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Cureus Oct 2023Eosinophilic annular erythema (EAE) is a rare skin disease characterized by relapsing and remitting pruritic, annular erythematous plaques and tissue eosinophilia. A...
Eosinophilic annular erythema (EAE) is a rare skin disease characterized by relapsing and remitting pruritic, annular erythematous plaques and tissue eosinophilia. A 39-year-old male presented with a mildly pruritic, relapsing, and remitting urticarial rash. A biopsy revealed superficial and deep perivascular dermatitis with numerous eosinophils and some neutrophils, with an absence of flame figures. Based on clinical and histopathologic findings, the patient was given a diagnosis of eosinophilic annular erythema. Treatment was initiated with doxycycline 100 mg twice daily. The patient reported substantial improvement at three months and sustained clearance at one year, remaining on doxycycline well tolerated throughout. To our knowledge, no cases of EAE improving with doxycycline have been reported in the literature and, thus, our findings highlight a potential new therapy to consider in a patient with EAE.
PubMed: 38022231
DOI: 10.7759/cureus.47478 -
Clinical Microbiology and Infection :... Aug 2023Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of azithromycin and doxycycline on the vaginal microbiota of women with urogenital Chlamydia trachomatis infection: a substudy of the Chlazidoxy randomized controlled trial.
OBJECTIVES
Dysbiotic bacterial communities within the vagina are associated with Chlamydia trachomatis infection. We compared the effect of treatment with azithromycin and doxycycline on the vaginal microbiota in a cohort of women with a urogenital C. trachomatis infection randomly assigned to one of these treatments (Chlazidoxy trial).
METHODS
We analysed vaginal samples from 284 women (135 in the azithromycin group and 149 in the doxycycline group) collected at baseline and 6 weeks after treatment initiation. The vaginal microbiota was characterized using 16S rRNA gene sequencing and classified into community state types (CSTs).
RESULTS
At baseline, 75% (212/284) of the women had a high-risk microbiota (CST-III or CST-IV). A cross-sectional comparison 6 weeks after treatment showed that 15 phylotypes were differentially abundant, but this difference was not reflected at the CST (p 0.772) or diversity level (p 0.339). Between baseline and the 6-week visit, α-diversity (p 0.140) and transition probabilities between CSTs were not significantly different between the groups, and no phylotype was differentially abundant.
DISCUSSION
In women with urogenital C. trachomatis infection, the vaginal microbiota does not seem to be affected by azithromycin or doxycycline 6 weeks after treatment. Because the vaginal microbiota remains susceptible to C. trachomatis infection (with CST-III or CST-IV) after antibiotic treatment, women remain at risk of reinfection, which could originate from unprotected sexual intercourse or untreated anorectal C. trachomatis infection. This last consideration advocates for the use of doxycycline instead of azithromycin because of its higher anorectal microbiological cure rate.
Topics: Female; Humans; Azithromycin; Doxycycline; Chlamydia trachomatis; RNA, Ribosomal, 16S; Cross-Sectional Studies; Chlamydia Infections; Anti-Bacterial Agents; Vagina; Microbiota; Urinary Tract Infections
PubMed: 37100225
DOI: 10.1016/j.cmi.2023.04.020 -
Experimental Hematology Aug 2023Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested...
Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance.
Topics: Mice; Animals; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Fusion Proteins, bcr-abl; Hematopoietic Stem Cells; Cell Differentiation; Embryonic Stem Cells; Doxycycline
PubMed: 37331423
DOI: 10.1016/j.exphem.2023.06.002 -
Biomedicine & Pharmacotherapy =... Aug 2023Prolonged exposure to UV light can lead to photo-ageing of the skin. Therefore, the development and application of anti-photoaging drugs is urgent. In this study, we...
