key: cord-1027457-6b90z422 authors: Craig, Jessica; Frost, Isabel; Sriram, Aditi; Nuttall, James; Kapoor, Geetanjali; Alimi, Yewande; Varma, Jay K. title: Development of the first edition of African treatment guidelines for common bacterial infections and syndromes date: 2022-01-13 journal: J Public Health Afr DOI: 10.4081/jphia.2021.2009 sha: 0782e90c3250ea56e2d92692b0829517f8cf9c4c doc_id: 1027457 cord_uid: 6b90z422 Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines – including drug selection, route of administration, formulation, dosage, and therapy duration – and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines. Antimicrobial resistance (AMR) poses a significant and rapidly emerging public health challenge in Africa and around the world. [1] [2] [3] In many countries, drug-resistant infections have been associated with longer hospital stays, increased morbidity and mortality, and higher healthcare costs. [4] [5] [6] Despite the challenge, antimicrobial stewardship (AMS) solutions are not widespread. [7] [8] [9] [10] Standard treatment guidelines (STGs) are one important tool in ensuring high quality clinical care and prudent antimicrobial use, alongside other AMS and educational efforts. 11, 12 STGs, when developed and used properly, help clinicians prescribe the right antimicrobial for the right condition, ensuring that the selection, dosage, and duration align with local epidemiology, AMR prevalence, laboratory and other diagnostic capacities, and pharmaceutical availability. A 2019 study conducted in Norway found that adherence to national antibiotic guidelines was associated with favorable patient outcomes, including reduced mortality rates and length of hospital stay among inpatients. 13 In 2018, African Union (AU) member state representatives and stakeholders recognized the lack of STGs as a barrier to AMR mitigation and AMS efforts and identified the development of STGs as a priority activity. A previous review of existing STGs in AU member states identified only 28 relevant guidelines (excluding those that covered only treatment of HIV, malaria, and tuberculosis) from 17 of 55 (31%) member states that provided disease-or pathogenspecific antimicrobial treatment recommendations including drug selection, dosage, and therapy duration. 14 Of those, only 15 guidelines from 10 countries were developed or updated in the past five years. No identified guideline described their methodologies or adhered to standardized methodologies such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and few stated that they were based on local infectious disease epidemiology or AMR data. A comparison of the antimicrobial selection, dosage, and therapeutic duration set forth by the identified guidelines found wide variation including instances where for certain infections some guidelines recommended antimicrobial therapy and others discouraged antimicrobial therapy altogether. Given the lack of STGs in AU member states and to promote better quality healthcare and AMS across the continent, we convened expert panels to develop a first edition of African antibiotic treatment guidelines for priority infectious diseases and The development of the guidelines was led by a steering committee composed of six physicians, epidemiologists, and public health researchers from the Africa Centres for Disease Control and Prevention (CDC) and the Center for Disease Dynamics, Economics & Policy (CDDEP). The steering committee was responsible for managing the overall guidelines development project, assembling the expert panels, drafting and finalizing the guidelines, coordinating internal and external review, and disseminating the guidelines. The steering committee also drafted methodologies for the guideline development project including for convening an expert panel review, generating consensus treatment recommendations, and disseminating the findings. Finally, the committee conducted reviews for existing AMR data and national STGs from AU member states and synthesized the data into reports for expert panel review and to inform aspects of guidelines development, such as drug and formulation availability, preferred treatment paradigms in various countries, and drug selection in settings with high AMR prevalence rates. Results of both reviews have been submitted for publication. 14, 15 Briefly, the paucity of locally derived data about AMR prevalence meant that such data had little impact on panel decision-making. The steering committee invited physicians, pharmacists, and other relevant experts involved in diagnosing and treating infectious diseases and/or prescribing antimicrobials to participate in one of two guidelines development panels. In selecting participants, the steering committee strove to represent each African region and balance gender. The first panel consisted of nine expert clinicians representing each African region (per the United Nations) and seven countries (Northern: Egypt; Southern: South Africa; Eastern: Kenya, Zambia; Middle: Republic of the Congo; Western: Ghana, Senegal) and convened in August 2019 at AU headquarters in Addis Ababa, Ethiopia to develop treatment recommendations for adult patient populations. 