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PloS One 2022Antimicrobial resistance (AMR) is a global public health emergency driven by the indiscriminate use of antimicrobial agents in humans and animals. Antimicrobial...
BACKGROUND
Antimicrobial resistance (AMR) is a global public health emergency driven by the indiscriminate use of antimicrobial agents in humans and animals. Antimicrobial consumption surveillance guides its containment efforts. In this study, we estimated, for the first time, veterinary consumption of Critically Important Antimicrobials with Highest Priority (CIA-HtP) for Pakistan.
METHODS
The study used an export/import database which provided imports data collected from the Pakistan Customs Authority. We investigated imports of 7 CIA-HtP and various poultry feed additives/growth promoters (FAs/GPs) identified from a survey of 10 poultry and dairy farms in Punjab province in Pakistan and a previously published study, over a three-year period of 2017-2019. Antimicrobial consumption was estimated in mg/kg of country's animal biomass.
FINDINGS
Imports, in tonnes, for these 7 CIA-HtP were for the years 2017-19: tylosin 240.84, enrofloxacin 235.14, colistin 219.73, tilmicosin 97.32, spiramycin 5.79, norfloxacin 5.55, ceftiofur 1.02 for a total 805.39 tonnes. The corresponding antimicrobial consumption was 10.05 mg/kg of animal biomass. The poultry FAs/GPs contained: zinc bacitracin, enramycin, bacitracin methylene disalicylate, tylosin, tiamulin, colistin, lincomycin, streptomycin, flavophospholipol, tilmicosin, and penicillin with a total antimicrobial chemical compound (ACC) import volume of 577.18 tonnes for the years 2017-2019; and an estimated consumption of 96.53 mg/kg of poultry biomass.
INTERPRETATION
These antimicrobials were a mix of macrolides, quinolones, polymyxins and cephalosporins, among which are some also on the Watch or Reserve list by the WHO, indicating the need for stewardship and to conserve essential antimicrobials to contain AMR. The finding that a yearly average of 192.39 tonnes of the ACC imported were FAs/GPs further highlight the need for stronger regulation and enforcement.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Colistin; Humans; Pakistan; Poultry; Tylosin
PubMed: 36103474
DOI: 10.1371/journal.pone.0273821 -
The Korean Journal of Parasitology Jun 2021Toxoplasma gondii infection is widespread worldwide, not only posing a serious threat to human food safety and animal husbandry, but also endangering human health. The...
Toxoplasma gondii infection is widespread worldwide, not only posing a serious threat to human food safety and animal husbandry, but also endangering human health. The selectivity index was employed to measure anti-T. gondii activity. Hederagenin (HE) exhibited potent anti-T. gondii activity and low cytotoxicity. For this reason, HE was selected for in vivo experiments. HE showed 64.8%±13.1% inhibition for peritoneal tachyzoites in mice, higher than spiramycin 56.8%±6.0%. Biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde, illustrated that HE was a good inhibitor of T. gondii in vivo. This compound was also effective in relieving T. gondii-induced liver damage. Collectively, it was demonstrated that HE had potential as an anti-T. gondii agent.
Topics: Animals; Aspartate Aminotransferases; Mice; Oleanolic Acid; Toxoplasma; Toxoplasmosis
PubMed: 34218602
DOI: 10.3347/kjp.2021.59.3.297 -
Emerging Infectious Diseases Aug 2020Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients...
Necrotizing pneumonia induced by Panton-Valentine leukocidin-secreting Staphylococcus aureus is a rare but life-threatening infection that has been described in patients after they had influenza. We report a fatal case of this superinfection in a young adult who had coronavirus disease.
Topics: Adult; Anti-Bacterial Agents; Bacterial Toxins; Betacoronavirus; COVID-19; COVID-19 Testing; Cefotaxime; Clindamycin; Clinical Laboratory Techniques; Coronavirus Infections; Exotoxins; Fatal Outcome; Humans; Leukocidins; Linezolid; Male; Metronidazole; Necrosis; Pandemics; Pneumonia, Staphylococcal; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Spiramycin; Staphylococcus aureus; Tomography, X-Ray Computed
PubMed: 32298228
DOI: 10.3201/eid2608.201413 -
Antibiotics (Basel, Switzerland) Jul 2022() is a highly contagious avian pathogen responsible for significant economic losses for the poultry industry. In some circumstances, antimicrobial treatment is useful...
