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Clonal complex 398 (CC398) livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been reported worldwide in a variety of food-animal species. Although CC398 is synonymous with LA-MRSA, community-associated MRSA (CA-MRSA) variants have emerged, including the Panton–Valentine leukocidin (PVL)-positive ST398-V and ST398 single-locus variant ST1232-V, and the PVL-negative ST398-V clones. Using comparative genomic analysis, we determined whether ten CC398 MRSA bacteraemia episodes recently identified in Australia were due to LA-MRSA or CA-MRSA CC398. Isolates were sourced from the Australian Group on Antimicrobial Resistance S. aureus surveillance programme and episodes occurred across Australia. Whole-genome sequencing (WGS) and phylogenetic comparison of the ten CC398 bacteraemia isolates with previously published CC398 MRSA whole-genome sequences identified that the Australian CC398 isolates were closely related to the human-associated II-GOI clade and the livestock-associated IIa clade. The identified CC398 MRSA clones were: PVL-positive ST1232-V (5C2&5), PVL-negative community-associated ST398-V (5C2&5) and livestock-associated ST398-V (5C2&5). Our findings demonstrate the importance of using WGS and comparing the sequences with international sequences to distinguish between CC398 CA-MRSA and LA-MRSA and to determine the isolates’ origin. Furthermore, our findings suggest that CC398 CA-MRSA has become established in the Australian community and that ST398-V (5C2&5) LA-MRSA is now widespread in Australian piggeries. Our study emphasises the need for national One Health antimicrobial resistance surveillance programmes to assist in monitoring the ongoing epidemiology of MRSA and other clinically significant antimicrobial-resistant organisms.

Background Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. Objectives To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. Methods A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. Results All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM) = 0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to ≥3 antimicrobial classes, was low (1.7%; 19/1091). Conclusions The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected.

Background: Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. Objective(s): To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. Method(s): A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. Result(s): All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM)=0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to >=3 antimicrobial classes, was low (1.7%; 19/1091). Conclusion(s): The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected. Copyright © 2021 The Author(s). Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Corynebacterium macginleyi has long been associated with ocular infections and has more recently been rarely implicated in systemic infections. There is a paucity of literature regarding the rate of C. macginleyi co-infection with other bacterial and viral pathogens and regarding the incidence of C. macginleyi infection in the paediatric population. In this study, we report 30 isolates of C. macginleyi of ocular origin from 26 patients, identified using matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). The rates of co-isolation with bacterial and viral pathogens were 62% (n=16/26) and 39% (n=5/13), respectively, in this study. Of these, 13 patients had molecular testing performed as requested by treating clinicians for either the Chlamydia trachomatis/Neisseria gonorrhoeae PCR or herpes/enterovirus/adenovirus multiplex PCR. All isolates tested susceptible to linezolid, vancomycin and ciprofloxacin, with variable resistance to tetracycline, clindamycin and penicillin using EUCAST breakpoints.Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Trichomonas vaginalis (TV) infection is the leading cause of non-viral sexually transmitted infection (STI) globally and is endemic in rural and remote Australia. However, current accurate prevalence data for TV in urban Australia are scarce as TV is not a notifiable infection outside of the Northern Territory (NT). This study evaluated Australian guidelines for TV testing and determined TV prevalence among patients at a large urban public hospital in Melbourne, Australia. A retrospective analysis of genitourinary samples screened for STIs by multiplex polymerase chain reaction (MPCR) between May 2017 and April 2019 was performed. A total of 7155 results (5064 females) were included in the analysis. A prevalence for TV of 1.7% (n=123) was found, which was higher than Neisseria gonorrhoeae (1.4%, n=103) but less than Chlamydia trachomatis (5%, n=358). The highest rate of TV (3%) was found in females aged 30-44 years (n = 48). Routine MPCR improved TV detection almost six-fold compared with clinician request based testing. Current targeted testing guidelines for TV were inadequate for case finding in an urban setting, and clinical request among symptomatic patients was rare. MPCR testing provides a comprehensive testing strategy for curable STI, and removes the need for clinical suspicion of TV. Implementation of MPCR for STI screening can improve TV detection in populations not normally suspected to be at risk and therefore potentially reduce disease transmission or complications associated with undiagnosed infection.Copyright © 2020

