Antibiotic resistance, stewardship, and consumption
Authors: Koen B Pouwels, Anuja Chatterjee, Ben S Cooper, Julie V Robotham
Journal: The Lancet Planetary Health (2019)

Peter Collignon and colleagues1Collignon P Beggs JJ Walsh TR Gandra S Laxminarayan R Anthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysis.Lancet Planet Health. 2018; 2: e398-e405Summary Full Text Full Text PDF PubMed Scopus (293) Google Scholar aim to improve understanding of global antibiotic resistance drivers by quantifying associations between antibiotic resistance and potential contributing factors. A recent systematic review including 565 studies primarily reporting patient-level data found that antibiotic exposure, underlying disease, and invasive procedures had the greatest evidence of being antibiotic resistance drivers.2Chatterjee A Modarai M Naylor NR et al.Quantifying drivers of antibiotic resistance in humans: a systematic review.Lancet Infect Dis. 2018; 18: e368-e378Summary Full Text Full Text PDF PubMed Scopus (152) Google Scholar Given the small evidence base for the role of community factors,2Chatterjee A Modarai M Naylor NR et al.Quantifying drivers of antibiotic resistance in humans: a systematic review.Lancet Infect Dis. 2018; 18: e368-e378Summary Full Text Full Text PDF PubMed Scopus (152) Google Scholar we fully concur with Collignon and colleagues about the importance of considering such factors in the spread of antibiotic resistance.1Collignon P Beggs JJ Walsh TR Gandra S Laxminarayan R Anthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysis.Lancet Planet Health. 2018; 2: e398-e405Summary Full Text Full Text PDF PubMed Scopus (293) Google Scholar However, as the authors recognise, correlation does not imply causation—indeed, national meticillin-resistant Staphylococcus aureus rates strongly correlate with unfair play of national football teams.3Meyer E Gastmeier P Schwab F National MRSA rates run along with fair play of national football teams: a cross-sectional data analysis of the European Football Championship, 2008.Infection. 2013; 41: 215-218Crossref PubMed Scopus (3) Google Scholar Conversely, it would be a mistake to conclude that weak (or even inverse) correlation between antibiotic use and antibiotic resistance at the national level implies an absence of a strong causal relationship (appendix). There are several limitations to using current global data. First, important between-country differences in the quality and representativeness of data are likely to exist. For example, blood cultures are less frequently taken in resource-poor settings than in resource-rich settings, and often only when patients do not respond to empirical therapy, leading to inflated estimates of resistance.4De Kraker ME Stewardson AJ Harbarth S Will 10 million people die a year due to antimicrobial resistance by 2050?.PLoS Med. 2016; 13: e1002184Crossref PubMed Scopus (606) Google Scholar Moreover, in lower income countries, a substantial proportion of antibiotics used might come from informal providers and not appear in consumption data. Both factors would be expected to weaken associations between reported antibiotic use and resistance, and could lead to positive associations between governance and infrastructure and antibiotic resistance, even if these factors have no effect on antibiotic resistance. Additionally, comparisons based on national-level data can be problematic, particularly when many countries have a sharp divide between subpopulations that overuse antibiotics and those that are without access. Patients lacking access to antibiotics are also less likely to have access to health-care facilities where blood samples are taken. Considering antibiotic consumption only on a national per capita basis could therefore considerably underestimate antibiotic consumption in subpopulations where resistance is being measured. Using a multivariable model will unfortunately not overcome such biases. Finally, the analysis simplifies antibiotic use such that the matter of which antibiotic is consumed is not considered, which will have importance in terms of resistance development.5Pouwels KB Freeman R Muller-Pebody B et al.Association between use of different antibiotics and trimethoprim resistance: going beyond the obvious crude association.J Antimicrob Chemother. 2018; 73: 1700-1707Crossref PubMed Scopus (37) Google Scholar Combined antibiotic consumption measures might therefore not be optimal for determining the contribution of antibiotic consumption to resistance. While we welcome the central conclusion of the study about the need for efforts to reduce the spread of antibiotic resistance in the community, we are concerned that fundamental limitations of the data could have led to an undervaluing of the role of antibiotic stewardship. We declare no competing interests. Download .pdf (.43 MB) Help with pdf files Supplementary appendix Antibiotic resistance, stewardship, and consumptionWe read with interest the work of Peter Collignon and colleagues,1 in which the authors studied the effect of cofactors on the prevalence of precise antibiotic resistance profiles. Amongst their discoveries, the authors identified inverse relationships between global antibiotic consumption and the antibiotic resistance profiles that they studied. Full-Text PDF Open AccessAntibiotic resistance, stewardship, and consumption – Authors' replyWe agree with Koen B Pouwels and colleagues, that association does not mean cause and effect. In our paper, we acknowledged limitations in using national-level data on antibiotic usage and resistance patterns, and that antibiotic use is an important factor in antibiotic resistance. We note that our results, which show that the spread of resistant bacteria by anthropological factors is at least as important as antibiotic use, are supported by other studies.1 Full-Text PDF Open AccessAnthropological and socioeconomic factors contributing to global antimicrobial resistance: a univariate and multivariable analysisReduction of antibiotic consumption will not be sufficient to control antimicrobial resistance because contagion—the spread of resistant strains and resistance genes—seems to be the dominant contributing factor. Improving sanitation, increasing access to clean water, and ensuring good governance, as well as increasing public health-care expenditure and better regulating the private health sector are all necessary to reduce global antimicrobial resistance. Full-Text PDF Open Access