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BackgroundProspective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting.Materials/methodsWe prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MSLT) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams.ResultsOver four years (April 2017 to July 2021) 2,660 isolates were sequenced. This included MDR gram-negative bacilli (n=293 CPE, n=1309 ESBL), MRSA (n=620) and VRE (n=433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the three target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In one hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy.ConclusionsImplementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.SummaryWe initiated a program of routine sequencing of multi-drug resistant organisms. A custom analysis pipeline was used to automate reporting by incorporating clinical meta-data with genomics to define clusters and support infection control interventions.

Background COVID‐19 is known to cause an acute respiratory illness, although clinical manifestations outside of the respiratory tract may occur. Early reports have identified SARS‐CoV‐2 as a cause of subacute thyroiditis (SAT). Methods A systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Web of Science and PubMed databases were queried in February 2021 for studies from December 2019 to February 2021. MeSH search terms “COVID‐19”, “SARS‐CoV‐2” and “coronavirus” along with search terms “thyroiditis”, “thyrotoxicosis”, “thyroid” were used. Descriptive statistics for continuous variables and proportions for categorical variables were calculated. Results 15 publications reporting on 17 individual cases of COVID‐19 induced SAT were identified. Age ranged from 18 to 69 years old. The majority of the cases were female (14 of 17, 82%). The delay between onset of respiratory symptoms and diagnosis of SAT ranged from 5 to 49 days (mean, 26.5). Systemic inflammatory response syndrome (SIRS) related to viral infection was uncommonly reported at the time of SAT diagnosis. Thyroid ultrasonography frequently reported an enlarged hypoechoic thyroid with decreased vascularity and heterogenous echotexture. Elevated CRP was common at the time of SAT diagnosis, with results ranging from 4.5 to 176 mg/L (mean, 41 mg/L). Anti‐thyroid antibodies were frequently negative. SAT specific treatment included corticosteroids for 12/17 (70.5%) patients. Most return to normal thyroid status. Conclusion COVID‐19 associated SAT may be difficult to identify in a timely manner due to potential absence of classic symptoms, as well as cross‐over of common clinical features between COVID‐19 and thyrotoxicosis. This article is protected by copyright. All rights reserved.

People who inject drugs (PWID) are susceptible to endovascular and deep-seated infections which require prolonged antibiotic therapy. There are concerns regarding this cohort's suitability for outpatient parenteral antimicrobial therapy (OPAT), but relatively little published data. Our aim is to publish our outcomes in this setting, to inform other clinicians' decisions regarding PWID in OPAT. We reviewed case records of all PWID in our OPAT service from July 2015 to December 2017. Successful completion of OPAT care was defined as completing the duration of parenteral therapy as planned at the outset, with expected clinical improvement. Data was collected on complications including hospital re-admission, new blood stream infections, patient non-compliance including ongoing non-prescribed intravenous drug use, and staff safety compromise. Twenty-eight of 38 (76.2%) episodes of OPAT care for PWID were completed successfully, with 724 bed days of care provided. The cohort was labour intensive to manage with high rates of re-admission, non-attendance and line-associated infections. There were no adverse events for staff safety, and no patient deaths on the programme. OPAT can be a viable option for PWID provided there is careful patient selection, good patient engagement and sufficient resources allocated for patient management.

Background. Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016–2018. Methods. A. baumannii, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa isolates were sequenced using the Illumina platform primarily to establish isolate relationships based on core-genome SNPs, MLST and antimicrobial resistance gene profiles. Representative isolates were selected for PacBio sequencing. Environmental metagenomic sequencing with Illumina was used to detect persistence of the outbreak strain in the hospital. Results. In response to a suspected polymicrobial outbreak between May to August of 2016, 28 CR-Ab (and 21 other MDR Gram-negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7 day turn-around time in clinical reporting. All CR-Ab were sequence type (ST)1050 (Pasteur ST2) and within 10 SNPs apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since. Conclusion. We implemented a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole genome sequencing (WGS) response to a polymicrobial outbreak in a Brisbane hospital between 2016-2018. 28 CR-Ab (and 21 other MDR Gram negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7-day turn-around-time in clinical reporting. All CR-Ab were sequence type (ST)1050 and within 10 single nucleotide polymorphisms (SNPs) apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since. Here we demonstrate implementation of a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.

Objectives Candidaemia carries a mortality of up to 40% and may be related to increasing complexity of medical care. Here, we determined risk factors for the development of candidaemia. Methods We conducted a prospective, multi-centre, case-control study over 12 months. Cases were aged ≥18 years with at least one blood culture positive for Candida spp. Each case was matched with two controls, by age within 10 years, admission within 6 months, admitting unit, and admission duration at least as long as the time between admission and onset of candidaemia. Results A total of 118 incident cases and 236 matched controls were compared. By multivariate analysis, risk factors for candidaemia included neutropenia, solid organ transplant, significant liver, respiratory or cardiovascular disease, recent gastrointestinal, biliary or urological surgery, central venous access device, intravenous drug use, urinary catheter and carbapenem receipt. Conclusions Risk factors for candidaemia derive from the infection source, carbapenem use, host immune function and organ-based co-morbidities. Preventive strategies should target iatrogenic disruption of mucocutaneous barriers and intravenous drug use.

ObjectiveThis study compared the costs and patient movements of a new hospital protocol to discontinue contact precautions for patients with non-multiresistant methicillin-resistant Staphylococcus aureus (nmMRSA), based on whole-genome sequencing (WGS) of pathogens with current practice. MethodsA hybrid simulation model was constructed and analysed over a 12-month time horizon. Six multidrug-resistant organisms and influenza were modelled concurrently where infected patients competed for isolation beds. Model inputs included pathogen incidence, resources for WGS, staff and contact precautions, hospital processes, room allocations and their associated costs. Data were sourced from aggregated records of patient admissions during 2017–18, clinical records and published reports. ResultsThe WGS protocol resulted in 389 patients isolated (44% of current practice), 5223 ‘isolation bed days’ (56%) and 268 closed-bed days (88%). Over 1 year, the mean (±s.d.) total cost for the WGS protocol was A$749243±126667; compared with current practice, the overall cost savings were A$690864±300464. ConclusionUsing WGS to inform infection control teams of pathogen transmission averts patients from isolation rooms and reduces significant resources involved in implementing contact precautions. What is known about the topic?There are an estimated 265000 hospital-acquired infections (HAI) in Australia each year. WGS can accurately identify the genetic lineage among HAIs and determine transmission clusters that can help infection control staff manage patients. Economic appraisals are lacking to inform whether pathogen genomics services should be adopted within already-stretched hospital budgets. What does this paper add?An isolation protocol using pathogen genomics to provide additional information on the relatedness of a pathogen between colonised patients showed favourable results for healthcare costs and patient flow. Using WGS, in a confirmatory role, to discontinue certain patients from contact precautions and isolation rooms resulted in cost savings of A$690864 across 1 year for a single major hospital. What are the implications for practitioners?Using pathogen WGS services for infection control potentially curbs hospital spending, averts patient isolations and improves patient flow within hospitals.

Objectives: To investigate the epidemiology, clinical characteristics and outcomes of those with hepatitis delta virus (HDV) infection in Queensland, Australia. Design: Retrospective cohort study of individuals tested for HDV between 1997 and 2016 in the public healthcare system in Queensland. Results: 179 individuals recorded positive HDV serology between 1997 and 2016, with a total of 4407 individuals undergoing testing (seroprevalence 4.1%). The majority of HDV positive individuals were male and were born overseas. Those born in Africa had a higher risk ratio (RR) for HDV infection (RR, 1.55; 95% CI, 1.14-2.09); being born in Asia was associated with a relatively lower risk of HDV infection (RR, 0.36; 95% CI, 0.27-0.58). Positive hepatitis C virus (HCV) serology was significantly associated with positive HDV serology (RR, 2.98; 95% CI, 2.36-3.78). Of the HDV positive individuals born in Australia, the majority were HCV positive (69.8%). HDV positive individuals were less likely to be Hepatitis B e antigen (HBeAg) positive (RR, 0.64; 95% CI, 0.45-0.93) and recorded lower hepatitis B virus (HBV) viral loads. Positive HDV serology was associated with increased risk of liver cirrhosis (RR, 2.3; 95% CI 1.73-3.07) and liver transplantation (RR, 1.93; CI 1.31-2.85). Only 8% of HDV positive individuals underwent HDV treatment. Conclusions: In Queensland, HDV seropositivity is associated with overseas birth, particularly in Africa. HDV infection is associated with decreased HBV viraemia and more advanced liver disease. Keywords: Hepatitis D virus, HDV, Viral hepatitis, Epidemiology Australia

