Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women.

BACKGROUND: Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking. METHODS: We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Hair samples were collected quarterly for objective assessment of doxycycline use. RESULTS: A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae-positive isolates were resistant to doxycycline. CONCLUSIONS: Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).

A dual-mode green emissive fluorescent probe for real-time detection of doxycycline in milk using a smartphone sensing platform.

Real-time quantitative analysis of tetracyclines is urgently needed to provide consumers with early warning of potential risks. Herein, we report a dual-mode green emissive fluorescent probe, which refers to the liquid mode and the solid mode of electrospun films doped with nitride-doped carbon nanosheets (NCNSs) for real-time detection of doxycycline (DOX). Highly fluorescent NCNSs were prepared by low-temperature solid treatment of urea and sodium citrate. With the addition of DOX, the green emission intensity of NCNSs at 475 nm can be obviously reduced. Method validation exhibited a good linear relationship in 0.05-150 µM between the fluorescence quenching of NCNSs and the concentration of DOX with a limit of detection (LOD) of 0.0127 µM. Furthermore, the immobilization of NCNSs in PAN carriers forming electrospun films stabilizes the green fluorescence of NCNSs. Additionally, electrospun films integrated into a smartphone were developed for real-time detection of DOX with LOD of 0.285 µM. Additionally, DOX in milk was monitored with satisfactory recoveries. Therefore, the integration of the smartphone and electrospun film provides a promising and convenient method for real-time identification of DOX in food analysis.

Integrated Multiomics and Synergistic Functional Network Revealed the Mechanism in the Tolerance of Different Ecotypes of Salvia miltiorrhiza Bge. to Doxycycline Pollution.

Tetracycline pollution in soil irreversibly damages the biosafety of plants by inhibiting the mitochondrial function. Some traditional Chinese medicine (TCM) plants, such as Salvia miltiorrhiza Bunge, have a strong tolerance to mitochondrial damage. We comprehensively compared the doxycycline (DOX) tolerances of two ecotypes of S. miltiorrhiza in the Sichuan and Shandong provinces and found that the Sichuan ecotype had a lower yield reduction, more stable accumulation of medicinal ingredients, higher mitochondrial integrity, and a more robust antioxidant system. The synergetic response networks under DOX pollution of both ecotypes were constructed using RNA sequencing and ultrahigh-performance liquid chromatography-tandem mass spectrometry. The differentiation of the downstream pathways of aromatic amino acids (AAAs) produced variations in the DOX tolerance of S. miltiorrhiza in different regions. The Sichuan ecotype maintained redox homeostasis and xylem development by activating salvianolic acid and indole biosynthesis, while the Shandong ecotype balanced chemical and mechanical defenses by regulating the flavonoid biosynthesis. Rosmarinic acid, a downstream AAA molecule, maintains the mitochondrial homeostasis of plant seedlings under DOX pollution by targeting the ABCG28 transporter. We also highlight the significance of downstream AAA small molecules in guiding the development of bio-based environmental pollution remediation agents.

New method for morphological identification and simultaneous quantification of multiple tetracyclines by a white fluorescent probe.

The threat of tetracycline antibiotics to the environment and human health is attracting widespread attention. The development of morphological analysis and quantitative techniques of multiple tetracyclines is of great significance for the evaluation of biochemical toxicity, wide-spectrum antibacterial property and degradation cycle between different tetracyclines. In this study, the white fluorescent Eu/Tb@CDs was synthesized and applied successfully to the identification and detection of the most widely used tetracycline antibiotics (tetracycline (TC), oxytetracycline (OC), chlortetracycline (CC) and doxycycline (DC)) with detection limits all below 1 nM. For the actual water samples with coexistence of the above 4 tetracyclines, their simultaneous morphology identification and accurate quantitative detection can also be realized through simple spectrometric measurement. In addition, the selective and competitive experiments have been carried out on the pollutants widely present in water, and the results have also confirmed that other pollutants could not interfere with the detection of the above 4 tetracyclines. It is undeniable that this work will conveniently and visually reveal the existence information and geographical distribution characteristics of different tetracycline antibiotics in the environment and their action mechanism on organisms.

