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Background: Effective management of drug-food interactions is crucial for enhancing antibiotics' efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines., Methods: We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided., Results: We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption., Discussion: Interactions depend on antibiotics' physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia , tetracycline-resistant Streptococcus pneumonia , MRSA and β -lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Background: Macrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children's health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children., Methods: This retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student's t-test, Mann-Whitney U test, and χ 2 or Fisher's exact tests were used for group comparisons., Results: A total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022)., Conclusion: Doxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy were evaluated using data from omadacycline-treated patients with acute bacterial skin and skin structure infections (ABSSSI) enrolled in two phase 3 studies. Patients received omadacycline 100 mg intravenously (IV) every 12 hours for two doses, followed by 100 mg IV every 24 hours (q24h), with the option to switch to 300 mg oral (PO) q24h after 3 days or 450 mg PO q24h for two doses, followed by 300 mg PO q24h for a total duration of 7-14 days. Clinical response was evaluated at 48-72 hours [early clinical response (ECR)], end of treatment (EOT), and 7-14 days after EOT. Using a population pharmacokinetic (PK) model and PK data from patients with Staphylococcus aureus at baseline, omadacycline free-drug plasma area under the concentration-time curve (AUC) values were determined, and the relationships between free-drug plasma AUC:MIC ratio and dichotomous efficacy endpoints were evaluated. Using these relationships, the population PK model, simulation, and an omadacycline MIC distribution for S. aureus , mean percent probabilities of response were evaluated. Statistically significant PK--PD relationships were identified for ECR ( P = 0.016 and 0.013 for optimized two- and three-group free-drug plasma AUC:MIC ratios, respectively). At an MIC value of 0.5 µg/mL, percent probabilities of model-predicted success for ECR based on the univariable PK-PD relationships using continuous and two-group free-drug plasma AUC:MIC ratio variables were 91.9 and 95.6%, respectively, for the IV-to-PO dosing regimen and 89.3 and 88.4%, respectively, for the PO-only dosing regimen. These data support for omadacycline IV-to-PO and PO-only dosing regimens for ABSSSI and an omadacycline susceptibility breakpoint of 0.5 µg/mL for S. aureus ., Competing Interests: S.M.B., J.P.H., K.L., C.M.R., and P.G.A. are employees of the Institute for Clinical Pharmacodynamics, Inc., which has received research support from Paratek Pharmaceuticals, Inc. E.A.L. was an employee of ICPD at the time the analyses were conducted and is currently an employee of Vertex Pharmaceuticals, Inc. M.T. was an employee of ICPD at the time the analyses were conducted and is currently an employee of Janssen Research and Development LLC, a Johnson and Johnson company. L.F. was an employee of Paratek Pharmaceuticals, Inc., at the time the analyses were conducted and is currently an employee of AN2 Therapeutics, Inc. J.N.S. was an employee of Paratek Pharmaceuticals, Inc., at the time the analyses were conducted and is currently an employee of Scientific and Medical Affairs Consulting, LLC. E.T. was an employee of Paratek Pharmaceuticals, Inc., at the time the analyses were conducted and is currently an employee of Neuraptive Therapeutics, Inc.

Purpose: Omadacycline is a new broad-spectrum aminomethylcycline antibiotic. However, there have been limited pharmacokinetic and pharmacodynamic (PK/PD) studies of omadacycline in patients with hepatic impairment. The aim of this study was to explore the PK/PD of omadacycline intravenous administration in healthy and hepatically impaired populations., Methods: A physiologically based pharmacokinetic (PBPK) model of omadacycline was developed and validated based on published demographic data and the physiochemical properties of omadacycline. The PK processes in healthy adults were simulated and then extrapolated to a hepatically impaired population. Monte Carlo simulations were performed for PD evaluation by calculating the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the approved dosages., Findings: In the hepatically impaired population, there was no significant difference in the maximum concentration (C max ) compared with the healthy population, while the area under the plasma concentration-time curve from the first data point extrapolated to infinity (AUC&#95;inf) showed a slight increase. Monte Carlo simulations indicated that the dosage of 200 mg once daily or 100 mg twice daily intravenously (loading dose) and 100 mg once daily intravenously (maintenance dose) could cover the common pathogens of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) : Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus., Implications: Hepatic impairment exerts little impact on the PK properties of omadacycline, and no dosage adjustments are necessary for patients with mild and moderate hepatic impairment. Current dosing regimens are predicted to produce satisfactory therapeutic effects against non-drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae but may not produce the desired AUC/MIC ratios in patients with Escherichia coli or Klebsiella pneumoniae., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Tetracyclines are the standard treatment for rickettsiosis, including Japanese spotted fever (JSF), a tick-borne rickettsiosis caused by Rickettsia japonica. While some specialists in Japan advocate combining fluoroquinolones with tetracyclines for treating JSF, the negative aspects of combination therapy have not been thoroughly evaluated. Whether fluoroquinolones should be combined with tetracyclines for JSF treatment is controversial. The study aimed to evaluate the disadvantages of fluoroquinolones combined with tetracyclines for JSF treatment., Methods: This retrospective cohort study was conducted using a Japanese database comprising claims data from April 2008 to December 2020. The combination therapy group (tetracyclines and fluoroquinolones) was compared with the monotherapy group (tetracycline only) regarding mortality and the incidence of complications., Results: A total of 797 patients were enrolled: 525 received combination therapy, and 272 received monotherapy. The adjusted odds ratio (OR) for mortality was 2.30 [95% confidence interval (CI): 0.28-18.77] in the combination therapy group with respect to the monotherapy group. According to the subgroup analysis, patients undergoing combination therapy with ciprofloxacin experienced higher mortality rates compared with those receiving monotherapy (adjusted OR = 25.98, 95% CI = 1.71-393.75). Additionally, 27.7% of the combination therapy group received NSAIDs concurrently with fluoroquinolones. The combination therapy with NSAIDs group was significantly more likely to experience convulsions than the monotherapy without NSAIDs group (adjusted OR: 5.44, 95% CI: 1.13-26.30)., Conclusions: This study found no evidence that combination therapy improves mortality outcomes and instead uncovered its deleterious effects. These findings facilitate a fair assessment of combination therapy that includes consideration of its disadvantages., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Treatment outcomes for Mycobacteroides abscessus ( Mab , also known as Mycobacterium abscessus ) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab . Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCE Mycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus . Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease., Competing Interests: Daniel H. Deck and Alisa W. Serio are employees of Paratek Pharmaceuticals, Inc. All authors vouch for the integrity, completeness, and accuracy of the data and analyses and assume responsibility for the fidelity of the study.

Background: The study aims to obtain the real-world safety profile of tetracyclines in children younger than 8 years old and provide reference for clinical drug applications., Research Design and Methods: We made a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database through OpenVigil 2 and conducted a review of case reports regarding adverse drug reactions (ADRs) of tetracyclines in children younger than 8-year-old., Results: FAERS analysis identified 32 ADRs of tetracyclines in children younger than 8-year-old. Respiratory, thoracic, and mediastinal disorders contained the most frequent ADRs among all system organ classes (SOCs). The top three positive signals with the highest proportional reporting ratio (PRR) were laryngeal injury, Horner's syndrome and methaemoglobinaemia. Sixteen published tetracyclines-associated cases in children younger than 8-year-old were identified in the literature, concentrating in three SOCs. Gastrointestinal disorders were the most commonly reported cases ( n  = 12)., Conclusions: Several ADRs were newly reported only in children younger than 8-year-old in our research, including Horner's syndrome and methemoglobinemia. We recommended that the clinical practitioners should pay attention to the ADRs both in instruction and beyond the label. Take close care of children and timely intervene when the treatment is inevitable.

Introduction: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity., Area Covered: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety., Expert Opinion: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

Introduction: Combat-related wound infections complicate the recovery of wounded military personnel, contributing to overall morbidity and mortality. Wound infections in combat settings present unique challenges because of the size and depth of the wounds, the need to administer emergency care in the field, and the need for subsequent treatment in military facilities. Given the increase in multidrug-resistant pathogens, a novel, broad-spectrum antibiotic is desired across this continuum of care when the standard of care fails. Omadacycline was FDA-approved in 2018 for treatment of adults with acute bacterial skin and skin structure infections (ABSSSI), as well as community-acquired bacterial pneumonia (CABP). It is a broad-spectrum antibiotic with activity against gram-positive, gram-negative, and atypical bacterial pathogens, including multidrug-resistant species. Omadacycline can overcome commonly reported tetracycline resistance mechanisms, ribosomal protection proteins, and efflux pumps, and is available in once-daily intravenous or oral formulations. In this review, we discuss the potential role of omadacycline, which is included in the Department of Defense Formulary, in the context of combat wound infections., Materials and Methods: A literature review was undertaken for manuscripts published before July 21, 2023. This included a series of publications found via PubMed and a bibliography made publicly available on the Paratek Pharmaceuticals, Inc. website. Publications presenting primary data published in English on omadacycline in relation to ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter species) pathogens and Clostridioides difficile, including in vitro, in vivo, and clinical data were included., Results: Of 260 identified records, 66 were included for evidence review. Omadacycline has in vitro activity against almost all the ESKAPEE pathogens, apart from P. aeruginosa. Importantly, it has activity against the four most prevalent bacterial pathogens that cause wound infections in the military healthcare system: S. aureus, including methicillin-resistant S. aureus, A. baumannii, K. pneumoniae, and E. coli. In vivo studies in rats have shown that omadacycline is rapidly distributed in most tissues, with the highest tissue-to-blood concentration ratios in bone mineral. The clinical efficacy of omadacycline has been assessed in three separate Phase 3 studies in patients with ABSSSI (OASIS-1 and OASIS-2) and with CABP (OPTIC). Overall, omadacycline has an established safety profile in the treatment of both ABSSSI and CABP., Conclusions: Omadacycline has broad-spectrum activity, the option to be orally administered and an established safety profile, making it a potentially attractive replacement for moxifloxacin in the military individual first aid kit, especially when accounting for the increasing resistance to fluoroquinolones. Further studies and clinical evaluation are warranted to support broader use of omadacycline to treat combat wound infections in the military healthcare system., (© The Association of Military Surgeons of the United States 2023.)

Background: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older., Objective: The objective of this study was to provide evidence-based recommendations for the management of acne., Methods: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations., Results: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements., Limitations: Analysis is based on the best available evidence at the time of the systematic review., Conclusions: These guidelines provide evidence-based recommendations for the management of acne vulgaris., Competing Interests: Conflicts of interest Rachel V.S. Reynolds, MD, Carol E. Cheng, MD, Kelly Druby, Megha M. Tollefson, MD, and Jung Min Han, PharmD, MS, have no relationships to disclose. Howa Yeung, MD, MS, serves as an investigator for American Acne & Rosacea Society, Department of Veterans Affairs, and National Institutes of Health receiving grants and research funding; as an independent contractor for American Academy of Dermatology and Journal of the American Medical Association receiving fees; as a speaker/faculty educator for Dermatology Digest receiving honoraria. Fran Cook-Bolden, MD, serves as an advisory board member for AbbVie, Dermavant Sciences, Inc., Galderma Global, Novartis, Ortho Dermatologics, and Pfizer Inc. receiving honoraria; as an investigator for Arcutis Biotherapeutics receiving grant and research funding; as a speaker for Galderma Laboratories, LP, Journey Medical Corporation, and Ortho Dermatologics receiving honoraria; as others for Topix Pharmaceuticals, Inc. receiving other financial benefit. Seemal R. Desai, MD, serves an advisory board member for Foundation for Research & Education of Dermatology receiving fees; as a consultant for AbbVie, Allergan, Inc, Almirall, Amgen, Apogee, Avita, Ballature Beauty, Beiersdorf, Inc., Bristol-Myers Squibb, Candela Corporation, Cassiopea S.p.A., Castle Biosciences, Cutera, Inc., Dermavant Sciences, Dermira, Eli Lilly and Company, EPI Health, Ferndale Laboratories, Inc., Foamix, Galderma Laboratories, LP, Gore Range Capital, Hyphens Pharma, Incyte Corporation, Janssen Pharmaceuticals, Inc, Johnson and Johnson, Leo Pharma Inc., L'Oreal USA Inc., Lyceum Health, Ortho Dermatologics, Pfizer Inc., Revision Skincare, Sanofi/Regeneron, Scientis, Skin Science Advisors, UCB, Verrica Pharmaceuticals Inc., and VYNE Therapeutics receiving fees, honoraria, and/or stock options; as an investigator for AOBiome, LLC, Atacama Therapeutics, Dermavant Sciences, Incyte Corporation, and SkinMedica, Inc. receiving grants and research funding; as a speaker for AbbVie, Dermira, Galderma Laboratories, LP., and Pfizer Inc. receiving fees; as a stockholder for Gore Range Capital; as other role for Medscape receiving fees. Esther E. Freeman, MD, PhD, serves as an investigator for International League of Dermatologic Societies and National Institutes of Health receiving grants and research funding; as an author for UptoDate, Inc. and British Journal of Dermatology, receiving honoraria or salary; as a speaker for Harvard University. Jonette E. Keri, MD, PhD, serves as an advisory board member for Ortho Dermatologics receiving honoraria; as a consultant for Almirall receiving fees; as an investigator for Galderma USA receiving grants and research funding; as a speaker for Foamix Pharmaceuticals Ltd and VYNE Therapeutics receiving honoraria. Linda F. Stein Gold, MD, serves as an advisory board member for AbbVie, Almirall, Aqua, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., GlaxoSmithKline, Incyte Corporation, La Roche-Posay Laboratorie Pharmaceutique, LEO Pharma, US, Lilly ICOS LLC, Merz Pharmaceuticals, LLC, Pfizer Inc., Promius Pharmaceuticals, Sanofi/Regeneron, Taro Pharm, and Valeant Pharmaceuticals International receiving honoraria; as a consultant for AnaptysBio, BMS, Botanix Pharmaceuticals, Cutera, Inc., Incyte Corporation, Janssen Scientific Affairs, LLC, Sol-Gel Technologies, Taro Pharm, The Acne Store, and UCB receiving honoraria or grants and research funding; as an investigator for AbbVie, Allergan, Inc., AnaptysBio, Galderma Laboratories, L.P., Leo Pharma Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., Topica, and Valeant Pharmaceuticals International receiving grants and research funding; as a speaker for Actavis, Almirall, BMS, Dermira, Pfizer Inc., Sanofi/Regeneron, Sun Pharmaceutical Industries Ltd., and VYNE Therapeutics receiving honoraria. Jerry K. L. Tan, MD, serves as an advisory board member for Abbott Laboratories, Cutera, Inc., Galderma Laboratories, L.P, and Sun Pharmaceutical Industries Ltd receiving honoraria or grants and research funding; as a consultant for Bausch Health, Boots, Galderma Research & Development, LLC, and Loreal Research and Innovation receiving honoraria; as an independent contractor for Norvatis receiving fees; as an investigator for Allergan, AnaptysBio, Cutera, Inc., Eli Lilly and Co., Galderma Laboratories, L.P, Lilly ICOS LLC, Pfizer, and UCB for receiving grants and research funding; as a speaker for Bausch Health, LEO Laboratories Ltd (LEO Pharma), and Vichy Laboratories receiving honoraria. Jonathan S. Weiss, MD, serves as an advisory board member for Bristol-Myers Squibb, Dermavant Sciences, Foamix, Galderma Laboratories, L.P., Incyte Corporation, Novartis, and UCB receiving honoraria; as a consultant for Arcutis, Inc., Biofrontera, Cutera, Inc., Leo Pharma Inc, Ortho Dermatologics, and UCB receiving fees or honoraria; as an investigator for AbbVie, Bausch Health, Biofrontera, Bristol-Myers Squibb, Cutera, Inc., Dermavant Sciences, Foamix, Galderma Laboratories, L.P., LEO Pharma, Mindera, Moberg Pharma North, America LLC, Novartis, Palvella Therapeutics, and Verrica Pharmaceuticals Inc receiving grants and research funding; as a speaker for AbbVie, Arcutis, Inc., Galderma Laboratories, L.P., Ortho Dermatologics, Regeneron, and Sanofi Genzyme receiving honoraria. Peggy A. Wu, MD, serves as others for UptoDate, Inc. receiving honoraria. Andrea L. Zaenglein, MD, serves as a consultant for Church & Dwight Co., Inc. and UCB receiving fees or honoraria; as an investigator for AbbVie, Arcutis Biotherapeutics, Biofrontera AG, Galderma Laboratories, L.P., and Incyte Corporation receiving grants and research funding. John S. Barbieri, MD, MBA serves as investigator for National Institutes of Health and National Psoriasis Foundation receiving grants and research funding., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia is associated with poor clinical outcomes and increased mortality. Clinical data regarding the optimal treatment of CRAB is limited, and combination therapy is often preferred. Eravacycline has demonstrated in-vitro activity against A. baumannii and has been considered for the treatment of pulmonary infections caused by CRAB., Objective: The objective of this case series was to describe clinical outcomes associated with eravacycline when utilized as part of a combination regimen for the treatment of CRAB pneumonia at a county hospital., Methods: A retrospective chart review was conducted from April 1, 2020, to October 1, 2020, which included hospitalized patients ≥18 years of age, diagnosed with coronavirus disease 2019 (COVID-19), with a sputum culture positive for CRAB, and receipt of at least one dose of eravacycline. The primary outcome studied was clinical resolution of CRAB pneumonia. A key secondary outcome was microbiological resolution., Results: A total of 24 patients received combination eravacycline therapy for a median of 10.5 days. Overall, 17 (71%) patients demonstrated clinical resolution of CRAB pneumonia. Repeat sputum cultures post-treatment were collected in 17 (71%) patients, of which 12 (71%) achieved microbiological resolution. No adverse events attributable to eravacycline were identified., Conclusion: With limited viable salvage treatment options, combination eravacycline therapy showed favorable microbiological and clinical outcomes in patients with CRAB pneumonia. In light of this, eravacycline could be considered as a potential treatment option when designing CRAB pneumonia salvage therapy regimens., (© 2024 Pharmacotherapy Publications, Inc.)

