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1.
Cochrane Database Syst Rev ; 1: CD013198, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448349

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day-to-day activities and overall quality of life. In carefully selected patients with COPD, long-term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations. OBJECTIVES: To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta-analyses (NMAs), and to provide rankings of identified antibiotics. SEARCH METHODS: To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020. SELECTION CRITERIA: We included RCTs with a parallel design of at least 12 weeks' duration evaluating long-term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD. DATA COLLECTION AND ANALYSIS: This Cochrane Review collected and updated pair-wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta-analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study's contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events. MAIN RESULTS: Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single-centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV1) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect-fixed class effect: mean difference (MD) -2.30, 95% CrI -3.61 to -0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect-fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance. AUTHORS' CONCLUSIONS: This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade-off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non-tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non-tuberculous mycobacteria.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Carga Bacteriana/efeitos dos fármacos , Progressão da Doença , Metanálise em Rede , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Teorema de Bayes , Viés , Feminino , Volume Expiratório Forçado , Humanos , Macrolídeos/efeitos adversos , Macrolídeos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/microbiologia , Qualidade de Vida , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Tetraciclinas/efeitos adversos , Tetraciclinas/uso terapêutico , Resultado do Tratamento
2.
Nat Metab ; 3(1): 33-42, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33462515

RESUMO

Mitochondrial diseases (MDs) are a heterogeneous group of disorders resulting from mutations in nuclear or mitochondrial DNA genes encoding mitochondrial proteins1,2. MDs cause pathologies with severe tissue damage and ultimately death3,4. There are no cures for MDs and current treatments are only palliative5-7. Here we show that tetracyclines improve fitness of cultured MD cells and ameliorate disease in a mouse model of Leigh syndrome. To identify small molecules that prevent cellular damage and death under nutrient stress conditions, we conduct a chemical high-throughput screen with cells carrying human MD mutations and discover a series of antibiotics that maintain survival of various MD cells. We subsequently show that a sub-library of tetracycline analogues, including doxycycline, rescues cell death and inflammatory signatures in mutant cells through partial and selective inhibition of mitochondrial translation, resulting in an ATF4-independent mitohormetic response. Doxycycline treatment strongly promotes fitness and survival of Ndufs4-/- mice, a preclinical Leigh syndrome mouse model8. A proteomic analysis of brain tissue reveals that doxycycline treatment largely prevents neuronal death and the accumulation of neuroimmune and inflammatory proteins in Ndufs4-/- mice, indicating a potential causal role for these proteins in the brain pathology. Our findings suggest that tetracyclines deserve further evaluation as potential drugs for the treatment of MDs.


Assuntos
Antibacterianos/uso terapêutico , Doenças Mitocondriais/tratamento farmacológico , Tetraciclinas/uso terapêutico , Fator 4 Ativador da Transcrição/metabolismo , Animais , Encéfalo/patologia , Células Cultivadas , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Doença de Leigh/tratamento farmacológico , Doença de Leigh/patologia , Expectativa de Vida , Metabolômica , Camundongos , Camundongos Knockout , Doenças Mitocondriais/mortalidade , Doenças Mitocondriais/patologia , Aptidão Física , Análise de Sobrevida
3.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33336780

RESUMO

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , /tratamento farmacológico , /terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Antiparasitários/uso terapêutico , Canabinoides/uso terapêutico , Cloroquina/uso terapêutico , Inativadores do Complemento/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferons/uso terapêutico , Ivermectina/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico , Tetraciclinas/uso terapêutico , Tiazóis/uso terapêutico
4.
F1000Res ; 9: 609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32934806

RESUMO

Background: Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Methods: Inhibition of angiotensin-converting enzyme 2 (ACE2) caused by the spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We performed drug repositioning analysis to identify drug candidates that reverse gene expression pattern in L1000 lung cell line HCC515 treated with ACE2 inhibitor. We confirmed these drug candidates by similar bioinformatics analysis using lung tissues from patients deceased from COVID-19. We further investigated deregulated genes and pathways related to lung injury, as well as the gene-pathway-drug candidate relationships. Results: We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19. Further bioinformatics analysis shows that 12 significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues. These include signaling pathways known to be associated with lung injury such as TNF signaling, MAPK signaling and chemokine signaling pathways. All 12 pathways are targeted in COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression. CGP-60474 shares 11 of 12 pathways with COL-3 and common target genes such as RHOA. It also uniquely targets other genes related to lung injury, such as CALR and MMP14. Conclusions: This study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have potential as repurposed drugs for its treatment.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumopatias/tratamento farmacológico , Pneumopatias/virologia , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Humanos , Pandemias , Peptidil Dipeptidase A , Tetraciclinas/uso terapêutico
6.
Brasília; s.n; 4 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117744

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 13 protocolos.


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Tetraciclinas/uso terapêutico , Vitamina D/uso terapêutico , Cloroquina/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Antirreumáticos/uso terapêutico , Ritonavir/uso terapêutico , Etoposídeo/uso terapêutico , Lopinavir/uso terapêutico , Hidroxicloroquina/uso terapêutico
8.
Nursing ; 50(2): 31-38, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31895198
9.
Ann Pharmacother ; 54(2): 164-170, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31462063

RESUMO

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.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Tetraciclinas/uso terapêutico , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Estudos Multicêntricos como Assunto , Tetraciclinas/administração & dosagem , Tetraciclinas/efeitos adversos , Tetraciclinas/sangue , Estados Unidos , United States Food and Drug Administration
10.
J Pediatric Infect Dis Soc ; 9(1): 56-66, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31872226

RESUMO

Infections due to carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent in children and are associated with poor clinical outcomes. Optimal treatment strategies for CRE infections continue to evolve. A lack of pediatric-specific comparative effectiveness data, uncertain pediatric dosing regimens for several agents, and a relative lack of new antibiotics with pediatric indications approved by the US Food and Drug Administration (FDA) collectively present unique challenges for children. In this review, we provide a framework for antibiotic treatment of CRE infections in children, highlighting relevant microbiologic considerations and summarizing available data related to the evaluation of FDA-approved antibiotics (as of September 2019) with CRE activity, including carbapenems, ceftazidime-avibactam, meropenem-vaborbactam, imipenem/cilastatin-relebactam, polymyxins, tigecycline, eravacycline, and plazomicin.


Assuntos
Antibacterianos/uso terapêutico , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Antibacterianos/administração & dosagem , Carbapenêmicos/uso terapêutico , Criança , Quimioterapia Combinada , Infecções por Enterobacteriaceae/microbiologia , Humanos , Polimixinas/uso terapêutico , Sisomicina/análogos & derivados , Sisomicina/uso terapêutico , Tetraciclinas/uso terapêutico , Tigeciclina/uso terapêutico , Inibidores de beta-Lactamases/administração & dosagem , Inibidores de beta-Lactamases/uso terapêutico
11.
Medicine (Baltimore) ; 98(51): e18426, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861009

RESUMO

BACKGROUND: This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections in adult patients through meta-analysis. METHODS: PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated omadacycline and other comparators for treating acute bacterial infections in adult patients were included. The primary outcome was the clinical response rate at the posttreatment evaluation, whereas the secondary outcomes were risk of an adverse event (AE) and mortality. RESULTS: Four RCTs were included. Overall, omadacycline had a clinical response rate noninferior to comparators in the treatment of acute bacterial infection in the modified intent-to-treat population (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04-1.65; I = 0%) and in the clinically evaluable population (OR, 1.53; 95% CI, 1.11-2.11; I = 0%). Furthermore, no significant differences were found between omadacycline and comparators for the risk of treatment-emergent AEs (OR, 1.13; 95% CI, 0.60-2.14; I = 93%), treatment-related AEs (OR, 0.70; 95% CI, 0.46-1.04; I = 56%), serious AEs (OR, 1.01; 95% CI, 0.64-1.58; I = 0%), and discontinuation of study drug due to an AE (OR, 0.78; 95% CI, 0.47-1.29; I = 0%). However, in the clinical trial, NCT02877927, in which omadacycline was used in only oral form, the reported incidence of nausea and vomiting were 30.2% (111/368) and 16.9% (62/368), respectively. Finally, the mortality rate was similar between omadacycline and comparator in the treatment of acute bacterial infection (OR, 1.32; 95% CI, 0.47-3.67; I = 0%). CONCLUSION: The clinical efficacy of omadacycline is not inferior to that of comparators in the treatment of acute bacterial infections in adult patients, and this antibiotic is also well tolerated.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Tetraciclinas/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Drugs Today (Barc) ; 55(10): 615-625, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31720559

RESUMO

Sarecycline hydrochloride (Seysara) is a novel, narrow-spectrum tetracycline derivative approved by the U.S. Food and Drug Administration (FDA) in October 2018 for the treatment of inflammatory non-nodular moderate to severe acne vulgaris. It was initially developed by Paratek Pharmaceuticals, Inc. (U.S.) and Allergan plc (U.S.), which later was acquired by Almirall S.A. (Barcelona, Spain). Almirall S.A. obtained U.S. FDA approval of oral sarecycline tablets under the trade name Seysara. Sarecycline exhibits antibacterial activity against important skin/soft tissue pathogens with targeted activity against Cutibacterium acnes--an anaerobic Gram-positive bacterium linked with acne lesions--and also exerts anti-inflammatory effects as do other tetracyclines used in the treatment of acne vulgaris. Interestingly, unlike the broad-spectrum tetracyclines, sarecycline is less potent against aerobic Gram-negative bacilli and anaerobic bacteria associated with endogenous intestinal microbial flora. This provides it with a more specific antibacterial spectra with lower chances of adverse off-target antibacterial effects, thus making it a promising choice of treatment over others in its class. It has also demonstrated low propensity to resistance as compared with other tetracyclines and is also active against tetracycline-resistant Staphylococcus aureus as well as erythromycin- and clindamycin-resistant C. acnes strains. Sarecycline has successfully undergone numerous phase I, phase II and three phase III studies establishing it as a well-tolerated once-daily oral drug available as a tablet for the treatment of patients 9 years of age or above.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Tetraciclinas/uso terapêutico , Aprovação de Drogas , Humanos , Estados Unidos , United States Food and Drug Administration
13.
Am Fam Physician ; 100(9): 562-569, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674740

RESUMO

Hidradenitis suppurativa is a chronic folliculitis affecting intertriginous areas. Onset generally occurs in young adulthood to middle adulthood (18 to 39 years of age). Females and blacks are more than twice as likely to be affected. Additional risk factors include family history, smoking, and obesity. Hidradenitis suppurativa is associated with several comorbidities, including diabetes mellitus and Crohn disease. The clinical presentation of hidradenitis suppurativa ranges from rare, mild inflammatory nodules to widespread abscesses, sinus tracts, and scarring. Quality of life is often affected, and patients should be screened for depression. Treatment includes wearing loose-fitting clothes, losing weight if overweight, and smoking cessation. Topical clindamycin alone can be effective for patients with mild disease. Patients with moderate disease can be treated with oral antibiotics, such as tetracyclines, in addition to topical clindamycin. Adalimumab, a tumor necrosis factor alpha inhibitor, is effective for patients with moderate to severe hidradenitis suppurativa. Surgical procedures are often necessary for definitive treatment and include local procedures, such as punch debridement and unroofing/deroofing. Wide excision is indicated for patients with severe, extensive disease and scarring.


Assuntos
Adalimumab/uso terapêutico , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Tratamento Farmacológico/normas , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Tetraciclinas/uso terapêutico , Adolescente , Adulto , Currículo , Educação Médica Continuada , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Fatores de Risco , Adulto Jovem
15.
Future Microbiol ; 14: 1293-1308, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31570004

RESUMO

Aim: Recently approved for use in complicated intra-abdominal infection, eravacycline is a novel fluorocycline with broad spectrum of activity against resistant Gram-negative pathogens. This manuscript is a pooled analysis of two Phase III trials. Clinical efficacy: Clinical cure rates were 86.8% for eravacycline versus 87.6% for ertapenem, and 90.8% for eravacycline versus 91.2% for meropenem in the Intent to Treat (micro-ITT) populations, and 87.0% for eravacycline versus 88.8% ertapenem, and 92.4 versus 91.6% for meropenem in the Modified Intent to Treat (MITT) populations. Safety: Eravacycline is well tolerated, with lower rates of nausea, vomiting and diarrhea than other tetracyclines. Conclusion: Eravacycline is an effective new option for use in complicated intra-abdominal infections, and in particular, for the treatment of extended-spectrum ß-lactamase- and carbapenem-resistant Enterobacteriaceae-expressing organisms.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/microbiologia , Tetraciclinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carbapenêmicos/uso terapêutico , Interpretação Estatística de Dados , Enterobacteriaceae/enzimologia , Ertapenem/uso terapêutico , Feminino , Humanos , Infecções Intra-Abdominais/complicações , Masculino , Meropeném/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem , beta-Lactamases
16.
Lancet Infect Dis ; 19(10): 1080-1090, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31474458

