RESUMO
INTRODUCTION: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB. METHODS AND ANALYSIS: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study. ETHICS AND DISSEMINATION: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL8347 (the Netherlands Trial Register).
Assuntos
Bacteriemia , Infecções Estafilocócicas , Adulto , Humanos , Antibacterianos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Bacteriemia/microbiologia , Duração da Terapia , Staphylococcus aureus , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Staphylococcus aureas bacteraemia can spread to cause endocartitis, spondylodiscitis or infection of vascular or joint prostheses. Endogenous endophtalmitis is a serious complication which may result in permanent visual loss of the affected eye. Treatment consists of intra-ocular injection of antibiotics or a vitrectomy. CASE DESCRIPTION: A 79-year-old man attended the emergency department because of septic arthritis. Blood cultures were positive for a S. aureus bacteraemia. On the second day of admission he developed a blurred vision and he was diagnosed with an endophtalmitis. The patient was referred to an academic hospital for treatment with intra-ocular antibiotics. After treatment his vision improved again. CONCLUSION: Visual complaints should be taken seriously when a patient has a proven S. aureus bacteraemia. Infectious disease consultation may accelerate early recognition, referral and treatment. When endophtalmitis is suspected, it is essential to refer the patient to a treatment centre where intra-ocular antibiotics can be administered.
Assuntos
Bacteriemia/microbiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Transtornos da Visão/microbiologia , Idoso , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/microbiologia , Bacteriemia/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Humanos , Masculino , Infecções Estafilocócicas/tratamento farmacológico , Transtornos da Visão/tratamento farmacológicoRESUMO
Tularemia is a zoonosis caused by different subspecies of the Gram-negative bacterium Francisella tularensis. We report the first case in the Netherlands of pneumonic tularemia caused by the F. tularensis subspecies holarctica after probable occupational inhalation of contaminated aerosols. Notification of cases of tularemia has been mandatory by law in the Netherlands since 1 November 2016.
Assuntos
Francisella tularensis , Pneumonia Bacteriana/microbiologia , Tularemia/complicações , Jardinagem , Humanos , Pessoa de Meia-Idade , Países BaixosRESUMO
Bacterial infections such as febrile urinary tract infection (fUTI) may run a complicated course that is difficult to foretell on clinical evaluation only. Because the conventional biomarkers erythrocyte sedimentation rate (ESR), leucocyte count, C-reactive protein (CRP) and procalcitonin (PCT) have a limited role in the prediction of a complicated course of disease, a new biomarker-plasma midregional pro-adrenomedullin (MR-proADM)-was evaluated in patients with f UTI. We conducted a prospective multicentre cohort study including consecutive patients with f UTI at 35 primary-care centres and eight emergency departments. Clinical and microbiological data were collected and plasma biomarker levels were measured at presentation to the physician. Survival was assessed after 30 days. Of 494 fUTI patients, median age was 67 (interquartile range 49-78) years, 40% were male; two-thirds of them had significant co-existing medical conditions. Median MR-proADM level was 1.42 (interquartile range 0.67-1.57) nM; significantly elevated MR-proADM levels were measured in patients with bacteraemia, those admitted to the intensive care unit, and in 30-day and 90-day non-survivors, compared with patients without these characteristics. The diagnostic accuracy for predicting 30-day mortality in fUTI, reflected by the area-under-the-curve of receiver operating characteristics were: MR-proADM 0.83 (95% CI 0.71-0.94), PCT 0.71 (95% CI 0.56-0.85); whereas CRP, ESR and leucocyte count lacked diagnostic value in this respect. This study shows that MR-proADM assessed on first contact predicts a complicated course of disease and 30-day mortality in patients with fUTI and in this respect has a higher discriminating accuracy than the currently available biomarkers ESR, CRP, PCT and leucocyte count.
Assuntos
Adrenomedulina/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Febre/complicações , Febre/mortalidade , Precursores de Proteínas/sangue , Infecções Urinárias/mortalidade , Idoso , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Febre/sangue , Febre/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Infecções Urinárias/sangue , Infecções Urinárias/microbiologiaRESUMO
As patients with diabetes mellitus are at increased risk of developing tuberculosis, we hypothesized that this susceptibility to mycobacterial infection is due to a defective Th1-cytokine response. To explore this hypothesis, we examined four groups of subjects in Indonesia: 23 patients with tuberculosis, 34 patients with tuberculosis and diabetes, 32 patients with diabetes only and 36 healthy controls. Ex-vivo production of interferon (IFN)gamma, tumour necrosis factor-alpha and interleukin (IL)-1beta, 6, 10, -12 and -4 was measured following stimulation with Mycobacterium tuberculosis, Escherichia coli lipopolysaccharide and phytohaemagglutinin. Patients with active tuberculosis were found to have lower IFNgamma levels and a higher production of other pro-inflammatory cytokines and IL-4, both in the presence and absence of diabetes. Diabetes patients without tuberculosis, however, showed strongly reduced non-specific IFNgamma production, which is essential for inhibition of the initial growth of M. tuberculosis. Our data suggest that a defective non-specific immune response in diabetes may contribute to an increased susceptibility to develop tuberculosis.