Nonbiomedical factors affecting antibiotic use in the community: authors' response
Authors: Ruyu Sun, Xudong Zhou, Leesa Lin
Journal: Clinical Microbiology and Infection (2022)

We appreciate the positive comments received [[1]Laytner L. Grigoryan L. Trautner B. Re: 'Non-biomedical factors affecting antibiotic use in the community' by Sun et al.Clin Microbiol Infect. 2022; 28: 893-894Abstract Full Text Full Text PDF Scopus (1) Google Scholar] and the two resources provided to complement our current review [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. Over the past 20 years, we have conducted a series of investigations providing a comprehensive sociocultural perspective for understanding regional disparities of antibiotic use. In our response to the comments, we expand our discussions on regional differences and sociocultural determinants of antibiotic use, as well as possible intervention strategies. In 2002, the emerging infectious diseases study by Harbarth et al. on outpatient antibiotic use in France and Germany compared the cultural patterns of antibiotic demand and prescription in these two countries [[3]Harbarth S. Albrich W. Brun-Buisson C. Outpatient antibiotic use and prevalence of antibiotic-resistant pneumococci in France and Germany: a sociocultural perspective.Emerg Infect Dis. 2002; 8: 1460-1467Crossref PubMed Scopus (131) Google Scholar]. They observed higher expectations for antibiotics from French patients with upper respiratory infection symptoms (e.g. cough and sputum production), pressuring physicians to prescribe antibiotics. On the contrary, German culture preferred promoting the human body's natural defence against such diseases by employing complementary medicine approaches; thus, antibiotics were consumed less.In 2008, Harbarth and Monnet again summarized the sociocultural determinants on antibiotic use in Chapter 3 of Antibiotic policies: Fighting resistance [[4]Harbarth S. Monnet D.L. Cultural and socioeconomic determinants of antibiotic use.in: Antibiotic policies: Fighting resistance. Springer-Verlag, New York, NY2008: 29-40Crossref Scopus (23) Google Scholar]. Similarly, our 2020 BMJ Global Health systematic review on factors influencing antibiotic use in both outpatient and clinical settings adopted behavioural theories in identifying sociocultural determinants around antibiotic use in China [[5]Lin L. Sun R. Yao T. Zhou X. Harbarth S. Factors influencing inappropriate use of antibiotics in outpatient and community settings in China: a mixed-methods systematic review.BMJ Glob Health. 2020; 5e003599Crossref Scopus (15) Google Scholar]. We found that many Chinese patients had the misunderstanding that antibiotics were anti-inflammatory drugs, a misconception rooted in folk knowledge. The prevailing logic that common upper respiratory infection symptoms were caused by inflammation and thus anti-inflammatory drugs should be administered for treatment drove Chinese patients to consume antibiotics unnecessarily. In addition, health care consumers' preference for intravenous antibiotic administration further contributed to outpatient antibiotic misuse in China.We echoed the opinion of Touboul-Lundgren et al. that culture is 'all around us' and could exert influences on antibiotic use [[6]Touboul-Lundgren P. Jensen S. Drai J. Lindbæk M. Identification of cultural determinants of antibiotic use cited in primary care in Europe: a mixed research synthesis study of integrated design "Culture is all around us".BMC Public Health. 2015; 15: 908Crossref PubMed Scopus (52) Google Scholar]. Hofstede's cultural dimensions were commonly applied in their study to measure cultural disparities, of which power distance, uncertainty avoidance, and masculinity versus femininity were associated with antibiotic consumption. Other cultural determinants included patients' work ethos (e.g. whether to continue working when stricken by illnesses), drug perception (e.g. fear of toxicity, taking antibiotics to speed up recovery), and practitioners' practice context (e.g. perceiving patients' expectations, patient education strategies). Factors such as day-care attendance and practices, living conditions, vaccination coverage, and social pressure could influence antibiotic use. In summary, the evidence base demonstrates that antibiotic use is not merely a medical issue, but a topic that also calls for solutions from sociocultural aspects [[7]Minssen T. Outterson K. Rogers Van Katwyk S. Batista P.H.D. Chandler C.I.R. Ciabuschi F. et al.Social, cultural and economic aspects of antimicrobial resistance.Bull World Health Organ. 