Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 330
Filtrar
2.
Pharmacotherapy ; 44(4): 301-307, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270447

RESUMO

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.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , COVID-19 , Carbapenêmicos , Pneumonia Associada à Ventilação Mecânica , Tetraciclinas , Humanos , Acinetobacter baumannii/efeitos dos fármacos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecções por Acinetobacter/tratamento farmacológico , Idoso , Carbapenêmicos/uso terapêutico , Carbapenêmicos/administração & dosagem , Carbapenêmicos/farmacologia , Tetraciclinas/uso terapêutico , Tetraciclinas/administração & dosagem , COVID-19/complicações , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Quimioterapia Combinada , Adulto , Resultado do Tratamento , Idoso de 80 Anos ou mais
3.
Pharmacotherapy ; 41(11): 915-931, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34558677

RESUMO

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.


Assuntos
Antibacterianos , Dermatopatias Bacterianas , Tetraciclinas , Administração Oral , Adulto , Assistência Ambulatorial , Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Humanos , Minociclina/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Tetraciclinas/administração & dosagem
4.
Respir Med ; 184: 106442, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058682

RESUMO

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.


Assuntos
Índice de Massa Corporal , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Tetraciclinas/administração & dosagem , Adulto , Idoso , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Moxifloxacina/administração & dosagem , Moxifloxacina/efeitos adversos , Segurança , Tetraciclinas/efeitos adversos , Resultado do Tratamento
5.
Intern Emerg Med ; 16(8): 2231-2241, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33956311

RESUMO

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.


Assuntos
Antibacterianos , Desenho de Fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/farmacologia , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/farmacologia , Ceftazidima/administração & dosagem , Ceftazidima/farmacologia , Cefalosporinas/administração & dosagem , Cefalosporinas/farmacologia , Combinação Imipenem e Cilastatina/administração & dosagem , Combinação Imipenem e Cilastatina/farmacologia , Combinação de Medicamentos , Bactérias Gram-Negativas/efeitos dos fármacos , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Compostos Heterocíclicos com 1 Anel/farmacologia , Humanos , Meropeném/administração & dosagem , Meropeném/farmacologia , Sisomicina/administração & dosagem , Sisomicina/análogos & derivados , Sisomicina/farmacologia , Tazobactam/administração & dosagem , Tazobactam/farmacologia , Tetraciclinas/administração & dosagem , Tetraciclinas/farmacologia , Cefiderocol
6.
J Drugs Dermatol ; 20(4): 426-431, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852248

RESUMO

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.


Assuntos
Antibacterianos/administração & dosagem , Rosácea/tratamento farmacológico , Tetraciclinas/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Rosácea/diagnóstico , Rosácea/microbiologia , Índice de Gravidade de Doença , Tetraciclinas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
J Neuroimmune Pharmacol ; 16(2): 213-218, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33534108

RESUMO

The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not fully understood. However, previous evidence about systemic viral infections pointed to an ongoing neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells from the periphery. Microglia cells mediate the overproduction of inflammatory cytokines, free radicals, and damage signals, culminating with neurotoxic consequences. Semi-synthetic second-generation tetracyclines, including minocycline (MINO) and doxycycline (DOXY), are safe bacteriostatic agents that have remarkable neuroprotective and anti-inflammatory properties. Promising results have been obtained in clinical trials using tetracyclines for major psychiatric disorders, such as schizophrenia and major depression. Tetracyclines can inhibit microglial reactivity and neuroinflammation by inhibiting nuclear factor kappa B (NF-kB) signaling, cyclooxygenase 2, and matrix metalloproteinases (MMPs). This drug class also has a broad profile of activity against bacteria associated with community-based pneumonia, including atypical agents. COVID-19 patients are susceptible to secondary bacterial infections, especially those on invasive ventilation. Therefore, we suggest tetracyclines' repurposing as a potential treatment for COVID-19 neuropsychiatric manifestations. These drugs can represent a valuable multi-modal treatment for COVID-19-associated neuroinflammatory alterations based on their broad antimicrobial profile and neuroinflammation control.


Assuntos
Anti-Inflamatórios/administração & dosagem , Tratamento Farmacológico da COVID-19 , Reposicionamento de Medicamentos/métodos , Transtornos Mentais/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Tetraciclinas/administração & dosagem , Antivirais/administração & dosagem , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/imunologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/imunologia
8.
Expert Rev Clin Pharmacol ; 14(3): 315-322, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33586566

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Tratamento Farmacológico da COVID-19 , Dexametasona/uso terapêutico , SARS-CoV-2 , Tetraciclinas/uso terapêutico , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Humanos , Tetraciclinas/administração & dosagem
9.
J Am Acad Dermatol ; 85(2): 369-378, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33484766

RESUMO

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.


