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European Journal of Neurology Dec 2023Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence-based recommendations for treatment of Lyme neuroborreliosis (LNB) should rely on the available literature. As new data emerges, close review and evaluation of the recent literature is needed to build evidence-based recommendations to inform clinical practice and management of LNB. We performed an update of a previous systematic review on treatment of LNB.
METHODS
A systematic literature search of Medline and CENTRAL was performed for published studies from 2015 to 2023 to update a previous systematic review. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs; NRS were assessed using the ROBINS-I-tool. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Data were integrated into an existing meta-analysis of the available literature.
RESULTS
After screening 1530 records, two RCTs and five NRS with new and relevant data were additionally identified. Meta-analysis showed no statistically significant difference between doxycycline and beta-lactam antibiotics regarding residual neurological symptoms after 12 months. Meta-analysis showed no benefit of extended antibiotic treatment of LNB. Three NRS show no benefit for additional steroid use in LNB with facial palsy.
DISCUSSION
Additional incorporated recent research corroborates existing guideline recommendations for treatment of LNB. New RCTs add to the certainty of previous analysis showing similar efficacy for doxycycline and beta-lactam antibiotics in LNB. Available evidence shows no benefit for extended antibiotic treatment in LNB. NRS do not suggest a role for steroids in facial palsy due to LNB.
Topics: Humans; Lyme Neuroborreliosis; Doxycycline; Facial Paralysis; Anti-Bacterial Agents; Monobactams
PubMed: 37565386
DOI: 10.1111/ene.16034 -
Military Medicine May 2024Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline-Global Snake Envenomation...
INTRODUCTION
Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline-Global Snake Envenomation Management snakebites are a concerning threat in all theaters of operation. Snake venom is a complex mixture of toxins including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP) that produce myotoxic, hemotoxic, and cytotoxic injuries. Antibody-based antivenom is the standard of care but new approaches including small-molecule inhibitors have gained attention in recent years. Doxycycline is an effective inhibitor of human metalloproteinases and PLA2. The enzymatic activities of 3 phylogenetically distinct snakes: Agkistrodon piscivorus, Naja kaouthia, and Daboia russelii were tested under inhibitory conditions using doxycycline.
MATERIALS AND METHODS
Enzymatic activity of PLA2 and SVMP was measured in N. kaouthia, D. russelii, and A. piscivorus venom alone and with doxycycline using EnzChek Phospholipase A2 and Gelatinase Assay Kits. A 1-way ANOVA with Tukey's post-hoc test was used to conduct comparative analysis. The median lethal dose of the venoms, the effective dose of doxycycline, and creatine kinase (CK) inhibition levels were measured in a murine model with adult Bagg Albino (BALB/c) mice using intramuscular injections. Median lethal and effective doses were determined using Spearman-Karber's method and a 1-way ANOVA with Tukey's post-hoc test was used to compare CK inhibition levels.
RESULTS
Phospholipases A2 activity was reduced to 1.5% to 44.0% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline when compared to venom-only controls (P < .0001) (Fig. 1A). Snake venom metalloproteinases activity was reduced to 4% to 62% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline (P < .0001) (Fig. 1B). The lethal dose (LD50) values of the venoms in the murine model were calculated as follows: A. piscivorus = 20.29 mg/kg (Fig. 2A), N. kaouthia = 0.38 mg/kg (Fig. 2B), and D. russelii = 7.92 mg/kg (Fig. 2C). The effective dose (ED50) of doxycycline in A. piscivorus was calculated to be 20.82 mg/kg and 72.07 mg/kg when treating D. russelii venom. No ED50 could be calculated when treating N. kaouthia venom (Fig. 3). Creatine kinase activity was significantly decreased in all 3 venoms treated with doxycycline (P < .0001) (Fig. 4).
