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1. Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Ming G., Tu, Quyen, Cotta, Menino O., Bauer, Michelle J., Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P. J., Mcwhinney, Brett C., Farkas, Andras, Paterson, David L., Clark, Julia E., Hajkowicz, Krispin, Raman, Sainath, Bialasiewicz, Seweryn, Lipman, Jeffrey, Forde, Brian M., Harris, Patrick N. A., Schlapbach, Luregn J., Coin, Lachlan, Roberts, Jason A., and Irwin, Adam D.

Published
2024
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2. Correction: Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Ming G., Tu, Quyen, Cotta, Menino O., Bauer, Michelle J., Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P. J., Mcwhinney, Brett C., Farkas, Andras, Paterson, David L., Clark, Julia E., Hajkowicz, Krispin, Raman, Sainath, Bialasiewicz, Seweryn, Lipman, Jeffrey, Forde, Brian M., Harris, Patrick N. A., Schlapbach, Luregn J., Coin, Lachlan, Roberts, Jason A., and Irwin, Adam D.

Published
2024
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4. Comparison of ceftazidime-avibactam susceptibility testing methods against OXA-48-like carrying Klebsiella blood stream isolates

Author

Isler, Burcu, Vatansever, Cansel, Özer, Berna, Çınar, Güle, Aslan, Abdullah Tarık, Stewart, Adam, Simos, Peter, Falconer, Caitlin, Bauer, Michelle J., Forde, Brian, Harris, Patrick, Şimşek, Funda, Tülek, Necla, Demirkaya, Hamiyet, Menekşe, Şirin, Akalin, Halis, Balkan, İlker İnanç, Aydın, Mehtap, Tigen, Elif Tükenmez, Demir, Safiye Koçulu, Kapmaz, Mahir, Keske, Şiran, Doğan, Özlem, Arabacı, Çiğdem, Yağcı, Serap, Hazırolan, Gülşen, Bakır, Veli Oğuzalp, Gönen, Mehmet, Saltoğlu, Neşe, Azap, Alpay, Azap, Özlem, Akova, Murat, Ergönül, Önder, Paterson, David L., and Can, Füsun

Published
2022
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6. Characterization of Gram-negative Bloodstream Infections in Hospitalized Australian Children and Their Clinical Outcomes.

Author

Wen, Sophie C H, Harris, Patrick N A, Forde, Brian, Permana, Budi, Chatfield, Mark D, Lau, Colleen L, Spurling, Geoffrey, Bauer, Michelle J, Balch, Ross, Chambers, Henry, Schlapbach, Luregn J, Clark, Julia E, Dougherty, Sonia, Blyth, Christopher C, Britton, Philip N, Clifford, Vanessa, Haeusler, Gabrielle M, McMullan, Brendan, Wadia, Ushma, and Paterson, David L

Subjects
RISK assessment, URINARY tract infections, THIRD generation cephalosporins, PUBLIC health surveillance, RESEARCH funding, MICROBIAL sensitivity tests, PATIENTS, ENTEROBACTERIACEAE diseases, CROSS infection, BACTEREMIA, BLOODBORNE infections, CATHETER-related infections, HOSPITAL admission & discharge, DRUG resistance in microorganisms, SYMPTOMS, SEVERITY of illness index, HOSPITAL mortality, CHILDREN'S hospitals, DESCRIPTIVE statistics, LONGITUDINAL method, ODDS ratio, INTENSIVE care units, RESEARCH, GRAM-negative bacterial diseases, BETA lactamases, CONFIDENCE intervals, COMMUNITY-acquired infections, HOSPITAL care of children, SEQUENCE analysis, COMORBIDITY, DISEASE incidence, C-reactive protein
Abstract

Background Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. Methods A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. Results There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6–8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were bla CTX-M-15 (34/94, 36%) and bla SHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6–6.4). Conclusions GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Ming G, Tu, Quyen, Cotta, Menino O, Bauer, Michelle J, Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P J, Mcwhinney, Brett C, Farkas, Andras, Paterson, David L, Clark, Julia E, Hajkowicz, Krispin, Raman, Sainath; https://orcid.org/0000-0002-0152-9980, Bialasiewicz, Seweryn; https://orcid.org/0000-0001-9474-6943, Lipman, Jeffrey, Forde, Brian M; https://orcid.org/0000-0002-2264-4785, Harris, Patrick N A; https://orcid.org/0000-0002-2895-0345, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Coin, Lachlan, Roberts, Jason A; https://orcid.org/0000-0001-6218-435X, Irwin, Adam D; https://orcid.org/0000-0001-8974-6789, Chai, Ming G, Tu, Quyen, Cotta, Menino O, Bauer, Michelle J, Balch, Ross, Okafor, Charles, Comans, Tracy, Kruger, Peter, Meyer, Jason, Shekar, Kiran, Brady, Kara, Fourie, Cheryl, Sharp, Natalie, Vlad, Luminita, Whiley, David, Ungerer, Jacobus P J, Mcwhinney, Brett C, Farkas, Andras, Paterson, David L, Clark, Julia E, Hajkowicz, Krispin, Raman, Sainath; https://orcid.org/0000-0002-0152-9980, Bialasiewicz, Seweryn; https://orcid.org/0000-0001-9474-6943, Lipman, Jeffrey, Forde, Brian M; https://orcid.org/0000-0002-2264-4785, Harris, Patrick N A; https://orcid.org/0000-0002-2895-0345, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Coin, Lachlan, Roberts, Jason A; https://orcid.org/0000-0001-6218-435X, and Irwin, Adam D; https://orcid.org/0000-0001-8974-6789

Abstract

PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.

Published
2024

8. Rapid nanopore sequencing and predictive susceptibility testing of positive blood cultures from intensive care patients with sepsis

Author

Papp-Wallace, Krisztina M, Papp-Wallace, K M ( Krisztina M ), Harris, Patrick N A; https://orcid.org/0000-0002-2895-0345, Bauer, Michelle J, Lüftinger, Lukas, Beisken, Stephan, Forde, Brian M; https://orcid.org/0000-0002-2264-4785, Balch, Ross, Cotta, Menino; https://orcid.org/0000-0002-2058-2314, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Raman, Sainath; https://orcid.org/0000-0002-0152-9980, Shekar, Kiran, Krüger, Peter; https://orcid.org/0000-0002-1247-9886, Lipman, Jeff, Bialasiewicz, Seweryn; https://orcid.org/0000-0001-9474-6943, Coin, Lachlan, Roberts, Jason A; https://orcid.org/0000-0001-6218-435X, Paterson, David L, Irwin, Adam D, Papp-Wallace, Krisztina M, Papp-Wallace, K M ( Krisztina M ), Harris, Patrick N A; https://orcid.org/0000-0002-2895-0345, Bauer, Michelle J, Lüftinger, Lukas, Beisken, Stephan, Forde, Brian M; https://orcid.org/0000-0002-2264-4785, Balch, Ross, Cotta, Menino; https://orcid.org/0000-0002-2058-2314, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Raman, Sainath; https://orcid.org/0000-0002-0152-9980, Shekar, Kiran, Krüger, Peter; https://orcid.org/0000-0002-1247-9886, Lipman, Jeff, Bialasiewicz, Seweryn; https://orcid.org/0000-0001-9474-6943, Coin, Lachlan, Roberts, Jason A; https://orcid.org/0000-0001-6218-435X, Paterson, David L, and Irwin, Adam D

Abstract

We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g.,Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8–16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use. IMPORTANCE Sepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We ass

Published
2024

9. The Genomic Epidemiology of Clinical Burkholderia pseudomallei Isolates in North Queensland, Australia.

Author

Gassiep, Ian, Chatfield, Mark D., Permana, Budi, Burnard, Delaney, Bauer, Michelle J., Cuddihy, Thom, Forde, Brian M., Mayer-Coverdale, Johanna, Norton, Robert E., and Harris, Patrick N. A.

Subjects
WHOLE genome sequencing, BURKHOLDERIA pseudomallei, INNER cities, DISEASE risk factors, GENETIC variation, MELIOIDOSIS
Abstract

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is highly genetically recombinant, resulting in significant genomic diversity. Multiple virulence factors have been associated with specific disease presentations. To date, there are limited data relating to genomic diversity and virulence factors associated with melioidosis cases in North Queensland, Australia. Aim: To describe the genetic diversity of B. pseudomallei and identify virulence factors associated with clinical risk factors and patient outcomes. Methods: Whole genome sequencing of clinical isolates was performed and analysed with clinical data obtained from a retrospective melioidosis cohort study. Results: Fifty-nine distinct sequence types (STs) were identified from the 128 clinical isolates. Six STs comprised 64/128 (50%) isolates. Novel STs accounted for 38/59 (64%) STs, with ST TSV-13 as the most prevalent (n = 7), and were less likely to possess an LPS A genotype or YLF gene cluster (p < 0.001). These isolates were most likely to be found outside the inner city (aOR: 4.0, 95% CI: 1.7–9.0, p = 0.001). ST TSV-13 was associated with increased mortality (aOR: 6.1, 95% CI: 1.2–30.9, p = 0.03). Patients with a history of alcohol excess were less likely to be infected by fhaB3 (aOR 0.2, 95% CI: 0.1–0.7, p = 0.01) or YLF (aOR: 0.4, 95% CI: 0.2–0.9, p = 0.04) positive isolates. Conclusions: There are a significant number of novel sequence types in Townsville, Australia. An emerging novel ST appears to have an association with geographic location and mortality. Ongoing investigation is required to further understand the impact of this ST on the Townsville region. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Rapid nanopore sequencing and predictive susceptibility testing of positive blood cultures from intensive care patients with sepsis

Author

Harris, Patrick N. A., primary, Bauer, Michelle J., additional, Lüftinger, Lukas, additional, Beisken, Stephan, additional, Forde, Brian M., additional, Balch, Ross, additional, Cotta, Menino, additional, Schlapbach, Luregn, additional, Raman, Sainath, additional, Shekar, Kiran, additional, Kruger, Peter, additional, Lipman, Jeff, additional, Bialasiewicz, Seweryn, additional, Coin, Lachlan, additional, Roberts, Jason A., additional, Paterson, David L., additional, and Irwin, Adam D., additional

Published
2024
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11. Achievement of therapeutic antibiotic exposures using Bayesian dosing software in critically unwell children and adults with sepsis

Author

Chai, Gene M, primary, Tu, Quyen, additional, Cotta, Menino O, additional, Bauer, Michelle J, additional, Balch, Ross, additional, Okafor, Charles, additional, Comans, Tracy, additional, Kruger, Peter, additional, Meyer, Jason, additional, Shekar, Kiran, additional, Brady, Kara, additional, Fourie, Cheryl, additional, Sharp, Natalie, additional, Vlad, Luminita, additional, Whiley, David, additional, Ungerer, Jacobus PJ, additional, Mcwhinney, Brett C, additional, Farkas, Andras, additional, Paterson, David L, additional, Clark, Julia E, additional, Hajkowicz, Krispin, additional, Raman, Sainath, additional, Bialasiewicz, Seweryn, additional, Lipman, Jeffrey, additional, Forde, Brian M, additional, Harris, Patrick NA, additional, Schlapbach, Luregn J, additional, Coin, Lachlan, additional, Roberts, Jason A, additional, and Irwin, Adam D, additional

Published
2023
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13. Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints

Author

Isler, Burcu, primary, Vatansever, Cansel, additional, Özer, Berna, additional, Çınar, Güle, additional, Aslan, Abdullah Tarık, additional, Falconer, Caitlin, additional, Bauer, Michelle J., additional, Forde, Brian, additional, Şimşek, Funda, additional, Tülek, Necla, additional, Demirkaya, Hamiyet, additional, Menekşe, Şirin, additional, Akalin, Halis, additional, Balkan, İlker İnanç, additional, Aydın, Mehtap, additional, Tigen, Elif Tükenmez, additional, Demir, Safiye Koçulu, additional, Kapmaz, Mahir, additional, Keske, Şiran, additional, Doğan, Özlem, additional, Arabacı, Çiğdem, additional, Yağcı, Serap, additional, Hazırolan, Gülşen, additional, Bakır, Veli Oğuzalp, additional, Gönen, Mehmet, additional, Saltoğlu, Neşe, additional, Azap, Alpay, additional, Azap, Özlem, additional, Akova, Murat, additional, Ergönül, Önder, additional, Can, Füsun, additional, Paterson, David L., additional, and Harris, Patrick N. A., additional

Published
2023
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15. Comparison of Low‐Level to High‐Level Disinfection in Eliminating Microorganisms From Ultrasound Transducers Used on Skin: A Noninferiority Randomized Controlled Trial.

