Antibiotic Overuse in a Contemporary Cohort of Children Hospitalized with Influenza, RSV, or SARS-CoV-2: A Retrospective Cohort Study

Antibiotic Overuse in a Contemporary Cohort of Children Hospitalized with Influenza, RSV, or SARS-CoV-2: A Retrospective Cohort 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 Antibiotic Overuse in a Contemporary Cohort of Children Hospitalized with Influenza, RSV, or SARS-CoV-2: A Retrospective Cohort Study Mrinmoyee Kalasikam, Natalia Jimenez-Truque, Anisa Kloek, Ritu Banerjee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4614400/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted 4 You are reading this latest preprint version Abstract Background Children hospitalized with viral respiratory tract infections (RTIs) are often prescribed antibiotics due to concern for bacterial co-infection, although most do not have concurrent bacterial infections. This unnecessary antibiotic treatment can lead to bacterial resistance and adverse events. The extent of antibiotic overuse in hospitalized children with community-onset viral RTIs has not been described in recent years. To identify antibiotic stewardship opportunities in this population, we quantified the extent of antibiotic overtreatment and determined predictors of antibiotic use among children hospitalized with influenza, respiratory syncytial virus (RSV), or SARS-CoV-2 (COVID-19). Methods We performed a single-center retrospective study evaluating antibiotic use and culture-confirmed bacterial co-infection among children and adolescents hospitalized with influenza, RSV, or COVID-19 between April 2020 and May 2023. Predictors of antibiotic treatment were determined using logistic regression. Results We included 1,718 patients (influenza: 188; RSV: 1,022; COVID-19: 535). Patients with RSV were younger and more likely to be in intensive care. Eight percent of patients had culture-confirmed bacterial co-infection. The proportion of children with culture-confirmed bacterial infection was low (8%) but the proportion receiving antibiotics was high and varied by virus (influenza: 60.6%, RSV:41.2%, COVID-19: 48.6%, p < 0.001). Independent predictors for receipt of antibiotics were elevated inflammatory markers, mechanical ventilation, and influenza infection. Among patients with the lowest severity of illness, 48% received ≥ 1 dose of antibiotics. Conclusions In children hospitalized with community-onset viral RTIs, antibiotic treatment is substantially higher than the burden of culture-confirmed bacterial infection, especially for influenza, suggesting antibiotic overuse and antibiotic stewardship opportunities. antibiotic overuse influenza RSV COVID-19 viral respiratory tract infection Figures Figure 1 Figure 2 Background The burden of pediatric hospitalizations for viral respiratory tract infections (RTIs) is substantial. In the U.S., over 22,000 children have been hospitalized with COVID-19 since 2020, 12,000–46,000 children are hospitalized with influenza each year, and up to 80,000 children < 5 years are hospitalized with RSV every year ( 1 , 2 , 3 ). Children hospitalized with viral RTIs are often treated with antibiotics due to concerns for bacterial co-infection, especially bacterial pneumonia, which can be preceded by viral infection ( 4 , 5 , 6 ). However, the majority of children with viral RTIs do not have concurrent bacterial infections, so this practice leads to unnecessary antibiotic treatment which, in turn, can lead to development of resistant bacteria and adverse events. Unlike in adults, the extent of antibiotic overuse in hospitalized children with community-onset viral RTI has not been well-quantified in recent years ( 4 ). Several studies have found that although there were low rates of bacterial co-infection in adults hospitalized with COVID-19, up to 75% received antibiotics ( 5 , 6 , 8 ). Similarly, a large multicenter study evaluating children with critical illness from COVID-19 found that 7% of children had bacterial coinfection but 63% received antibiotics ( 5 ). Studies of antibiotic treatment among children hospitalized with influenza or RSV before the COVID-19 pandemic demonstrated that 60–90% received antibiotics ( 9 , 10 ), but there were few evaluations of bacterial co-infection rates ( 11 , 12 , 13 , 14 ). Furthermore, most prior studies of viral RTI do not quantify antibiotic use and may have overestimated bacterial co-infection burden because they interpreted any respiratory culture with bacterial growth as indicative of bacterial infection, although many positive respiratory cultures likely reflected colonization ( 15 , 16 , 17 ). We sought to quantify the extent of antibiotic overuse in a contemporary cohort of children hospitalized with viral RTI, in the context of an active hospital-based antibiotic stewardship program. Methods Sampling and Exclusion Criteria We conducted a single center retrospective cohort study of all children and adolescents aged < 19 years old hospitalized at Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, TN who had a positive test for influenza, RSV, or COVID-19. Patients with RSV and influenza were hospitalized January 2021 to May 2023, and patients with COVID-19 were hospitalized April 2020 to February 2022. Patients were excluded if they were > 19 years of age or were not hospitalized. From 2021 onwards, the institutional antibiotic stewardship team performed daily audit and feedback of antibiotics prescribed in inpatients; feedback was provided to treating providers via telephone or in person discussion. Audit and feedback were performed inconsistently during 2020 due to disruptions from the COVID-19 pandemic. Data Collection Medical records were reviewed to identify patients with positive viral antigen or PCR tests for influenza, RSV, or COVID-19 within 48 hours of hospitalization and to collect demographic and clinical characteristics including age, sex, race, microbiology results, hospital length of stay, laboratory results, and antibiotic administration. Race and ethnicity were both self-reported. Culture-confirmed bacterial infection was defined as growth of clinically significant bacteria (non-commensal species) indicative of bacterial co-infection from any specimen source including blood, urine, pleural fluid, cerebrospinal fluid, and respiratory secretions throughout the hospitalization. We also used a second, more stringent definition of culture-confirmed bacterial infection that excluded cultures of respiratory specimens. We did not collect information on presence of white blood cells (WBC) in respiratory cultures. Cultures with growth of common commensals, including diphtheroids, Micrococcus species, and coagulase-negative Staphylococci were considered colonizers and not bacterial infection. Patients with multiple viruses were excluded from multivariable logistic regression models. Data Analysis A univariable analysis was conducted using the entire sample to compare demographic and clinical variables by virus type, using Pearson's chi-squared for categorical characteristics, and Kruskal Wallis H test for continuous variables. After excluding patients with detection of multiple viruses, two different multivariable logistic regression models were developed a priori to identify predictors of 1) at least one dose of antibiotic treatment and 2) greater than 3 days of antibiotic treatment. The model included variables that were deemed clinically significant based on clinical judgement and were also found to be statistically significant in the univariable analysis. The logistic regression models included the type of virus, age, presence of elevated inflammatory markers [procalcitonin, PCT, (≥ 0.5 ug/mL) or C-reactive protein, CRP (≥ 50 mg/L)], intensive care unit (ICU) status, and whether the patient received mechanical ventilation. Patients who did not have inflammatory markers measured were assumed to have normal inflammatory markers in the multivariable analysis. Bacterial co-infection and antibiotic utilization percentages were determined by type of virus. Patients with a low severity of illness were defined as having normal inflammatory markers [PCT < 0.5 ug/mL or CRP < 50 mg/L], and not admitted to the ICU. Patients without inflammatory markers measured were excluded from severity of illness analyses. Analyses were done using Stata 17 (Stata Corp BE). Results Demographic and clinical characteristics (Table 1 ) Table 1 Demographic and clinical characteristics of 1,718 pediatric patients by type of virus Characteristic Influenza (N = 188; 10.9%) a RSV (N = 1,022; 59.5%) b COVID-19 (N = 535; 31.1%) c Total (N = 1,718) d, e Demographics Median age in years (range) 5.18 (0.02–17.68) 0.61 (0.11–18.43) 6.06 (0–18.96) 1.35 (0–18.96) Male sex 108 (57.4%) 547 (53.5%) 278 (52.0%) 922 (53.7%) Race Asian 5 (2.66%) 6 (0.587%) 3 (0.561%) 14 (0.815%) Black or African American 27 (14.4%) 142 (13.9%) 114 (21.3%) 279 (16.2%) White 126 (67.0%) 673 (65.9%) 320 (59.8%) 1,104 (64.3%) Other Race/Unknown 30 (16.0%) 201 (19.7%) 98 (18.3%) 321 (18.7%) Ethnicity Hispanic or Latino 42 (22.3%) 185 (18.1%) 100 (18.7%) 320 (18.6%) Not Hispanic or Latino 81 (43.1%) 345 (33.8%) 150 (28.2%) 572 (33.3%) Unknown 65 (34.6%) 492 (48.1%) 285 (53.3%) 826 (48.1%) LOS, median days (range) 2.67 (0.39–57.55) 2.79 (0.01–98.46) 2.64 (0.06 -285.59) 2.75 (0.06-285.59) Severity ICU 55 (29.3%) 462 (45.2%) 117 (21.9%) 618 (36.0%) Mechanical Ventilation 23 (12.2%) 108 (10.6%) 63 (11.8%) 187 (10.9%) ECMO 2 (1.1%) 4 (0.39%) 4 (0.75%) 10 (0.58%) Death 3 (1.60%) 16 (1.57%) 31 (6.23%) 48 (2.79%) Symptomatic Respiratory Infection f 124 (66.0%) 849 (83.1%) 359 (67.1%) 1298 (75.6%) Microbiology Bacterial Infection 15 (8.0%) 70 (6.9%) 55 (10.3%) 138 (8.0%) Blood 5 (2.7%) 23 (2.3%) 18 (3.4%) 45 (2.6%) Respiratory secretions 8 (4.3%) 34 (3.3%) 16 (3.0%) 57 (3.3%) Urine 1 (0.53%) 11 (1.08%) 18 (3.36%) 30 (1.7%) Other body fluid 1 (0.53%) 2 (0.20%) 2 (0.37%) 5 (0.29%) Other 0 0 1 (0.19%) 1 (0.06%) g Inflammatory Markers Inflammatory markers (PCT or CRP) measured 87 (46.3%) 305 (29.8%) 296 (55.3%) 671 (39.1%) Elevated inflammatory markers [PCT (≥ 0.5 ug/mL) or CRP (≥ 50 mg/L)] h 44 (50.6%) 124 (40.7%) 102 (34.5%) 264 (39.3%) Very elevated inflammatory markers [PCT (> 1 ug/mL) or CRP (> 100 mg/L)] h 29 (33.3%) 81 (26.6%) 51 (17.2%) 156 (23.2%) PCT, median (range) [n = 426] 0.58 (0.06–100) 0.28 (0.06–100) 0.17 (0.06–100) 0.24 (0.06–100) CRP, median (range) [n = 378] 38.65 (1 -295.3) 32.7 (0.2–367.6) 24.7 (0.2 -361.8) 30.9 (0.2–480) Antibiotic Treatment Received any antibiotics 114 (60.6%) 421 (41.2%) 260 (48.6%) 785 (45.7%) Duration of antibiotics No antibiotics 74 (39.4%) 601 (58.8%) 275 (51.4%) 933 (54.3%) 1–3 days 42 (22.3%) 185 (18.1%) 109 (20.4%) 331 (19.3%) > 3 days 72 (38.3%) 236 (23.1%) 151 (28.2%) 454 (26.4%) Antibiotics DOT median, range [n = 775] 5 (1–93) 4 (1–94) 5 (1–401) 4 (1–401) a Hospital admission from 12/20/2020–05/27/2023 b Hospital admission from 04/01/2021–05/03/2023 c Hospital admission from 04/06/2020-2/14/2022 d Hospital admission from 04/06/2020–05/27/2023 e 6 participants had influenza and RSV coinfection; 3 had influenza and COVID-19; 17 had RSV and COVID-19 f ICD-10 diagnosis codes found in Supplemental Table 1 g Cultured from a wound h Percent of those with PCT or CRP obtained LOS, length of stay ECMO, extracorporeal membrane oxygenation PCT, procalcitonin CRP, C-reactive protein DOT, days of therapy We included 1,718 pediatric patients (188 with influenza, 1,022 with RSV, 535 with COVID-19). Patient demographic and clinical factors varied by virus type (Table 1 ). Median age was lowest for patients with RSV and highest for patients with COVID-19 (0.61 years vs. 6 years, p < 0.001). Racial distribution varied significantly by virus; Black patients comprised 21.3% of patients with COVID-19, and lower percentages of patients with RSV and influenza, while white patients comprised two-thirds of patients with influenza but lower percentages of patients with RSV or COVID-19. A greater proportion of patients with RSV (45%) were in the ICU, than patients with influenza or COVID-19 (p < 0.001). Mortality was highest in patients with COVID-19 at 6.2% but was significantly lower for patients with influenza or RSV (p < .001). Inflammatory markers among patients in whom they were measured, were elevated in almost half of patients with influenza, in 40% of patients with RSV and 35% patients of COVID-19 (p < 0.001). The overall rate of bacterial co-infection was 8% when including respiratory cultures and 5.4% when excluding respiratory cultures. Positive cultures (of all specimen types including respiratory) occurred more commonly in patients with COVID-19 (10.3%) than those with RSV (6.9%) or influenza (8%) (p = 0.03). The median number of days from admission to collection of a positive bacterial culture was 3 (IQR = 2) and did not vary by virus type (p = 0.204). Antibiotic Treatment Although few patients had culture-confirmed bacterial infections, 45.7% of patients received at least one dose of antibiotics and 26.4% received > 3 days of antibiotics (Fig. 1 ). Antibiotic treatment varied by virus type. Among patients with influenza, 60.6% received at least one antibiotic dose, and 38% received > 3 days of antibiotics. In contrast, only 23% of patients with RSV and 28% of patients with COVID-19 received > 3 days of antibiotics (p < 0.001). The percent of patients receiving antibiotic treatment was higher in ICU than non-ICU locations and higher among those with very elevated inflammatory markers vs. normal inflammatory markers (Fig. 2 ). Among a subgroup of patients with low severity of illness, 7.3% had culture-confirmed bacterial infection including respiratory cultures, while 48.1% received at least 1 dose of antibiotic and 20.8% received > 3 days of antibiotics; these percentages did not differ significantly by virus type. Predictors of Antibiotic Treatment Independent predictors of receiving > 3 days of antibiotic treatment were elevated inflammatory markers, being on mechanical ventilation, and having a diagnosis of influenza (Table 2 ). The same variables were independent predictors for receiving at least 1 dose of antibiotics. Patients with elevated inflammatory markers were significantly more likely to receive antibiotics than those without elevated inflammatory markers (OR 4.45, 95% CI 3.28 to 6.05) when adjusted for mechanical ventilation, influenza diagnosis, and age (Table 2 ). Table 2 Multivariable analysis to determine predictors of receiving > 3 days of antibiotic therapy. Characteristic Odds Ratio 95% CI P-Value Age 1.02 0.99–1.04 0.224 Elevated CRP (> 50 mg/L) or PCT (> 0.5 ug/L) 4.46 3.28–6.05 < 0.001 Mechanical Ventilation 7.36 4.82–11.24 < 0.001 ICU 1.21 0.90–1.63 0.201 Influenza 2.02 1.36–2.99 < 0.001 COVID 1.14 0.82–1.57 0.445 Discussion In this large contemporary cohort of children hospitalized with influenza, RSV, or COVID-19, we found that the percent of patients with bacterial co-infection was low, while the percent of patients receiving antibiotic treatment was high. Overall, the proportion of patients prescribed antibiotics for > 3 days was 46%, which is 4–6 times greater than the proportion that had culture-confirmed bacterial infections. This difference between antibiotic treatment and bacterial infection burden was greatest among patients with influenza and with elevated inflammatory markers in both ICU and non-ICU settings. Notably, among patients with the lowest severity of illness, in whom bacterial infection was least likely, any antibiotic treatment was administered to 48.1% of patients and > 3 days of antibiotics were given to 20.8% of patients, suggesting antibiotic overtreatment. For this group of patients, clinicians could consider withholding or promptly deescalating antibiotics. In contrast, for patients with high severity of illness, it is appropriate to initiate empiric and/or targeted antibiotic treatment. The rates of antibiotic use seen in our study are similar to those reported in earlier, studies, suggesting that antibiotic prescribing practices have not changed in recent years despite greater provider and public awareness of the importance of antibiotic stewardship ( 9 , 18 , 19 ). We observed that the proportion of patients receiving antibiotics was highest for patients with influenza (> 60%) and lowest for patients with RSV (41%). Previous studies spanning over 20 years have noted antibiotic use in 49–58% of children and adults diagnosed with influenza ( 9 , 18 , 19 ). The antibiotic utilization percentage we observed among patients with RSV is also comparable to findings from previous studies, in which 33–57% of children hospitalized with RSV who did not have a culture-confirmed bacterial infection were administered antibiotics ( 10 , 20 ). While the low bacterial co-infection rate we observed is supported by recent adult and pediatric studies of patients with COVID-19, it contrasts with some earlier studies of influenza and RSV that reported higher bacterial co-infection rates of 27–40% ( 15 , 16 , 17 ). This discrepancy may be due to fact that some earlier studies defined bacterial co-infection largely based on positive bacterial culture results from non-sterile sites such as sputum or respiratory secretions and used bacterial colony count thresholds that are not validated for diagnosis of bacterial pneumonia ( 15 , 16 , 17 , 21 ). Additionally, these studies found that S. pneumoniae and S. aureus , were the most commonly isolated bacterial pathogens among children with viral RTI ( 16 , 17 ). Though growth of these organisms from respiratory specimens may have reflected bacterial co-infection in some patients, they may have reflected colonization of the respiratory tract in others ( 22 ). Patient demographic and clinical factors differed by virus type, which may have influenced medical management and could explain why antibiotic treatment differed by virus. Hospitalized patients with RSV were significantly younger and less likely to receive antibiotics than patients with influenza. Clinicians may have been more likely to avoid antibiotics in patients hospitalized with RSV because these children were most commonly infants with bronchiolitis and were not as acutely ill as the patients with influenza. This hypothesis is supported by the fact that ICU admission was more common among patients with RSV than patients with influenza, but rates of mechanical ventilation were similar between the groups, likely because many infants with RSV received supplemental oxygen but did not require mechanical ventilation. We determined that several variables were independent predictors for receipt of antibiotic treatment, including having influenza, requiring mechanical ventilation, and having elevated inflammatory markers. Antibiotic treatment of patients with influenza may stem from widespread clinician awareness of reports of influenza-associated Gram-positive bacterial pneumonia and the associated high mortality ( 23 , 24 , 25 ). Mechanical ventilation is a predictor likely because it is a surrogate for severe illness in which antibiotic treatment may be warranted. High inflammatory markers is likely strongly associated with antibiotic treatment because of clinician confidence that these tests indicate bacterial infection. However, these tests, especially CRP, have low specificity and low positive predictive value (PPV) for bacterial infection and can be elevated in viral infections ( 26 ). Providers should be wary about prescribing antibiotics based solely on the results of inflammatory markers, without consideration of the clinical context. Strengths of our study are the large sample size, use of a stringent definition of bacterial co-infection, and evaluation of a contemporary cohort. Our study also has limitations, including its single center, retrospective nature, which may reduce its generalizability. However, our study corroborates findings of antibiotic overuse seen in earlier studies ( 5 , 6 , 7 ). Additionally, because bacterial pneumonia is not often confirmed by culture and we did not collect information about abnormal chest radiographs, we may have underestimated the occurrence of bacterial pneumonia. However, it is unlikely that almost half of patients (the proportion who received antibiotics) developed bacterial pneumonia after RTI ( 27 ). We identified subjects based on positive viral test results, determined symptomatic respiratory tract infection based on diagnosis codes, and did not confirm presence of respiratory symptoms through chart review. It is possible that antibiotic treatment was given for infections other than pneumonia (eg. acute otitis media), which we were not able to ascertain. In addition, antimicrobial stewardship interventions were inconsistently implemented throughout 2020 due to the COVID-19 pandemic. Despite these limitations, we demonstrate in a contemporary cohort that unnecessary antibiotic use persists in hospital settings, as the antibiotic treatment burden far exceeds bacterial co-infections for children hospitalized with influenza, RSV, or COVID-19. Antibiotic stewardship programs should encourage clinicians to withhold or promptly deescalate antibiotics, particularly for children hospitalized with low severity of viral RTI, in whom bacterial infection is very rare and stewardship interventions may have higher acceptance. Declarations Ethics approval and consent to participate: Not applicable. This study was approved with a waiver of consent by the Vanderbilt University IRB (#232179). Consent for publication: Not applicable. Availability of data and material: The datasets generated and analysed during the current study are not publicly available but are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: M.K. is a recipient of the Pediatric Infectious Diseases Society’s SUMMERS award. Authors' contributions: M.K. performed data collection and analysis and prepared the manuscript. N.J.T supervised data analysis. A.B.K. assisted with data collection and analysis of the patients with COVID-19. R.B supervised data collection, analysis, and manuscript preparation. All authors read and approved the final version of the manuscript. Acknowledgements : Not applicable. References Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. N Engl J Med. 2009;360(6):588–98. Rha B, Curns AT, Lively JY, Campbell AP, Englund JA, Boom JA, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015–2016. Pediatrics. 2020;146(1):e20193611. McLaughlin JM, Khan F, Schmitt HJ, Agosti Y, Jodar L, Simões EAF, et al. Respiratory Syncytial Virus–Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. J Infect Dis. 2020;225(6):1100–11. Malik SS, Mundra S. Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Anti-Microbial Resistance. Antibiot (Basel). 2022;12(1):45. Moffitt KL, Nakamura MM, Young CC, Newhams MM, Halasa NB, Reed JN, et al. Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Open Forum Infect Dis. 2023;10(3):ofad122. Vaughn VM, Gandhi TN, Petty LA, Patel PK, Prescott HC, Malani AN, et al. Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study. Clin Infect Dis. 2021;72(10):e533–41. Gillon J, Garguilo K, LeBlanc K, Banerjee R. Antibiotic Overuse Among Children with COVID-19 Hospitalized in a Pediatric Intensive Care Unit. Open Forum Infect Dis. 2022;9(Supplement2):ofac492318. Westblade LF, Simon MS, Satlin MJ. Bacterial Coinfections in Coronavirus Disease 2019. Trends Microbiol. 2021;29(10):930–41. Nitsch-Osuch A, Gyrczuk E, Wardyn A, Życinska K, Brydak L. Antibiotic Prescription Practices Among Children with Influenza. Adv Exp Med Biol. 2016;905:25–31. van Houten CB, Naaktgeboren C, Buiteman BJM, van der Lee M, Klein A, Srugo I, et al. Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory Tract Infection. Pediatr Infect Dis J. 2018;37(11):1077–81. Finelli L, Fiore A, Dhara R, Brammer L, Shay DK, Kamimoto L, et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics. 2008;122(4):805–11. Ghazaly M, Nadel S. Characteristics of children admitted to intensive care with acute bronchiolitis. Eur J Pediatr. 2018;177(6):913–20. Hishiki H, Ishiwada N, Fukasawa C, Abe K, Hoshino T, Aizawa J, et al. Incidence of bacterial coinfection with respiratory syncytial virus bronchopulmonary infection in pediatric inpatients. J Infect Chemother. 2011;17(1):87–90. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835–45. Thorburn K, Harigopal S, Reddy V, Taylor N, van Saene HKF. High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis. Thorax. 2006;61(7):611–5. Lin HC, Liu YC, Hsing TY, Chen LL, Liu YC, Yen TY, et al. RSV pneumonia with or without bacterial co-infection among healthy children. J Formos Med Assoc. 2022;121(3):687–93. Hedberg P, Johansson N, Ternhag A, Abdel-Halim L, Hedlund J, Nauclér P. Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus. BMC Infect Dis. 2022;22(1):108. Mazzaglia G, Caputi AP, Rossi A, Bettoncelli G, Stefanini G, Ventriglia G, et al. Exploring patient- and doctor-related variables associated with antibiotic prescribing for respiratory infections in primary care. Eur J Clin Pharmacol. 2003;59(8–9):651–7. Ochoa C, Eiros JM, Inglada L, Vallano A, Guerra L. Assessment of antibiotic prescription in acute respiratory infections in adults. The Spanish Study Group on Antibiotic Treatments. J Infect. 2000;41(1):73–83. Obolski U, Kassem E, Na’amnih W, Tannous S, Kagan V, Muhsen K. Unnecessary antibiotic treatment of children hospitalised with respiratory syncytial virus (RSV) bronchiolitis: risk factors and prescription patterns. J Glob Antimicrob Resist. 2021;27:303–8. Wiegers HMG, van Nijen L, van Woensel JBM, Bem RA, de Jong MD, Calis JCJ. Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study. BMC Infect Dis. 2019;19(1):938. Robinson J. Colonization and infection of the respiratory tract: What do we know? Paediatr Child Health. 2004;9(1):21. Rice TW, Rubinson L, Uyeki TM, Vaughn FL, John BB, Miller RR, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med. 2012;40(5):1487–98. Randolph AG, Vaughn F, Sullivan R, Rubinson L, Thompson BT, Yoon G, et al. Critically ill children during the 2009–2010 influenza pandemic in the United States. Pediatrics. 