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Objectives: New Delhi metallo-β-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel, but from 2019 we noted increasing incidence of NDM-positive clinical isolates. We investigated the clinical and genomic epidemiology of NDM carriage at a tertiary-care Australian hospital from 2016 to 2021., Methods: We identified 49 patients with 84 NDM-carrying isolates in an institutional database, and we collected clinical data from electronic medical record. Short- and long-read whole genome sequencing was performed on all isolates. Completed genome assemblies were used to assess the genetic setting of bla NDM genes and to compare NDM plasmids., Results: Of 49 patients, 38 (78%) were identified in 2019-2021 and only 11 (29%) of 38 reported prior travel, compared with 9 (82%) of 11 in 2016-2018 ( P = .037). In patients with NDM infection, the crude 7-day mortality rate was 0% and the 30-day mortality rate was 14% (2 of 14 patients). NDMs were noted in 41 bacterial strains (ie, species and sequence type combinations). Across 13 plasmid groups, 4 NDM variants were detected: bla NDM-1 , bla NDM-4 , bla NDM-5 , and bla NDM-7 . We noted a change from a diverse NDM plasmid repertoire in 2016-2018 to the emergence of conserved bla NDM-1 IncN and bla NDM-7 IncX3 epidemic plasmids, with interstrain spread in 2019-2021. These plasmids were noted in 19 (50%) of 38 patients and 35 (51%) of 68 genomes in 2019-2021., Conclusions: Increased NDM case numbers were due to local circulation of 2 epidemic plasmids with extensive interstrain transfer. Our findings underscore the challenges of outbreak detection when horizontal transmission of plasmids is the primary mode of spread.

Importance: There has been a decrease in healthcare-associated Clostridioides difficile infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of C. difficile isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources. Some types of isolates were more likely to carry antimicrobial resistance determinants, and many of these were associated with mobile genetic elements. These results correlate with those of other recent investigations, supporting the observed increase in genetic diversity and prevalence of community-associated C. difficile , and consequently the importance of sources of transmission other than symptomatic patients. Thus, they reinforce the importance of surveillance for in both hospital and community settings, including asymptomatic carriage, food, animals, and other environmental sources to identify and circumvent important sources of C. difficile transmission., Competing Interests: The authors declare no conflict of interest.

We collected 163 clinical Pseudomonas aeruginosa isolates at a tertiary hospital specialising in adult cystic fibrosis (CF) and lung transplantation (LTx) in Melbourne, Australia, to explore the activity of ceftolozane-tazobactam (C/T) in populations at high-risk for antimicrobial resistance. Of these, 144 (88.3%) were collected from sputum, and 19 (11.7%) from bronchoalveolar lavage. Most (85.3%) were derived from patients with cystic fibrosis and included a subset of patients that had undergone LTx. These isolates were tested against 11 antibiotics, including C/T, using Sensititre plates for broth microdilution (BMD) testing. Sixty (36.8%) isolates were classified as multidrug resistant (MDR) and 32 (19.6%) were extensively drug resistant (XDR). Overall, 133/163 (81.6%) isolates were susceptible to C/T. For MDR and XDR isolates, 88.3% and 28.1% were C/T susceptible, respectively. Among the non-MDR/XDR isolates, 100% remained susceptible to C/T. Comparisons of C/T susceptibility were made using BioMérieux Etests and Liofilchem MIC test strips (MTS). Categorical agreement to BMD was >93% for both test strips, but essential agreement to BMD was slightly higher with Etest (89.0%) compared to Liofilchem (74.8%). In conclusion, C/T retained activity against most MDR and over a quarter of XDR P. aeruginosa isolates from complex patients with CF and post-LTx., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Organ transplant guidelines in many settings recommend that people with potential hepatitis C virus (HCV) exposure or infection are deemed ineligible to donate. The recent availability of highly-effective treatments for HCV means that this may no longer be necessary. We used a mathematical model to estimate the expected difference in healthcare costs, difference in disability-adjusted life years (DALYs) and cost-effectiveness of removing HCV restrictions for lung and kidney donations in Australia. Our model suggests that allowing organ donations from people who inject drugs, people with a history of incarceration and people who are HCV antibody-positive could lead to an estimated 10% increase in organ supply, population-level improvements in health (reduction in DALYs), and on average save AU$2,399 (95%CI AU$1,155-3,352) and AU$2,611 (95%CI AU$1,835-3,869) per person requiring a lung and kidney transplant respectively. These findings are likely to hold for international settings, since this policy change remained cost saving with positive health gains regardless of HCV prevalence, HCV treatment cost and waiting list survival probabilities. This study suggests that guidelines on organ donation should be revisited in light of recent changes to clinical outcomes for people with HCV.

Hypermutable Pseudomonas aeruginosa isolates (hypermutators) have been identified in patients with cystic fibrosis (CF) and are associated with reduced lung function. Hypermutators display a greatly increased mutation rate and an enhanced ability to become resistant to antibiotics during treatment. Their prevalence has been established among patients with CF, but it has not been determined for patients with CF in Australia. This study aimed to determine the prevalence of hypermutable P. aeruginosa isolates from adult patients with CF from a health care institution in Australia and to characterize the genetic diversity and antibiotic susceptibility of these isolates. A total of 59  P. aeruginosa clinical isolates from patients with CF were characterized. For all isolates, rifampin (RIF) mutation frequencies and susceptibility to a range of antibiotics were determined. Of the 59 isolates, 13 (22%) were hypermutable. Whole-genome sequences were determined for all hypermutable isolates. Core genome polymorphisms were used to assess genetic relatedness of the isolates, both to each other and to a sample of previously characterized P. aeruginosa strains. Phylogenetic analyses showed that the hypermutators were from divergent lineages and that hypermutator phenotype was mostly the result of mutations in mutL or, less commonly, in mutS Hypermutable isolates also contained a range of mutations that are likely associated with adaptation of P. aeruginosa to the CF lung environment. Multidrug resistance was more prevalent in hypermutable than nonhypermutable isolates (38% versus 22%). This study revealed that hypermutable P. aeruginosa strains are common among isolates from patients with CF in Australia and are implicated in the emergence of antibiotic resistance., (Copyright © 2019 American Society for Microbiology.)

Background: Bali, Indonesia, presents significant infectious and non-infectious health risks for Australian travellers. Understanding this spectrum of illnesses has the potential to assist clinicians in evaluating unwell returning travellers and guide provision of pre-travel advice., Aim: To describe the spectrum of illnesses seen in returned travellers from Bali., Methods: Using a novel text mining approach, we performed a retrospective, observational study of all adult emergency department presentations to a metropolitan health service in Melbourne, from 2011 to 2015. Outcome measures included demographic, clinical and laboratory features of travel-related illnesses., Results: A total of 464 patients met inclusion criteria. Gastroenteritis (119/464, 26%), systemic febrile illness (88/464, 19%) and respiratory tract infection (51/464, 11%) were the most common diagnoses. Dengue was the most common laboratory-confirmed diagnosis (25/464, 5%). No cases of malaria were identified. Common non-infectious presentations included traumatic injury (47/464, 10%) and animal bites requiring rabies post-exposure prophylaxis (29/464, 6%). A total of 110 patients (24%) was admitted to the hospital; those presenting with systemic febrile illness were more likely to be admitted compared to those presenting with other illnesses (odds ratio 3.42, 95% confidence interval 2.02-5.75, P < 0.001)., Conclusion: This is the first study to use a text mining approach to identify and describe emergency department presentations related to diseases acquired in Bali by Australian travellers. Although infections are important causes of illness, trauma and animal bites account for a significant number of hospital presentations. Our findings contribute to the knowledge on the health risks for travellers to Bali, and will assist clinicians in relevant pre- and post-travel evaluations., (© 2018 Royal Australasian College of Physicians.)

Background: The use of fosfomycin for treatment of systemic infections due to MDR Pseudomonas aeruginosa is increasing. However, pharmacodynamic data for fosfomycin are limited., Methods: Sixty-four clinical isolates of P. aeruginosa (MDR and non-MDR) from two Australian hospitals were collected; 59 isolates were from patients with cystic fibrosis and 5 isolates were from critically ill patients. The in vitro pharmacodynamic properties of fosfomycin (disodium) were investigated via MICs (all isolates) and, for selected isolates, via time-kill kinetics (static and dynamic models; concentration range, 1-1024 mg/L), population analysis profiles (PAPs) and post-antibiotic effect (PAE). Two inocula (∼10(6) and ∼10(8) cfu/mL) were included in static time-kill studies to examine the effect of inocula on bacterial killing., Results: MICs ranged from 1 to >512 mg/L, with 61% of isolates considered fosfomycin susceptible (MIC ≤64 mg/L). The MIC distributions for MDR and non-MDR isolates were similar. Baseline PAPs indicated heteroresistance in all isolates tested. Time-kill studies showed moderate (maximum killing ∼3 log10 cfu/mL), time-dependent killing at the low inoculum with regrowth at 24 h. Most concentrations resulted in complete replacement of fosfomycin-susceptible colonies by fosfomycin-resistant colonies. Bacterial killing was virtually eliminated at the high inoculum. The PAE ranged from 0.3 to 5.5 h., Conclusions: These data suggest monotherapy with fosfomycin may be problematic for the treatment of infections caused by P. aeruginosa. Further investigation of fosfomycin combination therapy is warranted., (© 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.)