Background Rapid diagnosis and appropriate treatment is imperative in bacterial sepsis due increasing risk of mortality with every hour without appropriate antibiotic therapy. Atypical infections with fastidious organisms may take more than 4 days to diagnose leading to calls for improved methods for rapidly diagnosing sepsis. Capnocytophaga canimorsus is a slow-growing, fastidious gram-negative bacillus which is a common commensal within the mouths of dogs, but rarely cause infections in humans. C. canimorsus sepsis risk factors include immunosuppression, alcoholism and elderly age. Here we report on the application of emerging nanopore sequencing methods to rapidly diagnose an atypical case of C. canimorsus septic shock. Case presentation A 62 year-old female patient was admitted to an intensive care unit with septic shock and multi-organ failure six days after a reported dog bite. Blood cultures were unable to detect a pathogen after 3 days despite observed intracellular bacilli on blood smears. Real-time nanopore sequencing was subsequently employed on whole blood to detect Capnocytophaga canimorsus in 19 h. The patient was not immunocompromised and did not have any other known risk factors. Whole-genome sequencing of clinical sample and of the offending dog’s oral swabs showed near-identical C. canimorsus genomes. The patient responded to antibiotic treatment and was discharged from hospital 31 days after admission. Conclusions Use of real-time nanopore sequencing reduced the time-to-diagnosis of Capnocytophaga canimorsus in this case from 6.25 days to 19 h. Capnocytophaga canimorsus should be considered in cases of suspected sepsis involving cat or dog contact, irrespective of the patient’s known risk factors. Electronic supplementary material The online version of this article (10.1186/s12879-019-4173-2) contains supplementary material, which is available to authorized users.

Introduction: Individuals with chronic hepatitis B virus (HBV) infection or past exposure to HBV infection have a substantial risk of reactivation during immunosuppressive cancer therapy. HBV reactivation can lead to liver failure, cancer treatment interruption or death. Clinical concordance with screening and treatment guidelines is inconsistent in practice, and existing international guidelines are not specific to the Australian context. We developed an Australian consensus statement with infectious diseases, hepatology, haematology and oncology specialists to inform hepatitis B screening and antiviral management for immunocompromised patients with haematological and solid organ malignancies in Australia. Main recommendations: Recommendations address four key areas of HBV infection management for immunocompromised patients with haematological and solid organ malignancies: who to test for HBV infection, when to start antiviral agents, when to stop antiviral agents, and how to monitor patients during cancer therapy. We recommend testing all patients undergoing cancer treatment for hepatitis B (including HBV surface antigen [HBsAg], HBV core antibody [anti-HBc], and HBV surface antibody) before cancer treatment. Individuals with chronic HBV infection (HBsAg positive) or past exposure (HBsAg negative and anti-HBc positive) receiving higher risk chemotherapy require antiviral prophylaxis using entecavir or tenofovir. Changes in management as a result of this statement: This consensus statement will simplify the approach to testing and prophylaxis for HBV infection during cancer therapy, and harmonise approaches to discontinuing and monitoring individuals which have been highly variable in practice. We advocate for broader Medicare Benefits Schedule and Pharmaceutical Benefits Scheme access to HBV testing and treatment for patients undergoing cancer therapy.

Background Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. Methods Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. Results The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into

Materials. File documenting in detail the methods and results of the enhanced molecular testing and investigations. Table 1. PCR primer and probe and corresponding synthetic control sequences designed against the C. canimorsus sequences generated from the initial whole-blood nanopore sequencing run. Highlighting indicates oligo targeting in the synthetic control. Figure S2. MinION sequencing time and C. canimorsus read count plot from initial d0 EDTA blood sample. (DOCX 78 kb)

Figure S4. Droplet Digital PCR results of the bespoke C. canimorsus assay showing A) positive and negative droplet counts and B) calculated absolute quantification of the target C. canimorsus template. (PDF 144 kb)

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p

We present a case of Capnocytophaga canimorsus septic shock after a dog bite in an immunocompetent individual, where real-time nanopore metagenomic sequencing characterized the microbial agent within 19 hours, with subsequent confirmation using droplet digital PCR. Oral swabs from the dog demonstrated a nearly-identical C. canimorsus isolate by sequencing.

Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia. Changing human population demographics, climate change, and increased understanding of expanding vector distribution indicate QTT is an emerging public health threat. This review summarizes the epidemiology, pathogenesis, clinical features, treatment principles, and future directions of this disease. Increased recognition of QTT will enable consideration of and prompt treatment of R. australis infection by clinicians in Australia.

This review sets out to evaluate the current evidence on the impact of inappropriate therapy on bloodstream infections (BSI) and associated mortality. Based on the premise that better prescribing practices should result in better patient outcomes, BSI mortality may be a useful metric to evaluate antimicrobial stewardship (AMS) interventions. A systematic search was performed in key medical databases to identify papers published in English between 2005 and 2015 that examined the association between inappropriate prescribing and BSI mortality in adult patients. Only studies that included BSIs caused by ESKAPE (Enterococcus faecium/faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) organisms were included. Study quality was assessed using the GRADE criteria and results combined using a narrative synthesis. We included 46 studies. Inappropriate prescribing was associated with an overall increase in mortality in BSI. In BSI caused by resistant gram positive organisms, such as methicillin resistant S. aureus, inappropriate therapy resulted in up to a 3-fold increase in mortality. In BSI caused by gram negative (GN) resistant organisms a much greater impact ranging from 3 to 25 fold increase in the risk of mortality was observed. While the overall quality of the studies is limited by design and the variation in the definition of appropriate prescribing, there appears to be some evidence to suggest that inappropriate prescribing leads to increased mortality in patients due to GN BSI. The highest impact of inappropriate prescribing was seen in patients with GN BSI, which may be a useful metric to monitor the impact of AMS interventions.

Antimicrobial resistance is a major threat to the delivery of effective care and already causes 700000 excess deaths per year worldwide. International consensus on action to combat antimicrobial resistance was reached in 2015. Australia is implementing a national strategy. The clinical consequences of antimicrobial resistance are seen most acutely in multi-drug resistant Gram-negative bacterial infections, where they cause increased mortality and morbidity and threaten the delivery of once routine medical care. The solution to antimicrobial resistance is complex and multifaceted. Antimicrobial stewardship, that is optimising the use of the antibiotics we currently have, is the most rapidly deployable mitigation. Several novel antibiotics with activity against a range of drug-resistant bacteria are now available clinically, leading to hope that innovative solutions will reduce the impact of resistance. It is critical that these new drugs are protected from inappropriate use.

Clostridium difficile infection causes colitis and is closely associated with the use of antimicrobials, probably due to disruption of the normal bowel flora. Avoiding inappropriate antimicrobial use is the most important way to prevent this potentially life-threatening infection. Emergent hypervirulent variants of C. difficile are associated with increased transmission, morbidity and mortality and have caused epidemics in North America and Europe. Cases have also been reported in Australia so intensified surveillance and antimicrobial stewardship is more important than ever. While any antimicrobial can precipitate C. difficile, fluoroquinolones, clindamycin and cephalosporins are particularly implicated. Other drugs, such as proton pump inhibitors, have also been associated with an increased incidence of C. difficile. Severe disease is managed in hospital. For non-severe disease, treatment generally includes supportive measures and treatment with oral metronidazole. Relapse is common.

Background and Aim The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia. Methods Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene. Results Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients. Conclusions The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.

Background: Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants. Methods: Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined. Results: Annual C. gattii infection incidence was 0.61 per 10⁶ population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of >= 256 predicted death and/or neurological sequelae (P = .05). Conclusions: Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are >= 512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE) are becoming increasingly more prevalent and provide significant morbidity and mortality. Providing curative therapy and overcoming bacterial resistance are difficult tasks with limited antibiotic options. Alternative antibiotics and approaches to therapy are required, with often a compromise in patient outcome.To demonstrate the effective use of therapeutic drug monitoring (TDM) in difficult-to-treat infections due to multiresistant gram-negative bacteria.A case of an elderly woman with an invasive cervical spine infection due to CRE is presented. Her protracted therapeutic course was complicated by multiple treatment failures and severe cervical spine instability. Therapeutic success, as determined by wound healing, cervical spine stability, and continued suppression of inflammatory markers, was obtained by continuous daily ertapenem infusions with TDM guiding the optimal drug dosing.In this unusual setting, TDM was utilized successfully to achieve favorable serum antibiotic concentrations and lead to control of the infection. TDM may be a useful tool in difficult-to-treat infections caused by multiresistant bacteria.

