-
Journal of Infection in Developing... Feb 2023Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a...
INTRODUCTION
Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a prolonged duration of therapy. The aim of this study is to evaluate the incidence of esophagitis and other GI side effects in adults who received doxycycline for at least a month.
METHODOLOGY
This retrospective descriptive study included adults who received oral doxycycline for at least one month between 2016 and 2018. The primary outcome was the frequency of esophagitis. The secondary outcomes were frequency of and discontinuation due to GI adverse effects.
RESULTS
A total of 189 subjects were included with a median age of 32 years. The median duration of doxycycline use was 44 days (interquartile range 30-60). Twelve patients (6.3%) reported having GI adverse effects resulting in doxycycline discontinuation in five of them (2.6%), and three patients (1.6%) had esophagitis. The incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years than < 50 years old (8/50 vs. 4/139; p = 0.003) and in those who received a daily dose of 200 mg than 100 mg (12/93 vs. 0/96; p < 0.001).
CONCLUSIONS
GI adverse events, including esophagitis, are not rare with long-term use of oral doxycycline, particularly in older age and a higher dose of 200 mg/day. Future large and randomized studies are needed to compare the efficacy and safety of different doxycycline doses.
Topics: Adult; Humans; Doxycycline; Retrospective Studies; Anti-Bacterial Agents; Esophagitis
PubMed: 36897904
DOI: 10.3855/jidc.16677 -
Drug Discoveries & Therapeutics Mar 2021An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which began in Wuhan, China in December 2019, has rapidly spread all over the...
An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which began in Wuhan, China in December 2019, has rapidly spread all over the world. The World Health Organization characterized the disease caused by SARS-CoV-2 (COVID-19) as a pandemic in March 2020. In the absence of specific treatments for the virus, treatment options are being examined. Drug repurposing is a process of identifying new therapeutic uses for approved drugs. It is an effective strategy to discover drug molecules with new therapeutic indications. This strategy is time-saving, low-cost, and has a minimal risk of failure. Several existing approved drugs such as chloroquine, hydroxychloroquine, doxycycline, azithromycin, and ivermectin are currently in use because of their efficacy in inhibiting COVID-19. Multidrug therapy, such as a combination of hydroxychloroquine and azithromycin, a combination of doxycycline and ivermectin, or a combination of ivermectin, doxycycline, and azithromycin, has been successfully administered. Multidrug therapy is efficacious because the mechanisms of action of these drugs differ. Moreover, multidrug therapy may prevent the emergence of drug-resistant SARS-CoV-2.
Topics: Azithromycin; Doxycycline; Drug Repositioning; Drug Therapy, Combination; Humans; Hydroxychloroquine; Ivermectin; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33612572
DOI: 10.5582/ddt.2021.01005 -
Antimicrobial Agents and Chemotherapy Apr 2023Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor...
Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the susceptibility of 10 M. genitalium strains to metronidazole, secnidazole, and tinidazole. MICs ranged from 1.6 to 12.5 μg/mL for metronidazole, 3.1 to 12.5 μg/mL for secnidazole, and 0.8 to 6.3 μg/mL for tinidazole. None of these agents was synergistic with doxycycline in checkerboard broth microdilution assays. Tinidazole was superior to metronidazole and secnidazole in terms of MIC and time-kill kinetics and was bactericidal (>99.9% killing) at concentrations below reported serum concentrations. Mutations associated with nitroimidazole resistance were identified by whole-genome sequencing of spontaneous resistant mutants, suggesting a mechanism for reductive activation of the nitroimidazole prodrug by a predicted NAD(P)H-dependent flavin mononucleotide (FMN) oxidoreductase. The presence of oxygen did not affect MICs of wild-type M. genitalium, but a nitroimidazole-resistant mutant was defective for growth under anaerobic conditions, suggesting that resistant mutants may have a fitness disadvantage in anaerobic genital sites. Clinical studies are needed to determine if nitroimidazoles, especially tinidazole, are effective for eradicating M. genitalium infections in men and women.
Topics: Male; Female; Humans; Nitroimidazoles; Doxycycline; Metronidazole; Tinidazole; Mycoplasma genitalium; Anti-Bacterial Agents; Mycoplasma Infections; Drug Resistance, Bacterial
PubMed: 37070857
DOI: 10.1128/aac.00006-23 -
Oxidative Medicine and Cellular... 2021The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect...
