Impact of COVID-19 on people with non-functioning spleens in Australia.

BACKGROUND: COVID-19 has had enormous impact on health and social systems, with stringent public health measures enacted across Australia. The virus itself disproportionately affects immunocompromised individuals including people without functioning spleens. We thus sought to characterise the psychological and physical impact of COVID-19 and such measures upon this oft-neglected patient group. METHODS: Adults ≥ 18 years old identified from the Spleen Australia (SA) database were invited to participate in an online survey in November to December 2021 to assess the impact of the COVID-19 pandemic. Stata (v17, StataCorps, Texas, USA) was used to conduct descriptive and frequency analyses. RESULTS: 2864 respondents were surveyed. The majority were female (1473/2838, 51.9%), Australian-born (2257/2835, 79.6%), and living in Victoria (1755/2822, 62.2%). The largest age group was 61-70 years-old (841/2858, 29.4%). Trauma was the commonest reason for asplenia (826/2724, 30.3%). Respondents reported the pandemic reduced their ability to visit a GP (753/2864, 26.3%), access food (153/2864, 5.3%), medications (179/2864, 6.3%) or spleen-specific vaccines (120/2864, 4.2%), maintain relationships (503/2864, 17.6%), or care for children (127/2864, 4.4%). 84.8% of participants reported at least one impact of COVID, including negative physical health (1463/2864, 51.1%), mental health (733/2864, 25.6%) and financial repercussions (509/2864, 17.8%). 96.9% (2743/2831) had received at least one dose of COVID-19 vaccines. CONCLUSIONS: Overall, we found detailed evidence of the negative psychological and physical impacts of the pandemic upon this cohort. We recommend that providers consider people without functioning spleens as requiring extra social and psychological support in circumstances such as the COVID-19 pandemic.

Genomic investigation of multispecies and multivariant blaNDM outbreak reveals key role of horizontal plasmid transmission.

OBJECTIVES: New Delhi metallo-ß-lactamases (NDMs) are major contributors to the spread of carbapenem resistance globally. In Australia, NDMs were previously associated with international travel, but from 2019 we noted increasing incidence of NDM-positive clinical isolates. We investigated the clinical and genomic epidemiology of NDM carriage at a tertiary-care Australian hospital from 2016 to 2021. METHODS: We identified 49 patients with 84 NDM-carrying isolates in an institutional database, and we collected clinical data from electronic medical record. Short- and long-read whole genome sequencing was performed on all isolates. Completed genome assemblies were used to assess the genetic setting of blaNDM genes and to compare NDM plasmids. RESULTS: Of 49 patients, 38 (78%) were identified in 2019-2021 and only 11 (29%) of 38 reported prior travel, compared with 9 (82%) of 11 in 2016-2018 (P = .037). In patients with NDM infection, the crude 7-day mortality rate was 0% and the 30-day mortality rate was 14% (2 of 14 patients). NDMs were noted in 41 bacterial strains (ie, species and sequence type combinations). Across 13 plasmid groups, 4 NDM variants were detected: blaNDM-1, blaNDM-4, blaNDM-5, and blaNDM-7. We noted a change from a diverse NDM plasmid repertoire in 2016-2018 to the emergence of conserved blaNDM-1 IncN and blaNDM-7 IncX3 epidemic plasmids, with interstrain spread in 2019-2021. These plasmids were noted in 19 (50%) of 38 patients and 35 (51%) of 68 genomes in 2019-2021. CONCLUSIONS: Increased NDM case numbers were due to local circulation of 2 epidemic plasmids with extensive interstrain transfer. Our findings underscore the challenges of outbreak detection when horizontal transmission of plasmids is the primary mode of spread.

Genomic dissection of endemic carbapenem resistance reveals metallo-beta-lactamase dissemination through clonal, plasmid and integron transfer.

Infections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades of blaIMP-4 evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified the blaIMP-4 gene across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. We showed how an initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability of blaIMP-4 to disseminate in successful strain-genetic setting pairs we termed propagators, in particular Serratia marcescens and Enterobacter hormaechei. From this reservoir, blaIMP-4 persisted through diversification of genetic settings that resulted from transfer of blaIMP-4 plasmids between bacterial hosts and of the integron carrying blaIMP-4 between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.

Antimicrobial susceptibility of ceftolozane-tazobactam against multidrug-resistant Pseudomonas aeruginosa isolates from Melbourne, Australia.