Antimicrobial resistance is a growing threat to public health and an increasingly common problem for acute care physicians to confront. Several novel antibiotics have been approved in the past decade to combat these infections; however, physicians may be unfamiliar with how to appropriately utilize them. The purpose of this review is to evaluate novel antibiotics active against resistant gram-negative bacteria and highlight clinical information regarding their use in the acute care setting. This review focuses on novel antibiotics useful in the treatment of infections caused by resistant gram-negative organisms that may be seen in the acute care setting. These novel antibiotics include ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilistatin/relebactam, cefiderocol, plazomicin, eravacycline, and omadacycline. Acute care physicians should be familiar with these novel antibiotics so they can utilize them appropriately., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Oral tetracyclines have been used in clinical practice for over 60 years. One of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with skin and soft infections (SSTIs), including acute bacterial skin and skin structure infections (ABSSSIs). The 2014 Infectious Diseases Society of America (IDSA) skin and soft tissue guideline strongly recommends sulfamethoxazole/trimethoprim, clindamycin, and tetracyclines as oral treatment options for patients with purulent SSTIs, especially when methicillin-resistant Staphylococcus aureus is of clinical concern. Despite the long-standing use of tetracyclines, practice patterns indicate that they are often considered after other guideline-concordant oral options for the treatment of patients with SSTIs. Clinicians may therefore be less familiar with the clinical data associated with use of commercially available tetracycline agents for treatment of patients with SSTI. This review summarizes the literature on the use of oral tetracyclines (ie, doxycycline, minocycline, and omadacycline) for the treatment of adult patients with SSTIs. As part of this review, we describe their common mechanisms of resistance, susceptibility profiles against common SSTI pathogens, pharmacokinetics and pharmacodynamics, and comparative clinical data., (© 2021 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Background: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes., Objective: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin., Methods: A prospective, international cohort study performed between October 2018 and August 2019., Results: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain., Limitations: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline., Conclusion: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity., Competing Interests: Conflicts of interest Dr Tzellos has reported relationships with AbbVie, UCB, and Sanofi Genzyme. Dr Guillem has received honoraria from AbbVie and Novartis as a consultant and has given nonpaid lectures for AbbVie, Brothier, Cicaplus, Coloplast, Inresa, and Novartis. Dr Giamarellos-Bourboulis has received honoraria from Abbott CH, Angelini Italy, bioMérieux Inc, InflaRx GmbH, MSD Greece, and XBiotech Inc; independent educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, bioMérieux Inc, InflaRx GmbH, ThermoFisher Brahms GmbH, and XBiotech Inc; and funding from the FrameWork 7 program HemoSpec (granted to the National and Kapodistrian University of Athens), the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). Dr Jemec has received honoraria from AbbVie, Chemocentryx, Coloplast, Incyte, Inflarx, Kymera, Leo Pharma, Novartis, and UCB for participation on advisory boards; grants from AbbVie, AstraZeneca, Inflarx, Janssen-Cilag, Leo Pharma, Novartis, Regeneron, and Sanofi for participation as an investigator; speaker honoraria from AbbVie, Boehringer Ingelheim, Galderma, and Novartis; and unrestricted departmental grants from Leo Pharma and Novartis. Dr Katoulis has reported relationships with AbbVie, Novartis, Genesis Pharma, Mylan, Janssen, Leo Pharma, and Lilly. Dr Koenig was an investigator, speaker, or advisor for AbbVie, Braun-Stiftung, and Celgene. Dr Lazaridou has received speaker honoraria, and/or honoraria for participation in advisory boards, and/or grants from AbbVie, Novartis, Genesis Pharma, Mylan, Pfizer, Janssen, Leo Pharma, Roche, Lilly, UCB, and Sanofi. Dr Matusiak reports personal fees from AbbVie, Amgen, Galapagos, InflaRx, Janssen-Cilag, LEO, Menlo, Novartis, Pfizer, Pierre Fabre, Regeneron, Trevi, and UCB. Dr Pinter has been an investigator, speaker, or advisor for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough, and UCB Pharma. Dr Romani has reported relationships with AbbVie, Novartis, Leo Pharma, Janssen, Almirall, and Isdín. Dr Saunte was paid as a consultant for advisory board meeting by AbbVie, Janssen, Sanofi, and Leo Pharma and received speaker honoraria and/or grants from AbbVie, Pfizer, Galderma, Novartis, and Leo Pharma during the last 5 years. Dr Szepietowski reports personal fees from AbbVie, Amgen, Galapagos, InflaRx, Janssen-Cilag, LEO, Menlo, Novartis, Pfizer, Pierre Fabre, Regeneron, Sandoz, Sanofi, Sienna, Trevi, and UCB. Dr Trigoni has reported relationships with AbbVie, UCB, Novartis, and LEO. Dr Trigoni has reported relationships with AbbVie, UCB, Novartis, and LEO. Dr van der Zee has received honoraria from AbbVie. Drs van Straalen, Benhadou, Cuencia-Barrales, Daxhelet, Daoud, Efthymiou, Marzano, Molina-Leyva, Moltrasio, Potenza, Skroza, Stergianou, and Vilarrasa have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the safety and efficacy of omadacycline by body mass index (BMI) in adults with community-acquired bacterial pneumonia (CABP) from a Phase III trial., Methods: Patients hospitalized for suspected CABP were randomized 1:1 to receive intravenous omadacycline or moxifloxacin, with an optional transition to oral, for a total of 7-14 days. Early clinical response (ECR) was assessed 72-120 h after receipt of the first dose, and clinical success was assessed 5-10 days after the last dose (post-treatment evaluation [PTE]). ECR was defined as improvement in at least two CABP symptoms with no worsening of other symptoms or use of rescue antibacterial treatment; success at PTE was defined as resolution of signs and symptoms to the extent that further antibacterial therapy was unnecessary. Safety evaluations included treatment-emergent adverse events and laboratory measures. Between-treatment comparisons were made by World Health Organization BMI categories and by diabetes history., Results: Distribution of patients in the normal weight, overweight, and obese subgroups was fairly even. Clinical success for omadacycline-treated patients at ECR were similar across ascending BMI groups (OMC: 82.9%, 80.5%, 76.9%; MOX: 88.6%, 80.7%, 76.9%). Outcomes by diabetes status were generally similar in omadacycline- and moxifloxacin-treated patients. Patients who had clinical success or clinical stability at ECR generally showed continued clinical success at PTE. Safety profiles for omadacycline and moxifloxacin were largely similar across BMI subgroups and by diabetes history., Conclusion: The omadacycline fixed-dosing strategy showed consistent safety and efficacy in patients with CABP of different body sizes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cutaneous rosacea is a common inflammatory skin disorder that often presents with facial papulopustular lesions that are frequently bothersome to patients. Studies have shown oral sarecycline to be effective and safe for acne, with a low risk of side effects that are historically associated with other tetracycline-class drugs such as doxycycline and minocycline, in addition to offering a reduced risk of emergence of resistant bacteria due to its narrow-spectrum of antibiotic activity. Oral sarecycline is FDA-approved for the treatment of acne (2018)., Objective: A pilot study to evaluate the efficacy and safety of oral sarecycline in papulopustular rosacea., Methods: A 12-week, prospective, parallel-group, investigator-blinded, controlled pilot study was completed evaluating once-daily sarecycline, using weight-based oral dosing as recommended for acne vs control (multivitamin tablet), for the treatment of moderate-to-severe papulopustular rosacea in adult subjects (n=102), aged ≥18 years. The primary efficacy endpoint was Investigator’s Global score (IGA; clear or almost clear) and percent reduction in inflammatory lesion count at week 12. Safety and tolerability assessments were performed as well., Results: A total of 102 subjects were randomized; 97 completed the study. At week 12, IGA improvement was significantly greater for oral sarecycline when compared to the control (P<0.0001). Furthermore, absolute and percent reductions in inflammatory lesion counts were significantly greater in the sarecycline group for all weeks (4, 8, and 12) when compared to the control (P<0.001). Significant improvement in facial burning, erythema, and pruritus was reported in the sarecycline group, when compared to the control (P<0.05). No serious AEs were reported., Conclusion: Sarecycline was effective, safe, and well-tolerated for treating papulopustular rosacea in adults with marked superiority in efficacy compared to subjects in the control group. With its narrow-spectrum activity, oral sarecycline may be a good option for the treatment of papulopustular rosacea. Additional studies are warranted to confirm the positive results of this pilot study.

Objective: Community-acquired bacterial pneumonia (CABP) is a major clinical burden worldwide. In the phase III OPTIC study (NCT02531438) in CABP, omadacycline was found to be non-inferior to moxifloxacin for investigator-assessed clinical response (IACR) at post-treatment evaluation (PTE, 5-10 days after last dose). This article reports the efficacy findings, as specified in the European Medicines Agency (EMA) guidance., Methods: Patients were randomized 1:1 to omadacycline 100 mg intravenously (every 12 h for two doses, then every 24 h) with optional transition to 300 mg orally after 3 days, or moxifloxacin 400 mg intravenously (every 24 h) with optional transition to 400 mg orally after 3 days. The total treatment duration was 7-14 days. The primary endpoint for EMA efficacy analysis was IACR at PTE in patients with Pneumonia Patient Outcomes Research Team (PORT) risk class III and IV., Results: In total, 660 patients were randomized as PORT risk class III and IV. Omadacycline was non-inferior to moxifloxacin at PTE. The clinical success rates were 88.4% and 85.2%, respectively [intent-to-treat population; difference 3.3; 97.5% confidence interval (CI) -2.7 to 9.3], and 92.5% and 90.5%, respectively (clinically evaluable population; difference 2.0; 97.5% CI 3.2-7.4). Clinical success rates with omadacycline and moxifloxacin were similar against identified pathogens and across key subgroups., Conclusions: Omadacycline was non-inferior to moxifloxacin for IACR at PTE, with high clinical success across pathogen types and patient subgroups., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction : The global coronavirus disease-2019 (COVID-19) pandemic has posed a critical challenge to the research community as well as to the healthcare systems. Severe COVID-19 patients are at a higher risk of developing serious complications and mortality. There is a dire need for safe and effective pharmacotherapy for addressing unmet needs of these patients. Concomitant use of dexamethasone and tetracyclines, by virtue of their immunomodulatory and other relevant pharmacological properties, offers a potential strategy for synergy aimed at improving clinical outcomes. Areas covered : Here we review the potential benefits of combining dexamethasone and tetracyclines (minocycline or doxycycline) for the management of severe COVID-19 patients. We have critically examined the evidence obtained from in silico, experimental, and clinical research. We have also discussed the plausible mechanisms, advantages, and drawbacks of this proposed combination therapy for managing severe COVID-19. Expert opinion : The concomitant use of dexamethasone and one of the tetracyclines among severe COVID-19 patients offers several advantages in terms of additive immunomodulatory effects, cost-effectiveness, wide-availability, and well-known pharmacological properties including adverse-effect profile and contraindications. There is an urgent need to facilitate pilot studies followed by well-designed and adequately-powered multicentric clinical trials to generate conclusive evidence related to utility of this approach.

Purpose: This study aimed to elucidate the association between postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) and clinicopathological factors and intraoperative and postoperative epidural or intravenous patient-controlled analgesia (IV-PCA)., Methods: We reviewed data of 116 patients who underwent distal pancreatectomy at Gunma University Hospital from October 2000 to October 2019. Clinical POPF was defined as the International Study Group of Pancreatic Fistula grade B or C., Results: Intraoperative and postoperative analgesia included fentanyl-mediated IV-PCA (n = 37, 32%), fentanyl-mediated epidural analgesia (n = 39, 34%), and morphine-mediated epidural analgesia (n = 40, 34%). All patients had received analgesia. Clinical POPF occurred in 34 of the 116 (29%) DP cases. Male sex (P = 0.035) and the length of operation time (P = 0.0070) were significant risk factors of clinical POPF. Furthermore, a thick pancreas was more likely to cause clinical POPF than a thin one (P = 0.052). No statistically significant difference was found between other factors, including intraoperative and postoperative analgesia (P = 0.95), total median oral morphine equivalents (P = 0.23), and clinical POPF., Conclusion: Intraoperative and postoperative epidural analgesia and IV-PCA are not associated with clinical POPF after DP. Our results suggest that morphine and fentanyl can be used as IV-PCA or epidural analgesia.

