Tetracycline Class Of Antibiotics Research Articles

SAFETY OF TETRACYCLINES FOR PUBLIC HEALTH AND THE ENVIRONMENT

Antimicrobial veterinary medicinal products of the tetracycline class have been most widely used for many years in the veterinary practice, both in Ukraine and in European countries, the USA, Canada, etc. Teteracyclynes have a wide-spectrum activity against gram-positive and gram-negative microorganisms, rickettsia, mycoplasma, chlamydia and protozoan parasites and are successfully used for the treatment of infectious diseases of the gastrointestinal tract, respiratory organs, skin and urogenital infections. Antimicrobial veterinary medicinal products of this class belong to AMEG category D, which is the safest in terms of impact on public health. Tetracyclines are low cost agents, are not high toxic when used in animals, which justifies their frequent choice for empirical treatment. During the monitoring of sales volumes for 2016-2021, antimicrobial veterinary medicinal products of the tetracycline class occupied the largest share among all antimicrobials entering the market in Ukraine (25.9-39.4)%. Most frequently, these veterinary medicinal products are intended for oral administration, but since their low bioavailability (5-15)%, they are excreted from the body almost unchanged. However, there is a danger of the development of tetracyclines resistance and a hazard to the environment and public health, which is explained by the frequent use of this class substances, the permission of large amounts into the soil with manure and water following drinkers washing after the treatment. Tetracyclines are poorly metabolized, and their long-term use in veterinary practice contributes to the bioaccumulation of significant amounts in soil and water. The main goal of this study were the analysis of veterinary medicinal products containing tetracyclines which were authorized in Ukraine by the category of active substances and route of administration. Another problem of this article was to substantiate the impact of tetracycline class antibiotics on the environment and the acquired antimicrobial resistance in the view of the necessity of their reasonable and safety use for the animals treatment, taking into account the requirements of the current legislation in Ukraine and EU member states. The results of the study proved that antimicrobial veterinary medicinal products containing chlortetracycline, mainly for oral administration, prevail in Ukraine. The bias of this monitoring is the lack information on the volumes of their use in farms and for individual animal species. Although the tetracycline class antibiotics do not belong to persistent bio accumulative toxic substances (PBT), their long-term and widespread use causes concern in view of the possible acquiring antimicrobial resistance and harmful effects on the environment, which will have an impact on public health. It is necessary to introduce regulatory measures to limitation and optimal use of these compounds in veterinary medicine. It is also necessary to deliver information among stakeholders about the possible negative impact on the environment and plan activities to prevent the development of acquired antimicrobial resistance to the tetracycline class antibiotics.

Scientific Rationale and Clinical Basis for Clindamycin Use in the Treatment of Dermatologic Disease.

Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin's anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology.

Development and validation of LC-MS/MS for quantifying omadacycline from stool for gut microbiome studies

This study developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify omadacycline and its epimerization in stool to facilitate microbiome studies. Omadacycline was extracted in a methanol-water-ethylenediaminetetraacetic acid (ETDA) solvent containing deuterated omadacycline as internal standard, followed by dilution. In an optimal gradient elution mode, omadacycline and its C4 epimer were separated within 5 min on reversed-phase C18 column. The method showed a broad working range of 0.1–200 ng/ml with a limitation of detection (LOD) of 0.03 ng/ml, little fecal matrix effect, good intra-day and inter-day accuracy (90–101 %), precision (2–15 %), and recovery rate (99–105 %). The method was sufficiently sensitive to quantify omadacycline in human fecal samples (n = 82) collected during a 10-day therapy course and at follow-up (day 13 and day 30) that ranged from 1 to 4785 µg/g. Further analysis revealed that ∼9 % of omadacycline was epimerized in fecal matrix control while, on average, 37.4 % was epimerized in human fecal samples. This study developed and validated a novel, simple, sensitive, and accurate method utilizing LC-MS/MS to quantify omadacycline its epimerization in the human gut. This has important implications for future studies of omadacycline and other tetracycline-class antibiotics as part of gut microbiome studies.

Doxycycline is a viable alternative to tetracycline for use in insect Tet-Off transgenic sexing systems, as assessed in the blowflies Cochliomyia hominivorax and Lucilia cuprina (Diptera: Calliphoridae).

