Use of antimicrobials in pediatric wards of five Brazilian hospitals Thais de Barros Fernandes, Sheila Feitosa Ramos, Luísa Rodrigues Furtado Leitzke, Ronaldo Gomes Alexandre Júnior, Janaína Morais de Araújo, Alcidésio Sales de Souza Júnior, Alice Ramos Oliveira da Silva, Isabela Heineck, Marta Maria de França Fonteles, Louise E. Bracken, Matthew Peak, Divaldo Pereira de Lyra Junior, Claudia G S Osorio-de-Castro, Elisangela Costa Lima BMC Pediatrics, 2024 The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278–517) and LOT/1000PD (265–390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.
Adverse reactions to antimicrobials in pediatric patients admitted to a tertiary hospital: A cohort study Luísa Rodrigues Furtado Leitzke, Gabriele Lenhart, Allan Lemos Rocha, Samantha Zamberlan, Diego Gnatta, Elisangela da Costa Lima, Isabela Heineck European Journal of Hospital Pharmacy, 2024 BACKGROUND: Antimicrobials are widely used in hospitals and are often associated with adverse drug reactions (ADRs). The objective of this study was to determine the incidence of ADRs caused by antimicrobials and classify them according to the type of reaction, the class of antimicrobials used, causality, severity and avoidability. METHODS: A prospective cohort study was carried out with paediatric patients for 6 months. Causality was verified using the Naranjo and Liverpool algorithms, the severity was verified with the adapted scale of Hartwig and the avoidability was verified with the Liverpool Avoidability Assessment Tool. RESULTS: A total of 303 patients were followed, and 18.2% (55/303) of them had one or more ADRs during the hospital stay. Just over half of the patients (28/55) had diarrhea. The most used antimicrobials were beta-lactams and second-generation cephalosporins. Suspicions were classified mainly as possible 78.6% (55/70) according to the Naranjo algorithm, and as probable 48.6% (34/70) according to the Liverpool algorithm. The antimicrobial most involved with ADRs was cefepime. The risk of manifesting ADR was greater with the use of some antimicrobials such as clindamycin (relative risk (RR) 3.0, CI 1.67 to 5.4), as well as with the increase in hospitalisation days (OR 1.022, CI 1.008 to 1.036) and in the number of antimicrobials prescribed (OR 1.649, CI 1.360 to 2.001). CONCLUSION: ADRs were observed in approximately one-fifth of patients and were mostly gastrointestinal, moderate, unavoidable and with variable causality, depending on the algorithm used.
Moderate and serious adverse reactions to antimicrobials among hospitalized children: A systematic review Sheila Feitosa Ramos, Letícia Gomes do Sacramento, Rafaella Oliveira Santos de Silva, Giulyane Targino Aires‐Moreno, Jonas dos Santos Gomes, Alessandra Rezende Mesquita, Elisangela Costa Lima, Divaldo Pereira de Lyra British Journal of Clinical Pharmacology, 2024 AimsThis systematic review aimed to investigate the occurrence of moderate and severe adverse drug reactions (ADRs) to antimicrobials among hospitalized children.MethodsThe PubMed/Medline, Cochrane Library, Embase, Web of Science, Scopus, Lilacs and CINAHL databases were searched in April 2023 to systematically review the published data describing the characteristics of moderate and severe ADRs to antimicrobials among hospitalized children. The search was carried out without date restrictions, up to the search date (April, 2023).ResultsAt the end of the selection process, 30 articles met the inclusion criteria. Cutaneous reactions were the primary serious clinical manifestations in most articles (19/30), followed by erythema multiforme (71 cases), Stevens–Johnson syndrome (72 cases), and toxic epidermal necrolysis (22 cases). The main antimicrobials involved in moderate and severe ADRs were penicillins, cephalosporins and sulfonamides. Regarding the primary outcomes, 30% (9/30) of the articles reported deaths, and 46.7% (14/30) of studies reported increased lengths of hospital stay, need for intensive care, and transfer to another hospital. Regarding the main interventions, 10% (3/30) of the articles mentioned greater monitoring, suspension, medication substitution or prescription of specific medications for the symptomatology.ConclusionsThe findings of this review could be used to identify areas for improvement and help health professionals and policymakers develop strategies. In addition, we emphasize the importance of knowing about ADRs so that there is adequate management to avoid undesirable consequences.
Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use—A Narrative Review Valcieny Sandes, Albert Figueras, Elisangela Costa Lima Antibiotics, 2024 The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness, resistance, and inappropriate use of antibiotics (ABs). The terms “drug ineffective”, “therapeutic failure”, “drug resistance”, “pathogen resistance”, and “multidrug resistance” were found in PV databases and dictionaries, denoting ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors”, especially those related to dose and indication, and “Off-label use” are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR and use are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.