The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect of Dx on inflammatory cell recruitment and production of inflammatory mediators via and analysis. In addition, we analyzed neovascularization, extracellular matrix deposition, and antioxidant potential of Dx on cutaneous repair in Wistar rats. Male animals ( = 15) were divided into three groups with five animals each (protocol: 72/2017), and three skin wounds (12 mm diameter) were created on the back of the animals. The groups were as follows: C, received distilled water (control); Dx1, doxycycline hyclate (10 mg/kg/day); and Dx2, doxycycline hyclate (30 mg/kg/day). The applications were carried out daily for up to 21 days, and tissues from different wounds were removed every 7 days. Our analysis demonstrated that Dx led to macrophage proliferation and increased N-acetyl--D-glucosaminidase (NAG) production, besides decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and metalloproteinases (MMP), which indicates that macrophage activation and COX-2 inhibition are possibly regulated by independent mechanisms. , our findings presented increased cellularity, blood vessels, and the number of mast cells. However, downregulation was observed in the COX-2 and PGE2 expression, which was limited to epidermal cells. Our results also showed that the downregulation of this pathway benefits the oxidative balance by reducing protein carbonyls, malondialdehyde, nitric oxide, and hydrogen peroxide (HO). In addition, there was an increase in the antioxidant enzymes (catalase and superoxide dismutase) after Dx exposure, which demonstrates its antioxidant potential. Finally, Dx increased the number of types I collagen and elastic fibers and reduced the levels of MMP, thus accelerating the closure of skin wounds. Our findings indicated that both doses of Dx can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.
Topics: Animals; Male; Rats; Anti-Bacterial Agents; Antioxidants; Cyclooxygenase 2; Doxycycline; Matrix Metalloproteinases; Rats, Wistar; Wound Healing
PubMed: 33959214
DOI: 10.1155/2021/4681041 -
Clinical Infectious Diseases : An... May 2020Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific... (Review)
Review
Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific region with more than a billion people at risk. Treatment with antibiotics such as doxycycline or chloramphenicol is effective for the majority of patients. In the 1990s, reports from northern Thailand raised a troubling observation; some scrub typhus patients responded poorly to doxycycline, which investigators attributed to doxycycline resistance. Despite the controversial nature of these reports, independent verification was neglected, with subsequent studies speculating on the role of doxycycline resistance in contributing to failure of treatment or prophylaxis. In this review, we have outlined the evidence for drug-resistant Orientia tsutsugamushi, assessed the evidence for doxycycline resistance, and highlight more recent findings unsupportive of doxycycline resistance. We conclude that doxycycline resistance is a misconception, with treatment outcome likely to be determined by other bacterial, host, and pharmacological factors.
Topics: Anti-Bacterial Agents; Doxycycline; Humans; Orientia tsutsugamushi; Scrub Typhus; Thailand
PubMed: 31570937
DOI: 10.1093/cid/ciz972 -
The Journal of Clinical Investigation Sep 2022Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial...
Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress on eukaryotic cells. We demonstrate in cell and germ-free mouse models that tetracyclines induce a mild adaptive mitochondrial stress response (MSR), involving both the ATF4-mediated integrative stress response and type I interferon (IFN) signaling. To overcome the interferences of tetracyclines with the host microbiome, we identify tetracycline derivatives that have minimal antimicrobial activity, yet retain full capacity to induce the MSR, such as the lead compound, 9-tert-butyl doxycycline (9-TB). The MSR induced by doxycycline (Dox) and 9-TB improves survival and disease tolerance against lethal influenza virus (IFV) infection when given preventively. 9-TB, unlike Dox, did not affect the gut microbiome and also showed encouraging results against IFV when given in a therapeutic setting. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function, and with downregulation of inflammatory and immune gene sets in lungs, liver, and kidneys. Mitohormesis induced by non-antimicrobial tetracyclines and the ensuing IFN response may dampen excessive inflammation and tissue damage during viral infections, opening innovative therapeutic avenues.
Topics: Animals; Anti-Bacterial Agents; Doxycycline; Humans; Influenza, Human; Mice; Orthomyxoviridae Infections; Tetracycline; Tetracyclines
PubMed: 35787521
DOI: 10.1172/JCI151540 -
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 -
BioMed Research International 2023Tuberculosis (TB) of the spine is a highly disruptive disease, especially in underdeveloped and developing countries. This condition requires standard TB treatment for...
BACKGROUND
Tuberculosis (TB) of the spine is a highly disruptive disease, especially in underdeveloped and developing countries. This condition requires standard TB treatment for 9-18 months, which increases patient risk of drug-resistant TB. Consequently, this raises the concern of adopting additional therapies to shorten the treatment duration, improve the efficacy of anti-TB drugs, and further decrease damage in the affected tissues and organs. Matrix metalloproteinase- (MMP-) 1 is a key regulator of the destruction of the extracellular matrix and associated proteins and is a new potential target for TB treatment research. In the present study, we investigated the effects of doxycycline as an MMP-1 inhibitor in patients with spondylitis TB.
METHODS
Seventy-two New Zealand white rabbits with spondylitis TB were divided into 12 different groups based on incubation period (2, 4, 6, and 8 weeks) and doxycycline administration (without, 1 mg/kg body weight (BW), and 5 mg/kg BW). We observed the course of infection through the blood concentration changes and immunohistochemical examination of MMP-1, in addition to BTA staining, culture, polymerase chain reaction (PCR), and histopathological examination.
RESULTS
Treatment with once daily 5 mg/kg BW doxycycline significantly improved the blood MMP-1 level ( < 0.05) compared with the placebo and 1 mg/kg BW doxycycline. A significantly reduced ongoing infection and a higher healing rate were demonstrated in rabbits with a higher doxycycline dose through BTA staining, culture, PCR, and histopathology. Various degrees of vertebral endplates, vertebral body, and intervertebral disc destruction were observed in 32 rabbits with positive histopathological findings, in addition to positive inflammatory cell infiltration, characterized by numerous lymphocytes, macrophages, and epithelial cells, as well as abundant granulation tissue and necrotic substances proximal to the inoculated vertebral area. Bone and intervertebral disc destructions were more apparent in the untreated rabbits.
