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The environmental impacts of antibiotics in sediments, which are a key problem restricting the sustainable development of aquaculture, have been reported extensively. Biological denitrification is a low-cost means to remediate environment. To clarify the the remediation behavior of Paracoccus denitrificans in sewage environment, we studied the changes of bacterial community in sediments polluted by florfenicol after inoculation with P. denitrificans through amplicon technology. Our results showed that P. denitrificans continuously enriched some antibiotic-responsive small RNAs (sRNAs) in promotion of florfenicol degradation, making the abundance of denitrifying functional genes tend to be normalized. Florfenicol and NH 4 +-N are the main factors affecting bacterial communities regarding the results of redundancy analysis (RDA) and pearson's correlation analysis. In the denitrification-related functional categories, the function of nitrate reduction in the community was obviously enhanced. Furthermore, the risk of pathogen infection induced by florfenicol was reduced. In conclusion, our study exhibited the ability of strain P. denitrificans to degrade florfenicol and bioremediate, which provided a theoretical basis for the application of P. denitrificans in aquaculture industry. [Display omitted] • Paracoccus denitrificans promoted florfenicol degradation and denitrification by enriching antibiotic-responsive sRNAs and denitrification genes. [ABSTRACT FROM AUTHOR]

ABSTRACT: Excessive and nonstandard use of florfenicol (FFC) can damage animal body, pollute ecological environment, and even harm human health. The toxic and side effects of FFC directly affect the production performance of poultry and the safe supply of chicken-related food. Salvia miltiorrhaza polysaccharides (SMPs) are natural macromolecular compounds, and were proved to have the effect of protecting animal liver. We used transcriptome and proteome sequencing technologies to study the effect of FFC on specific signal transduction pathways in chick livers and further explored the regulatory effect of SMPs on the above same signal pathways, and finally revealed the intervention effect and mechanism of SMPs on FFC-induced changes of liver function. The screened sequencing results were verified by qPCR and PRM methods. The results showed that FFC changed significantly 9 genes and 5 proteins in drug metabolism-cytochrome P450 signaling pathway, and the intervention of SMPs adjusted the expression levels of 5 genes and 4 proteins of the above factors. In glycine, serine and threonine metabolism signaling pathway, 8 genes and 8 proteins were significantly changed due to FFC exposure, and SMPs corrected the expression levels of 5 genes and 6 proteins to a certain extent. In conclusion, SMPs alleviated FFC-induced liver metabolic disorder in chicks by regulating the drug and amino acid metabolism pathway. This study is of great significance for promoting the healthy breeding of broilers and ensuring the safe supply of chicken-related products.

Riemerella anatipestifer (RA) is an important pathogen found in poultry. RA infection can kill ducks and lead to significant economic losses. Seven RA strains with different susceptibility phenotypes were chosen to study the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) alone and in combination with doxycycline (DOX). The checkerboard assay indicated that synergy [fractional inhibitory concentration index (FICI) ≤ 0.5] was detected in the CVCC3952 strain of RA and that additivity (FICI >0.5 to ≤ 1) was observed in other strains. Static time–kill curves showed that the bactericidal effect of FF against RA was produced at a FF concentration ≥4 MIC, and the antibacterial activity of FF against RA was enhanced from the aspects of efficacy and efficacy in combination with DOX. Dynamic time–kill curves indicated that FF elicited bactericidal activity against the CVCC3857 strain with a reduction ≥4.88 log10CFU/ml when the dose was ≥8 mg/L. However, a bactericidal effect was not achieved at the maximum administered dose of FF monotherapy (20 mg/L) for isolates with a MIC ≥4 μg/ml. The effect of FF against RA was enhanced upon combination with DOX. The combination of FF with DOX reduced the bacterial burden ≥4.53 log10CFU/ml for all strains with a MIC ≥4 μg/ml. Data were fitted to a sigmoidal Emax model. The PK/PD parameters of AUC24h/MIC (the area under the concentration–time curve over 24 h divided by the MIC) and %T >MIC (the cumulative percentage of time over a 24-h period at which the concentration exceeded the MIC) of FF for eliciting a reduction of 3 log10CFU/ml was 40.10 h and 58.71, respectively. For strains with a MIC ≤ 16 μg/ml, the magnitude of the AUC24h/MIC and Cmax/MIC required for a 3 log10CFU/ml of bacterial killing was 34.84 h and 4.74 in the presence of DOX at 0.5 MIC, respectively. These data suggest that combination of FF with DOX enhanced the activity against RA strains with various susceptibilities to FF and DOX.

Florfenicol is a broad-spectrum antibiotic commonly prescribed in an extra-label manner for treating meat and dairy goats. Scientific data in support of a milk withdrawal interval recommendation is limited to plasma pharmacokinetic data and minimal milk residue data that is limited to cattle. Therefore, a rapid residue detection test (RRDT) could be a useful resource to determine if milk samples are free of drug residues and acceptable for sale. This study compared a commercially available RRDT (Charm® FLT strips) to detect florfenicol residues in fresh milk samples from healthy adult dairy breed goats treated with florfenicol (40 mg/kg subcutaneously twice 4 days apart) with quantitative analysis of florfenicol concentrations using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). In addition, storage claims for testing bovine milk using the RRDT were assessed using stored goat milk samples. Milk samples were collected every 12 h for a minimum of 26 days. Commercial RRDT strips remained positive in individual goats ranging from 528 to 792 h (22–33 days) after the second dose, whereas, UPLC-MS/MS indicated the last detectable florfenicol concentration in milk samples ranged from 504 to 720 h (21–30 days) after the second dose. Results from stored milk samples from treated goats indicate that samples can be stored for up to 5 days in the refrigerator and 60 days in the freezer after milking prior to being tested with a low risk of false-negative test results due to drug degradation. Elevated somatic cell counts and bacterial colony were noted in some of the milk samples in this study, but further study is required to understand the impact of these quality factors on RRDT results.

Florfenicol was widely used as antibiotic in the livestock and poultry breeding industry, resulting in a serious problem of drug resistance. In order to solve the resistance of florfenicol, this study designed and synthesized a new series of florfenicol-polyarginine conjugates and tested for antimicrobial activities. Drug-sensitive bacteria, gram-negative bacteria Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus), were sensitive to several of the compounds tested. These conjugates also showed excellent activity against drug-resistant strains such as methicillin-resistant S. aureus (MRSA) and florfenicol resistant Escherichia coli strains (2017XJ30, 2019XJ20), one of which as E6 had a minimum inhibitory concentration of 12.5 μmol/L. These conjugates did not allow bacteria to develop resistance and also decreased bacterial growth by membrane depolarization and disruption. Additionally, florfenicol succinate (C1) showed certain activity after coupling with arginine. This suggested that conjugating arginine to florfenicol succinate effectively modulated the properties of prodrugs. These new conjugates may provide useful insights for expanding the pool of antibiotics.

Abstract The pharmacokinetic properties and residue elimination of florfenicol (FLO) and its amine were investigated in European seabass Dicentrarchus labrax at 24°C. The trial mainly included analysis of FLO in plasma after a single dose dietary administration of 10 mg/kg and in muscle plus skin following a multiple dosing (10 mg kg−1 day−1 for 7 days) to estimate pharmacokinetics and residue depletion, respectively. The maximum plasma concentration of FLO was measured to be 1.64 μg/ml, 4 hr post administration. The elimination half‐life (t1/2b) and the area under the concentration‐time curve extrapolated to infinity (AUC0‐∞) were calculated to be 13.0 hr and 34.7 μg h−1 ml−1, respectively. Withdrawal times of FLO and its amine were calculated to be 46.3 degree‐days, indicating a fast removal from the edible tissues of treated European seabass. Overall, FLO can be considered as a potentially efficient antibacterial agent for farmed European seabass provided that additional efforts will be devoted towards its in vitro and clinical efficacy.