Transgenic insect strains with tetracycline repressible (Tet-Off) female-lethal genes provide significant advantages over traditional sterile insect techniques for insect population control, such as reduced diet and labor costs and more efficient population suppression. Tet-Off systems are suppressed by tetracycline-class antibiotics, most commonly tetracycline (Tc) or doxycycline (Dox), allowing for equal sex ratio colonies of transgenic insects when reared with Tc or Dox and male-only generations in their absence. Dox is a more stable molecule and has increased uptake than Tc, which could be advantageous in some insect mass-rearing systems. Here, we evaluated the suitability of Dox for rearing Tet-Off female-lethal strains of Australian sheep blowfly, Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae), and New World screwworm, Cochliomyia hominivorax (Coquerel, 1858) (Diptera: Calliphoridae), and the effects of dosage on strain performance. For both species, colonies were able to be maintained with mixed-sex ratios at much lower dosages of Dox than Tc. Biological yields of C. hominivorax on either antibiotic were not significantly different. Reduction of Dox dosages in C. hominivorax diet did not affect biological performance, though rearing with 10 or 25 μg/mL was more productive than 50 μg/mL. Additionally, C. hominivorax mating performance and longevity were equal on all Dox dosages. Overall, Dox was a suitable antibiotic for mass-rearing Tet-Off female-lethal L. cuprina and C. hominivorax and was functional at much lower dosages than Tc.

The effect of doxycycline on canine neutrophil functions

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.

Acne accounts for an almost 2.5-fold higher proportion of dermatology visits among adult females compared to adult males in the United States: A study of the national ambulatory medical care survey from 2002-2016.

Acne vulgaris affects a significant number of females into adulthood. Juvenile acne and adult acne have different presentations and potentially distinctive pathogeneses. However, patterns in treatments specifically related to the adult female population have previously not been studied. Retrospective database analysis of healthcare utilization and medications prescribed for acne using the National Ambulatory Medical Care Survey (NAMCS) data from 2002-2016 was performed. After age 20, acne accounted for an almost 2.5-fold higher proportion of dermatology visits among females compared to males (10.1% vs. 4.1%, P < 0.001). Tetracycline-class antibiotics were the most prescribed therapy within all age groups of females between 2002-2016. However, there was also a substantial rise in prescriptions of spironolactone beginning in 2012. A significantly greater proportion of dermatology visits by adult females are for acne in comparison to adult males. Tetracycline-class antibiotics remain the most prescribed therapy in adult age groups despite a potentially different pathogenesis of adult acne. Therefore, there is a need for further studies comparing the effectiveness of therapies specifically for adult female acne.

In vitro susceptibility testing of tetracycline‐class antibiotics against slowly growing non‐tuberculous mycobacteria

Non-tuberculous mycobacterial infections are gradually increasing worldwide, with slow-growing mycobacteria such as Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium kansasii accounting for the majority of cases. The use of tetracyclines has received renewed attention in recent years, and this study was designed to investigate the antibacterial activity of omadacycline, eravacycline, tigecycline, sarecycline, minocycline and doxycycline against M. avium, M. intracellulare and M. kansasii. Susceptibility testing of six tetracyclines was conducted against M. avium, M. intracellulare and M. kansasii isolates, and all the clinical isolates were collected from January 2012 to December 2018. All six agents exhibited poor antibacterial activity against slowly growing mycobacteria (SGM) isolates of three subspecies with MIC50 and MIC90 ≥8 μg/mL. M. intracellulare and M. kansasii had lower resistance rates to omadacycline than the other five drugs. The severe resistance of SGM to tetracycline suggests that developing tetracycline-class antibiotics needs to overcome existing resistance mechanisms.

Review of Novel Third-Generation Tetracyclines: Eravacycline, Omadacycline, and Sarecycline

Tetracycline class antibiotics have activity against a wide range of Gram-positive, Gram-negative, and atypical bacterial pathogens, and they have been used for treatment of various infections, including respiratory infections, skin and soft tissue infections, and sexually transmitted infections. Increases in morbidity and mortality associated with infections by multidrug-resistant organisms have highlighted the need for new antibiotics. In 2018, three novel tetracyclines were approved by the FDA: eravacycline, omadacycline, and sarecycline. This review discusses the pharmacological properties and microbiological and clinical aspects of these new tetracyclines.

