key: cord-0763604-s0w37vx5 authors: Yock‐Corrales, Adriana; Lenzi, Jacopo; Ulloa‐Gutiérrez, Rolando; Gómez‐Vargas, Jessica; Antúnez‐Montes, Omar Yassef; Rios Aida, Jorge Alberto; del Aguila, Olguita; Arteaga‐Menchaca, Erick; Campos, Francisco; Uribe, Fadia; Parra Buitrago, Andrea; Maria Betancur Londoño, Lina; Brizuela, Martin; Buonsenso, Danilo title: High rates of antibiotic prescriptions in children with COVID‐19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America date: 2021-03-26 journal: Acta Paediatr DOI: 10.1111/apa.15847 sha: c2577a3289529122668c3ac9a5395477d6fcd52d doc_id: 763604 cord_uid: s0w37vx5 AIM: This study aims to assess rates of antibiotic prescriptions and its determinants in in children with COVID‐19 or Multisystem Inflammatory Syndrome (MIS‐C). METHODS: Children <18 years‐old assessed in five Latin Americas countries with a diagnosis of COVID‐19 or MIS‐C were enrolled. Antibiotic prescriptions and factors associated with their use were assessed. RESULTS: A total of 990 children were included: 921 (93%) with COVID‐19, 69 (7.0%) with MIS‐C. The prevalence of antibiotic use was 24.5% (n = 243). MIS‐C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X‐rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals. CONCLUSION: Our study showed a high rate of antibiotic prescriptions in children with COVID‐19, in particular in those with severe disease or MIS‐C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID‐19 children. YOCK-CORRALES Et AL. Months after the first description of COVID-19 in China, growing evidence is raising about the impact of SARS-CoV-2 infection on the pediatric population. Several studies from China, 1 Europe, 2,3 United States 4 and Latin America 5 are clarifying that COVID-19 in children is typically mild, although patients with medically complex conditions or those of minority race/ethnicity deserve more attention because they may be at risk of more severe disease. 4 The Multisystem Inflammatory Syndrome (MIS-C), an entity not yet fully clarified related to SARS-CoV-2, is a severe complication of the exposition to the virus, which may require Intensive Care Admission, mechanical ventilation and cardio-respiratory support, rarely leading to death. 6 This clinical syndrom is characterized, by fever, systemic inflammation, and multisystem involvement, most commonly abdominal and cardiac, apparently driven by an uncontrolled immune response activated by the virus, where specific immune cells and autoantibodies can play a role. 7 This scenario overlaps also the toxic shock syndrome related with Staphylococcus aureus and other bacteria, making the clinical differential diagnosis difficult. Because SARS-CoV-2 is a viral infection, and the resulting disease is usually mild in children, it is not expected that a child with COVID-19 would routinely receive antimicrobials. This is particularly true for the second period of the pandemic, when the non-utility of azithromycin, initially suggested as a drug with potential anti-viral properties, 8 has been showed. 9 The MIS-C can be an exception to this concept, since the severe and acute presentation may be similar to the toxic-shock syndrome and available consensus documents suggest empiric widespectrum antibiotic therapy until bacterial infections are ruled-out. 10 Nevertheless, there are growing concerns about the possible negative impact of the pandemic on antimicrobial use. While this is particularly discussed for adults with COVID-19, 11 Velasco-Arnaiz et al 12 reported preliminary data suggesting that the pandemic has the potential to have a significant impact on antimicrobial use in the pediatric inpatient population. They did assess antibiotic prescriptions during and before the pandemic, but did not assess directly antibiotic use and its determinants in COVID-19 children. Since cases are constantly raising worldwide, it is expected that SARS-CoV-2 will circulate still for a long time, therefore the appropriate management of children with COVID-19 is a priority. While the pandemic only determined a limited direct impact on children, inappropriate prescriptions have the potential of worsening an already dangerous situation, i.e. antimicrobial resistance. Due to the gap in available literature, we performed a multinational study in Latin America aiming to assess the use of antibiotics in children with COVID-19 and understand the determinants of its use. This study is part of an ongoing independent project assessing COVID-19 and MIS-C in Latin American children, already presented elsewhere 13 and with a previous published paper describing an initial group of 409 children with confirmed COVID-19. 5 For the current study, we aimed to assess determinants of antibiotic use in children with COVID-19 or with MIS-C. We implemented the previously used dataset 2,5 including data regarding name of antibiotic used and the reason why the attending clinician decided to administer antibiotics. The remaining variables are those previously used and included age, gender, symptoms, imaging, underlying medical conditions, need for hospital and NICU/PICU admission, respiratory and cardiovascular support, other viral coinfections, drugs used to treat COVID-19, development of MIS-C and type of organ involvement, and outcome. (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals. Our study showed a high rate of antibiotic prescriptions in children with COVID-19, in particular in those with severe disease or MIS-C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID-19 children. The study was conducted in accordance with the Declaration of Helsinki and its amendments. No personal or identifiable data were collected during the conduct of this study. Summary statistics for the study sample were presented as counts and percentages. The association of relevant demographic and clinical characteristics with antibiotic use was assessed using a multivariable logistic regression model; the effect size of covariates was expressed by odds ratios (ORs) with 95% confidence intervals (CIs). The variables considered in this analysis were age, sex, medical history of immunodeficiency, immunosuppressants or chemotherapy, hospital care, pyrexia, upper and lower respiratory tract infections, gastrointestinal symptoms, headache, chest X-ray abnormalities, respiratory support, administration of systemic corticosteroids, and diagnosis of MIS-C, both with and without cardiac involvement. A set of dummy variables for individual hospitals was also included in the model to adjust for the potential bias of confounding by center. All data were analyzed using the Stata 15 software (StataCorp. 2017. Stata Statistical Software: Release 15. StataCorp LLC). The significance level was set at 5% and all tests were 2-sided. The prevalence of antibiotic use was 24.5% (n = 243). As shown in Figure 1 , sepsis was the most common reason for administering antibiotics (22.6%), followed by pneumonia (13.6%), surgical causes (11.5%) and upper or mild respiratory infections (9.5%). Information about the classes of antibiotics used was available for 153 (63.0%) patients. Among the 84 patients that received single antibiotic therapies, 32 (13.2%) were prescribed ceftriaxone, 13 (5.3%) azithromycin, 10 (4.1%) cefotaxime, 9 (3.7%) amoxicillin, 6 (2.5%) clindamycin, 2 (0.8%) ampicillin, 2 (0.8%) cefalexine, 2 (0.8%) cefalotin, 2 (0.8%) cefepime, 2 (0.8%) trimethoprim, and the remaining 4 (1.6%) ami- On multivariable analysis (Table 2) In conclusion, our study showed a high rate of antibiotic pre- We are grateful to all collaborators that helped the development of the DOMINGO study group. Nothing to declare. Approved by each institution (codes provided in methods). The dataset generated for this study is available upon request to the corresponding author. 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Clinical management of COVID-19 COVID-19: don't neglect antimicrobial stewardship principles! Understanding the mechanisms and drivers of antimicrobial resistance The unrecognized threat of secondary bacterial infections with COVID-19 How to cite this article: Yock-Corrales A High rates of antibiotic prescriptions in children with COVID-19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America