Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens.

BACKGROUND: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting. METHODS: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E), and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites, or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MLST) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams. RESULTS: Over 4 years (April 2017 to July 2021) 2660 isolates were sequenced. This included MDR gram-negative bacilli (n = 293 CPE, n = 1309 ESBL), MRSA (n = 620), and VRE (n = 433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the 3 target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In 1 hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy. CONCLUSIONS: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.

Quality measurement and surveillance platforms in critically ill children: A scoping review.

BACKGROUND/AIM: The objective of this study was to describe current surveillance platforms which support routine quality measurement in paediatric critical care. METHOD: Scoping review. The search strategy consisted of a traditional database and grey literature search as well as expert consultation. Surveillance platforms were eligible for inclusion if they collected measures of quality in critically ill children. RESULTS: The search strategy identified 21 surveillance platforms, collecting 57 unique outcome (70%), process (23%), and structural (7%) quality measures. Hospital-associated infections were the most commonly collected outcome measure across all platforms (n = 11; 52%). In general, case definitions were not harmonised across platforms, with the exception of nationally mandated hospital-associated infections (e.g., central line-associated blood stream infection). Data collection relied on manual coding. Platforms typically did not provide an evidence-based rationale for measures collected, with no identifiable reports of co-designed, consensus-derived measures or consumer involvement in measure selection or prioritisation. CONCLUSIONS: Quality measurement in critically ill children lacks uniformity in definition which limits local and international benchmarking. Current surveillance activities for critically ill children focus heavily on outcome measurement, with process, structural, and patient-reported measures largely overlooked. Long-term outcome measures were not routinely collected. Harmonisation of paediatric intensive care unit quality measures is needed and can be achieved using prioritisation and consensus/co-design methods.

Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)-non-inferiority (peripheral arterial catheter) trial.

BACKGROUND: The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters. METHODS: We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device-peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete. FINDINGS: Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference [ARD] 0·32%, 95% CI -0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, -0·27% to 0·83%). There were no treatment-related adverse events. INTERPRETATION: Infusion set use can be safely extended to 7 days with resultant cost and workload reductions. FUNDING: Australian National Health and Medical Research Council.

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Infective Endocarditis: A Contemporary Study of Microbiology, Echocardiography and Associated Clinical Outcomes at a Major Tertiary Referral Centre.

BACKGROUND: The epidemiology of infective endocarditis (IE) continues to evolve, with antimicrobial resistance and clinical outcomes largely dependent on the environment of acquisition. This study aimed to provide a contemporary review of the microbiology and antimicrobial management of IE and report echocardiographic findings and predictors of adverse outcomes in community-acquired and health care-associated IE. METHODS: Consecutive presentations of IE to a major Australian tertiary referral centre between January 2011 and April 2016 were examined. Culprit organisms and resistance patterns were recorded, as was transthoracic and transoesophageal echocardiography. Real-world antimicrobial prescription and use of an outpatient parenteral antimicrobial therapy (OPAT) service were also assessed, and clinical outcomes analysed. RESULTS: Of 204 consecutive cases, 30% were associated with health care, a group with a higher burden of comorbidities and more prone to complications. Health care-associated cases had lower rates of surgical intervention but higher mortality. A history of intravenous drug use (IVDU) conferred risk for recurrent IE whereas multivalvular involvement predicted heart failure hospitalisation. Staphylococcus aureus was isolated in 45%. Whilst methicillin resistance remains low, the prevalence of S. aureus IE is increasing. Single antimicrobial agents were commonly used (83%) and therapy via OPAT was safe and significantly reduced length of hospital stay. Not undergoing transoesophageal echocardiography (TOE) or definitive surgical management conferred poorer prognosis. CONCLUSIONS: The epidemiology of IE is evolving and there is need for updated epidemiological data and associated clinical outcomes. Environment of acquisition remains important in the face of increasing health care provision and the changing predominance of culprit microorganisms.

Dressings and securements for the prevention of peripheral intravenous catheter failure in adults (SAVE): a pragmatic, randomised controlled, superiority trial.