2011;128(6):e1450–1458. Centers for Disease Control and Prevention (CDC). Surveillance for pediatric deaths associated with 2009 pandemic influenza A (H1N1) virus infection - United States, April-August 2009. MMWR Morb Mortal Wkly Rep. 2009;58(34):941–7. Staiano A, Bjerrum L, Llor C, Melbye H, Hopstaken R, Gentile I, et al. C-reactive protein point-of-care testing and complementary strategies to improve antibiotic stewardship in children with acute respiratory infections in primary care. Front Pediatr. 2023;11:1221007. Liu Y, Ling L, Wong SH, Wang MH, Fitzgerald JR, Zou X, et al. Outcomes of respiratory viral-bacterial co-infection in adult hospitalized patients. EClinicalMedicine. 2021;37:100955. Additional Declarations No competing interests reported. Supplementary Files Diagnosiscodessupplementaltable20240618.docx Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 26 Jun, 2024 Editor assigned by journal 26 Jun, 2024 Submission checks completed at journal 26 Jun, 2024 First submitted to journal 20 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4614400","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":319182895,"identity":"23babfbf-0aaa-41fc-a931-7da4d104c199","order_by":0,"name":"Mrinmoyee Kalasikam","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mrinmoyee","middleName":"","lastName":"Kalasikam","suffix":""},{"id":319182898,"identity":"5ddc7e92-9469-4b47-a7d1-9e683e42039c","order_by":1,"name":"Natalia Jimenez-Truque","email":"","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natalia","middleName":"","lastName":"Jimenez-Truque","suffix":""},{"id":319182901,"identity":"89bdeb85-b4ee-41b4-82fa-3151a1f7bf01","order_by":2,"name":"Anisa Kloek","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anisa","middleName":"","lastName":"Kloek","suffix":""},{"id":319182902,"identity":"48c8895d-d53c-45e7-8f2d-02e2c6fdb5b8","order_by":3,"name":"Ritu Banerjee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYDACZiBmbAAzExgYKojSwoys5Qyx1kC1ABltRGgwb+c/JsG4wy6PX/rAwwcf5x1OXNt+gPFxxS/cWmQOM7NJMJ5JLpbsS0g2nLntcOK2MwnMhmf7cGuRYAZpaWNO3HCGIU2ad1ta4rYbDGySjT0EtdQn7j/DkP777xzitRxO3MDDkMbM2GAD0dLwA68WY4vEM8cTZ5xhSJbsOWZjvO1MYrNhYwMeLfwHH974uKM6sb+HJ/HDjxoJ2W3HDx982PAHtxYwSACTPAlQLjCaiIogBgb2A0gcQraMglEwCkbBSAIAAIRPqXnIWe8AAAAASUVORK5CYII=","orcid":"","institution":"Vanderbilt University Medical Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ritu","middleName":"","lastName":"Banerjee","suffix":""}],"badges":[],"createdAt":"2024-06-21 02:29:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4614400/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4614400/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06165-8","type":"published","date":"2025-10-03T15:57:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60634500,"identity":"5a7c4fe9-7e92-40d6-8108-45638fa3bd75","added_by":"auto","created_at":"2024-07-19 01:47:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":248340,"visible":true,"origin":"","legend":"\u003cp\u003eBacterial co-infection and antibiotic utilization among patients hospitalized with influenza, RSV, and COVID-19. Black, percentage of patients who had a culture-confirmed bacterial infection, including respiratory specimens; gray, percentage of patients who received at least one dose of antibiotic; horizontal lines, percentage of patients who received \u0026gt;3 days of antibiotics.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4614400/v1/717777ad1aa3160d59f075c1.jpg"},{"id":60634498,"identity":"b0ad886f-ec7c-4b16-8f5c-f89ed4b16468","added_by":"auto","created_at":"2024-07-19 01:47:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":304534,"visible":true,"origin":"","legend":"\u003cp\u003eBacterial co-infection and antibiotic utilization by inflammatory markers and severity of illness. Very elevated, [PCT (\u0026gt;1 ug/mL) or CRP (\u0026gt;100 mg/L)]; elevated, [PCT (≥0.5 ug/mL) or CRP (≥50 mg/L)]; normal, [PCT (\u0026lt;0.5 ug/mL) or CRP (\u0026lt;50 mg/L)]. Black, percentage of patients who had a culture-confirmed bacterial infection, including respiratory cultures; gray, percentage of patients who received at least one dose of antibiotic. ICU, intensive care unit\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4614400/v1/8d381f8f4c94caa0780d9e91.jpg"},{"id":92883780,"identity":"073ffd98-b82c-46b7-a6bf-ad30306af98a","added_by":"auto","created_at":"2025-10-06 16:09:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1439284,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4614400/v1/ad9f3889-1899-4b79-bfed-d1da2a66d25b.pdf"},{"id":60634499,"identity":"47cea904-3ddd-4baf-8494-2678d2614762","added_by":"auto","created_at":"2024-07-19 01:47:02","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19106,"visible":true,"origin":"","legend":"","description":"","filename":"Diagnosiscodessupplementaltable20240618.docx","url":"https://assets-eu.researchsquare.com/files/rs-4614400/v1/7ef5908130df69ea433a4f55.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibiotic Overuse in a Contemporary Cohort of Children Hospitalized with Influenza, RSV, or SARS-CoV-2: A Retrospective Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eThe burden of pediatric hospitalizations for viral respiratory tract infections (RTIs) is substantial. In the U.S., over 22,000 children have been hospitalized with COVID-19 since 2020, 12,000\u0026ndash;46,000 children are hospitalized with influenza each year, and up to 80,000 children\u0026thinsp;\u0026lt;\u0026thinsp;5 years are hospitalized with RSV every year (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Children hospitalized with viral RTIs are often treated with antibiotics due to concerns for bacterial co-infection, especially bacterial pneumonia, which can be preceded by viral infection (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, the majority of children with viral RTIs do not have concurrent bacterial infections, so this practice leads to unnecessary antibiotic treatment which, in turn, can lead to development of resistant bacteria and adverse events. Unlike in adults, the extent of antibiotic overuse in hospitalized children with community-onset viral RTI has not been well-quantified in recent years (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral studies have found that although there were low rates of bacterial co-infection in adults hospitalized with COVID-19, up to 75% received antibiotics (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Similarly, a large multicenter study evaluating children with critical illness from COVID-19 found that 7% of children had bacterial coinfection but 63% received antibiotics (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Studies of antibiotic treatment among children hospitalized with influenza or RSV before the COVID-19 pandemic demonstrated that 60\u0026ndash;90% received antibiotics (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), but there were few evaluations of bacterial co-infection rates (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Furthermore, most prior studies of viral RTI do not quantify antibiotic use and may have overestimated bacterial co-infection burden because they interpreted any respiratory culture with bacterial growth as indicative of bacterial infection, although many positive respiratory cultures likely reflected colonization (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). We sought to quantify the extent of antibiotic overuse in a contemporary cohort of children hospitalized with viral RTI, in the context of an active hospital-based antibiotic stewardship program.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSampling and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eWe conducted a single center retrospective cohort study of all children and adolescents aged\u0026thinsp;\u0026lt;\u0026thinsp;19 years old hospitalized at Monroe Carell Jr. Children\u0026rsquo;s Hospital at Vanderbilt, Nashville, TN who had a positive test for influenza, RSV, or COVID-19. Patients with RSV and influenza were hospitalized January 2021 to May 2023, and patients with COVID-19 were hospitalized April 2020 to February 2022. Patients were excluded if they were \u0026gt;\u0026thinsp;19 years of age or were not hospitalized.\u003c/p\u003e \u003cp\u003eFrom 2021 onwards, the institutional antibiotic stewardship team performed daily audit and feedback of antibiotics prescribed in inpatients; feedback was provided to treating providers via telephone or in person discussion. Audit and feedback were performed inconsistently during 2020 due to disruptions from the COVID-19 pandemic.