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Background Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (B Cs) embedded within antimicrobial stewardship programs (ASPs) is unknown. Methods We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. Results Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI],.59–.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI,.63–.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI,.84–.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (−29 hours; 95% CI, −35 to −23), BC + ASP (−18 hours; 95% CI, −27 to −10), and to RDT alone (−12 hours; 95% CI, −20 to −3). Conclusions The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC. [ABSTRACT FROM AUTHOR]

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]

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 prioritize outcome measures by relative clinical importance. Methods The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. Results With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI],.22–.71]; P =.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI,.68–.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI,.60–.99; P =.04). Conclusions The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials. [ABSTRACT FROM AUTHOR]

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 association between SeptiScore and persistent bacteraemia as well as metastatic and persistent infection in the context of a proven bacteraemia episode. This is a prospective multicentre observational 14-month study on patients with proven bacteraemia caused by Staphylococcus aureus or Gram-negative bacilli. Samples for assessment by SeptiCyte were collected with paired blood cultures for 4 consecutive days after the index blood culture. We included 86 patients in the study, 40 with S. aureus and 46 with Gram-negative bacilli bacteraemia. SeptiScores over the follow-up were higher in patients with Gram-negative compared to S. aureus bacteraemia (median 6.4, IQR 5.5–7.4 vs 5.6 IQR 5.1–6.2, p = 0.002). Higher SeptiScores were found to be associated with positive blood cultures at follow-up (AUC = 0.86, 95%CI 0.68–1.00) and with a diagnosis of metastatic infection at day 1 and 2 of follow-up (AUC = 0.79, 95%CI 0.57–1.00 and AUC = 0.82, 95%CI 0.63–1.00 respectively) in the context of Gram-negative bacteraemia while no association between SeptiScore and the outcomes of interest was observed in S. aureus bacteraemia. Mixed models confirmed the association of SeptiScore with positive blood cultures at follow-up (p = 0.04) and metastatic infection (p = 0.03) in the context of Gram-negative bacteraemia but not S. aureus bacteraemia after adjusting for confounders. SeptiScores differ in the follow-up of S. aureus and Gram-negative bacteraemia. In the setting of Gram-negative bacteraemia SeptiScore demonstrated a good negative predictive value for the outcomes of interest and might help rule out the persistence of infection defined as metastatic spread, lack of source control or persistent bacteraemia. [ABSTRACT FROM AUTHOR]

Background Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia 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 value and guide management decisions is unknown. Methods We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance–DNAemia [MR-DNAemia]) and clinical outcomes. Results Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR,.54; 95% CI,.39–.75) and did not differ according to the causative pathogen (P =.5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45–2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12–3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35–3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21–2.56). Conclusions T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Background: Vibrio species bloodstream infections have been associated with significant mortality and morbidity. Limited information is available regarding the epidemiology of bloodstream infections because of Vibrio species in the Australian context. Aims: The objective of this study was to define the incidence and risk factors for developing Vibrio species bloodstream infections and compare differences between different species. Methods: All patients with Vibrio spp. isolated from positive blood cultures between 1 January 2000 and 31 December 2019 were identified by the state‐wide Pathology Queensland laboratory. Demographics, clinical foci of infections and comorbid conditions were collected in addition to antimicrobial susceptibility results. Results: About 100 cases were identified between 2000 and 2019 with an incidence of 1.2 cases/1 million person‐years. Seasonal and geographical variation occurred with the highest incidence in the summer months and in the tropical north. Increasing age, male sex and multiple comorbidities were identified as risk factors. Vibrio vulnificus was isolated most frequently and associated with the most severe disease. Overall case fatality was 19%. Conclusions: There is potential for increasing cases of Vibrio species infections globally with ageing populations and climate change. Ongoing clinical awareness is required to ensure optimal patient outcomes. [ABSTRACT FROM AUTHOR]

Piperacillin-tazobactam (PTZ) is one of the most common antibiotics administered to hospitalized patients. Its broad activity against gram-negative, gram-positive, and anaerobic pathogens; efficacy in clinical trials across diverse infection types and patient populations; and generally favorable toxicity profile make it a particularly appealing antibiotic agent. PTZ susceptibility interpretive criteria (ie, breakpoints) for the Enterobacterales were initially established in 1992, as the drug was undergoing approval by the US Food and Drug Administration. In the ensuing 30 years, changes in the molecular epidemiology of the Enterobacterales and its impact on PTZ susceptibility testing, mounting pharmacokinetic/pharmacodynamic data generated from sophisticated techniques such as population pharmacokinetic modeling and Monte Carlo simulation, and disturbing safety signals in a large clinical trial prompted the Clinical Laboratory and Standards Institute (CLSI) to review available evidence to determine the need for revision of the PTZ breakpoints for Enterobacterales. After an extensive literature review and formal voting process, the susceptibility criteria were revised in the 2022 CLSI M100 document to the following: ≤8/4 µg/mL (susceptible), 16/4 µg/mL (susceptible dose-dependent), and ≥32/4 µg/mL (resistant). Herein, we provide a brief overview of the CLSI process of antibiotic breakpoint revisions and elaborate on the available data that ultimately led to the decision to revise the PTZ breakpoints. [ABSTRACT FROM AUTHOR]

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]