Impact of source of infection and vancomycin AUC0–24/MICBMD targets on treatment failure in patients with methicillin-resistant Staphylococcus aureus bacteraemia

AbstractDespite recent controversies about toxicity and reduced efficacy, vancomycin remains the current treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. The parameter associated with treatment success is the vancomycin 24-h area under concentration-time curve to MIC ratio (AUC0–24/MIC). We aimed to determine the utility of calculated AUCs and explore the optimal AUC0–24/MIC targets associated with treatment success. In this single-centre retrospective observational cohort study of 127 patients with MRSA bacteraemia, forty-five (35.4%) did not respond to vancomycin treatment. Patient characteristics were essentially the same between those who did not respond to vancomycin treatment and those with treatment success, with independent predictors of treatment failure being source of bacteraemia (odds ratio (OR), 4.29; 95% confidence interval (CI), 1.50–12.26; p 0.007) and not achieving an AUC0–24/MICBMD (using broth microdilution) target of ≥398 (OR, 11.4; 95% CI, 4.57–28.46; p< 0.001). Bacteraemic source-specific thresholds were observed with a higher AUC0–24/MICBMD target of 440 required for high-risk sources (e.g. infective endocarditis) compared with 330 for low-risk sources (line related bacteraemia). Overall treatment success in patients with MRSA bacteraemia was associated with a vancomycin AUC0–24/MICBMD target of ≥398, with source-specific targets observed. Future vancomycin practice guidelines will need to take into account MIC methodology, source of bacteraemia and patient populations prior to setting targets and monitoring recommendations

Mucormycosis in Australia: Contemporary epidemiology and outcomes

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004–2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1–42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2–481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3–25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3–13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome

Antimicrobial resistance in the next 30 years, humankind, bugs and drugs: a visionary approach

Purpose: To describe the current standards of care and major recent advances with regard to antimicrobial resistance (AMR) and to give a prospective overview for the next 30 years in this field. Methods: Review of medical literature and expert opinion were used in the development of this review. Results: There is undoubtedly a large clinical and public health burden associated with AMR in ICU, but it is challenging to quantify the associated excess morbidity and mortality. In the last decade, antibiotic stewardship and infection prevention and control have been unable to prevent the rapid spread of resistant Gram-negative bacteria (GNB), in particular carbapenem-resistant Pseudomonas aeruginosa (and other non-fermenting GNB), extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE). The situation appears more optimistic currently for Gram-positive, where Staphylococcus aureus, and particularly methicillin-resistant S. aureus (MRSA), remains a cardinal cause of healthcare-associated infections worldwide. Recent advancements in laboratory techniques allow for a rapid identification of the infecting pathogen and antibiotic susceptibility testing. Their impact can be particularly relevant in settings with prevalence of MDR, since they may guide fine-tuning of empirically selected regimen, facilitate de-escalation of unnecessary antimicrobials, and support infection control decisions. Currently, antibiotics are the primary anti-infective solution for patients with known or suspected MDR bacteria in intensive care. Numerous incentives have been provided to encourage researchers to work on alternative strategies to reverse this trend and to provide a means to treat these pathogens. Although some promising antibiotics currently in phase 2 and 3 of development will soon be licensed and utilized in ICU, the continuous development of an alternative generation of compounds is extremely important. There are currently several promising avenues available to fight antibiotic resistance, such as faecal microbiota, and phage therapy. © 2017, Springer-Verlag GmbH Germany and ESICM

Universal scaling in highly doped conducting polymer films

Electrical transport of a highly doped disordered conducting polymer, viz. poly-3,4-ethylenedioxythiophene stabilized with poly-4-styrenesulphonic acid, is investigated as a function of bias and temperature. The transport shows universal power-law scaling with both bias and temperature. All measurements constitute a single universal curve, and the complete J(V,T) characteristics are described by a single equation. We relate this scaling to dissipative tunneling processes, such as Coulomb blockade. © 2010 The American Physical Society

A multicentre outbreak of ST45 MRSA containing deletions in the spa gene in New South Wales, Australia

Background Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45. Objectives To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia. Methods WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed. Results Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this ‘spa-deletion’ MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations. Conclusions This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new ‘spa-deletion’ MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time

Assessment of Inter-Laboratory Differences in SARS-CoV-2 Consensus Genome Assemblies between Public Health Laboratories in Australia

Whole-genome sequencing of viral isolates is critical for informing transmission patterns and for the ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences in consensus genome assemblies of 72 matched SARS-CoV-2-positive specimens sequenced at different laboratories in Sydney, Australia. Raw sequence data were assembled using two different bioinformatics pipelines in parallel, and resulting consensus genomes were compared to detect laboratory-specific differences. Matched genome sequences were predominantly concordant, with a median pairwise identity of 99.997%. Identified differences were predominantly driven by ambiguous site content. Ignoring these produced differences in only 2.3% (5/216) of pairwise comparisons, each differing by a single nucleotide. Matched samples were assigned the same Pango lineage in 98.2% (212/216) of pairwise comparisons, and were mostly assigned to the same phylogenetic clade. However, epidemiological inference based only on single nucleotide variant distances may lead to significant differences in the number of defined clusters if variant allele frequency thresholds for consensus genome generation differ between laboratories. These results underscore the need for a unified, best-practices approach to bioinformatics between laboratories working on a common outbreak problem

Mucormycosis in Australia: contemporary epidemiology and outcomes

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p &lt;0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR&nbsp;=&nbsp;24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR&nbsp;=&nbsp;7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR&nbsp;=&nbsp;4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome