Irrational use of antibiotics in Iran from the perspective of complex adaptive systems: redefining the challenge.

BACKGROUND: Irrational use of antibiotics is proving to be a major concern to the health systems globally. This results in antibiotics resistance and increases health care costs. In Iran, despite many years of research, appreciable efforts, and policymaking to avoid irrational use of antibiotics, yet indicators show suboptimal use of antibiotics, pointing to an urgent need for adopting alternative approaches to further understand the problem and to offer new solutions. Applying the Complex Adaptive Systems (CAS) theory, to explore and research health systems and their challenges has become popular. Therefore, this study aimed to better understand the complexity of the irrational use of antibiotics in Iran and to propose potential solutions. METHOD: This research utilized a CAS observatory tool to qualitatively collect and analyse data. Twenty interviews and two Focus Group discussions were conducted. The data was enriched with policy document reviews to fully understand the system. MAXQDA software was used to organize and analyze the data. RESULT: We could identify several diverse and heterogeneous, yet highly interdependent agents operating at different levels in the antibiotics use system in Iran. The network structure and its adaptive emergent behavior, information flow, governing rules, feedback and values of the system, and the way they interact were identified. The findings described antibiotics use as emergent behavior that is formed by an interplay of many factors and agents over time. According to this study, insufficient and ineffective interaction and information flow regarding antibiotics between agents are among key causes of irrational antibiotics use in Iran. Results showed that effective rules to minimize irrational use of antibiotics are missing or can be easily disobeyed. The gaps and weaknesses of the system which need redesigning or modification were recognized as well. CONCLUSION: The study suggests re-engineering the system by implementing several system-level changes including establishing strong, timely, and effective interactions between identified stakeholders, which facilitate information flow and provision of on-time feedback, and create win-win rules in a participatory manner with stakeholders and the distributed control system.

Pyocyanin Restricts Social Cheating in Pseudomonas aeruginosa.

Quorum sensing (QS) in Pseudomonas aeruginosa coordinates the expression of virulence factors, such as exoproteases and siderophores, that are public goods utilized by the whole population of bacteria, regardless of whether they invested or not in their production. These public goods can be used by QS defective mutants for growth, and since these mutants do not contribute to public goods production, they are considered social cheaters. Pyocyanin is a phenazine that is a toxic, QS-controlled metabolite produced by P. aeruginosa. It is a redox-active compound and promotes the generation of reactive oxygen species; it also possesses antibacterial properties and increases fitness in competition with other bacterial species. Since QS-deficient individuals are less able to tolerate oxidative stress, we hypothesized that the pyocyanin produced by the wild-type population could promote selection of functional QS systems in this bacterium. Here, we demonstrate, using competition experiments and mathematical models, that, indeed, pyocyanin increases the fitness of the cooperative QS-proficient individuals and restricts the appearance of social cheaters. In addition, we also show that pyocyanin is able to select QS in other bacteria such as Acinetobacter baumannii.