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1.
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
2.
Front Cell Infect Microbiol ; 10: 589505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364201

RESUMO

The coronavirus disease 2019 (COVID-19) pandemics is a challenge without precedent for the modern science. Acute Respiratory Discomfort Syndrome (ARDS) is the most common immunopathological event in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. Fast lung deterioration results of cytokine storm determined by a robust immunological response leading to ARDS and multiple organ failure. Here, we show cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. CatL is a lysosomal enzyme that participates in numerous physiological processes, including apoptosis, antigen processing, and extracellular matrix remodeling. CatL is implicated in pathological conditions like invasion and metastasis of tumors, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, viral infection, and other diseases. CatL expression is up-regulated during chronic inflammation and is involved in degrading extracellular matrix, an important process for SARS-CoV-2 to enter host cells. In addition, CatL is probably involved in processing SARS-CoV-2 spike protein. As its inhibition is detrimental to SARS-CoV-2 infection and possibly exit from cells during late stages of infection, CatL could have been considered a valuable therapeutic target. Therefore, we describe here some drugs already in the market with potential CatL inhibiting capacity that could be used to treat COVID-19 patients. In addition, we discuss the possible role of host genetics in the etiology and spreading of the disease.


Assuntos
/complicações , Catepsina L/fisiologia , Pandemias , /fisiologia , Lesão Renal Aguda/etiologia , Amantadina/uso terapêutico , /tratamento farmacológico , Catepsina L/antagonistas & inibidores , Catepsina L/genética , Cloroquina/uso terapêutico , Inibidores de Cisteína Proteinase/uso terapêutico , Predisposição Genética para Doença , Heparina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lisossomos/enzimologia , Terapia de Alvo Molecular , Receptores Virais/metabolismo , /ultraestrutura , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Teicoplanina/uso terapêutico , Internalização do Vírus
3.
Virus Res ; 286: 198073, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32592817

RESUMO

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. Up to now, numerous medicines have been applied or approved for the prevention and control of the virus infection. However, the efficiency of each medicine or combination is completely different or still unknown. In this review, we discuss the types, characteristics, antiviral mechanisms, and shortcomings of recommended candidate medicines for SARS-CoV-2 infection, as well as perspectives of the drugs for the disease treatment, which may provide a theoretical basis for drug screening and application.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Betacoronavirus/imunologia , China/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Indóis/uso terapêutico , Interferons/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Pirazinas/uso terapêutico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico , Análise de Sobrevida , Teicoplanina/uso terapêutico
4.
BMC Infect Dis ; 20(1): 322, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375669

RESUMO

BACKGROUND: Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis. CASE PRESENTATION: A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient's condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient's hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus-IgM antibodies positive on rapid diagnostic test. The patient's symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis. CONCLUSIONS: Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.


Assuntos
Antibacterianos/uso terapêutico , Pielonefrite/tratamento farmacológico , Pielonefrite/etiologia , Tifo por Ácaros/complicações , Tifo por Ácaros/tratamento farmacológico , Ceftriaxona/uso terapêutico , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/etiologia , Doxiciclina/uso terapêutico , Febre/tratamento farmacológico , Humanos , Masculino , Meropeném/uso terapêutico , Pessoa de Meia-Idade , Nepal , Teicoplanina/uso terapêutico
6.
J Microbiol Immunol Infect ; 53(3): 436-443, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32307245

RESUMO

An outbreak related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019. An extremely high potential for dissemination resulted in the global coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in clinical treatment of COVID-19 patients in large-scale studies. Remdesivir is considered the most promising antiviral agent; it works by inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A large-scale study investigating the clinical efficacy of remdesivir (200 mg on day 1, followed by 100 mg once daily) is on-going. The other excellent anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard care. However, the regimen of LPV/RTV plus ribavirin was shown to be effective against SARS-CoV in vitro. Another promising alternative is hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1, followed by 250 mg once daily on day 2-5), which showed excellent clinical efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro. The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm) and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are under investigation. Avoiding the prescription of non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or angiotensin II type I receptor blockers is advised for COVID-19 patients.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva/métodos , Lopinavir/uso terapêutico , Pandemias , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico , Teicoplanina/uso terapêutico
7.
Int J Antimicrob Agents ; 55(6): 105969, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32278811

