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The Cochrane Database of Systematic... Jun 2021Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence...
BACKGROUND
Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis.
OBJECTIVES
To assess the benefits and harms of oral antibiotic use for people with chronic blepharitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total). The two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) -4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD -0.01, 95% CI -0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD -0.56, 95% CI -0.95 to -0.17; n = 93 (high-dose doxycycline versus placebo); MD -0.48, 95% CI -0.86 to -0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low. One study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain. One study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low.
AUTHORS' CONCLUSIONS
There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Bias; Blepharitis; Chronic Disease; Doxycycline; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic
PubMed: 34107053
DOI: 10.1002/14651858.CD013697.pub2 -
Neurobiology of Disease Apr 2021Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn)....
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.
Topics: Animals; Caenorhabditis elegans; Cell Line; Doxycycline; Humans; Inclusion Bodies; Neuroprotective Agents; Protein Aggregation, Pathological; Synucleinopathies; alpha-Synuclein
PubMed: 33429042
DOI: 10.1016/j.nbd.2021.105256 -
Sexually Transmitted Diseases Sep 2021Editorial for Sexually Transmitted Diseases (STD20–495): Interest, concerns, and attitudes among men who have sex with men and healthcare providers toward prophylactic...
Editorial for Sexually Transmitted Diseases (STD20–495): Interest, concerns, and attitudes among men who have sex with men and healthcare providers toward prophylactic use of doxycycline against infections and syphilis.
Topics: Chlamydia Infections; Doxycycline; Humans; Sexually Transmitted Diseases
PubMed: 34117188
DOI: 10.1097/OLQ.0000000000001501 -
Biomolecules Sep 2023Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune...
Periodontitis (PD) is a degenerative, bacteria-induced chronic disease of periodontium causing bone resorption and teeth loss. It includes a strong reaction of immune cells through the secretion of proinflammatory factors such as Interleukin-17 (IL-17). PD treatment may consider systemic oral antibiotics application, including doxycycline (Dox), exhibiting antibacterial and anti-inflammatory properties along with supportive activity in wound healing, thus affecting alveolar bone metabolism. In the present study, we aimed to determine whether Dox can affect the regenerative potential of periodontal ligament mesenchymal stem cells (PDLSCs) modulated by IL-17 in terms of cell migration, osteogenic potential, bioenergetics and expression of extracellular matrix metalloproteinase 2 (MMP-2). Our findings indicate that Dox reduces the stimulatory effect of IL-17 on migration and MMP-2 expression in PDLSCs. Furthermore, Dox stimulates osteogenic differentiation of PDLSCs, annulling the inhibitory effect of IL-17 on PDLSCs osteogenesis. In addition, analyses of mitochondrial respiration reveal that Dox decreases oxygen consumption rate in PDLSCs exposed to IL-17, suggesting that changes in metabolic performance can be involved in Dox-mediated effects on PDLSCs. The pro-regenerative properties of Dox in inflammatory microenvironment candidates Dox in terms of regenerative therapy of PD-affected periodontium are observed.
Topics: Humans; Matrix Metalloproteinase 2; Periodontal Ligament; Interleukin-17; Osteogenesis; Doxycycline; Periodontitis; Stem Cells; Cell Differentiation; Cells, Cultured
PubMed: 37892119
DOI: 10.3390/biom13101437 -
Canadian Family Physician Medecin de... Jul 2016To review the literature about lymphogranuloma venereum (LGV) and to provide an overview and discussion of practice guidelines. (Review)
Review
OBJECTIVE
To review the literature about lymphogranuloma venereum (LGV) and to provide an overview and discussion of practice guidelines.
SOURCES OF INFORMATION
The terms Chlamydia trachomatis and lymphogranuloma venereum were searched separately in PubMed. Empirical studies, practice reviews, and clinical guidelines were included. All reference lists were reviewed for additional articles.
MAIN MESSAGE
Since 2003, there has been a resurgence of LGV among men who have sex with men in many Western countries, including Canada. Although LGV is a serovar of Chlamydia trachomatis (serovar L), it can invade regional lymph nodes, and consequently presents with different symptoms than the other subtypes of chlamydia (serovars A through K). Specifically, LGV transitions through 3 phases: a painless papule or ulcer at the site of inoculation; invasion of the regional lymph nodes, which can present with an inguinal or rectal syndrome; and irreversible destruction of lymph tissue. In contrast, chlamydia serovars A to K exclusively produce superficial mucosal infections. Lymphogranuloma venereum also requires a different treatment regimen than other chlamydia serovars.
CONCLUSION
In light of the current resurgence of LGV, its unique symptoms and clinical course, and its requirement for a different treatment than other chlamydia serovars, it is important for primary care providers to recognize when LGV should be included as an appropriate differential diagnosis.
Topics: Adult; Anti-Bacterial Agents; Chlamydia trachomatis; Doxycycline; Humans; Lymphogranuloma Venereum; Male; Practice Guidelines as Topic
PubMed: 27412206
DOI: No ID Found -
Journal of Translational Medicine Dec 2023Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health... (Review)
Review
Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.
Topics: Animals; Mice; Humans; Syphilis; Treponema pallidum; Anti-Bacterial Agents; Doxycycline; Vaccines
PubMed: 38105236
DOI: 10.1186/s12967-023-04685-4 -
Drug Safety Jun 2021Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic...
INTRODUCTION AND OBJECTIVE
Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.
METHODS
After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design.
RESULTS
Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality.
CONCLUSIONS
Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.
SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS
Open Science Framework: https://osf.io/n7r2j .