Data quality review of the Brazilian nosocomial infections surveillance system Alice Ramos Silva, Nicolas Guedes Hoffmann, Fernando Fernandez-Llimos, Elisangela Costa Lima Journal of Infection and Public Health, 2024 BACKGROUND: Surveillance of healthcare-associated infections (HAIs) is an essential component of hospital infection prevention and control systems. We aimed to assess the quality of the data compiled by the Brazilian HAI Surveillance System from pediatric (PICUs) and neonatal intensive care units (NICUs), between 2012 and 2021. METHODS: Data Quality Review, including adherence, completeness, internal consistency, consistency over time, and consistency of population trend, were computed at both national and state levels based on quality metrics from World Health Organization Toolkit. Incidence rates (or incidence density) of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) were obtained from the Brazilian National Nosocomial Infections Surveillance (NNIS) system. Data on sepsis-related mortality, spanning the period from 2012 to 2021, were extracted from the Brazilian National Health Service database (DATASUS). Additionally, correlations between sepsis-related mortality and incidence rates of VAP or CLABSI were calculated. RESULTS: Throughout the majority of the study period, adherence to VAP reporting remained below 75%, exhibiting a positive trend post-2016. Widespread outliers, as well as inconsistencies over time and in population trends, were evident across all 27 states. Only four states maintained consistent adherence levels above 75% for more than 8 years regarding HAI incidence rates. Notably, CLABSI in NICUs boasted the highest reporting adherence among all HAIs, with 148 periods out of 270 (54.8%) exhibiting reporting adherence surpassing 75%. Three states achieved commendable metrics for CLABSI in PICUs, while five states demonstrated favorable results for CLABSI in NICUs. CONCLUSIONS: While adherence to HAI report is improving among Brazilian states, an important room for improvement in the Brazilian NNIS exists. Additional efforts should be made by the Brazilian government to improve the reliability of HAI data, which could serve as valuable guidance for hospital infection prevention and control policies.
Detection of potential safety signals related to the use of remdesivir and tocilizumab in the COVID era during pregnancy, resorting to open data from the FDA adverse event reporting system (FAERS) Beatriz Marinho Silva Romão, Felipe Vieira Duval, Elisângela Costa Lima, Fabrício Alves Barbosa da Silva, Guacira Correa de Matos Frontiers in Pharmacology, 2024 Background: The in-hospital treatment for COVID-19 may include medicines from various therapeutic classes, such as antiviral remdesivir and immunosuppressant tocilizumab. Safety data for these medicines are based on controlled clinical trials and case reports, limiting the knowledge about less frequent, rare or unique population adverse events excluded from clinical trials.Objective: This study aims at analyzing the reports of Adverse Drug Events (ADEs) related to these two medicines, focusing on events in pregnant women and foetuses.Methods: Data from the open-access FDA Adverse Event Reporting System (FAERS) from 2020 to 2022 were used to create a dashboard on the Grafana platform to ease querying and analyzing report events. Potential safety signals were generated using the ROR disproportionality measure.Results: Remdesivir was notified as the primary suspect in 7,147 reports and tocilizumab in 19,602. Three hundred and three potential safety signals were identified for remdesivir, of which six were related to pregnant women and foetuses (including abortion and foetal deaths). Tocilizumab accumulated 578 potential safety signals, and three of them were associated with this population (including neonatal death).Discussion: None of the possible signals generated for this population were found in the product labels. According to the NIH and the WHO protocols, both medicines are recommended for pregnant women hospitalized with COVID-19.Conclusion: Despite the known limitations of working with open data from spontaneous reporting systems (e.g., absence of certain clinical data, underreporting, a tendency to report severe events and recent medicines) and disproportionality analysis, the findings suggest concerning associations that need to be confirmed or rejected in subsequent clinical studies.
Root cause analysis of safety incidents in antineoplastic use in children Elizangela Domiciano Garcia Barreto, Valcieny Souza Sandes, Gustavo Cattelan Nobre, Monica Martins, Sima Esther Ferman, Elisangela Costa Lima Revista Brasileira De Enfermagem, 2024 Objectives: to identify and analyze the factors that contribute to safety incident occurrence in the processes of prescribing, preparing and dispensing antineoplastic medications in pediatric oncology patients. Methods: a quality improvement study focused on oncopediatric pharmaceutical care processes that identified and analyzed incidents between 2019-2020. A multidisciplinary group performed root cause analysis (RCA), identifying main contributing factors. Results: in 2019, seven incidents were recorded, 57% of which were prescription-related. In 2020, through active search, 34 incidents were identified, 65% relating to prescription, 29% to preparation and 6% to dispensing. The main contributing factors were interruptions, lack of electronic alert, work overload, training and staff shortages. Conclusions: the results showed that adequate recording and application of RCA to identified incidents can provide improvements in the quality of pediatric oncology care, mapping contributing factors and enabling managers to develop an effective action plan to mitigate risks associated with the process.
