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Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 ( n =169), 002 ( n =77) and 056 ( n =36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLS B agents in vitro , but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n =36) to 115.6 (RT002, ST8, n =77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n =169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n =14; RT002, n =3; RT056, n =2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen.

Background: Nocardia is a ubiquitous saprophyte capable of causing human disease. Disease is primarily respiratory or cutaneous, usually acquired via inhalation or inoculation. Under the influence of environmental and host factors, Nocardia incidence and species distribution demonstrate geographical variation., Aims: To examine for differences in Nocardia incidence within Western Australia (WA) and analyse species distribution in the context of prior published studies. To analyse antibiogram data from a nationwide passive antimicrobial resistance surveillance program., Methods: Retrospective extraction of laboratory data for Western Australian Nocardia isolates over a 21-year period. Analysis of Nocardia antimicrobial susceptibility testing data submitted to the Australian Passive Antimicrobial Resistance Surveillance (APAS) program between 2005 and 2022., Results: Nine hundred sixty WA isolates were identified, giving an annual incidence of 3.03 per 100 000 population with apparent latitudinal variation. The four most common species identified within WA and amongst APAS isolates were N. nova, N. cyriacigeorgica, N. brasiliensis and N. farcinica. APAS data demonstrated that all species exhibited high rates of susceptibility to linezolid (100%) and trimethoprim-sulfamethoxazole (98%). Amikacin (>90% susceptibility for all species except N. transvalensis) was the next most active parenteral agent, superior to both carbapenems and third-generation cephalosporins. Susceptibility to oral antimicrobials (other than linezolid) demonstrated significant interspecies variation., Conclusions: We demonstrate geographical variation in the distribution of Nocardia incidence. Four species predominate in the Australian setting, and nationwide data confirm a high in vitro susceptibility to trimethoprim-sulphamethoxazole and linezolid, justifying their ongoing role as part of first-line empiric therapy., (© 2023 Royal Australasian College of Physicians.)

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., (Copyright © 2022. Published by Elsevier Ltd.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

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: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia., Methods: 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., Results: 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., Conclusions: 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., (© 2021 Royal Australasian College of Physicians.)

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.)

Background: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID)., Aims: To describe the burden of IE and its outcomes in PWID., Methods: 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., Results: 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., Conclusions: 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., (© 2019 Royal Australasian College of Physicians.)

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.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate., Setting: 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., Results: 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., Conclusions: 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., (© 2020 AMPCo Pty Ltd.)

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: To evaluate the extent that Australian non-HIV specialty guidelines mention and recommend HIV testing in HIV indicator conditions., Methods: 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., Results: 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., Conclusions: 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., (© 2019 Royal Australasian College of Physicians.)

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., Methods: 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., Results: 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: 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.

Aim: To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection., Design: Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation., Method: The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions., Results: Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection., Discussion/ Conclusion: Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis.

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 2.41/105 population. The median patient age was 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., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

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%.

The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children., (© 2016 Royal Australasian College of Physicians.)

Objectives: The objective of this study was to determine the activity of fidaxomicin and comparator antimicrobials against Clostridium difficile isolated from patients with C. difficile infection (CDI) in Australian hospitals and in the community., Methods: One private and one public laboratory from five states in Australia submitted a total of 474 isolates/PCR-positive stool samples during three collection periods in August-September 2013 (n = 175), February-March 2014 (n = 134) and August-September 2014 (n = 165). Isolate identification was confirmed by selective culture for C. difficile and a proportion of isolates from each state were characterized by PCR for toxin genes and PCR ribotyping. MICs of fidaxomicin and eight comparator antimicrobials were determined for all isolates using agar methodology., Results: Site collection yielded 440 isolates of C. difficile and PCR revealed a heterogeneous strain population comprising 37 different PCR ribotypes (RTs), 95% of which were positive for tcdA and tcdB (A+B+). The most common RTs were 014 (29.8%) and 002 (15.9%). Epidemic RT 027 was not identified; however, small numbers of virulent RTs 078 and 244 were found. Resistance to vancomycin, metronidazole and fidaxomicin was not detected and resistance to moxifloxacin was very low (3.4%). Fidaxomicin showed potent in vitro activity against all 440 isolates (MIC50/MIC90 0.03/0.12 mg/L) and was superior to metronidazole (MIC50/MIC90 0.25/0.5 mg/L) and vancomycin (MIC50/MIC90 1/2 mg/L)., Conclusions: These data confirm the potent in vitro activity of fidaxomicin against C. difficile. Moreover, this study provides an important baseline for ongoing long-term surveillance of antimicrobial resistance and prospective tracking of prominent and emerging strain types., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

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 <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season., (This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.)

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.

