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Annals of Medicine Dec 2022The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select... (Review)
Review
The progressive increase in antibiotic resistance in recent decades calls for urgent development of new antibiotics and antibiotic stewardship programs to help select appropriate treatments with the goal of minimising further emergence of resistance and to optimise clinical outcomes. Three new tetracycline-class antibiotics, eravacycline, omadacycline, and tigecycline, have been approved within the past 15 years, and represent a new era in the use of tetracyclines. These drugs overcome the two main mechanisms of acquired tetracycline-class resistance and exhibit a broad spectrum of activity against gram-positive, gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains. We provide an overview of the three generations of tetracycline-class drugs, focussing on the efficacy, safety, and clinical utility of these three new third-generation tetracycline-class drugs. We also consider various scenarios of unmet clinical needs where patients might benefit from re-engagement with tetracycline-class antibiotics including outpatient treatment options, patients with known β-lactam antibiotic allergy, reducing the risk of infection, and their potential as monotherapy in polymicrobial infections while minimising the risk of any potential drug-drug interaction. KEY MESSAGESThe long-standing safety profile and broad spectrum of activity of tetracycline-class antibiotics made them a popular choice for treatment of various bacterial infections; unfortunately, antimicrobial resistance has limited the utility of the early-generation tetracycline agents.The latest generation of tetracycline-class antibiotics, including eravacycline, tigecycline, and omadacycline, overcomes the most common acquired tetracycline resistance mechanisms.Based on characteristics and clinical data, these newer tetracycline agents provide an effective antibiotic option in the treatment of approved indications in patients with unmet clinical needs - including patients with severe penicillin allergy, with renal or hepatic insufficiency, recent infection, or polymicrobial infections, and those at risk of drug-drug interactions.
Topics: Anti-Bacterial Agents; Coinfection; Drug Resistance, Multiple, Bacterial; Humans; Hypersensitivity; Microbial Sensitivity Tests; Tetracycline; Tetracyclines; Tigecycline
PubMed: 35723082
DOI: 10.1080/07853890.2022.2085881 -
Metabolic Engineering Mar 2009Tetracyclines have been important agents in combating infectious disease since their discovery in the mid-20th century. Following widespread use, tetracycline resistance... (Review)
Review
Tetracyclines have been important agents in combating infectious disease since their discovery in the mid-20th century. Following widespread use, tetracycline resistance mechanisms emerged and continue to create a need for new derivatives that are active against resistant bacterial strains. Semisynthesis has led to second and third generation tetracycline derivatives with enhanced antibiotic activity and pharmacological properties. Recent advancement in understanding of the tetracycline biosynthetic pathway may open the door to broaden the range of tetracycline derivatives and afford analogs that are difficult to access by synthetic chemistry.
Topics: Models, Biological; Protein Engineering; Recombinant Proteins; Signal Transduction; Streptomyces; Tetracycline
PubMed: 19007902
DOI: 10.1016/j.ymben.2008.10.001 -
Chinese Medical Journal Apr 2023Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens.
METHODS
This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables.
RESULTS
As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups.
CONCLUSION
The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance.
TRIAL REGISTRATION
ClinicalTrials.gov, ChiCTR 1900023646.
Topics: Humans; Bismuth; Metronidazole; Esomeprazole; Minocycline; Helicobacter pylori; Potassium Citrate; Anti-Bacterial Agents; Tetracycline; Helicobacter Infections; Drug Therapy, Combination; Amoxicillin
PubMed: 37010246
DOI: 10.1097/CM9.0000000000002629 -
Acta Crystallographica. Section F,... Jul 2023The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection...
The resistance of the emerging human pathogen Stenotrophomonas maltophilia to tetracycline antibiotics mainly depends on multidrug efflux pumps and ribosomal protection enzymes. However, the genomes of several strains of this Gram-negative bacterium code for a FAD-dependent monooxygenase (SmTetX) homologous to tetracycline destructases. This protein was recombinantly produced and its structure and function were investigated. Activity assays using SmTetX showed its ability to modify oxytetracycline with a catalytic rate comparable to those of other destructases. SmTetX shares its fold with the tetracycline destructase TetX from Bacteroides thetaiotaomicron; however, its active site possesses an aromatic region that is unique in this enzyme family. A docking study confirmed tetracycline and its analogues to be the preferred binders amongst various classes of antibiotics.