The frequent occurrence of antibiotics in the aquatic environment has engendered negative impacts on non-target organisms. The effects of the veterinary antibiotic florfenicol (FLO) during the embryo-larval development of the sea urchin, Paracentrotus lividus was assessed using four increasing concentrations (1, 2, 5 and 10 mg/L). Furthermore, FLO toxicity to adults was investigated through the analysis of oxidative damage, histopathological alterations, lipid metabolism and acetylcholinesterase activity following an exposure period of 96 h. FLO induced embryotoxicity with estimated EC50 values of 5.75, 7.56 and 3.29 mg/L after 12 h, 24 h and 48 h, respectively. It generated oxidative stress assessed as lipid peroxidation in gonads despite the increased antioxidant activity of catalase (CAT). Neurotoxicity was also evident since the AChE activity significantly decreased. Moreover, FLO affected the lipid metabolism by increasing saturated fatty acid (SFA) and monounsaturated fatty acid proportions (MUFA), except in the group exposed to 5 mg/L. The increase in polyunsaturated fatty acid (PUFA) levels and docosahexaenoic acid (DHA, C22:6n-3) proportions were noted with all FLO concentrations. Eicosapentaenoic acid (EPA, C20:5n-3) decreased, while arachidonic acid (ARA, C20:4n-6) increased in sea urchins exposed to 5 and 10 mg/L FLO. Histopathological alterations of gonadal tissues represent an additional confirmation about the toxicity of this antibiotic that might decrease the reproductive performance of this species. Nevertheless, even if reproduction of sea urchins would be partially successful, the embryotoxicity would compromise the normal development of the embryos with consequences on the population. [Display omitted] • FLO effects were assessed for the first time in sea urchin. • FLO induced oxidative and neurotoxicity in gonads sea urchin. • FLO affected the lipid metabolism and induced histopathological alterations. • FLO induced embryotoxicity in sea urchin. • FLO affects the reproduction and the development of sea urchin. [ABSTRACT FROM AUTHOR]

The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 μM) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 μM curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h·ug/L) and a higher C max values (9.94 vs. 7.61 μg/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol. [ABSTRACT FROM AUTHOR]

Florfenicol is a broad-spectrum bacteriostatic antibiotic used exclusively in veterinary medicine in order to treat the pathology of farm and aquatic animals. It is a synthetic fluorinated analog of thiamphenicol and chloramphenicol that functions by inhibiting ribosomal activity, which disrupts bacterial protein synthesis and has shown over time a strong activity against Gram-positive and negative bacterial groups. Florfenicol was also reported to have anti-inflammatory activity through a marked reduction in immune cell proliferation and cytokine production. The need for improvement came from (1) the inappropriate use (to an important extent) of this antimicrobial, which led to serious concerns about florfenicol-related resistance genes, and (2) the fact that this antibiotic has a low water solubility making it difficult to formulate an aqueous solution in organic solvents, and applicable for different routes of administration. This review aims to synthesize the various applications of florfenicol in veterinary medicine, explore the potential use of nanotechnology to improve its effectiveness and analyze the advantages and limitations of such approaches. The review is based on data from scientific articles and systematic reviews identified in several databases.

[Display omitted] • The Zn substituted Co 3 O 4 catalysts were prepared and applied in PMS activation for florfenicol removal. • The Zn substitution induced electron rearrangement and promoted oxygen vacancies formation in Co 3 O 4. • The Zn substituted Co 3 O 4 (Zn 0.03 Co) exhibited superior florfenicol removal and higher reaction rate than Co 3 O 4. • The florfenicol degradation is highly dependent on PMS/Zn 0.03 Co/florfenicol dosage, temperature and initial pH. • The degradation mechanism and routes were proposed combining LC-MS/MS and theoretical calculation results. Florfenicol (FLO) is a broad-spectrum halogenated antibiotic (containing F and Cl atoms), and the discharged FLO in wastewater exhibits potential biotoxicity. Peroxymonosulfate (PMS) activation can generate reactive oxygen species (ROSs) to realize efficient degradation of organic pollutants. Herein, Zn-substituted Co 3 O 4 (Zn x Co) catalysts were prepared and applied in PMS activation for FLO degradation. The physicochemical properties were systematically studied by combining experiments and density functional theory (DFT) calculation. The Zn partial substitution induced electron rearrangement and promoted oxygen vacancy (OV) formation in Co 3 O 4. Zn 0.03 Co catalyst exhibited superior FLO removal, achieving a higher reaction rate of 0.112 min−1 than Co 3 O 4 (0.053 min−1). The FLO degradation was highly dependent on the factors of PMS/Zn 0.03 Co/FLO dosage, temperature, initial pH, and coexisting inorganic anions. The Zn 0.03 Co also displayed outstanding performance in PMS activation for degradation of various typical organic pollutants. Electron paramagnetic resonance (EPR) spectra and quenching experiments indicated that both radical species ( · OH , SO 4 · - , and · O 2 -) and nonradical species (1O 2) contribute to FLO removal. The redox cycle of Co3+/Co2+ and OVs played an essential role in PMS activation. The electron structure of FLO and parameters of PMS adsorbed on Zn x Co were calculated. The longer length of Co O and O O bonds for the adsorbed PMS could enhance its activation to generate ROSs. The intermediates were detected, and five degradation pathways were proposed. The acute and chronic toxicities of intermediates suggested that the dechlorination process is important for the toxicity attenuation of FLO. This study clarified the performance enhancement mechanism of Zn substitution on FLO degradation by PMS activation using Co 3 O 4 based catalyst, which favors the development of PMS-based advanced oxidation processes for wastewater treatment. [ABSTRACT FROM AUTHOR]

The widespread use and subsequent accumulation of florfenicol (FFC), a common antibiotic, through the food chain poses significant risks to aquatic ecosystems and human health, necessitating effective strategies for its removal from water bodies. To solve the challenge, herein, we developed a novel aluminum-based metal–organic framework CAU-1, engineered for the efficient adsorption of FFC. CAU-1 contains the plentiful –NH 2 and μ-OH groups with the positively charged on the surface. In the adsorption process, CAU-1 perform hydrogen bonding interactions with FFC's functional groups (−F, –OH, −Cl, –NH–, and −SO 2 –). Furthermore, the positively charged surface of CAU-1 enhances FFC adsorption via electrostatic attraction together. FFC adsorption equilibrium on CAU-1 is attained within 180 min with a monolayer adsorption capacity of 386 mg/g at 303 K, surpassing most of the reported adsorbents. The exothermic FFC adsorption process on CAU-1 remains largely unaffected by coexisting ions. Additionally, CAU-1 can be efficiently regenerated using a mixed solution of 0.1 M HCl and ethanol–water as an eluent. This work highlights CAU-1's potential as an effective adsorbent for FFC removal, emphasizing the importance of tuning or designing surface functional groups on adsorbents to boost their adsorption capabilities. [ABSTRACT FROM AUTHOR]

A major problem of our time is the ever-increasing resistance to antimicrobial agents in bacterial populations. One of the most effective ways to prevent these problems is to target antibacterial therapies for specific diseases. In this study, we investigated the in vitro effectiveness of florfenicol against S. suis, which can cause severe arthritis and septicemia in swine herds. The pharmacokinetic and pharmacodynamic properties of florfenicol in porcine plasma and synovial fluid were determined. After a single intramuscular administration of florfenicol at 30 mg/kgbw, the AUC0–∞ was 164.45 ± 34.18 µg/mL × h and the maximum plasma concentration was 8.15 ± 3.11 µg/mL, which was reached in 1.40 ± 0.66 h, whereas, in the synovial fluid, these values were 64.57 ± 30.37 µg/mL × h, 4.51 ± 1.16 µg/mL and 1.75 ± 1.16 h, respectively. Based on the MIC values of the 73 S. suis isolates tested, the MIC50 and MIC90 values were 2 µg/mL and 8 µg/mL, respectively. We successfully implemented a killing–time curve in pig synovial fluid as a matrix. Based on our findings, the PK/PD breakpoints of the bacteriostatic (E = 0), bactericidal (E = −3) and eradication (E = −4) effects of florfenicol were determined and MIC thresholds were calculated, which are the guiding indicators for the treatment of these diseases. The AUC24h/MIC values for bacteriostatic, bactericidal and eradication effects were 22.22 h, 76.88 h and 141.74 h, respectively, in synovial fluid, and 22.42 h, 86.49 h and 161.76 h, respectively, in plasma. The critical MIC values of florfenicol against S. suis regarding bacteriostatic, bactericidal and eradication effects in pig synovial fluid were 2.91 ± 1.37 µg/mL, 0.84 ± 0.39 µg/mL and 0.46 ± 0.21 µg/mL, respectively. These values provide a basis for further studies on the use of florfenicol. Furthermore, our research highlights the importance of investigating the pharmacokinetic properties of antibacterial agents at the site of infection and the pharmacodynamic properties of these agents against different bacteria in different media.

