Comparison of national antimicrobial treatment guidelines, African Union

Bull World Health Organ 2022;100:50–59 | doi: http://dx.doi.org/10.2471/BLT.21.286689 Research 50 Introduction Antimicrobial resistance poses significant public health challenges and threatens the ability to treat many common infectious diseases. Across Africa, rising rates of drug resis- tance have been documented for the pathogens that cause tuberculosis, pneumonia, diarrhoeal diseases, malaria and sexually transmitted infections.1 Documented levels of anti- microbial resistance rates are likely lower than the actual level due to limited surveillance activities and laboratory capacity and lack of consistent access and utilization of antimicrobial susceptibility testing.2 Major drivers of antimicrobial resistance include: the misuse and overuse of antimicrobials in the human health and agricultural sectors; lack of access to clinically appropriate antimicrobials; lack of regulation and/or regulatory enforce- ment restricting access to antimicrobials to prescription-only use; and a higher burden of infectious diseases which is driven by low vaccination coverage and limited water, sanitation and hygiene infrastructure.2–4 Given these risk factors for antimicrobial resistance, low- and middle-income countries are at a higher risk for the propagation of resistant pathogens compared to high-income countries. Moreover, the public health consequences of antimicrobial resistance may be higher in African countries because of failure to diagnose antimicrobial-resistant infections and the absence of expensive second-line therapies. In 2018, the Africa Centres for Disease Control and Prevention (Africa CDC) released its Framework for An- timicrobial Resistance, a strategy to improve surveillance, delay emergence, limit transmission and mitigate harm from antimicrobial-resistant pathogens in Africa.5 African Union (AU) Member States and stakeholders identified priority ac- tivities for implementing Africa CDC’s framework. To delay the emergence and mitigate harm of antimicrobial resistance, many expert organizations recommended that antimicrobials only be used in accordance with established clinical guide- lines that outline when, what and how to prescribe. However, representatives of the AU Member States noted that, except for select diseases such as human immunodeficiency virus (HIV) infection, tuberculosis and malaria, many health-care providers do not have country-specific guidelines and must rely on individual judgement or treatment guidelines devel- oped outside of Africa. Standardized treatment guidelines are an important tool to ensure the appropriate and optimal use of antimicrobials in the human health sector, particularly when informed by local data and combined with antimicrobial stewardship programmes.6,7 We sought to identify existing standardized treatment guidelines from African government agencies or public health institutes, to assess their completeness and quality, and compare the antimicrobial treatment therapies described across the guidelines. Methods We reviewed the websites of health ministries, national public health institutes or equivalent national government agencies of all 55 AU Member States for relevant published standard- ized treatment guidelines.8 We conducted two reviews, the first between December 2018 and March 2019 and the second between May and June 2021. For countries without functioning a Center for Disease Dynamics, Economics & Policy, 5636 Connecticut Ave NW, Washington, DC 20015, United States of America. b Center for Disease Dynamics, Economics & Policy, New Delhi, India. c Africa Centres for Disease Control and Prevention, Addis Ababa, Ethiopia. Correspondence to Jessica Craig (email: craig@ cddep .org). (Submitted: 23 June 2021 – Revised version received: 29 October 2021 – Accepted: 1 November 2021 – Published online: 26 November 2021 ) Comparison of national antimicrobial treatment guidelines, African Union Jessica Craig,a Kayli Hiban,a Isabel Frost,b Geetanjali Kapoor,b Yewande Alimic & Jay K Varmac Objective To identify and compare antimicrobial treatment guidelines from African Union (AU) Member States. Methods We reviewed national government agency and public health institutes’ websites and communicated with country or regional focal points to identify existing treatment guidelines from AU Member States. We included guidelines if they contained disease-, syndrome- or pathogen-specific treatment recommendations and if those recommendations included antimicrobial name or class, dosage and therapy duration. The scope of the review was limited to infections and clinical syndromes that often have a bacterial cause. We assessed treatment guidelines for alignment with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We compared treatment recommendations for various common bacterial infections or clinical syndromes described across national guidelines and those described in three World Health Organization guidelines. Findings We identified 31 treatment guidelines from 20 of the 55 (36%) AU Member States; several countries had more than one treatment guideline that met our inclusion criteria. Fifteen (48%) guidelines from 10 countries have been published or updated since 2015. Methods used to develop the guidelines were not well described. No guidelines were developed according to the GRADE approach. Antimicrobial selection, dosage and duration of recommended therapies varied widely across guidelines for all infections and syndromes. Conclusion AU Member States lack antimicrobial treatment guidelines that meet internationally accepted methods and that draw from local evidence about disease burden and antimicrobial susceptibility. 51Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, AfricaJessica Craig et al. health ministry websites or for coun- tries where guidelines were not readily or apparently available, we contacted in-country Africa CDC focal points by email to help identify existing standard- ized treatment guidelines. In-country focal points were identified through Africa CDC Regional Collaborating Centres and included regional World Health Organization (WHO) staff. Two subsequent emails were sent to each focal person if immediate response did not occur. We were unable to identify specific in-country focal points in Dji- bouti, Libya, and Somalia; a regional fo- cal point was contacted in these cases. In total, 15 national or regional focal points were contacted with two not responding. To inform our work, we presented our proposed methods and inclusion criteria to a panel of 28 infectious dis- ease clinicians and public health experts representing 13 AU Member States. This consultation resulted in exclusion of na- tional and regional guidelines developed by professional bodies and organiza- tions, given that these guidelines may not be widely or systematically available or used in health facilities across the continent. An evaluation of the access and utilization of guidelines developed by these bodies would be required to determine if they are consistently used by clinicians treating infectious diseases. Furthermore, these guidelines may not represent feasible clinical options at the national or continental level given challenges in access to various antimi- crobials or other diagnostic or treatment paradigms. We limited the scope of the review to bacterial infections and clinical syndromes that often have a bacterial cause. Disease-specific guidelines for HIV, malaria, tuberculosis and other infections or syndromes addressed by national or vertical disease control pro- grammes in Africa were excluded. We considered guidelines published in any major continental language. For final review, we included guidelines only if they contained disease-, syndrome- or pathogen-specific treatment recommen- dations and recommendations included specific name or class of antimicrobial, dosage and duration of therapy. Standardized treatment guidelines that met the inclusion criteria were assessed for alignment with the Grad- ing of Recommendations Assessment, Development and Evaluation (GRADE) criteria.9 This included a review of in- formation describing the methods used in guidelines development including whether the guidelines underwent ex- ternal technical review or were informed by a systematic review of local, national or regional antimicrobial resistance or disease burden data.9 We compiled antimicrobial treat- ment recommendations provided in each guideline for common bacterial diseases, including information on drug (or class of antimicrobial) selection, dosage and duration of therapy. Recom- mendations were segregated by adult, paediatric and/or neonatal patient populations as specified in the source guidelines. Special populations (e.g. pregnant women, patients with penicil- lin allergies) were included if noted in the source guidelines. Alternative and second-line therapy recommendations were also recorded. We did not extract other clinical information, such as case definition, recommended diagnostic testing and non-antimicrobial therapy treatments (e.g. vitamin supplements or pain management). For comparison regarding first- and second-line antimicrobial selection, we also consulted the 2019 WHO Model list of essential medicines,10 the 2019 WHO Model list of essential medicines for Children11 and the Pocket book of hospi- tal care for children, 2nd edition.12 The WHO model lists only provided drug selection recommendations and did not provide recommended treatment dosages or durations; therefore, further comparison of recommended therapy was not possible. Finally, we compared treatment regimens provided across in- dividual guidelines, including the WHO model lists, to assess variability in anti- microbial treatment recommendations. Results Description of guidelines Table 1 presents the 31 standardized treatment guidelines from 20 countries that met the inclusion criteria.13–43 Several countries had more than one published guideline included for final review: Ethiopia (2 guidelines), Kenya (2), the Seychelles (2), South Africa (5), Tunisia (3), Uganda (2) and Zambia (2). Despite extensive efforts, we did not identify existing standardized treatment guidelines for the remaining 35 AU Member States. Year of publication or last update ranged from 2001 to 2018; two standardized treatment guidelines did not state the year of publication. Only 15 (48%) of 31 standardized treatment guidelines from 10 countries have been published or updated since 2015. Four guidelines were published in French and the remaining were published in English. All guidelines were published by the health minis- try or other national health agencies or research institutes. Twenty-three (74%) guidelines provided treatment recommendations for both adult and paediatric patient populations, five