2020; 98: 823Crossref PubMed Scopus (6) Google Scholar].To address the gap, Dr Lin led an implementation science systematic review in 2020, identifying 25 public target intervention studies with behavioural change techniques aiming to reduce unnecessary antibiotic use [[8]Lin L. Alam P. Fearon E. Hargreaves J.R. Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review.Implement Sci. 2020; 15: 90Crossref PubMed Scopus (3) Google Scholar]. Most conducted campaigns for public education and were in high-income settings. However, intervention assessments revealed that conveying knowledge to the public did not change people's attitudes and behaviours. Globally, similar education materials were used in different contexts, but many lacked culturally sensitive and theoretically grounded adaptations [[9]Huttner B. Saam M. Moja L. Mah K. Sprenger M. Harbarth S. et al.How to improve antibiotic awareness campaigns: findings of a WHO global survey.BMJ Glob Health. 2019; 4e001239Crossref PubMed Scopus (42) Google Scholar]. Dr Lin also identified the research gap that public target interventions were absent in low-to-middle-income settings [[8]Lin L. Alam P. Fearon E. Hargreaves J.R. Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review.Implement Sci. 2020; 15: 90Crossref PubMed Scopus (3) Google Scholar]. According to our data (unpublished), most interventions that aimed to reduce inappropriate antibiotic use in China were implemented in primary care settings to reduce inappropriate antibiotic prescribing, largely ignoring demand-side factors, and sociocultural determinants were scarcely embedded in the intervention designs. Therefore, we very much agree with the correspondents that few interventions tailored the interventions to specific settings and individuals. Campaigns should convey information targeting multiple components, such as incorporating a theory-grounded framework in our recent publication (Health Belief Model and Socio-ecological Model) [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar].There is a need to share pilot and formative findings of intervention development in advancing implementation science to more effectively address regional differences and sociocultural determinants of antibiotic (mis)use. For example, a cost-effective point-of-care C-reactive protein testing intervention conducted in Myanmar and Thailand [[10]Althaus T. Greer R.C. Swe M.M.M. Cohen J. Tun N.N. Heaton J. et al.Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial.Lancet Glob Health. 2019; 7: e119-e131Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar] could be consulted in regions with limited resources, including some regions in Western China where health care providers routinely prescribe antibiotics out of fear for severe complications when C-reactive protein and other diagnostic testing was unavailable [[5]Lin L. Sun R. Yao T. Zhou X. Harbarth S. Factors influencing inappropriate use of antibiotics in outpatient and community settings in China: a mixed-methods systematic review.BMJ Glob Health. 2020; 5e003599Crossref Scopus (15) Google Scholar].In conclusion, grounded in work of the past 20 years, our recent publication [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar] has again highlighted the critical challenge of reducing antibiotic use and combating antimicrobial resistance from multiple nonclinical aspects. We demonstrated the necessity to incorporate sociocultural perspectives, as well as evidence-based and theory-grounded framework for effective and appropriate interventions for prudent antibiotic use.Transparency declarationThe authors declare that they have no conflicts of interest. This research was funded, in whole or in part, by the Wellcome Trust (grant number 215373/A/19/Z ) and by [email protected] administered by Innovation and Technology Commission. For the purpose of open access, the author has applied for a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. The funder had no role in study design, decision to publish, or preparation of the manuscript. We appreciate the positive comments received [[1]Laytner L. Grigoryan L. Trautner B. Re: 'Non-biomedical factors affecting antibiotic use in the community' by Sun et al.Clin Microbiol Infect. 2022; 28: 893-894Abstract Full Text Full Text PDF Scopus (1) Google Scholar] and the two resources provided to complement our current review [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. Over the past 20 years, we have conducted a series of investigations providing a comprehensive sociocultural perspective for understanding regional disparities of antibiotic use. In our response to the comments, we expand our discussions on regional differences and sociocultural determinants of antibiotic use, as well as possible intervention strategies. In 2002, the emerging infectious diseases study by Harbarth et al. on outpatient antibiotic use in France and Germany compared the cultural patterns of antibiotic demand and prescription in these two countries [[3]Harbarth S. Albrich W. Brun-Buisson C. Outpatient antibiotic use and prevalence of antibiotic-resistant pneumococci in France and Germany: a sociocultural perspective.Emerg Infect Dis. 2002; 8: 1460-1467Crossref PubMed Scopus (131) Google Scholar]. They observed higher expectations for antibiotics from French patients with upper respiratory infection symptoms (e.g. cough and sputum production), pressuring physicians to prescribe antibiotics. On the contrary, German culture preferred promoting the human body's natural defence against such diseases by employing complementary medicine approaches; thus, antibiotics were consumed less. In 2008, Harbarth and Monnet again summarized the sociocultural determinants on antibiotic use in Chapter 3 of Antibiotic policies: Fighting resistance [[4]Harbarth S. Monnet D.L. Cultural and socioeconomic determinants of antibiotic use.in: Antibiotic policies: Fighting resistance. Springer-Verlag, New York, NY2008: 29-40Crossref Scopus (23) Google Scholar]. Similarly, our 2020 BMJ Global Health systematic review on factors influencing antibiotic use in both outpatient and clinical settings adopted behavioural theories in identifying sociocultural determinants around antibiotic use in China [[5]Lin L. Sun R. Yao T. Zhou X. Harbarth S. Factors influencing inappropriate use of antibiotics in outpatient and community settings in China: a mixed-methods systematic review.BMJ Glob Health. 2020; 5e003599Crossref Scopus (15) Google Scholar]. We found that many Chinese patients had the misunderstanding that antibiotics were anti-inflammatory drugs, a misconception rooted in folk knowledge. The prevailing logic that common upper respiratory infection symptoms were caused by inflammation and thus anti-inflammatory drugs should be administered for treatment drove Chinese patients to consume antibiotics unnecessarily. In addition, health care consumers' preference for intravenous antibiotic administration further contributed to outpatient antibiotic misuse in China. We echoed the opinion of Touboul-Lundgren et al. that culture is 'all around us' and could exert influences on antibiotic use [[6]Touboul-Lundgren P. Jensen S. Drai J. Lindbæk M. Identification of cultural determinants of antibiotic use cited in primary care in Europe: a mixed research synthesis study of integrated design "Culture is all around us".BMC Public Health. 2015; 15: 908Crossref PubMed Scopus (52) Google Scholar]. Hofstede's cultural dimensions were commonly applied in their study to measure cultural disparities, of which power distance, uncertainty avoidance, and masculinity versus femininity were associated with antibiotic consumption. Other cultural determinants included patients' work ethos (e.g. whether to continue working when stricken by illnesses), drug perception (e.g. fear of toxicity, taking antibiotics to speed up recovery), and practitioners' practice context (e.g. perceiving patients' expectations, patient education strategies). Factors such as day-care attendance and practices, living conditions, vaccination coverage, and social pressure could influence antibiotic use. In summary, the evidence base demonstrates that antibiotic use is not merely a medical issue, but a topic that also calls for solutions from sociocultural aspects [[7]Minssen T. Outterson K. Rogers Van Katwyk S. Batista P.H.D. Chandler C.I.R. Ciabuschi F. et al.Social, cultural and economic aspects of antimicrobial resistance.Bull World Health Organ. 2020; 98: 823Crossref PubMed Scopus (6) Google Scholar]. To address the gap, Dr Lin led an implementation science systematic review in 2020, identifying 25 public target intervention studies with behavioural change techniques aiming to reduce unnecessary antibiotic use [[8]Lin L. Alam P. Fearon E. Hargreaves J.R. Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review.Implement Sci. 2020; 15: 90Crossref PubMed Scopus (3) Google Scholar]. Most conducted campaigns for public education and were in high-income settings. However, intervention assessments revealed that conveying knowledge to the public did not change people's attitudes and behaviours. Globally, similar education materials were used in different contexts, but many lacked culturally sensitive and theoretically grounded adaptations [[9]Huttner B. Saam M. Moja L. Mah K. Sprenger M. Harbarth S. et al.How to improve antibiotic awareness campaigns: findings of a WHO global survey.BMJ Glob Health. 