Background: Universal screening has been proposed as a strategy to identify asymptomatic individuals infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mitigate transmission. Aim(s): To investigate the rate of positive tests among pregnant women in Melbourne, Australia. Method(s): We performed a cross-sectional prevalence study at three maternity hospitals (one tertiary referral hospital and two secondary maternities) in Melbourne, Australia. SARS-CoV-2 testing was offered to all pregnant women attending face-to-face antenatal visits and to those attending the hospital with symptoms of possible coronavirus disease, between 6th and 19th of May 2020. Testing was performed by multiplex-tandem polymerase chain reaction (PCR) on combined oropharyngeal and nasopharyngeal swabs. The primary outcome was the proportion of positive SARS-CoV-2 tests. Finding(s): SARS-CoV-2 testing was performed in 350 women, of whom 19 had symptoms of possible COVID-19. The median maternal age was 32 years (IQR 28-35 years), and the median gestational age at testing was 33 weeks and four days (IQR 28 weeks to 36 weeks and two days). All 350 tests returned negative results (p = 0%, 95% CI 0-1.0%). Conclusion(s): In a two-week period of low disease prevalence, the rate of asymptomatic coronavirus infection among pregnant women in Australia during the study period was negligible, reflecting low levels of community transmission.Copyright © 2020 Australian College of Midwives

Background: On 31 December 2019, the World Health Organization recognised clusters of pneumonia-like cases due to a novel coronavirus disease (COVID-19). COVID-19 became a pandemic 71 days later. Aim(s): To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia. Method(s): This is a retrospective, multi-centre case series. All patients with confirmed COVID-19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. Result(s): The median age of the patient cohort was 42 years (interquartile range (IQR), 24-53 years) with six men and five women. Eight (72.7%) patients had returned from Wuhan, one from Shenzhen, one from Japan and one from Europe. Possible human-to-human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co-morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75-21), all patients were discharged. Conclusion(s): This is a historical record of the first COVID-19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID-19 models of care and informing the management of COVID-19 over time as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection.Copyright © 2021 Royal Australasian College of Physicians

We present a case of late symptom onset of COVID-19 infection 72 days after initial diagnosis in an immunocompromised 53-year-old man. SARS-CoV-2 was cultured from his sputum sample at this time, and genomic sequencing suggested reinfection was unlikely. After receipt of convalescent plasma, SARS-CoV-2 became undetectable by PCR 111 days after diagnosis, although SARS-CoV-2 antibodies remained not detectable. This case posed difficult public health management issues in a low prevalence COVID-19 setting as the person required extended home isolation given his prolonged SARS-CoV-2 PCR detection.Copyright © 2021 by The Society for Healthcare Epidemiology of America. All rights reserved.

© 2020 Elsevier Ltd Of 1033 Escherichia coli urinary tract infection isolates collected from females >12 years of age in Australia in 2019, only 2 isolates were resistant to fosfomycin with a minimum inhibitory concentration (MIC) of >256 mg/L. Despite having different multilocus sequence types, the two isolates harboured an identical plasmid-encoded fosA4 gene. The fosA4 gene has previously been identified in a single clinical E. coli isolate cultured in Japan in 2014. Each fosfomycin-resistant isolate harboured two conjugative plasmids that possessed an array of genes conferring resistance to aminoglycosides, β-lactams, macrolides, quinolones, sulfonamides and/or trimethoprim.

In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.