Background: Long-term care facilities (LTCFs) are a potentially important reservoir of multidrug-resistant (MDR) organisms; however, limited data exist., Methods: A point-prevalence study was conducted in four co-located LTCFs in Australia. Nasal and rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and MDR Gram-negative bacilli (GNB). Molecular typing and resistance detection were performed. Risk factors for colonization with an MDR organism were determined using a nested case-control study., Results: Consent was obtained from 115 (85%) of 136 eligible participants. Forty-one (36%) residents carried at least one type of MDR organism. The prevalence was 16% MRSA (n = 18), 6% VRE (n = 7) and 21% MDR GNB [n = 24; including extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 12) and Acinetobacter baumannii (n = 6)]. The majority of ESBL-producing E. coli and A. baumannii were clonal. Current wound management [adjusted OR (AOR) 8.81 (95% CI 2.78-27.94), P < 0.001], medical device in situ [AOR 5.58 (95% CI 1.34-23.32), P = 0.018] and pressure ulcer [AOR 3.69 (95% CI 1.06-12.86), P = 0.04] were independent risk factors for MDR organism colonization. Advanced dementia [AOR 3.54 (95% CI 1.23-10.23), P = 0.02] and prolonged antibiotic use [AOR 2.95 (95% CI 1.01-8.60), P = 0.047] were independently associated with MRSA colonization, whilst current wound management [AOR 15.59 (95% CI 4.85-50.10), P < 0.001] and fluoroquinolone use [AOR 4.27 (95% CI 1.20-15.25), P = 0.025] were risk factors for MDR GNB colonization., Conclusions: LTCFs are an important reservoir of MDR organisms, with person-to-person transmissions being a potential issue. We have identified several predictors of colonization with MDR organisms, allowing a more targeted management of high-risk residents., (© The Author 2014. 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.)

Enterobacter cloacae is a major nosocomial pathogen that causes serious infections, including bloodstream infections (BSIs). The clinical significance of extended-spectrum β-lactamase (ESBL) production in E. cloacae is not well established. A multicentre, retrospective, cohort study was conducted to identify clinical characteristics of patients with E. cloacae BSI. ESBL production was confirmed by genotypic methods. A total of 159 patients with E. cloacae BSI were identified at three medical centres in north-eastern USA. Amongst them, 16 patients (10.1%) harboured ESBL-producing E. cloacae. Independent risk factors for ESBL production included admission from a nursing home, the presence of a gastrostomy tube and history of transplant. For the outcome analysis, 15 consecutive patients who had ESBL-producing E. cloacae BSI prior to the study were included. Amongst the 31 patients with ESBL-producing E. cloacae, 8, 9, 4 and 2 patients received a carbapenem, cefepime, piperacillin/tazobactam and ciprofloxacin, respectively, as initial therapy. All patients who received a carbapenem (n=8) were alive at 28 days, whereas 7 (38.9%) of 18 patients who received a non-carbapenem antibiotic did not survive (P=0.06). Clinical failure at 96 h was observed in 2 (25.0%) of 8 patients who received a carbapenem and in 14 (77.8%) of 18 patients who received a non-carbapenem antibiotic (P=0.03). Pulsed-field gel electrophoresis showed little clonality amongst the study isolates. The majority of isolates produced SHV-type ESBL, whereas two isolates produced CTX-M-type ESBL. Initial therapy with a carbapenem appears to be associated with improved clinical outcome in BSI due to ESBL-producing E. cloacae., (Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: The clinical utility of carbapenems is under threat because of the emergence of acquired metallo-beta-lactamase (MBL) genes. We describe the first outbreak in Australia of infection and/or colonization with gram-negative pathogens carrying the MBL gene blaIMP-4., Methods: MBL-producing organisms were identified using susceptibility data in conjunction with MBL screening methods. PCR and sequence analysis were performed to characterize the resistance gene and identify the presence of integrons. DNA profiles were determined by ribotyping. Clinical and epidemiological data were prospectively collected from January-July 2004., Results: A total of 19 isolates were recovered from 16 patients: Serratia marcescens (10 isolates), Klebsiella pneumoniae (4 isolates), Pseudomonas aeruginosa (3 isolates), Escherichia coli (1 isolate), and Enterobacter cloacae (1 isolate). Isolates were resistant to most beta-lactams except aztreonam, and variable resistance to carbapenems was observed (MIC range, 2 to >8 mg/L). PCR and sequence analysis identified the blaIMP-4 gene and a class 1 integrase (IntI1) in all isolates. Of the 16 patients, 12 (75%) had infection; 5 had septicemia, 5 had ventilator-associated pneumonia, 1 had a urinary tract infection, and 1 had a superficial central venous line infection. Six (38%) of the 16 patients died, and 5 of those 6 (31% of the group of 16) had clinical infection with an MBL-producing organism. All except 2 patients had spatio-temporal epidemiological links in the intensive care unit. All K. pneumoniae isolates were of different ribogroups, whereas the S. marcescens and P. aeruginosa isolates were predominately of the same ribogroup., Conclusions: MBL-producing gram-negative organisms have now emerged in Australia. The resistance gene, blaIMP-4, appears highly mobile; this outbreak involved 5 different gram-negative genera from patients with close epidemiological links.