This experiment explored the mechanism of Salvia miltiorrhiza polysaccharides (SMPs) on florfenicol (FFC)-induced kidney injury in broilers. Ninety healthy 1-day-old Arbor Acres broilers were randomly divided into 3 groups with 6 replicates in each group and 5 chickens in each replicate. The three groups included control group, model group (0.15 g/L FFC), and SMPs group (0.15 g/L FFC + 5.00 g/L SMPs). After 5 days of experimental period, blood was collected, and kidney tissues were extracted. Renal injury was evaluated by serum biochemical indicators and pathological sections. Renal oxidative stress indexes were detected; transcriptomics and proteomics were used to comprehensively analyze the effects of SMPs on broiler kidney injury. The results showed that the model group inhibited average day gain (P < 0.01) and significantly adjusted blood urea nitrogen (BUN), uric acid (UA), and creatinine (Cr) (P < 0.01 or P < 0.05). The histological observation of the kidneys in the model group showed abnormal morphology, and the oxidative stress parameters showed that FFC induced oxidative stress in the kidneys. Comprehensive transcriptome proteomic analysis data showed phosphoribose pyrophosphate synthase 2 (PRPS2), cytochrome 2AC1 (CYP2AC1), cytochrome 2D6 (CYP2D6), glutathione transferase (GST), and sulfotransferase 1B (SULT1B) expression levels changed. It is worth noting that our data showed that supplementation of 5.00 g/L SMPs in drinking water reversed the changes in BUN, Cr, and daily weight gain (P < 0.05) and relieved the abnormal kidney morphology caused by FFC. After SMPs processing, it improved the detoxification process of drug-metabolizing enzymes and improved the oxidative stress state induced by FFC. Therefore, SMPs reduced the nephrotoxicity caused by FFC by promoting drug-metabolizing enzymes and alleviating oxidative stress in the kidneys. [ABSTRACT FROM AUTHOR]

Previous studies implied that elevated exposure to amphenicol antibiotics may induce increased oxidative stress. However, the effects of amphenicol antibiotics exposure on oxidative stress damage in human have not been well studied. This study examined the associations between amphenicol antibiotics exposure and oxidative damage biomarkers in school children. Three major amphenicols including chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF) and two biomarkers of 8-hydroxydeoxyguanosine (8-OHdG) for oxidative DNA damage and 8-oxo-7,8- dihydroguanosine (8-OHG) for oxidative RNA damage were measured in 414 morning urine samples collected from 70 school children in Shanghai, China. School children were exposed to CAP, TAP, and FF with median concentrations of 1.37, 0.36, and 0.06 μg/g Cre, respectively. Linear mixed models revealed that an interquartile range (IQR) increase of urinary TAP was positively associated with 7.75%(95% CI: 4.40%, 11.1%) increase of 8-OHdG and 7.48%(95% CI: 2.49%, 15.6%) increase of 8-OHG, respectively; in addition, CAP was associated with elevated 8-OHdG. Although FF was not found to be significantly associated with either 8-OHdG or 8-OHG, it is warranted to further investigate FF and its metabolites levels in relation to oxidative stress in future study. Our findings provide new evidence for the effects of exposure to TAP and CAP on nucleic acid oxidative damage in Children. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the chemical composition of Lippia alba and two genotypes of L. origanoides, L. origanoides A and L. origanoides B (syn. Lippia sidoides) essential oils(EOs) and to investigate the antibacterial activity against 27 Aeromonas spp. isolated from tambaqui (Colossoma macropomum). The activity of the antibiotics Florfenicol and Oxytetracycline was also compared. The EOs were obtained by hydrodistillation and their composition determined by CG-MS. Antibacterial activity was assessed based in the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using microdilution method. The main compounds identified were carvone (55.9%) and limonene (21.9%) in L. alba EO, carvacrol (35.6%) and p‐cymene (15.7%) in L. origanoides A EO and thymol (53.5%) and p‐cymene (15.5%) in L. origanoides B EO. The Lippia species showed bacteriostatic and bactericidal action against Aeromonas isolates with MICs and MBCs ranging from 104.17 to 16,666.67 μg.mL−1. Among the tested EOs, the best performance was obtained by that of the L. origanoides B genotype, followed by L. origanoides A and L. alba respectively. Among antibiotics, the best performance was of oxytetracycline (MICs and MBCs ranging from 0.195 to 0.78 μg.mL−1) compared to florfenicol (MICs and MBCs ranging from 0.195 to 3.12 μg.mL−1). [ABSTRACT FROM AUTHOR]

A competitive electrochemiluminescence immunoassay was established based on the isoluminol-H2O2 (ABEI-H2O2) system catalyzed by cobalt hydroxide (Co(OH)2) to detect florfenicol residues in food. First , ultra-thin two-dimensional Co(OH)2 nanosheets were used as the catalyst of ABEI-H2O2 system, and excellent catalytic effects were acquired by catalytic decomposition of hydrogen peroxide with cobalt ions. Then, bimetal PdAg (Pd/Ag) alloy nanoparticles were used as a bridge to connect ABEI and antibody due to their good biocompatibility; Pd/Ag alloy nanoparticles also had a catalytic effect to further amplify the ECL signal in the system due to the synergistic catalytic effect of the bimetal. A competitive immunoassay strategy was used to detect florfenicol, where the florfenicol in the sample will compete with the antibody for the limited binding sites on the coating antigen. The ECL immunosensor for florfenicol detection shows high sensitivity, with a linear range from 10−4 to 102 ng mL−1, and a detection limit of 3.1 × 10−5 ng mL−1, where the scan potential was varied from 0 to 0.6 V vs Ag/AgCl. This work was the first to use Co(OH)2 nanosheets and bimetal PdAg catalytic signal amplification methods to design the sensor, which provides a novel, convenient and reliable strategy for ultra-sensitive detection of florfenicol, and other biological small molecules. A novel ECL immunosensor based on ABEI-H2O22 [ABSTRACT FROM AUTHOR]

A study is performed of the sorption of chloramphenicol, florfenicol, and thiamphenicol on magnetic hypercrosslinked polystyrene (HCPS/Fe3O4). Magnetic HCPS is obtained via the sorption of Fe3O4 nanoparticles on commercially available HCPS Diapak P-3. The specific surface areas and parameters of the porous structure of the magnetic HCPS are determined by means of low-temperature nitrogen adsorption. It is found that introducing Fe3O4 nanoparticles into the HCPS matrix slightly lowers the specific surface area of the sorbent (from 1132 to 1080 m2/d) and the volume of pores, but these characteristics are strong enough to use the resulting composite as a sorbent. It is established that the HCPS-based magnetic sorbent exhibits superparamagnetic properties. The saturation magnetization is 1.7 emu/g, enough to extract the sorbent from the solution under the action of the magnetic field of a permanent magnet. It is shown that magnetic HCPS can be used for the group sorption concentration of amphenicols via magnetic solid-phase extraction. [ABSTRACT FROM AUTHOR]

Florfenicol (FFC) is a synthetic broad-spectrum antibiotic and garlic has a bactericidal action against coliforms. This study was carried out to compare the antimicrobial, immunological and biochemical effects of florfenicol and garlic, for their ability to treat enteropathogenic Escherichia coli serotype O55: H7 infection in rabbits. Four groups (G1-G4) were included. G1 group was the negative control; G2 group was the infected with a field-isolated strain of E. coli and untreated; G3 group was the infected+treated with FFC for 5 days; and G4 group was the infected+treated with garlic tablets for 14 days. The rabbits were observed for clinical signs, growth performance and mortality rates. Garlic-infused disks had a larger clear zone of inhibition than other antibiotic disks. Garlic treatment improved growth performance, biochemical parameters, and immunological response and reduced the fecal shedding and histopathological lesions in E. coli O55: H7 infected rabbits compared to the other groups. Colonization of E. coli more rapidly declined in G3 & G4 than in G2. Hepatic and intestinal gene expressions; tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly elevated in G2 compared to the other groups, and their levels were elevated more in G3 than in G4. Serum interferon-gamma (IFN-γ) and phagocytic activity were significantly elevated in G4 compared to G3. G3 revealed macrocytic hypochromic anaemia that was confirmed histopathologically by moderate haematopoiesis of the bone marrow. In conclusion, garlic powder can reduce rabbit colibacillosis, like FFC, and can enhance the immune status of rabbits. [ABSTRACT FROM AUTHOR]