Background. Recommended management of Staphylococcus aureus bacteremia (SAB) includes follow-up blood culture sets (BCs) to determine the duration of bacteremia. Duration of bacteremia is an important prognostic factor in SAB, and follow-up BCs have a critical role in differentiation of uncomplicated and complicated SAB. However, intermittent negative BCs occur in SAB. Clinical guidelines for SAB management do not specify an approach to follow-up BCs' collection or define the number of negative BCs required to demonstrate resolution of bacteremia. This study assessed the frequency of intermittent negative BCs in SAB and used these findings to formulate a recommendation for collection of follow-up BCs. Methods. This retrospective study reviewed 1071 episodes of SAB. Clinical and microbiological data including the duration of bacteremia and the occurrence of intermittent negative BCs (those preceded and followed by positive cultures) were considered. Results. Intermittent bacteremia occurred in 13% (140/1071) of episodes. A single negative BC on days 1-3 had a predictive value of 87%-93% for resolution of bacteremia, although this was improved if all BCs collected within the same day were considered. Conclusions. Intermittent negative BCs are common in SAB. Given this, we would not recommend accepting a single negative BC as demonstrating resolution of the bacteremia. This is particularly important if a patient is to be classified as having uncomplicated SAB.Copyright © The Author(s) 2019.

Objectives: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. Setting(s): SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. Major outcomes: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. Result(s): A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. Conclusion(s): The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.Copyright © 2020 AMPCo Pty Ltd

Objectives: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. Design(s): Pilot prospective multicenter surveillance study. Setting(s): The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. Method(s): All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: VanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. Result(s): In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure. Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). Conclusion(s): Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively. Copyright © 2020 by The Society

Background: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). Aim(s): To describe the burden of IE and its outcomes in PWID. Method(s): Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. Result(s): Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P < 0.005). Twenty (16%) episodes resulted in death. Predictors of mortality on univariable analysis were left-sided cardiac involvement (RR 6.4), and not completing treatment (RR 0.12; both P < 0.001). The average estimated cost per episode was AU$74 168. Conclusion(s): IE causes a considerable burden of disease in PWID, with significant healthcare utilisation and cost. Surgery and death are not infrequent complications. In addition to ensuring completion of antimicrobial therapy, strategies such as opioid maintenance programmes may be useful in improving health outcomes for PWID.Copyright © 2019 Royal Australasian College of Physicians

Of 1033 Escherichia coli urinary tract infection isolates collected from females >12 years of age in Australia in 2019, only 2 isolates were resistant to fosfomycin with a minimum inhibitory concentration (MIC) of >256 mg/L. Despite having different multilocus sequence types, the two isolates harboured an identical plasmid-encoded fosA4 gene. The fosA4 gene has previously been identified in a single clinical E. coli isolate cultured in Japan in 2014. Each fosfomycin-resistant isolate harboured two conjugative plasmids that possessed an array of genes conferring resistance to aminoglycosides, beta-lactams, macrolides, quinolones, sulfonamides and/or trimethoprim.Copyright © 2020 Elsevier Ltd

High-throughput and rapid serology assays to detect the antibody response specific to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in human blood samples are urgently required to improve our understanding of the effects of COVID-19 across the world. Short-term applications include rapid case identification and contact tracing to limit viral spread, while population screening to determine the extent of viral infection across communities is a longer-term need. Assays developed to address these needs should match the ASSURED criteria. We have identified agglutination tests based on the commonly employed blood typing methods as a viable option. These blood typing tests are employed in hospitals worldwide, are high-throughput, fast (10-30 min), and automated in most cases. Herein, we describe the application of agglutination assays to SARS-CoV-2 serology testing by combining column agglutination testing with peptide-antibody bioconjugates, which facilitate red cell cross-linking only in the presence of plasma containing antibodies against SARS-CoV-2. This simple, rapid, and easily scalable approach has immediate application in SARS-CoV-2 serological testing and is a useful platform for assay development beyond the COVID-19 pandemic.