RESUMO

Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Pandemias , Teicoplanina/uso terapêutico
9.
Int J Antimicrob Agents ; 55(4): 105944, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32179150

RESUMO

In December 2019, a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China causing pneumonia outbreaks, first in the Wuhan region of China and then spread worldwide because of its probable high transmission efficiency. Owing to the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the best tool to find a therapeutic solution. Chloroquine, remdesivir, lopinavir, ribavirin and ritonavir have shown efficacy to inhibit coronavirus in vitro. Teicoplanin, an antibiotic used to treat staphylococcal infections, previously showed efficacy to inhibit the first stage of the Middle East respiratory syndrome coronavirus (MERS-CoV) viral life cycle in human cells. This activity is conserved against SARS-Cov-2, thus placing teicoplanin as a potential treatment for patients with this virus.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Teicoplanina/uso terapêutico , Betacoronavirus , Reposicionamento de Medicamentos , Humanos , Pandemias
10.
Medicine (Baltimore) ; 99(10): e18954, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150046

RESUMO

RATIONALE: In patients receiving biological therapies, serious infections are a major concern. Infections associated with anti-tumor necrosis factor antibody therapy include tuberculosis, viral, fungal, and bacterial infections. Likewise, severe infections of the upper and lower respiratory tract, lung, skin and soft tissue, urinary tract, gastrointestinal tract, joint, and bone have also been reported previously. However, infections involving the central nervous system are rare, especially an intracranial infection caused by odontogenic infection. To date, only few cases have been reported of this infection. This is the first case of a patient with psoriatic arthritis receiving adalimumab and developing brain abscess of odontogenic origin. PATIENT CONCERNS: A 39-year-old male with psoriatic arthritis receiving adalimumab treatment came to the emergency department with initial presentation of sudden onset convulsions. He had been receiving adalimumab treatment for 1 month. Two days after the third injection, the patient had an episode of sudden-onset general convulsion for nearly 5 min with the upgazing and general tonic presentation. Magnetic resonance imaging (MRI) showed left frontal lobe brain abscess. Pus culture from the brain abscess detected Streptococcus sanguinis (S. sanguinis), Fusobacterium nucleatum (F. nucleatum), and Parvimonas micra (P. micra). DIAGNOSIS: Brain abscess with odontogenic infection. INTERVENTIONS: The patient received left frontal craniotomy, abscess drainage and systemic empiric antibiotics treatment with vancomycin, cefepime, and metronidazole. Due to drug rash with eosinophilia and systemic symptoms during the treatment, vancomycin and metronidazole were discontinued, and systemic antibiotics were switched to teicoplanin and ceftriaxone. OUTCOMES: A brain MRI follow-up performed after 1 month of initial treatment revealed the reduced size of the abscess lesion and minimal oedema. The patient was discharged with stable condition. LESSONS: To the best of our knowledge, this is the first case of a patient with psoriatic arthritis receiving adalimumab and developing brain abscess of odontogenic origin. Such a rare diagnosis must be kept in mind when patients treated with adalimumab present with sudden-onset convulsions. Careful dental examination should be performed before administration of adalimumab.


Assuntos
Adalimumab/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Abscesso Encefálico/diagnóstico , Cérebro , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/etiologia , Abscesso Encefálico/microbiologia , Ceftriaxona/administração & dosagem , Ceftriaxona/uso terapêutico , Terapia Combinada , Craniotomia , Diagnóstico Diferencial , Firmicutes/isolamento & purificação , Fusobacterium nucleatum/isolamento & purificação , Humanos , Imagem por Ressonância Magnética , Masculino , Periodontite/complicações , Streptococcus/isolamento & purificação , Streptococcus sanguis , Teicoplanina/administração & dosagem , Teicoplanina/uso terapêutico
11.
J Knee Surg ; 33(2): 100-105, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31470454

