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Clinical Infectious Diseases : An... Aug 2023
Meta-Analysis
Topics: Humans; Doxycycline; Anti-Bacterial Agents; Treatment Outcome
PubMed: 37099366
DOI: 10.1093/cid/ciad252 -
Veterinary Immunology and... Jan 2024Doxycycline is a broad-spectrum tetracycline-class antibiotic that is frequently used to treat bacterial infections. Its use has also been described in immune-mediated...
Doxycycline is a broad-spectrum tetracycline-class antibiotic that is frequently used to treat bacterial infections. Its use has also been described in immune-mediated diseases due to its immunomodulatory properties. The aim of this study was to evaluate the immunomodulatory effect of doxycycline on canine neutrophil functions. Therefore, the release of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) were determined after incubation of canine PMNs with doxycycline in three different concentrations (4 µg/mL, 20 µg/mL and 200 µg/mL) for one and three hours, respectively. Additionally, a neutrophil killing assay with a doxycycline-resistant Staphylococcus aureus was performed to determine the bactericidal effect of doxycycline treated PMNs in presence of plasma. Doxycycline significantly diminished the production of ROS. However, doxycycline concentrations of 4 µg/mL and 20 µg/mL significantly induced NETs. A synergistic bacteriostatic effect of PMNs and doxycycline on a doxycycline-resistant Staphylococcus aureus isolate was detectable. However, already PMNs and especially doxycycline alone inhibited the growth. In summary, doxycycline showed a concentration-dependent immunomodulatory property in canine PMNs with a reduced ROS production and increased NET-induction. This immunomodulatory effect resulted in a slightly increased elimination of a doxycycline-resistant Staphylococcus aureus by the doxycycline plasma concentrations achieved in dogs.
Topics: Dogs; Animals; Doxycycline; Neutrophils; Reactive Oxygen Species; Methicillin-Resistant Staphylococcus aureus; Extracellular Traps; Staphylococcal Infections; Staphylococcus aureus; Dog Diseases
PubMed: 38147695
DOI: 10.1016/j.vetimm.2023.110701 -
Journal of Clinical Microbiology Apr 2024is known to cause human disease, particularly in elderly and immunocompromised hosts. There are limited published data for antimicrobial susceptibility patterns with... (Review)
Review
UNLABELLED
is known to cause human disease, particularly in elderly and immunocompromised hosts. There are limited published data for antimicrobial susceptibility patterns with this organism, and no interpretive criteria are available. We reviewed antimicrobial susceptibilities of isolates tested at a tertiary care center and reference laboratory over an 11-year period. isolates from patients treated at Mayo Clinic and those sent as referrals for identification and susceptibility were included. Antimicrobial susceptibility testing was performed using agar dilution for ciprofloxacin, doxycycline, erythromycin, gentamicin, meropenem, and tetracycline. Geographic distribution, culture source, organism minimal inhibitory concentration (MIC) distributions, and MIC and MIC were examined. Excluding duplicates, 105 unique isolates were identified from 110 positive cultures. Blood cultures represented the most common source, followed by body fluids, skin and soft tissue, and central nervous system. Gentamicin and meropenem had favorable MIC and MIC of 1 µg/mL. Ciprofloxacin demonstrated an MIC of 1 µg/mL; however, the MIC was >2 µg/mL. Erythromycin demonstrated MIC and MIC of 2 µg/mL. Tetracycline and doxycycline were tested on a limited number of isolates and showed a wide range of MICs. Gentamicin and meropenem demonstrated favorable MICs in isolates. These may represent therapeutic options for consideration in serious infections, pending susceptibility results. Ciprofloxacin, which showed variable results, may be more appropriate for use only after susceptibility testing. interpretive criteria are needed to aid clinicians in selection of both empiric and definitive therapies.
IMPORTANCE
Our findings contribute to the scant literature on antimicrobial susceptibility test results. We used a reference test method of agar dilution and provide MICs for a large number of organisms and antimicrobial agents.
Topics: Humans; Aged; Campylobacter fetus; Doxycycline; Meropenem; Agar; Anti-Bacterial Agents; Ciprofloxacin; Erythromycin; Tetracycline; Anti-Infective Agents; Gentamicins; Microbial Sensitivity Tests; Campylobacter
PubMed: 38421164
DOI: 10.1128/jcm.01447-23 -
Journal of Veterinary Pharmacology and... Mar 2024This study aimed to evaluate the administration of doxycycline hyclate in a long-acting pharmaceutical preparation in pigs when administered either ad libitum as a feed...
This study aimed to evaluate the administration of doxycycline hyclate in a long-acting pharmaceutical preparation in pigs when administered either ad libitum as a feed medication or an oral bolus dose. In all instances, the studied dose was 20 mg/kg b.w. A total of 48 healthy crossbred, castrated male pigs (Landrace-Yorkshire) weighing 23 ± 4.3 kg were included in this trial. They were randomly assigned to six groups as follows: two groups for the experimental prototype 1 of doxycycline hyclate administering it ad libitum (Fad-lib) or as forced bolus (Fbolus); two groups for the experimental prototype 2 of doxycycline hyclate as for the former groups (FCad-lib and FCbolus), and two control groups receiving the same dose of doxycycline hyclate, but of a commercial premix, also as previously explained (Cbolus and Cad-lib). Statistical analysis of the mean pharmacokinetic values was carried out with Kruskal-Wallis and Dunn's tests. The relative bioavailability (Fr) of the best prototype, when administered ad libitum (FCad-lib), was five times larger than the reference group (Cadlib). These results allow the proposal that the referred differences achieved in the presented prototypes can mark a notable clinical difference, particularly in pathogens with some resistance.
Topics: Male; Animals; Swine; Doxycycline; Anti-Bacterial Agents; Biological Availability; Area Under Curve; Half-Life
PubMed: 38014818
DOI: 10.1111/jvp.13419 -
Journal of Neurointerventional Surgery Sep 2023Percutaneous sclerotherapy is an effective technique for treating lymphatic malformations of the head and neck, with clinical success rates exceeding 84%.1 Sodium...
Percutaneous sclerotherapy is an effective technique for treating lymphatic malformations of the head and neck, with clinical success rates exceeding 84%.1 Sodium tetradecyl, which damages lipid membranes and stimulates free radical-induced local damage, and doxycycline, which inhibits angiogenesis, have emerged as the safest and most effective of several available sclerosants.2-4 Although severe periprocedural morbidity is rare, temporary local complications are reported in 14% and skin necrosis or scarring in up to 0.8-5.8% of sclerotherapy procedures.5 As these lesions are frequently located in the face and/or neck, even minor complications can be disfiguring and must be avoided. This technical video describes a 'dual-agent' approach for percutaneous sclerotherapy of macrocystic lymphatic malformations using sodium tetradecyl as a 'primer' followed by doxycycline as a definitive sclerosant (video 1). This technique emphasizes meticulous backtable preparation and effective use of ultrasound and fluoroscopy to minimize complications. neurintsurg;15/9/931/V1F1V1Video 1 .
Topics: Humans; Sclerotherapy; Doxycycline; Treatment Outcome; Retrospective Studies; Sclerosing Solutions; Lymphatic Abnormalities; Sodium; Vascular Malformations
PubMed: 35977819
DOI: 10.1136/jnis-2022-019255 -
Biomolecules Aug 2023The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the...
The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against and erythromycin against . Compounds , , , , , , , , and exhibited strong growth inhibition of methicillin-resistant (MRSA) and , with minimum inhibitory concentrations (MIC) typically less than 0.2 µM. Four analogues, including a 5-bromo and three 5-methoxyls - also exhibited intrinsic activity towards . Antibiotic kill curve analysis of identified it to be a bactericide. While only one derivative was found to (weakly) enhance the action of erythromycin against , three examples, including , were found to be strong enhancers of the antibiotic action of doxycycline against . Collectively, these results highlight the promising potential of α,ω-disubstituted indole-3-acetamido polyamine conjugates as antimicrobials and antibiotic adjuvants.
Topics: Anti-Bacterial Agents; Doxycycline; Escherichia coli; Methicillin-Resistant Staphylococcus aureus; Anti-Infective Agents; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Erythromycin; Fatty Acids, Omega-3; Indoles; Polyamines; Pseudomonas aeruginosa
PubMed: 37627291
DOI: 10.3390/biom13081226 -
European Journal of Pharmaceutical... Sep 2023Despite significant advances in infection control guidelines and practices, surgical site infections remain a substantial cause of morbidity, prolonged hospitalization,...
Despite significant advances in infection control guidelines and practices, surgical site infections remain a substantial cause of morbidity, prolonged hospitalization, and mortality. The most effective component of SSI reduction strategies is the preoperative administration of intravenous antibiotics; however, systemic antibiotics drug exposure diminishes rapidly and may result in insufficient prophylactic activity against susceptible and resistant SSI pathogens at the wound. D-PLEX (D-PLEX) is an antibiotic-releasing drug (doxycycline) that is supplied as a sterile powder for paste reconstitution with sterile saline. D-PLEX paste is administered locally into the incision site along the entire length of soft tissue and sternal bone wound surfaces prior to skin closure. A single D-PLEX administration is intended for 30 days of constant antimicrobial prophylaxis in the prevention of incisional SSIs. We evaluated D-PLEX minimal bactericidal concentration (MBC) against a panel of bacteria that is prevalent in the abdominal wall and sternal surgical procedures including doxycycline susceptible and resistant strains. D-PLEX in vivo efficacy was assessed in incisional infection rabbit models (abdominal wall and sternal) challenged with a similar bacterial panel. The D-PLEX drug exposure profile was determined by in vitro release assay, and in vivo by quantitative pharmacokinetic parameters of local and systemic doxycycline concentrations released from D-PLEX after local administration in incisional rabbit models. Analyses of pathogens and variations in antibiotic resistance from wound isolates were determined from patients who participated in a previously reported prospective randomized trial that assessed the SSI rate in D-PLEX plus standard of care (SOC) versus SOC alone in colorectal resection surgery. The D-PLEX MBC values demonstrated >3- Log reduction in all the organisms tested relative to untreated controls, including doxycycline-resistant bacteria (i.e., Methicillin-resistant Staphylococcus aureus (MRSA), K. pneumoniae, and P. aeruginosa). In vivo, D-PLEX significantly reduced the bacterial loads in all the bacteria tested in both animal models (p=0.0001) with a marked impact observed in E. Coli (>6.5 Log reduction). D-PLEX exhibited a zero-order release kinetics profile in vitro for 30 days (R = 0.971) and the matched in vivo release profile indicated a constant local release of protein-unbound doxycycline for 30 days at 3-5 mcg/mL with significantly lower (>3 orders of magnitudes) systemic levels. In colorectal surgery patients, where significant SSI reduction was observed, analysis of the positive cultures in the overall population indicated similar pathogen diversity and antibiotic resistance rates in both treatment arms. However, almost all the patients with positive culture in the SOC arm were adjudicated as SSI (94%) compared to only 28% in the D-PLEX arm. The SSI-adjudicated D-PLEX patients also exhibited lower resistance rates to the SOC antibiotics and to MDRs compared to patients in the SOC arm. Thus, D-PLEX provides safe and effective prophylaxis activity against the most prevalent SSI pathogens including doxycycline-susceptible and resistant bacteria. Our findings suggest that D-PLEX is a promising addition to SSI prophylactic bundles and may address the gaps in current SSI prophylaxis. D-PLEX is now evaluated in Phase 3 clinical trial.
PubMed: 37353092
DOI: 10.1016/j.ejps.2023.106504 -
International Journal of Molecular... Feb 2024Periodontitis is a complex condition. Left untreated, it leads to tooth loss and the need for prosthetic treatment. The incidence of periodontitis is steadily... (Review)
Review
Periodontitis is a complex condition. Left untreated, it leads to tooth loss and the need for prosthetic treatment. The incidence of periodontitis is steadily increasing, so new methods are being sought to aid in the diagnosis of the disease. Among the methods postulated is the determination of concentrations of bioactive compounds which include extracellular matrix metalloproteinases (MMPs). These enzymes are present in various structural elements of the stomatognathic system. The most promising enzyme of this group appears to be metalloproteinase 8 (MMP-8). MMP-8 assays are performed in gingival fluid or saliva, and MMP-8 levels have been shown to be higher in patients with periodontitis compared to healthy subjects and correlated with some clinical parameters of the condition and the severity of the disease. In addition, the preliminary usefulness of this enzyme in evaluating the effectiveness of periodontal treatment and doxycycline therapy has been demonstrated. Determination of the active form of MMP-8 (aMMP-8) in oral rinse fluid using off-the-shelf assays shows the highest potential. Despite reports about aMMP-8 and promising data on the role of MMP-8 in periodontal diagnosis, a clear determination of the usefulness of this enzyme requires further research.
Topics: Humans; Matrix Metalloproteinase 8; Gingival Crevicular Fluid; Periodontitis; Doxycycline
PubMed: 38473967
DOI: 10.3390/ijms25052721 -
Sexually Transmitted Diseases Nov 2023Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as...
BACKGROUND
Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as chemoprophylaxis (i.e., postexposure prophylaxis) offers promise for addressing bacterial STIs. The goal of the current study was to evaluate the safety of longer-term doxycycline use (defined as 8 or more weeks) in the context of potential use as STI chemoprophylaxis through a systematic literature review and meta-analysis.
METHODS
This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to search MEDLINE/PubMed for clinical studies published from August 2003 to January 2023 that reported on adverse events with doxycycline use with a focus on side effects and metabolic effects of long-term use.
RESULTS
A total of 67 studies were included in the systematic review. Overall, studies on longer-term doxycycline use reported 0% to greater than 50% adverse events ranging from mild to severe. Most common adverse events included gastrointestinal symptoms (i.e., nausea, vomiting, and abdominal pain), dermatologic (i.e., rash), and neurological (i.e., headache and dizziness) symptoms. Discontinuation of doxycycline due to adverse events was relatively uncommon in most studies. A meta-analysis of placebo controlled clinical trials (N = 18) revealed that gastrointestinal and dermatological adverse events were more likely to occur in the doxycycline group.
CONCLUSIONS
Longer-term (8+ weeks) doxycycline use is generally safe and may be associated with minor side effects. Further research is needed on the potential metabolic impact of longer-term doxycycline use.
PubMed: 37732844
DOI: 10.1097/OLQ.0000000000001865 -
Biology Aug 2023This study aimed to analyze the hematological parameters, blood viscosity, and cytokines of dogs infected by untreated and treated with doxycycline. Initially, 47 dogs...
This study aimed to analyze the hematological parameters, blood viscosity, and cytokines of dogs infected by untreated and treated with doxycycline. Initially, 47 dogs were examined, and 36 were suspected to have canine monocytic ehrlichiosis, which was confirmed through molecular polymerase chain reaction tests. This study consisted of 25 dogs, with 11 being healthy and 14 testing positive for . The dogs were divided into experimental groups based on their test results, including a control group of healthy dogs ( = 11), a group of infected dogs without treatment ( = 7), and a group of infected dogs treated with doxycycline ( = 7) at a 10 mg/kg dose every 12 h for 28 days. Blood samples were taken to determine hematological parameters, viscosity, and cytokine levels. It was observed that, regardless of doxycycline treatment, there was a reduction in total leukocytes and lymphocytes in infected dogs with The eosinophils and platelets decreased in dogs with infections without treatment. Monocytes, eosinophils, and platelets increased when the dogs were treated with doxycycline. Regardless of treatment, infected dogs' blood viscosity was lower than uninfected dogs. Infected dogs showed lower TNF-α and increased IL-1β. There was a correlation between the blood viscosity with the cytokines IL-10 and IL-12 in the infected dogs. The eosinophil count correlated with TNF-α in the group of infected and untreated dogs. In conclusion, treating dogs with monocytic ehrlichiosis using doxycycline can increase platelet and eosinophil levels but may also increase IL-1β and monocyte levels, exacerbating inflammation. Therefore, evaluating viscosity and cytokine levels is important when treating dogs with this condition.
PubMed: 37627021
DOI: 10.3390/biology12081137