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In the aquaculture sector, there is an increased interest in developing environmentally friendly alternatives to antibiotics in the treatment and prevention of bacterial infections. This requires an understanding of the effects of different treatments on the fish microbiota as a measure for improving the fish health status. In this study, we focused on the freshwater pathogen Flavobacterium psychrophilum and investigated the effects of antibiotics (florfenicol) and phage therapies on the gut microbiota of healthy and infected rainbow trout fry (1–2 g). Florfenicol-coated feed was administered for 10 days, starting two days after the infection procedure. A two-component mix of phage targeting F. psychrophilum (FpV4 and FPSV-D22) was continuously delivered by feed with a prophylactic period of 12 days. Samples of the distal intestine were collected over time (day -1 and 1, 8, and 33 days post-infection) and analyzed by community analysis targeting the 16S rRNA gene (V3–V4 region). Results showed the dysbiosis effect caused both by the infection and by florfenicol administration. Shifts in the overall composition were detected by β-diversity analysis, and changes in specific populations were observed during taxonomic mapping. Measures of α-diversity were only affected in infected fish (large variation observed 1 and 8 dpi). These community alterations disappeared again when fish recovered from the infection and the antibiotic treatment was terminated (33 dpi). Interestingly, phage addition altered the microbiota of the fish independently of the presence of their target bacterium. The overall gut bacterial community in fish fed phage-treated feed was different from the controls at each time point as revealed by β-diversity analysis. However, it was not possible to identify specific bacterial populations responsible for these changes except for an increase of lactic acid bacteria 33 dpi. Overall, the results indicate that the administered phages might affect the complex network of phage-bacteria interactions in the fish gut. Nevertheless, we did not observe negative effects on fish health or growth, and further studies should be directed in understanding if these changes are beneficial or not for the fish health with an additional focus on the host immune response. [ABSTRACT FROM AUTHOR]

The use of florfenicol in farm animals may select enterococci that carry resistance genes that confer resistance to linezolid, a critically important oxazolidinone antibiotic used in human medicine. This cross-sectional study aimed to assess the occurrence of oxazolidinone resistance genes in florfenicol-resistant enterococci from fattening pigs in Switzerland and to characterize a subset of the isolates using whole genome sequencing. A total of 31 florfenicol-resistant enterococcal isolates were obtained from 27 (5%) of 565 cecal samples of fattening pigs from seven (11%) of 62 farms. Screening by PCR revealed the presence of cfr-poxtA in 1 of 31, optrA in 15 of 31, and poxtA in 15 of 31 enterococcal isolates. One randomly selected isolate per PCR-positive Enterococcus species and positive farm was selected for further analysis (n = 10). In nine of the 10 isolates, the presence of oxazolidinone resistance genes did not result in phenotypic resistance. Whole genome sequencing analysis showed the presence of E. faecalis (n = 1), E. faecium (n = 1), and E. hirae (n = 1), harboring optrA18, optrA7, and a new optrA allele, respectively. E. durans (n = 1), E. faecium (n = 4), and E. hirae (n = 1) carried the wild-type poxtA, and E. faecalis (n = 1) coharbored cfr(D) and poxtA2. Except for optrA7, all oxazolidinone resistance genes were found on plasmids. Multilocus sequence typing analysis identified E. faecalis ST19 and ST376, E. faecium ST80 belonging to hospital-adapted clade A1, and E. faecium ST21, ST55, ST269, and ST416 belonging to clade A2, which represents human commensals and animal strains. The occurrence of cfr(D), optrA, and poxtA in various porcine Enterococcus spp. demonstrates the spread of oxazolidinone resistance genes among enterococci from fattening pigs in Switzerland. The presence in one sample of poxtA-carrying E. faecium ST80 emphasizes the potential risk to human health through dissemination of strains carrying oxazolidinone resistance genes into the food chain. cfr, optrA, and poxtA were detected in porcine florfenicol-resistant enterococci. cfr, optrA, and poxtA did not usually confer phenotypic linezolid resistance. E. faecium ST80 belonging to hospital-adapted clade A1 was found. E. durans harboring optrA is described for the first time in pigs. Enterococci from fattening pigs are a reservoir of oxazolidinone resistance genes. [ABSTRACT FROM AUTHOR]

Amphenicols are broad-spectrum antibiotics. Despite their benefits, they also present toxic effects and therefore their presence in animal-derived food was regulated. Various analytical methods have been reported for their trace analysis in food and environmental samples, as well as in the quality control of pharmaceuticals. Among these methods, the electrochemical ones are simpler, more rapid and cost-effective. The working electrode is the core of any electroanalytical method because the selectivity and sensitivity of the determination depend on its surface activity. Therefore, this review offers a comprehensive overview of the electrochemical sensors and methods along with their performance characteristics for chloramphenicol, thiamphenicol and florfenicol detection, with a focus on those reported in the last five years. Electrode modification procedures and analytical applications of the recently described devices for amphenicol electroanalysis in various matrices (pharmaceuticals, environmental, foods), together with the sample preparation methods were discussed. Therefore, the information and the concepts contained in this review can be a starting point for future new findings in the field of amphenicol electrochemical detection. [ABSTRACT FROM AUTHOR]

Large quantities of the antibiotic florfenicol are used in animal farming and aquaculture, contaminating the ecosystem with antibiotic residues and promoting antimicrobial resistance, ultimately leading to untreatable multidrug-resistant pathogens. Florfenicol-resistant bacteria often activate export mechanisms that result in resistance to various structurally unrelated antibiotics. We devised novel strategies for the enzymatic inactivation of florfenicol in different media, such as saltwater or milk. Using a combinatorial approach and selection, we optimized a hydrolase (EstDL136) for florfenicol cleavage. Reaction kinetics were followed by time-resolved NMR spectroscopy. Importantly, the hydrolase remained active in different media, such as saltwater or cow milk. Various environmentally-friendly application strategies for florfenicol inactivation were developed using the optimized hydrolase. As a potential filter device for cost-effective treatment of waste milk or aquacultural wastewater, the hydrolase was immobilized on Ni-NTA agarose or silica as carrier materials. In two further application examples, the hydrolase was used as cell extract or encapsulated with a semi-permeable membrane. This facilitated, for example, florfenicol inactivation in whole milk, which can help to treat waste milk from medicated cows, to be fed to calves without the risk of inducing antibiotic resistance. Enzymatic inactivation of antibiotics, in general, enables therapeutic intervention without promoting antibiotic resistance. [ABSTRACT FROM AUTHOR]

The pharmacokinetic variables of a new formulation of florfenicol included in dried bean of alginate (FADBs), its acceptance as in food medication, and its relationship with theoretical minimum inhibitory concentration (MIC) values of the main pathogens in rabbits, are presented. FADBs sought to mask the unpleasant taste of florfenicol while enhancing sustained absorption in a day to facilitate and optimise its dosage in this species. The entrapment efficiency was determined to be 94-98% and 73.56±3.26% of drug loading. No reduction in food consumption was detected, nor selectivity when choosing from their usual food. The elimination half-life was 1.23 to 2.4 h slower than the one previously reported in the literature. Possible flip-flop pharmacokinetics is proposed for FADBs in rabbits, thus complying better with the key pharmacokinetics/pharmacodynamics (PK/PD) ratio of t≥MIC. Also, if a MIC2.0 μg/mL is taken as the cut-off point for florfenicol in rabbits, then ad libitum intake of FADBs in their standard diet is sufficient to maintain plasma concentrations of florfenicol above this level during the whole dosing interval of 24 h. Additionally, FADBs are a low-cost and attractive drug delivery system for the oral controlled release of florfenicol in rabbits. [ABSTRACT FROM AUTHOR]

Florfenicol, apramycin, and danofloxacin are antibiotics approved only for veterinary use and that have good therapeutic effects on chicken respiratory infections caused by Escherichia coli. We established epidemiological cutoff values (ECV) for these antibiotics using 363 E. coli isolates from tracheal samples of chickens in 5 veterinary clinics in Guangdong Province, China. The minimum inhibitory concentrations (MIC) were determined using the agar dilution method as per Clinical and Laboratory Standards Institution guidelines. The ECV were then calculated using the statistical method and verified by normalized resistance interpretation and ECOFFinder software programs. The ECV of florfenicol, apramycin, and danofloxacin against E. coli were 16, 16, and 0.125 μg/mL, respectively. Susceptibility tests indicated that these isolates were resistant to florfenicol (66.7%), apramycin (22.3%), and danofloxacin (92.3%). Strains carrying floR were distributed in the range of MIC ≥32 μg/mL for florfenicol. Apramycin resistance was found in 77 strains (77/363, 21.1%), and isolates that carried aac(3)-IV were all in the range of MIC ≥512 μg/mL. Danofloxacin resistance was found in the range of MIC ≤0.125 μg/mL, but there were no mutations in the quinolone resistance–determining regions and plasmid-mediated quinolone resistance genes qnrA, qnrB, qnrC, qnrD, aac-(6′)-Ib-cr, qep, and oqxB. The presence of the qnrS gene was verified in a few of the strains with an MIC of 0.06 μg/mL. The establishment of ECV was significant for monitoring of resistance development and therapy guidance.