In vitro activity of tetracycline analogs against multidrug-resistant and extensive drug resistance clinical isolates of Mycobacterium tuberculosis

BackgroundMultidrug-resistant tuberculosis (MDR-TB) has become a big threaten to global health. The current strategy for treatment of MDR-TB and extensive drug resistant tuberculosis (XDR-TB) is with low efficacy and high side effect. While new drug is fundamental for cure MDR-TB, repurposing the Food and Drug Administration (FDA)-approved drugs represents an alternative soluation with less cost. MethodsThe activity of 8 tetracycline-class antibiotics against mycobacterium tuberculosis (M.tb) were determined by Minimum Inhibitory Concentration (MIC) in vitro. A transposon M.smeg libraries was generated by using the Harm phage and then used to isolate the conditional growth mutants in doxycycline containing plate. Eleven mutants were isolated and genomic DNAs were extracted using the cetyltrimethyl ammonium bromide (CTAB) method and analyzed by whole genome sequencing. ResultsWe found that three of eight drugs efficiently inhibited mycobacteria growth under the peak plasma concentration in the human body. Further tests showed these three tetracycline analogs (demeclocycline, doxycycline and methacycline) had antimicrobial activity against seven clinical isolates, including MDR and XDR strains. Among them, Doxycycline had the lowest MICs in all mycobacteria strains tested in this study. By using a transposon library, we identify the insertion of transposon in two genes, porin and MshA, associatewith the resistant to doxycycline. ConclusionsOur findings show that tetracycline analogs such as doxycycline, has bactericidal activity against not only drug sensitive M.tb, but also clinical MDR and XDR strains, provided proof of concept to repurpose doxycycline to fight MDR-TB and XDR-TB. Further investigations are warranted to clarify the underlying mechanism and optimize the strategy in combination with other anti-TB drugs.

Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice

Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.

The Thyroid Pathologist Meets Therapeutic Pharmacology.

The effects of many pharmacological agents on thyroid function are well known. Direct influences on measurements of thyroid function tests are also described. However, certain classes of drugs produce morphological changes in the gland. This review focuses on the significance of the following drug classes for the thyroid pathologist: iodine, antithyroid drugs, psychotropic drugs, antibiotics, cardiotropic drugs, antidiabetic drugs, and immunomodulatory agents. Radioactive iodine initially induces mild histologic changes; however, the long-term effects include marked follicular atrophy, fibrosis, and nuclear atypia-changes that vary depending on the pre-therapy condition of the gland. Some psychotropic drugs have been associated with a spectrum of inflammatory changes throughout the gland. The tetracycline class of antibiotics, namely minocycline, can lead to a grossly black thyroid gland with pigment seen in both colloid and follicular epithelial cells while variably present within thyroid nodules. The surgical pathologist most commonly sees an amiodarone-affected gland removed for hyperthyroidism, and the histologic findings again depend on the pre-therapy condition of the gland. While GLP-1 receptor agonists carry an FDA black box warning for patients with a personal or family history of multiple endocrine neoplasia or medullary thyroid carcinoma, the C cell hyperplasia originally noted in rats has not borne out in human studies. Finally, thyroiditis and hypothyroidism are well known complications of checkpoint inhibitor therapy, and rare cases of severe thyroiditis requiring urgent thyroidectomy have been reported with unique histologic findings. In this review, we describe the histologic findings for these drugs and more, in many cases including their functional consequences.

Trends in Oral Antibiotic Use for Acne Treatment: A Retrospective, Population-Based Study in the United States, 2014 to 2016.

Antibiotic resistance related to prolonged antibiotic use is an emerging threat to public health. To evaluate recent trends in oral antibiotic use for acne treatment. A retrospective study was conducted from January 2014 through September 2016 using the IBM MarketScan&reg; claims database. Patients were aged &ge;9 years, prescribed an oral antibiotic, and diagnosed with acne vulgaris on 2 separate occasions. The primary outcome was the duration of oral antibiotic treatment over 12 months; continuous use was defined as &le;30-day gap between prescriptions. The most commonly prescribed antibiotic treatments (N=46,267) were doxycycline (36.7%) and minocycline (36.5%). Overall, 36%, 18%, 10%, and 5% of patients continuously used any oral antibiotic at 3, 6, 9, and 12 months, respectively. Among patients who continuously used tetracyclines, a similar percentage was prescribed minocycline (40.2%, 18.6%, 10.5%, and 5.1%) vs doxycycline (34.7%, 14.6%, 7.7%, and 3.9%) at 3, 6, 9, and 12 months, respectively. A greater percentage of patients continued use of tetracyclineclass antibiotics than other therapeutic classes. Retrospective analysis of health-care claims data. Relatively short study duration. Nearly 20% of patients continuously used oral antibiotics for &ge;6 months, exceeding American Academy of Dermatology guideline recommendations of 3 to 4 months. J Drugs Dermatol. 2023;22(3):265-270. doi:10.36849/JDD.7345.