The Monitoring of Minimum Inhibitory Concentrations during the Last Decade (2010-2020) Seems to Reveal a Comeback of Susceptibility to Macrolides, Tiamulin, and Lincomycin.
() is a highly contagious avian pathogen responsible for significant economic losses for the poultry industry. In some circumstances, antimicrobial treatment is useful to contain clinical signs of infection in birds. However, antimicrobial resistance emergence is now common among animal pathogens, becoming a worldwide health concern. The collection of minimum inhibitory concentration (MIC) data is fundamental for an appropriate antimicrobial use and for fighting antimicrobial resistance emergence. However, MIC data can only be generated in specialized laboratories, and therefore they are not regularly available. MICs of 67 non-vaccine-derived isolates collected in Italy between 2010 and 2020 were obtained. Although 79.1% of the isolates showed enrofloxacin MICs ≥ 8 µg/mL, a statistically significant trend toward low MICs of erythromycin, tylosin, tilmicosin, spiramycin, tiamulin, and lincomycin was observed, indicating a comeback to susceptibility of toward these drugs. Doxycycline proved to be slightly more effective than oxytetracycline. The present study shows that changed its susceptibility toward many of the drugs most commonly used for its containment over a ten-year period.
PubMed: 36009890
DOI: 10.3390/antibiotics11081021 -
RSC Advances Oct 2019In this work, a new and simple method was developed for the synthesis of uncovered and high-selectivity spiramycin-based molecularly imprinted microspheres (SP-MIMs) by...
In this work, a new and simple method was developed for the synthesis of uncovered and high-selectivity spiramycin-based molecularly imprinted microspheres (SP-MIMs) by Pickering emulsion polymerization using spiramycin as templates. And surprisingly the solid particles were absent on the surface of imprinted microspheres, which can be ascribed to the spores (GLS): they were firstly selected to be the stabilizers for the Pickering emulsion in this new strategy. Through a series of adsorption experiments, the uncovered SP-MIMs were proven to possess more excellent selective recognition and removal ability for template SP in aqueous solution. And SP-MIMs could be reused for many times without significant loss of adsorption capacity, indicating the satisfactory regeneration performance. Therefore, SP-MIMs can be employed as a promising adsorbent for the selective removal of SP from aqueous media, and this strategy will contribute to overcoming the shortcomings of stabilizer particles on the surface of the as-prepared imprinting microspheres, because these solid particles lack the special selective recognition activity of template molecules, and may disturb the adsorption effect of imprinting microspheres.
PubMed: 35530711
DOI: 10.1039/c9ra07745f -
Journal of Enzyme Inhibition and... Dec 2023Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke...
Investigating the potential anticancer activities of antibiotics as topoisomerase II inhibitors and DNA intercalators: , molecular docking, molecular dynamics, and SAR studies.
Topoisomerase II (TOP-2) is a promising molecular target for cancer therapy. Numerous antibiotics could interact with biologically relevant macromolecules and provoke antitumor potential. Herein, molecular docking studies were used to investigate the binding interactions of 138 antibiotics against the human topoisomerase II-DNA complex. Followed by the MD simulations for 200 ns and MM-GBSA calculations. On the other hand, the antitumor activities of the most promising candidates were investigated against three cancer cell lines using doxorubicin (DOX) as a reference drug. Notably, spiramycin () and clarithromycin () showed promising anticancer potentials on the MCF-7 cell line. Moreover, azithromycin () and exhibited good anticancer potentials against the HCT-116 cell line. Finally, the TOP-2 enzyme inhibition assay was carried out to confirm the proposed rationale. Briefly, potent TOP-2 inhibitory potentials were recorded for erythromycin () and roxithromycin (). Additionally, a SAR study opened eyes to promising anticancer pharmacophores encountered by these antibiotics.HighlightsMolecular docking studies of 139 antibiotics against the topoisomerase II-DNA complex., , , , and were the most promising and commercially available candidates.Molecular dynamics simulations for 200 ns for the most promising five complexes.MM-GBSA calculations for the frontier five complexes. and showed promising anticancer potentials on the MCF-7 cell line, besides, and exhibited good anticancer potentials against the HCT-116 cell line.Potent TOP-2 inhibitory potentials were recorded for and .
Topics: Humans; Topoisomerase II Inhibitors; Molecular Docking Simulation; Molecular Structure; Antineoplastic Agents; Intercalating Agents; Anti-Bacterial Agents; Structure-Activity Relationship; Molecular Dynamics Simulation; Cell Line, Tumor; DNA; DNA Topoisomerases, Type II; Drug Screening Assays, Antitumor
PubMed: 36701269
DOI: 10.1080/14756366.2023.2171029 -
Microbiological Research Oct 2020The PhoRP two-component system (TCS), one of the most important signaling pathways in Bacillus subtilis, regulates cell physiological reactions mainly under phosphate...
Using a phenotype microarray and transcriptome analysis to elucidate multi-drug resistance regulated by the PhoR/PhoP two-component system in Bacillus subtilis strain NCD-2.
The PhoRP two-component system (TCS), one of the most important signaling pathways in Bacillus subtilis, regulates cell physiological reactions mainly under phosphate starvation conditions. The mechanism by which PhoRP TCS regulates resistance towards antibiotics in B. subtilis strain NCD-2 was investigated in this study. Using phenotype microarray (PM) technology, the susceptibility of B. subtilis to 240 antimicrobial compounds was compared among the wild-type strain NCD-2, the phoR-null mutant (MR), and the phoP-null mutant (MP). Compared with the wild type, the MR mutant was more resistant to 13 antibiotics with different functions, and the MP mutant was more resistant to 14 antibiotics, of which 8 were 30S/50S ribosome-targeted. To investigate the molecular mechanisms involved in changing the level of antibiotic resistance, transcriptional analysis was performed to compare the differentially expressed genes among the wild-type strain and the MR and MP mutants. Compared with the wild-type strain, 294 genes were differentially expressed in the MR mutant, including 97 up-regulated genes and 197 down-regulated genes. Most of the differently expressed genes were associated with carbohydrate mechanism, amino acid mechanism, ABC-transporters and phosphotransferase systems. A total of 212 genes were differentially expressed in the MP mutant, including 10 up-regulated genes and 202 down-regulated genes, and most were associated with ribosome synthesis, amino acid metabolism, carbohydrate metabolism and ABC-transporters. The khtSTU operon (encoding the K efflux pump) that was up-regulated in the MP mutant was deleted by in-frame deletion in the MP mutant. The phoP and khtSTU operon double mutant MPK showed decreased antibiotic resistance to doxycycline, chlortetracycline, spiramycin, puromycin, and paromomycin when compared with the MP mutant. Thus, the results indicated that the khtSTU operon was responsible for the PhoP-mediated multiple antibiotic resistance.
Topics: Bacillus subtilis; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Oligonucleotide Array Sequence Analysis; Operon; Phenotype; Promoter Regions, Genetic; Signal Transduction; Transcription, Genetic
PubMed: 32688186
DOI: 10.1016/j.micres.2020.126557 -
Journal of Food Protection Oct 2019Mandated authorities have developed principles for evaluating the safety of antimicrobial residues in food and have established microbiological acceptable daily intakes...
Mandated authorities have developed principles for evaluating the safety of antimicrobial residues in food and have established microbiological acceptable daily intakes (ADIs) and recommended maximum residue limits (MRLs) for antibiotic residues in food products. The evaluation of the ADI is based in relevant scientific information such as MIC data of predominant human intestinal bacteria. However, it does not include data derived from minimal selective concentration (MSC) predictions that estimate the lowest concentration of an antibiotic that will provide resistant bacteria an advantage over susceptible bacteria. Based on these insights, we sought to determine whether human exposure to selected antibiotics through ingestion of foodstuffs could result in colon concentrations exceeding apparent MSCs. Nine antibiotics-tetracycline, oxytetracycline, ciprofloxacin, sarafloxacin, erythromycin, spiramycin, tilmicosin, tylosin, and lincomycin-were selected for analysis. Dietary exposure was estimated either using published measured antibiotic concentrations in foodstuffs or using ADI values or food MRLs and a conservative diet. Using the ADI, the estimated antibiotic residue concentrations in the human colon of all antibiotics assessed may be up to a 1,000-fold greater than the predicted MSCs. When the dietary exposure assessment used MRLs or measured concentration in foodstuffs, the estimated concentrations were considerably lower but still within the MSC range for most of the foodstuffs assessed. These results suggest that the ingestion of antibiotic residues through food consumption may expose intestinal microbiota to antibiotic concentrations exceeding the MSC boundaries, thus favoring the growth of potential resistant bacteria. We suggest that MRL and ADI values be revisited in light of the recognition that antibiotic concentrations significantly below the MIC may select for resistance.