Florfenicol (FFC) is a common antibiotic for animals. The nonstandard and excessive use of FFC can cause veterinary drug residues in animals, pollute soil and marine environment, and even threaten human health. Therefore, it is necessary to study the toxicity and side effects of FFC on animals. Our previous studies have proved that FFC can cause liver injury in chicks, but there are few in-depth studies on the mechanism of FFC causing liver injury at the level of signaling pathway in chicks. Therefore, transcriptome and proteome sequencing were performed and combined analysis was performed. Sequencing results showed that 1989 genes and 917 proteins were significantly changed in chick livers after FFC exposure. These genes and proteins are related to redox, glutathione transferase activity and lipid metabolism. There are 9 significantly different genes and 7 significantly different proteins in glutathione signaling pathway. Oxidative stress may occur in the liver of chicks through the change of activation state of glutathione signaling pathway. And there are 13 significantly different genes and 18 significantly different proteins in PPAR signaling pathway. The changes of PPAR signaling pathway may induce lipid metabolism disorder in liver. The verification results of qPCR and PRM were consistent with the sequencing results. We also detected GSH-Px, GSH, GST, TG, TC and ANDP levels in liver. These changes of biochemical indicators directly confirmed oxidative stress and lipid metabolism disorders were occurred in the livers of chicks treated by FFC. In conclusion, FFC could induce liver injury in chicks by regulating the expression levels of significantly different genes and proteins in glutathione signaling pathway and PPAR signaling pathway.

Florfenicol (FLO), which is widely used in veterinary clinics and aquaculture, can disrupt the protein synthesis of bacteria and mitochondria and, thus, lead to antibacterial and toxic effects in plants, insects, and mammals. FLO was found to repress chicken embryonic development and induce early embryonic death previously, but the underlying mechanism is not fully understood. Clarifying the mechanism of FLO-induced embryonic toxicity is important to the research and development of new drugs and the rational use of FLO to ensure human and animal health and ecological safety. In this study, the effects of FLO on pluripotency, proliferation, and differentiation were investigated in P19 stem cells (P19SCs). We also identified differentially expressed genes and performed bioinformatics analysis to obtain hub genes and conducted some functional analysis. FLO inhibited the proliferation and pluripotency of P19SCs and repressed the formation of embryoid bodies derived from P19SCs. A total of 2,396 DEGs were identified using RNA-Seq in FLO-treated P19SCs, and these genes were significantly enriched in biological processes, such as angiogenesis, embryonic organ development, and morphogenesis of organs. Kyoto encyclopedia of genes and genome-based pathway analysis also showed that five relevant pathways, especially the canonical Wnt pathway, were engaged in FLO-induced toxicity of pluripotent stem cells. We further analyzed modules and hub genes and found the involvement of ubiquitin-mediated proteolysis, DNA replication, and cell cycle machinery in regulating the pluripotency and proliferation of FLO-treated P19SCs. In summary, our data suggest that FLO disrupts the signaling transduction of pathways, especially the canonical Wnt pathway, and further inhibits the expression of target genes involved in regulating DNA replication, cell cycle, and pluripotency. This phenomenon leads to the inhibition of proliferation and differentiation in FLO-treated P19SCs. However, further experiments are required to validate our findings and elucidate the potential mechanisms underlying FLO-induced embryonic toxicity. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR) is always used in combination with florfenicol for treating avian in China. Objective: This study aims to investigate the effects of BBR on the pharmacokinetics of florfenicol in broilers. Methods: Male broilers were randomly divided into the control group and the BBR group (BG). Note that 50 mg/kg BBR or sterile water was orally administrated to broilers. On the 8th day, florfenicol [30 mg/kg body weight (BW)] was orally administered to broilers in both groups. The plasma concentrations of florfenicol were determined by ultra‐high‐performance liquid chromatography (UHPLC). The levels of cytochrome P450 (CYP) 3A37, multidrug resistance 1 (MDR1), and chicken xenobiotic‐sensing orphan nuclear receptor (CXR) mRNA expression in the liver and jejunum were determined by the real‐time PCR. Results: The results showed that the Cmax, t1/2z, MRT(0‐∞), and AUC(0‐∞) of florfenicol in BG were significantly increased (by 55.71%, 28.32%, 35.19%, and 55.62%, respectively), while the Tmax and CLz/F of florfenicol were significantly decreased (by 52.13% and 35.82%, respectively). In BG, the levels of CYP3A37, MDR1, and CXR mRNA expression in the liver were significantly decreased to 0.72‐fold, 0.67‐fold, and 0.59‐fold, respectively, and the corresponding mRNA expression in the jejunum were significantly decreased to 0.66‐fold, 0.55‐fold, and 0.64‐fold levels, respectively, relative to their levels in the control group. Conclusions: BBR altered the pharmacokinetics of florfenicol, probably related to its inhibition of CYP3A37, MDR1, and CXR mRNA expression in the jejunum and liver. [ABSTRACT FROM AUTHOR]

From 45 private fish farms, 641 tilapia samples were collected, which suffered from tilapia summer mortality outbreaks at different localities. The findings of the conventional test and 16S rRNA gene sequence recognition indicated that the isolated bacterium from the examined farms is Aeromonas veronii. A 15‐day feeding trial was conducted to determine the effects of formic acid (FA) on biochemical parameters, immunological status, cortisol levels and total gut bacterial population of A. veronii‐challenged tilapia. Fish were divided into five groups. The first and second groups served as control‐negative and control‐positive groups, which were intraperitoneally injected with 0.2‐ml sterilized tryptic soy broth and A. veronii (4.3 × 106), respectively, and both were fed with a basal diet. Groups 3–5 were intraperitoneally injected with 0.2‐ml A. veronii (4.3 × 106), fed a basal diet until clinical signs appeared and fed on a medicated diet containing florfenicol 15 mg/kg fish body weight and 0.5% and 1% FA respectively. The results suggest that including 1% FA in the diet lowered mortality and relieved the pathogenic effects of A. veronii on the general health status of tilapia fish. [ABSTRACT FROM AUTHOR]

In order to explore the transcriptomics and proteomics targets and pathways of Salvia miltiorrhiza polysaccharides (SMPs) alleviating florfenicol (FFC)-induced liver injury in broilers, 60 1-day-old broilers were randomly divided into 3 groups: control group (GP1) was fed tap water, FFC model (GP2) was given tap water containing FFC 0.15 g/L, and SMPs treatment group (GP3) was given tap water containing FFC 0.15 g/L and SMPs 5 g/L. Starting from 1 day of age, the drug was administered continuously for 5 days. On the 6th day, blood was collected from the heart and the liver was taken. Then 3 chickens were randomly taken from each group, and their liver tissues were aseptically removed and placed in an enzyme-free tube. Using high-throughput mRNA sequencing and TMT-labeled quantitative proteomics technology, the transcriptome and proteome of the three groups of broiler liver were analyzed, respectively. The results of the study showed that the liver tissue morphology of the chicks in the GP1 and GP3 groups was complete and there were no obvious necrotic cells in the liver cells. The liver tissue cells in the GP2 group showed obvious damage, the intercellular space increased, and the liver cells showed extensive vacuolation and steatosis. Compared with the GP1 group, the daily gain of chicks in the GP2 group was significantly reduced (P < 0.0 5 or P < 0.01). Compared with the GP2 group, the GP3 group significantly increased the daily gain of chicks (P <0.0 5 or P <0.01). Compared with the GP1 group, the serum levels of ALT, AST, liver LPO, ROS, and IL-6 in the GP2 group were significantly increased (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4, and IL-10 in the liver were significantly decreased (P < 0.0 5 or P < 0.01). After SMPs treatment, the serum levels of ALT, AST, liver LPO, ROS, and IL-6 were significantly reduced (P < 0.0 5 or P < 0.01), and the contents of T-AOC, GSH-PX, IL-4, and IL-10 in the liver were significantly increased (P < 0.0 5 or P < 0.01). There were 380 mRNA and 178 protein differentially expressed between GP2 group and GP3 group. Part of DEGs was randomly selected for QPCR verification, and the expression results of randomly selected FABP1, SLC16A1, GPT2, AACS, and other genes were verified by QPCR to be consistent with the sequencing results, which demonstrated the accuracy of transcriptation-associated proteomics sequencing. The results showed that SMPs could alleviate the oxidative stress and inflammatory damage caused by FFC in the liver of chicken and restore the normal function of the liver. SMPs may alleviate the liver damage caused by FFC by regulating the drug metabolism-cytochrome P450, PPAR signaling pathway, MAPK signaling pathway, glutathione metabolism, and other pathways. [ABSTRACT FROM AUTHOR]