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eMedical records were reviewed to identify patients with positive viral antigen or PCR tests for influenza, RSV, or COVID-19 within 48 hours of hospitalization and to collect demographic and clinical characteristics including age, sex, race, microbiology results, hospital length of stay, laboratory results, and antibiotic administration. Race and ethnicity were both self-reported. Culture-confirmed bacterial infection was defined as growth of clinically significant bacteria (non-commensal species) indicative of bacterial co-infection from any specimen source including blood, urine, pleural fluid, cerebrospinal fluid, and respiratory secretions throughout the hospitalization. We also used a second, more stringent definition of culture-confirmed bacterial infection that excluded cultures of respiratory specimens. We did not collect information on presence of white blood cells (WBC) in respiratory cultures. Cultures with growth of common commensals, including diphtheroids, \u003cem\u003eMicrococcus\u003c/em\u003e species, and coagulase-negative \u003cem\u003eStaphylococci\u003c/em\u003e were considered colonizers and not bacterial infection. Patients with multiple viruses were excluded from multivariable logistic regression models.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eA univariable analysis was conducted using the entire sample to compare demographic and clinical variables by virus type, using Pearson's chi-squared for categorical characteristics, and Kruskal Wallis H test for continuous variables. After excluding patients with detection of multiple viruses, two different multivariable logistic regression models were developed \u003cem\u003ea priori\u003c/em\u003e to identify predictors of 1) at least one dose of antibiotic treatment and 2) greater than 3 days of antibiotic treatment. The model included variables that were deemed clinically significant based on clinical judgement and were also found to be statistically significant in the univariable analysis. The logistic regression models included the type of virus, age, presence of elevated inflammatory markers [procalcitonin, PCT, (\u0026ge;\u0026thinsp;0.5 ug/mL) or C-reactive protein, CRP (\u0026ge;\u0026thinsp;50 mg/L)], intensive care unit (ICU) status, and whether the patient received mechanical ventilation. Patients who did not have inflammatory markers measured were assumed to have normal inflammatory markers in the multivariable analysis. Bacterial co-infection and antibiotic utilization percentages were determined by type of virus. Patients with a low severity of illness were defined as having normal inflammatory markers [PCT\u0026thinsp;\u0026lt;\u0026thinsp;0.5 ug/mL or CRP\u0026thinsp;\u0026lt;\u0026thinsp;50 mg/L], and not admitted to the ICU. Patients without inflammatory markers measured were excluded from severity of illness analyses. Analyses were done using Stata 17 (Stata Corp BE).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and clinical characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical characteristics of 1,718 pediatric patients by type of virus\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInfluenza (N\u0026thinsp;=\u0026thinsp;188; 10.9%)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRSV (N\u0026thinsp;=\u0026thinsp;1,022; 59.5%)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCOVID-19 (N\u0026thinsp;=\u0026thinsp;535; 31.1%)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;1,718)\u003csup\u003ed, e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age in years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.18 (0.02\u0026ndash;17.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.61 (0.11\u0026ndash;18.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.06 (0\u0026ndash;18.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.35 (0\u0026ndash;18.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108 (57.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e547 (53.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e278 (52.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e922 (53.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0.587%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (0.561%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14 (0.815%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack or African American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (14.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142 (13.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e114 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e279 (16.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e126 (67.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e673 (65.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e320 (59.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1,104 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Race/Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e201 (19.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98 (18.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e321 (18.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic or Latino\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (22.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (18.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e320 (18.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Hispanic or Latino\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (43.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e345 (33.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e150 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e572 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e492 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e285 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e826 (48.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLOS, median days (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.67 (0.39\u0026ndash;57.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.79 (0.01\u0026ndash;98.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.64 (0.06 -285.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.75 (0.06-285.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeverity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (29.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e462 (45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e117 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e618 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical Ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (10.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e187 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECMO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (0.39%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (0.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (0.58%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (1.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (6.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48 (2.79%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic Respiratory Infection\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (66.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e849 (83.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e359 (67.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1298 (75.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMicrobiology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial Infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e138 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45 (2.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory secretions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (1.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (3.36%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther body fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (0.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (0.29%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (0.06%)\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInflammatory Markers\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammatory markers (PCT or CRP) measured\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (46.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e305 (29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e296 (55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e671 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated inflammatory markers\u003c/p\u003e \u003cp\u003e[PCT (\u0026ge;\u0026thinsp;0.5 ug/mL) or CRP (\u0026ge;\u0026thinsp;50 mg/L)]\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (50.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (40.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e264 (39.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery elevated inflammatory markers [PCT (\u0026gt;\u0026thinsp;1 ug/mL) or CRP (\u0026gt;\u0026thinsp;100 mg/L)]\u003csup\u003eh\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (26.