BACKGROUND: Two billion peripheral intravenous catheters (PIVCs) are used globally each year, but optimal dressing and securement methods are not well established. We aimed to compare the efficacy and costs of three alternative approaches to standard non-bordered polyurethane dressings. METHODS: We did a pragmatic, randomised controlled, parallel-group superiority trial at two hospitals in Queensland, Australia. Eligible patients were aged 18 years or older and required PIVC insertion for clinical treatment, which was expected to be required for longer than 24 h. Patients were randomly assigned (1:1:1:1) via a centralised web-based randomisation service using random block sizes, stratified by hospital, to receive tissue adhesive with polyurethane dressing, bordered polyurethane dressing, a securement device with polyurethane dressing, or polyurethane dressing (control). Randomisation was concealed before allocation. Patients, clinicians, and research staff were not masked because of the nature of the intervention, but infections were adjudicated by a physician who was masked to treatment allocation. The primary outcome was all-cause PIVC failure (as a composite of complete dislodgement, occlusion, phlebitis, and infection [primary bloodstream infection or local infection]). Analysis was by modified intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000769987. FINDINGS: Between March 18, 2013, and Sept 9, 2014, we randomly assigned 1807 patients to receive tissue adhesive with polyurethane (n=446), bordered polyurethane (n=454), securement device with polyurethane (n=453), or polyurethane (n=454); 1697 patients comprised the modified intention-to-treat population. 163 (38%) of 427 patients in the tissue adhesive with polyurethane group (absolute risk difference -4·5% [95% CI -11·1 to 2·1%], p=0·19), 169 (40%) of 423 of patients in the bordered polyurethane group (-2·7% [-9·3 to 3·9%] p=0·44), 176 (41%) of 425 patients in the securement device with poplyurethane group (-1·2% [-7·9% to 5·4%], p=0·73), and 180 (43%) of 422 patients in the polyurethane group had PIVC failure. 17 patients in the tissue adhesive with polyurethane group, two patients in the bordered polyurethane group, eight patients in the securement device with polyurethane group, and seven patients in the polyurethane group had skin adverse events. Total costs of the trial interventions did not differ significantly between groups. INTERPRETATION: Current dressing and securement methods are commonly associated with PIVC failure and poor durability, with simultaneous use of multiple products commonly required. Cost is currently the main factor that determines product choice. Innovations to achieve effective, durable dressings and securements, and randomised controlled trials assessing their effectiveness are urgently needed. FUNDING: Australian National Health and Medical Research Council.

Whole genome analysis of cephalosporin-resistant Escherichia coli from bloodstream infections in Australia, New Zealand and Singapore: high prevalence of CMY-2 producers and ST131 carrying blaCTX-M-15 and blaCTX-M-27.

Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore. Methods: We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial from February 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest. Results: A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P = 0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n = 6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P < 0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF. Conclusions: In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.

Early use of peripherally inserted central catheters is safe in Staphylococcus aureus bacteraemia.

BACKGROUND: Management of Staphylococcus aureus bacteraemia (SAB) includes prolonged intravenous antibiotics often administered through a peripherally inserted central catheter (PICC). Optimal timing of PICC insertion for SAB treatment is unknown. There are concerns that early insertion may increase the risk of subsequent line infection. AIMS: This retrospective audit aims to determine if early PICC insertion is safe. The outcomes considered included crude mortality, attributable mortality, PICC line infections, duration of bacteraemia and relapsed SAB. METHODS: Patients with SAB at our institution between March 2013 and September 2016 were identified. Early PICC line insertion was defined as occurring within 48 h of index positive blood culture. RESULTS: This retrospective audit identified 357 patients with SAB who subsequently received a PICC. This study did not show any significant differences between the early and late PICC insertion groups for attributable mortality (6.3% and 4.8%, P = 0.27), duration of bacteraemia (median 2 days for both groups, P = 0.48) and relapsed SAB (4.7% and 4.1%, P = 0.74). Importantly, no confirmed PICC infections were identified in either group. CONCLUSIONS: Early PICC insertion in SAB appears safe in this retrospective audit. If validated in prospective studies, this should allow for the early establishment of safe, reliable intraveous access in SAB patients.

Characterising health care-associated bloodstream infections in public hospitals in Queensland, 2008-2012.