Japanese encephalitis (JE) virus is a mosquito-borne flavivirus endemic throughout Asia. Incidence in non-endemic countries is rare, with an estimate of less than one case per one million travelers. Most human JE infections are asymptomatic or cause a mild, nonspecific febrile illness. Neurological involvement, if present, is usually severe and associated with high mortality or ongoing neurological sequelae in survivors. Ocular manifestations are rare with JE, but uveitis has been described to be associated with other flavivirus infections, including West Nile virus. We report the first probable case of JE chorioretinitis acquired by a 45-year-old Australian traveler to Bali. This case highlights the importance of a detailed ocular examination when there is clinical suspicion of JE.Copyright © 2020 by The American Society of Tropical Medicine and Hygiene

Background: Australian National human immunodeficiency virus (HIV) Testing policy recommends HIV indicator condition-based testing, adapted from the European AIDS Clinical Society (EACS) guidelines. Aim(s): To evaluate the extent that Australian non-HIV specialty guidelines mention and recommend HIV testing in HIV indicator conditions. Method(s): EACS guidelines were reviewed to produce a list of 24 AIDS-defining conditions (ADC) and 31 indicator conditions (IC) where HIV prevalence >0.1%, and 5 IC where HIV non-diagnosis would have adverse effect on patients' management. Australian guidelines for these conditions were identified from websites of specialty societies, electronic Therapeutic Guidelines, National Health and Medical Research Council (NHMRC), state governments, MEDLINE and Google searches. We identified eight key IC as that were part of the HIDES I study. Result(s): Overall, 51 ADC and IC had Australian guidelines: 24/51(47%) mention association with HIV and 14/51 (27%) recommend HIV testing. Twenty-five out of 51 (49%) Australian guidelines were for ADC: 18/25(72%) mention association with HIV and 5/25 (20%) recommend testing. Twenty-five out of 51 (49%) were guidelines IC with HIV prevalence of 0.1%: 6/25 (24%) mention HIV association and 8/25 (32%) recommend HIV testing. Two of eight (25%) key IC had no Australian guidelines and 3/8 (38%) do not mention HIV association or recommend HIV testing. Conclusion(s): Although almost half of HIV non-HIV guidelines for ADC and IC mention HIV association, only 27% specifically recommend HIV testing. This suggests partnership with guideline development and specialist groups may be useful to ensure patients diagnosed with ADC/IC are tested for HIV.Copyright © 2019 Royal Australasian College of Physicians

Background: In the context of the pandemic, the rapid emergency use authorisation of diagnostic assays for SARS-CoV-2 has meant there are few peer-reviewed published studies of clinical performance of commercial assays. Aim(s): To evaluate the clinical performance of AusDiagnostics respiratory multiplex tandem PCR assay including SARS-CoV-2. Method(s): We reviewed the results following implementation of AusDiagnostics respiratory multiplex tandem PCR assay including SARS-CoV-2, and compared with an in-house RT-PCR assay at our State Reference Laboratory. Result(s): Initial validation using AusDiagnostics coronavirus multiplex tandem PCR assay including SARS-CoV-2 demonstrated good concordance with the State Reference Laboratory. After implementing the AusDiagnostics respiratory multiplex tandem PCR assay including SARS-CoV-2, we tested 7839 samples. 127 samples in which SARS-CoV-2 was detected using the AusDiagnostics assay were referred for testing at the State Reference Laboratory, with concordant results in 118/127 (92.9%) of samples. After resolution of discrepancies, 125/127 (98.4%) of AusDiagnostics results were determined to be true positive results. Out of 7839 samples tested for SARS-CoV-2 during this period, only 2 tests (0.02%) were indeterminate results. Conclusion(s): The AusDiagnostics respiratory MT-PCR assay is a reliable assay for detection of SARS-CoV-2.Copyright © 2020