provided only adult-specific guidelines and three provided paediatric-only rec- ommendations. Overall, the description methods used in the development of the guidelines was poor and no guide- lines were developed according to the GRADE approach. Only three (10%) guidelines reported that the treatment recommendations considered available antimicrobial resistance data, while 10 (32%) guidelines stated that data on lo- cal disease burden was considered when developing recommendations. We extracted and compiled treat- ment regimen recommendations for 27 infections and/or syndromes for adult patients and 26 for paediatric patients (Table 2). Meningitis, conjunctivitis, mild, moderate or non-severe pneu- monia and urinary tract infection were the most common bacterial infections or clinical syndromes included in guidelines for adult patients; each were covered by 14 (70%) countries. Thirteen (65%) countries had guidelines that provided treatment recommendations for adult patients for acute otitis media, cholera, impetigo and pelvic inflam- matory disease, while guidelines from 12 (60%) countries provided recom- mendations for acute and/or chronic bronchitis, syphilis and typhoid or en- teric fever. Cholera and meningitis were the most frequently included infections or clinical syndromes for paediatric patients followed by acute otitis media, conjunctivitis, impetigo and typhoid or enteric fever. The WHO model list provided treatment regimen recom- mendations for adult populations for 48% (13/27) of the bacterial infections or syndromes commonly included in the standardized treatment guidelines of AU Member States. The WHO model list for children and the pocket book provided recommendations for 50% (13) and 27% (7), respectively, of the 26 infections or syndromes covered by the guidelines. 52 Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, Africa Jessica Craig et al. Comparison of regimens Antimicrobial selection and dosage and duration of recommended therapies varied across guidelines for all bacterial infections or clinical syndromes in- cluded in this analysis. Few guidelines provided organism-specific treatment recommendations or guidance on tai- loring antimicrobial therapy according to bacterial culture or antimicrobial susceptibility testing results. Complete data sets for all infections and clinical syndromes are available in the authors’ data repository.44 For brevity, we pres- ent illustrative examples below showing the range of recommendations: a com- parison of treatment recommendations for bacterial meningitis in paediatric and neonatal patient populations and for bronchitis in adult patients. Paediatric population A total of 14 countries provided rec- ommendations for the treatment of acute bacterial or suspected bacterial meningitis in paediatric and/or neo- natal patient populations (Table 3). Of those, eight (57%) countries provided organism-specific drug selection rec- ommendations or provided organism- specific therapy durations whereas the Table 1. Summary of standard treatment guidelines included in the study on antimicrobial treatment recommendations, African Union Country Title Publication year Adult Paediatric Eswatini13 Standard treatment guidelines and essential medicines list of common medical conditions in the Kingdom of Swaziland 2012 Yes Yes Ethiopia14 Guideline on cholera outbreak management 2011 Yes Yes Ethiopia15 National guidelines for the management of sexually transmitted infections using syndromic approach 2015 Yes Yes Gambia16 The Gambia standard drug treatment guide 2001 Yes Yes Ghana17 Standard treatment guidelines 2010 Yes Yes Kenya18 Clinical guidelines for the management and referral of common conditions at levels 4–6: hospitals 2009 Yes Yes Kenya19 Guidelines on cholera control 2002 Yes Yes Liberia20 2nd edition national standard therapeutic guidelines and essential medicines list Liberia, 2017 2017 Yes Yes Malawi21 Malawi standard treatment guidelines (MSTG) 2015 Yes Yes Morocco22 Directives de prise en charge de l'enfant malade de moins de cinq ansa 2016 No Yes Namibia23 Namibia standard treatment guidelines 2011 Yes Yes Nigeria24 Nigeria standard treatment guidelines 2016 Yes Yes Rwanda25 Internal medicine clinical treatment guidelines 2012 Yes Yes Seychelles26 Antimicrobial guidelines for management of infections in hospitals 2018 Yes Yes Seychelles27 Guidelines for antibiotic prescribing in the primary health care services 2017 Yes Yes Somalia28 Somali treatment guidelines in line with the essential package of health services, primary health unit STGs 2015 Yes Yes South Africa29 Standard treatment guidelines and essential medicines list for South Africa: hospital level paediatrics 2017 No Yes South Africa30 Standard treatment guidelines and essential medicines list for South Africa: hospital level adults 2015 Yes Yes South Africa31 Standard treatment guidelines and essential medicines list for South Africa: primary health care level 2018 Yes Yes South Africa32 Guidelines on leprosy control in South Africa 2011 Yes No South Africa33 Listeriosis: clinical recommendations for diagnosis and treatment 2017 Yes No Sudan34 Sudan national standard treatment guidelines 2014 Yes Yes Tunisia35 Antibiotherapie des infectious osteo-articulaires aigues communautaires a pyogenes – recommandations nationales fevrier 2006a 2006 Yes No Tunisia36 Antibiotherapie des pyelonephrities aigues communautaires de l'adultea NA Yes No Tunisia37 L'Antibiotherapie dans les infections respiratoires basses acquises de l'adulte traité en villea NA Yes No Uganda38 Prevention and control of cholera 2017 Yes Yes Uganda39 Uganda clinical guidelines 2016 2016 Yes Yes United Republic of Tanzania40 Standard treatment guidelines (STG) & the national essential medicines list for mainland Tanzania 2007 Yes Yes Zambia41 Standard treatment guidelines, essential medicines list and essential laboratory supplies list for Zambia 2013 Yes Yes Zambia42 Essential newborn care guidelines 2014 No Yes Zimbabwe43 7th essential medicines list and standard treatment. Guidelines for Zimbabwe 2015 Yes Yes NA: not available. a Guideline published in French. 53Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, AfricaJessica Craig et al. other standardized treatment guidelines did not specify a causative agent or pro- vided recommendations in situations when the causative agent was unknown. The WHO model list for children also provided treatment recommendations for acute bacterial meningitis with no organism-specific recommendations where the first-choice drug selections were cefotaxime for neonates and cef- triaxone for children. Second-choice antimicrobials included meropenem for neonates and amoxicillin, ampicillin, benzylpenicillin and chloramphenicol for children older than 2 years. Across the guidelines that provided treatment recommendations for bacterial menin- gitis in paediatric patients (excluding neonates) where the causative agent was not specified or in cases where it is unknown, recommended drug selec- tions for monotherapy included benzyl- penicillin, ampicillin, ceftriaxone and chloramphenicol. The recommended combination therapies were benzyl- penicillin plus chloramphenicol. For neonates, recommended drug selections for monotherapy included ceftriaxone and fluconazole, and combination therapies included ampicillin IV plus gentamicin and benzylpenicillin plus chloramphenicol. Multiple guidelines recommended the same first-choice antimicrobial; however, dosage and therapy duration varied. For instance, dosage and duration recommendations for monotherapy treatment of paediatric patients (excluding neonates) with cef- triaxone ranged from 100 mg/kg daily for 7 days to 100 mg/kg daily for 10 to 14 days and 50–100 mg/kg every 12 hours for 14 days. The variation between guidelines was less when the causative microorgan- ism of the infection or syndrome was specified. For example, five guidelines provided recommendations for the treatment of acute meningitis in pae- diatric patients (excluding neonates) caused by Streptococcus pneumoniae. All five guidelines recommended mono- therapy with either benzylpenicillin or ceftriaxone for 10 to 14 days; dosage recommendations were similar across the four guidelines that provided such information (Table 3). Of the 14 countries that had na- tional guidelines for the treatment of meningitis, only six (43%) included guidance or instructions for obtaining cultures and antimicrobial susceptibil- ity testing or tailoring drug selection or duration accordingly (available in data repository).44 For example, the Standard treatment guidelines and es- sential medicines list for South Africa, hospital level paediatrics provide recom- mendations for empirical treatment of meningitis and instruct users to “Adjust antimicrobial therapy according to cul- ture and sensitivity” and to “Re-assess antimicrobial therapy when blood and CSF [cerebrospinal fluid] culture and sensitivity results become available, or Table 2. Bacterial infections or syndromes covered by African standard treatment guidelines, WHO Model list of essential medicines and Pocket book of hospital care for children, 2001–2019 Infection or syndrome With adult patient recommendations With paediatric patient recommendations No. of countries Covered by WHO Model lista No. of countries Covered by WHO Model list for childrenb Covered by the pocket bookc Meningitis 14 Yes 14 Yes Yes Non-severe pneumoniad 14 Yes 9 Yes Yes Urinary tract infection 14 Yes 7 Yes Yes Conjunctivitis 14 No 11 No No Cholera 13 Yes 14 Yes No Acute otitis media 13 Yes 13 Yes No Impetigo 13 No 11 No No Pelvic inflammatory disease 13 No 1 No No Typhoid or enteric fever 12 Yes 10 Yes Yes Syphilis 12 Yes 6 Yes No Acute and/or chronic bronchitis 12 No 4 No No Gonorrhoea or chlamydia 11 Yes 1 Yes No Dental abscess 10 Yes 7 Yes No Trichomoniasis and bacterial vaginosis 10 Yes 1 No No Cellulitis 10 No 9 No No Tonsilitis 10 No 8 No No Dysenterye 9 Yes 9 Yes Yes Chronic otitis media 9 Yes 7 Yes No Tetanus 9 No 9 No No Severe pneumonia 8 Yes 8 Yes Yes Sepsis or septicaemia 7 No 9 Yes Yes Gingivitis 7 No 6 No No Brucellosis 6 No 4 No No Diphtheria 6 No 3 No No Cutaneous anthrax 6 No 2 No No Peritonsillar abscess 6 No 0 No No Plague 5 No 4 No No WHO: World Health Organization. a 2019 WHO Model list of essential medicines.10 b 2019 WHO Model list of essential medicines for children.11 c Pocket book of hospital care for children.12 d Includes also moderate or mild pneumonia. e Includes bacillary dysentery and shigellosis. 