16 The second panel, composed of 19 experts representing each African region and 12 countries (Northern: Egypt; Southern: South Africa; Eastern: Ethiopia, Kenya, Mozambique, Tanzania, Uganda; Middle: Gabon; Western: Gambia, Ghana, Nigeria, Senegal), convened in October 2020 via virtual webinar (due to the SARS-CoV-2 pandemic) to develop treatment recommendations for pediatric patient populations. The panels reviewed and finalized the methodology prepared by the steering committee and results of the committee's analysis of existing AMR data and STGs in Africa. The panels also established a standardized format for presenting the treatment recommendations and clinical guidance. The panels were tasked with selecting infections and clinical syndromes for inclusion in the first edition guidelines. For each selected infection or syndrome, each panel set forth treatment recommendations which included antibiotic selection, dosage, and duration and principles of stewardship and other clinical notes, as applicable. Preferred and alternative antibiotic choices were discussed and provided, as needed, as were treatment recommendations for special cases such as in case of confirmed allergy or medical contra-indication. The treatment recommendations were developed through round-table discussions, led by the panel chair, and were finalized by consensus. Draft guidelines and methodologies were developed and disseminated to panelists for review and approval prior to external review. Once final drafts of the guidelines were developed, we posted them on the Africa CDC website and used social media and existing e-mail list servs to request comment from people with relevant expertise. Additional clinicians based in Africa were identified through a web search and literature review and were sent targeted e-mails inviting them to review the guidelines. At least two clinicians from each African country were contacted, while additional experts were contacted in under-represented countries and regions including central and francophone West African countries. The final guidelines were compiled into a single report and into two quick reference guides, one each for adult and pediatric patient populations, and translated into all official AU languages: Arabic, French, Portuguese, and Spanish. [17] [18] [19] A user-friendly website displaying the treatment recommendations and other information about the guidelines development process is now available at https://africacdc.org/africanantibiotic-treatment-guidelines-for-common-bacterial-infections-and-syndromes/ and at https://africaguidelines.cddep.org/; the guidelines report and quick reference guides are also available for download. Ethics approval was not required for this study as no human subjects research was conducted, and all data utilized was in the public domain. Panelists were required to report any potential conflicts of interest including intellectual property and financial ties to pharmaceutical companies before participation. The first-convened panel agreed to focus on empiric antibiotic therapy guidelines, because appropriate specimen collection and diagnostic testing to identify causative pathogens is not universally available in Africa. Therefore, the panel sought to provide appropriate antibiotic choice(s) to treat an infection for which a specific etiological diagnosis has not been made, targeting the most likely pathogen(s) with the narrowest-spectrum, single antibiotic whenever possible while also accounting for the likelihood of antibiotic resistance, potential medical contraindications (i.e. allergies, pregnancy) and target tissue penetration. The panel elected to limit the scope of the first edition guidelines to include only common bacterial infections and syndromes; therefore, this scope was maintained during the second panel convening. The guidelines set forth recommended antibiotic therapies for 28 infections or clinical syndromes; 11 are common to both adult and pediatric patient populations including acute, community-acquired bacterial meningitis; acute otitis media; bacterial pharyngotonsillitis; dental abscess; infective endocarditis; acute diarrheal dis-Article Article Clinical definition: Inflammation of meninges of the brain and spinal cord. Clinical features may be non-specific in neonates and young infants (e.g. poor feeding, apathy, jaundice, apnoea, full fontanelle, fever, hypothermia) and in older infants may include irritability, drowsiness, poor feeding, high fever, and/or vomiting. Older children may present similarly to adults with headache, fever, photophobia, vomiting, neck stiffness, and/or altered level of consciousness. [ The guidelines include an introductory section with general principles of stewardship and instructions for guideline use. Pediatric and adult treatment recommendations are presented in separate sections and are organized by the following body system or grouping classifications: Central nervous system; head, eye, ear, nose, and throat; cardiac; respiratory; gastrointestinal; genitourinary; skin, soft