https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50934 Wed 28 Feb 2024 16:27:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30053 Wed 11 Apr 2018 13:04:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28622 Nocardia asteroides and Nocardia cyriacigeorgica (each 11%). Linezolid was the only antimicrobial to which isolates were universally susceptible; 89% (48 of 54), 60% (32 of 53), and 48% (26 of 54) of isolates were susceptible to trimethoprim-sulfamethoxazole, ceftriaxone, and imipenem, respectively. Eighteen patients (30%) required intensive care unit (ICU) admission, and 1-year mortality was 31%. Conclusions: The incidence of nocardiosis in tropical Australia is amongst the highest reported globally. Nocardiosis occurs in both immunocompromised and immunocompetent hosts, and it is associated with high rates of ICU admission, 1-year mortality, and resistance to commonly recommended antimicrobials. Diagnosis should be considered in patients with consistent clinical features, particularly if they are Indigenous or have chronic lung disease.]]> Wed 11 Apr 2018 12:43:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24771 Staphylococcus aureus (MRSA) bacteraemia is a serious infection resulting in 20–50 % 90-day mortality. The limitations of vancomycin, the current standard therapy for MRSA, make treatment difficult. The only other approved drug for treatment of MRSA bacteraemia, daptomycin, has not been shown to be superior to vancomycin. Surprisingly, there has been consistent in-vitro and in-vivo laboratory data demonstrating synergy between vancomycin or daptomycin and an anti-staphylococcal β-lactam antibiotic. There is also growing clinical data to support such combinations, including a recent pilot randomised controlled trial (RCT) that demonstrated a trend towards a reduction in the duration of bacteraemia in patients treated with vancomycin plus flucloxacillin compared to vancomycin alone. Our aim is to determine whether the addition of an anti-staphylococcal penicillin to standard therapy results in improved clinical outcomes in MRSA bacteraemia. Methods/Design: We will perform an open-label, parallel-group, randomised (1:1) controlled trial at 29 sites in Australia, New Zealand, Singapore, and Israel. Adults (aged 18 years or older) with MRSA grown from at least one blood culture and able to be randomised within 72 hours of the index blood culture collection will be eligible for inclusion. Participants will be randomised to vancomycin or daptomycin (standard therapy) given intravenously or to standard therapy plus 7 days of an anti-staphylococcal β-lactam (flucloxacillin, cloxacillin, or cefazolin). The primary endpoint will be a composite outcome at 90 days of (1) all-cause mortality, (2) persistent bacteraemia at day 5 or beyond, (3) microbiological relapse, or (4) microbiological treatment failure. The recruitment target of 440 patients is based on an expected failure rate for the primary outcome of 30 % in the control arm and the ability to detect a clinically meaningful absolute decrease of 12.5 %, with a two-sided alpha of 0.05, a power of 80 %, and assuming 10 % of patients will not be evaluable for the primary endpoint. Discussion: Key potential advantages of adding anti-staphylococcal β-lactams to standard therapy for MRSA bacteraemia include their safety profile, low cost, and wide availability. Trial registration: ClinicalTrials.gov Identifier: NCT02365493. Registered 24 February 2015.]]> Wed 11 Apr 2018 11:47:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49739 Tue 30 May 2023 14:27:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54570 Tue 14 May 2024 14:06:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28396 Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.]]> Sat 24 Mar 2018 07:36:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28522 Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. Methods: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. Results: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P =. 06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Conclusions: Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).]]> Sat 24 Mar 2018 07:29:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54577 Sat 02 Mar 2024 10:02:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28017 Staphylococcus aureus (MRSA). Vancomycin remains an acceptable treatment option, with moves toward individualized dosing to a pharmacokinetic/pharmacodynamic (PK/PD) target. Numerous practicalities, however, would need to be resolved before implementation. Lipoglycopeptides as a class show excellent in vitro potency. Their long half-lives and complex PKs may preclude these agents being used in critically ill patients. Anti-MRSA cephalosporins provide great promise in the treatment of MRSA. These agents, despite broad-spectrum activity, should be reserved for patients with MRSA infections as it is likely that usage will be associated with increased rates of resistance. Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. The results of an open-labeled trial to address the superiority of daptomycin compared with vancomycin in reduced vancomycin susceptibility infections are eagerly anticipated. No drug to date has shown superiority to vancomycin in the treatment of MRSA infections with the possible exception of linezolid in hospital-acquired pneumonia (HAP), making linezolid an important option in the treatment of MRSA-proven HAP. Whether these strengths and features are agent or class specific are unclear but will likely be answered with the marketing of tedizolid. There are insufficient data to recommend either quinupristin/dalfopristin or tigecycline, as first line in the treatment of severe MRSA infections. These agents however remain options in patients with no other alternatives.]]> Fri 30 Jun 2017 16:44:10 AEST ]]>