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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 Mar 2023The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear.
METHODS
In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5.
RESULTS
Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups.
CONCLUSIONS
Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).
Topics: Animals; Humans; Middle Aged; Anti-Bacterial Agents; Azithromycin; Doxycycline; Scrub Typhus; Zoonoses; Double-Blind Method; Drug Therapy, Combination; Administration, Intravenous
PubMed: 36856615
DOI: 10.1056/NEJMoa2208449 -
Australian Family Physician 2017Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for...
BACKGROUND
Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for rosacea is varied, and there are four primary subtypes, which may overlap - erythrotelangiectatic, inflammatory, phymatous and ocular. It is important to recognise the different subtypes because of the differences in therapy.
OBJECTIVE
The objective of this article is to provide evidence-based clinical updates to clinicians, specifically general practitioners (GPs), to assist with their everyday practice, and effective assessment and treatment of rosacea.
DISCUSSION
Therapeutic modalities are chosen on the basis of the subtypes and clinical features identified; often a combination of these therapies is required.
Topics: Anti-Bacterial Agents; Brimonidine Tartrate; Diagnosis, Differential; Doxycycline; Humans; Isotretinoin; Ivermectin; Laser Therapy; Metronidazole; Rosacea
PubMed: 28472572
DOI: No ID Found -
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 -
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 -
Journal of Veterinary Pharmacology and... Nov 2021The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations...
The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations have been performed to investigate the predicted plasma concentration after either a 10 or 20 mg/kg daily administration repeated consecutively for 5 days. Ten geese were enrolled in a two-phase cross-over study with a washout period of two weeks. All animals were treated intravenously and orally with doxycycline, and blood samples were collected up to 48 h after drug administration. Sample analysis was performed using a validated HPLC-UV method. A non-compartmental approach was used to evaluate the pharmacokinetic parameters of the drug. A long elimination half-life was observed (13 h). The area under the curve was statistically different between the two treatments, with the oral bioavailability being moderate (43%). The pharmacokinetic/pharmacodynamic index (%T>MIC) during the 48 h treatment period in the present study (71%) suggests that doxycycline appears to have therapeutic efficacy against some Mycoplasma species in the goose. The multiple-dose simulations showed a low accumulation index. A dosage of 10 mg/kg/day for 5 days seemed to be adequate for a good therapeutic efficacy without reaching unnecessarily high plasma concentrations.
Topics: Administration, Oral; Animals; Area Under Curve; Cross-Over Studies; Doxycycline; Geese; Half-Life
PubMed: 34318509
DOI: 10.1111/jvp.13002 -
Clinical Infectious Diseases : An... Aug 2022Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal... (Observational Study)
Observational Study
BACKGROUND
Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia.
METHODS
We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality.
RESULTS
Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline.
CONCLUSIONS
In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Doxycycline; Drug Therapy, Combination; Humans; Pneumonia; Retrospective Studies; beta-Lactams
PubMed: 34751745
DOI: 10.1093/cid/ciab863 -
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 -
Clinical Infectious Diseases : An... May 2020Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific... (Review)
Review
Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific region with more than a billion people at risk. Treatment with antibiotics such as doxycycline or chloramphenicol is effective for the majority of patients. In the 1990s, reports from northern Thailand raised a troubling observation; some scrub typhus patients responded poorly to doxycycline, which investigators attributed to doxycycline resistance. Despite the controversial nature of these reports, independent verification was neglected, with subsequent studies speculating on the role of doxycycline resistance in contributing to failure of treatment or prophylaxis. In this review, we have outlined the evidence for drug-resistant Orientia tsutsugamushi, assessed the evidence for doxycycline resistance, and highlight more recent findings unsupportive of doxycycline resistance. We conclude that doxycycline resistance is a misconception, with treatment outcome likely to be determined by other bacterial, host, and pharmacological factors.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Orientia tsutsugamushi; Scrub Typhus; Thailand
PubMed: 31570937
DOI: 10.1093/cid/ciz972