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Current Molecular Pharmacology 2021Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has... (Review)
Review
Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications. The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline. Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords 'minocycline and doxycycline'. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and the number of other non-antibiotic effects were compiled for minocycline and doxycycline.
Topics: Anti-Bacterial Agents; Doxycycline; Minocycline; Tetracycline
PubMed: 33568043
DOI: 10.2174/1874467214666210210122628 -
Skin Therapy Letter Jul 2021The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the...
The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the presence of either (1) phymatous changes, or (2) centrofacial persistent erythema. In their absence, diagnosis can be established by presence of any two of: flushing/transient erythema, papules and pustules, telangiectases, or ocular manifestations. Management of rosacea depends on presenting feature(s), their severity, and impact. General management includes gentle skin care, sun protection, and trigger avoidance. Evidence-based treatment recommendations include topical brimonidine and oxymetazoline for persistent erythema; topical azelaic acid, ivermectin, metronidazole, minocycline and oral doxycycline, tetracycline and isotretinoin for papules and pustules; vascular lasers and light devices for telangiectases; and omega-3 fatty acids and cyclosporine ophthalmic emulsion for ocular rosacea. While surgical or laser therapy can be considered for clinically noninflamed phyma, there are no trials on their utility. Combination therapies include topical brimonidine with topical ivermectin, or topical metronidazole with oral doxycycline. Topical metronidazole, topical ivermectin, and topical azelaic acid are appropriate for maintenance therapy. In conclusion, the updated phenotype approach, based on presenting clinical features, is the foundation for current diagnosis, classification, and treatment of rosacea.
Topics: Brimonidine Tartrate; Dermatologic Agents; Doxycycline; Humans; Metronidazole; Rosacea
PubMed: 34347259
DOI: No ID Found -
The New England Journal of Medicine Dec 2023Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from... (Comparative Study)
Comparative Study Randomized Controlled Trial
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 , , or . 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 -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.).
Topics: Female; Humans; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; HIV Infections; Kenya; Neisseria gonorrhoeae; Pre-Exposure Prophylaxis; Sexually Transmitted Diseases; Unsafe Sex; Anti-Infective Agents; Adolescent; Young Adult; Adult; Gonorrhea; Treponema pallidum; Syphilis; Drug Monitoring; Hair
PubMed: 38118022
DOI: 10.1056/NEJMoa2304007 -
Expert Opinion on Drug Safety 2016Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its... (Comparative Study)
Comparative Study Review
INTRODUCTION
Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood.
AREAS COVERED
A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratogenic effects during pregnancy or dental staining in children was found.
EXPERT OPINION
The change of the US FDA pregnancy classification scheme to an evidence-based approach will enable adequate evaluation of doxycycline in common tropical illnesses and in vulnerable populations in clinical treatment trials, dosage-optimization pharmacokinetic studies and for the empirical treatment of undifferentiated febrile illnesses, especially in pregnant women and children.
Topics: Age Factors; Animals; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Contraindications; Doxycycline; Female; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome
PubMed: 26680308
DOI: 10.1517/14740338.2016.1133584 -
The Lancet. Infectious Diseases Mar 2018Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP)... (Randomized Controlled Trial)
Randomized Controlled Trial
Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial.
BACKGROUND
Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of STIs.
METHODS
All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472.
FINDINGS
Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8·7 months (IQR 7·8-9·7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280-1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15-32) and 45 in the no-PEP group (42%, 33-53; log-rank test p=0·007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio [HR] 0·53; 95% CI 0·33-0·85; p=0·008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0·30; 95% CI 0·13-0·70; p=0·006) and of syphilis (0·27; 0·07-0·98; p=0·047); for a first episode of gonorrhoea the results did not differ significantly (HR 0·83; 0·47-1·47; p=0·52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0·05).
INTERPRETATION
Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men.
FUNDING
France Recherche Nord & Sud Sida-HIV Hépatites (ANRS) and Bill & Melinda Gates Foundation.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Doxycycline; Homosexuality, Male; Humans; Male; Middle Aged; Post-Exposure Prophylaxis; Sexually Transmitted Diseases; Young Adult
PubMed: 29229440
DOI: 10.1016/S1473-3099(17)30725-9 -
Malaria Journal Nov 2015Malaria, a parasite vector-borne disease, is one of the greatest health threats in tropical regions, despite the availability of malaria chemoprophylaxis. The emergence... (Review)
Review
Malaria, a parasite vector-borne disease, is one of the greatest health threats in tropical regions, despite the availability of malaria chemoprophylaxis. The emergence and rapid extension of Plasmodium falciparum resistance to various anti-malarial drugs has gradually limited the number of potential malaria therapeutics available to clinicians. In this context, doxycycline, a synthetically derived tetracycline, constitutes an interesting alternative for malaria treatment and prophylaxis. Doxycycline is a slow-acting blood schizontocidal agent that is highly effective at preventing malaria. In areas with chloroquine and multidrug-resistant P. falciparum parasites, doxycycline has already been successfully used in combination with quinine to treat malaria, and it has been proven to be effective and well-tolerated. Although not recommended for pregnant women and children younger than 8 years of age, severe adverse effects are rarely reported. In addition, resistance to doxycycline is rarely described. Prophylactic and clinical failures of doxycycline have been associated with both inadequate doses and poor patient compliance. The effects of tetracyclines on parasites are not completely understood. A better comprehension of the mechanisms underlying drug resistance would facilitate the identification of molecular markers of resistance to predict and survey the emergence of resistance.