CONCLUSION
Our study demonstrated the potential of doxycycline as an adjunctive treatment in spondylitis TB. However, limitations remain regarding the differences in the pathogenesis and virulence of between rabbit and human systems, sample size, and the dose-dependent effect of doxycycline. Further studies are needed to address these issues.
Topics: Animals; Humans; Rabbits; Doxycycline; Matrix Metalloproteinase 1; Mycobacterium tuberculosis; Spondylitis; Tuberculosis; Matrix Metalloproteinase Inhibitors
PubMed: 36743515
DOI: 10.1155/2023/7421325 -
Genome Biology Jan 2023CRISPR-based toolkits have dramatically increased the ease of genome and epigenome editing. SpCas9 is the most widely used nuclease. However, the difficulty of...
BACKGROUND
CRISPR-based toolkits have dramatically increased the ease of genome and epigenome editing. SpCas9 is the most widely used nuclease. However, the difficulty of delivering SpCas9 and inability to modulate its expression in vivo hinder its widespread adoption in large animals.
RESULTS
Here, to circumvent these obstacles, a doxycycline-inducible SpCas9-expressing (DIC) pig model was generated by precise knock-in of the binary tetracycline-inducible expression elements into the Rosa26 and Hipp11 loci, respectively. With this pig model, in vivo and/or in vitro genome and epigenome editing could be easily realized. On the basis of the DIC system, a convenient Cas9-based conditional knockout strategy was devised through controlling the expression of rtTA component by tissue-specific promoter, which allows the one-step generation of germline-inherited pigs enabling in vivo spatiotemporal control of gene function under simple chemical induction. To validate the feasibility of in vivo gene mutation with DIC pigs, primary and metastatic pancreatic ductal adenocarcinoma was developed by delivering a single AAV6 vector containing TP53-sgRNA, LKB1-sgRNA, and mutant human KRAS gene into the adult pancreases.
CONCLUSIONS
Together, these results suggest that DIC pig resources will provide a powerful tool for conditional in vivo genome and epigenome modification for fundamental and applied research.
Topics: Animals; Humans; CRISPR-Cas Systems; Doxycycline; Gene Editing; Genome; Mutation; Swine; RNA, Guide, CRISPR-Cas Systems
PubMed: 36650523
DOI: 10.1186/s13059-023-02851-x -
Contraception Nov 2022To describe the rate of vomiting from oral doxycycline 200 mg given the night before second trimester dilation and evacuation (D&E), proportion of anesthesia modalities,... (Review)
Review
OBJECTIVE
To describe the rate of vomiting from oral doxycycline 200 mg given the night before second trimester dilation and evacuation (D&E), proportion of anesthesia modalities, and anesthetic complications.
STUDY DESIGN
We conducted a single-institution retrospective cohort study of patients presenting for second trimester D&E (14-0/7 to 23-6/7 weeks gestation) July 1, 2019-June30, 2020 following their scheduled preoperative visit as identified by billing codes. We recorded vomiting within 30 minutes of ingestion, anesthetic modality, and anesthetic complications. We tested for associations using chi-square or Fisher's exact test for categorical variables and Wilcoxon-rank sum for non-normal numeric variables.
RESULTS
We reviewed 702 charts, of which 461 (66%) met inclusion criteria and 420 (60%) took doxycycline as prescribed. Of those who took doxycycline as prescribed, 30 (7.14%) reported vomiting within 30 minutes of ingestion. Nulliparity, primigravida and age less than 30 were significantly associated with vomiting (p = 0.005, p < 0.001 and p = 0.03, respectively), but gestational age (p = 0.53), BMI (p = 0.93), and gastrointestinal conditions (p > 0.99) were not. Only gravidity (p < 0.001) and parity (p = 0.01) remained significant in each of their respective multivariate models. None of the 10 patients who received general endotracheal tube anesthesia (2.4%) had vomited from doxycycline preoperatively. We observed 5 (1.2%) anesthetic complications (postoperative nausea or vomiting, anaphylaxis, and aspiration) that occurred only in those without vomiting.
CONCLUSIONS
Vomiting rates following doxycycline were lower than those previously published. We found no significant association between doxycycline-associated vomiting and increased need for general endotracheal tube anesthesia or anesthetic complications; however, our study is underpowered to draw further conclusions.
IMPLICATIONS
The findings of this study are consistent with guidelines indicating deep sedation as an effective anesthetic modality with low complication rates. Nulliparous patients may benefit from administration of an antiemetic prior to doxycycline prophylaxis, but routine antiemetic use may not be necessary.
Topics: Antiemetics; Dilatation; Doxycycline; Female; Humans; Intubation, Intratracheal; Pregnancy; Retrospective Studies; Vomiting
PubMed: 35718137
DOI: 10.1016/j.contraception.2022.06.002