Healthcare workers are at increased risk of occupational transmission of SARS-CoV-2. We report two instances of healthcare workers contracting SARS-CoV-2 despite no known breach of personal protective equipment. Additional specific equipment cleaning was initiated. Viral genomic sequencing supported this transmission hypothesis and our subsequent response.Copyright © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The decision to prescribe long-term or 'life-long' antibiotics in patients requires careful consideration by the treating clinician. While several guidelines exist to help assist in this decision, the long-term consequences are yet to be well studied. In this review, we aim to provide a summary of the available evidence for patient populations where long-term antibiotic therapy is currently recommended in clinical practice. We will also discuss the pitfalls of this approach, including medication adverse effects, economic cost and any possible contribution to the emerging epidemic of microbial resistance.Copyright © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Background: Some patients receive long-term or life-long antibiotics for suppression of infections deemed otherwise incurable. Little is known about the consequences of this strategy. We aimed to explore patients' attitudes towards and knowledge concerning prolonged antibiotic therapy. Method(s): A cross-sectional cohort pilot study of outpatients on long-term antibiotics was performed. Surveys were conducted at our healthcare network in Victoria, Australia between April and December 2015. Microbiological screening for multi-resistant organisms (MRO) was also performed. Result(s): Heterogeneity was noted in the prescribed antibiotics and documented indications, with rifampicin and fusidic acid for suppression of prosthetic joint infection the most common regimen and indication. 41% (12/29) of participants reported side-effects attributed to their antibiotics, but 72% (21/29) still declared complete adherence to their prescribed regimen. 76% (22/29) of participants stated that they would cease their long-term antibiotics based on medical advice. 19/29 (66%) participants consented to microbiological screening and 4 were found to be colonised with MROs. They had spent more days as an inpatient in the preceding 12 months than the screened participants who were not colonised. Conclusion(s): Participants in this study had a good understanding of their infection and the indications for their long-term antibiotic therapy, and were adherent to this therapy despite many experiencing side-effects attributed to their antibiotics. Patients who are prescribed life-long antibiotics can be carriers of multi-resistant organisms, but both the drivers of this resistance, and the broader impact of colonisation with MRO in this population is unclear.Copyright © 2019

Background: Gonorrhoea is usually managed in community sexual health or general practice, but a proportion of cases present to hospital settings. In this study, we examined how gonorrhoea was managed through a large hospital network and what the implications may be for public health management. Method(s): A retrospective chart review was performed of the management of patients with Neisseria gonorrhoeae infection diagnosed at a large Australian healthcare network from January 2015 to May 2018. Documentation rates of five parameters of care were assessed: (1) the presence (or absence) of previous sexually transmissible infections (STIs); (2) recent travel; (3) discussion of HIV testing; (4) contact tracing; and (5) public health notification. Result(s): In all, 110 cases (48 male, 62 female) were analysed. Most cases were in the 15-39 years age group; 98 cases (89%) were symptomatic, and 12 (11%) were screening tests. The most common presenting syndromes were pelvic inflammatory disease (32%; 31/98 symptomatic cases), urethritis (26%; 25/98) and epididymo-orchitis (13%; 13/98). None of the five parameters assessed were documented in most cases. Documentation was most likely to occur in patients admitted to hospital. When HIV testing was performed, no new cases of HIV were identified. Conclusion(s): Infections with gonorrhoea present on a regular basis to hospital practice, but overall management is suboptimal. Automated prompts for other recommended tests, including HIV testing when testing for other sexually transmissible diseases is ordered, may improve management. Better awareness of best practice is needed, which can be facilitated with ongoing education. However, the greatest benefit is likely achieved by linking patients back to community-based services, which are best placed to provide ongoing long-term care.Copyright © CSIRO 2019 Open Access.

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 x 10-9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.Copyright © 2019, & 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Background: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. Methods: Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. Results: Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. Conclusions: This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications.

