement changes in patients nasal function and innate immunity have appeared leading to some fragility (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Thirdly, because of the retrospective nature of the study, there were numerous missing data. However, to compensate for these missing data, we performed data imputation (multiple imputation, MICE Package) after sensitivity analyses of the missing data. In addition, multivariate analysis was used to control for potential confounding effects of multiple variables simultaneously and to better understand the independent associations between predictors and the outcome of interest. This approach enables adjustment for various covariates, thus providing a more accurate estimation of the true effect sizes. Fourthly, we did not consider important criteria related to antibiotic usage, such as the delay between the onset of symptoms and access to primary care, or the delay in taking antibiotics due to supply difficulties during periods of shortage (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Finally, for two reasons, we included patients for whom no antibiotic prescription had been recorded: \u003cem\u003ei)\u003c/em\u003e to reduce the risk of selection bias; and \u003cem\u003eii)\u003c/em\u003e because we suspected that a significant proportion of these patients may have received antibiotics before reaching the ENT emergency, but did not mention it to the ENT physician.\u003c/p\u003e\u003cp\u003eIn conclusion, our results suggest that shortages of amoxicillin and amoxicillin/clavulanate are associated with a higher likelihood of complicated sinusitis. To mitigate this effect, therapeutic alternatives to these first-line treatments, adapted to local recent bacterial epidemiology, need to be identified and public health actions to anticipate antibiotic shortages reinforced.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Dr. Karen Pickett for her editorial suggestions.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORSHIP CONTRIBUTION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sandra Devatine, Sarah Atallah, David Lebeaux, Clara Maubaret and No\u0026eacute;mie Leclerc Du Sablon. The first draft of the manuscript was written by Sandra Devatine and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch4\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u0026nbsp;\u003c/h4\u003e\n\u003cp\u003eThe datasets generated during and analysed during the current study are not publicly available due to patient confidentiality agreement but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS APPROVAL\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments. This study was approved by the Infectious and Tropical Diseases ethics committee (2024-0505) and was registered on the APHP internal data processing register (registration number: 20230821123620)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT TO PARTICIPATE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eInformed consent was obtained from all individual participants included in the study\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHUIART L, Sant\u0026eacute; Publique France. Surveillance syndromique SurSaUD\u0026reg; Bulletin du r\u0026eacute;seau OSCOUR\u0026reg; / Sant\u0026eacute; publique France Point hebdomadaire num\u0026eacute;ro 935 du 14/03/2023. 2023. \u003c/li\u003e\n\u003cli\u003eThomas M, Yawn BP, Price D, Lund V, Mullol J, Fokkens W, et al. EPOS Primary Care Guidelines: European Position Paper on the Primary Care Diagnosis and Management of Rhinosinusitis and Nasal Polyps 2007 - a summary. Prim Care Respir J J Gen Pract Airw Group. juin 2008;17(2):79‑89. \u003c/li\u003e\n\u003cli\u003eKoizumi M, Ishimaru M, Matsui H, Fushimi K, Yamasoba T, Yasunaga H. Outcomes of endoscopic sinus surgery for sinusitis-induced intracranial abscess in patients undergoing neurosurgery. Neurosurg Focus. 1 ao\u0026ucirc;t 2019;47(2):E12. \u003c/li\u003e\n\u003cli\u003eChalstrey S, Pfleiderer AG, Moffat DA. Persisting incidence and mortality of sinogenic cerebral abscess: a continuing reflection of late clinical diagnosis. J R Soc Med. avr 1991;84(4):193‑5. \u003c/li\u003e\n\u003cli\u003eBandino F, Thota R, Pendolino AL, Chaidas K, Jeyaretna S, Lawrence T, et al. A surgical protocol for sinogenic brain abscess: the Oxford experience and a review of the literature. Rhinology. 1 oct 2022;60(5):357‑67. \u003c/li\u003e\n\u003cli\u003eCarr TF. Complications of sinusitis. Am J Rhinol Allergy. juill 2016;30(4):241‑5. \u003c/li\u003e\n\u003cli\u003eClayman GL, Adams GL, Paugh DR, Koopmann CF. 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Eur Neurol. 2020;83(4):369‑79. \u003c/li\u003e\n\u003cli\u003eHAS. Sinusite de l\u0026rsquo;adulte [Internet]. 2021. Disponible sur: https://www.has-sante.fr/upload/docs/application/pdf/2021-08/fiche_memo_sinusite_adulte_durees_antibiotherapies.pdf\u003c/li\u003e\n\u003cli\u003eChow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJC, Hicks LA, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis Off Publ Infect Dis Soc Am. avr 2012;54(8):e72‑112. \u003c/li\u003e\n\u003cli\u003eFokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. Executive summary of EPOS 2020 including integrated care pathways. Rhinology. 1 avr 2020;58(2):82‑111. \u003c/li\u003e\n\u003cli\u003eCamacho AE, Cobo R, Otte J, Spector SL, Lerner CJ, Garrison NA, et al. Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis. Am J Med. sept 1992;93(3):271‑6. \u003c/li\u003e\n\u003cli\u003eGehanno P, Berche P, Hercot O, d\u0026rsquo;Arras L, Cabrillac-Rives S, Derobert E, et al. [Efficiency of a four-day course of pristinamycin compared to a five-day course of cefuroxime axetil for acute bacterial maxillary sinusitis in adult outpatients]. Med Mal Infect. juill 2004;34(7):293‑302. \u003c/li\u003e\n\u003cli\u003eP\u0026eacute;nurie de m\u0026eacute;dicaments dans l\u0026rsquo;UE : les causes et les solutions [Internet]. 2022. Disponible sur: https://www.europarl.europa.eu/topics/fr/article/20200709STO83006/penurie-de-medicaments-dans-l-ue-les-causes-et-les-solutions\u003c/li\u003e\n\u003cli\u003eAntibiotic availability and shortages in the human and animal sectors in France. Gen\u0026egrave;ve: World Health Organization; 2022. Report No.: CC BY-NC-SA 3.0 IGO. \u003c/li\u003e\n\u003cli\u003eP\u0026eacute;nurie de m\u0026eacute;dicaments : le plan d\u0026rsquo;actions du Leem [Internet]. 