Diagnosis of septic arthritis in the acute care setting: the value of routine intra-operative sample culture.

Objective: Diagnosing septic arthritis can be challenging and frequently involves clinical assessment, laboratory investigations and synovial fluid analysis. We sought to determine the utility of synovial aspiration and intra-operative synovial fluid and tissue culture for the accurate diagnosis of septic arthritis. Methods: We carried out a retrospective review of the records of patients referred to a tertiary orthopaedic unit with possible septic arthritis between 2015 and 2019 inclusive, including clinical and laboratory data for this cohort study. Performance characteristics were determined for synovial aspiration, intra-operative synovial fluid and tissue culture in diagnosing expert review-determined true septic arthritis. Concordance between discharge diagnosis, antibiotic prescribing and true septic arthritis was determined. Results: Of 268 patients identified with suspected septic arthritis, 143 underwent both synovial fluid aspiration and intra-operative synovial fluid and tissue biopsy culture. True septic arthritis was not differentiated significantly by laboratory parameters including serum white cell count (WCC), CRP or synovial WCC. Considering only patients with negative pre-operative synovial aspirate cultures, intra-operative samples led to diagnosis of true septic arthritis in 6 of 63 patients [number needed to treat (NNT) 10.5]. For all patients sampled in theatre, positive synovial tissue biopsy was the only evidence of true septic arthritis in six (NNT 23.9). Despite insufficient microbiological evidence, 27 of the 59 patients who did not have septic arthritis received a discharge diagnosis of septic arthritis, 26 of whom were discharged with antibiotics. Conclusion: Intra-operative sample collection, particularly tissue biopsy, increases the likelihood of a true septic arthritis diagnosis. Such measures might help to reduce diagnostic ambiguity in clinical practice and might therefore reduce overtreatment.

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis.

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control. Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec), or ESBL Klebsiella pneumoniae (ESBL-Kp). Genomic and epidemiologic data were integrated to assess MDRO transmission. Findings: In total, 2275 isolates were included from 1970 patients, predominantly ESBL-Ec (40·8%) followed by MRSA (35·6%), vanA VRE (15·2%), and ESBL-Kp (8·3%).Overall, hospital and genomic epidemiology showed 607 patients (30·8%) acquired their MDRO in hospital, including the majority of vanA VRE (266 patients, 86·4%), with lower proportions of ESBL-Ec (186 patients, 23·0%), ESBL-Kp (42 patients, 26·3%), and MRSA (113 patients, 16·3%). Complex patient movements meant the majority of MDRO transmissions would remain undetected without genomic data.The genomics implementation had major impacts, identifying unexpected MDRO transmissions prompting new infection control interventions, and contributing to vanA VRE becoming a notifiable condition. We identified barriers to implementation and recommend strategies for mitigation. Interpretation: Implementation of a multi-centre genomics-informed infection control workflow is feasible and identifies many unrecognised MDRO transmissions. This provides critical opportunities for interventions to improve patient safety in hospitals. Funding: Melbourne Genomics Health Alliance (supported by State Government of Victoria, Australia), and National Health and Medical Research Council (Australia).

Evaluation of the VITEK 2 Advanced Expert System performance for predicting resistance mechanisms in Enterobacterales acquired from a hospital-based screening program.

There is limited literature examining the accuracy of the VITEK 2 Advanced Expert System (AES) in characterisation of ß-lactamase resistance patterns. We present a prospective single centre study to better ascertain the performance characteristics of this program. The VITEK 2 AES interpretation was compared to established laboratory phenotypic methods. The overall sensitivity for detection of broad-spectrum ß-lactamase by the AES was 95%, with a specificity of 78%. One or more discrepancies were noted in 36% of samples, with the majority of these (87/100) due to incorrect 'overcall' of a resistance mechanism. AES characterisation of AmpC resistance mechanisms was excellent. In contrast, the AES had poor specificity in classifying extended spectrum ß-lactamases (ESBLs). As a screening aid, the AES can be a valuable tool. However, optimal use requires an adequate working knowledge of resistance mechanisms in order to correctly interpret and accept the result output.

Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia.

OBJECTIVES: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission. DESIGN: Pilot prospective multicenter surveillance study. SETTING: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals. METHODS: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data. RESULTS: In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients). CONCLUSIONS: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.

Case Report: Confirmation by Metagenomic Sequencing of Visceral Leishmaniasis in an Immunosuppressed Returned Traveler.