CONCLUSION
Doxycycline reduced PLA2- and SVMP-related lethality, particularly in A. piscivorus envenomings and in a limited capacity with D. russelii revealing its promise as a treatment for snakebites. In addition, CK activity, a common indicator of muscle damage was inhibited in mice that received doxycycline-treated venom. The doxycycline concentrations identified in the ED50 studies correspond to 1,456 to 5,061 mg dosages for a 70 kg human. Factors including venom yield and snake species would affect the actual dosage needed. Studies into high-dose doxycycline safety and its effectiveness against several snake species is needed to fully translate its use into humans. Based on this work, doxycycline could be used as a treatment en route to higher echelons of care, providing protection from muscle damage and reducing lethality in different snake species.
PubMed: 38748405
DOI: 10.1093/milmed/usae184 -
The British Journal of Dermatology Feb 2024Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment...
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but are rarely offered in the UK.
OBJECTIVES
To describe current UK HS management pathways and influencing factors to inform the design of future randomized controlled trials (RCTs).
METHODS
THESEUS was a nonrandomized 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200 mg daily; oral clindamycin and rifampicin both 300 mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing; and conventional surgery. The primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. The secondary outcomes were the proportion of participants selecting each intervention as their final treatment option; the proportion who switch treatments; treatment fidelity; and attrition rates. THESEUS was prospectively registered on the ISRCTN registry: ISRCTN69985145.
RESULTS
The recruitment target of 150 participants was met after 18 months, in July 2021, with two pauses due to the COVID-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36 years, 81% female, 20% non-White, 64% current or ex-smokers, 86% body mass index ≥ 25, 68% with moderate disease, 19% with severe disease and 13% with mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after 3 and 6 months, respectively. Concordance with doxycycline was 52% after 3 months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing, respectively, after 3 months. Uptake of conventional surgery was too small to characterize the intervention. Switching treatment was uncommon and there were no serious adverse events.
CONCLUSIONS
THESEUS has established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs.
Topics: Female; Humans; Adult; Male; Clindamycin; Rifampin; Hidradenitis Suppurativa; Doxycycline; Cohort Studies
PubMed: 37823414
DOI: 10.1093/bjd/ljad388 -
Current HIV/AIDS Reports Oct 2023This article reviews current efforts to control bacterial sexually transmitted infections (STIs) among HIV pre-exposure prophylaxis (PrEP) users and outlines the... (Review)
Review
PURPOSE OF REVIEW
This article reviews current efforts to control bacterial sexually transmitted infections (STIs) among HIV pre-exposure prophylaxis (PrEP) users and outlines the opportunities and challenges to controlling STIs within HIV PrEP programs.
RECENT FINDINGS
The incidence of STIs continues to rise globally especially among HIV PrEP users, with an estimated 1 in 4 PrEP users having a curable bacterial STI. STIs and HIV comprise a syndemic needing dual interventions. The majority of STIs are asymptomatic, and when testing is available, many STIs occur in extragenital sites that are missed when relying on urine testing or genital swabs. Optimal testing and treatment, including testing for antimicrobial resistance, pose difficulties in high income countries and is essentially non-existent in most low- and middle-income countries. Novel STI primary prevention strategies, like doxycycline post-exposure prophylaxis (PEP) for STI prevention, have proven to be highly efficacious in some populations. A few jurisdictions have issued normative guidelines and position statements for doxycycline PEP; however, clinical standards for implementation and data on public health impact are limited. STI incidence rates are high and rising in sexually active populations. Sexual health programs should leverage the expansion of HIV PrEP delivery services to integrate STI testing, surveillance, and novel STI prevention services.
Topics: Humans; Male; HIV Infections; Doxycycline; Sexually Transmitted Diseases; Sexual Health; Pre-Exposure Prophylaxis; Homosexuality, Male
PubMed: 37751130
DOI: 10.1007/s11904-023-00666-w -
Journal of Cosmetic Dermatology Oct 2023Insulin-like growth factor 1 (IGF-1) plays a role in the pathogenesis of acne vulgaris. Metformin can reduce IGF-1 levels and insulin resistance, so it may be useful in... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Insulin-like growth factor 1 (IGF-1) plays a role in the pathogenesis of acne vulgaris. Metformin can reduce IGF-1 levels and insulin resistance, so it may be useful in treating acne.
OBJECTIVE
This study compared the efficacy of metformin and doxycycline in treating patients with acne vulgaris.