Author

Peters, Nathan, Williamson, Frances, Bauer, Michelle J., Llewellyn, Stacey, Snelling, Peter J., Marsh, Nicole, Harris, Patrick N. A., Stewart, Adam G., and Rickard, Claire M.

Subjects
TRANSDUCERS, ULTRASONIC imaging, MICROBIAL growth, MICROORGANISMS
Abstract

Introduction: There is a lack of international consensus as to whether high‐ or low‐level disinfection (HLD or LLD) is required for ultrasound (US) transducers used during percutaneous procedures. This study compared the effectiveness of LLD to HLD on US transducers contaminated with microorganisms from skin. Methods: Two identical linear US transducers repeatedly underwent either LLD or HLD during the study. Randomization determined which of these transducers was applied to left and right forearms of each participant. Swabs taken from transducers before and after reprocessing were plated then incubated for 4–5 days, after which colony forming units (CFU) were counted and identified. The primary hypothesis was the difference in the proportion of US transducers having no CFUs remaining after LLD and HLD would be less than or equal to the noninferiority margin of −5%. Results: Of the 654 recruited participants 73% (n = 478) had microbial growth from both transducers applied to their left and right forearms before reprocessing. These were included in the paired noninferiority statistical analysis where, after disinfection, all CFUs were eliminated in 100% (95% CI: 99.4–100.0%) of HLD transducer samples (n = 478) and 99.0% (95% CI: 97.6–99.7%) of LLD transducer samples (n = 473). The paired difference in the proportion of transducers having all CFUs eliminated between LLD and HLD was −1.0% (95% CI: −2.4 to −0.2%, P‐value <.001). Conclusions: Disinfection with LLD is noninferior to HLD when microorganisms from skin have contaminated the transducer. Therefore, using LLD for US transducers involved in percutaneous procedures would present no higher infection risk compared with HLD. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Optimized Method for Bacterial Nucleic Acid Extraction from Positive Blood Culture Broth for Whole-Genome Sequencing, Resistance Phenotype Prediction, and Downstream Molecular Applications

Author

Bauer, Michelle J., primary, Peri, Anna Maria, additional, Lüftinger, Lukas, additional, Beisken, Stephan, additional, Bergh, Haakon, additional, Forde, Brian M., additional, Buckley, Cameron, additional, Cuddihy, Thom, additional, Tan, Patrice, additional, Paterson, David L., additional, Whiley, David M., additional, and Harris, Patrick N. A., additional

Published
2022
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19. Higher rates of cefiderocol resistance among NDM producing Klebsiella bloodstream isolates applying EUCAST over CLSI breakpoints

Author

Isler, Burcu, Vatansever, Cansel, Özer, Berna, Çınar, Güle, Aslan, Abdullah Tarık, Falconer, Caitlin, Bauer, Michelle J., Forde, Brian, Şimşek, Funda, Tülek, Necla, Demirkaya, Hamiyet, Menekşe, Şirin, Akalin, Halis, Balkan, İlker İnanç, Aydın, Mehtap, Tigen, Elif Tükenmez, Demir, Safiye Koçulu, Kapmaz, Mahir, Keske, Şiran, Doğan, Özlem, Arabacı, Çiğdem, Yağcı, Serap, Hazırolan, Gülşen, Bakır, Veli Oğuzalp, Gönen, Mehmet, Saltoğlu, Neşe, Azap, Alpay, Azap, Özlem, Akova, Murat, Ergönül, Önder, Can, Füsun, Paterson, David L., and Harris, Patrick N. A.

Abstract

Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24–26 mm) for all isolates and 18 mm (IQR 15–21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing.

Published
2023
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20. Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum β-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model

Author

Islam, Kamrul, primary, Sime, Fekade B., additional, Wallis, Steven C., additional, Bauer, Michelle J., additional, Naicker, Saiyuri, additional, Won, Hayoung, additional, Zowawi, Hosam M., additional, Choudhury, Md Abu, additional, Shirin, Tahmina, additional, Habib, Zakir H., additional, Harris, Patrick N. A., additional, Flora, Meerjady S., additional, and Roberts, Jason A., additional

Published
2022
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21. Pharmacodynamic evaluation of piperacillin/tazobactam against extended-spectrum β-lactamase (ESBL)-producing versus non-ESBL-producing Escherichia coli in a hollow-fibre infection model

Author

Islam, Kamrul, primary, Sime, Fekade B., additional, Bauer, Michelle J., additional, Forde, Brian M., additional, Wallis, Steven C., additional, Harris, Patrick, additional, Naicker, Saiyuri, additional, Shirin, Tahmina, additional, Habib, Zakir H., additional, Flora, Meerjady S., additional, and Roberts, Jason A., additional

Published
2022
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22. Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model

Author

Islam, Kamrul, primary, Sime, Fekade B, additional, Wallis, Steven C, additional, Bauer, Michelle J, additional, Forde, Brian M, additional, Harris, Patrick, additional, Shirin, Tahmina, additional, Habib, Zakir H, additional, Flora, Meerjady S, additional, and Roberts, Jason A, additional

Published
2022
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27. Rescuing Tetracycline Class Antibiotics for the Treatment of Multidrug-Resistant Acinetobacter baumannii Pulmonary Infection

Author

De Oliveira, David M. P., primary, Forde, Brian M., additional, Phan, Minh-Duy, additional, Steiner, Bernhard, additional, Zhang, Bing, additional, Zuegg, Johannes, additional, El-deeb, Ibrahim M., additional, Li, Gen, additional, Keller, Nadia, additional, Brouwer, Stephan, additional, Harbison-Price, Nichaela, additional, Cork, Amanda J., additional, Bauer, Michelle J., additional, Alquethamy, Saleh F., additional, Beatson, Scott A., additional, Roberts, Jason A., additional, Paterson, David L., additional, McEwan, Alastair G., additional, Blaskovich, Mark A. T., additional, Schembri, Mark A., additional, McDevitt, Christopher A., additional, von Itzstein, Mark, additional, and Walker, Mark J., additional

Published
2022
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28. Plasmid-Mediated Ciprofloxacin Resistance Imparts a Selective Advantage on Escherichia coli ST131

Author

Phan, Minh-Duy, primary, Peters, Kate M., additional, Alvarez Fraga, Laura, additional, Wallis, Steven C., additional, Hancock, Steven J., additional, Nhu, Nguyen Thi Khanh, additional, Forde, Brian M., additional, Bauer, Michelle J., additional, Paterson, David L., additional, Beatson, Scott A., additional, Lipman, Jeffrey, additional, and Schembri, Mark A., additional

Published
2022
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29. Genomic analysis of Elizabethkingia species from aquatic environments: Evidence for potential clinical transmission

Author

Hem, Sopheak, primary, Jarocki, Veronica M., additional, Baker, Dave J., additional, Charles, Ian G., additional, Drigo, Barbara, additional, Aucote, Sarah, additional, Donner, Erica, additional, Burnard, Delaney, additional, Bauer, Michelle J., additional, Harris, Patrick N.A., additional, Wyrsch, Ethan R., additional, and Djordjevic, Steven P., additional

Published
2022
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34. Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)

Author

Irwin, Adam D., primary, Coin, Lachlan J. M., additional, Harris, Patrick N. A., additional, Cotta, Menino Osbert, additional, Bauer, Michelle J., additional, Buckley, Cameron, additional, Balch, Ross, additional, Kruger, Peter, additional, Meyer, Jason, additional, Shekar, Kiran, additional, Brady, Kara, additional, Fourie, Cheryl, additional, Sharp, Natalie, additional, Vlad, Luminita, additional, Whiley, David, additional, Beatson, Scott A., additional, Forde, Brian M., additional, Paterson, David, additional, Clark, Julia, additional, Hajkowicz, Krispin, additional, Raman, Sainath, additional, Bialasiewicz, Seweryn, additional, Lipman, Jeffrey, additional, Schlapbach, Luregn J., additional, and Roberts, Jason A., additional

Published
2021
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36. Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections caused by AmpC β-Lactamase–producing enterobacter spp, citrobacter freundii, morganella morganii, providencia spp, or serratia marcescens: A pilot multicenter randomized controlled trial (MERINO-2)

Author

Stewart, Adam G, Paterson, David L, Young, Barnaby, Lye, David C, Davis, Joshua S, Schneider, Kellie, Yilmaz, Mesut, Dinleyici, Rumeysa, Runnegar, Naomi, Henderson, Andrew, Archuleta, Sophia, Kalimuddin, Shirin, Forde, Brian M, Chatfield, Mark D, Bauer, Michelle J, Lipman, Jeffrey, Harris-Brown, Tiffany, Harris, Patrick N A, and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
Editor's Choice, AcademicSubjects/MED00290, Enterobacterales, polycyclic compounds, bacteria, Medicine [Science], biochemical phenomena, metabolism, and nutrition, Piperacillin-Tazobactam, bacterial infections and mycoses, Carbapenem, Clinical Trial, Major Articles, Ampc β-Lactamase
Abstract

Background Carbapenems are recommended treatment for serious infections caused by AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative. Methods We enrolled adult patients with bloodstream infection due to chromosomal AmpC producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure, and microbiological relapse at 30 days. Results Seventy-two patients underwent randomization and were included in the primary analysis population. Eleven of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8% [95% confidence interval {CI}, –12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI, 2% to 24%]). In contrast, 0% vs 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. Susceptibility to piperacillin-tazobactam and meropenem using broth microdilution was found in 96.5% and 100% of isolates, respectively. The most common AmpC β-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3, and blaACT-17. No ESBL, OXA, or other carbapenemase genes were identified. Conclusions Among patients with bloodstream infection due to AmpC producers, piperacillin-tazobactam may lead to more microbiological failures, although fewer microbiological relapses were seen. Clinical Trials Registration NCT02437045., Among patients with bloodstream infection due to AmpC-producing Enterobacterales, no difference in clinical and microbiological efficacy was observed between piperacillin-tazobactam and meropenem. More microbiological failures occurred in the piperacillin-tazobactam group, although fewer relapses were seen. A larger trial is required.

Published
2021

37. Optimising Treatment Outcomes for Children and Adults Through Rapid Genome Sequencing of Sepsis Pathogens. A Study Protocol for a Prospective, Multi-Centre Trial (DIRECT)

Author

Irwin, Adam D, Coin, Lachlan J M, Harris, Patrick N A, Cotta, Menino Osbert, Bauer, Michelle J, Buckley, Cameron, et al, Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598, Irwin, Adam D, Coin, Lachlan J M, Harris, Patrick N A, Cotta, Menino Osbert, Bauer, Michelle J, Buckley, Cameron, et al, and Schlapbach, Luregn J; https://orcid.org/0000-0003-2281-2598

Abstract

Background Sepsis contributes significantly to morbidity and mortality globally. In Australia, 20,000 develop sepsis every year, resulting in 5,000 deaths, and more than AUD$846 million in expenditure. Prompt, appropriate antibiotic therapy is effective in improving outcomes in sepsis. Conventional culture-based methods to identify appropriate therapy have limited yield and take days to complete. Recently, nanopore technology has enabled rapid sequencing with real-time analysis of pathogen DNA. We set out to demonstrate the feasibility and diagnostic accuracy of pathogen sequencing direct from clinical samples, and estimate the impact of this approach on time to effective therapy when integrated with personalised software-guided antimicrobial dosing in children and adults on ICU with sepsis. Methods The DIRECT study is a pilot prospective, non-randomized multicentre trial of an integrated diagnostic and therapeutic algorithm combining rapid direct pathogen sequencing and software-guided, personalised antibiotic dosing in children and adults with sepsis on ICU. Participants and interventions DIRECT will collect microbiological and pharmacokinetic samples from approximately 200 children and adults with sepsis admitted to one of four ICUs in Brisbane. In Phase 1, we will evaluate Oxford Nanopore Technologies MinION sequencing direct from blood in 50 blood culture-proven sepsis patients recruited from consecutive patients with suspected sepsis. In Phase 2, a further 50 consecutive patients with suspected sepsis will be recruited in whom MinION sequencing will be combined with Bayesian software-guided (ID-ODS) personalised antimicrobial dosing. Outcome measures The primary outcome is time to effective antimicrobial therapy, defined as trough drug concentrations above the MIC of the pathogen. Secondary outcomes are diagnostic accuracy of MinION sequencing from whole blood, time to pathogen identification and susceptibility testing using sequencing direct from whole blood