Topics: Anti-Infective Agents; Doxycycline; Drug Therapy, Combination; Humans; Ivermectin; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33864232
DOI: 10.1007/s40264-021-01066-y -
The Journal of International Medical... Oct 2021The anti-cancer activity of doxycycline has been reported in many cancers but not renal cell carcinoma (RCC). This study aimed to determine the efficacy of doxycycline...
OBJECTIVES
The anti-cancer activity of doxycycline has been reported in many cancers but not renal cell carcinoma (RCC). This study aimed to determine the efficacy of doxycycline alone and in combination with paclitaxel and analyze the underlying mechanism in RCC.
METHODS
Proliferation, colony formation and apoptosis assays were performed in RCC cell lines after drug treatments. An RCC xenograft mouse model was generated, and tumor growth was monitored. Mechanistic studies focused on mitochondrial translation and functions.
RESULTS
Doxycycline at clinically achievable concentrations inhibited proliferation and colony formation and induced apoptosis in RCC cell lines. In normal kidney cells, doxycycline at the same concentrations either had no effect or was less effective. The combination index value demonstrated that doxycycline and paclitaxel were synergistic . Consistently, this combination therapy was significantly more effective than the monotherapy in RCC xenograft mice without causing significant toxicity. Mechanistic studies revealed that doxycycline acts on RCC cells via preferentially inhibiting mitochondrial DNA translation, thereby disrupting multiple mitochondrial complexes and impairing mitochondrial respiration.
CONCLUSIONS
Doxycycline is a useful addition to the treatment strategy for RCC. Our work also highlights the therapeutic value of mitochondrial translation inhibition in sensitizing RCC to chemotherapy.
Topics: Animals; Apoptosis; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Proliferation; Doxycycline; Kidney Neoplasms; Mice; Xenograft Model Antitumor Assays
PubMed: 34644207
DOI: 10.1177/03000605211044368 -
WMJ : Official Publication of the State... Feb 2024Acute pancreatitis is a common cause of hospitalizations in the United States, causing approximately 230 000 to 275 000 annual admissions We present the case of a...
INTRODUCTION
Acute pancreatitis is a common cause of hospitalizations in the United States, causing approximately 230 000 to 275 000 annual admissions We present the case of a patient with acute pancreatitis likely due to doxycycline.
CASE PRESENTATION
A 64-year-old male was admitted after developing acute epigastric pain radiating to his back, a lipase of 6611 (units/L), and a computed tomography scan showing moderate peripancreatic inflammation. He had no recent alcohol use, his gallbladder was surgically absent, and he had no gallbladder pathology on evaluation; however, he had been started on doxycycline 10 days prior. While hospitalized, he was treated with pain medications, fluids, and antibiotics for aspiration pneumonia. His acute symptoms resolved, except for minor intermittent abdominal pain 2 months after discharge.
DISCUSSION
Doxycycline-induced pancreatitis has been reported within 3 to 17 days of medication initiation. Given the temporal correlation and lack of other inciting etiologies, we determined the most likely etiology was doxycycline.
CONCLUSIONS
Further study is needed to understand the pathophysiology and incidence of doxycycline-induced pancreatitis.
Topics: Male; Humans; Middle Aged; Doxycycline; Pancreatitis; Acute Disease; Anti-Bacterial Agents; Acute Pain
PubMed: 38436639
DOI: No ID Found -
Travel Medicine and Infectious Disease 2023Only a few well-designed studies that have investigated the effectiveness of azithromycin in treating adult patients hospitalized with scrub typhus are currently...
Treatment outcomes of oral doxycycline versus intravenous azithromycin in adults hospitalized with scrub typhus: A retrospective study using inverse probability treatment weighting (IPTW) propensity analysis.
OBJECTIVE
Only a few well-designed studies that have investigated the effectiveness of azithromycin in treating adult patients hospitalized with scrub typhus are currently available. The purpose of our study was to compare the effects of intravenous azithromycin administration with those of oral doxycycline, and to evaluate cardiovascular death associated with intravenous azithromycin in adult patients hospitalized with scrub typhus.
METHODS
This retrospective study investigated Korean National Infectious Disease Cohort Collaborative-registered scrub typhus-infected patients who were hospitalized between January 1, 2013, and December 31, 2021, and who were ≥18 years old. The primary outcome was time to fever clearance and the secondary outcomes were treatment failure, relapse, scrub typhus-related death, or azithromycin-related cardiovascular death. To address any indication bias, inverse probability of treatment weighting (IPTW) analysis was performed. Times to fever clearance between the doxycycline and azithromycin groups were compared using log-rank tests and Kaplan-Meier curves.
RESULTS
A total of 326 consecutive patients with laboratory-confirmed scrub typhus were included in this study of whom 109 were treated with azithromycin and 217 with doxycycline. Using IPTW, there were no statistically significant differences in the following end points between the azithromycin and doxycycline groups: median time to fever clearance (3 days vs. 3 days, P = 0.649), treatment failure (0.71% vs. 0.42%, P = 0.702), relapse (0.0% vs. 0.0%), and scrub typhus-related death (5.12% vs. 0.0%, P = 0.155). No azithromycin-related cardiovascular deaths occurred. In the sensitivity analyses, there were no significant changes in effect size.
CONCLUSIONS
Our study showed that the therapeutic effects and safety of intravenous azithromycin are comparable to those of oral doxycycline administration in patients hospitalized with scrub typhus. A well-designed randomized controlled trial may help further evaluate the most adequate route of administration, dose and duration of treatment with azithromycin.
Topics: Humans; Adult; Adolescent; Doxycycline; Azithromycin; Anti-Bacterial Agents; Retrospective Studies; Scrub Typhus; Treatment Outcome; Probability; Fever; Recurrence
PubMed: 36549418
DOI: 10.1016/j.tmaid.2022.102525