Assuntos
Clindamicina/administração & dosagem , Hidradenite Supurativa/tratamento farmacológico , Rifampina/administração & dosagem , Tetraciclinas/administração & dosagem , Adulto , Clindamicina/efeitos adversos , Estudos de Coortes , Combinação de Medicamentos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/efeitos adversos , Tetraciclinas/efeitos adversos , Resultado do Tratamento
10.
Int J Infect Dis ; 104: 501-509, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33484864

RESUMO

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.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Moxifloxacina/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Tetraciclinas/uso terapêutico , Administração Intravenosa , Idoso , Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/microbiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina/administração & dosagem , Pneumonia Bacteriana/microbiologia , Tetraciclinas/administração & dosagem
11.
J Drugs Dermatol ; 20(1): 98-100, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33400418

RESUMO

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’s. J Drugs Dermatol. 2021;20(1):98-100. doi:10.36849/JDD.5678.


Assuntos
Antibacterianos/administração & dosagem , Queilite/tratamento farmacológico , Doença de Crohn/complicações , Dermatite/tratamento farmacológico , Tetraciclinas/administração & dosagem , Administração Oral , Adulto , Biópsia , Bochecha , Queilite/diagnóstico , Queilite/imunologia , Queilite/patologia , Doença de Crohn/imunologia , Dermatite/diagnóstico , Dermatite/imunologia , Dermatite/patologia , Feminino , Humanos , Pele/patologia , Resultado do Tratamento
12.
Surg Today ; 51(2): 276-284, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32734348

RESUMO

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.


Assuntos
Analgesia Epidural/métodos , Analgesia Controlada pelo Paciente/métodos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Fentanila/administração & dosagem , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pâncreas/patologia , Período Pós-Operatório , Fatores de Risco , Fatores Sexuais , Tetraciclinas/administração & dosagem , Adulto Jovem
13.
Expert Opin Pharmacother ; 22(2): 145-154, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32924666

RESUMO

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.


Assuntos
Acne Vulgar/tratamento farmacológico , Tetraciclinas/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Feminino , Humanos , Resultado do Tratamento
14.
Eur J Drug Metab Pharmacokinet ; 46(1): 85-92, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33180250

RESUMO

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 (AUC0-24), from time 0 to the last quantifiable concentration (AUC0-t), from time 0 extrapolated to infinity (AUC0-inf), and by maximum (peak) observed plasma concentration (Cmax). 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.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antibacterianos/farmacocinética , Interações Medicamentosas/fisiologia , Voluntários Saudáveis , Tetraciclinas/farmacocinética , Verapamil/farmacocinética , Adulto , Antibacterianos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Tetraciclinas/administração & dosagem , Verapamil/administração & dosagem , Adulto Jovem
15.
J Drugs Dermatol ; 19(11): s6-s13, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33196746

RESUMO

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.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Dermatologia/métodos , Disbiose/induzido quimicamente , Propionibacteriaceae/efeitos dos fármacos , Acne Vulgar/microbiologia , Administração Oral , Antibacterianos/efeitos adversos , Ensaios Clínicos como Assunto , Doxiciclina/administração & dosagem , Doxiciclina/efeitos adversos , Farmacorresistência Bacteriana , Disbiose/microbiologia , Disbiose/prevenção & controle , Face , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Minociclina/administração & dosagem , Minociclina/efeitos adversos , Estudos Observacionais como Assunto , Pele/microbiologia , Tetraciclina/administração & dosagem , Tetraciclina/efeitos adversos , Tetraciclinas/administração & dosagem , Tetraciclinas/efeitos adversos , Resultado do Tratamento
17.
Drugs ; 80(3): 285-313, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31970713

RESUMO

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 (Vd) ranging from 190 to 204 L, a terminal elimination half-life (t½) of 13.5-17.1 h, total clearance (CLT) 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 (Cmax) of 0.5-0.6 mg/L and an area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) of 9.6-11.9 mg h/L. The free plasma area under concentration-time curve divided by the minimum inhibitory concentration (i.e., fAUC24h/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.


Assuntos
Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Dermatopatias Bacterianas/tratamento farmacológico , Tetraciclinas/administração & dosagem , Tetraciclinas/farmacologia , Administração Intravenosa , Administração Oral , Antibacterianos/administração & dosagem , Humanos
18.
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
19.
Expert Rev Anti Infect Ther ; 17(11): 851-863, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31622119

RESUMO

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.


Assuntos
Antibacterianos/administração & dosagem , Infecções Intra-Abdominais/tratamento farmacológico , Tetraciclinas/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Infecções Intra-Abdominais/microbiologia , Testes de Sensibilidade Microbiana , Tetraciclinas/efeitos adversos , Tetraciclinas/farmacocinética
20.
Semin Respir Crit Care Med ; 40(3): 375-385, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31525812

RESUMO

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.


Assuntos
Doenças Pleurais/terapia , Pleurodese/métodos , Soluções Esclerosantes/administração & dosagem , Humanos , Derrame Pleural Maligno/terapia , Pneumotórax/terapia , Povidona-Iodo/administração & dosagem , Nitrato de Prata/administração & dosagem , Talco/administração & dosagem , Tetraciclinas/administração & dosagem , Toracoscopia/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA