In a recent review published in Nature Communications, researchers reviewed existing data on the association between substandard or falsified (SF) antibiotics and antimicrobial resistance (AMR).
Study: The uncertain role of substandard and falsified medicines in the emergence and spread of antimicrobial resistance. Image Credit: Fahroni/Shutterstock.com
Background
Antimicrobial resistance is a population health concern worldwide, especially with counterfeit and inferior medications. Despite the harmful impact on morbidity and mortality, the association has not been extensively investigated.
Further research is required to understand the effects, how medication exposure affects resistance, and how active pharmaceutical substances in these treatments are distributed.
About the review
In the present review, researchers describe the impact of SF antibiotic usage on AMR.
An introduction to substandard antimicrobials
Substandard medications are approved medical items that fail to fulfill quality standards or specifications owing to manufacturing faults or supply chain deterioration. Falsified pharmaceuticals purposefully mislead their identity, composition, or source and may include an excessive or insufficient amount of active pharmaceutical ingredients (API).
Both low-quality goods can have an excessive or insufficient amount of active pharmaceutical ingredients (API), no API, an API that differs from the claimed one, and/or fail dissolution tests. These goods may result in worse patient outcomes and an increased strain on healthcare systems and economies.
The conventional approach to antimicrobial dosage regimens, founded on the hitting hard and early concept, minimizes infection-related morbidities and can be justified to combat AMR by ensuring optimal dosage to destroy even partly resistant microorganisms.
Furthermore, by decreasing the duration of therapy, the harsh chemotherapy method minimizes the selection window for the emergence of resistant mutants. A larger dose, on the other hand, provides a stronger selection advantage to resistant mutants.
The compromise between microbe density and the selection advantage of AMR indicates that intermediate doses would result in a faster rate of resistance development.
The inverted-U curve expands on the theoretical concepts of mutation-selection window (MSW), mutant prevention concentration (MPC), and minimum inhibitory concentration (MIC), indicating the probability of sub-MIC resistance emergence and emphasizing that all concentrations in the expanded MSW would not result in a similar AMR rate.
The link between substandard antimicrobials and antibiotic resistance
Degraded rifampicin, a first-line TB treatment, has been demonstrated in vitro to select for resistance genes in Mycobacterium smegmatis and Escherichia coli. At the same time, subtherapeutic doses of dihydroartemisinin, a critical malaria medicine, have been found to prefer resistant strains of Plasmodium falciparum.
The impact of substandard antibiotics on AMR is determined by the volume and bioavailability (the extent of API accessibility at the infection site) of the active pharmaceutical ingredients in the usual course of treatment with supreme-quality antimicrobials and how these changes in SF medicine.
SF drugs would contribute to AMR in cases where the bioavailable active pharmaceutical ingredient in the medication has a greater incidence of AMR emergence than the initial dosage.
Based on the biological mechanism, the API absorption rate could also influence AMR rates since lower absorption rates reduce the concentration of the peak drug. Substandard and falsified medications may also have an API other than the one specified.
SF medications may induce an increase in AMR if they contain marginally lesser than expected quantities of the specified API or have poor bioavailability due to improper dissolution and absorption; however, SF medications may lower the AMR rate if they include no API, considerably lesser API, or APIs for which the offending pathogen may not have susceptibility.
Nonetheless, clinical effects are likely to be substantially poorer. Since the connection between the ARM rate and dosage is likely biased in favor of AMR, only significant or entire decreases in the API content could result in AMR.
Furthermore, if an individual using SF drugs subsequently completes a regular course of high-quality antibiotics, AMR may increase. Similarly, SF medications containing excessive API may induce greater toxicity and prompt patients to discontinue treatment early.
In the cases of untreated infections, the likelihood of the transfer of resistant strains increases. API% fraction and bioavailability might influence the transfer of resistant microorganisms via various methods.
Treatment with a lower percentage of active pharmaceutic ingredients or lesser bioavailable antibiotics may impact resistant microwave density in an infected person differently than a conventional course of superior-quality antibiotics.
Suppose an individual acquires low-level infection by a resistant pathogenic organism and subsequently receives treatment that confers a competitive advantage to the pathogen or allows the microbe to increase its population size. In that case, this may increase resistant microbe density and lead to onward transmission.
SF medications may enhance susceptibility to resistant microbial infections while decreasing transmission from individuals infected with that microbe.
Both methods occur when individuals with sensitive infections recover but become vulnerable to re-infection with the resistant microbe in the previous instance and no longer contribute to transmission, allowing for the spread of resistant microbes in the latter situation. In both circumstances, SF medications can mitigate the effects by decreasing the chance of infection clearance.
Based on the review findings, substandard and counterfeit drugs can alter AMR levels, influenced by the antibiotic combination and the infection. Epidemiological models can shed light on the frequency, percentage API, and bioavailability of SF medications.
Understanding the influence of SF veterinary drugs on human, animal, and environmental health requires a One Health viewpoint. Worldwide initiatives such as political will, increased risk-based surveillance, empowerment of medicine inspectors, improved regulation, and reduced deterioration during transit are required to lessen the burden of SF medications.
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