Topics: Humans; Stenotrophomonas maltophilia; Crystallography, X-Ray; Anti-Bacterial Agents; Tetracycline; Oxytetracycline; Microbial Sensitivity Tests
PubMed: 37405486
DOI: 10.1107/S2053230X23005381 -
Virulence Dec 2022The extensive use of tetracycline antibiotics has led to the widespread presence of tetracycline-resistance genes in Gram-negative bacteria and this poses serious...
The extensive use of tetracycline antibiotics has led to the widespread presence of tetracycline-resistance genes in Gram-negative bacteria and this poses serious threats to human and animal health. In our previous study, we reported a method for rapid detection of Tet(X)-producers using MALDI-TOF MS. However, there have been multiple machineries involved in tetracycline resistance including efflux pump, and ribosomal protection protein. Our previous demonstrated the limitation in probing the non-Tet(X)-producing tetracycline-resistant strains. In this regard, we further developed a MALDI-TOF MS method to detect and differentiate Tet(X)-producers and non-Tet(X)-producing tetracycline-resistant strains. Test strains were incubated with tigecycline and oxytetracycline in separate tubes for 3 h and then analyzed spectral peaks of tigecycline, oxytetracycline, and their metabolite. Strains were distinguished using MS ratio for [metabolite/(metabolite+ tigecycline or oxytetracycline)]. Four control strains and 319 test strains were analyzed and the sensitivity was 98.90% and specificity was 98.34%. This was consistent with the results obtained from LC-MS/MS analysis. Interestingly, we also found that the reactive oxygen species (ROS) produced by tetracycline-susceptible strains were able to promote the degradation of oxytetracycline. Overall, the MALDI test represents a rapid and reliable method to detect Tet(X)-producers, non-Tet(X)-producing tetracycline-resistant strains, and tetracycline-susceptible strains.
Topics: Animals; Anti-Bacterial Agents; Chromatography, Liquid; Gram-Negative Bacteria; Microbial Sensitivity Tests; Oxytetracycline; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry; Tetracycline; Tigecycline
PubMed: 34951562
DOI: 10.1080/21505594.2021.2018768 -
Bone Jun 2022Tetracyclines are a broad-spectrum class of antibiotics that have unclear actions with potentially lasting effects on bone metabolism. Initially isolated from... (Review)
Review
Tetracyclines are a broad-spectrum class of antibiotics that have unclear actions with potentially lasting effects on bone metabolism. Initially isolated from Streptomyces, tetracycline proved to be an effective treatment for Gram +/- infections. The emergence of resistant bacterial strains commanded the development of later generation agents, including minocycline, doxycycline, tigecycline, sarecycline, omadacycline, and eravacycline. In 1957, it was realized that tetracyclines act as bone fluorochrome labels due to their high affinity for the bone mineral matrix. Over the course of the next decade, researchers discerned that these compounds are retained in the bone matrix at high levels after the termination of antibiotic therapy. Studies during this period provided evidence that tetracyclines could disrupt prenatal and early postnatal skeletal development. Currently, tetracyclines are most commonly prescribed as a long-term systemic therapy for the treatment of acne in healthy adolescents and young adults. Surprisingly, the impact of tetracyclines on physiologic bone modeling/remodeling is largely unknown. This article provides an overview of the pharmacology of tetracycline drugs, summarizes current knowledge about the impact of these agents on skeletal development and homeostasis, and reviews prior work targeting tetracyclines' effects on bone cell physiology. The need for future research to elucidate unclear effects of tetracyclines on the skeleton is addressed, including drug retention/release mechanisms from the bone matrix, signaling mechanisms at bone cells, the impact of newer third generation tetracycline antibiotics, and the role of the gut-bone axis.
Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Humans; Minocycline; Tetracycline
PubMed: 35248788
DOI: 10.1016/j.bone.2022.116377 -
Biosensors Dec 2022As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion...
As an antibody-free sensing membrane for the detection of the antibiotic tetracycline (TC), a liquid PVC membrane doped with the ion-pair tetracycline/θ-shaped anion [3,3'-Co(1,2-CBH)] ([-COSAN]) was formulated and deposited on a SWCNT modified gold microelectrode. The chosen transduction technique was electrochemical impedance spectroscopy (EIS). The PVC membrane was composed of: the tetracycline/[-COSAN] ion-pair, a plasticizer. A detection limit of 0.3 pg/L was obtained with this membrane, using bis(2-ethylhexyl) sebacate as a plasticizer. The sensitivity of detection of tetracycline was five times higher than that of oxytetracycline and of terramycin, and 22 times higher than that of demeclocycline. A shelf-life of the prepared sensor was more than six months and was used for detection in spiked honey samples. These results open the way to having continuous monitoring sensors with a high detection capacity, are easy to clean, avoid the use of antibodies, and produce a direct measurement.