OBJECTIVE: To describe the epidemiology and rates of all health care-associated bloodstream infections (HA-BSIs) and of specific HA-BSI subsets in public hospitals in Queensland. DESIGN AND SETTING: Standardised HA-BSI surveillance data were collected in 23 Queensland public hospitals, 2008-2012. MAIN OUTCOME MEASURES: HA-BSIs were prospectively classified in terms of place of acquisition (inpatient, non-inpatient); focus of infection (intravascular catheter-associated, organ site focus, neutropenic sepsis, or unknown focus); and causative organisms. Inpatient HA-BSI rates (per 10,000 patient-days) were calculated. RESULTS: There were 8092 HA-BSIs and 9418 causative organisms reported. Inpatient HA-BSIs accounted for 79% of all cases. The focus of infection in 2792 cases (35%) was an organ site, intravascular catheters in 2755 (34%; including 2240 central line catheters), neutropenic sepsis in 1063 (13%), and unknown in 1482 (18%). Five per cent (117 of 2240) of central line-associated BSIs (CLABSIs) were attributable to intensive care units (ICUs). Eight groups of organisms provided 79% of causative agents: coagulase-negative staphylococci (18%), Staphylococcus aureus (15%), Escherichia coli (11%), Pseudomonas species (9%), Klebsiella pneumoniae/oxytoca (8%), Enterococcus species (7%), Enterobacter species (6%), and Candida species (5%). The overall inpatient HA-BSI rate was 6.0 per 10,000 patient-days. The rates for important BSI subsets included: intravascular catheter-associated BSIs, 1.9 per 10,000 patient-days; S. aureus BSIs, 1.0 per 10,000 patient-days; and methicillin-resistant S. aureus BSIs, 0.3 per 10,000 patient-days. CONCLUSIONS: The rate of HA-BSIs in Queensland public hospitals is lower than reported by similar studies elsewhere. About one-third of HA-BSIs are attributable to intravascular catheters, predominantly central venous lines, but the vast majority of CLABSIs are contracted outside ICUs. Different sources of HA-BSIs require different prevention strategies.

Community-onset Escherichia coli infection resistant to expanded-spectrum cephalosporins in low-prevalence countries.

By global standards, the prevalence of community-onset expanded-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR]=11.13, 95% confidence interval [95% CI]=2.17 to 56.98, P=0.003), urinary tract infection in the past year (per-infection OR=1.430, 95% CI=1.13 to 1.82, P=0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR=3.089, 95% CI=1.29 to 7.38, P=0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR=3.665, 95% CI=1.30 to 10.35, P=0.014), and health care exposure in the previous 6 months (OR=3.16, 95% CI=1.54 to 6.46, P=0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both "export" from health care facilities into the community and direct "import" into the community from high-prevalence regions.

Incidence and risk factors for central venous access device failure in hospitalized adults: A multivariable analysis of 1892 catheters.

BACKGROUND: Central venous access devices (CVADs) allow intravenous therapy, haemodynamic monitoring and blood sampling but many fail before therapy completion. OBJECTIVE: To quantify CVAD failure and complications; and identify risk factors. DESIGNS, SETTINGS AND PARTICIPANTS: Secondary analysis of multicentre randomised controlled trial including patients aged ≥16 years with a non-tunnelled CVAD (NTCVAD), peripherally-inserted central catheter (PICC) or tunnelled CVAD (TCVAD). Primary outcome was incidence of all-cause CVAD failure (central line-associated bloodstream infection [CLABSI], occlusion, accidental dislodgement, catheter fracture, thrombosis, pain). Secondary outcomes were CLABSI, occlusion and dislodgement. Cox regression was used to report time-to-event associations. RESULTS: In 1892 CVADs, all-cause failure occurred in 10.2% of devices: 49 NTCVADs (6.1%); 100 PICCs (13.2%); 44 TCVADs (13.4%). Failure rates for CLABSI, occlusion and dislodgement were 5.3%, 1.8%, and 1.7%, respectively. Independent CLABSI predictors were blood product administration through PICCs (hazard ratio (HR) 2.62, 95% confidence interval (CI) 1.24-5.55); and in TCVADs, one or two lumens, compared with three to four (HR 3.36, 95%CI 1.68-6.71), intravenous chemotherapy (HR 2.96, 95%CI 1.31-6.68), and diabetes (HR 3.25, 95%CI 1.40-7.57). Independent factors protective for CLABSI include antimicrobial NTCVADs (HR 0.23, 95%CI 0.08-0.63) and lipids in TCVADs (HR 0.32, 95%CI 0.14-0.72). NTCVADs inserted at another hospital (HR 7.06, 95%CI 1.48-33.7) and baseline infection in patients with PICCs (HR 2.72, 95%CI 1.08-6.83) were predictors for dislodgement. No independent occlusion predictors were found. Modifiable risk factors were identified for CVAD failure, which occurred for 1-in-10 catheters. Strict infection prevention measures and improved CVAD securement could reduce CLABSI and dislodgement risk.

Molecular analysis of the Acinetobacter baumannii biofilm-associated protein.

Acinetobacter baumannii is a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability of A. baumannii to survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of the A. baumannii biofilm-associated protein (Bap) in 24 carbapenem-resistant A. baumannii ST92 strains isolated from a single institution over a 10-year period. The bap gene was highly prevalent, with 22/24 strains being positive for bap by PCR. Partial sequencing of bap was performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that BapMS1968 clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, the bapMS1968 gene was cloned, and its expression in a recombinant Escherichia coli strain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority of A. baumannii strains expressed an ∼200-kDa Bap protein. Further analysis of three Bap-positive A. baumannii strains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth by A. baumannii clinical isolates.

Case report: a missed case of chronic Q fever infective endocarditis demonstrating the ongoing diagnostic challenges.

Diagnosis of chronic Q fever is often difficult for clinicians, particularly in the presence of a second pathology. In addition to the chronic constitutional symptoms, the most common manifestations of chronic Q fever include infective endocarditis and endovascular infection. We describe a case of prosthetic valve infective endocarditis caused by both Streptococcus sanguinis and Coxiella burnetti on a background of a previous aortic graft and bioprosthetic aortic valve replacement 2 years earlier. The diagnosis of chronic Q fever infective endocarditis was delayed because the significance of the abnormal valve histology from the patient's previous surgery was initially overlooked. It was only after the patient had relapsed on appropriate therapy for the S. sanguinis prosthetic valve endocarditis that a subsequent review of the operative valve histology, along with the patient's epidemiological risk factors, led to consideration of an additional culture-negative cause for infective endocarditis. Histological examination of the valve tissue had shown exophytic fibrin vegetations and acute inflammation. Further clinical assessment revealed previous exposure to Q fever and C. burnetti DNA was detected via polymerase chain reaction on the valve tissue. Q fever infective endocarditis must be considered if valves are inflamed or have vegetations with a subsequent negative culture. It should also still be considered in the presence of an alternative bacteraemia if the patient has risk factors for exposure.

Peritoneal Dialysis-Related Infections.

Peritoneal dialysis (PD) represents an important treatment choice for patients with kidney failure. It allows them to dialyze outside the hospital setting, facilitating enhanced opportunities to participate in life-related activities, flexibility in schedules, time and cost savings from reduced travel to dialysis centers, and improved quality of life. Despite its numerous advantages, PD utilization has been static or diminishing in parts of the world. PD-related infection, such as peritonitis, exit-site infection, or tunnel infection, is a major concern for patients, caregivers, and health professionals-which may result in hesitation to consider this as treatment or to cease therapy when these complications take place. In this review, the definition, epidemiology, risk factors, prevention, and treatment of PD-related infection on the basis of the contemporary evidence will be described.

Association between parenteral nutrition-containing intravenous lipid emulsion and bloodstream infections in patients with single-lumen central venous access: A secondary analysis of a randomized trial.

BACKGROUND: Distinguishing primary bloodstream infections (BSIs) related to central venous access devices (CVADs) from those that occur through other mechanisms, such as a damaged mucosal barrier, is difficult. METHODS: Secondary analysis was conducted on data from patients with CVADs that were collected for a large, randomized trial. Patients were divided into two groups: those who received parenteral nutrition (PN)-containing intravenous lipid emulsion (ILE) and those who did not have PN-containing ILE. This study investigated the influence of PN-containing ILE (ILE PN) on primary BSIs in patients with a CVAD. RESULTS: Of the 807 patients, 180 (22%) received ILE PN. Most (627/807; 73%) were recruited from the hematology and hematopoietic stem cell transplant unit, followed by surgical (90/807; 11%), trauma and burns (61/807; 8%), medical (44/807; 5%), and oncology (23/807; 3%). When primary BSI was differentiated as a central line-associated BSI (CLABSI) or mucosal barrier injury laboratory-confirmed BSI (MBI-LCBI), the incidence of CLABSI was similar in the ILE PN and non-ILE PN groups (15/180 [8%] vs 57/627 [9%]; P = 0.88) and the incidence of MBI-LCBI was significantly different between groups (31/180 [17%] ILE PN vs 41/627 [7%] non-ILE PN; P < 0.01). CONCLUSION: Our data indicate that twice as many primary BSIs in ILE PN patients are due to MBIs than CVADs. It is important to consider the MBI-LCBI classification, as some CLABSI prevention efforts aimed at CVADs for the ILE PN population may be better directed to gastrointestinal tract protection interventions.