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e156 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCT, median (range)\u003c/p\u003e \u003cp\u003e[n\u0026thinsp;=\u0026thinsp;426]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.58 (0.06\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.28 (0.06\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17 (0.06\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.24 (0.06\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP, median (range) [n\u0026thinsp;=\u0026thinsp;378]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.65 (1 -295.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.7 (0.2\u0026ndash;367.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.7 (0.2 -361.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.9 (0.2\u0026ndash;480)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntibiotic Treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReceived any antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (60.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e421 (41.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e260 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e785 (45.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (39.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e601 (58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e275 (51.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e933 (54.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (22.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e185 (18.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e331 (19.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e236 (23.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e151 (28.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e454 (26.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics DOT median, range [n\u0026thinsp;=\u0026thinsp;775]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1\u0026ndash;93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1\u0026ndash;94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (1\u0026ndash;401)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (1\u0026ndash;401)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Hospital admission from 12/20/2020\u0026ndash;05/27/2023\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e Hospital admission from 04/01/2021\u0026ndash;05/03/2023\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ec\u003c/sup\u003e Hospital admission from 04/06/2020-2/14/2022\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ed\u003c/sup\u003e Hospital admission from 04/06/2020\u0026ndash;05/27/2023\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ee\u003c/sup\u003e 6 participants had influenza and RSV coinfection; 3 had influenza and COVID-19; 17 had RSV and COVID-19\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ef\u003c/sup\u003e ICD-10 diagnosis codes found in Supplemental Table\u0026nbsp;1\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eg\u003c/sup\u003e Cultured from a wound\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eh\u003c/sup\u003e Percent of those with PCT or CRP obtained\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eLOS, length of stay\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eECMO, extracorporeal membrane oxygenation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePCT, procalcitonin\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCRP, C-reactive protein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eDOT, days of therapy\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe included 1,718 pediatric patients (188 with influenza, 1,022 with RSV, 535 with COVID-19). Patient demographic and clinical factors varied by virus type (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Median age was lowest for patients with RSV and highest for patients with COVID-19 (0.61 years vs. 6 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Racial distribution varied significantly by virus; Black patients comprised 21.3% of patients with COVID-19, and lower percentages of patients with RSV and influenza, while white patients comprised two-thirds of patients with influenza but lower percentages of patients with RSV or COVID-19. A greater proportion of patients with RSV (45%) were in the ICU, than patients with influenza or COVID-19 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Mortality was highest in patients with COVID-19 at 6.2% but was significantly lower for patients with influenza or RSV (p\u0026thinsp;\u0026lt;\u0026thinsp;.001). Inflammatory markers among patients in whom they were measured, were elevated in almost half of patients with influenza, in 40% of patients with RSV and 35% patients of COVID-19 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The overall rate of bacterial co-infection was 8% when including respiratory cultures and 5.4% when excluding respiratory cultures. Positive cultures (of all specimen types including respiratory) occurred more commonly in patients with COVID-19 (10.3%) than those with RSV (6.9%) or influenza (8%) (p\u0026thinsp;=\u0026thinsp;0.03). The median number of days from admission to collection of a positive bacterial culture was 3 (IQR\u0026thinsp;=\u0026thinsp;2) and did not vary by virus type (p\u0026thinsp;=\u0026thinsp;0.204).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAntibiotic Treatment\u003c/h2\u003e \u003cp\u003eAlthough few patients had culture-confirmed bacterial infections, 45.7% of patients received at least one dose of antibiotics and 26.4% received\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotics (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Antibiotic treatment varied by virus type. Among patients with influenza, 60.6% received at least one antibiotic dose, and 38% received\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotics. In contrast, only 23% of patients with RSV and 28% of patients with COVID-19 received\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotics (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe percent of patients receiving antibiotic treatment was higher in ICU than non-ICU locations and higher among those with very elevated inflammatory markers vs. normal inflammatory markers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Among a subgroup of patients with low severity of illness, 7.3% had culture-confirmed bacterial infection including respiratory cultures, while 48.1% received at least 1 dose of antibiotic and 20.8% received\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotics; these percentages did not differ significantly by virus type.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePredictors of Antibiotic Treatment\u003c/h2\u003e \u003cp\u003eIndependent predictors of receiving\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotic treatment were elevated inflammatory markers, being on mechanical ventilation, and having a diagnosis of influenza (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The same variables were independent predictors for receiving at least 1 dose of antibiotics. Patients with elevated inflammatory markers were significantly more likely to receive antibiotics than those without elevated inflammatory markers (OR 4.45, 95% CI 3.28 to 6.05) when adjusted for mechanical ventilation, influenza diagnosis, and age (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable analysis to determine predictors of receiving\u0026thinsp;\u0026gt;\u0026thinsp;3 days of antibiotic therapy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026ndash;1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eElevated CRP (\u0026gt;\u0026thinsp;50 mg/L) or PCT (\u0026gt;\u0026thinsp;0.5 ug/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e4.46\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3.28\u0026ndash;6.05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMechanical Ventilation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e7.36\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.82\u0026ndash;11.24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.90\u0026ndash;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfluenza\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.36\u0026ndash;2.99\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.82\u0026ndash;1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.445\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large contemporary cohort of children hospitalized with influenza, RSV, or COVID-19, we found that the percent of patients with bacterial co-infection was low, while the percent of patients receiving antibiotic treatment was high. Overall, the proportion of patients prescribed antibiotics for \u0026gt;\u0026thinsp;3 days was 46%, which is 4\u0026ndash;6 times greater than the proportion that had culture-confirmed bacterial infections. This difference between antibiotic treatment and bacterial infection burden was greatest among patients with influenza and with elevated inflammatory markers in both ICU and non-ICU settings.