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Disponible sur: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.senat.fr/rap/r22-828-1/r22-828-11.pdf\u003c/li\u003e\n\u003cli\u003ePeters G. The health and national security risks of Drug shortage [Internet]. US Senate Committee on Homeland Security and Governmental Affairs; 2023 mars. Disponible sur: https://www.hsgac.senate.gov/wp-content/uploads/2023-06-06-HSGAC-Majority-Draft-Drug-Shortages-Report.-FINAL-CORRECTED.pdf\u003c/li\u003e\n\u003cli\u003eTENSIONS D\u0026rsquo;APPROVISIONNEMENT EN PRODUIT DE SANT\u0026Eacute; [Internet]. ANSM (Agence nationale de s\u0026eacute;curit\u0026eacute; du m\u0026eacute;dicament et des produits de sant\u0026eacute;); 2023 avr. Disponible sur: https://ansm.sante.fr/uploads/2023/04/27/20230414-point-de-situation-pp8-tensions-en-produits-de-sante-14-avril-23.pdf\u003c/li\u003e\n\u003cli\u003eCohen R, Pettoello-Mantovani M, Giardino I, Carrasco-Sanz A, Somekh E, Levy C. The Shortage of Amoxicillin: An Escalating Public Health Crisis in Pediatrics Faced by Several Western Countries. J Pediatr. juin 2023;257:113321. \u003c/li\u003e\n\u003cli\u003eMorrow M, Ogino M, Shah A, Ning J. Extensive Invasive Sinusitis Secondary to Streptococcus Intermedius Infection. Clin Med Res. sept 2024;22(3):160‑4. \u003c/li\u003e\n\u003cli\u003ePlainvert C, Matuschek E, Dmytruk N, Gaillard M, Frigo A, Ballaa Y, et al. Microbiological Epidemiology of Invasive Infections Due to Non-Beta-Hemolytic Streptococci, France, 2021. Microbiol Spectr. 15 juin 2023;11(3):e0016023. \u003c/li\u003e\n\u003cli\u003eCushen R, Francis NA. Antibiotic use and serious complications following acute otitis media and acute sinusitis: a retrospective cohort study. Br J Gen Pract J R Coll Gen Pract. avr 2020;70(693):e255‑63. \u003c/li\u003e\n\u003cli\u003eWeinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Mast cell activation symptoms are prevalent in Long-COVID. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. nov 2021;112:217‑26. \u003c/li\u003e\n\u003cli\u003eHultman Dennison S, Granath A, Holmstrom M, Stjarne P, Hertting O. Complications to acute bacterial rhinosinusitis in children - a prospective study; bacterial cultures, virus detection, allergy sensitization and immunoglobulins. Rhinology. 1 oct 2023;61(5):412‑20. \u003c/li\u003e\n\u003cli\u003eMillien C, Chaput H, Cavillon M. La moiti\u0026eacute; des rendez-vous sont obtenus en 2 jours chez le g\u0026eacute;n\u0026eacute;raliste, en 52 jours chez l\u0026rsquo;ophtalmologiste [Internet]. DRESS; 2018 oct. Disponible sur: https://drees.solidarites-sante.gouv.fr/publications/etudes-et-resultats/la-moitie-des-rendez-vous-sont-obtenus-en-2-jours-chez-le\u003c/li\u003e\n\u003cli\u003eLe quotiden du m\u0026eacute;decin [Internet]. Consultations : face au casse-t\u0026ecirc;te des d\u0026eacute;lais d\u0026rsquo;attente qui s\u0026rsquo;allongent, les Fran\u0026ccedil;ais renoncent. Disponible sur: https://www.lequotidiendumedecin.fr/archives/consultations-face-au-casse-tete-des-delais-dattente-qui-sallongent-les-francais-renoncent\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Comparison of baseline characteristics in patients with non-complicated and complicated sinusitis.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"677\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=142 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon complicated sinusitis (n=116)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplicated sinusitis (n=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 233px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds ratio (OR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCI 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e26 - 65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e93 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026le; 25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e13 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e3.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.92-15.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026gt; 65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e36 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.07-1.56]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e72 (51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.97-7.39]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic shortage period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e82 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[2.04-40.15]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e (n=101)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026lt;25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e46 (46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e25-30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e34 (34%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.02-1.19]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026gt; 30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e21 (21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.04-2.08]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior antibiotic prescription (n=139)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e83 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.86-8.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior Amox-Amox/ac clav antibiotic prescription (n=69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e39 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.03-0.59]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior other antibiotic*\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(n=69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e40 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e7.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[1.58-77.87]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior prescription of both\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAmox-Amox/ac clav and other antibiotic (n=69)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e10 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.07-4.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFever** (n=53)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e7 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e5.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.75-42.64]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh C-Reactive protein (CRP)*** (n=58)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e48 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[1.38-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh blood leukocyte**** (n=79)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e26 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.95-8.