A propensity score matched cohort study identifying an association of acne, but not oral antibiotic or isotretinoin use, with risk of incident inflammatory bowel disease

Concerns remain regarding whether oral antibiotic or isotretinoin use for acne is associated with increased risk of inflammatory bowel disease (IBD); little is known about whether acne itself is associated with IBD. To determine whether isotretinoin exposure, oral tetracycline-class antibiotic exposure, and/or acne itself are associated with IBD. A propensity score matched cohort study was performed using TriNetX between 2001 and 2022 to compare the 1-year incidence of IBD between those without acne compared to those with acne managed without systemic medications, acne managed with oral tetracycline-class antibiotics, and acne managed with isotretinoin. There was a statistically significant association between acne and risk of incident IBD (odds ratio: 1.42; 95% confidence interval: 1.23-1.65). There was no statistically significant association between oral tetracycline-class antibiotic or isotretinoin exposure and IBD. Use of electronic health data; potential for misclassification bias. This matched cohort study identifies an association between acne and IBD. These data provide further reassurance regarding the use of isotretinoin in the treatment of acne.

Effect of Sarecycline on the Acne Symptom and Impact Scale and Concerns in Moderate-to-Severe Truncal Acne in Open-Label Pilot Study.

Truncal acne is common, and the psychosocial burden may be underestimated as patients most often complain of facial acne. The Acne Symptom and Impact Scale (ASIS) is a 17-item patient-reported outcome (PRO) measure designed to assess the signs and impacts of acne vulgaris. ASIS has previously been validated in a prospective, non-interventional study as a reliable PRO instrument for facial acne. In a pilot study, ASIS, and an additional 10 new questions that focused on the concerns of patients (ASIS-C), were given to 10 patients with moderate-to-severe truncal acne vulgaris who received 3 months of monotherapy with oral sarecycline, a narrow-spectrum tetracycline-class antibiotic. ASIS-C questionnaires were also given to 10 acne-free control subjects. Average ASIS-C answers decreased by 4% for Signs, 15% for Impact, and 16% for Concerns in the 10 patients, with greater decreases of 5% for Signs, 20% for Impact, and 19% for Concerns in the 60% of patients whose truncal acne was clear or almost clear after 12 weeks of sarecycline treatment. In this study, sarecycline was effective in reducing the psychosocial burden associated with truncal acne based on the ASIS-C PRO measures.

In Vitro Antimicrobial Activities of Tigecycline, Eravacycline, Omadacycline, and Sarecycline against Rapidly Growing Mycobacteria.

Infections caused by rapidly growing mycobacteria (RGM) have increased globally. Chemotherapy against these infections is challenging due to the minimal antimicrobial choices available. The main aim of this study was to evaluate the in vitro susceptibilities of four tetracyclines against different RGM species. The MICs of eravacycline (ERC), omadacycline (OMC), sarecycline (SAC), and tigecycline (TGC) against the reference strains of 27 RGM species and 121 RGM clinical isolates were determined by microtiter plate assay. The minimum bactericidal concentrations (MBCs) and cytotoxicities of these antibiotics were also tested. Except for SAC, the other three tetracyclines had MICs of ≤0.5 μg/mL against all 27 RGM reference strains. ERC generally presented the lowest MICs, with MIC90s against the clinical isolates of Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense, and Mycobacterium fortuitum of 0.25 μg/mL, 0.25 μg/mL, and 0.06 μg/mL, respectively. TGC and OMC also showed equivalent in vitro inhibitory activities against the isolates, while the TGC MIC90s for M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum were lower than or equal to the OMC MIC90s (1, 1, and 0.25 μg/mL versus 1, 2, and 2 μg/mL). In addition, the MIC50s of three of the antibiotics for each species were always 2-fold lower than the corresponding MIC90s. MBC and cytotoxicity assays indicated that all four tetracycline antibiotics tested were bacteriostatic agents with low toxicity to the THP-1 cell line. Tetracycline antibiotics are efficacious in RGM infection treatment, with omadacycline showing the best promise for clinical application due to its potent antimicrobial activity, safety, and convenient administration route. IMPORTANCE The global rise in antibiotic-resistant nontuberculous mycobacteria has prompted the urgent need for new antimicrobials, especially oral antibiotics. Currently, adverse effects have limited the use of tetracycline-class antibiotics, particularly tigecycline (TGC), in the treatment of rapidly growing mycobacteria (RGM). However, several new tetracycline-class antibiotics might overcome the limitations of TGC. We assessed the in vitro antibiotic susceptibilities of four tetracyclines (eravacycline, omadacycline, sarecycline, and tigecycline) against reference RGM strains and clinical isolates of different RGM species. We showed that three of these antibiotics (tigecycline, eravacycline, and omadacycline) might be efficacious in M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. fortuitum treatment. Furthermore, omadacycline was more promising for clinical application for M. abscessus infections as an oral drug, whereas sarecycline, which had the best safety parameters, should be considered a potential antibiotic for M. abscessus infections caused by susceptible strains. Our work underscores the possible clinical applications of tetracycline-class antibiotics in the treatment of RGM infections.