Introduction: Sarecycline is a novel, tetracycline-class antibiotic specifically designed to treat inflammatory acne. It offers a narrow spectrum of activity (mainly against Cutinebacterium acnes), and it shows less in vitro activity than other tetracyclines against enteric Gram-negative bacteria, offering advantages over older tetracyclines by decreasing the disruption of the gastrointestinal microbiome and the likelihood of developing bacterial resistance., Areas Covered: The drug's pharmacology, safety profile, and clinical efficacy are discussed. Results of phase I, II and III clinical trials have shown that 1.5 mg/kg/day sarecycline is safe, well tolerated and more effective than placebo in treating inflammatory acne in patients 9 years old and older. Furthermore, sarecycline's narrow spectrum of activity leads to a lower incidence of undesirable off-target antibacterial effects and consequently less adverse events such as diarrhea, fungal overgrowth and vaginal candidiasis., Expert Opinion: Sarecycline could become the first-line antibiotic therapy used in acne in the near future as it is an effective option for treating inflammatory acne lesions. Due to its narrow spectrum of activity, it could have a more adequate safety profile than older tetracyclines; however, head-to-head trials comparing the efficacy and safety profile of sarecycline with other tetracyclines are still needed to prove sarecycline's superiority.

Background: Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class. It is approved in the USA to treat adults with acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia., Objectives: This phase I, open-label study evaluated the effect of a potential drug-drug interaction of verapamil-a known P-glycoprotein (P-gp) inhibitor-with omadacycline on the pharmacokinetic profile of omadacycline in healthy adults. The safety and tolerability of omadacycline taken alone and in combination with verapamil were also evaluated., Methods: A single oral dose of 240 mg verapamil extended release (ER) was given 2 h prior to a single oral dose of 300 mg omadacycline., Results: Ten (83.3%) of the 12 participants enrolled in the study completed the study, and all enrolled participants were included in the safety and pharmacokinetic populations. An increase of 14-25% in systemic exposure to omadacycline was seen when administered following a single oral dose of 240 mg verapamil ER compared with omadacycline alone, as measured by the area under the concentration-time curve (AUC) from time 0 to 24 h after dosing (AUC 0-24 ), from time 0 to the last quantifiable concentration (AUC 0-t ), from time 0 extrapolated to infinity (AUC 0-inf ), and by maximum (peak) observed plasma concentration (C max ). Treatment-emergent adverse events were reported by one participant (nausea and headache)., Conclusions: These findings suggest that, if given with a known P-gp inhibitor, dose adjustment of oral omadacycline is not warranted based on small increases in absorption and systemic exposure. No safety signals were identified.

Broad spectrum tetracyclines are a well-known, widely used, and often successful treatment for use in inflammatory skin pathologies such as acne and rosacea. However, the steady rise of antibiotic resistance and gut dysbiosis associated with broad spectrum tetracyclines emphasizes the importance and responsibility of antibiotic stewardship. Narrow spectrum antibiotics have become increasingly important therapies to slow the progression of resistance as well as decrease negative side effect profiles, particularly those associated with broad spectrum tetracyclines. This case shows the successful treatment of periorificial dermatitis with a novel, narrow spectrum tetracycline, sarecycline, in a patient with underlying Crohn&rsquo;s. J Drugs Dermatol. 2021;20(1):98-100. doi:10.36849/JDD.5678.

Oral tetracyclines are the most widely prescribed systemic antibiotic for acne. Synthesis of efficacy and safety of traditional and novel oral tetracyclines is highly informative to clinical practice. We conducted a systematic search of PubMed to identify large interventional and observational studies utilizing oral tetracyclines as an acne treatment. We identified 13 articles meeting inclusion for this review, which represented 226,019 pediatric and adult acne patients. Oral tetracyclines that were included in this systematic review were sarecycline (a novel narrow-spectrum tetracycline), doxycycline, minocycline, and tetracycline. Based on shared and divergent outcome measures, different oral tetracyclines were variably effective against facial acne. Sarecycline also demonstrated efficacy in truncal acne. Members of the oral tetracycline class also differed in their ability to minimize antibiotic resistance and gut dysbiosis. J Drugs Dermatol. 2020;19:11(Suppl):s4-11.

Objective: Sarecycline is a new oral tetracycline antibiotic recently approved by the US Food and Drug Administration. The aim of this article was to evaluate the data from published clinical trials of sarecycline in the treatment of acne, review the drug's pharmacology, and understand how this new medication may apply to clinical practice. Data Sources: A systematic literature review was performed using the terms sarecycline (Seysara), P005672, and WC-3035 in the MEDLINE and EMBASE databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles in English between January 2000 and April 2019 relating to clinical trials, pharmacology, safety, and microbiological profile were evaluated. Data Synthesis: In a phase 3 clinical trial (SC1401), absolute change from baseline in facial inflammatory lesion count at week 12 was -15.3 for the sarecycline arm and -10.1 for placebo ( P < 0.01). In another phase 3 clinical trial (SC1402), the absolute change in this category was -15.7 for sarecycline and -10.7 for placebo ( P < 0.01). Mean percentage change in facial inflammatory lesion count was higher in the sarecycline group than in the placebo group in both studies ( P < 0.01). Relevance to Patient Care and Clinical Practice: The 1.5-mg/kg sarecycline dose has efficacy in reducing inflammatory lesions, is well tolerated, and has more targeted antimicrobial activity, which may help reduce the risk of developing antibiotic resistance. Conclusions: This novel, once-daily treatment may represent a useful treatment for patients with moderate to severe acne.

Omadacycline is a novel aminomethylcycline antibiotic developed as a once-daily, intravenous and oral treatment for acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP). Omadacycline, a derivative of minocycline, has a chemical structure similar to tigecycline with an alkylaminomethyl group replacing the glycylamido group at the C-9 position of the D-ring of the tetracycline core. Similar to other tetracyclines, omadacycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Omadacycline possesses broad-spectrum antibacterial activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical bacteria. Omadacycline remains active against bacterial isolates possessing common tetracycline resistance mechanisms such as efflux pumps (e.g., TetK) and ribosomal protection proteins (e.g., TetM) as well as in the presence of resistance mechanisms to other antibiotic classes. The pharmacokinetics of omadacycline are best described by a linear, three-compartment model following a zero-order intravenous infusion or first-order oral administration with transit compartments to account for delayed absorption. Omadacycline has a volume of distribution (V d ) ranging from 190 to 204 L, a terminal elimination half-life (t ½ ) of 13.5-17.1 h, total clearance (CL T ) of 8.8-10.6 L/h, and protein binding of 21.3% in healthy subjects. Oral bioavailability of omadacycline is estimated to be 34.5%. A single oral dose of 300 mg (bioequivalent to 100 mg IV) of omadacycline administered to fasted subjects achieved a maximum plasma concentration (C max ) of 0.5-0.6 mg/L and an area under the plasma concentration-time curve from 0 to infinity (AUC 0-∞ ) of 9.6-11.9 mg h/L. The free plasma area under concentration-time curve divided by the minimum inhibitory concentration (i.e., fAUC 24h /MIC), has been established as the pharmacodynamic parameter predictive of omadacycline antibacterial efficacy. Several animal models including neutropenic murine lung infection, thigh infection, and intraperitoneal challenge model have documented the in vivo antibacterial efficacy of omadacycline. A phase II clinical trial on complicated skin and skin structure infection (cSSSI) and three phase III clinical trials on ABSSSI and CABP demonstrated the safety and efficacy of omadacycline. The phase III trials, OASIS-1 (ABSSSI), OASIS-2 (ABSSSI), and OPTIC (CABP), established non-inferiority of omadacycline to linezolid (OASIS-1, OASIS-2) and moxifloxacin (OPTIC), respectively. Omadacycline is currently approved by the FDA for use in treatment of ABSSSI and CABP. Phase II clinical trials involving patients with acute cystitis and acute pyelonephritis are in progress. Mild, transient gastrointestinal events are the predominant adverse effects associated with use of omadacycline. Based on clinical trial data to date, the adverse effect profile of omadacycline is similar to studied comparators, linezolid and moxifloxacin. Unlike tigecycline and eravacycline, omadacycline has an oral formulation that allows for step-down therapy from the intravenous formulation, potentially facilitating earlier hospital discharge, outpatient therapy, and cost savings. Omadacycline has a potential role as part of an antimicrobial stewardship program in the treatment of patients with infections caused by antibiotic-resistant and multidrug-resistant Gram-positive [including methicillin-resistant Staphylococcus aureus (MRSA)] and Gram-negative pathogens.