Published
2021

38. Clinical Burkholderia pseudomallei isolates from north Queensland carry diverse bimABm genes that are associated with central nervous system disease and are phylogenomically distinct from other Australian strains.

Author

Burnard, Delaney, Bauer, Michelle J., Falconer, Caitlin, Gassiep, Ian, Norton, Robert E., Paterson, David L., and Harris, Patrick NA

Subjects
*MELIOIDOSIS, *BURKHOLDERIA pseudomallei, *CENTRAL nervous system diseases, *GENOMICS, *COMPARATIVE genomics, CENTRAL nervous system infections
Abstract

Background: Burkholderia pseudomallei is an environmental gram-negative bacterium that causes the disease melioidosis and is endemic in many countries of the Asia-Pacific region. In Australia, the mortality rate remains high at approximately 10%, despite curative antibiotic treatment being available. The bacterium is almost exclusively found in the endemic region, which spans the tropical Northern Territory and North Queensland, with clusters occasionally present in more temperate climates. Despite being endemic to North Queensland, these infections remain understudied compared to those of the Northern Territory. Methodology/Principal findings: This study aimed to assess the prevalence of central nervous system (CNS) disease associated variant bimABm, identify circulating antimicrobial resistance mutations and genetically distinct strains from Queensland, via comparative genomics. From 76 clinical isolates, we identified the bimABm variant in 20 (26.3%) isolates and in 9 (45%) of the isolates with documented CNS infection (n = 18). Explorative analysis suggests a significant association between isolates carrying the bimABm variant and CNS disease (OR 2.8, 95% CI 1.3–6.0, P = 0.009) compared with isolates carrying the wildtype bimABp. Furthermore, 50% of isolates were identified as novel multi-locus sequence types, while the bimABm variant was more commonly identified in isolates with novel sequence types, compared to those with previously described. Additionally, mutations associated with acquired antimicrobial resistance were only identified in 14.5% of all genomes. Conclusions/Significance: The findings of this research have provided clinically relevant genomic data of B. pseudomallei in Queensland and suggest that the bimABm variant may enable risk stratification for the development CNS complications and be a potential therapeutic target. Author summary: Melioidosis is a life-threatening infection, caused by the Gram-negative bacterium Burkholderia pseudomallei, which is endemic to tropical regions in Australia. Variants of the bimA gene have been proposed as a virulence factor associated with more severe disease. In a genomic analysis of 76 clinical B. pseudomallei isolates from Queensland, Australia, we identified that the bimABm variant was associated with infection involving the central nervous system (odds ratio 2.8, 95% Confidence Interval: 1.3–6.0, P = 0.009), compared to isolates with the wild-type allele bimABp. Half of the isolates from this region were novel multi-locus sequence types, and bimABm was more commonly seen in these novel sequence types. Early genomic characterisation to identify virulence factors such as bimABm, may be useful as an early marker of more complex disease that could guide further investigation and help determine optimal treatment. Further investigation of a "genomics-guided" approach to the clinical management of this complex infectious disease are warranted. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis

Author

De Oliveira, David M. P., primary, Bohlmann, Lisa, additional, Conroy, Trent, additional, Jen, Freda E.-C., additional, Everest-Dass, Arun, additional, Hansford, Karl A., additional, Bolisetti, Raghu, additional, El-Deeb, Ibrahim M., additional, Forde, Brian M., additional, Phan, Minh-Duy, additional, Lacey, Jake A., additional, Tan, Aimee, additional, Rivera-Hernandez, Tania, additional, Brouwer, Stephan, additional, Keller, Nadia, additional, Kidd, Timothy J., additional, Cork, Amanda J., additional, Bauer, Michelle J., additional, Cook, Gregory M., additional, Davies, Mark R., additional, Beatson, Scott A., additional, Paterson, David L., additional, McEwan, Alastair G., additional, Li, Jian, additional, Schembri, Mark A., additional, Blaskovich, Mark A. T., additional, Jennings, Michael P., additional, McDevitt, Christopher A., additional, von Itzstein, Mark, additional, and Walker, Mark J., additional

Published
2020
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43. Smile - Secure my intravenous line effectively: A pilot randomised controlled trial of peripheral intravenous catheter securement in paediatrics

Author

Kleidon, Tricia M., primary, Rickard, Claire M., additional, Gibson, Victoria, additional, Mihala, Gabor, additional, Schults, Jessica A., additional, Xu, Hui (Grace), additional, Bauer, Michelle J., additional, Marsh, Nicole, additional, Larsen, Emily N., additional, Cattanach, Paula, additional, and Ullman, Amanda J., additional

Published
2020
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46. Heteroatom-Interchanged Isomers of Lissoclinamide 5: Copper(II) Complexation, Halide Binding, and Biological Activity

Author

Xie, Sida, primary, Savchenko, Andrei I., additional, Kerscher, Marion, additional, Grange, Rebecca L., additional, Krenske, Elizabeth H., additional, Harmer, Jeffrey R., additional, Bauer, Michelle J., additional, Broit, Natasa, additional, Watters, Dianne J., additional, Boyle, Glen M., additional, Bernhardt, Paul V., additional, Parsons, Peter G., additional, Comba, Peter, additional, Gahan, Lawrence R., additional, and Williams, Craig M., additional

Published
2018
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47. Evaluation of Skin Colonisation And Placement of vascular access device Exit sites (ESCAPE Study).

Author

Moureau, Nancy L., Marsh, Nicole, Zhang, Li, Bauer, Michelle J., Larsen, Emily, Mihala, Gabor, Corley, Amanda, Lye, India, Cooke, Marie, and Rickard, Claire M.

Subjects
PREVENTION of bloodborne infections, SKIN microbiology, CATHETER-related infections, BLOOD vessels, CHI-squared test, CONFIDENCE intervals, HOST-bacteria relationships, MEDICAL equipment, RESEARCH funding, STATISTICAL sampling, LOGISTIC regression analysis, ODDS ratio, COLONY-forming units assay, INFECTION prevention
Abstract

Background: Skin microorganisms may contribute to the development of vascular access device (VAD) infections. Baseline skin microorganism type and quantity vary between body sites, yet there is little evidence to inform choice of VAD site selection. Objective: To compare microorganisms present at different body sites used for VAD insertions and understand the effect of transparent dressings on skin microflora. Methods: The ESCAPE observational study consisted of three phases: (1) skin swabs of four sites (mid-neck, base neck, chest, upper arm) from 48 hospital patients; (2) skin swabs of five body sites (mid-neck, base neck, chest, upper arm, lower arm) from 10 healthy volunteers; and (3) paired skin swabs (n = 72) under and outside of transparent dressings from 36 hospital patients (16 mid/base neck, 10 chest, upper arm). Specimens were cultured for 72 h, species identified and colony-forming units (CFU) counted. Ordinal logistic regression compared CFU categories between variables of interest. Results: The chest and upper arm were significantly associated with fewer microorganisms compared to neck or forearm (odds ratio [OR] = 0.40, 95% confidence interval [CI] = 0.25–0.65, P < 0.05). CFU levels under transparent dressings were not significantly different from outside (OR = 0.57, 95% CI = 0.22–1.45). Staphylococci were predominant at all sites. Other significant (P < 0.05) predictors of higher CFU count included prolonged hospitalisation and medical/surgical patient status. Discussion: Skin microorganism load was significantly lower at the upper arm or chest, compared to the mid- or base neck. This may impact VAD site selection and subsequent infection risk. [ABSTRACT FROM AUTHOR]

Published
2019
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