-
Infectious Disease Clinics of North... Mar 2019Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness... (Review)
Review
Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness throughout the world. Rickettsioses present as an acute undifferentiated febrile illness and are often accompanied by headache, myalgias, and malaise. Cutaneous manifestations include rash and eschar, which both occur at varying incidence depending on the infecting species. Serology is the mainstay of diagnosis, and the indirect immunofluorescence assay is the test of choice. Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice.
Topics: Animals; Anti-Bacterial Agents; Arthropod Vectors; Doxycycline; Humans; Rickettsia Infections; Rocky Mountain Spotted Fever
PubMed: 30712763
DOI: 10.1016/j.idc.2018.10.010 -
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 -
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... Apr 2021Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and doxycycline for 14 days has limited anaerobic activity. The need for broader anaerobic coverage is unknown and concerns have been raised about metronidazole tolerability.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial comparing ceftriaxone 250 mg intramuscular single dose and doxycycline for 14 days, with or without 14 days of metronidazole in women with acute PID. The primary outcome was clinical improvement at 3 days following enrollment. Additional outcomes at 30 days following treatment were the presence of anaerobic organisms in the endometrium, clinical cure (absence of fever and reduction in tenderness), adherence, and tolerability.
RESULTS
We enrolled 233 women (116 to metronidazole and 117 to placebo). Clinical improvement at 3 days was similar between the 2 groups. At 30 days following treatment, anaerobic organisms were less frequently recovered from the endometrium in women treated with metronidazole than placebo (8% vs 21%, P < .05) and cervical Mycoplasma genitalium was reduced (4% vs 14%, P < .05). Pelvic tenderness was also less common among women receiving metronidazole (9% vs 20%, P < .05). Adverse events and adherence were similar in each treatment group.
CONCLUSIONS
In women treated for acute PID, the addition of metronidazole to ceftriaxone and doxycycline was well tolerated and resulted in reduced endometrial anaerobes, decreased M. genitalium, and reduced pelvic tenderness compared to ceftriaxone and doxycycline. Metronidazole should be routinely added to ceftriaxone and doxycycline for the treatment of women with acute PID.
CLINICAL TRIALS REGISTRATION
NCT01160640.
Topics: Anti-Bacterial Agents; Ceftriaxone; Doxycycline; Female; Humans; Metronidazole; Mycoplasma genitalium; Pelvic Inflammatory Disease
PubMed: 32052831
DOI: 10.1093/cid/ciaa101 -
Lancet (London, England) Apr 2017Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids.
METHODS
We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3-5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604.
FINDINGS
Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1-26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9-30·1), p=0·001.
INTERPRETATION
Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term.
FUNDING
NIHR Health Technology Assessment Programme.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clinical Trials as Topic; Doxycycline; Equivalence Trials as Topic; Female; Germany; Glucocorticoids; Humans; Male; Middle Aged; Pemphigoid, Bullous; Prednisolone; Treatment Outcome; United Kingdom
PubMed: 28279484
DOI: 10.1016/S0140-6736(17)30560-3 -
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 -
Ugeskrift For Laeger Oct 2023Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available...
Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available to confirm the diagnosis. This is a case report of a 38-year-old male admitted to hospital with high fever, severe malaise and headache after returning from Malaysia. Scrub typhus was suspected and the patient recovered after one week of doxycycline treatment. The pathogen was identified by use of microbiome 16S/18S rRNA next-generation sequencing on ethylenediamine tetraacetic acid (EDTA) blood, which in the future may serve an important role in the investigation of travel-associated infections.
Topics: Male; Humans; Adult; Orientia tsutsugamushi; Scrub Typhus; Travel; Doxycycline; Travel-Related Illness; RNA, Ribosomal, 16S
PubMed: 37873999
DOI: No ID Found -
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