Introduction : Complicated intra-abdominal infections (cIAIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Several medical needs remain unmet, related to the pharmacokinetic capacities of the available drugs and their limited spectrum of activity for targeting multidrug-resistant Gram-negative and Gram-positive bacteria. Eravacycline, a new synthetic fluorocycline, could have useful properties in cIAIs. Areas covered : The antimicrobial activity of eravacycline against the microorganisms most frequently cultured in cIAIs has been confirmed in worldwide panels of clinical isolates, including enterococci, ESBL-producing Enterobacteriaceae, Acinetobacter baumannii and anaerobes. Pharmacokinetic data demonstrate interesting characteristics with good tissue concentrations including biliary tract and digestive tissues. At a conventional dosage of 1 mg/kg q12h, no adjustment is required on the basis of race or gender, or in elderly (≥ 65 years old) patients, patients with renal impairment or patients undergoing hemodialysis. Phase 2 and 3 trials assessing the clinical efficacy and safety of eravacycline demonstrated non-inferiority versus carbapenems and a good safety profile. Expert opinion : Eravacycline may be particularly suitable for the treatment of cIAIs. Results from clinical trials and real-world data are now expected in specific subgroups of patients to confirm the safety profile and efficacy observed in registration trials.

Purpose: Eravacycline is a broad-spectrum, intravenous fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections in adults. A 60-minute infusion is recommended for each infused dose. Compatibility data that may allow convenient Y-site administration of eravacycline with other parenteral medications are unavailable. We aimed to determine the physical compatibility of eravacycline with other intravenous medications by simulated Y-site administration., Methods: Eravacycline was reconstituted according to published prescribing information and diluted with 0.9% sodium chloride to a concentration of 0.6 mg/mL. Simulated Y-site administration was performed by mixing 5 mL of eravacycline with an equal volume of 51 other intravenous medications, including crystalloid and carbohydrate hydration fluids and 20 antimicrobials. Secondary medications were assessed at the upper range of concentrations considered standard for intravenous infusion. Mixtures underwent visual inspection and turbidity measurement immediately on mixture and at 3 subsequent time points (30, 60, and 120 minutes after admixture), and pH was measured at 60 minutes for comparison with the baseline value of the secondary medication., Findings: Eravacycline was physically compatible with 41 parenteral drugs (80%) by simulated Y-site administration. Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, colistimethate sodium, furosemide, meropenem, meropenem/vaborbactam, micafungin sodium, propofol, and sodium bicarbonate., Implications: Eravacycline for injection was physically compatible with most parenteral medications assessed. Pharmacists and nurses should be knowledgeable of the observed incompatibilities with eravacycline to prevent the unintentional mixing of incompatible intravenous medications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pathogen resistance and safety concerns limit oral antibiotic options for the treatment of acute bacterial skin and skin structure infections (ABSSSI). We aimed to compare the efficacy and safety of once-daily oral omadacycline, an aminomethylcycline antibiotic, versus twice-daily oral linezolid for treatment of ABSSSI., Methods: In this phase 3, double-blind, randomised, non-inferiority study, eligible adults with ABSSSI at 33 sites in the USA were randomly assigned (1:1) to receive omadacycline (450 mg orally every 24 h over the first 48 h then 300 mg orally every 24 h) or linezolid (600 mg orally every 12 h) for 7-14 days. Randomisation was done via an interactive response system using a computer-generated schedule, and stratified by type of infection (wound infection, cellulitis or erysipelas, or major abscess) and receipt (yes or no) of allowed previous antibacterial treatment. Investigators, funders, and patients were masked to treatment assignments. Primary endpoints were early clinical response, 48-72 h after first dose, in the modified intention-to-treat (mITT) population (randomised patients without solely Gram-negative ABSSSI pathogens at baseline), and investigator-assessed clinical response at post-treatment evaluation, 7-14 days after the last dose, in the mITT population and clinically evaluable population (ie, mITT patients who had a qualifying infection as per study-entry criteria, received study drug, did not receive a confounding antibiotic, and had an assessment of outcome during the protocol-defined window). The safety population included randomised patients who received any amount of study drug. We set a non-inferiority margin of 10%. This study is registered with ClinicalTrials.gov, NCT02877927, and is complete., Findings: Between Aug 11, 2016, and June 6, 2017, 861 participants were assessed for eligibility. 735 participants were randomly assigned, of whom 368 received omadacycline and 367 received linezolid. Omadacycline (315 [88%] of 360) was non-inferior to linezolid (297 [83%] of 360) for early clinical response (percentage-point difference 5·0, 95% CI -0·2 to 10·3) in the mITT population. For investigator-assessed clinical response at post-treatment evaluation, omadacycline was non-inferior to linezolid in the mITT (303 [84%] of 360 vs 291 [81%] of 360; percentage-point difference 3·3, 95% CI -2·2 to 9·0) and clinically evaluable (278 [98%] of 284 vs 279 [96%] of 292; 2·3, -0·5 to 5·8) populations. Mild to moderate nausea and vomiting were the most frequent treatment-emergent adverse events in omadacycline (111 [30%] of 368 and 62 [17%] of 368, respectively) and linezolid (28 [8%] of 367 and 11 [3%] of 367, respectively) groups., Interpretation: Once-daily oral omadacycline was non-inferior to twice-daily oral linezolid in adults with ABSSSI, and was safe and well tolerated. Oral-only omadacycline represents a new treatment option for ABSSSI, with potential for reduction in hospital admissions and cost savings., Funding: Paratek Pharmaceuticals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

On 27 August, 2018, the US Food and Drug Administration approved eravacycline, a fluorocycline antimicrobial agent within the tetracycline class of antibacterial drugs, for the treatment of complicated intra-abdominal infections in patients aged 18 years and older. This decision was based on substantial clinical and pre-clinical data, including rigorous pharmacokinetic and pharmacodynamic work. This paper examines the in-vivo pharmacokinetic/pharmacodynamic work that led to the approval of eravacycline and explores how this important new antibiotic may be used to treat aggressive multidrug-resistant infections in the years ahead.