Aim: This hospital network-based retrospective observational study aimed to describe the prevalence and seasonality of paediatric and adult viral respiratory pathogens and their rates of co-infections, following the introduction of a rapid multiplex molecular diagnostic assay. Method(s): All nasopharyngeal samples tested in patients presenting to Monash Health, Melbourne, Australia, from August 2009 to July 2015 by means of multiplex tandem polymerase chain reaction using the Respiratory Pathogen 12Plex kit (AusDiagnostics) were included in the analysis. Result(s): There were 28 729 patient samples analysed after duplicate samples were excluded. Positive results were twice as likely in paediatrics, 7573/11 491 (65.9%), compared to adults, 5410/17 238 (31.4%). Co-infection was more frequent in paediatrics, 1642/7573 (21.7% of positives), compared to adults 299/5410 (5.5%). Adenovirus had a high prevalence as a co-infection, 639/990 (64.5%), in paediatrics. Testing frequency increased by 179% in the paediatric group and by 949% for adults over the 6 years of observation. Conclusion(s): This study demonstrated a significant difference in the positive detection rate of pathogens and co-infections between the population groups. Adenovirus had a surprisingly high prevalence as a co-infection, especially in paediatric patients. Over the study period, rapid uptake of the test was observed, especially in adults. This raises concerns about how we can ensure that testing remains rational and is able to be provided in a cost-effective manner in the future.Copyright © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)

Alcohol-based disinfectants and particularly hand rubs are a key way to control hospital infections worldwide. Such disinfectants restrict transmission of pathogens, such as multidrug-resistant Staphylococcus aureus and Enterococcus faecium. Despite this success, health care infections caused by E. faecium are increasing. We tested alcohol tolerance of 139 hospital isolates of E. faecium obtained between 1997 and 2015 and found that E. faecium isolates after 2010 were 10-fold more tolerant to killing by alcohol than were older isolates. Using a mouse gut colonization model of E. faecium transmission, we showed that alcohol-tolerant E. faecium resisted standard 70% isopropanol surface disinfection, resulting in greater mouse gut colonization compared to alcohol-sensitive E. faecium. We next looked for bacterial genomic signatures of adaptation. Alcohol-tolerant E. faecium accumulated mutations in genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed the roles of these genes in the tolerance of E. faecium to isopropanol. These findings suggest that bacterial adaptation is complicating infection control recommendations, necessitating additional procedures to prevent E. faecium from spreading in hospital settings.Copyright © 2018 The Authors, some rights reserved;.

To identify risk factors for infection in patients with diffuse large B cell lymphoma (DLBCL) undergoing rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone (R-CHOP) treatment. All patients with DLBCL who received R-CHOP from 2004-2014 in a tertiary Australian hospital were identified and information collected from hospital admission data, laboratory results and medical record review. Infection was defined as hospitalisation with an ICD-10-AM diagnostic code for infection. Risk factors for infection and association between infection and survival were modelled using Cox proportional hazards regression. Over the 10-year period there were 325 patients; 191 (58.8%) males, median age 66 years. 206 (63.4%) patients experienced >=1 infection. Independent predictors of infection were Charlson comorbidity index score (hazard ratio [HR] 3.60, p=0.002), Eastern Cooperative Oncology Group (ECOG) performance status (HR 2.09 p=<0.001) and neutropenia (HR 2.46, p=<0.001). 99 (31%) patients died. Infection was an independent predictor of survival (HR 3.27, p=<0.001, as were age (HR 2.49, p=0.001), Charlson comorbidity index (HR 4.34, p=<0.001), ECOG performance status (HR 4.33, p=0.045) and neutropenia (HR 1.95, p=0.047). Infections are common and infection itself is an independent predictor of survival. Patients at highest risk of infection and death are those with multiple comorbidities, poor performance status and neutropenia.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a reliable tool for bacterial identification. This study compared the Bruker MALDI-TOF BioTyper MS (MBT) and 16S rRNA gene sequencing for the identification of Actinomyces and Actinotignum spp. The MBT identified 68/77 (88.3%) of Actinomyces isolates to the genus-level and 44/77 (57.1%) of Actinomyces isolates to the species-level using the manufacturer's identification criteria. The MBT did not yield reliable identification for only 1/77 (1.3%) and generated no identification for 8/77 (10.4%) of the isolates. No misidentifications were found. Discordance at the species level was observed for eight isolates. Overall, the MBT demonstrated good concordance with the 16S rRNA gene sequencing with the exception of the closely related species A. naeslundii, A. viscosus and A. oris. A variety of Actinomyces spp. were isolated from orocervicofacial/dental specimens, but only a limited number of species were isolated from urine or intra-abdominal specimens. This study confirms the utility of MBT in the identification of Actinomyces spp. and describes the diversity and anatomic niche of species in human clinical specimens from various body sites.Copyright © 2018 Elsevier Ltd