54 Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, Africa Jessica Craig et al. when improvement is not evident within 72–96 hours.”29 The Gambia standard drug treatment guide provides a recom- mendation to treat paediatric patients older than 2 months of age and present- ing with meningitis with a combination therapy of benzylpenicillin plus chlor- amphenicol.16 Alongside the antimicro- bial treatment recommendation, there is also guidance to “Continue until culture result is known, after which use a single drug therapy with chloramphenicol, benzylpenicillin or ampicillin.”16 Adult population There were discrepancies among guide- lines regarding the use of antimicrobials for the treatment of certain conditions for adult population. For example, guidelines from eight countries de- scribed recommendations for the treat- ment of acute bronchitis. Of those, three recommended treatments with various antimicrobial therapy regimens including 250–500 mg of amoxicillin for 5 days, 500 mg of amoxicillin every 8 hours for 7 days, 200 mg of doxycy- cline on the first day of treatment fol- lowed by 100 mg once a day for 5 days, and 500 mg of amoxicillin/clavulanic acid every 12 hours for 7 days (Table 4). Four other guidelines stated that an- timicrobial use was not indicated for the treatment of acute bronchitis while a fifth guideline stated that antibiotics were not indicated for uncomplicated bronchitis but for purulent bronchitis, treatment with amoxicillin at a dosage of 500 mg every 8 hours for 4 or more days was indicated. All four guidelines for the treatment of chronic bronchitis indicated treatment with an antimicro- bial agent. The WHO model list10 did not provide clinical guidance for the treatment of acute or chronic bronchitis in adults. Discussion The misuse and overuse of antimicrobi- als in the human health sector is a major driver of antimicrobial resistance global- ly. Per capita antimicrobial consumption in Africa and other low- and middle- income countries is rising at a faster rate than high-income countries.45 In part, this consumption pattern may be due to a lack of clear guidance for the use of antimicrobials in the clinical setting, improved access to antimicrobials, and non-prescription use of antimicrobials.45 Here, we found that only one third of Table 3. Recommendations for the treatment of bacterial meningitis in neonatal and paediatric patients from a subset of African standard treatment guidelines, 2001–2019 Country Recommended first-line drug selection (dosage) Treatment duration Meningitis in neonates, causative agent not specified or unknown NA (WHO Model list of essential medicines for children)11 First choice: Cefotaxime Second choice: Meropenem (dosage recommendation not provided) NA NA (Pocket book of hospital care for children)12 First choice: Ampicillin (dosage based on patient age and weight) and gentamicin (dosage based on patient age and weight). Alternatively: third-generation cephalosporin such as ceftriaxone (50 mg/kg every 12 hours if < 7 days of age and 75 mg/kg after 1 week) or cefotaxime (50 mg/kg every 12 hours if < 7 days or every 6–8 hours if > 7 days of age), and gentamicin for 3 weeks 3 weeks Ghana17 Ceftriaxone (20–50 mg/kg once daily) 21 days Malawi21 Benzylpenicillin (100 000 units/kg 6 hourly) plus gentamicin (2.5 mg/kg 8 hourly) 14–21 days Nigeria24 Ceftriaxone (20–50 mg/kg daily, maximum dose: 50 mg/kg daily) NA Uganda39 Ampicillin IV (50–100 mg/kg every 8 hours for neonates < 7 days old or every 12 hours if > 7 days old) plus gentamicin (2.5 mg/kg every 12 hours) 21 days Zambia42 Ceftriaxone (20–50 mg/kg daily as a single dose) NA Zimbabwe43 Fluconazole (6–12 mg/kg every 72 hours for neonates < 2 weeks old or every 48 hours for those 2 to 4 weeks old) NA Meningitis in children, causative agent not specified or unknowna NA (WHO Model list of essential medicines for children)11 First choice: Ceftriaxone Second choice: Amoxicillin, ampicillin, benzylpenicillin, chloramphenicol (for children > 2 years old) NA Liberia20 Ceftriaxone (50–100 mg/kg every 12 hours) or chloramphenicol (25 mg/kg/dose every 6 hours) 14 days Malawi21 Benzylpenicillin (100 000 units/kg 6 hourly) plus chloramphenicol (25 mg/kg 8 hourly) or ceftriaxone (100 mg/kg every 24 hours) 7 days Seychelles26 Benzylpenicillin (300 mg for infants < 1 year, 600 mg for 1- to 9-year-olds and 1 200 mg for children > 10 years) NA Uganda39 Ceftriaxone (100 mg/kg daily dose) 10–14 days United Republic of Tanzania40 Ampicillin (50–100 mg/kg 6 hourly) or chloramphenicol (50 mg/kg 6 hourly) 10 days Meningitis caused by Streptococcus pneumoniae in paediatric patientsa Eswatini13 Benzylpenicillin (100 000 IU/kg per dose) or ceftriaxone (50–100 mg/kg in 1–2 divided doses) 10–14 days Gambia16 Benzylpenicillin (dosage recommendation not provided) 10–14 days Liberia20 Benzylpenicillin (100 000 IU/kg/dose every 4 hours) or ceftriaxone (50–100 mg/kg/dose once/twice a day) 10–14 days South Africa29 Ceftriaxone (50 mg/kg/dose 12 hourly) 10 days Uganda39 Benzylpenicillin (100 000 IU/kg per dose) or ceftriaxone (100 mg/kg daily dose) 10–14 days or up to 21 days in severe cases IU: international unit; NA: not available; WHO: World Health Organization. a Excluding neonates. Note: Antimicrobial treatment recommendations are summarized from selected standard treatment guidelines to illustrate the range of recommendations; additional standard treatment guidelines set forth recommendations and guidance but are not included here for brevity. Treatment recommendations were edited for grammar, clarity and/or length. 55Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, AfricaJessica Craig et al. AU Member States had any relevant standardized treatment guidelines for the treatment of common bacterial infections or syndromes. No guidelines stated that they were based on local disease burden or resistance profiles; one explanation for this finding may be the lack of national laboratory and surveil- lance capacities leading to gaps in the lo- cal evidence base. Only a small number of guidelines cited published literature or other clinical evidence supporting the rationale for certain drug, dosage and duration recommendations. Few guidelines incorporated antimicrobial stewardship principles, culture or anti- microbial susceptibility testing results into treatment recommendations. Only about half of the bacterial infections and/or syndromes covered in existing standardized treatment guide- lines from AU Member States across adult and paediatric patient populations were addressed in WHO model lists10,11 and less than a third were included in the Pocket book of hospital care for chil- dren.12 This finding indicates a potential discrepancy between disease burden and priorities at the international and regional contexts and reinforces the need for context-specific standardized treatment guidelines to guide the appro- priate clinical treatment of these infec- tions and clinical syndromes. Finally, the recommended drug selection, dosage and duration of therapy varied across the guidelines, indicating a lack of clear, consensus clinical guidance and poten- tial for the misuse of antimicrobials. Clinical guidelines that provide explicit recommendations for the treat- ment of infectious diseases and aid in clinical decision-making have been shown to reduce inappropriate antimi- crobial prescribing as well as improve the quality of care.46,47 High quality treatment guidelines should be based on a rigorous multidisciplinary evalu- ation of all available scientific evidence about treatment effectiveness and local disease and antimicrobial resistance burden.7,48,49 Moreover, as antimicrobial resistance increasingly poses a public health threat, guidelines must also encourage clinicians to obtain cultures, identify the causative microorganism and conduct antimicrobial susceptibil- ity testing before or during therapeutic intervention. This study had several limitations. First, we did not include guidelines de- veloped by nongovernmental public or private institutions, professional organi- zations or individual health facilities in this review, which may have limited the number of total countries represented in this study. Moreover, guidelines developed outside of the national gov- ernment infrastructure may represent an important source for information guiding clinical decision-making and antimicrobial prescribing practices at the facility, national and regional levels. While we made every effort to identify all existing guidelines for each eligible country, some guidelines used in clinical practice may not be publicly available or easily searchable online and may have been omitted from inclusion. In the future, all efforts should be exhausted to ensure that all applicable guidelines are identified and considered for inclusion; maintenance of a guidelines database may also be useful. In addition, this study does not account for the aware- ness of, utilization of and/or adherence to standardized treatment guidelines at the local or national levels nor other factors that may influence feasibility of using guidelines, such as availability and cost of recommended antimicrobials. As such, antimicrobial treatment regimens Table 4. Summary of treatment recommendations from included African standard treatment guidelines for acute and chronic bronchitis for adult patient populations, 2001–2019 Country Recommended first-line drug selection (dosage)a Treatment duration Acute bronchitis Eswatini13 Antibiotics are not indicated for uncomplicated bronchitis, but if purulent treat with amoxicillin (500 mg every 8 hours) 4 or more days Ghana17 Amoxicillin (500 mg 8 hourly) or amoxicillin/clavulanic acid (one 500/125 tablet 12 hourly); double the dose if severe 7 days Kenya18 Amoxicillin (250–500 mg three times a day) or tetracycline 5 days Malawi21 Amoxycillin (500 mg three times/day) or doxycycline (200 mg on first day followed by 100 mg once/day) 5 days Nigeria24 Not required unless clear evidence of primary bacterial etiology or secondary bacterial infection Not applicable Seychelles26 Consider 7-day delayed antibiotic with symptomatic advice/leaflet. Care should be taken to exclude a differential diagnosis of pneumonia. Antibiotics are not indicated in people who are otherwise well. Routine follow-up is not necessary. However, patients should be advised to seek advice if their condition deteriorates significantly, or symptoms persist for longer than 3 weeks. Consider antibiotics for those with pre-existing conditions that impair their ability to fight infection or are likely to deteriorate with acute bronchitis Not applicable United Republic of Tanzania40 There is no benefit from antibiotic use. Pertussis is the only indication for antibacterial agents in the treatment of acute bronchitis Not applicable Zimbabwe43 No antibiotics required Not applicable Chronic bronchitis Eswatini13 If there is infection, treat with amoxicillin (500 mg every 8 hours) Not specified Gambia16 For secondary infection: amoxicillin (500 mg 8 hourly) or erythromycin (500 mg 6 hourly) or azithromycin (500 mg daily) Amoxicillin, erythromycin: 7 days Azithromycin: 3 days Liberia20 Co-trimoxazole (960 mg every 12 hours) or amoxicillin (500 mg over 8 hours) 5 days Zimbabwe43 Treat with antibiotics (amoxicillin 500 mg three times/day) or doxycycline (100 mg once/day for 7 days) if sputum colour has changed to purulent, if there is fever or new chest X-ray infiltrates 7 days a We summarized treatment recommendations from the standard treatment guidelines and edited for grammar, clarity and/or length. 