\u003c/p\u003e \u003cp\u003eNotably, among patients with the lowest severity of illness, in whom bacterial infection was least likely, any antibiotic treatment was administered to 48.1% of patients and \u0026gt;\u0026thinsp;3 days of antibiotics were given to 20.8% of patients, suggesting antibiotic overtreatment. For this group of patients, clinicians could consider withholding or promptly deescalating antibiotics. In contrast, for patients with high severity of illness, it is appropriate to initiate empiric and/or targeted antibiotic treatment.\u003c/p\u003e \u003cp\u003eThe rates of antibiotic use seen in our study are similar to those reported in earlier, studies, suggesting that antibiotic prescribing practices have not changed in recent years despite greater provider and public awareness of the importance of antibiotic stewardship (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). We observed that the proportion of patients receiving antibiotics was highest for patients with influenza (\u0026gt;\u0026thinsp;60%) and lowest for patients with RSV (41%). Previous studies spanning over 20 years have noted antibiotic use in 49\u0026ndash;58% of children and adults diagnosed with influenza (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The antibiotic utilization percentage we observed among patients with RSV is also comparable to findings from previous studies, in which 33\u0026ndash;57% of children hospitalized with RSV who did not have a culture-confirmed bacterial infection were administered antibiotics (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile the low bacterial co-infection rate we observed is supported by recent adult and pediatric studies of patients with COVID-19, it contrasts with some earlier studies of influenza and RSV that reported higher bacterial co-infection rates of 27\u0026ndash;40% (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This discrepancy may be due to fact that some earlier studies defined bacterial co-infection largely based on positive bacterial culture results from non-sterile sites such as sputum or respiratory secretions and used bacterial colony count thresholds that are not validated for diagnosis of bacterial pneumonia (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Additionally, these studies found that \u003cem\u003eS. pneumoniae\u003c/em\u003e and \u003cem\u003eS. aureus\u003c/em\u003e, were the most commonly isolated bacterial pathogens among children with viral RTI (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Though growth of these organisms from respiratory specimens may have reflected bacterial co-infection in some patients, they may have reflected colonization of the respiratory tract in others (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatient demographic and clinical factors differed by virus type, which may have influenced medical management and could explain why antibiotic treatment differed by virus. Hospitalized patients with RSV were significantly younger and less likely to receive antibiotics than patients with influenza. Clinicians may have been more likely to avoid antibiotics in patients hospitalized with RSV because these children were most commonly infants with bronchiolitis and were not as acutely ill as the patients with influenza. This hypothesis is supported by the fact that ICU admission was more common among patients with RSV than patients with influenza, but rates of mechanical ventilation were similar between the groups, likely because many infants with RSV received supplemental oxygen but did not require mechanical ventilation.\u003c/p\u003e \u003cp\u003eWe determined that several variables were independent predictors for receipt of antibiotic treatment, including having influenza, requiring mechanical ventilation, and having elevated inflammatory markers. Antibiotic treatment of patients with influenza may stem from widespread clinician awareness of reports of influenza-associated Gram-positive bacterial pneumonia and the associated high mortality (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Mechanical ventilation is a predictor likely because it is a surrogate for severe illness in which antibiotic treatment may be warranted. High inflammatory markers is likely strongly associated with antibiotic treatment because of clinician confidence that these tests indicate bacterial infection. However, these tests, especially CRP, have low specificity and low positive predictive value (PPV) for bacterial infection and can be elevated in viral infections (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Providers should be wary about prescribing antibiotics based solely on the results of inflammatory markers, without consideration of the clinical context.\u003c/p\u003e \u003cp\u003eStrengths of our study are the large sample size, use of a stringent definition of bacterial co-infection, and evaluation of a contemporary cohort. Our study also has limitations, including its single center, retrospective nature, which may reduce its generalizability. However, our study corroborates findings of antibiotic overuse seen in earlier studies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Additionally, because bacterial pneumonia is not often confirmed by culture and we did not collect information about abnormal chest radiographs, we may have underestimated the occurrence of bacterial pneumonia. However, it is unlikely that almost half of patients (the proportion who received antibiotics) developed bacterial pneumonia after RTI (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). We identified subjects based on positive viral test results, determined symptomatic respiratory tract infection based on diagnosis codes, and did not confirm presence of respiratory symptoms through chart review. It is possible that antibiotic treatment was given for infections other than pneumonia (eg. acute otitis media), which we were not able to ascertain. In addition, antimicrobial stewardship interventions were inconsistently implemented throughout 2020 due to the COVID-19 pandemic.\u003c/p\u003e \u003cp\u003eDespite these limitations, we demonstrate in a contemporary cohort that unnecessary antibiotic use persists in hospital settings, as the antibiotic treatment burden far exceeds bacterial co-infections for children hospitalized with influenza, RSV, or COVID-19. Antibiotic stewardship programs should encourage clinicians to withhold or promptly deescalate antibiotics, particularly for children hospitalized with low severity of viral RTI, in whom bacterial infection is very rare and stewardship interventions may have higher acceptance.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eNot applicable. \u0026nbsp;This study was approved with a waiver of consent by the Vanderbilt University IRB (#232179).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u0026nbsp;\u003c/strong\u003eThe datasets generated and analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e M.K. is a\u0026nbsp;recipient of the Pediatric Infectious Diseases Society\u0026rsquo;s SUMMERS award.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e M.K. performed data collection and analysis and prepared the manuscript. N.J.T supervised data analysis. A.B.K. assisted with data collection and analysis of the patients with COVID-19. R.B supervised data collection, analysis, and manuscript preparation. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: \u0026nbsp;Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. N Engl J Med. 2009;360(6):588\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRha B, Curns AT, Lively JY, Campbell AP, Englund JA, Boom JA, et al. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015\u0026ndash;2016. Pediatrics. 2020;146(1):e20193611.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcLaughlin JM, Khan F, Schmitt HJ, Agosti Y, Jodar L, Sim\u0026otilde;es EAF, et al. Respiratory Syncytial Virus\u0026ndash;Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis. J Infect Dis. 2020;225(6):1100\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalik SS, Mundra S. Increasing Consumption of Antibiotics during the COVID-19 Pandemic: Implications for Patient Health and Emerging Anti-Microbial Resistance. Antibiot (Basel). 2022;12(1):45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoffitt KL, Nakamura MM, Young CC, Newhams MM, Halasa NB, Reed JN, et al. Community-Onset Bacterial Coinfection in Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Open Forum Infect Dis. 2023;10(3):ofad122.