A Case of Doxycycline-induced Melanin in the Gingiva Tissue: Case Report.

BACKGROUND: Gingival pigmentation is a discoloration of the gingiva due to a variety of lesions and conditions associated with several endogenous and exogenous etiologic features. OBJECTIVE: The purpose of this study is to describe a report of gingival pigmentation in a patient who used doxycycline. CASE REPORT: A 21-year-old Caucasian female was under dermatological treatment and antibiotic therapy with doxycycline 100 mg (one time a day) for 90 days. She presented brown pigmentation at the gingival margin on the facial surfaces of the upper and lower anterior incisors and premolars. The patient was evaluated by immunohistochemical (S-100, Melan-A, and HMB-45) and histopathologic analyses, and clinical history. Blood levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were analyzed by UV/Vis spectroscopy. The adrenaline, noradrenaline, and dopamine in blood were analyzed by high-performance liquid chromatography (HPLC); dehidroepiandrosterone (DHEA) in serum by radioimmunoassay; and luteinizing hormone (LH) and 25-Hydroxyvitamin D by chemiluminescence. Hematoxylin-eosin stained sections revealed keratinocytes with pigment compatible with melanin. The Fontana-Masson staining was positive in melanophages and in some basal keratinocytes. S-100, Melan A and HMB-45 were confirmed as positive markers of melanocytic differentiation in gingival tissue. We observed a significant increase in malondialdehyde (p˂0.05) and a decrease in superoxide dismutase levels (p˂0.05). The dopamine value was found to be 15 pg/ml (reference value ≤ 10 pg/ml). CONCLUSION: The use of doxycycline is associated with an increase in oxidative stress and of dopamine with melanin pigments in the gingival tissue. This case report showed a cause-effect relationship between exposure to doxycycline and pigmentation of the marginal gingiva.

Uptake of Pharmaceutical Pollutants and Their Metabolites from Soil Fertilized with Manure to Parsley Tissues.

Manure is a major source of soil and plant contamination with veterinary drugs residues. The aim of this study was to evaluate the uptake of 14 veterinary pharmaceuticals by parsley from soil fertilized with manure. Pharmaceutical content was determined in roots and leaves. Liquid chromatography coupled with tandem mass spectrometry was used for targeted analysis. Screening analysis was performed to identify transformation products in the parsley tissues. A solid-liquid extraction procedure was developed combined with solid-phase extraction, providing recoveries of 61.9-97.1% for leaves and 51.7-95.6% for roots. Four analytes were detected in parsley: enrofloxacin, tylosin, sulfamethoxazole, and doxycycline. Enrofloxacin was detected at the highest concentrations (13.4-26.3 ng g-1). Doxycycline accumulated mainly in the roots, tylosin in the leaves, and sulfamethoxazole was found in both tissues. 14 transformation products were identified and their distribution were determined. This study provides important data on the uptake and transformation of pharmaceuticals in plant tissues.

Doxycycline detection and degradation in aqueous media via simultaneous synthesis of Fe-N@carbon dots and Fe3O4-carbon dot hybrid nanoparticles: a one arrow two hawk approach.