Topics: Plasticizers; Tetracycline; Anti-Bacterial Agents; Microelectrodes; Antibodies; Oxytetracycline
PubMed: 36671906
DOI: 10.3390/bios13010071 -
Skin Therapy Letter May 2022Tetracycline-class drugs have been used for first-line treatment of moderate-to-severe acne and rosacea for decades. Recently, a new third generation tetracycline,...
Tetracycline-class drugs have been used for first-line treatment of moderate-to-severe acne and rosacea for decades. Recently, a new third generation tetracycline, sarecycline, was US FDA-approved for the treatment of moderate-to-severe acne. This narrow-spectrum tetracycline-derived antibiotic has been shown to be effective with an improved safety profile.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Humans; Protein Synthesis Inhibitors; Tetracycline; Tetracyclines
PubMed: 35533371
DOI: No ID Found -
Antimicrobial Resistance and Infection... Mar 2020The overuse of antimicrobials in food animals and the subsequent contamination of the environment have been associated with development and spread of antimicrobial... (Review)
Review
BACKGROUND
The overuse of antimicrobials in food animals and the subsequent contamination of the environment have been associated with development and spread of antimicrobial resistance. This review presents information on antimicrobial use, resistance and status of surveillance systems in food animals and the environment in Africa.
METHODS
Information was searched through PubMed, Google Scholar, Web of Science, and African Journal Online databases. Full-length original research and review articles on antimicrobial use, prevalence of AMR from Africa covering a period from 2005 to 2018 were examined. The articles were scrutinized to extract information on the antimicrobial use, resistance and surveillance systems.
RESULTS
A total of 200 articles were recovered. Of these, 176 studies were included in the review while 24 articles were excluded because they were not relevant to antimicrobial use and/or resistance in food animals and the environment. The percentage of farms using antimicrobials in animal production ranged from 77.6% in Nigeria to 100% in Tanzania, Cameroon, Zambia, Ghana and Egypt. The most antibiotics used were tetracycline, aminoglycoside and penicillin groups. The percentage of multi drug resistant isolates ranged from 20% in Nigeria to 100% in South Africa, Zimbabwe and Tunisia. In the environment, percentage of multi drug resistant isolates ranged from 33.3% in South Africa to 100% in Algeria. None of the countries documented national antimicrobial use and resistance surveillance system in animals.
CONCLUSION
There is high level of antimicrobial use, especially tetracycline, aminoglycoside and penicillin in animal production systems in Africa. This is likely to escalate the already high prevalence of antimicrobial resistance and multi drug resistance in the continent. This, coupled with weak antimicrobial resistance surveillance systems in the region is a great concern to the animals, environment and humans as well.
Topics: Africa; Aminoglycosides; Animals; Anti-Bacterial Agents; Antimicrobial Stewardship; Drug Resistance, Multiple, Bacterial; Food Microbiology; Penicillins; Population Surveillance; Tetracycline
PubMed: 32122406
DOI: 10.1186/s13756-020-0697-x -
Frontiers in Bioscience (Landmark... Jun 2015Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught with challenges. Early compounds largely failed due to poor selectivity and... (Review)
Review
Development of inhibitors of matrix metalloproteinases (MMPs) has been fraught with challenges. Early compounds largely failed due to poor selectivity and bioavailability. Dose-limiting side effects, off-target interactions, and improperly designed clinical trials significantly impeded clinical success. As information becomes available and technology evolves, tools to combat these obstacles have been developed. Improved methods for high throughput screening and drug design have led to identification of compounds exhibiting high potency, binding affinity, and favorable pharmacokinetic profiles. Current research into MMP inhibitors employs innovative approaches for drug delivery methods and allosteric inhibitors. Such innovation is key for development of clinically successful compounds.
Topics: Binding Sites; Computational Biology; Drug Delivery Systems; Drug Discovery; Matrix Metalloproteinase Inhibitors; Peptidomimetics; Tetracycline
PubMed: 25961551
DOI: 10.2741/4365