Lumpfish is a novel farmed species used as cleaner fish for the removal of lice from farmed salmon. As often with new, farmed species, there are challenges with bacterial infections. The frequency of prescription of antibiotic agents to lumpfish is increasing, despite the lack of knowledge about appropriate doses, duration of treatment and application protocols for the various antibacterial agents. In the current study, we have tested the effect of medicated feed with florfenicol (FFC), oxolinic acid (OA) and flumequine (FLU) on lumpfish experimentally challenged with Vibrio anguillarum, atypical Aeromonas salmonicida and Pasteurella atlantica. We found that all three antibacterial agents efficiently treated lumpfish with vibriosis using 10 and 20 mg kg−1 day−1 of FFC, 25 mg kg−1 day−1 of OA and 25 mg kg−1 day−1 FLU, whereas only FFC (20 mg kg−1 day−1) had good effect on lumpfish with pasteurellosis. None of the antibacterial agents were efficient to treat lumpfish with atypical furunculosis. FFC 20 mg kg−1 day−1 showed promising results in the beginning of the experiment, but the mortality increased rapidly 14 days post‐medication. Efficient treatment is important for the welfare of lumpfish and for reducing the risk of development of antibiotic‐resistant bacteria. To our knowledge, this is the first study to establish protocols for antibacterial treatment of lumpfish. [ABSTRACT FROM AUTHOR]

The study aimed to examine the effect of simultaneous application of florfenicol and lasalocid on the performance and vital organ function of chickens. For this, 300 chicks were divided into four groups. Group one to three received florfenicol, lasalocid and lasalocid plus florfenicol, respectively. Group four as the control group received a basic diet without lasalocid or florfenicol. Lasalocid was used from 7 to 35 days old, continuously. Florfenicol was used at 21 days old for 5 days. The growth indices were measured at the end of each week. The chickens were euthanized at the ages of 28 and 35 days old after collecting blood samples with and without anticoagulants. The liver, heart, muscle, kidney and sciatic nerve were collected in formalin 10% for histopathological examination. The blood and serum samples were used to determine clinical pathologic and hematologic indices. The ratio of internal organs to body weight and ratio of the right ventricle to the total ventricles (RV/TV) of the heart was measured. Results showed, the use of lasalocid decreased feed conversion rate and triglyceride, and increased total protein. Simultaneous administration of lasalocid and florfenicol affected histopathology of the liver and heart and significantly increased creatine phosphokinase, uric acid and the ratio of RV/TV of heart. The eosinophil percentage in the chickens who received florfenicol plus lasalocid was significantly higher than chickens who received florfenicol alone (p < 0.05). In conclusion, it seems that simultaneous administration of the florfenicol and lasalocid induces side‐effects especially on cardiac function and it is not recommended. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the presence and genetic environment of the multiresistance gene cfr gene in Pasteurella multocida of avian origin from China. Methods: A total of 113 P. multocida isolates were collected from sick poultries (ducks, chickens and geese) from 2003 to 2016 in Southern China and were screened for the presence of the cfr gene by PCR. The cfr-carrying P. multocida strains were subjected to antimicrobial susceptibility testing, S1 nuclease PFGE and Southern blot hybridisation, conjugative transfer and analysis of genetic environment of the cfr gene. Results: Among 113 P. multocida isolates, strains FJ6671 and FJ6683 from Muscovy duck harboured the cfr gene and presented a multiresistant phenotype. The cfr gene in the two strains was located on an ∼40-kb conjugative plasmid in different genetic environments, including ISApl12–cfr–IS26 and IS26–cfr–IS256. Conclusions: These results demonstrate plasmid-carried cfr in P. multocida and suggest that transposition and homologous recombination mediated by IS26, ISApl1 and IS256 might have played an important role in transfer of the cfr gene in P. multocida. To the best of our knowledge, this is the first report of the cfr gene in P. multocida. Active and ongoing surveillance of cfr in P. multocida is urgently warranted.

Florfenicol (FLO) is one of the most popular antibacterial drugs used in veterinary clinics and aquaculture. The drug was found to decrease the hatchability of eggs laid by treated hens in veterinary clinics and research work. However, the pathological changes in developing embryos and their cardiovascular system and the mechanism underlying FLO-induced embryonic death remain unclear. In the present study, fertilized eggs laid by hens treated with a therapeutic dose of FLO were collected and incubated. Results showed that FLO exposure repressed embryonic development and induced early embryonic death. As a result, FLO decreased the hatchability and increased the proportion of weak chicks. Moreover, FLO exposure led to embryonic lethality and inhibited the development of chick embryos as characterized by decreased weights, lagging distribution of Hamburger–Hamilton stages, and dysplastic eyes. Pathological examination indicated that FLO exposure affected the normal development of the heart in 4.5-day-old chick embryos, as characterized by shorter transverse cardiac diameter, disordered arrangement of trabecular muscles in ventricles, and reduced thickness of ventricular walls. Furthermore, FLO decreased blood vascular densities and downregulated the expression levels of key angiogenesis-related genes, including the vascular endothelial growth factor and fibroblast growth factor, in the yolk sac membrane. These findings indicated that FLO exposure restricted vascular development during early embryonic development. In summary, our data suggest that the restricted growth and abnormal cardiovascular development may be responsible for FLO-induced early embryonic death. Thus, these findings can be useful for guiding the proper use of FLO and in laying a foundation for further studies on the mechanism of FLO-induced embryonic toxicity.

A monoclonal antibody against florfenicol amine (FFA) was produced, and a competitive enzyme-linked immunosorbent assay (ELISA) was developed for detecting florfenicol (FF) and FFA in eggs. This proposed method exhibited the 50% inhibiting concentrations (IC50) of 0.120 ng/mL for FF and 0.118 ng/mL for FFA under the optimization of experimental parameters. At the fortified levels of 0.4, 0.8, 2.4, and 30.0 μg/kg, the inter-assay recoveries of the target compounds ranged from 78.3 to 103.2%, and the intra-assay recoveries ranged from 81.5 to 104.1%, respectively. The coefficients of variation were all below 12%. Results for the determination of spiked samples by this ELISA showed a good relationship with the high-performance liquid chromatography (HPLC) technique. This newly developed method confirmed to be rapid, user-friendly, and sensitivity for simultaneous detecting FF and FFA in eggs.

Abstract Background Antibiotics exposure has been implicated in the emergence of bacterial strains that are resistant to structurally related or unrelated antibiotics. Tylosin is a macrolide antibiotic that has been administered to treat respiratory pathogenic bacteria in swine. Thus, this study was undertaken to evaluate the impact of exposure to a constant (3 μg/mL) and decreasing concentrations of tylosin on the susceptibility of Salmonella enterica serovar Typhimurium to various antibiotics. Results S. Typhimurium strains exposed to tylosin for 12 and 24 h in the in vitro dynamic model demonstrated at least an eight-fold increase in the minimum inhibitory concentrations (MICs) of florfenicol and tetracycline. Exposure to tylosin extended the lag-time of the growth curve and enhanced the generation of reactive oxygen species. Gene expression analysis demonstrated up-regulation of the acrAB and tolC Salmonella efflux pump genes and its global regulators (marA and soxS). Besides, the expression of ompC gene was down-regulated in tylosin exposed S. Typhimurium. Conclusion Exposure to decreasing concentrations of tylosin could reduce the susceptibility of S. Typhimurium to florfenicol and tetracycline.

Florfenicol (FFC) is a commonly used antibiotic in animal husbandry, which is easy to cause organs damage in a variety of animals. It has been proved to have nephrotoxicity and affect the yield and quality of meat products. Salvia miltiorrhiza polysaccharides (SMPs) have been proved to have the pharmacological effects of regulating immunity and protecting the liver of animals, and its alleviative effect on renal injury is unclear. In order to investigate the alleviating effect of SMPs on drug nephrotoxicity and determine its potential molecular mechanism, we took chicks as the research object, FFC as the induced drug, and established the model by adding SMPs in drinking water. The chicks were randomly divided into control group, FFC model group (0.15 g/L FFC), FFC + low, medium and high dose of SMPs groups (0.15 g/L FFC + 1.25, 2.5, 5 g/L SMPs) and SMPs group (5 g/L SMPs). The results showed that, SMPs increased the average weight gain and renal index of chicks, alleviated the pathological changes of renal structure induced by FFC, decreased the contents of uric acid, blood urea nitrogen and creatinine in serum and malondialdehyde in renal tissue, increased the levels of glutathione, superoxide dismutase and catalase in renal tissue, up-regulated the relative expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1) mRNA and protein, and down-regulated the relative expression levels of p53, Caspase-3 and Caspase-6 mRNA and protein and the apoptosis rate of renal histiocytes. It is concluded that SMPs could significantly alleviate the renal injury induced by FFC, and its mechanism may be related to improving renal antioxidant capacity and inhibiting abnormal apoptosis of renal histiocytes.