Epstein-Barr virus (EBV) is typically associated with post transplant lymphoproliferative disease (PTLD) after solid organ and stem cell transplantation. However, it is rarely associated with neurological complications. We report a case of severe encephalitis complicating primary EBV infection six months post renal transplantation, and review the literature on EBV encephalitis in solid organ transplantation in adults. A 55-year-old male presented 6 months post cadaveric renal transplant with headache, fever and confusion. Neuroimaging was unremarkable, but an electroencephalogram was consistent with diffuse encephalopathy. EBV DNA was detected in both cerebrospinal fluid (13,177 copies/ml), and plasma (14,166 copies/ml). Management included reduction of immunosuppression, intravenous ganciclovir and intravenous immunoglobulin, and resulted in a reduction in EBV viral load in both plasma and cerebrospinal fluid. The patient made a full recovery with no long-term neurological deficits and preservation of the graft. This case highlights the importance of knowing donor and recipient EBV serostatus at time of transplant, and closely monitoring EBV DNA when there is a mismatch. Ganciclovir or valganciclovir prophylaxis has also been shown to reduce the incidence of primary EBV infection in renal transplantation in these recipients. Treatment options for EBV infection post-transplant include reduction of immunosuppression, antiviral therapy, IVIg, and monoclonal antibody therapy directed toward infected B lymphocytes.

Background: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. Method(s): Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. Result(s): Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score >= 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. Conclusion(s): This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications.Copyright © 2018 The Author(s).

We describe unanticipated detection of respiratory infection with Chlamydia trachomatis and Chlamydia psittaci after introduction of respiratory multiplex polymerase chain reaction assay that includes Chlamydiaceae family primers. We detected cases of pediatric C. trachomatis and of adult C. psittaci infection in patients with previously unrecognized risk factors. Directed testing for C. trachomatis and C. psittaci based on clinical features and risk factors alone is likely to miss the majority of infected cases.Copyright © 2017 Elsevier Inc.

Alcohol-based disinfectants and particularly hand rubs are a key way to control hospital infections worldwide. Such disinfectants restrict transmission of pathogens, such as multidrug-resistant Staphylococcus aureus and Enterococcus faecium. Despite this success, health care infections caused by E. faecium are increasing. We tested alcohol tolerance of 139 hospital isolates of E. faecium obtained between 1997 and 2015 and found that E. faecium isolates after 2010 were 10-fold more tolerant to killing by alcohol than were older isolates. Using a mouse gut colonization model of E. faecium transmission, we showed that alcohol-tolerant E. faecium resisted standard 70% isopropanol surface disinfection, resulting in greater mouse gut colonization compared to alcohol-sensitive E. faecium. We next looked for bacterial genomic signatures of adaptation. Alcohol-tolerant E. faecium accumulated mutations in genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed the roles of these genes in the tolerance of E. faecium to isopropanol. These findings suggest that bacterial adaptation is complicating infection control recommendations, necessitating additional procedures to prevent E. faecium from spreading in hospital settings.