RESUMO

The risk of surgical site infection in primary total knee arthroplasty (TKA) has been reduced with the use of prophylactic antibiotics. First or second generation cephalosporins are still recommended as the primary prophylactic choice, but with the rise in the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections, evidence has emerged in favor of using dual antibiotics including vancomycin. However, it is unclear whether these combinations of antibiotic regimens further reduce postoperative infection rates. As a result, the objective of this review is to summarize the current literature concerning the use of dual prophylactic antibiotics in TKA. The most common dual prophylactic antibiotic combination is cefazolin (C) and vancomycin (V). In general, when comparing the effectiveness of single versus dual antibiotics, conflicting results have been reported. Three studies demonstrated no substantial decrease in overall postoperative infection rates with the use of dual antibiotics when compared with cefazolin alone. One found a significant decrease only in MRSA infection rates when using cefazolin and vancomycin (CV) (0.8% C alone vs. 0.08% CV, p < 0.05). Another investigation evaluated revision TKA patients who had combined cefazolin and vancomycin prophylaxis and showed a significant decline in both overall infection (7.89% [C] vs. 3.13% [CV]) and MRSA infection rates (4.21% [C] vs. 0.89% [CV]; p < 0.05). Concerning the safety profile of dual antibiotics, particular precautions must be adopted with the use of vancomycin because of the risk of acute kidney injury. Instead of vancomycin, an alternate less nephrotoxic antibiotic option might be teicoplanin. Unfortunately, this latter agent is only available outside of the United States. In conclusion, the value of dual antibiotic prophylaxis for the prevention of periprosthetic knee infections remains unclear primarily because all comparative studies performed between dual and single antibiotics have been of low evidence with retrospective designs. Larger multicenter randomized controlled trials are warranted.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/normas , Artroplastia do Joelho , Cefazolina/administração & dosagem , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/administração & dosagem , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Artroplastia do Joelho/efeitos adversos , Cefazolina/uso terapêutico , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/microbiologia , Teicoplanina/administração & dosagem , Teicoplanina/uso terapêutico , Vancomicina/uso terapêutico
12.
J Infect Chemother ; 26(2): 242-251, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31575499

RESUMO

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia. This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed. In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31-14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35-7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26-9.92) were risk factors for mortality. In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.


Assuntos
Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Pneumonia Estafilocócica/tratamento farmacológico , Teicoplanina/uso terapêutico , Vancomicina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Monitoramento de Medicamentos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Pneumonia Estafilocócica/mortalidade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
13.
Int J Infect Dis ; 91: 202-205, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31841726

RESUMO

There is a paucity of literature on the use of dalbavancin, a long-acting lipoglycopeptide, in infective endocarditis. Existing case reports have investigated dalbavancin in endocarditis as a sequential treatment after clearance of bacteria from the bloodstream with conventional therapy. A 27-year-old female who injects drugs presented with fever and pleuritic chest pain and was found to have methicillin-sensitive Staphylococcus aureus tricuspid-valve endocarditis with septic pulmonary emboli. Given non-adherence with conventional therapy, she was successfully treated off-label with once-weekly dalbavancin infusions in an outpatient setting. We summarize the patient's clinical course and review published reports of endocarditis treated with dalbavancin in the peer-reviewed literature. Our case supports further investigation of outpatient dalbavancin infusions as a reasonable therapeutic alternative to standard treatment with daily intravenous therapy for serious staphylococcal infections among patients who have difficulty engaging with conventional therapy.


Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Doenças das Valvas Cardíacas/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/análogos & derivados , Valva Tricúspide , Adulto , Antibacterianos/administração & dosagem , Usuários de Drogas , Endocardite Bacteriana/diagnóstico , Feminino , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/microbiologia , Humanos , Infusões Intravenosas , Pacientes Ambulatoriais , Infecções Estafilocócicas/diagnóstico , Teicoplanina/administração & dosagem , Teicoplanina/uso terapêutico , Resultado do Tratamento
14.
J Infect Chemother ; 26(5): 459-464, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31870587