The overuse of antibiotics in recent years presents a huge challenge to society for their removal from the environment. The prolonged presence of antibiotics as environmental pollutants results in the emergence of drug-resistant bacteria faster than new antibiotics to treat diseases they cause. Therefore, a rapid, sensitive, and cost-effective method is urgently required to detect and degrade antibiotics. Given this, a novel strategy has been devised for synthesizing Fe-doped carbon dots (Fe-N@CDs) and iron oxide-carbon dot hybrid nanoparticles (Fe3O4-CDs) in a single step for doxycycline detection and its degradation. For the very first time, the formation of two simultaneous products, i.e., Fe-N@CDs (0 D fluorescent carbon dots) and Fe3O4-CDs (magnetic nanoparticles) in a single step hydrothermal carbonization process by using a sole iron salt (FeCl2) and carbon precursor (citric acid) in the presence of ethylenediamine is reported. The as prepared Fe-N@CDs selectively detect doxycycline with a limit of detection value of 66 ng mL-1 and in the linear range from 0 mg mL-1 to 50 mg mL-1, whereas the other formed products, i.e., Fe3O4-CDs, degrade doxycycline by 70.26% in just 5 min by applying shear force using simply a kitchen blender. The results demonstrated the suitability and application scope in food and environment safety.

[Investigation and health risk assessment of veterinary drug residues in chickens and eggs sold in Ningxia from 2016 to 2020].

OBJECTIVE: To understand the monitoring status of veterinary drug residues in chickens and eggs sold in Ningxia from 2016 to 2020, and to evaluate the health risks of human intake. METHODS: A total of 303 chicken and 237 eggs were collected from 2016 to 2020, and the veterinary drug residues in chickens and eggs sold in Ningxia were detected and analyzed by high performance liquid chromatography-tandem mass spectrometry. The food safety index method was used to assess the health risks in combination with the dietary intake of residents. RESULTS: The detection rate of veterinary drug residues in chicken was 38.0%(115/303), and the over-standard rate was 7.6%(23/303). The detection rate of veterinary drug residues in eggs was 26.6%(63/237), and the over-standard rate was 19.8%(47/237). The food safety index of doxycycline in chicken was 4.59, and the food safety indexes of doxycycline, flumequine and flufenicol in eggs were 7.09, 26.5 and 2.33, respectively, all of which were much higher than 1, suggesting that there were health risks. The food safety indexes of other substances were all less than 1, and the food safety indexes were all acceptable. CONCLUSION: Veterinary drugs were widely detected in chicken and eggs in Ningxia from 2016 to 2020. Some veterinary drugs had hidden health risks.

Risk to Public Health Regarding Doxycycline Residues in Chicken Claws.

Doxycycline residues in claws may pose a potential risk to humans. A study with broiler chickens was performed to find the concentrations of doxycycline in claws after treatment. For the quantification of the antibiotic of interest in claws, an ultrahigh-performance liquid chromatography-tandem mass spectrometry method was developed. Doxycycline was detectable at 3043 µg/kg at sub-therapeutic treatment, 223 µg/kg after therapeutic doses, and 14 µg/kg after spray application on the last day of the experiment (day 22). Almost 70 days is required for the concentration of doxycycline to reach zero. The obtained results show that monitoring of doxycycline in claws should be implemented.

A ratiometric fluorescence-scattering sensor for rapid, sensitive and selective detection of doxycycline in animal foodstuffs.

The residue problem of tetracycline antibiotics, especially doxycycline (DC), in animal foodstuffs has attracted much attention. This paper reported ZIF-8 and bovine serum albumin (BSA) as a ratiometric fluorescence-scattering sensor for DC. The mechanism relied on the disassembly of ZIF-8 caused by DC, bringing weakened second-order scattering, and the double fluorescence amplification of DC under ZIF-8 with BSA, inducing enhanced fluorescence. The response of the sensor was completed within 1 min, and the detection limit for DC (3.4 nM) was 1-2 orders of magnitude lower than the reported ones. The distinguishment of DC from other tetracycline antibiotics was also achieved by the sensor. The sensor was applied to detecting DC in animal foodstuffs with satisfactory recoveries (80.0-104.0%). Hence, this work develops a rapid, sensitive and selective ratiometric sensor to monitor the DC residue in animal foodstuffs, also opens the window to construct ratiometric DC sensors with the fluorescence-scattering strategy.

Simultaneous Determination of Tetracyclines and Fluoroquinolones in Poultry Eggs by UPLC Integrated with Dual-Channel-Fluorescence Detection Method.

