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Microbiology Spectrum Jun 2023As multidrug-resistant pathogens emerge and spread rapidly, novel antibiotics urgently need to be discovered. With a dwindling antibiotic pipeline, antibiotic adjuvants...
As multidrug-resistant pathogens emerge and spread rapidly, novel antibiotics urgently need to be discovered. With a dwindling antibiotic pipeline, antibiotic adjuvants might be used to revitalize existing antibiotics. In recent decades, traditional Chinese medicine has occupied an essential position in adjuvants of antibiotics. This study found that baicalein potentiates doxycycline against multidrug-resistant Gram-negative pathogens. Mechanism studies have shown that baicalein causes membrane disruption by attaching to phospholipids on the Gram-negative bacterial cytoplasmic membrane and lipopolysaccharides on the outer membrane. This process facilitates the entry of doxycycline into bacteria. Through collaborative strategies, baicalein can also increase the production of reactive oxygen species and inhibit the activities of multidrug efflux pumps and biofilm formation to potentiate antibiotic efficacy. Additionally, baicalein attenuates the lipopolysaccharide-induced inflammatory response . Finally, baicalein can significantly improve doxycycline efficacy in mouse lung infection models. The present study showed that baicalein might be considered a lead compound, and it should be further optimized and developed as an adjuvant that helps combat antibiotic resistance. Doxycycline is an important broad-spectrum tetracycline antibiotic used for treating multiple human infections, but its resistance rates are recently rising globally. Thus, new agents capable of boosting the effectiveness of doxycycline need to be discovered. In this study, it was found that baicalein potentiates doxycycline against multidrug-resistant Gram-negative pathogens and . Due to its low cytotoxicity and resistance, the combination of baicalein and doxycycline provides a valuable clinical reference for selecting more effective therapeutic strategies for treating infections caused by multidrug-resistant Gram-negative clinical isolates.
Topics: Animals; Mice; Humans; Doxycycline; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Flavanones; Gram-Negative Bacteria; Lipopolysaccharides; Microbial Sensitivity Tests; Gram-Negative Bacterial Infections
PubMed: 37070985
DOI: 10.1128/spectrum.04702-22 -
Journal of the American Veterinary... Oct 2017OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use <...
OBJECTIVE To determine drug content (potency) of compounded doxycycline formulations for veterinary use and of US FDA-approved doxycycline formulations for human use < 24 hours after receipt (day 1) and after 21 days of storage under recommended conditions (day 21). DESIGN Evaluation study. SAMPLE FDA-approved doxycycline tablets (100 mg), capsules (100 mg), and liquid suspension (10 mg/mL) and compounded doxycycline formulations from 3 pharmacies (tablets [25, 100, and 150 mg; 1 product/source], chews [100 mg; 1 product/source], and liquid suspensions or solution [6 mg/mL {2 sources} and 50 mg/mL {1 source}]). PROCEDURES Doxycycline content was measured in 5 samples of each tablet, chew, or capsule formulation and 5 replicates/bottle of liquid formulation on days 1 and 21 by liquid chromatography and compared with US Pharmacopeia acceptable ranges. RESULTS All FDA-approved formulations had acceptable content on days 1 and 21. On day 1, mean doxycycline content for the 3 compounded tablet formulations was 89%, 98%, and 116% (3/5, 5/5, and 1/5 samples within acceptable ranges); day 21 content range was 86% to 112% (1/5, 5/5, and 4/5 samples within acceptable ranges). Day 1 content of chews was 81%, 78%, and 98% (0/5, 0/5, and 5/5 samples within acceptable ranges), and that of compounded liquids was 50%, 52%, and 85% (no results within acceptable ranges). No chews or compounded liquid formulations met USP standards on day 21. CONCLUSIONS AND CLINICAL RELEVANCE FDA-approved doxycycline should be prescribed when possible. Whole tablets yielded the most consistent doxycycline content for compounded formulations.
Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Doxycycline; Drug Compounding; Drug Stability; Drug Storage; Humans; Tablets; Time Factors; United States; United States Food and Drug Administration; Veterinary Drugs
PubMed: 28967825
DOI: 10.2460/javma.251.7.835 -
The New England Journal of Medicine Jun 2021Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment.
METHODS
In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks.
RESULTS
From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2).
CONCLUSIONS
A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).
Topics: Adult; Anti-Bacterial Agents; Asymptomatic Infections; Australia; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Double-Blind Method; Doxycycline; Homosexuality, Male; Humans; Intention to Treat Analysis; Male; Nucleic Acid Amplification Techniques; Rectal Diseases; Rectum
PubMed: 34161706
DOI: 10.1056/NEJMoa2031631 -
Nature Communications Oct 2022The experimental need to engineer the genome both in time and space, has led to the development of several photoactivatable Cre recombinase systems. However, the...
The experimental need to engineer the genome both in time and space, has led to the development of several photoactivatable Cre recombinase systems. However, the combination of inefficient and non-intentional background recombination has prevented thus far the wide application of these systems in biological and biomedical research. Here, we engineer an optimized photoactivatable Cre recombinase system that we refer to as doxycycline- and light-inducible Cre recombinase (DiLiCre). Following extensive characterization in cancer cell and organoid systems, we generate a DiLiCre mouse line, and illustrated the biological applicability of DiLiCre for light-induced mutagenesis in vivo and positional cell-tracing by intravital microscopy. These experiments illustrate how newly formed HrasV12 mutant cells follow an unnatural movement towards the interfollicular dermis. Together, we develop an efficient photoactivatable Cre recombinase mouse model and illustrate how this model is a powerful genome-editing tool for biological and biomedical research.
Topics: Mice; Animals; Doxycycline; Optogenetics; Mice, Transgenic; Gene Editing; Integrases; Mice, Inbred Strains
PubMed: 36307419
DOI: 10.1038/s41467-022-33863-z -
Scientific Reports Oct 2019Doxycycline, a member of the tetracycline family, is a drug used as an antibiotic (dosage of 100 mg/day) and as an anti-inflammatory drug on the dosage of 20 mg...
Doxycycline, a member of the tetracycline family, is a drug used as an antibiotic (dosage of 100 mg/day) and as an anti-inflammatory drug on the dosage of 20 mg twice a day, this use has Matrix Metalloproteinases (MMP) inhibitor action. Doxycycline is a calcium chelator and therefore interferes in bone remodeling. The main objective of this study was to evaluate the action of the drug doxycycline in the control of osteopenia. Sixty three Wistars rats were divided into 9 groups with n = 7 each, as follow: the control group with doxycycline 10 mg/kg/day (C10), control with doxycycline 30 mg/kg/day (C30) and control (C), ovariectomized group with doxycycline 10 mg/kg/day (OVX10), ovariectomized with doxycycline 30 mg/kg/day (OVX30), and ovariectomized with water (OVX), sedentary group with 10 mg/kg/day (Se10), sedentary with doxycycline 30 mg/kg/day (Se30), and sedentary group with water (Se). Left femoral bone was used for bone densitometry, right femoral bone for histological analysis. The right tibia was intended for chemical quantifications, the total serum was used for cholesterol and calcium quantification. The length of the left femoral bone was measured after the densitometry analysis. Statistical analysis was performed using multivariate general linear model (ANOVA two factors with Bonferroni adjustment) and the TRAP analysis was subjected to normality test and then were subjected to nonparametric test, both with p < 0.05 significance. Statistically significant differences were found, with better results for the groups exposed to the medication (10 and 30 mg/kg/day): Se vs. Se10 and Se vs. Se30 for BMC, quantification of magnesium, amount of cancellous bone in the distal portion; OVX vs. OVX10 for BMC, BMD and calcium in serum; OVX vs. OVX10 and OVX30 for quantification in proximal and distal portion of cancellous bone; Se vs. Se30 and OVX vs. OVX30 for immunostaining for TRAP, all results with minimum of p ≤ 0.05. Doxycycline had a deleterious effect on control groups and positive action for bone organization on female rats affected by bilateral ovariectomy-induced osteopenia and sedentary lifestyle.