RESUMO

Empirical combination therapy with ß-lactams and glycopeptides is recommended for patients with presumed staphylococcal bloodstream infection (BSI). While coagulase-negative staphylococci (CNS) remain susceptible to vancomycin, such isolates have become less susceptible to teicoplanin. The aim of this retrospective study was to evaluate the clinical efficacy of teicoplanin in the treatment of BSI caused by methicillin-resistant CNS according to teicoplanin susceptibility. Inclusion criteria were patients with intravascular-catheter related BSIs caused by methicillin-resistant CNS (positive for two or more specimens); teicoplanin therapy; and at least one of the signs or symptoms caused by BSI. Antimicrobial resistance was defined as minimum inhibitory concentration (MIC) ≥8 µg/mL. The primary efficacy endpoint was clinical success evaluated 2 weeks after the completion of teicoplanin therapy [test of cure (TOC)]. Resistant rate of CNS was 0% for vancomycin and 22.9% for teicoplanin, and geometric mean MICs were 1.31 µg/mL and 3.41 µg/mL, respectively (p < 0.001). The catheter was removed in all patients except one, and high early clinical response at 72 h after starting therapy was obtained irrespective of teicoplanin susceptibility. The clinical success rate at TOC was 60% in patients with BSIs caused by teicoplanin-resistant strains, while 90% in patients with BSIs caused by susceptible strains (p = 0.052). In multivariate analyses, teicoplanin resistance was significant factor for decreased clinical success at TOC (adjusted odds ratio 0.138, 95% confidence interval 0.020-0.961, p = 0.045). Because of the poor clinical efficacy of teicoplanin against teicoplanin-resistant CNS, combination therapy comprising vancomycin and ß-lactam antibiotics should be considered in presumed staphylococci BSI.


Assuntos
Bacteriemia/tratamento farmacológico , Resistência a Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/isolamento & purificação , Teicoplanina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Coagulase/metabolismo , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus haemolyticus/efeitos dos fármacos , Staphylococcus haemolyticus/isolamento & purificação , Resultado do Tratamento , Vancomicina/uso terapêutico
15.
O.F.I.L ; 30(2): 127-130, 2020.
Artigo em Espanhol | IBECS | ID: ibc-190990

RESUMO

La pandemia del coronarius (COVID-19) desencadenada en China en diciembre de 2019 representa un desafío terapéutico mundial. A la fecha se han propuesto gran diversidad de fármacos con potencial para tratar la enfermedad. La gran mayoría de los mismos ya existían, previo a la pandemia, para el tratamiento de otras patologías. Sin embargo, ninguno ha demostrado eficacia, en ensayos clínicos de calidad, que avalen su empleo de manera específica para COVID-19. En este contexto, el costo de los mismos y su disponibilidad se vuelven factores fundamentales, particularmente en el ámbito de Latinoamérica. En el presente artículo, se revisarán características claves de medicamentos conocidos y asequibles en la República Argentina y resto de América Latina que han demostrado potencialidad para el abordaje terapéutico del COVID-19: hidroxicloroquina, cloroquina, ivermectina y teicoplanina


The coronavirus (COVID-19) pandemic triggered in China in December 2019 represents a global therapeutic challenge. To date, a wide variety of drugs, with potential to treat the disease, have been proposed. The vast majority of them, are medications that existed, prior to the pandemic, used to treat other pathologies. However, none has demonstrated to be effective in well designed clinical trials that specifically endorse its use for COVID-19. In this context, their cost and availability becomes a fundamental factor, particularly in Latin America. This article will review key characteristics of known and affordable medications in Argentina and the rest of Latin America: hydroxychloroquine, chloroquine, ivermectin and teicoplanin


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Pandemias , Hidroxicloroquina/uso terapêutico , Cloroquina/uso terapêutico , Ivermectina/uso terapêutico , Teicoplanina/uso terapêutico
16.
Klin Mikrobiol Infekc Lek ; 26(2): 51-53, 2020 Jun.
Artigo em Eslovaco | MEDLINE | ID: mdl-33389741

RESUMO

The article discusses dalbavancin, a relatively new lipoglycopeptide antibiotic brought to market. It briefly describes the spectrum and mechanism of its antibacterial effect and dosing regimens that can be used in the treatment of skin and soft tissue infections. The authors present a case of a patient with shoulder phlegmon caused by MRSA who was successfully treated with this antibiotic.


