Entity

Time filter

Source Type

Heidelberg, Australia

Holmes N.E.,Austin Center for Infection Research | Howden B.P.,Austin Center for Infection Research | Howden B.P.,University of Melbourne | Howden B.P.,Monash University
Current Opinion in Infectious Diseases | Year: 2014

Purpose of review Vancomycin has been the cornerstone of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections. This review describes new MRSA-active antibiotics that have recently been introduced and highlights emerging resistance. Recent findings Elevations in the vancomycin minimum inhibitory concentration within the susceptible range are associated with treatment failure and mortality in the treatment of MRSA infections. Ceftaroline and ceftobiprole are anti-MRSA cephalosporins and are noninferior to comparator agents in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and pneumonia. Tedizolid is more potent than linezolid, has improved pharmacokinetics and reduced toxicity and is active against cfr-containing S. aureus. Telavancin now has approval for treatment of hospital-acquired pneumonia, and recent phase 2 trial data showed similar cure rates in S. Aureus bacteremia. Dalbavancin and oritavancin are administered once weekly and are noninferior to comparators for acute bacterial skin and skin structure infections. Resistance has emerged against many new anti-MRSA antimicrobials including ceftaroline. Combination therapy of b-lactams with vancomycin or daptomycin is increasing. Summary Several new MRSA-active agents are now approved for use, although much of the data is derived from treatment of acute bacterial skin and skin structure infections or pneumonia. Further studies are required for more invasive infections, such as bacteremia and endocarditis. © 2014 Wolters Kluwer Health-Lippincott Williams & Wilkins. Source


Tomasini A.,University of Strasbourg | Francois P.,University of Geneva | Howden B.P.,Austin Center for Infection Research | Howden B.P.,University of Melbourne | And 4 more authors.
Infection, Genetics and Evolution | Year: 2014

RNA molecules with regulatory functions in pathogenic bacteria have benefited from a renewed interest these two last decades. In Staphylococcus aureus, recent genome-wide approaches have led to the discovery that almost 10-20% of genes code for RNAs with critical regulatory roles in adaptive processes. These RNAs include trans-acting RNAs, which mostly act through binding to target mRNAs, and cis-acting RNAs, which include regulatory regions of mRNAs responding to various metabolic signals. Besides recent analysis of S. aureus transcriptome has revealed an unprecedented existence of pervasive transcription generating a high number of weakly expressed antisense RNAs along the genome as well as numerous mRNAs with overlapped regions. Here, we will illustrate the diversity of trans-acting RNAs and illustrate how they are integrated into complex regulatory circuits, which link metabolism, stress response and virulence. © 2013 Elsevier B.V. Source


Omansen T.F.,University of Melbourne | Omansen T.F.,University of Groningen | Porter J.L.,University of Melbourne | Johnson P.D.R.,University of Melbourne | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2015

Mycobacterium ulcerans causes Buruli ulcer (BU), a debilitating infection of subcutaneous tissue. There is a WHO-recommended antibiotic treatment requiring an 8-week course of streptomycin and rifampicin. This regime has revolutionized the treatment of BU but there are problems that include reliance on daily streptomycin injections and side effects such as ototoxicity. Trials of all-oral treatments for BU show promise but additional drug combinations that make BU treatment safer and shorter would be welcome. Following on from reports that avermectins have activity against Mycobacterium tuberculosis, we tested the in-vitro efficacy of ivermectin and moxidectin on M. ulcerans. We observed minimum inhibitory concentrations of 4–8 μg/ml and time-kill assays using wild type and bioluminescent M. ulcerans showed a significant dose-dependent reduction in M. ulcerans viability over 8-weeks. A synergistic killing-effect with rifampicin was also observed. Avermectins are well tolerated, widely available and inexpensive. Based on our in vitro findings we suggest that avermectins should be further evaluated for the treatment of BU. © 2015 Omansen et al. Source


Holmes N.E.,Austin Center for Infection Research | Hal S.J.V.,Royal Prince Alfred Hospital | Hal S.J.V.,University of Western Sydney
Seminars in Respiratory and Critical Care Medicine | Year: 2015

There has been a welcome increase in the number of agents available for the treatment of methicillin-resistant 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. © 2015 by Thieme Medical Publishers, Inc. Source


Holmes N.E.,Austin Center for Infection Research | Howden B.P.,Austin Center for Infection Research | Howden B.P.,University of Melbourne | Howden B.P.,Monash University
Expert Review of Anti-Infective Therapy | Year: 2011

The Australian Society for Antimicrobials aims to facilitate the acquisition and dissemination of knowledge in the field of antimicrobials. Members and delegates come from a diverse range of professions including physicians, microbiologists, scientists, pharmacists, veterinarians and industry representatives from pharmaceutical and biomedical companies. Membership is primarily based in Australia and New Zealand, but extends to Asia, North America, Europe and the UK. A total of 330 participants attended the 2011 Annual Scientific Meeting with plenary speakers from the USA, Spain and Australia. This meeting report focuses on two key areas of antimicrobial resistance: community-associated methicillin-resistant Staphylococcus aureus and resistance in Gram-negative organisms. © 2011 Expert Reviews Ltd. Source

Discover hidden collaborations