56 Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, Africa Jessica Craig et al. employed in clinical practice may vary widely from those recommended in any standardized treatment guidelines. In addition to the suboptimal treat- ment guidelines, the high antimicrobial consumption rates in the African Region may reflect the higher burden of infec- tious diseases, the high prevalence of substandard pharmaceutical agents, the lack of access to health-care services and lack of regulation around prescription- only use of antimicrobials. These factors lead to high rates of self-medication and non-prescription antimicrobials sales and consumption.50 Therefore, while the development and implementation of standardized treatment guidelines offer an opportunity to reduce the misuse and overuse of antimicrobials in the human health sector, other antimicrobial stew- ardship interventions that address other drivers of antimicrobial overuse and misuse and the emergence and spread of antimicrobial resistance more broadly must also be implemented. In conclusion, AU Member States need to develop standardized treatment guidelines that meet internationally accepted standards for methods and are based on locally derived clinical evidence, disease burden and resistance profiles. To achieve this, countries must also increase their capacity for evidence building, including antimicrobial re- sistance and infectious disease surveil- lance. Furthermore, many countries across the continent lack adequate access to clean water and sanitation facilities, and have vaccination coverage below recommended levels. In addition to ensuring antimicrobial treatment is appropriate, preventing infections where possible is essential to reduce antimicrobial use, slow the emergence of resistance and ultimately improve health outcomes and save lives. ■ Competing interests: None declared. 摘要 非洲联盟国家抗菌药物指南的比较 目的 旨在明确和比较非洲联盟 (AU) 成员国的抗菌药 物指南。 方法 我们审查了国家政府机关和公共卫生机构的网站 并与国家或地方性的联络点取得了沟通，以确定非洲 联盟成员国的当前药物指南。如果指南包含与具体疾 病、综合征或病原体有关的药物推荐，而且这些推荐 中提及了抗菌药物的名称或级别、剂量和治疗周期， 那么我们将这些指南纳入我们的研究中。审查的范围 限于通常由细菌引起的感染和临床症状。我们根据推 荐、评估、发展和评估等级 (GRADE) 标准评估了药物 指南。我们针对国家指南和世界卫生组织指南中描述 的各种常见细菌感染或临床症状对不同治疗推荐进行 了比较。 结果 我们确定了来自 55 个非洲联盟成员国中的 20 个 国家 (36%) 的 31 项治疗指南 ；有几个国家的多项治疗 指南符合我们的纳入标准。自 2015 年以来，来自 10 个国家的十五项 (48%) 指南已发布或更新。。但并未 清楚描述制定指南所采用的方法，也没有指南是依据 GRADE 方法制定的。不同指南针对各种感染和综合 征推荐的抗菌药物选择、剂量和持续时间差异很大。 结论 非洲联盟成员国缺乏按照国际公认的方法且借鉴 关于疾病负担和抗菌药物耐药性的地方性证据制定的 抗菌药物治疗指南。 صخلم يقيرفلأا داتحلاا ،تابوركيلما تاداضمب جلاعلل ةينطولا ةيهيجوتلا ئدابلما ينب ةنراقم ،تابوركيلما تاداضمب جلاعلل ةيهيجوتلا ئدابلما ديدتح ضرغلا .(AU) يقيرفلأا داتحلاا في ءاضعلأا لودلا عم اهتنراقمو ةيموكلحا ةلاكولل ةينوتركللإا عقاولما ةعجارمب انمق ةقيرطلا ةيزكرلما طاقنلا عم انلصاوتو ،ةماعلا ةحصلا دهاعمو ،ةينطولا جلاعلل ةيلالحا ةيهيجوتلا ئدابلما ديدحتل ةيميلقلإا وأ ةيرطقلا ئدابلما ينمضتب انمق .يقيرفلأا داتحلاا في ءاضعلأا لودلا نم ،ضرلماب ةصاخ جلاعلل تايصوت لىع يوتتح تناك اذإ ةيهيجوتلا كلت تنمضت اذإو ،ضرملل ةببسلما لماوعلاب وأ ،ةمزلاتلماب وأ ةدمو ،ةعرلجاو ،تابوركيلما تاداضم ةئف وأ مسا تايصوتلا تامزلاتلماو ىودعلا عاونأ لىع ةعجارلما قاطن صرتقا .جلاعلا مييقتب انمقو .ييرتكب ببس اله نوكي ام اًبلاغ يتلا ةيكينيلكلإا تاجرد يرياعم عم اهقفاوت ثيح نم جلاعلل ةيهيجوتلا ئدابلما ةنراقمب انمق .(GRADE) اهمييقتو اهريوطتو تايصوتلا مييقت وأ ،ةعئاشلا ةييرتكبلا ىودعلا عاونأ فلتخلم جلاعلا تايصوت كلتو ،ةينطولا ةيهيجوتلا ئدابلما في ةدراولا ةيكينيلكلإا تامزلاتلما .ةيلماعلا ةحصلا ةمظنلم ثلاثلا ةيهيجوتلا ئدابلما في ةحضولما 20 نم جلاعلل ةيهيجوتلا ئدابلما نم 31 ديدحتب انمق جئاتنلا داتحلاا في ءاضعلأا لودلا نم (36%) ةلود 55 لياجمإ نم ةلود يهيجوت أدبم نم رثكأ لودلا نم ديدعلا ىدل ناكو ؛يقيرفلأا شرع ةسخم ثيدتح وأ شرن مت .انيدل ينمضتلا يرياعمب يفي دحاو متي لم .2015 ماع ذنم لود 10 نم ةيهيجوتلا ئدابلما نم (48%) لم .ديج لكشب ةيهيجوتلا ئدابلما ريوطتل ةمدختسلما قرطلا فصو فلتخا .GRADE بولسلأ اًقفو ةيهيجوت ئدابم ةيأ ريوطت متي صىولما تاجلاعلا ةدمو اهتعرجو تابوركيلما تاداضم رايتخا ىودعلا عاونأ عيملج ةيهيجوتلا ئدابلما برع عساو قاطن لىع ابه .تامزلاتلماو ئدابلما لىإ يقيرفلأا داتحلاا في ءاضعلأا لودلا رقتفت جاتنتسلاا بيلاسلأاب يفت يتلا تابوركيلما تاداضمب جلاعلل ةيهيجوتلا ضرلما ءبع لوح ةيلحلما ةلدلأا لىع دمتعت يتلاو ،اًيلود ةلوبقلما .تابوركيلما تاداضمب رثأتلا ةيلباقو 57Bull World Health Organ 2022;100:50–59| doi: http://dx.doi.org/10.2471/BLT.21.286689 Research Antimicrobial treatment recommendations, AfricaJessica Craig et al. Résumé Comparaison entre les directives nationales de traitement antimicrobien, Union africaine Objectif Identifier et comparer les directives de traitement antimicrobien des États Membres de l'Union africaine (UA). Méthodes Nous avons examiné les sites Internet de l'agence gouvernementale nationale et des organismes de santé publique, mais aussi contacté les points focaux nationaux et régionaux afin d'identifier les directives de traitement existant au sein des États Membres de l'UA. Nous avons inclus toute directive incluant des recommandations de prise en charge spécifique des maladies, syndromes ou agents pathogènes, et