Prolonged exposure to UV light can lead to photo-ageing of the skin. Therefore, the development and application of anti-photoaging drugs is urgent. In this study, we co-loaded apigenin (Apn) and doxycycline (Doc), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), into flexible liposomes to exert anti-photoaging effects by combating oxidative stress, anti-inflammation, reducing the activation of MMPs and preventing collagen loss. The results showed that we prepared a flexible liposome (A/D-FLip) containing Apn and Doc. Its appearance, particle size and Zeta potential were normal and it had good encapsulation efficiency, drug loading, in vitro release and transdermal efficiency. In cellular experiments, A/D-FLip could inhibit oxidative stress damage, reduce inflammatory factors and decrease the activation of MMPs in Human immortalized keratinocytes (HaCaT) cells; in animal experiments, A/D-FLip could inhibit skin damage and reduce skin collagen loss by decreasing the activation of MMPs, thus inhibiting skin photoaging in mice. In conclusion, A/D-FLip has good anti-photoaging effects and it has the potential to become an effective skin care product or drug against UV damage and skin photoaging in the future.
Topics: Animals; Mice; Humans; Liposomes; Apigenin; Doxycycline; Skin; Collagen; Skin Aging; Matrix Metalloproteinases; Ultraviolet Rays
PubMed: 37301137
DOI: 10.1016/j.biopha.2023.114998 -
Parasites & Vectors Oct 2023In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical... (Review)
Review
In its 'Road map for neglected tropical diseases 2021-2030', the World Health Organization outlined its targets for control and elimination of neglected tropical diseases (NTDs) and research needed to achieve them. For many NTDs, this includes research for new treatment options for case management and/or preventive chemotherapy. Our review of small-molecule anti-infective drugs recently approved by a stringent regulatory authority (SRA) or in at least Phase 2 clinical development for regulatory approval showed that this pipeline cannot deliver all new treatments needed. WHO guidelines and country policies show that drugs may be recommended for control and elimination for NTDs for which they are not SRA approved (i.e. for 'off-label' use) if efficacy and safety data for the relevant NTD are considered sufficient by WHO and country authorities. Here, we are providing an overview of clinical research in the past 10 years evaluating the anti-infective efficacy of oral small-molecule drugs for NTD(s) for which they are neither SRA approved, nor included in current WHO strategies nor, considering the research sponsors, likely to be registered with a SRA for that NTD, if found to be effective and safe. No such research has been done for yaws, guinea worm, Trypanosoma brucei gambiense human African trypanosomiasis (HAT), rabies, trachoma, visceral leishmaniasis, mycetoma, T. b. rhodesiense HAT, echinococcosis, taeniasis/cysticercosis or scabies. Oral drugs evaluated include sparfloxacin and acedapsone for leprosy; rifampicin, rifapentin and moxifloxacin for onchocerciasis; imatinib and levamisole for loiasis; itraconazole, fluconazole, ketoconazole, posaconazole, ravuconazole and disulfiram for Chagas disease, doxycycline and rifampicin for lymphatic filariasis; arterolane, piperaquine, artesunate, artemether, lumefantrine and mefloquine for schistosomiasis; ivermectin, tribendimidine, pyrantel, oxantel and nitazoxanide for soil-transmitted helminths including strongyloidiasis; chloroquine, ivermectin, balapiravir, ribavirin, celgosivir, UV-4B, ivermectin and doxycycline for dengue; streptomycin, amoxicillin, clavulanate for Buruli ulcer; fluconazole and isavuconazonium for mycoses; clarithromycin and dapsone for cutaneous leishmaniasis; and tribendimidine, albendazole, mebendazole and nitazoxanide for foodborne trematodiasis. Additional paths to identification of new treatment options are needed. One promising path is exploitation of the worldwide experience with 'off-label' treatment of diseases with insufficient treatment options as pursued by the 'CURE ID' initiative.
Topics: Humans; Ivermectin; Rifampin; Doxycycline; Fluconazole; Off-Label Use; Anti-Infective Agents; Drug Combinations; Neglected Diseases
PubMed: 37907954
DOI: 10.1186/s13071-023-05909-8 -
Cureus Sep 2023Hypoglycaemia with tetracycline use is a very rare and unknown side effect of the antibiotic. The case highlights the importance of recognizing and managing this...