2019; 4e001239Crossref PubMed Scopus (42) Google Scholar]. Dr Lin also identified the research gap that public target interventions were absent in low-to-middle-income settings [[8]Lin L. Alam P. Fearon E. Hargreaves J.R. Public target interventions to reduce the inappropriate use of medicines or medical procedures: a systematic review.Implement Sci. 2020; 15: 90Crossref PubMed Scopus (3) Google Scholar]. According to our data (unpublished), most interventions that aimed to reduce inappropriate antibiotic use in China were implemented in primary care settings to reduce inappropriate antibiotic prescribing, largely ignoring demand-side factors, and sociocultural determinants were scarcely embedded in the intervention designs. Therefore, we very much agree with the correspondents that few interventions tailored the interventions to specific settings and individuals. Campaigns should convey information targeting multiple components, such as incorporating a theory-grounded framework in our recent publication (Health Belief Model and Socio-ecological Model) [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. There is a need to share pilot and formative findings of intervention development in advancing implementation science to more effectively address regional differences and sociocultural determinants of antibiotic (mis)use. For example, a cost-effective point-of-care C-reactive protein testing intervention conducted in Myanmar and Thailand [[10]Althaus T. Greer R.C. Swe M.M.M. Cohen J. Tun N.N. Heaton J. et al.Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial.Lancet Glob Health. 2019; 7: e119-e131Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar] could be consulted in regions with limited resources, including some regions in Western China where health care providers routinely prescribe antibiotics out of fear for severe complications when C-reactive protein and other diagnostic testing was unavailable [[5]Lin L. Sun R. Yao T. Zhou X. Harbarth S. Factors influencing inappropriate use of antibiotics in outpatient and community settings in China: a mixed-methods systematic review.BMJ Glob Health. 2020; 5e003599Crossref Scopus (15) Google Scholar]. In conclusion, grounded in work of the past 20 years, our recent publication [[2]Sun R. Yao T. Zhou X. Harbarth S. Lin L. Non-biomedical factors affecting antibiotic use in the community: a mixed-methods systematic review and meta-analysis.Clin Microbiol Infect. 2022; 28: 345Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar] has again highlighted the critical challenge of reducing antibiotic use and combating antimicrobial resistance from multiple nonclinical aspects. We demonstrated the necessity to incorporate sociocultural perspectives, as well as evidence-based and theory-grounded framework for effective and appropriate interventions for prudent antibiotic use. Transparency declarationThe authors declare that they have no conflicts of interest. This research was funded, in whole or in part, by the Wellcome Trust (grant number 215373/A/19/Z ) and by [email protected] administered by Innovation and Technology Commission. For the purpose of open access, the author has applied for a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. The funder had no role in study design, decision to publish, or preparation of the manuscript. The authors declare that they have no conflicts of interest. This research was funded, in whole or in part, by the Wellcome Trust (grant number 215373/A/19/Z ) and by [email protected] administered by Innovation and Technology Commission. For the purpose of open access, the author has applied for a CC BY public copyright licence to any author-accepted manuscript version arising from this submission. The funder had no role in study design, decision to publish, or preparation of the manuscript. Re: non-biomedical factors affecting antibiotic use in the communityClinical Microbiology and InfectionVol. 28Issue 6PreviewIn their recent publication, Sun et al. found that community antibiotic use was prevalent and influenced by multifaceted, nonbiomedical factors across high- and low-to-middle–income countries [1]. This publication emphasizes the importance of antibiotic stewardship and has notable strengths in the breadth of works, holistic nature, and socioecological and health belief theory–driven assessment. In addition, the authors further highlight the need for One Health stewardship by revealing that Chinese pig farmers who purchased and stored nonprescription antibiotics for their pigs were more likely to buy and keep nonprescription antibiotics for themselves in their homes [1]. Full-Text PDF