Objectives: Clinical utility of carbapenem antibiotics is under threat because of the emergence of acquired metallo-β-lactamase (MBL) genes. We describe an outbreak in an intensive care unit (ICU) possibly associated with contaminated sinks., Design, Setting and Participants: Four clusters of gram-negative bacteria harbouring the MBL gene blaIMP-4 were detected in the ICU at Dandenong Hospital between November 2009 and July 2012. Epidemiological investigations were undertaken in order to identify a common point source. During September 2012, screening using rectal swabs for all ICU patients, and environmental swabs targeting all ICU handwashing sinks and taps were collected. Samples were cultured onto selective carbapenem-resistant Enterobacteriaceae (CRE) agar. Suspected CRE isolates were further characterised using the modified Hodge test and VITEK 2 and confirmed by polymerase chain reaction and sequencing of MBL genes. Clinical and environmental CRE isolates were typed by pulsed-field gel electrophoresis., Results: Ten clinical isolates and one screening isolate of CRE (consisting of Klebsiella pneumoniae [5], Serratia marcescens [4], Enterobacter cloacae [1] and Escherichia coli [1]) were detected with the blaIMP-4 gene over the 30-03 period. S. marcescens was isolated persistently from the grating and drain of eight central sinks. Molecular typing confirmed that clinical and environmental isolates were related. Tap water cultures were negative. Several attempts to clean and decontaminate the sinks using detergents and steam cleaning proved unsuccessful., Conclusion: This report highlights the importance of identification of potential environmental reservoirs, such as sinks, for control of outbreaks of environmentally hardy multiresistant organisms.

We aimed to estimate the effectiveness of H1N1/09 containing influenza vaccines against hospitalization from influenza in Australia. We performed a test-negative case control study in patients hospitalized in 15 sentinel Australian hospitals between March and November 2010, comparing influenza vaccination (H1N1/09 monovalent or 2010 seasonal trivalent) in hospitalized patients with PCR-confirmed influenza compared to PCR-negative controls. Between March and November 2010, 1169 hospitalized patients were tested for suspected influenza, of which influenza vaccine status was ascertained in 165/238 patients with H1N1/09 influenza, 40/64 with seasonal influenza and 558/867 test negative controls; 24% of H1N1/09 cases, 43% of seasonal influenza cases and 54% of controls were vaccinated. VE against hospitalisation with H1N1/09 influenza after adjusting for age, medical comorbidities and pregnancy status was estimated at 49% (95% CI: 13%, 70%). Influenza vaccination was associated with a reduction in hospitalisation caused by H1N1/09 influenza in the 2010 southern hemisphere winter season., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Clostridium difficile is the most common cause of health care-associated and antibiotic-associated diarrhoea. These guidelines are intended to provide advice to clinicians on the clinical assessment, diagnosis and management of C. difficile infection (CDI). Hypervirulent strains of C. difficile, including PCR ribotype 027 strains recently identified in Australia, have been associated elsewhere with epidemic spread and high rates of severe disease and death. Diagnostic tests include stool culture, polymerase chain reaction-based assays, cell-culture cytotoxicity assays and enzyme immunoassays detecting C. difficile glutamate dehydrogenase, and/or toxin A and/or B. To treat an initial episode and a first recurrence, metronidazole is the preferred antibiotic, with oral vancomycin reserved for severe disease and subsequent recurrences. Surgery should be considered for fulminant disease., (©The Medical Journal of Australia 2011)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159) to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs) distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL) and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total). These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300) share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2). This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid dissemination of a highly conserved accessory genome from a common source.

Introduction: To estimate the incidence of intensive care unit (ICU)-acquired bloodstream infection (BSI) and its independent effect on hospital mortality., Methods: We retrospectively studied acquisition of BSI during admissions of >72 hours to adult ICUs from two university-affiliated hospitals. We obtained demographics, illness severity and co-morbidity data from ICU databases and microbiological diagnoses from departmental electronic records. We assessed survival at hospital discharge or at 90 days if still hospitalized., Results: We identified 6339 ICU admissions, 330 of which were complicated by BSI (5.2%). Median time to first positive culture was 7 days (IQR 5-12). Overall mortality was 23.5%, 41.2% in patients with BSI and 22.5% in those without. Patients who developed BSI had higher illness severity at ICU admission (median APACHE III score: 79 vs. 68, P < 0.001). After controlling for illness severity and baseline demographics by Cox proportional-hazard model, BSI remained independently associated with risk of death (hazard ratio from diagnosis 2.89; 95% confidence interval 2.41-3.46; P < 0.001). However, only 5% of the deaths in this model could be attributed to acquired-BSI, equivalent to an absolute decrease in survival of 1% of the total population. When analyzed by microbiological classification, Candida, Staphylococcus aureus and gram-negative bacilli infections were independently associated with increased risk of death. In a sub-group analysis intravascular catheter associated BSI remained associated with significant risk of death (hazard ratio 2.64; 95% confidence interval 1.44-4.83; P = 0.002)., Conclusions: ICU-acquired BSI is associated with greater in-hospital mortality, but complicates only 5% of ICU admissions and its absolute effect on population mortality is limited. These findings have implications for the design and interpretation of clinical trials.

