Abstract
Background: The reasons underpinning the large differences in the prevalence of resistance to macrolides in Streptococcus pneumoniae are imperfectly understood. We assessed if the volume of macrolides used in food-animals could play a role. Methods: Logistic regression was used to assess if the country-level prevalence of pneumococcal macrolide resistance was associated with country-level macrolide consumption in food animals and humans. Results: In both univariate and multivariate models, macrolide use in food-producing animals was significantly associated with pneumococcal macrolide resistance (coeff. = 339, 95% CI 21658; P = 0.037). Conclusions: In vitro and individual-level studies are required to verify or refute the hypothesis that macrolides used in food animals can promote the spread of macrolide resistance in humans. © 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
Generated Summary
This study examines the relationship between macrolide use in food-producing animals and the prevalence of macrolide resistance in Streptococcus pneumoniae. Employing a global ecological analysis, the research investigates whether the volume of macrolides used in food animals plays a role in the increasing resistance to macrolides in S. pneumoniae. The study utilizes logistic regression to assess the association between country-level macrolide consumption in food animals and humans, and the prevalence of pneumococcal macrolide resistance. Data on macrolide consumption in food-producing animals, human macrolide consumption, and macrolide resistance prevalence were gathered from various sources, including the Center for Disease Dynamics, Economics & Policy (CDDEP) ResistanceMap database and IQVIA. The analysis involved statistical modeling to explore the correlations, with the aim of providing insights into the factors driving macrolide resistance.
Key Findings & Statistics
- The study found that in the 35 countries with available data, the prevalence of macrolide resistance in S. pneumoniae varied considerably, with a median of 17% (IQR 11-31%).
- Among these countries, macrolide consumption data for both animal food and humans were available for 24 and 33 countries, respectively.
- The use of macrolides in food-producing animals and humans varied widely.
- The median macrolide use in food-animals was 0.00087 kg/PCU (IQR 0.00032-0.00208 kg/PCU).
- The median human macrolide consumption was 998 DID (IQR 593-1301 DID).
- In the univariate analysis, macrolide use in food-producing animals showed a positive association with macrolide resistance, but this association was only significant for food-animals (coeff. = 315 [95% CI 12-618]; P=0.041).
- In the multivariate model, macrolide use in food-producing animals remained significantly associated with pneumococcal macrolide resistance (coeff. = 339 [95% CI 21-658]; P=0.037).
- The study references a 2000 study where macrolide consumption in China was less than one-sixth of the median consumption in European countries, yet by 2001, 74% of S. pneumoniae isolates in China were resistant to erythromycin, rising to 96% by 2009.
- The erythromycin MSC for Escherichia coli was found to be <0.2 µg/ml.
Other Important Findings
- The study highlights that global variations in macrolide resistance in S. pneumoniae are not fully understood.
- The study points out that population-level consumption of macrolides is positively associated with the prevalence of macrolide resistance.
- The research notes that the explosive emergence of macrolide resistance in certain bacterial species in Asia in the 1990s could not be fully explained by population-level macrolide consumption.
- The study references that macrolide consumption in food-animals could also play a role in antimicrobial resistance.
- The study mentions that in vitro and individual-level studies are needed to verify or refute the hypothesis that macrolides used in food animals can promote the spread of macrolide resistance in humans.
- The study references that ecological studies have found a positive country-level association between the consumption of quinolones in food-producing animals and the prevalence of ciprofloxacin resistance in four gram-negative species.
- The study indicates that an ecological analysis of countries in Europe found a positive association between macrolide use in animal husbandry and macrolide resistance in Campylobacter spp. in humans.
- A systematic review and meta-analysis found that restricting the use of macrolides in food-producing animals was associated with a decline of macrolide resistance in both animals and humans.
Limitations Noted in the Document
- The study is an ecological study, thus it is susceptible to the ecological inference fallacy.
- The study only had data available for a limited number of countries for all the three variables considered.
- The macrolide resistance prevalence data obtained from CDDEP are based on various methodologies, making cross-country comparisons sub-optimal.
- The study could not adjust the analyses for differences in susceptibility testing strategies between countries or over time.
- The study acknowledges that there are many other risk factors apart from the volume of macrolides consumed that could drive pneumococcal macrolide resistance.
- The study did not control for factors such as pneumococcal vaccination coverage, excessive consumption of other classes of antimicrobials, weak antimicrobial stewardship, travel by humans, and variations in environmental temperatures.
Conclusion
The research reveals a positive ecological-level association between the use of macrolides in food-producing animals and the prevalence of macrolide resistance in S. pneumoniae. This finding supports the hypothesis that the use of macrolides in food animals may contribute to the spread of macrolide resistance in humans. However, the study acknowledges the limitations inherent in ecological studies and calls for further investigation through in vitro and individual-level studies. The authors emphasize the need for in vitro studies to determine the minimum selection concentrations (MSCs) of macrolides for S. pneumoniae and to assess the impact of macrolides in combination with other agents. Randomized controlled trials in humans or animal models are suggested to determine macrolide MSCs for commensal streptococci/S. pneumoniae. The study’s findings underscore the importance of considering the role of food-animal macrolide use in the context of global efforts to combat antimicrobial resistance. The positive association found in this study provides a basis for further research and potential policy interventions aimed at reducing the use of macrolides in food production, with the ultimate goal of mitigating the spread of macrolide-resistant S. pneumoniae in human populations. These findings support and are consistent with previous studies that have found connections between antimicrobial use in animal husbandry and resistance in human populations.