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Melbourne, Australia

Abbott I.J.,Peter Doherty Institute | Peleg A.Y.,Alfred HospitalVIC | Peleg A.Y.,Monash University
Seminars in Respiratory and Critical Care Medicine | Year: 2015

Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and nonmelioid Burkholderia species, namely, Burkholderia cepacia complex, collectively are a group of troublesome nonfermenters. Although not inherently virulent organisms, these environmental Gram negatives can complicate treatment in those who are immunocompromised, critically ill in the intensive care unit and those patients with suppurative lung disease, such as cystic fibrosis. Through a range of intrinsic antimicrobial resistance mechanisms, virulence factors, and the ability to survive in biofilms, these opportunistic pathogens are well suited to persist, both in the environment and the host. Treatment recommendations are hindered by the difficulties in laboratory identification, the lack of reproducibility of antimicrobial susceptibility testing, the lack of clinical breakpoints, and the absence of clinical outcome data. Despite trimethoprim-sulfamethoxazole often being the mainstay of treatment, resistance is widely encountered, and alternative regimens, including combination therapy, are often used. This review will highlight the important aspects and unique challenges that these three nonfermenters pose, and, in the absence of clinical outcome data, our therapeutic recommendations will be based on reported antimicrobial susceptibility and pharmacokinetic/pharmacodynamic profiles.

News Article | April 22, 2016
Site: www.biosciencetechnology.com

Melbourne researchers have uncovered the genes responsible for the way the body fights infection at the point of 'invasion' - whether it's the skin, liver, lungs or the gut. Research led by Dr. Axel Kallies and Dr. Klaas van Gisbergen at the Walter and Eliza Hall Institute of Medical Research, and Dr. Laura Mackay from the University of Melbourne at the Peter Doherty Institute for Infection and Immunity has identified the genes Hobit and Blimp1 and found that these genes control a universal molecular program responsible for placing immune cells at the 'front lines' of the body to fight infection and cancer. The presence of these organ-residing cells, which differ strikingly from their counterparts circulating in the blood stream, is key to local protection against viruses and bacteria. Walter and Eliza Hall Institute's Dr. Kallies said the human body was fighting disease-causing pathogens every minute of its life. Dr. Kallies said identifying how immune cells remain in the part of the body where they are needed most was critical to developing better ways to protect us from infections such as malaria or HIV. "Discovering these 'local heroes' and knowing how the localised immune response is established allows us to find ways to ensure the required cells are positioned where they are needed most," Dr. Kallies said. "This research will help us understand how immune cells adapt, survive and respond within the organs they protect. This is critical to rid the body of pathogens even before they are established and may also have implications for understanding how the spread of cancer could be prevented." The Doherty Institute's Dr. Laura Mackay, who is also an associate investigator with the Australian Research Council Centre of Excellence in Advanced Molecular Imaging, said the factors that control the 'tissue-residency' of immune cells - their ability to locally reside in different organs of the body - was previously unknown. "These results have major implications for developing strategies to induce immune cells in tissues that protect against infectious diseases," Dr. Mackay said. "It's a crucial discovery for future vaccine strategies - Hobit and Blimp1 would be key to placing immune cells in the tissues, which we know are really important for protection." The findings have just been published in the journal Science.

Trubiano J.A.,Peter MacCallum Cancer Center | Leung V.K.,Peter MacCallum Cancer Center | Chu M.Y.,Peter MacCallum Cancer Center | Worth L.J.,Peter MacCallum Cancer Center | And 4 more authors.
Antimicrobial Resistance and Infection Control | Year: 2015

Background: Antibiotic allergy labels are associated with sub-optimal prescribing patterns and poorer clinical outcomes in non-cancer populations, but the effect of labelling on antimicrobial usage in patients with cancer is unknown. Findings: A retrospective review of hospitalized patients admitted to the Peter MacCallum Cancer Centre (2010-2012) identified 23 % of cancer patients (n = 198) with an antimicrobial allergy label (AA). Comparison of those with an antimicrobial allergy label to those without demonstrated increased antibiotic use per admission (3 vs. 2, p = 0.01), increased fluoroquinolone use (11 % vs. 6 %, p < 0.05), increased antibiotic course duration (15 vs. 13 days, p = 0.09), higher readmission rates (53 % vs. 28 %, p < 0.001) and poorer concordance with prescribing guidelines (47 % vs. 91 %, p < 0.001). Patients in the AA group on multivariate analysis had a higher number of antibiotics employed, longer duration of antibiotic therapy and higher rate of readmission. Conclusions: Antimicrobial usage, including the use of restricted antibiotics, is higher in patients with cancer. Antibiotic de-labelling strategies in cancer patients must be evaluated to aid antimicrobial stewardship initiatives. © 2015 Trubiano et al.; licensee BioMed Central.

Stratov I.,Peter Doherty Institute | Stratov I.,Melbourne Sexual Health Center | Kent S.J.,Peter Doherty Institute | Kent S.J.,Melbourne Sexual Health Center
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

Human immunodeficiency virus (HIV) management is entering a “universal test and treat” phase, although the benefits from this approach in developed world scenarios are uncertain. We analyzed 79 combination anti-retroviral therapy (cART)-naïve HIV-positive individuals who were intensively prospectively followed from 2004 to 2013. We studied HIV-related illnesses, potential HIV transmissions, impact on sexual behavior, and factors impeding earlier cART initiation. Sixty-eight (86 %) subjects commenced cART at a mean of 6.0 years after diagnosis: 71 % with a CD4 T-cell count <350 cells/μl. A significant minority of subjects (29 %) resisted initiation of cART despite physician recommendation for a mean of 18 months. Only one HIV-related illness occurred in a patient who had not previously recorded a CD4 T-cell count <500 cell/μl, totaling 195 person-years of observation. A 40 % increase in sexually transmitted infections (STIs) occurred after commencing cART. We detected six HIV transmissions in our cohort, all of which were before initiating cART and 5 of them had a prior CD4 T-cell count <500 cells/μl. Illnesses related to cART deferral were rare and most HIV transmissions we detected occurred in people with a prior CD4 T-cell count <500 cells/μl. Our study raises concerns about increasing STI rates after cART initiation. Focusing resources on cART initiation among patients with CD4 T-cell counts <500 cells/μl and enhancing safe sexual practices should remain a priority. © 2014, Springer-Verlag Berlin Heidelberg.

Towns J.M.,Melbourne Sexual Health Center | Leslie D.E.,Peter Doherty Institute | Denham I.,Melbourne Sexual Health Center | Azzato F.,Peter Doherty Institute | And 4 more authors.
Sexually Transmitted Infections | Year: 2016

Background Chancres, the hallmark of primary syphilis, are classically described as single, painless ulcers at the site of Treponema pallidum inoculation. We aimed to determine the frequency of painful or multiple anogenital lesions of primary syphilis among men, whether there was concurrent herpes simplex virus (HSV) infection and whether HIV status altered clinical presentations. Methods This study was conducted among men with T. pallidum PCR-positive lesions, attending a clinic in Melbourne, Australia, between 2009 and 2014. Lesions were also tested with HSV PCR, and syphilis serology undertaken. Results 183 men with T. pallidum PCR-positive primary anogenital lesions were included. 89% were men who have sex with men, and 10.9% were heterosexual. 38 men (20.8%) were HIV positive. Anal lesions were more common in HIV-positive men (34.2%) than in HIV-negative men (11.6%). Primary lesions were frequently painful (49.2%) or multiple (37.7%), and infrequently associated with HSV (2.7%). Of 37 men with both painful and multiple primary lesions, only 8% had concurrent HSV. Presentation was not significantly altered by HIV status. Conclusions Primary syphilis lesions are often painful and/or multiple in the absence of herpes coinfection, and may be clinically misdiagnosed.

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