Use of second-generation antipsychotics in autism spectrum disorder: a systematic review and meta-analysis protocol Luis Phillipe Nagem Lopes, Jardel Corrêa de Oliveira, Cristiane de Cássia Bergamaschi, Izabela Fulone, Elisangela da Costa Lima, Flávia Casale Abe, Lauren Giustti Mazzei, Mabel Fernandes Figueiró, Luciane Cruz Lopes BMJ Open, 2023 IntroductionAtypical antipsychotics have been studied to treat autism spectrum disorder (ASD). However, like little is known about whether these drugs are effective and safe when compared in controlled and non-controlled settings. This study aims to assess the efficacy and safety of second-generation antipsychotics in ASD in randomised controlled trials (RCT) and observational studies.Methods and analysisThis systematic review will include RCT and prospective cohorts evaluating second-generation antipsychotics in people 5 years and older diagnosed with ASD. Searches will be conducted in Medline, Embase, Cochrane Library, Epistemonikos, Lilacs, CINAHL, PsycINFO, trial registries and grey literature databases without restriction on publication status, year of publication and language. The primary outcomes will be symptoms of aggressive behaviour, quality of life for the individual or their careers, and discontinuation or dropouts/withdrawals of antipsychotics due to adverse events. The secondary outcomes are other not serious adverse events and adherence to pharmacotherapy. Selection, data extraction, and quality assessment will be performed by pairs of reviewers, independently. The Risk of Bias 2 (RoB 2) and Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tools will be used to assess the risk of bias in the included studies. If appropriate, a meta-analysis and network meta-analysis will be conducted to synthesise the results. The overall quality of the evidence for each outcome will be determined by the Recommendation, Assessment, Development and Evaluation approach.Ethics and disseminationThis study will systematically summarise the existing evidence evaluating the use of second-generation antipsychotics for treating ASD, in controlled and uncontrolled studies. The results of this review will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42022353795.
Geographical variation in antimicrobial use and multiresistant pathogens in Brazilian intensive care units: a nationwide study Alice Ramos Oliveira Silva, Constanza Xavier Borges Barbosa, Raianne Soares Rebelo, Fernando Fernandez-Llimos, Elisangela Costa Lima Journal of Infection in Developing Countries, 2023 Introduction: Geographical analyses of antibiotic use identify regions with the highest consumption and help design policies for strategic patient groups. Methodology: We conducted a cross-sectional study based on official data available in July 2022 from Brazilian Health Surveillance Agency (Anvisa). Antibiotics are reported as a defined daily dose (DDD) per 1,000 patient-days, and central line-associated bloodstream infection (CLABSI) is defined according to Anvisa criteria. We also considered multi-drug resistant (MDR) as the critical pathogens the World Health Organization listed. We measured antimicrobial use and CLABSI trends per ICU bed using the compound annual growth rate (CAGR). Results: we evaluated the regional variation in CLABSI by multidrug-resistant pathogens and the antimicrobial use in 1,836 hospital intensive care units (ICUs). In 2020, the leader in use in intensive care units (ICUs) in the North was piperacillin/tazobactam (DDD = 929.7) in the Northeast. Midwest and South were meropenem (DDD = 809.4 and DDD = 688.1, respectively), and Southeast was ceftriaxone (DDD = 751.1). The North has reduced polymyxin use (91.1%), and ciprofloxacin increased (439%) in the South. There was an increase in CLABSI by carbapenem-resistant Pseudomonas aeruginosa in the North region (CAGR = 120.5%). Otherwise, CLABSI by vancomycin-resistant Enterococcus faecium (VRE) increased in all regions except the North (CAGR = -62.2%), while that carbapenem-resistant Acinetobacter baumannii increased in the Midwest (CAGR = 27.3%). Conclusions: we found heterogeneity in antimicrobial use patterns and CLABSI etiology among Brazilian ICUs. Although Gram-negative bacilli were the primary responsible agent, we observed a notable increase trend of CLABSI by VRE.
Adverse Drug Reactions to Anti-infectives in Hospitalized Children: A Multicenter Study in Brazil Sheila Feitosa Ramos, Thais de Barros Fernandes, Dyego Carlos Araújo, Luísa Rodrigues Furtado Leitzke, Ronaldo Gomes Alexandre Júnior, Janaína Morais de Araújo, Alcidésio Sales de Souza Júnior, Isabela Heineck, Marta Maria de França Fonteles, Claudia G S Osorio-de-Castro, Louise E Bracken, Matthew Peak, Divaldo Pereira de Lyra Junior, Elisangela Costa Lima Journal of the Pediatric Infectious Diseases Society, 2023 IntroductionAdverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems.ObjectiveTo assess ADRs associated with anti-infective use in Brazilian hospitalized children.MethodsA prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0–11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included.ResultsA total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001).ConclusionAlmost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.
Data sources for drug utilization research in Latin American countries—A cross-national study: DASDUR-LATAM study Luciane C. Lopes, Maribel Salas, Claudia Garcia Serpa Osorio‐de‐Castro, Lisiane Freitas Leal, Svetlana V. Doubova, Martín Cañás, Anahi Dreser, Angela Acosta, Andre Oliveira Baldoni, Cristiane de Cássia Bergamaschi, Daniel Marques Mota, Diana L. Gómez‐Galicia, Dino Sepúlveda‐Viveros, Edgard Narvaez Delgado, Elisangela da Costa Lima, Felipe Vera Chandia, Felipe Ferre, Gustavo H. Marin, Ismael Olmos, Ivan R. Zimmermann, Izabela Fulone, Juan Roldán‐Saelzer, Juan Carlos Sánchez‐Salgado, Lucila I. Castro‐Pastrana, Luiz Jupiter Carneiro de Souza, Manuel Machado Beltrán, Marcus Tolentino Silva, María Belén Mena, Marta Maria de França Fonteles, Martín A. Urtasun, Mónica Tarapués, Patricia Granja Hernández, Natalia Medero, Raquel Herrera‐Comoglio, Silvio Barberato‐Filho, Taís Freire Galvão, Vera Lucia Luiza, Yared Santa‐Ana‐Tellez, Yesenia Rodríguez ‐ Tanta, Monique Elseviers Pharmacoepidemiology and Drug Safety, 2022
Data Sources for Drug Utilization Research in Brazil—DUR-BRA Study Lisiane Freitas Leal, Claudia Garcia Serpa Osorio-de-Castro, Luiz Júpiter Carneiro de Souza, Felipe Ferre, Daniel Marques Mota, Marcia Ito, Monique Elseviers, Elisangela da Costa Lima, Ivan Ricardo Zimmernan, Izabela Fulone, Monica Da Luz Carvalho-Soares, Luciane Cruz Lopes Frontiers in Pharmacology, 2022
Challenges facing drug utilization research in the Latin American region Maribel Salas, Luciane C. Lopes, Brian Godman, Ilse Truter, Abraham G. Hartzema, Bjorn Wettermark, Joseph Fadare, Johanita R. Burger, Kwame Appenteng, Macarius Donneyong, Ariel Arias, Daniel Ankrah, Olayinka O. Ogunleye, Martha Lubbe, Laura Horne, Jorgelina Bernet, Diana L. Gómez‐Galicia, Miriam del Carmen Garcia Estrada, Margaret N. Oluka, Amos Massele, Luis Alesso, Raquel Herrera Comoglio, Elisangela da Costa Lima, Carmen Vilaseca, Ulf Bergman Pharmacoepidemiology and Drug Safety, 2020
Predictive factors for sepsis by carbapenem resistant Gram-negative bacilli in adult critical patients in Rio de Janeiro: A case-case-control design in a prospective cohort study Elisangela M. Lima, Patrícia A. Cid, Debora S. Beck, Luiz Henrique Z. Pinheiro, João Pedro S. Tonhá, Marcio Z. O. Alves, Newton D. Lourenço, Roberto Q. Santos, Marise D. Asensi, José Aurélio Marques, Carolina S. Bandeira, Caio Augusto S. Rodrigues, Saint Clair S. Gomes Junior, Marisa Z. R. Gomes, the Nucleus of Hospital Research study collaborators, Glória Regina A. A. Magalhães, Priscila P. Silva, Scyla Maria S. A. S. Reis Di Chiara, Amanda Aparecida S. Machado, Thaisa M. Tozo, Lucas Lameirão P. A. Rosas, Paulo C. M. Barros, Wania V. de Freitas, Ana Paula D. C. Assef Antimicrobial Resistance and Infection Control, 2020
Phytotherapy as an integrative and complementary practice: investigation of the risk of herb-drug interactions with Diabetes mellitus type II treatment Revista Brasileira De Plantas Medicinais, 2020
An ontology of pharmaceutical services in the pages of Journal Ciência & Saúde Coletiva Claudia Garcia Serpa Osorio-de-Castro, Tatiana de Jesus Nascimento Ferreira, Mario Jorge Sobreira da Silva, Elaine Silva Miranda, Cristiane Roberta dos Santos Teodoro, Elaine Lazzaroni Moraes, Elisangela da Costa Lima, Cláudia Du Bocage Santos-Pinto Ciencia E Saude Coletiva, 2020
Natural products for dengue transmission control - Larvicidal activity of Myroxylon balsamum (red oil) and of terpenoids and phenylpropanoids Quimica Nova, 2004