Background: Available data on the etiology of community-acquired pneumonia (CAP) in Australia are very limited. Local treatment guidelines promote the use of combination therapy with agents such as penicillin or amoxycillin combined with either doxycycline or a macrolide., Methods: The Australian CAP Study (ACAPS) was a prospective, multicenter study of 885 episodes of CAP in which all patients underwent detailed assessment for bacterial and viral pathogens (cultures, urinary antigen testing, serological methods, and polymerase chain reaction). Antibiotic agents and relevant clinical outcomes were recorded., Results: The etiology was identified in 404 (45.6%) of 885 episodes, with the most frequent causes being Streptococcus pneumoniae (14%), Mycoplasma pneumoniae (9%), and respiratory viruses (15%; influenza, picornavirus, respiratory syncytial virus, parainfluenza virus, and adenovirus). Antibiotic-resistant pathogens were rare: only 5.4% of patients had an infection for which therapy with penicillin plus doxycycline would potentially fail. Concordance with local antibiotic recommendations was high (82.4%), with the most commonly prescribed regimens being a penicillin plus either doxycycline or a macrolide (55.8%) or ceftriaxone plus either doxycycline or a macrolide (36.8%). The 30-day mortality rate was 5.6% (50 of 885 episodes), and mechanical ventilation or vasopressor support were required in 94 episodes (10.6%). Outcomes were not compromised by receipt of narrower-spectrum beta-lactams, and they did not differ on the basis of whether a pathogen was identified., Conclusions: The vast majority of patients with CAP can be treated successfully with narrow-spectrum beta-lactam treatment, such as penicillin combined with doxycycline or a macrolide. Greater use of such therapy could potentially reduce the emergence of antibiotic resistance among common bacterial pathogens.

Background: Peritonitis remains one of the major complications of peritoneal dialysis (PD) and results in reduced technique survival and increased patient morbidity and mortality., Methods: We prospectively recorded comprehensive data on all episodes of PD peritonitis over a 25-year period, including organisms isolated and antibiotic sensitivities. Data on 1588 PD patient-years with 2073 episodes of peritonitis were analyzed; 2089 organisms were isolated in 608 patients. Peritoneal dialysis technique and patient survival were also recorded., Results: There was a significant decline over the years in the incidence of peritonitis, from 6.5 to 0.35 episodes/patient-year, with the decline in the post twin-bag era from 2.3 to 0.47 (p < 0.001) due primarily to a decrease in gram-positive organisms. The most common isolates (68.9%) were gram-positive organisms; gram-negative organisms comprised 26.8% and fungi 4.1%. Coagulase-negative staphylococci were the most common pathogen isolated (35.3%). Culture-negative peritonitis was seen in 13.4% of episodes., Conclusion: This is the largest series of PD peritonitis reported, demonstrating a dramatic reduction over a 25-year period and also detailing the changing trends of organisms isolated in association with improved technique and patient survival. Although rates have improved, peritonitis remains a major complication and further research needs to be done to improve both PD technique and patient survival.

Objective: Stenotrophomonas maltophilia is an important nosocomial pathogen and a therapeutic challenge. A ten-year review of episodes of bacteraemia due to S. maltophilia was undertaken in light of reports of an increasing frequency of infection., Methods: A retrospective analysis of bloodstream infections due toS. maltophilia at a tertiary care hospital in Melbourne, Australia. Cases were identified via microbiology laboratory reports, and relevant clinical data were collected from the medical record of each patient., Results: Eighty per cent of these 45 episodes were nosocomial. The most common characteristics in cases of bacteraemia were the presence of an indwelling central venous catheter (CVC) (38/45, 84%) and previous antibiotic therapy (33/45, 73%). There were 8 deaths (8/44, 18%) within 7 days of bacteraemia. A significant correlation was found between deaths and a failure to remove the CVC (P = 0.01) or treat with appropriate antimicrobials (P = 0.01). Antibiotic susceptibility testing revealed that isolates were most sensitive to sulphamethoxazole (80%), chloramphenicol (75.5%) and ceftazidime (64.5%)., Conclusions: S. maltophilia is an important pathogen especially in the highly compromised host. Isolation of this organism from a blood culture should prompt a careful review of the patient with particular emphasis on removal of indwelling CVCs and commencement of appropriate antibiotic therapy., (Copyright 2002 The British Infection Society)