Assuntos
Infecções Estafilocócicas , Teicoplanina/análogos & derivados , Antibacterianos/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/microbiologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/uso terapêutico , Extremidade Superior/patologia
17.
Sci Rep ; 9(1): 18533, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811214

RESUMO

Staphylococcus epidermidis infections are a common occurrence in hospitals, particularly in catheter-related bloodstream and surgical site infections and infective endocarditis. Higher daptomycin minimum inhibitory concentration (MIC) values may be associated with daptomycin treatment failure among patients with S. epidermidis infections. We therefore conducted a retrospective cohort study to determine the predictive value of daptomycin susceptibility. A retrospective study was undertaken in 1,337 patients with S. epidermidis infections. Data were collected from 1 January 2013 to 31 December 2016 at Ehime University Hospital, and included the following clinicopathological factors for evaluation: age, sex, resistance to vancomycin or teicoplanin, and history of antimicrobial therapy. Multiple analysis was performed using logistic regression to identify factors that independently and significantly affected the daptomycin resistance. Daptomycin-resistant S. epidermidis was identified in 38 (2.8%) patients. According to the multiple analysis, only higher MIC values (≥16 mg/L) for teicoplanin (P < 0.0001) were independently associated with an increased risk of developing daptomycin resistance. In conclusion, higher teicoplanin MIC values may predict resistance to daptomycin treatment in S. epidermidis infections.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Farmacorresistência Bacteriana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Teicoplanina/farmacologia , Idoso , Antibacterianos/uso terapêutico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Daptomicina/uso terapêutico , Relação Dose-Resposta a Droga , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/isolamento & purificação , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia , Teicoplanina/uso terapêutico , Falha de Tratamento
18.
PLoS One ; 14(12): e0227009, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887179

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 µg/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Teicoplanina/uso terapêutico , Resistência a Vancomicina/genética , Vancomicina/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Análise Mutacional de DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Regulação para Baixo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Índia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Mutação/efeitos dos fármacos , Óperon/efeitos dos fármacos , Óperon/genética , Proteínas de Ligação às Penicilinas/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções Estafilocócicas/microbiologia , Teicoplanina/farmacologia , Falha de Tratamento , Regulação para Cima , Vancomicina/uso terapêutico , Resistência a Vancomicina/efeitos dos fármacos
19.
Ann Clin Microbiol Antimicrob ; 18(1): 30, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31629409

RESUMO

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.


Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Sepse/tratamento farmacológico , Teicoplanina/análogos & derivados , Idoso , Antibacterianos/efeitos adversos , Análise Custo-Benefício , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Teicoplanina/efeitos adversos , Teicoplanina/uso terapêutico , Resultado do Tratamento
20.
Infection ; 47(6): 1013-1020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520397

RESUMO

PURPOSE: Dalbavancin is a novel lipoglycopeptide with potent activity against several gram-positive pathogens, an excellent safety profile and a long elimination half-life. METHODS: In this case series observed at the University Hospital of Vienna between 2015 and 2017, all adult patients with gram-positive infections who received at least one dosage of dalbavancin were screened (n = 118). A total of 72 patients were included in the final analysis. The number of included patients stratified by the source of infection was: skin and soft tissue infection (SSTI) (n = 26), osteomyelitis (n = 20), spondylodiscitis (n = 14), acute septic arthritis (n = 4) and prosthetic joint infection (n = 8). RESULTS: In 46 patients (64%), clinical cure was detected at the end of dalbavancin therapy without additional antibiotic therapy. Of the 26 patients who received additional antibiotic therapy other than dalbavancin, 15 patients (21%) showed no clinical improvement under dalbavancin therapy, four patients (5%) had side effects (nausea n = 1, exanthema n = 2, hyperglycemia n = 1), and in seven patients (10%) clinical improvement under dalbavancin therapy was detected but antibiotic therapy was de-escalated to an oral drug. CONCLUSION: We demonstrated high clinical effectiveness of dalbavancin for acute gram-positive infections primarily acute SSTI, acute septic arthritis, acute osteomyelitis and spondylodiscitis. In patients with biofilm-associated infection (chronic infection or joint prosthesis), source control was absolutely necessary for treatment success.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Dermatopatias Infecciosas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Teicoplanina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias Infecciosas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Teicoplanina/uso terapêutico , Adulto Jovem
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