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Research in Social & Administrative... Aug 2023Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This...
Antimicrobial resistance (AMR) is a global healthcare challenge that governments and health systems are tackling primarily through antimicrobial stewardship (AMS). This should, improve antibiotic use, avoid inappropriate prescribing, reduce prescription numbers, aligning with national/international AMS targets. In primary care in the United Kingdom (UK) antibiotics are mainly prescribed for patients with urinary and respiratory symptoms (22.7% and 46% of all antibiotic prescriptions respectively). This study aimed to capture the time-series trends (2014-2022) for commonly prescribed antibiotics for respiratory and urinary tract infections in primary care in England. Trends for Amoxicillin, Amoxicillin sodium, Trimethoprim, Clarithromycin, Erythromycin, Erythromycin ethylsuccinate, Erythromycin stearate, Doxycycline hyclate, Doxycycline monohydrate and Phenoxymethylpenicillin (Penicillin V) were determined. In doing so providing evidence regarding meeting UK antibiotic prescribing rate objectives (a 15% reduction in human antibiotic use 2019-2024). Time series trend analysis of 62,949,272 antibiotic prescriptions from 6,370 General Practices in England extracted from the National Health Service (NHS) Business Services Authority web portal were explored. With additional investigation of prescribing rate trends by quintiles of the Index of Multiple Deprivation (IMD). Overall, there is a downwards trend in antibiotic prescribing for those explored. There is an association between IMD, geographical location, and higher antibiotic prescribing levels (prescribing hot spots). England has a well-documented North-South divide of health inequalities, this is reflected in antibiotic prescribing. The corona virus pandemic (COVID-19) impacted on AMS, with a rise in doxycycline and trimethoprim prescriptions notable in higher IMD areas. Since then, prescribing appears to have returned to pre-pandemic levels in all IMDs and continued to decline. AMS efforts are being adhered to in primary care in England. This study provides further evidence of the link between locality and poorer health outcomes (reflected in higher antibiotic prescribing). Further work is required to address antibiotic use in hot spot areas.
Topics: Humans; Anti-Bacterial Agents; State Medicine; COVID-19; Amoxicillin; Doxycycline; Inappropriate Prescribing; Penicillin V; Trimethoprim; Erythromycin; Primary Health Care; Practice Patterns, Physicians'
PubMed: 37183105
DOI: 10.1016/j.sapharm.2023.05.001 -
Acta Orthopaedica Belgica Dec 2006Doxycycline exhibits various effects apart from its antimicrobial activity, such as inhibition of matrix metalloproteinases (MMPs). MMPs, mainly collagenases and...
Doxycycline exhibits various effects apart from its antimicrobial activity, such as inhibition of matrix metalloproteinases (MMPs). MMPs, mainly collagenases and gelatinases, are capable of degrading virtually all constituents of the extracellular matrix and are critical to connective tissue remodelling and healing. We therefore hypothesised that doxycycline would negatively influence the rat tendon healing process and impede tendon regeneration. The Achilles tendon of 60 Sprague Dawley rats was transected transversely. The animals were treated with doxycycline, 130 mg/kg body weight/day. The healing tendons were evaluated mechanically at 5, 8 and 14 days. Doxycycline significantly decreased force at failure (p < 0.005) and energy uptake (p < 0.001). Doxycycline serum concentration was 3.4 (SD 1.0) microg/ml. In conclusion, tendon healing can be affected by doxycycline at clinically relevant serum concentrations. This observation might be of relevance to further studies exploring effects of MMP-inhibitors on tendon tissue.
Topics: Achilles Tendon; Animals; Doxycycline; Female; Matrix Metalloproteinase Inhibitors; Rats; Rats, Sprague-Dawley; Time Factors; Wound Healing
PubMed: 17260615
DOI: No ID Found -
Journal of the American Veterinary... Oct 2003To determine whether plasma doxycycline concentrations considered effective for treatment of avian chlamydiosis could be safely established and maintained in budgerigars...
