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Antimicrobial Agents and Chemotherapy Sep 2022Nontuberculous mycobacteria (NTM) infections are increasing worldwide. Mycobacterium avium complex (MAC) and the M. abscessus species are the most commonly cultured NTM...
Nontuberculous mycobacteria (NTM) infections are increasing worldwide. Mycobacterium avium complex (MAC) and the M. abscessus species are the most commonly cultured NTM and treatment options are limited, especially for the M. abscessus species. In this study, the activity of eravacycline, a new tetracycline derivative, was tested against 110 clinical isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 60 isolates of rapidly growing mycobacteria (RGM), of which ~70% were tetracycline resistant. These included M. abscessus subsp. (8 isolates), M. abscessus subsp. (5), M. chelonae (10), (3), M. fortuitum group (20) including 12 doxycycline-resistant isolates, and M. mucogenicum group (10) including three doxycycline-resistant isolates. Due to trailing, eravacycline MICs were read at 80% and 100% inhibition. Eravacycline was active against all RGM species, with MIC ranges of ≤0.015 to 0.5 and ≤0.015 to 0.12 μg/mL for 100% and 80% inhibition, respectively. For M. abscessus subsp. , MIC values were 0.12 and 0.03 μg/mL with 100% and 80% inhibition, respectively. MICs for tigecycline were generally within 1 to 2 dilutions of the 100%-inhibition eravacycline MIC values. Fifty isolates of slowly growing mycobacteria (SGM) species, including 16 isolates of MAC, were also tested. While there was no trailing observed in most SGM, the eravacycline MICs were higher (MIC range of >8 μg/mL), except for M. kansasii and M. marinum which had MIC values of 1 μg/mL. This study supports further evaluation of eravacycline, including clinical trials for the development of RGM treatment regimens, especially for M. abscessus.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Nontuberculous Mycobacteria; Tetracycline; Tetracyclines; Tigecycline
PubMed: 35943269
DOI: 10.1128/aac.00689-22 -
Dental and Medical Problems 2023Periodontitis is an inflammatory disease caused by a group of specific microorganisms that provoke the destruction of the periodontal ligament and the alveolar bone,...
BACKGROUND
Periodontitis is an inflammatory disease caused by a group of specific microorganisms that provoke the destruction of the periodontal ligament and the alveolar bone, along with pocket formation or recession, or both.
OBJECTIVES
The present study aimed to compare the efficacy of tetracycline, doxycycline and minocycline in improving fibrin clot adhesion over manually instrumented periodontally affected root surfaces with the use of scanning electron microscopy (SEM).
MATERIAL AND METHODS
A total of 45 single-rooted extracted teeth were sectioned into 45 dentinal blocks and divided into 3 groups: tetracycline (group I); doxycycline (group II); and minocycline (group III). A drop of blood was added over the dentinal blocks, allowed to clot, and later rinsed with phosphatebuffered saline (PBS),1% formaldehyde, and 0.02% glycine. Then, the surfaces were post-fixed in 2.5% glutaraldehyde and dehydrated in a graded ethanol series of 30%, 50%, 75%, 90%, 95%, and 100%. Afterward, the samples were examined under a SEM to assess fibrin clot adhesion and the number of blood cells.
RESULTS
Minocycline demonstrated better fibrin clot adhesion, followed by tetracycline and doxycycline. Statistical significance was observed at ×2,000 magnification (p = 0.021), whereas no significance was noted at ×5,000 magnification.
CONCLUSIONS
Dentinal blocks treated with minocycline had a better fibrin network and a greater number of entrapped erythrocytes, which is vital in the early wound-healing process leading to the formation of connective tissue attachment.
Topics: Humans; Doxycycline; Minocycline; Fibrin Tissue Adhesive; Microscopy, Electron, Scanning; Anti-Bacterial Agents; Tetracycline; Fibrin
PubMed: 37384897
DOI: 10.17219/dmp/149278 -
Brazilian Journal of Microbiology :... Sep 2023Acinetobacter baumannii infection presents a high mortality rate and few therapeutic options. This study aimed to evaluate clinical-microbiological characteristics and...