An innovative, rapid and stable method for simultaneous determination of three tetracycline (oxytetracycline, tetracycline and doxycycline) and two fluoroquinolone (ciprofloxacin and enrofloxacin) residues in poultry eggs by ultra-high performance liquid chromatography-fluorescence detection (UPLC-FLD) was established and optimized. The samples were homogenized and extracted with acetonitrile/ultrapure water (90:10, v/v) and then purified by solid-phase extraction (SPE). LC separation was achieved on an ACQUITY UPLC BEH C18 column (1.7 µm, 2.1 mm × 100 mm), and the mobile phase was composed of acetonitrile and a 0.1 mol/L malonic acid solution containing 50 mmol/L magnesium chloride (the pH was adjusted to 5.5 with ammonia). When the five target drugs were spiked at the limit of quantification, 0.5 times the maximum residue limit (MRL), 1.0 MRL and 2.0 MRL, the recoveries were above 83.5% and the precision ranged from 1.99% to 6.24%. These figures of merit complied with the parameter validation regulations of the EU and U.S. FDA. The limits of detection and quantifications of the targets were 0.1-13.4 µg/kg and 0.3-40.1 µg/kg, respectively. The proposed method was easily extended to quantitative analyses of target drug residues in 85 egg samples, thus demonstrating its reliability and applicability.

A ratiometric fluorescent probe based on sulfur quantum dots and calcium ion for sensitive and visual detection of doxycycline in food.

The residue of doxycycline in food can cause harm to human. Therefore, the detection of doxycycline residue is necessary. Herein, a ratiometric fluorescent probe was designed based on sulfur quantum dots (S dots) and Ca2+. Due to static quenching and inter filter effect between doxycycline and S dots, doxycycline quenched fluorescence of S dots at 450 nm. Meanwhile, doxycycline and Ca2+ formed fluorescent complex through coordination to produce new peak at 520 nm. The ratio of fluorescence intensity (F520/F450) and doxycycline concentration showed good linear relationship with detection limit of 0.19 µM. The fluorescence color of S dots/Ca2+ changed from blue to light green with increasing doxycycline concentration, which was applied for visual semi-quantitative detection of doxycycline. Moreover, the method was used for detecting doxycycline in milk and fish samples with recoveries in the range of 91%-110%. The method showed good application potential in detection of doxycycline in food samples.

When is it safe to eat different broiler chicken tissues after administration of doxycycline and tylosin mixture?

Residues of veterinary drugs in poultry meat have serious health effects on humans (e.g., antimicrobial resistance, carcinogenicity, and hypersensitivity), which make the control of veterinary drug residues an important parameter in ensuring consumer protection.  This work was performed to quantitatively determine two co-formulated anti-infective veterinary agents, tylosin tartrate (TYT) and doxycycline hydrochloride (DOX) in different tissues of broiler chickens (liver, muscles, and fat) using high performance liquid chromatography. The chicken was treated with the recommended dose of a binary mixture of the drugs (Tydovet). Moreover, the study aimed to estimate the withdrawal time of both drugs in chicken tissues. The analysis was done by solvent extraction and solid-phase extraction for clean-up of samples from the tissue matrix, followed by liquid chromatographic determination of the cited drugs with UV-detection. Residue decline with time was tracked, and both antibiotics were found to be more persistent in liver tissues than other tissues (muscle and fat). The effect of freezing and cooking was investigated on tissue residue levels. While freezing had little effect on the concentration of both antibiotics; cooking, as anticipated, led to a marked decline. Therefore, it is recommended to pay attention to the proper withdrawal periods before marketing to ensure the hygienic suitability of broilers edibles for safe human consumption. PRACTICAL APPLICATION: This novel study measures tylosin and doxycycline residues simultaneously in different tissues (muscle, fat, and liver) after administration of Tydovet powder to the broiler chicken. Residues in fat persisted for a longer time than in muscle in case of TYT, whereas the reverse was noticed in DOX.