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAffected sinus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eMaxillary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e96 (68%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.19-1.28]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eEthmoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e69 (49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[1.07-8.21]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e46 (32%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.78-5.36]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eSphenoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e42 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.74-5.26]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eOrbital cellulitis or abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e12 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[19.5-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eEmpyema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e8 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[9.69-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eCerebral venous thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e6 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[6.12-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 163px;\"\u003e\n \u003cp\u003eBrain abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e6 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[6.12-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMicrobiological data\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e36 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.11-1.57]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cem\u003eH. influenzae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e20 (14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[0.13-2.97]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cem\u003eP. aeruginosa\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e15 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[inf-1.78]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 179px;\"\u003e\n \u003cp\u003eOral streptococci\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e17 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"87\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 87px;\"\u003e\n \u003cp\u003e9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e[2.82-34.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.0001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 677px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNOTE\u003c/strong\u003e. Data are presented as No. (%) unless otherwise indicated. n=number of data analysed (when \u0026lt;142);\u0026nbsp;univariate analysis, Fisher\u0026apos;s exact test, probability values lower than 0.05 were considered statistically significant and depicted in bold).\u003c/p\u003e\n \u003cp\u003e*Other antibiotic included: oral cephalosporins, pristinamycin, clindamycin, fluoroquinolone, macrolides ** Fever was defined as T\u0026deg; \u0026gt; 38\u0026deg;C; ***High CRP was defined as \u0026gt; 5 mg/L; **** High blood leukocyte was defined as \u0026gt; 10 G/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Factors associated with complicated sinusitis in multivariate model\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=142 (100%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon complicated sinusitis (N= 116)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplicated sinusitis (N=26)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e72 (51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eShortage period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e82 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior Amox-Amox/ac clav antibiotic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e39 (57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrior other antibiotic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e40 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFever\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7 (13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh C-reactive protein (CRP)** (n=58)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e48 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAffected sinus\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Ethmoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e69 (49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Sphenoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e42 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOral streptococci\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 68px;\"\u003e\n \u003cp\u003e17 (12%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLogistic multimodal regression model and stepwise method, probability values \u0026lt; 0.05 were considered statistically significant and are shown in bold. *Fever was defined as T\u0026deg; \u0026gt; 38\u0026deg;C ; **High CRP was defined as \u0026gt; 5 mg/L\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e. Comparison of outcomes and surgical management of patients with non-complicated and with complicated sinusitis\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-complicated sinusitis (N=116)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplicated sinusitis (N=26\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOdds Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCI 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeurosurgery (n=141)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e3 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[1.91-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.006*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOrbital drainage (n=141)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e9 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[11.65-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSinus drainage (n=141)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e104 (74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[inf-2.88]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.0002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExternal sinus approach (n=141)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e11 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e19.