OBJECTIVE
To determine whether plasma doxycycline concentrations considered effective for treatment of avian chlamydiosis could be safely established and maintained in budgerigars via administration of doxycycline in water or seed.
DESIGN
Prospective study.
ANIMALS
68 healthy mature budgerigars.
PROCEDURE
In 14-day trials, plasma doxycycline concentrations were measured in budgerigars provided with water containing 0, 50, 100, 200, or 400 mg of doxycycline hyclate/L or a hulled seed diet containing 0, 100, 200, or 400 mg of doxycycline hyclate/kg. On the basis of these results, birds were fed seed containing 300 mg of doxycycline/kg for 42 days, and a control group received unmedicated seed. Blood samples for plasma doxycycline analysis were collected either in the morning on treatment days 4, 7 14, 21, 28, 35, and 42 or in the afternoon on days 12, 26, and 40. Birds were observed daily. On days 14, 28, and 42, physical and plasma biochemical variables, PCV, and total solids concentration were measured; cloacal specimens were obtained for bacteriologic and fungal culture.
RESULTS
During a 14-day period, treatment with water containing < or = 400 mg of doxycycline/L did not maintain plasma doxycycline concentrations of > or = 1 microg/mL, but seed containing 300 mg of doxycycline hyclate/kg maintained mean plasma doxycycline concentrations > 0.98 microg/mL for 42 days without notable adverse effects.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggest that hulled seed containing 300 mg of doxycycline hyclate/kg can safely establish and maintain plasma doxycycline concentrations that are considered adequate for treatment of chlamydiosis in adult nonbreeding budgerigars.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Bird Diseases; Chlamydophila Infections; Dose-Response Relationship, Drug; Doxycycline; Female; Male; Parrots; Prospective Studies
PubMed: 14552488
DOI: 10.2460/javma.2003.223.993 -
Journal of Veterinary Pharmacology and... Sep 2021The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses...
The objectives of this study were to investigate the pharmacokinetics (PK), pharmacodynamics (PD), and the efficacy of oral administration of doxycycline (DXC) in horses with Streptococcus zooepidemicus tissue infections. Tissue chambers (TC) were implanted subcutaneously in the cervical region of 7 horses and inoculated with a single S. zooepidemicus isolate with a minimum inhibitory concentration (MIC) of 0.25 µg/ml, determined by agar dilution. Doxycycline hyclate (10 mg/kg, orally, q 12 h, for 5 days) mixed with poloxamer gel was started following inoculation. The TC fluid was sampled prior to and following inoculation for cytology analysis, quantitative culture, and DXC determination. Plasma DXC concentrations were measured over 48 h following the last dose of DXC administered. The mean plasma peak concentration (C ) of DXC was 0.32 µg/ml, and concentrations above the MIC were only reached in 3 TC samples. In plasma, mean T > MIC was 2.4 h, mean C /MIC was 1.30, and mean AUC /MIC was 11.63 h. These PK/PD indices did not reach the suggested targets for DXC treatments of infections, and the TC abscessed in all horses. This is the first study to evaluate the recommended dose of DXC in horse in an infection model.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Doxycycline; Horses; Microbial Sensitivity Tests; Streptococcus equi
PubMed: 34057219
DOI: 10.1111/jvp.12982 -
JCI Insight Nov 2022Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggesting that...
Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggesting that rosacea is associated with metabolic disorders, the role of metabolism in rosacea pathogenesis remains unknown. Here, via a targeted metabolomics approach, we characterized significantly altered metabolic signatures in patients with rosacea, especially for amino acid-related metabolic pathways. Among these, glutamic acid and aspartic acid were highlighted and positively correlated with the disease severity in patients with rosacea. We further demonstrated that glutamic acid and aspartic acid can facilitate the development of erythema and telangiectasia, typical features of rosacea, in the skin of mice. Mechanistically, glutamic acid and aspartic acid stimulated the production of vasodilation-related neuropeptides from peripheral neurons and keratinocytes and induced the release of nitric oxide from endothelial cells and keratinocytes. Interestingly, we provided evidence showing that doxycycline can improve the symptoms of patients with rosacea possibly by targeting the amino acid metabolic pathway. These findings reveal that abnormal amino acid metabolism promotes neurovascular reactivity in rosacea and raise the possibility of targeting dysregulated metabolism as a promising strategy for clinical treatment.