RESUMO

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.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Linezolida/administração & dosagem , Linezolida/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Tetraciclinas/administração & dosagem , Tetraciclinas/uso terapêutico , Administração Oral , Adulto , Antibacterianos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação , Linezolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Tetraciclinas/efeitos adversos , Resultado do Tratamento , Vômito/etiologia
17.
Future Microbiol ; 14: 1235-1242, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31475868

RESUMO

Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Tetraciclinas/uso terapêutico , Acne Vulgar/microbiologia , Anti-Inflamatórios/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Propionibacteriaceae/efeitos dos fármacos
18.
Clin Infect Dis ; 69(Suppl 1): S1-S5, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31367739

RESUMO

When tetracyclines were introduced in the 1940s, these antibiotics offered a broad spectrum of activity against multiple types of pathogens. However, their utility waned after the selection of tetracycline resistance in the pathogens against which they were effective. Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class of antibiotics that is unaffected by these resistance mechanisms. It has an appropriate spectrum of activity for community-acquired infections, including those caused by many resistant organisms. Omadacycline offers a well-tolerated treatment for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Omadacycline has minimal known drug-drug interactions, and should be administered in a fasting state, avoiding dairy and cation-containing products for at least 4 hours after dosing. It does not require dose adjustments for sex, age, or hepatic or renal impairment, and has a safety profile similar to that of other oral tetracyclines. Because omadacycline can be administered effectively orally, it can help reduce hospitalization costs associated with intravenous antibiotic administration. This special supplement to Clinical Infectious Diseases offers an in-depth examination of omadacycline development, including discussions of pharmacokinetic and pharmacodynamic trials, spectrum of activity and preclinical data, early clinical trials, phase III clinical trials, and an integrated safety summary.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Tetraciclinas/uso terapêutico , Antibacterianos/química , Bactérias/efeitos dos fármacos , Ensaios Clínicos como Assunto , Infecções Comunitárias Adquiridas/microbiologia , Interações Medicamentosas , Humanos , Testes de Sensibilidade Microbiana , Tetraciclinas/química
19.
Clin Infect Dis ; 69(Suppl 1): S40-S47, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31367740

RESUMO

Omadacycline is a semisynthetic tetracycline antibiotic. Phase III clinical trial results have shown that omadacycline has an acceptable safety profile in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Similar to most tetracyclines, transient nausea and vomiting and low-magnitude increases in liver aminotransferases were the most frequent treatment-emergent adverse events in phase III studies but were not treatment limiting. Package insert warnings and precautions for omadacycline include tooth discoloration; enamel hypoplasia; inhibition of bone growth following use in late pregnancy, infancy, or childhood up to 8 years of age; an imbalance in mortality (2%, compared with 1% in moxifloxacin-treated patients) was observed in the phase III study in patients with community-acquired bacterial pneumonia. Omadacycline has no effect on the QT interval, and its affinity for muscarinic M2 receptors resulted in transient heart rate increases following dosing.


Assuntos
Antibacterianos/efeitos adversos , Bactérias/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Tetraciclinas/efeitos adversos , Fatores Etários , Antibacterianos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Infecções Comunitárias Adquiridas/microbiologia , Esquema de Medicação , Feminino , Humanos , Masculino , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Tetraciclinas/uso terapêutico
20.
Clin Infect Dis ; 69(Suppl 1): S33-S39, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31367741

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Adulto , Antibacterianos/administração & dosagem , Método Duplo-Cego , Aprovação de Drogas , Humanos , Internacionalidade , Moxifloxacina/administração & dosagem , Moxifloxacina/uso terapêutico , Valor Preditivo dos Testes , Tetraciclinas/administração & dosagem , Tetraciclinas/uso terapêutico
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