Drug-Based Gold Nanoparticles Overgrowth for Enhanced SPR Biosensing of Doxycycline.

In clinical chemistry, frequent monitoring of drug levels in patients has gained considerable importance because of the benefits of drug monitoring on human health, such as the avoidance of high risk of over dosage or increased therapeutic efficacy. In this work, we demonstrate that the drug doxycycline can act as an Au nanoparticle (doxy-AuNP) growth and capping agent to enhance the response of a surface plasmon resonance (SPR) biosensor for this drug. SPR analysis revealed the high sensitivity of doxy-AuNPs towards the detection of free doxycycline. More specifically, doxy-AuNPs bound with protease-activated receptor-1 (PAR-1) immobilized on the SPR sensing surface yield the response in SPR, which was enhanced following the addition of free doxy (analyte) to the solution of doxy-AuNPs. This biosensor allowed for doxycycline detection at concentrations as low as 7 pM. The study also examined the role of colloidal stability and growth of doxy-AuNPs in relation to the response-enhancement strategy based on doxy-AuNPs. Thus, the doxy-AuNPs-based SPR biosensor is an excellent platform for the detection of doxycycline and demonstrates a new biosensing scheme where the analyte can provide enhancement.

Pharmacokinetics, bioavailability and tissue residues of doxycycline in Japanese quails (Coturnix coturnix japonica) after oral administration.

This study aimed to determine the bioavailability, tissue residue and withdrawal time of doxycycline after oral administration in Japanese quails (Coturnix coturnix japonica). Japanese quails received doxycycline at 20 mg/kg dose following either single intravenous or oral administration, or 5-day oral administration. Doxycycline concentrations in plasma, liver, kidney, muscle, and skin + fat were determined using high-performance liquid chromatography-ultraviolet. The Withdrawal Time v1.4 software was used to calculate withdrawal times. Following single oral administration, terminal elimination half-life, area under the concentration-time curve from 0 to infinitive time, peak plasma concentration (Cmax) and time to reach Cmax were 10.98 h, 215.84 (h*µg)/mL, 15.33 µg/mL, and 2 h, respectively. The oral bioavailability was 25.84% in quails. In this study, the mean doxycycline concentration was below the maximum residue limit (MRL) at day 4 in skin + fat (0.120 µg/g), and at day 5 in kidney (0.41 µg/g), liver (0.26 µg/g), and muscle (<0.05 µg/g lowest limit of quantification). The highest concentrations of doxycycline after 5-day oral administration were found in kidney compared with other tissues and plasma. These results indicate that the withdrawal times required for doxycycline to reach concentrations

Exposure pathways and ecological risk assessment of common veterinary antibiotics in the environment through poultry litter in Bangladesh.

Veterinary antibiotics (VAs) have entered the ecosystem principally through the application of organic fertilizer. However, factors influencing the contributions made by the prescribers and users thereof with respect to VAs in poultry manure have not been investigated. The purpose of this paper, therefore, is to identify factors associated with the VA prescription and usage as well as to measure the residual concentration along with the ecological risk of common VAs in poultry litter in Bangladesh. Structured questionnaire surveys were conducted so as to provide an understanding the perspective of prescribers and farmers. Ciprofloxacin (CIP), enrofloxacin (ENR), oxytetracycline (OTC), and doxycycline (DOX) were screened through the use of thin-layer chromatography (TLC) and quantified through high-performance liquid chromatography (HPLC). Also, methods of risk quotient (RQ) were applied to assess ecotoxicity. Most VAs were prescribed without a confirmatory diagnosis. The residue of CIP was dominant with a high concentration, followed by OTC but with a low concentration. A high ecological risk was associated with the use of OTC and DOX whereas the risk associated with the use of CIP and ENR was insignificant to low. The study highlights prescriber and user factors along with the variable ecological risk of VAs in litter.

