Rational Pharmacotherapy in Infectious Diseases: Issues Related to Drug Residues in Edible Animal Tissues

Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs through the diet, residues in food are evaluated for effects following chronic exposures. Parameters such as an acceptable daily intake (ADI), the no-observed-adverse-effect level (NOAEL), maximum residue limits (MRLs), and the withdrawal periods (WPs) are determined for each drug used in livestock. Drug residues in food exceeding the MRLs usually appear when failing the GVP application. Different factors related either to the treated animal or to the type of drug administration, and even the type of cooking can affect the level of residues in edible tissues. Residues above the MRLs can have a diverse negative impact, mainly on the consumer’s health, and favor antimicrobial resistance (AMR). Drug residue monitoring programmes are crucial to ensure that prohibited or authorized substances do not exceed MRLs. This comprehensive review article addresses different aspects of drug residues in edible tissues produced as food for human consumption and provides relevant information contributing to rational pharmacotherapy in food-producing animals.

The system of monitoring of inhibitory drug residues in raw cows' milk in Slovakia

This article provides brief information on the system of monitoring raw cows’ milk for the presence of inhibitory veterinary drug residues in the Slovak Republic. We are describing in detail how the monitoring is carried out and what laboratory methods are used for this monitoring. We also deal with the issue of the disposal of contaminated milk. The presence of inhibitory veterinary drugs like antibiotics or residues of these drugs in milk in an amount exceeding maximal residual limits defined in legislation is illegal. Milk supplies containing detectable concentrations are not acceptable. The reputation of milk as a healthy and safe food should be protected. Dairy companies and consequently consumers want to be confident that milk and milk products are free of inhibitory veterinary drugs contamination. Small amounts of certain antimicrobial agents may affect antibiotic resistance in the human population, some percentage of the population is hypersensitive to antibiotics and other drugs. The presence of drug residues in milk affects the technological process of the production of fermented dairy products. Each country should implement a system of monitoring these drugs' residues in food. The system, which is applied in Slovakia, is effective, it can detect and the presence of these substances before milk processing in dairies. The total incidence of these substances in 2020 was 0.025% of all 12,181 samples tested in central testing laboratories. During the last 20 years.

The impact of the COVID-19 pandemic on the financial sector in medicine: features of centralized state procurement of drugs and medical devices in Ukraine for the period 2018-2021

ABSTRACT. Coronavirus disease (COVID-19) has deeply impacted the global health care system, and the redistribution of funding for medical care violated the prevention and treatment of chronic non-communicable diseases, including hypertension, tuberculosis, and HIV. In 2020, centralized state procurement of medicines in Ukraine was for the first time conducted via the online platform Prozorro. Of the 483 items planned to be purchased, 375 items (78 %) were successfully contracted. In the current 2021, tenders were announced for the purchase of 555 of 562 items. In most fields of medicine, the drugs to be purchased are 100 % covered by tenders. The lowest percentage of coverage is observed for pulmonary arterial hypertension (66.67 %). In today’s complex environment, not only COVID-19 should be actively combated, but other diseases should be also kept in mind when carefully planning the funding of various fields of medicine through the analysis of data from previous years. The money saved can be used to eliminate the consequences of the COVID-19 pandemic, and to purchase the necessary medicines. The creation of a single database of drug residues in medical institutions (chatbot in the Telegram messenger) can be called a positive innovation. Control of drug residues and their adequate redistribution makes it possible to rationally use this resource without spending money on unnecessary purchases. In general, despite the medical and financial impact of COVID-19, Ukraine’s healthcare system continues to withstand pressure and change for the better. Further improvement of the system of centralized procurement of medicines will be able to overcome the problem of lack of necessary drugs.

Which illicit drugs are injected in Oslo? A study based on analysis of drug residues in used injection equipment and self-reported information

Background People who inject drugs (PWID) have a high risk of premature death due to fatal overdoses. Newly emerged fentanyls, much more potent than heroin and other opioids, may increase this risk further. Therefore, precise information on injected drugs is critical to improving prevention strategies. Aims This study aimed to analyse drug residues in used injection equipment in order to determine drug and drug combinations and compare and complement findings with self-reported information. Methods Used syringes and needles ( n=766) were collected at the supervised drug consumption facilities, the needle exchange service and two low-threshold health services for problem drug users in Oslo, Norway. The material was collected every third month from June 2019 to June 2020 and analysed for 64 substances using highly specific analytical methods (ultra–high performance liquid chromatography tandem mass spectrometry). Additionally, a street-recruited sample of PWID was interviewed from 2017 to 2019 regarding their drug injection habits ( n=572). Results Heroin (65.5%) or amphetamines (59.8%), often in combination (30.5%), were commonly detected in drug residues. Other opioids, stimulants or benzodiazepines were rarely detected (6.1%). Fentanyl was detected in only one syringe. Heroin was the most reported drug (77.6% during the past four weeks, 48.3% daily/almost daily), followed by amphetamines (57.5% during the past four weeks, 23.1% daily or almost daily). Injection of methadone, buprenorphine and dissolved tablets was self-reported more frequently than determined in drug residue findings. Conclusions Analysis of the injection equipment proved useful as a non-invasive, rapid and accurate means to obtain detailed information on injected drugs in Oslo and supplement traditional PWID survey information.

Geraniol, a Potential Alternative to Antibiotics for Bovine Mastitis Treatment Without Disturbing the Host Microbial Community, Does Not Lead to Drug Residues or Induce Drug Resistance

BackgroundMastitis is one of the important diseases of the dairy cow. Currently, mastitis treatment in dairy cows is mainly based on antibiotics. However, the use of antibiotics causes adverse effects, including drug resistance, drug residues, host-microbiome destruction, and environmental pollution. Geraniol, extracted from Fructus Tsaoko, has demonstrated good antibacterial activity in mouse model. Geraniol and antibiotics were used to treat cows with clinical mastitis to test this possibility of geraniol as a potential alternative to antibiotics for bovine mastitis treatment. The effectiveness of treatment, improvement in inflammatory factors, the influence on microbiome, presence of drug residues, and induction of drug resistance were compared and analyzed.ResultsGeraniol demonstrated a better therapeutic rate than antibiotics on clinical mastitis of cows, with a longer course of treatment. Antibiotics and geraniol significantly reduced the abundance of pathogenic bacteria and restored the microbial community in milk. Meanwhile, geraniol increased the abundance of probiotics in milk. Interestingly, geraniol did not destroy the gut microbial community of cows, whereas antibiotics significantly reduced the diversity and destroyed the community structure of the gut microbiome in cows. Conversely, geraniol increased the diversity of the gut microbiome. Besides, no geraniol residue was detected in the milk four days after treatment discontinuation. However, antibiotic residues were detected in milk at the 7th day after drug withdrawal. In vitro experiments revealed that geraniol did not induce drug resistance in the Escherichia coli strain ATCC25922 after 120 generations of culturing, while antibiotics induced resistance after 10 generations. ConclusionsOur results suggest that geraniol has antibacterial and anti-inflammatory effects similar to antibiotics. Additionally, it retains the structure of the host-microbial community and does not lead to drug residues or induce drug resistance. Therefore, geraniol can be a potential substitute for antibiotics to treat mastitis and be widely used in the dairy industry.

Large-Scale Data Mining of Rapid Residue Detection Assay Data From HTML and PDF Documents: Improving Data Access and Visualization for Veterinarians

Extra-label drug use in food animal medicine is authorized by the US Animal Medicinal Drug Use Clarification Act (AMDUCA), and estimated withdrawal intervals are based on published scientific pharmacokinetic data. Occasionally there is a paucity of scientific data on which to base a withdrawal interval or a large number of animals being treated, driving the need to test for drug residues. Rapid assay commercial farm-side tests are essential for monitoring drug residues in animal products to protect human health. Active ingredients, sensitivity, matrices, and species that have been evaluated for commercial rapid assay tests are typically reported on manufacturers' websites or in PDF documents that are available to consumers but may require a special access request. Additionally, this information is not always correlated with FDA-approved tolerances. Furthermore, parameter changes for these tests can be very challenging to regularly identify, especially those listed on websites or in documents that are not publicly available. Therefore, artificial intelligence plays a critical role in efficiently extracting the data and ensure current information. Extracting tables from PDF and HTML documents has been investigated both by academia and commercial tool builders. Research in text mining of such documents has become a widespread yet challenging arena in implementing natural language programming. However, techniques of extracting tables are still in their infancy and being investigated and improved by researchers. In this study, we developed and evaluated a data-mining method for automatically extracting rapid assay data from electronic documents. Our automatic electronic data extraction method includes a software package module, a developed pattern recognition tool, and a data mining engine. Assay details were provided by several commercial entities that produce these rapid drug residue assay tests. During this study, we developed a real-time conversion system and method for reflowing contents in these files for accessibility practice and research data mining. Embedded information was extracted using an AI technology for text extraction and text mining to convert to structured formats. These data were then made available to veterinarians and producers via an online interface, allowing interactive searching and also presenting the commercial test assay parameters in reference to FDA-approved tolerances.