Background: Increasing antimicrobial resistance among pathogens that cause complicated intraabdominal infections (cIAIs) supports the development of new antimicrobials. Eravacycline, a novel member of the fluorocycline family, is active against multidrug-resistant bacteria including extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae., Methods: IGNITE4 was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either eravacycline 1 mg/kg every 12 hours or meropenem 1 g every 8 hours intravenously for 4-14 days. The primary objective was to demonstrate statistical noninferiority (NI) in clinical cure rates at the test-of-cure visit (25-31 days from start of therapy) in the microbiological intent-to-treat population using a NI margin of 12.5%. Microbiological outcomes and safety were also evaluated., Results: Eravacycline was noninferior to meropenem in the primary endpoint (177/195 [90.8%] vs 187/205 [91.2%]; difference, -0.5%; 95% confidence interval [CI], -6.3 to 5.3), exceeding the prespecified margin. Secondary endpoints included clinical cure rates in the modified ITT population (231/250 [92.4%] vs 228/249 [91.6%]; difference, 0.8; 95% CI, -4.1, 5.8) and the clinically evaluable population (218/225 [96.9%] vs 222/231 [96.1%]; (difference, 0.8; 95% CI -2.9, 4.5). In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 87.5% (14/16) and 84.6% (11/13) in the eravacycline and meropenem groups, respectively. Eravacycline had relatively low rates of adverse events for a drug of this class, with less than 5%, 4%, and 3% of patients experiencing nausea, vomiting, and diarrhea, respectively., Conclusions: Treatment with eravacycline was noninferior to meropenem in adult patients with cIAI, including infections caused by resistant pathogens., Clinical Trials Registration: NCT01844856., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Early clinical response (ECR) is a new endpoint to determine whether a drug should be approved for community-acquired bacterial pneumonia in the United States. The Omadacycline for Pneumonia Treatment In the Community (OPTIC) phase III study demonstrated noninferiority of omadacycline to moxifloxacin using this endpoint. This study describes the performance of the ECR endpoint and clinical stability relative to a posttreatment evaluation (PTE) of clinical success., Methods: ECR was defined as symptom improvement 72-120 hours after the first dose of study drug (ECR window), no use of rescue antibiotics, and patient survival. Clinical success at PTE was an investigator assessment of success. Clinical stability was defined based on vital sign stabilization, described in the American Thoracic Society and Infectious Diseases Society of America community-acquired pneumonia treatment guidelines., Results: During the ECR window, ECR was achieved in 81.1% and 82.7% of omadacycline and moxifloxacin patients, respectively. Similar numbers of patients achieved clinical stability in each treatment group (omadacycline 74.6%, moxifloxacin 77.6%). The proportion of patients with improved symptoms who were considered clinically stable increased across the ECR window (69.2-77.6% for omadacycline; 68.0-79.7% for moxifloxacin). There was high concordance (>70%) and high positive predictive value (>90%) of ECR and clinical stability with overall clinical success at PTE., Conclusions: Omadacycline was noninferior to moxifloxacin, based on a new ECR endpoint. Clinical stability was similarly high when measured in the same time frame as ECR. Both ECR and clinical stability showed high concordance and high positive predictive value with clinical success at PTE., Clinical Trials Registration: NCT02531438., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Within the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent cause of purulent skin and soft tissue infections. New therapeutic options are being investigated for these infections., Methods: We report an integrated analysis of 2 randomized, controlled studies involving omadacycline, a novel aminomethylcycline, and linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Omadacycline in Acute Skin and Skin Structure Infections Study 1 (OASIS-1) initiated patients on intravenous omadacycline or linezolid, with the option to transition to an oral formulation after day 3. OASIS-2 was an oral-only study of omadacycline versus linezolid., Results: In total, 691 patients received omadacycline and 689 patients received linezolid. Infection types included wound infection in 46.8% of patients, cellulitis/erysipelas in 30.5%, and major abscess in 22.7%. Pathogens were identified in 73.2% of patients. S. aureus was detected in 74.7% and MRSA in 32.4% of patients in whom a pathogen was identified. Omadacycline was noninferior to linezolid using the Food and Drug Administration primary endpoint of early clinical response (86.2% vs 83.9%; difference 2.3, 95% confidence interval -1.5 to 6.2) and using the European Medicines Agency primary endpoint of investigator-assessed clinical response at the posttreatment evaluation. Clinical responses were similar across different infection types and infections caused by different pathogens. Treatment-emergent adverse events, mostly described as mild or moderate, were reported by 51.1% of patients receiving omadacycline and 41.2% of those receiving linezolid., Conclusions: Omadacycline was effective and safe in ABSSSI., Clinical Trials Registration: NCT02378480 and NCT02877927., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Oral and intravenous (IV) omadacycline formulations are approved in the United States for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults. Oral omadacycline bioavailability is 34.5%; similar exposures are obtained following 300 mg oral and 100 mg IV doses. Oral administration should be in a fasted state, with dairy products, antacids, or multivitamins avoided for ≥4 hours after dosing. Low protein binding (21%), large volume of distribution (190 L), low systemic clearance (10 L/hour), and long elimination half-life (16-17 hours) support once-daily dosing. Omadacycline is excreted unchanged in feces (81.1%) and urine (14.4%), with low potential for drug-drug interactions. Dose adjustments are unnecessary for age, sex, and renal or hepatic impairment. Pharmacokinetic-pharmacodynamic studies identify fAUC0-24/MIC ratio as the parameter that correlates with in vivo efficacy. Systemic exposure of omadacycline in epithelial lining fluid is greater than/equal to plasma concentrations in healthy adults., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Drug development continues to focus on the challenge of treating acne effectively and safely. Inflammation is a backdrop to the commonly cited elements of the pathophysiology of acne: Propionibacterium acnes proliferation, increased sebum production with an increase in circulating androgens, and faulty keratinization. As such, there is increased emphasis on targeting inflammation and its effects. Vehicle innovations are optimizing existing active drugs and creating opportunities to deliver new compounds to the skin. Recently approved sarecycline is the first new chemical entity approved for acne in several years. It might be followed in coming years by other new actives, including clascoterone and cannabidiol (CBD).

Symptomatic pleural disease, specifically malignant pleural effusion, refractory benign pleural effusion, and pneumothoraces are common diseases that often require therapeutic interventions. The spectrum of management strategies often includes selection of a chemical pleurodesis agent administered in combination with an indwelling pleural catheter or chest tube.Additionally, there is a role for minimally invasive techniques which include medical thoracoscopy or more advanced video-assisted thoracoscopic approaches. Ongoing clinical trials continue to evolve best practices regarding the optimal sclerosant agents and procedural approaches in the management of these diseases., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Rationale: Increased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension, and their inhibition by minocycline-an anti-inflammatory antibiotic-produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for hypertension. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in hypertension. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3)-a derivative of tetracycline that has potent anti-inflammatory activity-to address this question., Objective: Test the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing hypertension-associated pathology, and attenuate hypertension., Methods and Results: Rats were implanted with radiotelemetry devices for recording mean arterial pressure. Ang II (angiotensin II) was infused subcutaneously using osmotic mini-pumps to induce hypertension. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly. Intracerebroventricular CMT- 3 infusion was also investigated in SHR (spontaneously hypertensive rats). Physiological, pathological, immunohistological parameters, and fecal microbiota were analyzed. Intracerebroventricular CMT-3 significantly inhibited Ang II-induced increases in number of microglia, their activation, and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, intracerebroventricular CMT-3 attenuated increased mean arterial pressure, normalized sympathetic activity, and left ventricular hypertrophy in Ang II rats, as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by Ang II and attenuated pathological alterations in gut wall., Conclusions: These observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes in gut microbial communities and profound attenuation of gut pathology. They suggest, for the first time, a link between microglia and certain microbial communities that may have implications for treatment of hypertension.