Florfenicol (FLO), which is widely used in veterinary clinics and aquaculture, can disrupt the protein synthesis of bacteria and mitochondria and, thus, lead to antibacterial and toxic effects in plants, insects, and mammals. FLO was found to repress chicken embryonic development and induce early embryonic death previously, but the underlying mechanism is not fully understood. Clarifying the mechanism of FLO-induced embryonic toxicity is important to the research and development of new drugs and the rational use of FLO to ensure human and animal health and ecological safety. In this study, the effects of FLO on pluripotency, proliferation, and differentiation were investigated in P19 stem cells (P19SCs). We also identified differentially expressed genes and performed bioinformatics analysis to obtain hub genes and conducted some functional analysis. FLO inhibited the proliferation and pluripotency of P19SCs and repressed the formation of embryoid bodies derived from P19SCs. A total of 2,396 DEGs were identified using RNA-Seq in FLO-treated P19SCs, and these genes were significantly enriched in biological processes, such as angiogenesis, embryonic organ development, and morphogenesis of organs. Kyoto encyclopedia of genes and genome-based pathway analysis also showed that five relevant pathways, especially the canonical Wnt pathway, were engaged in FLO-induced toxicity of pluripotent stem cells. We further analyzed modules and hub genes and found the involvement of ubiquitin-mediated proteolysis, DNA replication, and cell cycle machinery in regulating the pluripotency and proliferation of FLO-treated P19SCs. In summary, our data suggest that FLO disrupts the signaling transduction of pathways, especially the canonical Wnt pathway, and further inhibits the expression of target genes involved in regulating DNA replication, cell cycle, and pluripotency. This phenomenon leads to the inhibition of proliferation and differentiation in FLO-treated P19SCs. However, further experiments are required to validate our findings and elucidate the potential mechanisms underlying FLO-induced embryonic toxicity.

ABSTRACT: Florfenicol is a broad-spectrum antibacterial drug used in the treatment of farm animals, including poultry. This drug is poorly soluble in water, therefore, administration in drinking water may lead to high variability of concentrations in treated individuals. The use of injection preparations, however, requires individual administration and may have a negative effect on the quality of the carcass. In addition, the renal portal system in birds may reduce the bioavailability of the drug administered in the caudofemoral region of the body. The aim of this study was to compare the pharmacokinetics of florfenicol in turkeys after a single intravenous, intramuscular, and subcutaneous administration at a dose of 15 mg/kg body weight. Additionally, to evaluate the effect of renal portal system on drug kinetics, the intramuscular administration was divided into pectoral and caudofemoral administration. The study showed that the area under the concentration-time curve (AUC) was similar regardless of the route of administration. The mean values for clearance and volume of distribution were 0.33 L/kg/h and 0.92 L/kg, respectively. The mean residence time (MRT) was 2.87 h for an intravenous bolus, while for the extravascular administrations it was approx. 5.5 h. The elimination half-life was approx. 4 h regardless of the route of administration. The maximum plasma concentration did not differ statistically between intramuscular (approx. 6.8 mg/L) and subcutaneous (8.2 mg/L) administrations, while the time to appear for this concentration was the longest for caudofemoral administration (1.5 h). The bioavailability was 88.64% for subcutaneous administration, 77.95% for pectoral administration and 85.30% for caudofemoral administration. Overall, all 3 routes of extravascular administration allowed for efficient drug absorption. There was no evidence of an influence of the renal portal system on the kinetic parameters of the drug administered to the lower extremities of the body.

ABSTRACT: This study describes the spontaneous and experimental salinomycin poisoning associated with the use of florfenicol and warns about the effects of the administration of antibiotics to animals that receive ionophores in the feed as growth promoters. A batch with 1,200 finishing pigs fed a diet containing 30ppm of salinomycin received florfenicol (60ppm via feed) to control respiratory diseases. Twenty-seven pigs had difficulty walking, tip-toe walking, muscle tremors, and anorexia seven days after the start of treatment. Twenty-two animals died, 10 recovered, and two were sent to the Laboratory of Animal Pathology of CAV-UDESC to be necropsied. The experimental reproduction of the disease was carried out to clarify the possible influence of florfenicol on salinomycin poisoning using 12 pigs divided into four groups with three animals each, treated for 16 days with diets containing no additives (Group 1), 50ppm of salinomycin (Group 2), 40ppm of florfenicol (Group 3), and 50ppm of salinomycin and 40ppm of florfenicol (Group 4). Only animals in Group 4 became ill. The clinical disease was reproduced from the ingestion of 24.67mg/kg/LW of salinomycin and 19.74mg/kg/LW of florfenicol. Both natural and experimental salinomycin poisoning associated with the use of florfenicol caused a condition of myopathy characterized in histology by hyaline degeneration and floccular necrosis of skeletal fibers, with macrophage infiltrate, associated with the figures of regeneration in skeletal muscles and multifocal areas of the proliferation of fibroblasts, being more intense in the longissimus dorsi and semimembranosus muscles. Therefore, florfenicol can cause the accumulation of ionophore salinomycin in the animal organism, resulting in a condition of toxic myopathy.

The accumulation of antimicrobial residues in edible animal products and aquaculture products could pose health concerns to unsuspecting consumers. Hence, this study aimed to develop a validated method for simultaneous quantification of chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF), and florfenicol amine (FFA) in beef, pork, chicken, shrimp, eel, and flatfish using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Primary-secondary amine (PSA) and MgSO4 were used for sample purification. The analytes were separated on a reversed-phase analytical column. The coefficients of determination for the linear matrix-matched calibration curves were ≥0.9941. Recovery rates ranged between 64.26 and 116.51% for the four analytes with relative standard deviations (RSDs) ≤ 18.05%. The calculated limits of detection (LODs) and limits of quantification (LOQs) were 0.005–3.1 and 0.02–10.4 μg/kg, respectively. The developed method was successfully applied for monitoring samples obtained from local markets in Seoul, Republic of Korea. The target residues were not detected in any tested matrix. The designed method was versatile, sensitive, and proved suitable for quantifying residues in animal-derived products.

Background: Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the anti-inflammatory and immunomodulatory properties of pentoxifylline (PTX) as an adjuvant to enhance the efficacy of antibiotics, the anti-inflammatory effects of the interaction FFC/PTX over the E. coli Lipopolysaccharide (LPS)-induced acute inflammatory response was evaluated in rabbits. Methods: Twenty-five clinically healthy New Zealand rabbits (3.8 ± 0.2 kg body weight: bw), were distributed into five experimental groups. Group 1 (control): treated with 1 mL/4 kg bw of 0.9% saline solution (SS) intravenously (IV). Group 2 (LPS): treated with an IV dose of 5 µg/kg of LPS. Group 3 (pentoxifylline (PTX) + LPS): treated with an oral dose of 30 mg/kg PTX, followed by an IV dose of 5 µg/kg of LPS 45 min after PTX. Group 4 (Florfenicol (FFC) + LPS): treated with an IM dose of 20 mg/kg of FFC, followed by an IV dose of 5 µg/kg of LPS 45 min after FFC administration. Group 5 (PTX + FFC + LPS): treated with an oral dose of 30 mg/kg of PTX, followed by an IM dose of 20 mg/kg of FFC, and, 45 min after an IV dose of 5 µg/kg of LPS was administered. The anti-inflammatory response was evaluated through changes in plasma levels of interleukins (TNF-α, IL-1β and IL-6), C-reactive protein (CRP), and body temperature. Results: It has been shown that each drug produced a partial inhibition over the LPS-induced increase in TNF-α, IL-1β, and CRP. When both drugs were co-administered, a synergistic inhibitory effect on the IL-1β and CRP plasma concentrations was observed, associated with a synergic antipyretic effect. However, the co-administration of PTX/FFC failed to modify the LPS-induced increase in the TNF-α plasma concentrations. Conclusions: We concluded that the combination of FFC and PTX in our LPS sepsis models demonstrates immunomodulatory effects. An apparent synergistic effect was observed for the IL-1β inhibition, which peaks at three hours and then decreases. At the same time, each drug alone was superior in reducing TNF-α levels, while the combination was inferior. However, the peak of TNF-α in this sepsis model was at 12 h. Therefore, in rabbits plasma IL-1β and TNF-α could be regulated independently, thus, further research is needed to explore the effects of this combination over a more prolonged period.