METHODS
In this assessor-blind, add-on, randomized controlled clinical trial, we enrolled 40 patients with moderate acne vulgaris aged 15-40 and randomly divided them into two groups. For two months, the first group received doxycycline 100 mg capsules daily, and the second received metformin 500 mg tablets twice daily. The patients in both groups were adminitered to apply a fingertip (fourth finger) of 5% benzoyl peroxide gel (Pangel®) topically every night over the lesions, and to wash it off after 30 min. Patients were evaluated using the Global Acne Grading System (GAGS) score, Investigator Global Assessment for Acne (IGA) score, Cardiff Acne Disability Index (CADI), Total Acne Lesion Count (TLC), and the number of inflammatory and noninflammatory lesions.
RESULTS
By the end of the study, the GAGS, IGA, CADI, and TLC scores and the number of inflammatory and noninflammatory lesions decreased significantly in both groups (p < 0.001), with no significant difference between the two groups (p > 0.05).
CONCLUSION
This trial indicates equal efficacy of doxycycline and metformin in reducing acne vulgaris severity, with doxycycline performing better in reducing lesions of the inflammatory type. Confirmatory or equivalence clinical trials should be performed to confirm our results.
Topics: Humans; Doxycycline; Insulin-Like Growth Factor I; Metformin; Acne Vulgaris; Immunoglobulin A; Treatment Outcome; Gels; Double-Blind Method
PubMed: 37128834
DOI: 10.1111/jocd.15785 -
Microbial Pathogenesis Oct 2023Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically transmitted through contact with infected animals, unpasteurized dairy products, or airborne pathogens. Tetracyclines (tetracycline and doxycycline) are antibiotics commonly used to treat brucellosis; however, antibiotic resistance has become a major concern. This study assessed the worldwide prevalence of tetracycline-resistant Brucella isolates.
METHODS
A systematic search was conducted in Scopus, PubMed, Web of Science, and EMBASE using relevant keywords and Medical Subject Headings (MeSH) terms until August 13, 2022, to identify relevant studies for meta-analysis. A random effects model was used to estimate the proportion of resistance. Meta-regression analysis, subgroup analysis, and examination of outliers and influential studies were also performed.
RESULTS
The prevalence rates of resistance to tetracycline and doxycycline were estimated to be 0.017 (95% confidence interval [CI], 0.009-0.035) and 0.017 (95%CI, 0.011-0.026), respectively, based on 51 studies conducted from 1983 to 2020. Both drugs showed increasing resistance over time (tetracycline: r = 0.077, P = 0.012; doxycycline: r = 0.059, P = 0.026).
CONCLUSION
The prevalence of tetracycline and doxycycline resistance in Brucella was low (1.7%) but increased over time. This increase in tetracycline and doxycycline resistance highlights the need for further research to understand resistance mechanisms and develop more effective treatments.
Topics: Animals; Humans; Brucella melitensis; Brucella abortus; Tetracycline; Doxycycline; Prevalence; Brucellosis; Anti-Bacterial Agents; Tetracyclines
PubMed: 37673354
DOI: 10.1016/j.micpath.2023.106321 -
Acta Dermato-venereologica Feb 2024Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.
Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.
Topics: Adult; Humans; Female; Doxycycline; Spironolactone; Quality of Life; Prospective Studies; Acne Vulgaris; Benzoyl Peroxide; Treatment Outcome; Double-Blind Method
PubMed: 38380975
DOI: 10.2340/actadv.v104.26002 -
The Medical Clinics of North America Mar 2024Rates of sexually transmitted infections (STIs), especially cases of infectious and congenital syphilis, are increasing in the United States. Novel strategies for STI... (Review)
Review
Rates of sexually transmitted infections (STIs), especially cases of infectious and congenital syphilis, are increasing in the United States. Novel strategies for STI prevention are being explored and include doxycycline post-exposure prophylaxis and the potential utility of vaccines against gonorrhea. Self-collection of samples and point of care testing for STI are increasingly being employed in a variety of settings. Both can improve uptake of screening and lead to earlier detection and treatment of incident STI in target populations. Overcoming existing regulatory issues and optimizing implementation of current evidence-based strategies will be key to maximizing future STI prevention efforts. Here we provide an update for primary care providers on selected new strategies for STI prevention either currently available or under development for possible future use.