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVaughn VM, Gandhi TN, Petty LA, Patel PK, Prescott HC, Malani AN, et al. Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study. Clin Infect Dis. 2021;72(10):e533\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillon J, Garguilo K, LeBlanc K, Banerjee R. Antibiotic Overuse Among Children with COVID-19 Hospitalized in a Pediatric Intensive Care Unit. Open Forum Infect Dis. 2022;9(Supplement2):ofac492318.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWestblade LF, Simon MS, Satlin MJ. Bacterial Coinfections in Coronavirus Disease 2019. Trends Microbiol. 2021;29(10):930\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNitsch-Osuch A, Gyrczuk E, Wardyn A, Życinska K, Brydak L. Antibiotic Prescription Practices Among Children with Influenza. Adv Exp Med Biol. 2016;905:25\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Houten CB, Naaktgeboren C, Buiteman BJM, van der Lee M, Klein A, Srugo I, et al. Antibiotic Overuse in Children with Respiratory Syncytial Virus Lower Respiratory Tract Infection. Pediatr Infect Dis J. 2018;37(11):1077\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFinelli L, Fiore A, Dhara R, Brammer L, Shay DK, Kamimoto L, et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics. 2008;122(4):805\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhazaly M, Nadel S. Characteristics of children admitted to intensive care with acute bronchiolitis. Eur J Pediatr. 2018;177(6):913\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHishiki H, Ishiwada N, Fukasawa C, Abe K, Hoshino T, Aizawa J, et al. Incidence of bacterial coinfection with respiratory syncytial virus bronchopulmonary infection in pediatric inpatients. J Infect Chemother. 2011;17(1):87\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med. 2015;372(9):835\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThorburn K, Harigopal S, Reddy V, Taylor N, van Saene HKF. High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis. Thorax. 2006;61(7):611\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin HC, Liu YC, Hsing TY, Chen LL, Liu YC, Yen TY, et al. RSV pneumonia with or without bacterial co-infection among healthy children. J Formos Med Assoc. 2022;121(3):687\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHedberg P, Johansson N, Ternhag A, Abdel-Halim L, Hedlund J, Naucl\u0026eacute;r P. Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus. BMC Infect Dis. 2022;22(1):108.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMazzaglia G, Caputi AP, Rossi A, Bettoncelli G, Stefanini G, Ventriglia G, et al. Exploring patient- and doctor-related variables associated with antibiotic prescribing for respiratory infections in primary care. Eur J Clin Pharmacol. 2003;59(8\u0026ndash;9):651\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOchoa C, Eiros JM, Inglada L, Vallano A, Guerra L. Assessment of antibiotic prescription in acute respiratory infections in adults. The Spanish Study Group on Antibiotic Treatments. J Infect. 2000;41(1):73\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObolski U, Kassem E, Na\u0026rsquo;amnih W, Tannous S, Kagan V, Muhsen K. Unnecessary antibiotic treatment of children hospitalised with respiratory syncytial virus (RSV) bronchiolitis: risk factors and prescription patterns. J Glob Antimicrob Resist. 2021;27:303\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiegers HMG, van Nijen L, van Woensel JBM, Bem RA, de Jong MD, Calis JCJ. Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study. BMC Infect Dis. 2019;19(1):938.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson J. Colonization and infection of the respiratory tract: What do we know? Paediatr Child Health. 2004;9(1):21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRice TW, Rubinson L, Uyeki TM, Vaughn FL, John BB, Miller RR, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med. 2012;40(5):1487\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRandolph AG, Vaughn F, Sullivan R, Rubinson L, Thompson BT, Yoon G, et al. Critically ill children during the 2009\u0026ndash;2010 influenza pandemic in the United States. Pediatrics. 2011;128(6):e1450\u0026ndash;1458.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCenters for Disease Control and Prevention (CDC). Surveillance for pediatric deaths associated with 2009 pandemic influenza A (H1N1) virus infection - United States, April-August 2009. MMWR Morb Mortal Wkly Rep. 2009;58(34):941\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStaiano A, Bjerrum L, Llor C, Melbye H, Hopstaken R, Gentile I, et al. C-reactive protein point-of-care testing and complementary strategies to improve antibiotic stewardship in children with acute respiratory infections in primary care. Front Pediatr. 2023;11:1221007.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Ling L, Wong SH, Wang MH, Fitzgerald JR, Zou X, et al. Outcomes of respiratory viral-bacterial co-infection in adult hospitalized patients. EClinicalMedicine. 2021;37:100955.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"antibiotic overuse, influenza, RSV, COVID-19, viral respiratory tract infection","lastPublishedDoi":"10.21203/rs.3.rs-4614400/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4614400/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChildren hospitalized with viral respiratory tract infections (RTIs) are often prescribed antibiotics due to concern for bacterial co-infection, although most do not have concurrent bacterial infections. This unnecessary antibiotic treatment can lead to bacterial resistance and adverse events. The extent of antibiotic overuse in hospitalized children with community-onset viral RTIs has not been described in recent years. To identify antibiotic stewardship opportunities in this population, we quantified the extent of antibiotic overtreatment and determined predictors of antibiotic use among children hospitalized with influenza, respiratory syncytial virus (RSV), or SARS-CoV-2 (COVID-19).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a single-center retrospective study evaluating antibiotic use and culture-confirmed bacterial co-infection among children and adolescents hospitalized with influenza, RSV, or COVID-19 between April 2020 and May 2023. Predictors of antibiotic treatment were determined using logistic regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe included 1,718 patients (influenza: 188; RSV: 1,022; COVID-19: 535). Patients with RSV were younger and more likely to be in intensive care. Eight percent of patients had culture-confirmed bacterial co-infection. The proportion of children with culture-confirmed bacterial infection was low (8%) but the proportion receiving antibiotics was high and varied by virus (influenza: 60.6%, RSV:41.2%, COVID-19: 48.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Independent predictors for receipt of antibiotics were elevated inflammatory markers, mechanical ventilation, and influenza infection. Among patients with the lowest severity of illness, 48% received\u0026thinsp;\u0026ge;\u0026thinsp;1 dose of antibiotics.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn children hospitalized with community-onset viral RTIs, antibiotic treatment is substantially higher than the burden of culture-confirmed bacterial infection, especially for influenza, suggesting antibiotic overuse and antibiotic stewardship opportunities.\u003c/p\u003e","manuscriptTitle":"Antibiotic Overuse in a Contemporary Cohort of Children Hospitalized with Influenza, RSV, or SARS-CoV-2: A Retrospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 01:46:57","doi":"10.21203/rs.3.rs-4614400/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-26T07:48:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-26T07:00:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-26T06:59:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-06-21T02:27:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"76af45e9-8eed-4d69-b4b3-174d7c54078d","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:02:59+00:00","versionOfRecord":{"articleIdentity":"rs-4614400","link":"https://doi.org/10.1186/s12887-025-06165-8","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-10-03 15:57:39","publishedOnDateReadable":"October 3rd, 2025"},"versionCreatedAt":"2024-07-19 01:46:57","video":"","vorDoi":"10.1186/s12887-025-06165-8","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06165-8","workflowStages":[]},"version":"v1","identity":"rs-4614400","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4614400","identity":"rs-4614400","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}