tissue, bone and joints; and bloodstream. Pediatric treatment guidelines including those for neonates, children, and adolescents are presented together with subheadings indicating their applicability to each of the sub-patient populations, as applicable (Table 1) . Neonatal and pediatric age groups are defined as follows: Neonateless than 28 days old or if born prematurely, less than 42 weeks corrected gestational age; Infant-less than 1 year of age; Childless than 10 years of age; and adolescent-10 to 19 years of age. Treatment guidelines for each bacterial infection or syndrome are presented with the following information, as applicable: Clinical definition including common symptoms and causative microorganisms, preferred and alternative antibiotic choices, antibiotic choice in case of confirmed drug allergy or medical contraindication or in other specific circumstances, principles of stewardship, and other clinical notes ( Table 2) . Antibiotic choices include drug selection, route of administration, formulation, dosage, and duration. Drug formulations were obtained from the 2019 WHO Model List of Essential Medicines (MLEM,1 st list) and the 2019 WHO MLEM for Children (7 th list); for those drug formulations that were not listed in the WHO MLEMs or where the MLEMs listed a formulation not widely available in certain African countries, drug formulations were proposed by panelists or obtained from national Essential Medicines Lists or other relevant documents. 20,21 The purpose of these first edition guidelines is to provide African healthcare workers with expert recommendations for antimicrobial prescription and use including drug selection, dosage, and duration of treatment for neonatal, pediatric, and adult patient populations to improve clinical practice and promote antimicrobial stewardship. In addition, these guidelines set forth a methodology for continuous development and updating and serve as a model for other countries and/or facilities to develop their own future national guidelines. In developing these first edition guidelines and reviewing existing STGs, critical limitations and knowledge gaps emerged. First, the paucity of publicly available data on facility-level, national, or regional pathogen-specific infectious disease burden and AMR prevalence prevented these from being major considerations in infection/syndrome selection and drug selection and may represent a major limitation to their effective use. A detailed understanding of antimicrobial agent and formulation availability, including ease of access and cost considerations, at different healthcare facility levels in each AU country was also not available and may impact usability of the guidelines in certain settings. Finally, the expert panelists and external reviewers represented only a fraction of clinical care specialties and AU member states across the continent; future editions should aim to be more inclusive of non-physician clinical personnel such as nurses and community health workers. Antimicrobial resistance: a global multifaceted phenomenon The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report: Early Implementation 2020 Antimicrobial Resistance: Implications and Costs Multiple antibiotic resistance as a risk factor for mortality and prolonged hospital stay: A cohort study among neonatal intensive care patients with hospital-acquired infections caused by gram-negative bacteria in Vietnam Costs and Outcomes of 1-year post-discharge care trajectories of patients admitted with infection due to antibiotic-resistant bacteria Ashiru-Oredope D. Implementation of antimicrobial stewardship programmes in African countries: a systematic literature review Antimicrobial stewardship -can we afford to do without it? Antimicrobial stewardship across 47 South African hospitals: an implementation study Investigating the cultural and contextual determinants of antimicrobial stewardship programmes across low-, middle-and high-income countries-A qualitative study The Core Elements of Hospital Antibiotic Stewardship Programs Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach The association between adherence to national antibiotic guidelines and mortality, readmission ] and length of stay in hospital inpatients: results from a Norwegian multicentre, observational cohort study Comparison of national antimicrobial treatment guidelines, African Union The burden of antibiotic resistant bacterial pathogens among neonates and children in Africa: A systematic review and meta-analysis United Nations Statistics Division. Geospatial information, Methodology. 2022 African Antibiotic Treatment Guidelines for Common Bacterial Infections and Syndromes-First Edition African Antibiotic Treatment Guidelines for Common Bacterial Infections and Syndromes-Recommended Antibiotic Treatments in Adult Patients Quick Reference Booklet African Antibiotic Treatment Guidelines for Common Bacterial Infections and Syndromes Recommended Antibiotic Treatments in Pediatric Patients-Quick Reference Booklet World Health Organization. Model List of Essential Medicines for Children, 7th list