David Paterson

Royal Brisbane Hospital | RBWH · University of Queensland Centre for Clinical Research

Objectives Randomised trials for the management of drug-resistant infections are challenging to conduct as target patient populations often lack decision-making capacity, and enrolment windows are typically short. Improving informed consent and risk communication in these trials is especially crucial for protecting patient interests and maximising...

OBJECTIVES Enterobacterales bloodstream infections (E-BSI) cause a significant burden of disease in children and are associated with antimicrobial resistance. We assessed temporal changes in the population-based incidence of E-BSI in children in Queensland, Australia. METHODS We conducted a cohort study of incidents of E-BSI occurring in children...

Objective Knowledge of local antibiotic resistance data, provided by antibiograms (a cumulative summary of in vitro-antimicrobial-susceptibility-test results), can aid prescribing of appropriate empirical antibiotics. This study aimed to explore the feasibility of antibiogram development for residential aged care facilities (RACFs). Design Retrosp...

Background The global burden of the opportunistic fungal disease Pneumocystis jirovecii pneumonia (PJP) remains substantial. Polymerase chain reaction (PCR) on nasopharyngeal swabs (NPS) has high specificity and may be a viable alternative to the gold standard diagnostic of PCR on invasively collected lower respiratory tract specimens, but has low...

Introduction Blood cultures have low sensitivity for candidemia. Sensitivity can be improved by the culture-independent system T2 Magnetic Resonance (T2). SeptiCyte RAPID is a host response assay quantifying the risk of infection-related inflammation through a scoring system (SeptiScore). We investigate the performance of SeptiScore in detecting pe...

Importance Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days...

Introduction The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and is recommended in many guidelines, but there is limited evidence underpinning this. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxin...

Background Evidence about the clinical impact of rapid diagnostic tests (RDT) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BC) embedded within antimicrobial stewardship programs (ASP) is unknown. Methods We performed network meta-analyses (NMA) using results from studies of pa...

Background Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. Methods We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB)....

Carbapenemase‐producing gram‐negative bacteria (CP‐GNB) infections threaten public health with high mortality, morbidity and treatment costs. Although frequencies remain low in Australia (total number of CP‐GNB infections reported was 907 in 2022), bla IMP‐4 has established low levels of endemicity in many states. Imipenemase metallo‐β‐lactamase ty...

Antimicrobial Surveillance

Background Knowledge of local antibiotic resistance data provided by antibiograms (cumulative-antimicrobial-susceptibility-tests) can assist prescribers to make appropriate empirical antibiotic choices. Objective This study explored the perceptions and knowledge of key stakeholders about the role of antibiograms in residential aged care facilities...

Background: The recognition of Pseudomonas stutzeri as a cause of infections in humans has been increasing. However, only case reports and small series of P. stutzeri bloodstream infections have been published. Epidemiological data on these infections are extremely scarce. Our objective was to describe the incidence, epidemiology, antimicrobial re...

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 antibio...

Background Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CRE) are a global health concern. Rapid identification of CRE may improve patient outcomes and reduce inappropriate antibiotic prescription. The use of risk-scoring tools (RSTs) can be valuable for optimizing the decision-making process for empirical antibioti...

Using nasopharyngeal swabs (NPS) instead of lower respiratory tract specimens for PCR to diagnose P. jirovecii pneumonia (PJP) may be better tolerated and improve diagnostic accessibility. In this two-year Australian retrospective cohort study of patients with clinically-suspected PJP, P. jirovecii PCR on NPS had perfect specificity but low sensiti...

Background Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritise o...

Existing tools for phylogeographic and epidemiological visualisation primarily provide a macro-geographic view of epidemic and pandemic transmission events but offer little support for detailed investigation of outbreaks in healthcare settings. Here, we present HAIviz, an interactive web-based application designed for integrating and visualising ge...

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...

Background: A prompt diagnosis of bacteraemia and sepsis is essential. Markers to predict the risk of persistent bacteraemia and metastatic infection are lacking. SeptiCyte RAPID is a host response assay stratifying patients according to the risk of infectious vs sterile inflammation through a scoring system (SeptiScore). In this study we explore...

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention mo...