Topics: Animals; Body Weight; Bone Diseases, Metabolic; Calcium; Cancellous Bone; Doxycycline; Female; Femur; Magnesium; Public Health; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Zinc
PubMed: 31653893
DOI: 10.1038/s41598-019-51702-y -
Scientific Reports Aug 2023Chlamydiosis remains the leading infectious disease and is one of the key factors responsible for the dramatic reduction of koala populations in South-East Queensland...
Chlamydiosis remains the leading infectious disease and is one of the key factors responsible for the dramatic reduction of koala populations in South-East Queensland (SEQ) and New South Wales (NSW) regions of Australia. Possible infection outcomes include blindness, infertility, painful cystitis, and death if left untreated. Studies have reported the treatment efficacy of chloramphenicol and doxycycline, which are the two most commonly administered treatments in diseased koalas, in clinical settings. However, none have directly compared the treatment efficacy of these antibacterials on koala survival. A retrospective study was essential to identify any relationships between the demographical information, and the animals' responses to the current treatment regimens. Associations were explored between six explanatory (sex; maturity; location; clinical signs, treatment; treatment duration) and two outcome variables (survival; post-treatment PCR). Results showed that female koalas had a statistical trend of lower odds of surviving when compared to males (OR = 0.36, p = 0.05). Koalas treated with chloramphenicol for ≥ 28 days had greater odds of surviving than when treated for < 28 days (OR = 8.8, p = 0.02), and those koalas administered doxycycline had greater odds of testing PCR negative when compared to chloramphenicol treatments (OR = 5.45, p = 0.008). There was no difference between the antibacterial treatments (chloramphenicol, doxycycline, and mixed/other) and the survival of koalas. Female koalas had greater odds of exhibiting UGT signs only (OR = 4.86, p < 0.001), and also greater odds of having both ocular and UGT clinical signs (OR = 5.29, p < 0.001) when compared to males. Of the koalas, 28.5% initially had no clinical signs but were PCR positive for C. pecorum. This study enables further understanding of the complex nature between chlamydial infection and response to antibacterial treatment.
Topics: Animals; Male; Female; Phascolarctidae; Retrospective Studies; Doxycycline; Chlamydia; Chlamydia Infections; Anti-Bacterial Agents; Chloramphenicol
PubMed: 37542093
DOI: 10.1038/s41598-023-39832-w -
Antimicrobial Agents and Chemotherapy Apr 2020Doxycycline, an FDA-approved tetracycline, is used in tuberculosis models for the temporal control of mycobacterial gene expression. In these models, animals are...
Doxycycline, an FDA-approved tetracycline, is used in tuberculosis models for the temporal control of mycobacterial gene expression. In these models, animals are infected with recombinant carrying genes of interest under transcriptional control of the doxycycline-responsive TetR- unit. To minimize fluctuations of plasma levels, doxycycline is usually administered in the diet. However, tissue penetration studies to identify the minimum doxycycline content in food achieving complete repression of TetR-controlled genes in tuberculosis (TB)-infected organs and lesions have not been conducted. Here, we first determined the tetracycline concentrations required to achieve silencing of target genes Next, we measured doxycycline concentrations in plasma, major organs, and lung lesions in TB-infected mice and rabbits and compared these values to silencing concentrations measured We found that 2,000 ppm doxycycline supplemented in mouse and rabbit feed is sufficient to reach target concentrations in TB lesions. In rabbit chow, the calcium content had to be reduced 5-fold to minimize chelation of doxycycline and deliver adequate oral bioavailability. Clearance kinetics from major organs and lung lesions revealed that doxycycline levels fall below concentrations that repress promoters within 7 to 14 days after doxycycline is removed from the diet. In summary, we have shown that 2,000 ppm doxycycline supplemented in standard mouse diet and in low-calcium rabbit diet delivers concentrations adequate to achieve full repression of promoters in infected tissues of mice and rabbits.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Biological Availability; Calcium; Disease Models, Animal; Doxycycline; Female; Gene Silencing; Lung; Mice; Mycobacterium tuberculosis; Rabbits; Tetracycline Resistance; Tissue Distribution; Transgenes; Tuberculosis
PubMed: 32041718
DOI: 10.1128/AAC.02479-19 -
European Journal of Pharmacology Feb 2022Colorectal cancer (CRC) is considered the second most frequent cancer globally and one of the deadliest malignancies in humans. On the other hand, over time and facing... (Review)
Review
Colorectal cancer (CRC) is considered the second most frequent cancer globally and one of the deadliest malignancies in humans. On the other hand, over time and facing the challenges of cancer treatment, several therapeutic approaches, including surgery, radiotherapy, chemotherapy, and immunotherapy, are being developed. Evidence showed that combination therapies had given relatively satisfactory clinical outcomes in inhibiting tumor progression and increasing patient survival compared with monotherapy. Among the available compounds and drugs used in chemotherapy, doxycycline, an antimicrobial drug, has been suitable for treating several malignancies such as CRC. It has been revealed that doxycycline has anti-tumor properties and can help control tumor growth in various mechanisms, such as inhibiting anti-apoptotic and angiogenic proteins. In addition, studies have shown that combination therapy with doxycycline and other anti-tumor drugs, such as doxorubicin, anti-angiogenic factors, and anti-check-point blockers, can inhibit tumor progression. Therefore, this review summarized the anti-tumor mechanisms of doxycycline in CRC treatment and related combination therapies.
Topics: Antineoplastic Agents; Colorectal Neoplasms; Combined Modality Therapy; Doxycycline; Humans; Immunotherapy
PubMed: 34973952
DOI: 10.1016/j.ejphar.2021.174593 -
Malaria Journal Apr 2017Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to... (Review)
Review
Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.
Topics: Antimalarials; Chemoprevention; Child; Child, Preschool; Dental Enamel Hypoplasia; Doxycycline; Drug-Related Side Effects and Adverse Reactions; Humans; Infant; Infant, Newborn; Malaria
PubMed: 28407772
DOI: 10.1186/s12936-017-1797-9 -
Colloids and Surfaces. B, Biointerfaces Sep 2020The objective of this study is to investigate the feasibility of delivery of novel levofloxacin/ doxycycline (LEVO/DOX) combination to the brain by intranasal route to...
The objective of this study is to investigate the feasibility of delivery of novel levofloxacin/ doxycycline (LEVO/DOX) combination to the brain by intranasal route to achieve a significant local concentration in the brain and a direct nose-to-brain pathway. Solid lipid nanoparticles (SLN) were selected as a drug carrier and employed Box-Behnken design for optimizing LEVO/DOX-SLN to achieve minimum particle size and maximum apparent entrapment efficiency (EE). SLNs were prepared by hot emulsification and characterized. In vitro release of optimized formulations showed prolonged drug release from the optimized formulation. The results of pharmacokinetic study of the optimized SLN-HPMC gel in plasma and brain revealed significant increase in the brain peak concentration (420, 315 ng/g), the AUC min (57130 and 48693.13 ng. min/g) in comparison to intranasal LEVO/DOX free solution with the values of (160, 120) ng/g, (36850, 27637.5 ng⋅min/g) for LEVO and DOX, respectively. The optimized LD-SLN-HPMC gel gave a drug-targeting efficiency (DTE %) of 149.815 and 161.969 for LEVO and DOX, respectively, in comparison to the intravenous route. Moreover, the optimized formulation had a direct transport percentage (DTP %) of 33.285 and 40.236 for LEVO and DOX, respectively, which indicates a significant contribution of direct nose-to-brain pathway in brain drug delivery.
Topics: Animals; Brain; Camelus; Doxycycline; Drug Compounding; Drug Delivery Systems; Levofloxacin; Lipids; Nanoparticles; Nasal Mucosa; Particle Size; Surface Properties
PubMed: 32408259
DOI: 10.1016/j.colsurfb.2020.111076