Hypoglycaemia with tetracycline use is a very rare and unknown side effect of the antibiotic. The case highlights the importance of recognizing and managing this potential adverse effect. We present a case of an adolescent male with acne vulgaris who developed hypoglycaemic episodes after initiating tetracycline treatment and was referred by his General Practitioner to the Endocrinology clinic. The hypoglycaemia symptoms settled once tetracyclines were stopped. Acne vulgaris is a prevalent skin condition among adolescents, and antibiotics such as doxycycline and tetracycline are commonly used to treat severe cases of acne. While generally well-tolerated, rare side effects on glucose metabolism have been reported. Antibiotics are not well known to cause hypoglycaemic spells on their own. It is mostly when these antibiotics are started in patients taking other regular medications that the interaction between these medications causes hypoglycaemia.
PubMed: 37854767
DOI: 10.7759/cureus.45406 -
Proceedings of the National Academy of... Oct 2023Antibiotics, by definition, reduce bacterial growth rates in optimal culture conditions; however, the real-world environments bacteria inhabit see rapid growth...
Antibiotics, by definition, reduce bacterial growth rates in optimal culture conditions; however, the real-world environments bacteria inhabit see rapid growth punctuated by periods of low nutrient availability. How antibiotics mediate population decline during these periods is poorly understood. Bacteria cannot optimize for all environmental conditions because a growth-longevity tradeoff predicts faster growth results in faster population decline, and since bacteriostatic antibiotics slow growth, they should also mediate longevity. We quantify how antibiotics, their targets, and resistance mechanisms influence longevity using populations of and, as the tradeoff predicts, populations are maintained for longer if they encounter ribosome-binding antibiotics doxycycline and erythromycin, a finding that is not observed using antibiotics with alternative cellular targets. This tradeoff also predicts resistance mechanisms that increase growth rates during antibiotic treatment could be detrimental during nutrient stresses, and indeed, we find resistance by ribosomal protection removes benefits to longevity provided by doxycycline. We therefore liken ribosomal protection to a "Trojan horse" because it provides protection from an antibiotic but, during nutrient stresses, it promotes the demise of the bacteria. Seeking mechanisms to support these observations, we show doxycycline promotes efficient metabolism and reduces the concentration of reactive oxygen species. Seeking generality, we sought another mechanism that affects longevity and we found the number of doxycycline targets, namely, the ribosomal RNA operons, mediates growth and longevity even without antibiotics. We conclude that slow growth, as observed during antibiotic treatment, can help bacteria overcome later periods of nutrient stress.
Topics: Anti-Bacterial Agents; Bacteria; Doxycycline; Escherichia coli; Ribosomes; Humans
PubMed: 37751555
DOI: 10.1073/pnas.2221507120 -
Water Research Jul 2023There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations.... (Review)
Review
There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations. Inappropriate use of antibiotics can harbour inherent antimicrobial resistance (AMR); therefore, it is important to understand and monitor community-wide prescribing and consumption behaviours throughout different communities around the world. Wastewater-Based Epidemiology (WBE) is a novel tool enabling low cost and large scale studies focussed on AA usage patterns. The back-calculation of community antimicrobial intake was performed from quantities measured in municipal wastewater and informal settlement discharge in the city of Stellenbosch, utilising WBE. Seventeen antimicrobials, and their human metabolites, were evaluated, in concordance with prescription records corresponding to the catchment region. The proportional excretion, biological/chemical stability, and method recovery of each analyte were all crucial factors in the efficacy of the calculation. Mass per day measurements were normalised to the catchment area via population estimates. Municipal wastewater treatment plant population estimates were used to normalise the wastewater samples and prescription data (mg/day/1000 inhabitants). Population estimates for the informal settlements were less accurate due to