There has been increased interest in using metagenomic next-generation sequencing as an unbiased approach for diagnosing infectious diseases. We describe a 61-year-old man on fingolimod therapy for multiple sclerosis with an extensive travel history who presented with 7 months of fevers, night sweats, and weight loss. Peripheral blood tests showed pancytopenia and abnormal acute phase reactants. A bone marrow aspirate showed the presence of numerous intracellular and extracellular amastigotes consistent with visceral leishmaniasis (VL). Metagenomic sequencing of the bone marrow aspirate confirmed Leishmania infantum, a species widely reported in the Mediterranean region. This correlated with acquisition of VL infection during the patient's most recent epidemiological exposure in southern Italy 12 months prior. This case demonstrates the potential application of metagenomic sequencing for identification and speciation of Leishmania in cases of VL; however, further assessment is required using other more readily obtained clinical samples such as blood.

Severe Disease Caused by Community-Associated MRSA ST398 Type V, Australia, 2017.

Using whole-genome sequencing, we identified a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) sequence type (ST) 398 type V (5C2&5) isolate (typically found in China) in Australia in 2017. This CA-MRSA ST398 variant was highly virulent, similar to other related CA-MRSAs of ST398. This strain should be monitored to prevent more widespread dissemination.

A multicentre survey of hepatitis C awareness in a high-risk population.

AIMS: To assess the awareness of hepatitis C virus (HCV) infection status in a high-risk population. METHODS: A targeted population survey of clients of methadone maintenance clinics in metropolitan and rural New South Wales, using an interviewer-administered face-to-face questionnaire. Main outcome measures include awareness of HCV status, time elapsed since last tested and children's HCV status. RESULTS: A total of 329 clients completed the survey, of which 97% perceived to have been tested for HCV in the past. One hundred and seventy (52%) participants considered themselves to be negative for HCV. Of these the median time since last tested was 2 years (2 weeks-25 years). Although 94% of all parents believed that their child's HCV status was negative, only 49% of respondents stated that their children had been tested for HCV. Voluntary testing was offered to all clients and their children with only one accepting. CONCLUSIONS: Awareness of HCV infection status in this high-risk population is suboptimal. This indicates that existing educational strategies are inadequate and that there is a disconnect between their health needs and the medical care they receive. Novel approaches need to be considered to improve the knowledge of HCV transmission and hopefully improve HCV-associated health outcomes in high-risk populations.

Limited diversity in the gene pool allows prediction of third-generation cephalosporin and aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae.

Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ≥ 2 µg/mL were collected from seven major hospitals in Sydney (Australia) in 2008-2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC ≥ 2 µg/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC ≥ 8 µg/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5-10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations.

Screening for hepatitis C virus infection in methadone-maintained mothers and their infants.

OBJECTIVE: To describe the patterns of screening for hepatitis C virus (HCV) infection in methadone-maintained pregnant women and their infants. DESIGN, SETTING AND PATIENTS: Retrospective review of medical records from one rural and two metropolitan hospitals in New South Wales for pregnant women on methadone maintenance treatment and infants born to these women between 1 January 2000 and 31 December 2006, as well as records for pregnant women who were not on methadone treatment. MAIN OUTCOME MEASURES: Rates of anti-HCV antibody and HCV RNA testing for pregnant women and their infants, and ages at which infants attended follow-up appointments. RESULTS: Of 295 pregnant women on methadone maintenance treatment, 288 were tested for anti-HCV antibodies (98%), compared with 1995 of 9987 women who were not on methadone treatment (20%) (P<0.001). Seropositive results were obtained for 243 women in the methadone group (84%) and 54 in the non-methadone group (3%) (P<0.001), of whom 44 (18%) and 17 (31%), respectively, were subsequently tested for HCV RNA (P=0.03). HCV RNA test results were positive for 31 (70%) and 10 (59%) seropositive women in the methadone and non-methadone groups, respectively (P=0.39). Of infants of HCV-seropositive methadone-maintained mothers, 27% of those for whom we had follow-up attendance data received HCV screening, and one of these infants tested positive for anti-HCV antibodies and HCV RNA. CONCLUSIONS: Screening for HCV infection in the high-risk population of pregnant women on methadone maintenance treatment and their infants is inadequate. This could lead to significant underdetection of active HCV infection in this high-risk population, and their infants. Current screening guidelines may therefore need to be revised.