mentionnant le nom ou la catégorie d'antimicrobiens, le dosage ainsi que la durée du traitement. La portée de notre revue s'est limitée aux infections et syndromes cliniques fréquemment causés par des bactéries. Nous avons ensuite évalué ces directives de traitement afin de déterminer leur correspondance avec les critères du système GRADE (Grading of Recommendations, Assessment, Development and Evaluation, soit «grade donné aux recommandations, examen, élaboration et évaluation»). Enfin, nous avons comparé les recommandations de traitement pour plusieurs infections bactériennes ou syndromes cliniques courants reprises dans les différentes directives nationales avec celles décrites dans trois des lignes directrices de l'Organisation mondiale de la Santé. Résultats Nous avons identifié 31 directives de traitement dans 20 des 55 (36%) États Membres de l'UA; de nombreux pays possédaient plus d'une directive répondant à nos critères d'inclusion. Quinze (48%) directives issues de 10 pays ont publiées ou mises à jour depuis 2015. Les méthodes employées pour les développer n'étaient pas bien documentées. Aucune directive n'avait été élaborée selon l'approche GRADE. Le choix des antimicrobiens, leur dosage et la durée de traitement conseillée variaient énormément d'une directive à l'autre, pour l'ensemble des syndromes et infections. Conclusion Les États Membres de l'UA manquent de directives de traitement antimicrobien conformes aux méthodes universellement reconnues, et qui s'inspirent des données locales relatives à la charge de morbidité et à la sensibilité aux antimicrobiens. Резюме Сравнение национальных руководств по применению противомикробных препаратов, Африканский союз Цель Определить и сравнить руководства по применению противомикробных препаратов в государствах-членах Африканского союза (АС). Методы Авторы изучили веб-сайты национальных правительственных ведомств и институтов общественного здравоохранения и связались с национальными или региональными координаторами, чтобы определить существующие руководства по применению противомикробных препаратов в государствах-членах Африканского союза. К рассмотрению допускались руководства, содержавшие рекомендации по лечению конкретных заболеваний, синдромов или патогенов, включавшие название или класс противомикробного препарата, дозировку и продолжительность терапии. Сфера охвата обзора ограничивалась инфекциями и клиническими синдромами, которые часто имеют бактериальное происхождение. Авторы оценили руководства по лечению на предмет их соответствия критериям Системы классификации, оценки, разработки и экспертизы рекомендаций (GRADE). Авторы сравнили рекомендации по лечению различных распространенных бактериальных инфекций или клинических синдромов, описанных в национальных руководствах и в трех руководствах Всемирной организации здравоохранения. Результаты Было рассмотрено 31 руководство по лечению в 20 государствах-членах АС из 55 (36%); в нескольких странах имелось несколько руководств по лечению, соответствующих критериям включения. Пятнадцать руководств (48%) из 10 стран были опубликованы или обновлены начиная с 2015 года. Методы, использованные для разработки руководств, описаны недостаточно хорошо. Никаких руководств в соответствии с подходом GRADE разработано не было. Выбор противомикробных препаратов, дозировка и продолжительность рекомендованной терапии для всех инфекций и синдромов существенно различались в руководствах. Вывод В государствах-членах АС отсутствуют руководства по применению противомикробных препаратов, которые соответствовали бы международно признанным методам и основывались на местных данных о бремени болезни и чувствительности к противомикробным препаратам. Resumen Comparación de las directrices nacionales de tratamiento antibiótico en la Unión Africana Objetivo Identificar y comparar las directrices de tratamiento antibiótico de los Estados miembros de la Unión Africana (UA). Métodos Se revisaron los sitios web de las agencias gubernamentales nacionales y de los institutos de salud pública y se consultó a los centros de coordinación nacionales o regionales para identificar las directrices de tratamiento existentes en los Estados miembros de la UA. Se incluyeron las directrices si contenían recomendaciones de tratamiento específicas para la enfermedad, el síndrome o el patógeno y si esas recomendaciones incluían el nombre o la clase de antibiótico, la dosis y la duración del tratamiento. El alcance de la revisión se limitó a las infecciones y los síndromes clínicos que suelen tener una causa bacteriana. Se evaluó la alineación de las directrices de tratamiento con los criterios de Evaluación, Desarrollo y Valoración de Grados de Recomendación (GRADE). Se compararon las recomendaciones de tratamiento para diversas infecciones bacterianas comunes o síndromes clínicos descritos en las directrices nacionales y las descritas en tres directrices de la Organización Mundial de la Salud. Resultados Se identificaron 31 directrices de tratamiento de 20 de los 55 (36 %) Estados miembros de la UA; varios países tenían más de una directriz de tratamiento que cumplía nuestros criterios de inclusión. Quince (48 %) directrices de 10 países se han publicado o actualizado desde 2015. Los métodos utilizados para elaborar las directrices no estaban bien descritos. Ninguna de las directrices se elaboró según el enfoque GRADE. 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