Topics: Antimalarials; Doxycycline; Humans; Malaria; Plasmodium
PubMed: 26555664
DOI: 10.1186/s12936-015-0980-0 -
The American Surgeon Nov 2023Esophageal and gastric mucosal injuries are well-documented adverse effects of doxycycline leading to odynophagia, chest pain, and abdominal pain. There are no clear...
Esophageal and gastric mucosal injuries are well-documented adverse effects of doxycycline leading to odynophagia, chest pain, and abdominal pain. There are no clear diagnostic criteria for such adverse effects; hence, the diagnosis depends heavily on thorough history. There is a paucity of literature describing life-threatening complications from doxycycline-induced mucosal injury, such as hemorrhage and perforation. We present the first case report describing a gastric perforation from doxycycline use.
Topics: Humans; Doxycycline; Stomach Diseases; Esophagus; Gastric Mucosa; Chest Pain; Iatrogenic Disease; Thoracic Injuries
PubMed: 34551605
DOI: 10.1177/00031348211047494 -
Current Opinion in Pharmacology Jun 2019Pemphigoid is the most common autoimmune blistering disease. IgG and IgE autoantibodies against the hemidesmosomal antigens Bullous Pemphigoid (BP) 180 and BP230 are of... (Review)
Review
Pemphigoid is the most common autoimmune blistering disease. IgG and IgE autoantibodies against the hemidesmosomal antigens Bullous Pemphigoid (BP) 180 and BP230 are of pathogenic relevance, since autoantibody-antigen binding results in complement activation, immune cells infiltration, impaired hemidesmosomal function, and loss of dermal-epidermal adhesion. Systemic steroids and immunosuppressants are frontline therapies in pemphigoid, but result in substantial morbidity and increased mortality. A large randomized multicenter study highlighted doxycycline as a feasible alternative to systemic corticosteroids in patients not suitable for long-term steroid use. In recent years, new targeted therapies, including intravenous immunoglobulin (IvIg), rituximab, omalizumab, and immunoadsorption, have proven efficacy in the refractory setting, but, with the exception of IVIG, large randomized trial has not been performed yet. Basic research studies have now shed light on the pathogenic role of eosinophils and autoreactive T-helper 2 cells in pemphigoid, inducing tissue damage and sustaining autoantibody production by autoreactive B-cells, respectively. Indeed, eosinophils and Th2-related cytokines have become attractive therapeutic options. Moreover, Interleukin-17 related inflammatory pathways have been also shown to participate in the blistering process. This review discusses current evidence for the use of targeted therapies in pemphigoid as well as most relevant pharmacologic advances and new drugs currently under clinical investigation.
Topics: Animals; Doxycycline; Humans; Molecular Targeted Therapy; Pemphigoid, Bullous
PubMed: 30769277
DOI: 10.1016/j.coph.2018.12.007 -
Biomedical Journal Dec 2022We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous...
BACKGROUND
We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous inflammation in S. mansoni-infected and doxycycline-treated mice.
METHODS
Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni, (iii) infected + 200 mg/kg praziquantel (Pzt), (iv) and (v) infected + 5 and 50 mg/kg doxycycline. Pzt (reference drug) was administered in a single dose and doxycycline for 60 days.
RESULTS
S. mansoni-infection determined extensive lung inflammation, marked recruitment of M2 macrophages, cytokines (IL-4, IL-5, IFN-γ, TNF-α) upregulation, intense eosinophil peroxidase (EPO) levels, arginase expression and activity, reduced iNOS expression and nitric oxide (NO) production. The higher dose of doxycycline aggravated lung granulomatous inflammation, downregulating IL-4 levels and M2 macrophages recruitment, and upregulating iNOS expression, EPO, NO, IFN-γ, TNF-α, M1 macrophages, protein carbonyl and malondialdehyde tissue levels. The number and size of granulomas in doxycycline-treated animals was higher than untreated and Pzt-treated mice. Exudative/productive granulomas were predominant in untreated and doxycycline-treated animals, while fibrotic/involutive granulomas were more frequent in Pzt-treated mice. The reference treatment with Pzt attenuated all these parameters.
CONCLUSION
Our findings indicated that doxycycline aggravated lung granulomatous inflammation in a dose-dependent way. Although Th1 effectors are protective against several intracellular pathogens, effective schistosomicidal responses are dependent of the Th2 phenotype. Thus, doxycycline contributes to the worsening of lung granulomatous inflammation by potentiating eosinophils influx and downregulating Th2 effectors, reinforcing lipid and protein oxidative damage in chronic S. mansoni infection.
Topics: Mice; Animals; Nitric Oxide Synthase Type II; Doxycycline; Arginase; Tumor Necrosis Factor-alpha; Interleukin-4; Schistosomiasis; Cytokines; Lung; Oxidative Stress; Inflammation; Granuloma; Nitric Oxide
PubMed: 34971826
DOI: 10.1016/j.bj.2021.12.007