Using Genomics To Investigate an Outbreak of Vancomycin-Resistant Enterococcus faecium ST78 at a Large Tertiary Hospital in Queensland.

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 population structure was reconstructed using phylogenetic analysis, and a collection of publicly available VREfm ST78 genomes were used to provide global context. Core genome single nucleotide polymorphism (SNP) distances and available clinical metadata were used to characterize outbreak clusters and reconstruct transmission events. In silico genotyping confirmed that all study isolates were vanB-type VREfm carrying virulence characteristics of the hospital-associated E. faecium. Phylogenetic analysis identified two distinct phylogenetic clades, only one of which was responsible for a hospital outbreak. Four outbreak subtypes could be defined with examples of recent transmissions. Inference on transmission trees suggested complex transmission routes with unknown environmental reservoirs mediating the outbreak. WGS-based cluster analysis with publicly available genomes identified closely related Australian ST78 and ST203 isolates, highlighting the capacity for WGS to resolve complex clonal relationships between the VREfm lineages. Whole genome-based analysis has provided a high-resolution description of an outbreak of vanB-type VREfm ST78 in a Queensland hospital. Combined routine genomic surveillance and epidemiological analysis have facilitated better understanding of the local epidemiology of this endemic strain, providing valuable insight for better targeted control of VREfm. IMPORTANCE Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of health care-associated infections (HAIs) globally. In Australia, the spread of hospital-adapted VREfm is largely driven by a single clonal group (clonal complex [CC]), CC17, to which the lineage ST78 belongs. While implementing a genomic surveillance program in Queensland, we observed increased incidence of ST78 colonizations and infections among patients. Here, we demonstrate the use of real-time genomic surveillance as a tool to support and enhance infection control (IC) practices. Our results show that real-time whole-genome sequencing (WGS) can efficiently disrupt outbreaks by identifying transmission routes that in turn can be targeted using resource-limited interventions. Additionally, we demonstrate that by placing local outbreaks in a global context, high-risk clones can be identified and targeted prior to them becoming established within clinical environments. Finally, the persistence of these organism within the hospital highlights the need for routine genomic surveillance as a management tool to control VRE transmission.

ISPD Catheter-related Infection Recommendations: 2023 Update.

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.

COVID-19 infection among patients with cancer in Australia from 2020 to 2022: a national multicentre cohort study.

Background: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia. Methods: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022. Data were analysed to determine varying characteristics between cancer types and changes in outcomes over time. Multivariable analysis was performed to determine risk factors associated with oxygen requirement. Findings: 620 patients with cancer from 15 hospitals had confirmed COVID-19. There were 314/620 (50.6%) male patients, median age 63.5 years (IQR 50-72) and majority had solid organ tumours (392/620, 63.2%). The rate of COVID-19 vaccination (≥1 dose) was 73.4% (455/620). Time from symptom onset to diagnosis was median 1 day (IQR 0-3), patients with haematological malignancy had a longer duration of test positivity. Over the study period, there was a significant decline in COVID-19 severity. Risk factors associated with oxygen requirement included male sex (OR 2.34, 95% CI 1.30-4.20, p = 0.004), age (OR 1.03, 95% CI 1.01-1.06, p = 0.005); not receiving early outpatient therapy (OR 2.78, 95% CI 1.41-5.50, p = 0.003). Diagnosis during the omicron wave was associated with lower odds of oxygen requirement (OR 0.24, 95% CI 0.13-0.43, p < 0.0001). Interpretation: Outcomes from COVID-19 in patients with cancer in Australia over the pandemic have improved, potentially related to changing viral strain and outpatient therapies. Funding: This study was supported by research funding from MSD.

Stability and compatibility of antibiotics in peritoneal dialysis solutions.

Intraperitoneal (IP) administration of antibiotics is a preferred treatment of peritoneal dialysis (PD)-related peritonitis. Given the treatment duration of up to 2-3 weeks, it is important that robust data on antibiotic stability and compatibility are available to achieve notable treatment success. This article provides a comprehensive review of recent stability and compatibility studies pertaining to a wide range of antibiotics admixed in various PD solutions.