In this report, we present 11 cases of HIV infection where, in hindsight, there was a missed opportunity to diagnose HIV at an earlier stage of infection and therefore commence antiretroviral therapy earlier...

We report an unusual case of multidrug-resistant Escherichia coli bacteraemia causing multifocal abscesses, septic arthritis, lumbar discitis and osteomyelitis after transrectal ultrasound-guided prostate biopsy, requiring restricted antibiotics and surgical debridement. This case highlights the importance of risk assessment, prophylactic and therapeutic antimicrobial use, and urology infectious diseases collaboration to improve clinical outcomes after such procedures.

Queensland Tick Typhus (QTT; Rickettsia australis) is a Spotted Fever Group (SFG) rickettsial infection endemic to Australia. It is an underreported and often unrecognized illness with poorly defined epidemiology. This article describes epidemiological features and the geographical distribution of QTT in hospitalized patients. Cases of QTT were identified retrospectively from 2000–2015 at five sites in Northern Brisbane through a pathology database. Included cases had a four-fold rise in SFG-specific serology, a single SFG-specific serology ≥256 or an SFG-specific serology ≥128 with a clinically consistent illness. Of the fifty cases identified by serology, 36 were included. Age ranged from 3–72 years (with a mean of 39.5 years) with a male-to-female ratio of 1:1.1. Fifteen of 36 (42%) study participants had hobbies and/or occupations linked with the acquisition of the disease. Seventeen of 36 (47%) identified a tick bite in the days preceding presentation to hospital, and reported exposure to a known animal host was minimal (25%). QTT infection occurred throughout the year, with half reported between April and July. Recent ecological and sociocultural changes have redefined the epidemiology of this zoonotic illness, with areas of heightened infection identified. Heightened public health awareness is required to monitor QTT disease activity.

Objectives: Knowledge of contemporary epidemiology of candidaemia is essential.We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/10 population. The median patient agewas 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/ echinocandin co-resistance. Conclusions:We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.

Background. We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months. Methods. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined. Results. Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema. Conclusions. Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.

The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia.Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene.Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients.The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.

1 Centre for Disease Control, Department of Health, Northern Territory, Australia, 2 Royal Darwin Hospital, Department of Health, Northern Territory, Australia, 3 Menzies School of Health Research, Darwin, Northern Territory, Australia, 4 School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia, 5 Public Health Virology, Forensic and Scientific Services, Queensland Health, Queensland, Australia

Owing to concern about aminoglycoside-related acute kidney injury (AKI) in therapy for febrile neutropenia, the aim of this study was to ascertain the incidence, severity and persistence of AKI secondary to aminoglycoside use for febrile neutropenia at an adult tertiary referral hospital. All admitted adults with neutropenia in a 27-month period were reviewed. Cases of febrile neutropenia due to chemotherapy who received an aminoglycoside were identified and renal function was assessed up to Day 30 after aminoglycoside administration. Transient renal impairment (TRI) was defined as any temporary rise in serum creatinine of >44 μmol/L within 30 days; and persistent, significant renal impairment (PSRI) was defined as an elevation of serum creatinine of >44 μmol/L at Day 30, or death from renal failure or need for dialysis. The Acute Kidney Injury Network (AKIN) stage for all episodes was also determined. Amongst 554 episodes of neutropenia, 148 episodes of chemotherapy-related febrile neutropenia with aminoglycoside treatment were identified. PSRI occurred in six episodes [4.1%; 95% confidence interval (CI) 1.9-8.6%] and TRI occurred in seven episodes (4.7%; 95% CI 2.3-9.4%). No PSRI was attributable to aminoglycoside therapy alone (0%; 95% CI 0-3.2%). Severe sepsis was the main cause of PSRI. Aminoglycoside therapy was the main contributing cause of TRI in two episodes (1.4%; 95% CI 0.2-5.3%). In conclusion, PSRI is a rare complication of aminoglycoside therapy for febrile neutropenia at this institution. AKIN stage 1 AKI is a common complication of febrile neutropenia episodes in which aminoglycosides are administered.

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p