We collected 163 clinical Pseudomonas aeruginosa isolates at a tertiary hospital specialising in adult cystic fibrosis (CF) and lung transplantation (LTx) in Melbourne, Australia, to explore the activity of ceftolozane-tazobactam (C/T) in populations at high-risk for antimicrobial resistance. Of these, 144 (88.3%) were collected from sputum, and 19 (11.7%) from bronchoalveolar lavage. Most (85.3%) were derived from patients with cystic fibrosis and included a subset of patients that had undergone LTx. These isolates were tested against 11 antibiotics, including C/T, using Sensititre plates for broth microdilution (BMD) testing. Sixty (36.8%) isolates were classified as multidrug resistant (MDR) and 32 (19.6%) were extensively drug resistant (XDR). Overall, 133/163 (81.6%) isolates were susceptible to C/T. For MDR and XDR isolates, 88.3% and 28.1% were C/T susceptible, respectively. Among the non-MDR/XDR isolates, 100% remained susceptible to C/T. Comparisons of C/T susceptibility were made using BioMérieux Etests and Liofilchem MIC test strips (MTS). Categorical agreement to BMD was >93% for both test strips, but essential agreement to BMD was slightly higher with Etest (89.0%) compared to Liofilchem (74.8%). In conclusion, C/T retained activity against most MDR and over a quarter of XDR P. aeruginosa isolates from complex patients with CF and post-LTx.

Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen.

Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.

Congenital asplenia study: clinical and laboratory characterisation of adults with congenital asplenia.

Congenital asplenia is a rare disorder commonly associated with other visceral and cardiac congenital anomalies. Isolated congenital asplenia is even less common than syndromic forms. The risk of severe bacterial infections associated with asplenia is the most concerning clinical implication and carries a significant mortality risk. Prophylactic measures against the clinical syndrome known as overwhelming postsplenectomy infections (OPSI) include vaccination, prophylactic and emergency antibiotics and health education including fever management and travel advice. This case series describes fourteen adults with congenital asplenia and polysplenia syndrome, most of whom were diagnosed incidentally as adults, and outlines the nature of their diagnosis, clinical phenotype, family history and key pathology findings.

Genomic characterisation of CC398 MRSA causing severe disease in Australia.

Clonal complex 398 (CC398) livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been reported worldwide in a variety of food-animal species. Although CC398 is synonymous with LA-MRSA, community-associated MRSA (CA-MRSA) variants have emerged, including the Panton-Valentine leukocidin (PVL)-positive ST398-V and ST398 single-locus variant ST1232-V, and the PVL-negative ST398-V clones. Using comparative genomic analysis, we determined whether ten CC398 MRSA bacteraemia episodes recently identified in Australia were due to LA-MRSA or CA-MRSA CC398. Isolates were sourced from the Australian Group on Antimicrobial Resistance S. aureus surveillance programme and episodes occurred across Australia. Whole-genome sequencing (WGS) and phylogenetic comparison of the ten CC398 bacteraemia isolates with previously published CC398 MRSA whole-genome sequences identified that the Australian CC398 isolates were closely related to the human-associated II-GOI clade and the livestock-associated IIa clade. The identified CC398 MRSA clones were: PVL-positive ST1232-V (5C2&5), PVL-negative community-associated ST398-V (5C2&5) and livestock-associated ST398-V (5C2&5). Our findings demonstrate the importance of using WGS and comparing the sequences with international sequences to distinguish between CC398 CA-MRSA and LA-MRSA and to determine the isolates' origin. Furthermore, our findings suggest that CC398 CA-MRSA has become established in the Australian community and that ST398-V (5C2&5) LA-MRSA is now widespread in Australian piggeries. Our study emphasises the need for national One Health antimicrobial resistance surveillance programmes to assist in monitoring the ongoing epidemiology of MRSA and other clinically significant antimicrobial-resistant organisms.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients.

BACKGROUND: Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts. METHODS: We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs (n = 287 and n = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing (n = 127 3GCR-GN, n = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references. RESULTS: Among 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species (n = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission (n = 2/33, 6% vs n = 4/254, 2%, respectively, p = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission (n = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN, with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p = 0.02). CONCLUSIONS: 3GCR-E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.

Group A streptococcal bacteraemia at a tertiary hospital in Melbourne: concern of an under-reported risk group in Australia.