Background: Pemphigus vulgaris (PV) is a life-long IgG autoantibody-mediated blistering disease affecting the mucosal surfaces lined by the stratified epithelium (oral, nasal, genital) and sometimes also the skin. While corticosteroid treatment is life saving, the high dose and prolonged courses required for disease control are associated with significant adverse effects, including death. Although introduction of rituximab (RTX) provided for a favorable outcome, the high relapse rate, that is, up to 80%, precludes successful use of RTX as a monotherapy. Intravenous immunoglobulin (IVIg) is being increasingly utilized as off-label therapy for a variety of autoimmune and inflammatory diseases, including PV and pemphigus foliaceus (PF)., Aims: The goal of pemphigus research is to develop an effective treatment modality that would allow patients to achieve and maintain a stable clinical remission without the need for additional treatments, or cure., Materials and Methods: This article summarizes clinical outcome of 123 pemphigus patients treated with a combination of IVIg, an immunosuppressive cytotoxic drug (ICD) and mitochondrion-protecting drugs in the Blistering Disease Clinic at the University of California, Irvine from 2007 to 2017., Results: The mean time to disease control was 0.2 months and time to complete remission - 1.7 months. Duration of complete remission on drugs until relapse or end of treatment was 19.3 months. The mean duration of complete remission off drugs until relapse was 15.8 months. That until end of follow up was 48.4 months, with a minimum of 14 and a maximum of 91 months. The overall complete remission rate off all drugs was 100%, with 12% overall relapse rate. Most relapses, 8.1 vs. 3.3%, occurred during the time of treatment, compared to posttreatment. No patients had more than a single relapse. The duration of the posttreatment follow-up ranged from 9 to 97 months with a mean of 64.8 months, or 5.4 years. The total number of IVIg cycles ranged from 26 in patients without a relapse to 37 in patients with a relapse. The clinical outcome in patients that received IVIg with RTX or another ICD were found to be very similar., Discussion: Thus, the multidrug IVIg regimen allowed to achieve three principal treatment objectives: (i) rapid control of pemphigus symptoms; (ii) stable disease remission; and (iii) overall safety of treatment., Conclusions: While the individualized therapeutic approaches to eradicate the autoreactive B cell clones causing disease in each particular PV or PF patient are being developed, all pemphigus patients can benefit from the treatment protocol described in this study., (© 2018 The International Society of Dermatology.)

Paratek Pharmaceuticals are developing omadacycline (NUZYRA™), a first-in-class orally active aminomethylcycline antibacterial, as a treatment for various bacterial infections. The drug, which is available in intravenous and oral formulations, has a broad spectrum of antibacterial activity and was recently approved in the USA as a treatment for the treatment of community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This article summarizes the milestones in the development of omadacycline leading to this first global approval for the treatment of CABP and ABSSSI.

Eravacycline is a novel, fully synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens, including multidrug-resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (i.v.) eravacycline were evaluated in single- and multiple-ascending-dose studies. Healthy subjects received single i.v. doses of 0.1 to 3 mg/kg of body weight or 10 days of treatment with 0.5 or 1.5 mg/kg every 24 h (q24h) over 30 min, 1.5 mg/kg q24h over 60 min, or 1 mg/kg q12h over 60 min. After single doses, total exposure (the area under the plasma concentration-time curve [AUC]) and the maximum plasma concentrations ( C max ) of eravacycline increased in an approximately dose-proportional manner. After multiple doses, steady state was achieved within 5 to 7 days. Accumulation ranged from approximately 7% to 38% with the q24h dosing regimens and was 45% with 1 mg/kg q12h. Eravacycline was generally well tolerated, with dose-related nausea, infusion site effects, and superficial phlebitis that were mild or moderate occurring. These results provide support for the 1-mg/kg q12h regimen used in clinical studies of eravacycline., (Copyright © 2018 Newman et al.)

Background: Side effects may limit the use of current tetracycline-class antibiotics for acne., Objective: Evaluate the efficacy and safety of once-daily sarecycline, a novel, narrow-spectrum tetracycline-class antibiotic, in moderate to severe acne., Methods: Patients 9-45 years with moderate to severe facial acne (Investigator's Global Assessment [IGA] score ≥ 3, 20-50 inflammatory and ≤ 100 noninflammatory lesions, and ≤ 2 nodules) were randomized 1:1 to sarecycline 1.5 mg/kg/day or placebo for 12 weeks in identically designed phase 3 studies (SC1401 and SC1402)., Results: In SC1401 (sarecycline n=483, placebo n=485) and SC1402 (sarecycline n=519, placebo n=515), at week 12, IGA success (≥ 2-grade improvement and score 0 [clear] or 1 [almost clear]) rates were 21.9% and 22.6% (sarecycline), respectively, versus 10.5% and 15.3% (placebo; P less than 0.0001 and P equals 0.0038). Onset of efficacy in inflammatory lesions occurred by the first visit (week 3), with mean percentage reduction in inflammatory lesions at week 12 in SC1401 and SC1402 of -51.8% and -49.9% (sarecycline), respectively, versus -35.1% and -35.4% (placebo; P less than 0.0001). Onset of efficacy for absolute reduction of noninflammatory lesion count occurred at week 6 in SC1401 (P less than 0.05) and week 9 in SC1402 (P less than 0.01). In SC1401, the most common TEAEs (in ≥ 2% of either sarecycline or placebo group) were nausea (4.6% [sarecycline]; 2.5% [placebo]), nasopharyngitis (3.1%; 1.7%), headache (2.7%; 2.7%), and vomiting (2.1%; 1.4%) and, in SC1402, nasopharyngitis (2.5%; 2.9%) and headache (2.9%; 4.9%). Most were not considered treatment-related. Vestibular (dizziness, tinnitus, vertigo) and phototoxic (sunburn, photosensitivity) TEAEs both occurred in ≤ 1% of sarecycline patients. Gastrointestinal TEAE rates for sarecycline were low. Among females, vulvovaginal candidiasis (SC1401: 1.1% [sarecycline] and 0 [placebo]; SC1402: 0.3% and 0) and mycotic infection (0.7% and 0; 1.0% and 0) rates were low., Conclusion: The narrow-spectrum antibiotic sarecycline was safe, well tolerated, and effective for moderate to severe acne, with low rates of side effects common with tetracycline antibiotics. J Drugs Dermatol. 2018;17(9):987-996.

Background: Long-term oral antibiotic use in acne may be associated with a variety of adverse effects including antibiotic resistance, pharyngitis, inflammatory bowel disease, and breast and colon cancer. Spironolactone may represent an effective and safe alternative to oral antibiotics for women with moderate to severe acne, however comparative studies are lacking., Methods: Using the OptumInsight™ Clinformatics™ DataMart, we conducted a retrospective analysis of the frequency of switching to a different systemic agent within the first year of therapy among women with acne who were started on either spironolactone or an oral tetracycline-class antibiotic between 2010-2016, after controlling for age, topical retinoid, and oral contraceptive use., Results: Among women with acne who were started on spironolactone, 14.4% were prescribed a different systemic agent within one year, compared with 13.4% started on an oral tetracycline-class antibiotic. After adjusting for age, topical retinoid, and oral contraceptive use, the odds ratio for being prescribed a different systemic agent within one year was 1.07 (95% CI 0.99-1.16) for those prescribed spironolactone when compared with oral tetracycline-class antibiotics and the risk difference was 0.007 (95% CI -0.002-0.017)., Conclusions: Based on the observation of similar switching between the two groups, spironolactone may have similar clinical effectiveness to that of oral tetracycline-class antibiotics. While ultimately large clinical trials are needed to determine the optimal management strategy for women with moderate to severe acne, these results provide additional support that spironolactone represents an effective treatment for women with acne. J Drugs Dermatol. 2018;17(6):632-638.