Topics: Animals; Mice; Endothelial Cells; Aspartic Acid; Glutamic Acid; Rosacea; Doxycycline
PubMed: 36219476
DOI: 10.1172/jci.insight.161870 -
Acta Biomaterialia Apr 2010Novel Sr-substituted calcium phosphate cement (CPC) loaded with doxycycline hyclate (DOXY-h) was employed to elucidate the effect of strontium substitution on antibiotic...
Novel Sr-substituted calcium phosphate cement (CPC) loaded with doxycycline hyclate (DOXY-h) was employed to elucidate the effect of strontium substitution on antibiotic delivery. The cement was prepared using as reactants Sr-substituted beta-tricalcium phosphate (Sr-beta-TCP) and acidic monocalcium phosphate monohydrate. Two different methods were used to load DOXY-h: (i) the adsorption on CPC by incubating the set cement in drug-containing solutions; and (ii) the use of antibiotic solution as the cement liquid phase. The results revealed that the Sr-substituted cement efficiently adsorbs the antibiotic, which is attributed to an enhanced accessibility to the drug-binding sites within this CPC. DOXY-h desorption is influenced by the initial adsorbed amount and the cement matrix type. Furthermore, the fraction of drug released from CPCs set with DOXY-h solution was higher, and the release rate was faster for the CPC prepared with 26.7% Sr-beta-TCP. The analysis of releasing profiles points to Fickian diffusion as the mechanism responsible for antibiotic delivery. We can conclude that Sr substitution in secondary calcium phosphate cements improves their efficiency for DOXY-h adsorption and release. The antibiotic loading method provides a way to switch from rapid and complete to slower and prolonged drug release.
Topics: Adsorption; Anti-Bacterial Agents; Calcium Phosphates; Doxycycline; Microbial Sensitivity Tests; Porosity; Porphyromonas gingivalis; Strontium; Temperature; Tensile Strength; Time Factors
PubMed: 19879982
DOI: 10.1016/j.actbio.2009.10.043 -
Antimicrobial Agents and Chemotherapy Jul 2004The prophylactic potential of a single injection of sustained-release doxycycline hyclate (Atridox) was compared to that of a single oral dose of doxycycline hyclate in...
The prophylactic potential of a single injection of sustained-release doxycycline hyclate (Atridox) was compared to that of a single oral dose of doxycycline hyclate in a murine model of Lyme borreliosis. Prophylaxis, as measured by the lack of cultivable spirochetes and demonstrable pathology, was noted for 43% of orally treated mice; in contrast, the sustained-release doxycycline hyclate completely protected mice from infection and resultant pathology.
Topics: Animals; Anti-Bacterial Agents; Bites and Stings; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Doxycycline; Female; Injections, Subcutaneous; Lyme Disease; Mice; Mice, Inbred C3H; Ticks
PubMed: 15215128
DOI: 10.1128/AAC.48.7.2697-2699.2004 -
Journal of the American Veterinary... Sep 2016OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study.... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Cross-Over Studies; Dogs; Dose-Response Relationship, Drug; Doxycycline; Female; Male; Tears
PubMed: 27556265
DOI: 10.2460/javma.249.5.508 -
Archives de Pediatrie : Organe Officiel... Jan 2006
Topics: Adolescent; Anti-Bacterial Agents; Doxycycline; Esophageal Diseases; Female; Humans; Ulcer
PubMed: 16330193
DOI: 10.1016/j.arcped.2005.10.014 -
Research in Veterinary Science Jun 2008Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically...
Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.
Topics: Animals; Anti-Bacterial Agents; Cattle; Delayed-Action Preparations; Doxycycline; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Kinetics
PubMed: 17720208
DOI: 10.1016/j.rvsc.2007.07.003