Widespread and inappropriate use of antibiotics has been shown to increase the spread of antibiotics and antimicrobial resistance genes (ARGs) in aquatic environments and organisms. Antibiotic use for the treatment of human and animal diseases is increasing continuously globally. However, the effects of legal antibiotic concentrations on benthic consumers in freshwater environments remain unclear. In the present study, we tested the growth response of Bellamya aeruginosa to florfenicol (FF) for 84 days under high and low concentrations of sediment organic matter (carbon [C] and nitrogen [N]). We characterized FF and sediment organic matter impact on the bacterial community, ARGs, and metabolic pathways in the intestine using metagenomic sequencing and analysis. The high concentrations of organic matter in the sediment impacted the growth, intestinal bacterial community, intestinal ARGs, and microbiome metabolic pathways of B. aeruginosa. B. aeruginosa growth increased significantly following exposure to high organic matter content sediment. Proteobacteria, at the phylum level, and Aeromonas at the genus level, were enriched in the intestines. In particular, fragments of four opportunistic pathogens enriched in the intestine of high organic matter content sediment groups, Aeromonas hydrophila, Aeromonas caviae, Aeromonas veronii, and Aeromonas salmonicida, carried 14 ARGs. The metabolic pathways of the B. aeruginosa intestine microbiome were activated and showed a significant positive correlation with sediment organic matter concentrations. In addition, genetic information processing and metabolic functions may be inhibited by the combined exposure to sediment C, N, and FF. The findings of the present study suggest that antibiotic resistance dissemination from benthic animals to the upper trophic levels in freshwater lakes should be studied further.

The diversity and composition of intestinal microbiota in rainbow trout have been studied using next-generation sequencing (NGS), although few studies have examined the effects of antimicrobials. We evaluated the effect of antibiotics florfenicol and erythromycin and infection with or without Flavobacterium psychrophilum on the intestinal microbiota in rainbow trout juveniles (30–40 g) using NGS. Prophylactic oral antibiotic treatments were administered for 10 days before groups of fish were injected intraperitoneally with virulent F. psychrophilum. Intestinal content (allochthonous bacteria) was collected at day −11, 0, 12, and 24 p.i., and the v3–v4 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Before prophylactic treatment, Tenericutes and Proteobacteria were the most abundant phyla identified and Mycoplasma was the most abundant genus. Fish infected with F. psychrophilum had decreased alpha diversity and a high abundance of Mycoplasma. Fish administered florfenicol had increased alpha diversity compared to the control at day 24 p.i., although both florfenicol and erythromycin-treated fish had a higher abundance of potential pathogens, specifically Aeromonas, Pseudomonas, and Acinetobacter. Mycoplasma disappeared after treatment but appeared again after day 24. This study demonstrates that prophylactic oral treatment with antibiotics florfenicol and erythromycin as well as F. psychrophilum infection changed the composition of intestinal microbiota in rainbow trout juveniles that did not recover by day 24 p.i. and further long-term effects on the host need to be investigated.

Antibiotic residue may pose a serious risk to aquaculture, and the culture of Litopenaeus vannamei in a low-salinity environment is a growing trend over the world. Here, we aimed to understand the combined effect of low salinity and sulfamethoxazole (SMZ) and florfenicol (FLO) antibiotics on L. vannamei. The growth performance, immune functions, antioxidant capacity and intestinal microbiota were investigated. Compared with the control group, the weight gain and survival rate significantly decreased (p < 0.05) in shrimp after they were exposed to low-salinity (salinity 3) water and the mixture of antibiotics and low-salt conditions for 28 days. The antioxidant activities of SOD and T-AOC, shown at low salinity and in the higher concentration of the SMZ treatment group (SMZH), were significantly decreased, while the GST activity was significantly increased in each treatment group in comparison with the control group. The expression of immune-related genes, including TOLL, LvIMD, PPO and HSP, in the low concentration of the SMZ treatment group (SMZL) was higher than that in the other groups. The diversity of intestine microbiota was disturbed with a lower Shannon index in the low-salinity and SMZH groups, and a higher Simpson index in the SMZH group. Proteobacteria, Actinobacteria and Bacteroidetes were the dominant phyla in the gut of L. vannamei. At the genus level, Microbacterium, Shewanella, Aeromonas, Acinetobacter, Gemmobacter, Paracoccus and Lysobacter were significantly decreased in the low-salinity group. However, the abundance of opportunistic pathogens belonging to the genus Aeromonas in the FLO group was increased. The predicted microbe-mediated functions showed that the pathway for “amino acid metabolism” and “replication and repair” was significantly inhibited in both the low-salinity and antibiotic-exposed groups. All the findings in this study indicate that the combined effect of antibiotics and low salinity on L. vannamei negatively impacted the physiological and intestinal microbiota functions.

Detection of florfenicol (FF) residues in animal-derived foods, as one of the most widely used antibiotics, is critically important to food safety. The fluorescent molecularly imprinted polymer (MIP) was synthesized by surface-initiated atom transfer radical polymerization technique with poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) microspheres, 4-vinylpyridine, ethylene glycol dimethacrylate, and FF as the matrix, functional monomer, crosslinker, and template molecule, respectively. Meanwhile, N-S co-doped carbon dot (CD) was synthesized with triammonium citrate and thiourea as precursors under microwave irradiation at 400 W for 2.5 min and then integrated into FF-MIP to obtain CD@FF-MIP. For comparison, non-imprinted polymer (NIP) without FF was also prepared. The adsorption capacity of CD@FF-MIP to FF reached 53.1 mg g -1 , which was higher than that of FF-MIP (34.7 mg g -1 ), whereas the adsorption capacity of NIP was only 17.3 mg g -1 . The adsorption equilibrium of three materials was reached within 50 min. Particularly, CD@FF-MIP exhibited an excellent fluorescence quenching response to FF in the concentration range of 3-50 µmol L -1 . As a result, CD@FF-MIP was successfully utilized to extract FF in milk samples, which were analyzed by high-performance liquid chromatography. The standard recoveries were 95.8%-98.2%, and the relative standard deviation was 1.6%-4.2%. The method showed the advantages of simple operation, high sensitivity, excellent selectivity, and low cost, and also demonstrated a great application prospect in food detection., (© 2024 Wiley‐VCH GmbH.)

Protein succinylation modification is a common post-translational modification (PTM) that plays an important role in bacterial metabolic regulation. In this study, quantitative analysis was conducted on the succinylated proteome of wild-type and florfenicol-resistant Vibrio alginolyticus to investigate the mechanism of succinylation regulating antibiotic resistance. Bioinformatic analysis showed that the differentially succinylated proteins were mainly enriched in energy metabolism, and it was found that the succinylation level of phosphoenolpyruvate carboxyl kinase (PEPCK) was highly expressed in the florfenicol-resistant strain. Site-directed mutagenesis was used to mutate the lysine (K) at the succinylation site of PEPCK to glutamic acid (E) and arginine (R), respectively, to investigate the function of lysine succinylation of PEPCK in the florfenicol resistance of V. alginolyticus . The detection of site-directed mutagenesis strain viability under florfenicol revealed that the survival rate of the E mutant was significantly higher than that of the R mutant and wild type, indicating that succinylation modification of PEPCK protein may affect the resistance of V. alginolyticus to florfenicol. This study indicates the important role of PEPCK during V. alginolyticus antibiotic-resistance evolution and provides a theoretical basis for the prevention and control of vibriosis and the development of new antibiotics.

Two rapid, simple, sensitive and selective derivative spectrofluorimetric methods (first and second derivative synchronous spectrofluorimetric (FDSFS and SDSFS) procedures) have been developed for the analysis of florfenicol in the presence of its various degradation products. FDSFS was applied to assay the drug in the presence of its alkaline, oxidative and photolytic degradation products while SDSFS was used to quantify it in the presence of its acidic degradation product. These methods permitted quantification of florfenicol at corresponding λ Em of 288, 287, 279 and 284 nm without interferences from any of its degradation products. Full validation procedures were applied to the suggested method according to International Conference of Harmonization guidelines. Moreover, different degradation kinetic parameters were calculated such as half-life ( t 1/2 ), degradation rate constant ( K ) and activation energy ( E a ). Using the analytical eco-scale, green analytical procedure index and analytical greenness metric approach AGREE as greenness assessment tools, the proposed method was found to be environmentally friendly., (© 2024 The Author(s).)