Introduction: Candida sp. are the leading cause of invasive fungal infection in hospitalized patients, and represent 8-10% of all bloodstream infections. Rates of candidaemia are increasing, and associated with significant morbidity, mortality and cost. Duration and choice of therapy is influenced by sites of dissemination, most importantly to the valves and the eye. However, the frequency of endocarditis is not well described. We describe the clinical and microbiological characteristics of a cohort of patients with candidaemia. Method(s): Patients were identified from our microbiology database. Clinical data was collected from the medical records. Blood culture time-topositivity was determined. Result(s): 71 patients were included. Median age was 66 (mean 63.2 +/- 17.1, range 16-94) and 41 were male. Median length of stay was 27.5 days (48.5 +/- 27.5, 2-184) and 50 were admitted to intensive care. C. albicans was the predominant species (56%) followed by C. glabrata (24%). Time to positivity was available for 23 episodes, with C. glabrata significantly longer than others (70.6 +/- 26.9 vs. 32.5 +/- 14.2 hours, p = 0.008). Transthoracic echocardiography was performed in 39 and transoesophageal echocardiography in 10 patients, with 3 cases of endocarditis identified. 41 underwent ophthalmological examination; 7 had retinal involvement and one had endophthalmitis. Mortality was 21% at 7 days, 37% at 30 days and 47% at 90 days. Only 5 patients received antifungal therapy before the blood culture flagged, with median delay to treatment 52 hours (57.8 +/- 28.5, 0.5-157.4). Empiric therapy was most often an echinocandin (52%), although the majority of isolates (66%) were susceptible to fluconazole. Conclusion(s): Antifungal therapy was delayed in most patients, likely contributing to high rates of ophthalmic complications and substantial mortality. This may represent a target to improve outcomes. Prolonged time to positivity is more likely to indicate C. glabrata, which c

OBJECTIVES: To describe the epidemiology, clinical and laboratory features and outcomes of dengue in returned Australian travellers, applying the revised WHO dengue classification (2009) to this population. DESIGN, SETTING AND PARTICIPANTS: Retrospective case series analysis of confirmed dengue cases hospitalised at one of four Australian tertiary hospitals, January 2012 - May 2015. MAIN OUTCOME MEASURES: Clinical features, laboratory findings and outcomes of patients with dengue; dengue classification according to 2009 WHO guidelines. RESULTS: 208 hospitalised patients (median age, 32 years; range, 4-76 years) were included in the study. Dengue was most frequently acquired in Indonesia (94 patients, 45%) and Thailand (40, 19%). The most common clinical features were fever (98% of patients) and headache (76%). 84 patients (40%) met the WHO criteria for dengue with warning signs, and one the criteria for severe dengue; the most common warning signs were mucosal bleeding (44 patients, 21%) and abdominal pain (43, 21%). Leukopenia (176 patients, 85%), thrombocytopenia (133, 64%), and elevated liver enzyme levels (154, 76%) were the most common laboratory findings. 46 patients (22%) had serological evidence of previous exposure to dengue virus. WHO guidelines were documented as a management benchmark in ten cases (5%); 46 patients (22%) received non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: A significant proportion of returning Australian travellers hospitalised for dengue have unrecognised warning signs of severe disease. Many received NSAIDs, which can increase the risk of haemorrhage in dengue. As travel to Asia from Australia continues to increase, it is vital for averting serious outcomes that clinicians can recognise and manage dengue.

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2015 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with an acute respiratory illness with influenza confirmed by nucleic acid detection. During the period 1 April to 30 October 2015 (the 2015 influenza season), 2,070 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 46% were elderly (>= 65 years), 15% were children (< 16 years), 5% were Indigenous Australians, 2.1% were pregnant and 75% had chronic co-morbidities. A high proportion were due to influenza B (51%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2015 with case numbers similar to that reported in 2014. The national immunisation program is estimated to avert 46% of admissions from confirmed influenza across all at-risk groups, but more complete vaccination coverage in target groups could further reduce influenza admissions by as much as 14%.

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. Method(s): 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 YeastOneTM. Result(s): A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 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. Conclusion(s):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.Copyright © The Author 2016.

In the original published version of this article two authors (Eunice Liu and Elaine Cheong) were inadvertently omitted from the author list during article preparation. This error has now been corrected. The authors apologize for this error.Copyright © The Author 2016.

Background: The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not "life-long" course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. Method(s): A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. Result(s): 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. Conclusion(s): Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged cou