Rapid liquid chromatographic method for the control of doxycycline and tiamulin residues and their metabolites in vivo assays with pigs: Treatment and depletion.

Results gained from in vivo metabolism could be more authentic to reflect the biotransformation of drugs than in vitro metabolism. This paper discusses the development and characterization of an analytical method for controlling tiamulin (TIA) and doxycycline (DOX) residues in pig plasma and urine, as well as their in vivo biotransformation during treatment and suppression steps at pig farms. For such a purpose, urine samples were taken daily (24-hr intervals) during treatment and until day 8 after last dose. Plasma samples were collected on the last treatment day and up to days 4 and 7 after the last dose. Only traces of TIA and their metabolites have been still detected 8 days after the last day of therapy, in agreement with the period of suppression of both antibiotics set by the manufacturers in 7 days. It was estimated that TIA and DOX half-lives were of two days and one day, respectively. TIA and DOX metabolites have been identified for the first time in plasma and urine pig samples during treatment and suppression steps.

Contamination of Animal Feed with Undeclared Tetracyclines-Confirmatory Analysis by Liquid Chromatography-Mass Spectrometry after Microbiological Plate Test.

The presence of tetracycline (TC) antibiotics was determined in animal feed that had been previously screened with a microbiological plate test. Feed samples were screened by a microbiological plate test on a pH 6.0 culture medium seeded with Bacillus cereus ATCC 11778 able to pre-reveal the presence of tetracyclines. Subsequently, confirmation and quantification were performed using a validated HPLC method with mass spectrometric detection. In 2013-2018, 353 feed samples were analysed to detect antibacterial substances, of which 186 (52.7%) were suspected to contain tetracyclines. Forty-two out of 186 (22.6%) samples analysed by the chromatographic method contained undeclared tetracyclines, which were determined at concentrations from 0.3 to 49 mg kg-1. The most frequently identified contaminating tetracyclines were doxycycline and chlortetracycline.

Doxycycline transfer from substrate to white button mushroom (Agaricus bisporus) and assessment of the potential consumer exposure.

The presence of antibiotic residues in the food chain may pose a serious risk to human health. Locating and evaluating new sources of consumer exposure to antibiotic residues in food is a very important element of health protection. The possibility of doxycycline uptake from the substrate for mushroom cultivation by the white button mushroom (Agaricus bisporus) fruit body was investigated. Mushrooms were experimentally cultivated on substrate contaminated with 8 different doxycycline concentrations in substrate and analyte concentrations in mushroom samples were measured using ultra-high performance liquid chromatography - triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) The obtained results clearly indicated that doxycycline transfers from contaminated substrate to mushrooms at concentrations ranging from 0.87 to 72.3 µg/kg, depending on substrate contamination concentration level and order of harvesting.

A physiologically based pharmacokinetic model of doxycycline for predicting tissue residues and withdrawal intervals in grass carp (Ctenopharyngodon idella).

The extensive use of doxycycline in aquaculture results in drug residue violations that negatively impact human food safety. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for doxycycline to predict drug residues and withdrawal times (WTs) in grass carp (Ctenopharyngodon idella) after daily oral administration for 3 days. Physiological parameters including cardiac output and organ weights were measured experimentally. Chemical-specific parameters were obtained from the literature or estimated by fitting to the observed data. The model properly captured the observed kinetic profiles of doxycycline in tissues (i.e., liver, kidney, muscle + skin and gill). The predicted WT in muscle + skin by Monte Carlo analysis based on sensitive parameters identified at 24 h after drug administration was 41 d, which was similar to 43 d calculated using the tolerance limit method. Sensitivity analysis identified two additional sensitive parameters at 6 weeks: intestinal transit rate constant and urinary elimination rate constant. The predicted WT in muscle + skin based on sensitive parameters identified at 6 weeks was 54 d. This model provides a useful tool to estimate tissue residues and withdrawal times for doxycycline in grass carp and also serves a foundation for extrapolation to other fish species and other tetracyclines.