Dissemination and prevalence of plasmid-mediated high-level tigecycline resistance gene tet (X4)

With the large-scale use of antibiotics, antibiotic resistant bacteria (ARB) continue to rise, and antibiotic resistance genes (ARGs) are regarded as emerging environmental pollutants. The new tetracycline-class antibiotic, tigecycline is the last resort for treating multidrug-resistant (MDR) bacteria. Plasmid-mediated horizontal transfer enables the sharing of genetic information among different bacteria. The tigecycline resistance gene tet(X) threatens the efficacy of tigecycline, and the adjacent ISCR2 or IS26 are often detected upstream and downstream of the tet(X) gene, which may play a crucial driving role in the transmission of the tet(X) gene. Since the first discovery of the plasmid-mediated high-level tigecycline resistance gene tet(X4) in China in 2019, the tet(X) genes, especially tet(X4), have been reported within various reservoirs worldwide, such as ducks, geese, migratory birds, chickens, pigs, cattle, aquatic animals, agricultural field, meat, and humans. Further, our current researches also mentioned viruses as novel environmental reservoirs of antibiotic resistance, which will probably become a focus of studying the transmission of ARGs. Overall, this article mainly aims to discuss the current status of plasmid-mediated transmission of different tet(X) genes, in particular tet(X4), as environmental pollutants, which will risk to public health for the “One Health” concept.

Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.

Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming •O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.

34086 Rapid response of truncal acne with oral sarecycline

Truncal acne affects 60-70% of acne patients and larger surface areas than facial acne. Topical treatment application becomes more difficult. Oral sarecycline, a narrow-spectrum, third-generation tetracycline-class antibiotic, is FDA-approved for moderate-to-severe acne vulgaris in patients aged 9 and older. Sarecycline’s potent anti-inflammatory activity, activity against Cutibacterium acnes and clinically relevant Gram-positive bacteria, but reduced activity against enteric Gram-negative bacteria, may contribute to its favorable safety and tolerability profile.

34077 Efficacy of oral sarecycline in Hispanics with facial inflammatory acne

In 2019, 60.6 million in the U.S. were Hispanics, with acne affecting 32% of Hispanic women. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic, FDA approved for the treatment of moderate-to-severe acne in patients aged 9 and older. With increasing focus on outcomes in skin of color, we report pooled post hoc analysis of efficacy and safety data on sarecycline in Hispanics from pivotal phase 3, multicenter, randomized, double-blind, placebo-controlled studies SC1401 and SC1402.

Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota.

Treatment for moderate-to-severe acne vulgaris relies on prolonged use of oral tetracycline-class antibiotics; however, these broad-spectrum antibiotics are often associated with off-target effects and negative gastrointestinal sequelae. Sarecycline is a narrow-spectrum antibiotic treatment option. Here, we investigated the effect of prolonged sarecycline exposure, compared with broad-spectrum tetracyclines (doxycycline and minocycline) upon the colonic microbiota. Three in vitro models of the human colon were instilled with either minocycline, doxycycline or sarecycline, and we measured microbiota abundance and diversity changes during and after antibiotic exposure. Significant reductions in microbial diversity were observed following minocycline and doxycycline exposure, which failed to recover post antibiotic withdrawal. Specifically, minocycline caused a ~10% decline in Lactobacillaceae and Bifidobacteriaceae abundances, while doxycycline caused a ~7% decline in Lactobacillaceae and Bacteroidaceae abundances. Both minocycline and doxycycline were associated with a large expansion (>10%) of Enterobacteriaceae. Sarecycline caused a slight decline in bacterial diversity at the start of treatment, but abundances of most families remained stable during treatment. Ruminococcaceae and Desulfovibrionaceae decreased 9% and 4%, respectively, and a transient increased in Enterobacteriaceae abundance was observed during sarecycline administration. All populations recovered to pre-antibiotic levels after sarecycline exposure. Overall, sarecycline had minimal and transient impact on the gut microbiota composition and diversity, when compared to minocycline and doxycycline.