Topics: Humans; United States; Sexually Transmitted Diseases; Doxycycline; Vaccines; HIV Infections
PubMed: 38331488
DOI: 10.1016/j.mcna.2023.10.003 -
Antibiotics (Basel, Switzerland) Jul 2023Tetracycline-class drugs are frequently used in dermatology for their anti-inflammatory properties to treat skin diseases such as acne, rosacea, and hidradenitis... (Review)
Review
Tetracycline-class drugs are frequently used in dermatology for their anti-inflammatory properties to treat skin diseases such as acne, rosacea, and hidradenitis suppurativa (HS). The American Academy of Dermatology (AAD) clinical guidelines do not offer guidance regarding the co-administration of food with tetracycline-class drugs. The objectives of this study were to review the available evidence regarding whether taking tetracycline-class drugs with food decreases systemic absorption and is associated with an impact on clinical efficacy. A literature search was conducted using the PubMed database between February to May 2023 using the keywords "tetracycline-class drugs", "pharmacokinetics", "absorption", and "dermatology". Inclusion criteria included articles written in English and relevant to the absorption and efficacy of tetracycline-class drugs. This search yielded 131 articles written between 1977 to 2022, of which 29 met the criteria for review. United States Food and Drug Administration (FDA)-approved prescribing information for oral formulations of tetracycline, doxycycline, minocycline, and sarecycline were reviewed. Systemic absorption of tetracycline decreased when co-administered with food. Systemic absorption of oral doxycycline and minocycline was variable with food co-administration. The impact on bioavailability varied with the drug formulation and dosage. The absorption of oral sarecycline decreased when administered with food. Sarecycline is the only oral antibiotic where population pharmacokinetic studies demonstrated limited or no impact of food intake on clinical efficacy. There are no available data for other tetracycline-class drugs in dermatology. If patients find it more tolerable to take doxycycline, minocycline, and sarecycline with food to avoid gastrointestinal distress, this may merit consideration to encourage patient adherence. Since the impact of food intake on absorption varied with the dosage form of doxycycline and minocycline, consulting the appropriate package insert may give clinicians additional insight into differences in the various formulations.
PubMed: 37508248
DOI: 10.3390/antibiotics12071152 -
Journal of Assisted Reproduction and... Oct 2023To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among...
PURPOSE
To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among patients in an academic fertility clinic.
METHODS
In this retrospective cohort study, data from patients who underwent endometrial sampling (ES) for CE evaluation at a single academic institution from 2014 to 2020 were collected and analyzed. Rates of CE were compared by indication for ES including recurrent pregnancy loss (RPL), implantation failure (IF), and recent first-trimester pregnancy loss. Treatment and pregnancy outcomes were also evaluated.
RESULTS
Six hundred fifty-three individuals underwent ES to evaluate for CE. The overall prevalence of CE was 28.5%; when stratified by indication, the prevalence of CE was 66.2% for recent first-trimester loss, 27.9% for RPL, and 13.1% for IF (p < .001). Of those with CE, 91.9% received antibiotics, most commonly doxycycline (76.0%). CE clearance was not significantly different when doxycycline was compared to all other regimens (71.3% vs. 58.8%, p = .17), and 68.5% of patients cleared CE after one course of antibiotics. Following two antibiotic courses, CE was cleared in 88.3% of patients. Live birth rates (LBRs) were higher for those with cleared CE compared to patients with untreated CE (34.1% vs. 5.6%, p = .014) and similar for those with cleared CE versus those without CE (34.1% vs. 29.3%, p = .297).
CONCLUSION
CE is common among patients with infertility, particularly those with a recent first-trimester loss. Treatment and clearance of CE were associated with higher LBRs; however, persistent CE was common despite treatment with antibiotics.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Endometritis; Retrospective Studies; Doxycycline; Chronic Disease; Abortion, Habitual; Anti-Bacterial Agents
PubMed: 37558906
DOI: 10.1007/s10815-023-02902-z