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[3.56-199.1]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEndonasal approach (n=141)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e104 (74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eInf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[inf-2.88]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.0002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable outcome D7 (n=133)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e106 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[0.11-0.89]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical revision D7 (n=138)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e6 (4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[5.91-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFavorable outcome M3 (n=126)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e93 (74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[0.33-3.45]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgical revision M12 (=128)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e6 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[0.2-17.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of surgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e36 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e93 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[1.8-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 143px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026ge; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e13 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 80px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003einf\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e[11.24-inf]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNOTE\u003c/strong\u003e. Data are presented as No. (%) unless otherwise indicated. n=number of data analysed (when \u0026lt;142); univariate analysis, Fisher\u0026apos;s exact test, probability values \u0026lt; 0.05 were considered statistically significant and are marked with an *\u0026nbsp;\u003c/p\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":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Community-acquired infections, Antibiotic policy, ENT infections, Sinusitis, Antibiotic shortage","lastPublishedDoi":"10.21203/rs.3.rs-6658540/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6658540/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives. \u003c/strong\u003eRecent shortages of amoxicillin and amoxicillin/clavulanate in France have raised concerns about a possible impact on the management and outcome of acute sinusitis. We therefore assessed the rates of complicated sinusitis occurring during two time periods, one with and one without antibiotic shortages.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods. \u003c/strong\u003eWe reviewed cases of sinusitis from two periods: December-February 2018-19 and 2019-20 (no antibiotic shortages) and December-February 2021-22 and 2022-23 (shortages of amoxicillin and amoxicillin/clavulanate). We included all patients over 15 years of age who had been treated in the hospital’s ear, nose and throat department of Lariboisiere hospital for sinusitis. The primary outcome was the rate of complicated sinusitis among the total number of cases of sinusitis treated at Lariboisière hospital during the two study periods.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003e One hundred and forty-two patients were treated for sinusitis during the study periods: 60 during the no-shortage period and 82 during the shortage period. The rate of complicated sinusitis was significantly higher during the shortage period (23/82, 28%) than during the no-shortage period (3/60, 5%) (OR 7.32, CI [2.04-40.15], p=0.0003). The use of alternative antibiotics prior to attendance was independently associated with an increased risk of complications (OR 7.88, CI [1.58-77.87], p=0.004). The presence of oral streptococci was also associated with complications, suggesting a correlation between microbial patterns and antibiotic shortages.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions.\u003c/strong\u003e Shortages of first-line antibiotics for sinusitis was associated with an increased rate of complications, highlighting the need to explore alternative treatments and reinforce public health actions to anticipate shortages.\u003c/p\u003e","manuscriptTitle":"Impact of shortages of amoxicillin and amoxicillin/clavulanate on the outcome of bacterial sinusitis in adults: a French retrospective, single-centre study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-08 16:16:47","doi":"10.21203/rs.3.rs-6658540/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-09T11:02:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-09T10:10:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-14T09:44:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"279564199507829996127351550969713978494","date":"2025-08-12T11:29:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103648099284572397914403057089178102282","date":"2025-08-05T00:49:11+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-04T14:29:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-14T02:18:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-14T02:18:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","date":"2025-05-13T20:12:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejcm","sideBox":"Learn more about [European Journal of Clinical Microbiology \u0026 Infectious Diseases](https://www.springer.com/journal/10096)","snPcode":"10096","submissionUrl":"https://submission.nature.com/new-submission/10096/3","title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ccddceb4-e75d-4d40-aad6-9f100b66543b","owner":[],"postedDate":"August 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:02:17+00:00","versionOfRecord":{"articleIdentity":"rs-6658540","link":"https://doi.org/10.1007/s10096-025-05305-3","journal":{"identity":"european-journal-of-clinical-microbiology-and-infectious-diseases","isVorOnly":false,"title":"European Journal of Clinical Microbiology \u0026 Infectious Diseases"},"publishedOn":"2025-11-15 15:58:06","publishedOnDateReadable":"November 15th, 2025"},"versionCreatedAt":"2025-08-08 16:16:47","video":"","vorDoi":"10.1007/s10096-025-05305-3","vorDoiUrl":"https://doi.org/10.1007/s10096-025-05305-3","workflowStages":[]},"version":"v1","identity":"rs-6658540","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6658540","identity":"rs-6658540","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}