Acinetobacter baumannii infection presents a high mortality rate and few therapeutic options. This study aimed to evaluate clinical-microbiological characteristics and prognosis factors of patients diagnosed with A. baumanni. infections treated with oral doxycycline. A retrospective cohort of hospitalized patients with confirmed Acinetobacter spp. infection between 2018 and 2020 receives at least 3 days of oral doxycycline. Clinical and microbiological data were evaluated, including the outcome and molecular characterization of A. baumannii. Doxycycline minimal inhibitory concentrations were evaluated by the broth dilution method. One hundred patients were included with a median age of 51 years. The leading site of infection was pulmonary (n = 62), followed by the soft tissues and skin (n = 28). A. baumannii resistant to carbapenem was found on 94%. The gene blaOXA-23 and blaOXA-51 were amplified in all recovered isolates of A. baumannii (n = 44). Doxycycline MIC50 and MIC90 were 1 µg/mL and 2 µg/mL, respectively. Death rate at 14 days and 28 days of follow-up was 9% and 14%, respectively. The prognostic factors related to death at end of follow-up were age > 49 years [85.7% vs. 46%, CI 95% 6.9 (1.4-32.6), P = 0.015] and hemodialysis [28.6% vs. 7%, CI 95% 5.33 (1.2-22.1), P = 0.021]. Patients treated with doxycycline to A. baumannii presented a relatively low death rate, and risk factors related to death were age and hemodialysis. Further and larger studies should compare polymyxin to doxycycline to better understand the differences between these therapeutic options.
Topics: Humans; Middle Aged; Doxycycline; Anti-Bacterial Agents; Acinetobacter baumannii; Polymyxins; Retrospective Studies; Carbapenems; Microbial Sensitivity Tests; Acinetobacter Infections; beta-Lactamases
PubMed: 37278889
DOI: 10.1007/s42770-023-01015-0 -
Doxycycline Malaria Prophylaxis Impact on Risk of Travelers' Diarrhea among International Travelers.The American Journal of Tropical... Nov 2020International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD...
International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD prevention. With increasing resistance and recommendations against antibiotic chemoprophylaxis, doxycycline fell out of use. We evaluated TD incidence and risk factors in a prospective cohort of travelers, specifically in regard to malaria prophylaxis. Travelers' diarrhea was defined as ≥ 3 loose stools in 24 hours or two loose stools in 24 hours associated with other gastrointestinal symptoms. The Poisson regression model with robust error variance was used to estimate the RR of TD. Three thousand two hundred twenty-seven trips were enrolled: 62.1% of participants were male, with a median age of 39 years (interquartile range [IQR] 27,59) and a median travel duration of 19 days (IQR 12,49); 17.4% developed TD; 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America; and 20% took doxycycline for malaria chemoprophylaxis, 50% took other antimalarials, and 30% took none. Decreased RR of TD was associated with doxycycline (RR 0.62 [0.47-0.82], < 0.01) and military travel (RR 0.57 [0.47-0.70], < 0.01). Increased risk of TD was associated with female gender (RR 1.28 [1.09-1.50], < 0.01), hotel accommodations (RR 1.30 [1.10-1.53], < 0.01), travel to tropical South America (RR 1.34 [1.09-1.64], < 0.01), and duration of travel (RR 1.00 [1.00-1.01], < 0.01). The use of doxycycline for malaria prophylaxis is associated with lower TD risk, suggesting increasing bacterial enteropathogen susceptibility similar to previous observations. Doxycycline selection for antimalarial chemoprophylaxis may provide additional traveler benefit in infection prevention.
Topics: Adult; Anti-Bacterial Agents; Cohort Studies; Diarrhea; Doxycycline; Female; Global Health; Humans; Malaria; Male; Middle Aged; Risk Factors; Travel
PubMed: 32815505
DOI: 10.4269/ajtmh.20-0241 -
Parasites & Vectors Jun 2023Microfilarial (mf) counts were monitored over 21.3 months for any rebound that might occur in counts, and adulticidal efficacy was assessed following administration of...
Long-term evaluation of viability of microfilariae and intravenously transplanted adult Dirofilaria immitis in microfilaremic dogs treated with low-dose, short- and long-treatment regimens of doxycycline and ivermectin.
BACKGROUND
Microfilarial (mf) counts were monitored over 21.3 months for any rebound that might occur in counts, and adulticidal efficacy was assessed following administration of low dosage with short- and long-treatment regimens of doxycycline and ivermectin to heartworm-microfilaremic dogs.
METHODS
Twelve heartworm-naïve beagles infected with 10 pairs of adult Dirofilaria immitis by intravenous transplantation were randomly allocated to three groups of four dogs. All treatments started on day 0. On day 0, Group 1 (short-treatment regimen) received doxycycline orally at 10 mg/kg once daily for 30 days plus ivermectin orally (minimum, 6 mcg/kg) on days 0 and 30. Group 2 (long-treatment regimen) received doxycycline orally at 10 mg/kg once daily until individual dogs became mf-negative (72-98 days) and ivermectin every other week until individual dogs became mf-negative (6-7 doses). Group 3 was the untreated control. Mf counts and antigen (Ag) tests were conducted. Dogs were necropsied for recovery and enumeration of heartworms on day 647.
RESULTS
Day -1 mean mf counts were 15,613, 23,950, and 15,513 mf/ml for groups 1, 2, and 3, respectively. Mean counts for Groups 1 and 2 declined until days 239 and 97, respectively, when all were negative. Group 3 had high mf counts throughout the study. There was not a rebound in mf counts in any of the treated dogs after they became amicrofilaremic. All dogs in group 1 and group 3 were Ag-positive throughout the study and had at least one live female worm at necropsy. All dogs in treated Group 2 were positive for Ag through day 154, but were antigen-negative on days 644 and 647, as all had only male worms. Mean live adult worm recoveries for Groups 1, 2, and 3 were 6.8 (range, 5-8), 3.3 (range, 1-6), and 16.0 (range, 14-17), respectively, with a percent reduction in adult worm counts of 57.5% for Group 1 and 79.3% for Group 2.
CONCLUSIONS
These data lend support to the use of the American Heartworm Society Canine Guidelines for adulticide therapy recommending the initiation of doxycycline plus a macrocyclic lactone (ML) at the time of the heartworm-positive diagnosis.
Topics: Animals; Dogs; Female; Male; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Doxycycline; Ivermectin; Microfilariae
PubMed: 37291586
DOI: 10.1186/s13071-023-05769-2 -
BMC Infectious Diseases Dec 2023Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence, clinical failure, mortality and treatment-related adverse effects of two common drugs (doxycycline and azithromycin) used for its treatment.
METHODOLOGY
This was a systematic review and meta-analysis. All studies up to 20.03.2023 were screened for eligibility in Pubmed and Embase using a search string containing terms related to scrub typhus, doxycycline and azithromycin. After two phases of screening, all comparative studies where doxycycline and azithromycin were used to treat scrub typhus were included. The studies were critically appraised using standardised tools, and a meta-analysis was performed for time to defervescence (primary outcome), clinical failure, mortality and treatment-related adverse effects.
RESULTS
Of 744 articles from two databases, ten were included in the meta-analysis. All but two studies had a high risk of bias. The meta-analysis for time to defervescence had a high heterogeneity and did not show any significant difference between doxycycline and azithromycin arms [Mean difference of -3.37 hours (95%CI: -10.31 to 3.57), p=0.34]. When the analysis was restricted to studies that included only severe scrub typhus, doxycycline was found to have a shorter time to defervescence [mean difference of -10.15 (95%CI: -19.83 to -0.46) hours, p=0.04]. Additionally, there was no difference between the two arms concerning clinical failure, mortality and treatment-related adverse effects.
CONCLUSION
The current data from studies with a high risk of bias did not find statistically significant differences in clinical outcomes between doxycycline and azithromycin for scrub typhus.
Topics: Humans; Azithromycin; Doxycycline; Anti-Bacterial Agents; Scrub Typhus; Patients; Drug-Related Side Effects and Adverse Reactions
PubMed: 38110855
DOI: 10.1186/s12879-023-08893-7 -
Emerging Infectious Diseases Oct 2016Rectal lymphogranuloma venereum (LGV) has reemerged as a sexually transmitted infection among men who have sex with men (MSM), particularly those who are HIV-positive.... (Meta-Analysis)
Meta-Analysis Review
Rectal lymphogranuloma venereum (LGV) has reemerged as a sexually transmitted infection among men who have sex with men (MSM), particularly those who are HIV-positive. We undertook a systematic review and meta-analysis to determine the efficacy of doxycycline (100 mg 2×/d for 21 days) for rectal LGV in MSM. Nine studies were included: 4 prospective, 4 retrospective, and 1 combined retrospective and prospective. In total, 282 MSM with rectal LGV were included in the studies. All studies reported using nucleic acid amplification tests to assess microbial cure. Most patients (>80%) had symptomatic rectal infection. The fixed-effects pooled efficacy for doxycycline was 98.5% (95% CI 96.3%-100%, I (2) = 0%; p = 0.993). Doxycycline at 100 mg twice daily for 21 days demonstrated a high microbial cure rate. These data support doxycycline at this dosage and duration as first-line therapy for rectal LGV in MSM.
Topics: Anti-Bacterial Agents; Chlamydia trachomatis; Doxycycline; Homosexuality, Male; Humans; Lymphogranuloma Venereum; Male; Rectal Diseases; Treatment Outcome
PubMed: 27513890
DOI: 10.3201/eid2210.160986 -
Cell Reports Aug 2023Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, is believed to underlie memory formation. Hebbian, postsynaptically expressed LTP...
Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, is believed to underlie memory formation. Hebbian, postsynaptically expressed LTP requires TARPγ-8 phosphorylation for synaptic insertion of AMPA receptors (AMPARs). However, it is unknown whether TARP-mediated AMPAR insertion alone is sufficient to modify behavior. Here, we report the development of a chemogenetic tool, ExSYTE (Excitatory SYnaptic Transmission modulator by Engineered TARPγ-8), to mimic the cytoplasmic interaction of TARP with the plasma membrane in a doxycycline-dependent manner. We use this tool to examine the specific role of synaptic AMPAR potentiation in amygdala neurons that are activated by fear conditioning. Selective expression of active ExSYTE in these neurons potentiates AMPAR-mediated synaptic transmission in a doxycycline-dependent manner, occludes synaptically induced LTP, and mimics freezing triggered by cued fear conditioning. Thus, chemogenetic controlling of the TARP-membrane interaction is sufficient for LTP-like synaptic AMPAR insertion, which mimics fear conditioning.
Topics: Long-Term Potentiation; Doxycycline; Synapses; Synaptic Transmission; Lipids
PubMed: 37471228
DOI: 10.1016/j.celrep.2023.112826 -
Clinical and Applied... 2023Doxycycline has revealed potential effects in animal studies to prevent thrombosis and reduce mortality. However, less is known about its antithrombotic role in patients...
Doxycycline has revealed potential effects in animal studies to prevent thrombosis and reduce mortality. However, less is known about its antithrombotic role in patients with COVID-19. Our study aimed to evaluate doxycycline's impact on clinical outcomes in critically ill patients with COVID-19. A multicenter retrospective cohort study was conducted between March 1, 2020, and July 31, 2021. Patients who received doxycycline in intensive care units (ICUs) were compared to patients who did not (control). The primary outcome was the composite thrombotic events. The secondary outcomes were 30-day and in-hospital mortality, length of stay, ventilator-free days, and complications during ICU stay. Propensity score (PS) matching was used based on the selected criteria. Logistic, negative binomial, and Cox proportional hazards regression analyses were used as appropriate. After PS (1:3) matching, 664 patients (doxycycline n = 166, control n = 498) were included. The number of thromboembolic events was lower in the doxycycline group (OR: 0.54; 95% CI: 0.26-1.08; = .08); however, it failed to reach to a statistical significance. Moreover, D-dimer levels and 30-day mortality were lower in the doxycycline group (beta coefficient [95% CI]: -0.22 [-0.46, 0.03; = .08]; HR: 0.73; 95% CI: 0.52-1.00; = .05, respectively). In addition, patients who received doxycycline had significantly lower odds of bacterial/fungal pneumonia (OR: 0.65; 95% CI: 0.44-0.94; = .02). The use of doxycycline as adjunctive therapy in critically ill patients with COVID-19 might may be a desirable therapeutic option for thrombosis reduction and survival benefits.
Topics: Humans; COVID-19; Doxycycline; SARS-CoV-2; Critical Illness; Retrospective Studies; Intensive Care Units; Hospital Mortality; Thrombosis
PubMed: 37322869
DOI: 10.1177/10760296231177017 -
Clinical Science (London, England :... Dec 2022Hypertension (HTN) is associated with renal proinflammatory immune cell infiltration and increased sodium retention. We reported previously that renal lymphatic vessels,...
BACKGROUND
Hypertension (HTN) is associated with renal proinflammatory immune cell infiltration and increased sodium retention. We reported previously that renal lymphatic vessels, which are responsible for trafficking immune cells from the interstitial space to draining lymph nodes, increase in density under hypertensive conditions. We also demonstrated that augmenting renal lymphatic density can prevent HTN in mice. Whether renal lymphangiogenesis can treat HTN in mice is unknown. We hypothesized that genetically inducing renal lymphangiogenesis after the establishment of HTN would attenuate HTN in male and female mice from three different HTN models.
METHODS
Mice with inducible kidney-specific overexpression of VEGF-D (KidVD) experience renal lymphangiogenesis upon doxycycline administration. HTN was induced in KidVD+ and KidVD- mice by subcutaneous release of angiotensin II, administration of the nitric oxide synthase inhibitor L-NAME, or consumption of a 4% salt diet following a L-NAME priming and washout period. After a week of HTN stimuli treatment, doxycycline was introduced. Systolic blood pressure (SBP) readings were taken weekly. Kidney function was determined from urine and serum measures. Kidneys were processed for RT-qPCR, flow cytometry, and imaging.
RESULTS
Mice that underwent renal-specific lymphangiogenesis had significantly decreased SBP and renal proinflammatory immune cells. Additionally, renal lymphangiogenesis was associated with a decrease in sodium transporter expression and increased fractional excretion of sodium, indicating improved sodium handling efficiency.
CONCLUSIONS
These findings demonstrate that augmenting renal lymphangiogenesis can treat HTN in male and female mice by improving renal immune cell trafficking and sodium handling.
Topics: Mice; Male; Female; Animals; Lymphangiogenesis; NG-Nitroarginine Methyl Ester; Doxycycline; Hypertension; Kidney; Sodium
PubMed: 36345993
DOI: 10.1042/CS20220547