a lack of reliable sources that were relevant to the sampling time period. Both mass loads and normalised loads suggested higher than average usage throughout the settlements, relative to municipal wastewater. This was seen most prominently in emtricitabine and lamivudine; but also, sulfamethoxazole, trimethoprim, sulfadiazine, clindamycin, ciprofloxacin, ofloxacin, and doxycycline. Urban water fingerprinting (UWF) data triangulation with prescription datasets showed good correlations for several antimicrobial agents (AAs) (e.g., clindamycin, clarithromycin, ofloxacin, and doxycycline). It also revealed discrepancies in usage for some compounds (e.g., tetracycline and sulfapyridine). This might be linked with a lack of pharma compliance in prescription datasets; erroneous association of prescription boundaries with the sewerage catchment; and/or uncertainties within the sewerage catchment (e.g., population estimations). The UWF tool provided a comprehensive overview of multiclass AAs usage, both prescription and over-the counter. For example, tetracycline was not reported in available prescription statistics, but was detected at an average of 18.4 mg/day/1000inh; and no antiviral prescriptions were obtained, but emtricitabine and lamivudine were quantified at 2415.4 and 144.4 mg/day/1000inh, respectively. A lack of clarity regarding prescriptions and a lack of inclusion of several critical (often over-the-counter) medications in public health databases makes WBE a useful and comprehensive epidemiology tool for tracking pharma usage within a catchment.
Topics: Humans; Anti-Bacterial Agents; Wastewater; Clindamycin; Doxycycline; South Africa; Lamivudine; Ofloxacin; Water Pollutants, Chemical
PubMed: 37247434
DOI: 10.1016/j.watres.2023.120110 -
PLoS Neglected Tropical Diseases Oct 2023Onchocerciasis is a neglected tropical disease with 217.5 million people globally at risk of having the infection. In both settled and semi-nomadic communities of...
BACKGROUND
Onchocerciasis is a neglected tropical disease with 217.5 million people globally at risk of having the infection. In both settled and semi-nomadic communities of Massangam Health District in Cameroon, Sightsavers has been carrying out test-and-treat with doxycycline and twice-yearly ivermectin distribution. This paper focuses on the cost of test-and-treat with doxycycline in the two community contexts of settled and semi-nomadic.
METHODS
For the valuation, a combination of gross or micro-costing was used to identify cost components, as well as bottom-up and top-down approaches. The opportunity costs of vehicle and equipment use were estimated and included. Not included, however, were the opportunity costs of building use and Ministry of Public Health staff salaries. We only captured the incremental costs of implementing test-and-treat activities as part of a functional annual community-directed treatment with the ivermectin programme.
RESULTS
We estimate the economic cost per person tested and cost per person treated in Massangam to be US$135 and US$667 respectively. Total implementation cost in the settled community was US$79,409, and in the semi-nomadic community US$69,957. Overall, the total economic cost of implementing the doxycycline test-and-treat strategy for onchocerciasis elimination in Massangam came to US$168,345. Financial costs represented 91% of total costs.
CONCLUSIONS
Unit costs of test-and-treat in both settled and semi-nomadic communities are higher than unit costs of community-directed treatment with ivermectin. However, it is critical to note that a two-year implementation shows a significantly larger reduction in infection prevalence than the preceding 20 years of annual community-directed treatment with ivermectin. Test-and-treat with doxycycline may be a cost-effective intervention in places where the prevalence of microfilaria is still high, or in hard-to-reach areas where community-directed treatment with ivermectin and MDA coverage are not high enough to stop transmission or where marginalised populations consistently miss treatment.
Topics: Humans; Onchocerciasis; Ivermectin; Doxycycline; Cameroon; Public Health
PubMed: 37851655
DOI: 10.1371/journal.pntd.0011670 -
Journal of Clinical Pharmacology Feb 2024Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been... (Meta-Analysis)
Meta-Analysis Review
Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.
Topics: Humans; Macrolides; Azithromycin; Doxycycline; Minocycline; Anti-Bacterial Agents
PubMed: 37751595
DOI: 10.1002/jcph.2358