Background & significance: Hypogammaglobulinemia is common in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), and associated with an increased risk of serious infection. Immunoglobulin (Ig) replacement therapy (IgRT) is widely used to reduce this risk, but national guidelines and clinical prac...

Background Although double carbapenem regimens have reliable synergy against carbapenemase-producing Klebsiella pneumoniae (CP-Kp), the capacity of piperacillin-tazobactam (TZP) to provide synergistic activity with meropenem (MEM) is uncertain. Methods We used time-kill assays to evaluate synergy between TZP and MEM and imipenem (IMI)-MEM against...

Background Elizabethkingia species are environmental opportunistic pathogens that are a rare but potentially severe cause of bloodstream infection (BSI). The objective of this study was to determine the incidence, risk factors, and outcomes of Elizabethkingia species BSI in a large Australian population. Methods Retrospective, laboratory-based sur...

Background Staphylococcus aureus bloodstream infection (bacteraemia) is traditionally treated with at least two weeks of IV antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteraemia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is bas...

Introduction: Persistent S. aureus bacteraemia is associated with metastatic infection and adverse outcomes while Gram-negative bacteraemia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic v...

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 ID-ODS™ to reduce time to effective antibiotic exposure in children and adults in ICU...

Background: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. Methods: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA...

BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patient...

Knowledge of the epidemiology of bloodstream infection (BSI) in haematology patients is essential to guide patient management. We investigated the epidemiology of BSI in patients with haematological malignancies in Queensland over the last 20 years (2000–2019), including all episodes diagnosed by the state-wide microbiology service. We identified 7...

Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is one of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals...

Introduction Carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alon...

Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurre...

Background: 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...

Plasmids are major drivers of increasing antibiotic resistance, necessitating an urgent need to understand their biology. Here we describe a detailed dissection of the molecular components controlling the genetics of I-complex plasmids, a group of antibiotic resistance plasmids found frequently in pathogenic Escherichia coli and other Enterobacteri...

Background Direct metagenomic sequencing from positive blood culture (BC) broths, to identify bacteria and predict antimicrobial susceptibility, has been previously demonstrated using Illumina-based methods, but is relatively slow. We aimed to evaluate this approach using nanopore sequencing to provide more rapid results. Methods Patients with sus...

To investigate an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) sequence type 78 (ST78) in a large tertiary Australian hospital. A collection of 63 VREfm ST78 isolates, identified during a routine genomic surveillance program, were subjected to genomic epidemiological analysis based on whole-genome sequencing (WGS) data. The populat...

Background Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality in both healthcare and community settings. We aimed to define the predisposing factors, risks for severe disease, and mortality determinants of CDI in eastern Australia over a 1-year period. Methods This is an observational retrospective stud...

Extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales as a cause of community-acquired uncomplicated urinary tract infection (UTI) is on the rise. Currently, minimal oral treatment options exist. New combinations of existing oral third generation cephalosporins paired with clavulanate may overcome resistance mechanisms seen in these em...

Background: Bloodstream infections may occur as a complication of colorectal cancer or be a marker for its occult presence. The objectives of this study were to quantify the overall and etiology-specific risks for incident colorectal cancer-associated bloodstream infection. Methods: Population-based surveillance for community-onset bloodstream i...

The emerging and global spread of a novel plasmid-mediated colistin resistance gene, mcr-1, threatens human health. It is accepted that MCR-1 affects bacterial fitness, and this fitness cost correlates with bacterial membrane lipid A perturbation. However, the detailed molecular mechanism remains unclear. Here, we screened out a novel MCR-1 variant...

Aim: This study was designed to understand current practice in duration of antibiotic treatment and timing of intravenous (iv) to oral switch for common bacteraemic conditions amongst infectious diseases (ID) and intensive care unit (ICU) physicians. Methods: An online survey consisting of 18 questions comprising five common clinical bacteremia...

Pseudomonas aeruginosa infective endocarditis (IE) is a rare disease associated with high mortality and complications. Here, we describe a contemporary set of patients aiming to improve the understanding of risk factors, clinical features, treatments, and outcomes. This retrospective case series reviewed cases from 3 tertiary metropolitan hospitals...

Purpose: We aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers. Methods: 91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis;...

Objectives: The dissemination of Escherichia coli –producing extended-spectrum β-lactamase (ESBL-Ec) is evident in the community. In this population-based spatial analysis, we sought to describe the distribution of ESBL-Ec and to identify predictors of incidence in the community. Methods: The study population was defined as individuals with the ESB...

Purpose: Although Klebsiella aerogenes (formerly Enterobacter aerogenes) and Enterobacter cloacae share many phenotypic characteristics, controversy exists as to whether they cause clinically distinguishable infections. The objective of this study was to determine the comparative incidence, determinants, and outcomes of K. aerogenes and E. cloacae...

Background There is increasing morbidity and mortality attributed to escalating incidence of Escherichia coli bloodstream infection (BSI). The epidemiology of E. coli BSI is dynamic and differs across populations, this study aimed to describe this epidemiology in Queensland, Australia. Methods Incident E. coli BSI (new or recurring at least 30 day...

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. Methods: We conducte...

The epidemiology of Moraxella species bloodstream infection (BSI) is poorly defined due to their rarity. We sought to determine the incidence, risk factors, and outcomes of Moraxella species BSI in a large Australian population. All Moraxella species BSIs in patients admitted to Queensland (population estimate 5 million) public health facilities be...

Background P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). Methods We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitali...

Introduction. Aminoglycosides are used for the treatment of carbapenemase-producing Klebsiella pneumoniae (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM. Hypothesis/Gap Statement. There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasiv...

Background Carbapenemase-producing (CP) Escherichia coli (CPEc) are a global public health threat. We describe the epidemiology and outcomes of patients with CPEc isolates obtained in CRACKLE 2, a prospective cohort study of hospitalized patients with positive cultures for CP Enterobacteriaceae. Methods In CRACKLE-2, patients with CPEc were enroll...

Background SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have...

BACKGROUND: Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS: In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to e...

Although new-generation antimicrobials, in particular β-lactam/β-lactamase inhibitors, have largely replaced polymyxins in carbapenem-resistant Gram-negative bacterial infections, polymyxins are still needed for carbapanem-resistant Acinetobacter baumannii infections and in settings where novel agents are not readily available. Despite their potent...

Background: Treatment outcomes in studies on prosthetic joint infection are generally assessed using a dichotomous outcome relating to treatment success or failure. These outcome measures neither include patient-centred outcome measures including joint function and quality of life, nor do they account for adverse effects of treatment. A desirabilit...

The application of direct metagenomic sequencing from positive blood culture broth may solve the challenges of sequencing from low-bacterial-load blood samples in patients with sepsis. Forty prospectively collected blood culture broth samples growing Gram-negative bacteria were extracted using commercially available kits to achieve high-quality DNA...

The dissemination of Escherichia coli producing extended-spectrum beta-lactamase (ESBL-Ec) is evident in the community. A population-based spatial analysis is necessary to investigate community risk factors for ESBL-Ec occurrence. The study population was defined as individuals with ESBL-Ec isolated in Queensland, Australia, from 2010 to 2019. Chor...

Background Early identification of bloodstream pathogens and their associated antimicrobial resistance may shorten time to optimal therapy in patients with sepsis. The BioFire Blood Culture Identification 2 Panel (BCID2) is a novel multiplex PCR detecting 43 targets directly from positive blood cultures, reducing turnaround times. Methods We have...

Background: Over 1000 solid-organ and close to 2000 stem-cell transplants are performed annually in Australia. Methods: Antimicrobial stewardship activities in transplant units in Australia were reviewed. Results: All health service organizations, and thus all transplant centers, in Australia are required to have an antimicrobial stewardship p...

Background: Antimicrobials for bloodstream infections due to ESBL- and AmpC-producing Escherichia coli and Klebsiella pneumoniae are significantly limited due to widespread antimicrobial resistance. Tebipenem, an oral carbapenem, exhibits stability against these resistance mechanisms and may prove an attractive alternative. Methods: The in vitro...

Introduction: : OXA-48 and NDM are amongst the most prevalent carbapenemase types associated with Klebsiella pneumoniae worldwide, with an increase in their prevalence in recent years. Knowledge on the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) comes from KPC-producing CRKP with limited data available for OXA-48-like and NDM pr...

Introduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Pros...

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria ( Staphylococcus aureus and Streptococcus pneumoniae ) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We h...