Topics: Anti-Bacterial Agents; Dietary Exposure; Drug Resistance, Microbial; Gastrointestinal Microbiome; Humans
PubMed: 31512932
DOI: 10.4315/0362-028X.JFP-19-158 -
Folia Microbiologica Aug 2023Microbial natural products are among the main sources of compounds used in the medical biotechnology field for the purpose of drug development. However, as antibiotic...
Microbial natural products are among the main sources of compounds used in the medical biotechnology field for the purpose of drug development. However, as antibiotic resistance in pathogenic microorganisms is known to be increasing dramatically, there exists a need to develop new antibiotics. Actinomycetia have proven to be a good source of biologically active compounds, although the rediscovery of previously known compounds significantly slows down the introduction of new antibiotics. As a consequence, increasing attention is being paid to the isolation of actinomycete strains from previously unexplored sources, which can significantly increase the likelihood of discovering new biologically active compounds. This study investigated the diversity and bioactive potential of 372 actinomycete strains isolated from the rhizosphere soil of Juniperus excelsa M. Bieb. The examined actinomycete strains belonged to 11 genera, namely, Actinoplanes, Actinorectispora, Amycolatopsis, Kribbella, Micrococcus, Micromonospora, Nocardia, Promicromonospora, Rhodococcus, Saccharopolyspora and Streptomyces. The bioactive potential of each isolated actinomycete strain was determined on the basis of its ability to produce antimicrobial metabolites against Gram-positive and Gram-negative bacteria and yeast. Some 159 strains (42.74%) exhibited antimicrobial activity against at least one of the tested microbial strains. The dereplication analysis of the extract of the Streptomyces sp. Je 1-651 strain, which exhibited strong antimicrobial activity, led to the annotation of spiramycins and stambomycins. Moreover, the phylogenetic analysis based on the 16S rRNA gene sequence of the Je 1-651 strain revealed it to be close to the S. ambofaciens.
Topics: Anti-Bacterial Agents; Juniperus; Rhizosphere; Phylogeny; RNA, Ribosomal, 16S; Soil; Gram-Negative Bacteria; Gram-Positive Bacteria; Anti-Infective Agents; Actinobacteria; Actinomycetales; Streptomyces; Soil Microbiology
PubMed: 36947395
DOI: 10.1007/s12223-023-01047-x -
Animals : An Open Access Journal From... May 2021Dogs with acute diarrhea are often presented to clinical practice and, although this generally represents a self-limiting condition, antibiotics are still frequently...
Dogs with acute diarrhea are often presented to clinical practice and, although this generally represents a self-limiting condition, antibiotics are still frequently used as treatment. The aim of this study was to evaluate the effects in dogs with acute non-hemorrhagic diarrhea of the administration of an antibiotic combination in comparison to a nutraceutical product. Thirty dogs were enrolled and randomly assigned to two groups: 15 dogs (group A) received a nutraceutical commercial product while 15 dogs (group B) received an antimicrobial combination of metronidazole and spiramycin. For each dog, the Canine Acute Diarrhea Severity Index, the fecal microbiota and the Dysbiosis Index were assessed. Both stool consistency and frequency decreased on day 2 in the dogs of group A compared to baseline, while in group B, these parameters significantly decreased at days 3 and 4. The global concern for rising antibiotic resistance associated with indiscriminate use of antimicrobials, in both humans and animals, suggests the necessity of avoiding empirical and injudicious use of these molecules in diarrheic dogs. These results suggest that the nutraceutical treatment had a similar clinical effect compared to the antibiotic formulation, representing a valid antibiotic-sparing therapeutic approach in canine acute diarrhea.
PubMed: 34063855
DOI: 10.3390/ani11061484