BACKGROUND: Invasive group A streptococcal (iGAS) infections are increasing worldwide with at-risk groups being children, pregnant women and the elderly. In 2017, there was a rise in iGAS cases in Victoria, prompting a Chief Health Officer advisory. AIMS: To describe the characteristics of patients with GAS bacteraemia admitted to a tertiary hospital. To compare at-risk groups in our population with those identified in the Victorian Government health alert. METHODS: Retrospective review of patients with GAS bacteraemia admitted between June 2014 and December 2017 at a tertiary hospital in Melbourne, Victoria. RESULTS: Forty-three cases of GAS bacteraemia occurred. Average age was 52 years (range 15-88 years) with 63% male. Average length of stay was 14 days (range 0-72 days) and all-cause mortality occurred in two (5%) cases. Twelve (28%) patients presented with shock, 11 (26%) required intensive care unit admission and 13 (30%) surgical intervention. A history of intravenous drug use was documented in 18 (42%) cases and was commonly complicated by bone or joint involvement or thrombosis. Typing of GAS samples identified 22 different emm-types. CONCLUSION: GAS bacteraemia resulted in significant morbidity and prolonged hospitalisation. In contrast to the at-risk groups identified in the Victorian Government health advisory, the commonest risk group in this series were people who inject drugs and most commonly middle-aged men. Invasive GAS should be considered if a person who injects drugs presents with acute severe sepsis.

Search and Contain: Impact of an Integrated Genomic and Epidemiological Surveillance and Response Program for Control of Carbapenemase-producing Enterobacterales.

BACKGROUND: Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). METHODS: A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program's first 3 years (2016-2018). RESULTS: CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45-0.60 infections/100 000 population, P = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9-14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1-19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4-13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. CONCLUSIONS: We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally.

Nocardia bacteremia: A single-center retrospective review and a systematic review of the literature.

OBJECTIVES: Nocardia bacteremia is a rare but severe disease associated with high mortality. This systematic review is the largest and most comprehensive review performed over the past 20 years. METHODS: A single-center retrospective review of Nocardia bacteremia was performed using hospital microbiology records from January 1, 2010 to December 31, 2017. A systematic literature review was also performed to identify cases of Nocardia bacteremia described in the NCBI PubMed database in English between January 1, 1999 and December 31, 2018. RESULTS: Four new cases of Nocardia bacteremia are described. The systematic review identified 134 cases with sufficient information available for analysis. Of the total 138 cases, the median age was 58 years (interquartile range (IQR) 44-69 years) and 70% were male. Eighty-one percent were immunocompromised (corticosteroid use (49%), hematological malignancy (20%), solid organ transplant (20%), solid organ malignancy (19%), and hematopoietic stem cell transplantation (15%)) and 29% had endovascular devices. Pulmonary infection was the most common concurrent site of clinical disease (67%). The median incubation time to the detection of Nocardia bacteremia was 4 days (IQR 3-6 days). Blood cultures were the only positive microbiological specimen in 38% of cases. The median total duration of treatment was 75 days (IQR 25-182 days). Thirty-day all-cause mortality was 28% and overall all-cause mortality was 40%. CONCLUSIONS: Nocardia bacteremia is most frequently identified in immunocompromised patients and those with intravascular devices. Although rare, it represents a serious infection with high associated overall mortality.

Splenic autotransplantation: a systematic review.

BACKGROUND: Splenectomy is a surgical procedure indicated in a variety of medical conditions including trauma. Post-operatively, there is a lifelong risk of developing overwhelming sepsis from encapsulated bacteria, most commonly due to Streptococcus pneumoniae. Splenic autotransplantation has been proposed as a method to recover splenic function in patients requiring splenectomy with otherwise normal spleens. This study aims to systematically review the literature to determine the efficacy of spleen autotransplantation. METHODS: MEDLINE, PubMed and the Cochrane Library were searched for all studies assessing splenic autotransplantation (January 1947 to July 2018). Data were extracted on study characteristics, outcomes assessed, including spleen scintigraphy results, blood film counts and serum immunoglobulin (Ig) levels. RESULTS: Data were obtained from 18 primary studies. All studies demonstrated return of regenerated spleen tissue in the majority of their patients (95.3%) on spleen scintigraphy. In 12 studies, 90.2% of patients had blood films return to normal following transplantation. Ig levels were shown to return to normal in all 12 studies where it was assessed. In 11 studies, 3.7% of patients had post-operative complications. In five studies, 1.3% of patients had post-operative infections in the follow-up period. CONCLUSION: Splenic autotransplantation is a safe procedure with minimal complications that can return splenic filtration function and Ig levels to normal ranges. It has not been confirmed whether autotransplantation provides meaningful protection against overwhelming post-splenectomy infections.

Post-splenectomy sepsis: preventative strategies, challenges, and solutions.

Removal of the spleen had already been established as a routine technique to treat splenic trauma and other diseases affecting the spleen before the anatomy, physiology, and function of the spleen were known in the mid-twentieth century. It is now widely accepted that the splenectomized individual is at increased risk for infection, in particular, overwhelming post-splenectomy infection (OPSI). OPSI is a syndrome of fulminant sepsis occurring in splenectomized (asplenic) or hyposplenic individuals that is associated with high mortality and morbidity. Poorly opsonized bacteria such as encapsulated bacteria, in particular, Streptococcus pneumoniae, are often implicated in sepsis. The spleen is a reticuloendothelial organ that facilitates opsonization and phagocytosis of pathogens, in addition to cellular maintenance. Splenectomy is associated with an impairment in immunoglobulin production, antibody-mediated clearance, and phagocytosis, leading to an increased risk of infection and sepsis. Early identification of the at-risk patient, early blood cultures prior to antibiotic administration, urgent blood smears and fast pathogen-detection tests, and sepsis bundles should be utilized in these patients. Prompt management and aggressive treatment can alter the course of disease in the at-risk splenectomized patient. Overwhelming post-splenectomy infection can be prevented through vaccination, chemoprophylaxis, and patient education. This article evaluates post-splenectomy sepsis by summarizing the anatomy and function of the spleen, physiological changes after splenectomy that predispose the splenectomized patient to infection, and current management and prevention strategies.

Improvement in turnaround time for rapid respiratory virus testing using Xpert® Flu/RSV: a retrospective cohort study during a high incidence influenza season.

Seasonal influenza like illness results in increased hospital presentations and unnecessary antibiotic use. Recent availability of rapid respiratory virus PCR testing allows rapid, accurate influenza diagnosis. A retrospective audit of turnaround time from sample collection to result availability after introduction of Xpert® Flu/RSV in a tertiary healthcare institution during a high incidence influenza season is described.

Mortality impact of empirical antimicrobial therapy in ESBL- and AmpC-producing Enterobacteriaceae bacteremia in an Australian tertiary hospital.

BACKGROUND: Treatment of ESBL- and AmpC-producing Enterobacteriaceae bacteremia is often complicated by lack of appropriate antibiotics. We aimed to determine the predictors of mortality and impact of empirical antibiotics. METHODS: A retrospective observational study was performed on consecutive adult cases of ESBL and AmpC bacteremia at the Alfred Hospital from 2014 through April 2018. RESULTS: Among 110 patients with ESBL (88.2%) and AmpC (14.5%) bacteremia episodes, 96.4% had comorbidities such as hematological malignancy (30%). Approximately 45% were on immunosuppressive drugs, while 69% had recent antibiotic exposure. Over 84% of bacteremias were hospital acquired or healthcare associated. Urinary tract was the main source of infection (40%) with E. coli being the commonest organism (66.4%). The isolates were least resistant to gentamicin (21.8%), which was often appropriately used in empirical therapy. About 34% of patients presented with severe sepsis or shock. The 30-day mortality rate was 20% with no correlation with inappropriate empirical antibiotics (52%). There was no significant mortality difference between carbapenem use in empirical and definitive therapy. Respiratory source [OR 11.77, 95% CI 1.30-106.85; p = 0.03], severe sepsis or shock [OR 5.17, 95% CI 1.37-19.55; p = 0.02] and inappropriate definitive therapy [OR 27.93, 95%CI 3.69-211.35; p = 0.001] were independent predictors for mortality. CONCLUSION: The choice and appropriateness of empirical therapy were not associated with mortality in ESBL and AmpC bacteremia. Prudent use of carbapenem is reasonable with gentamicin as alternative. Emphasis should be on prompt resuscitation in severe sepsis and early detection of ESBL and AmpC to facilitate appropriate switch to definitive therapy.

Evolution of Daptomycin Resistance in Coagulase-Negative Staphylococci Involves Mutations of the Essential Two-Component Regulator WalKR.

Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS. Here, we describe the prevalence of antimicrobial resistance in clinical CoNS strains from a tertiary care hospital over a 4-year period, and we observed a significant increase in resistance to daptomycin. Notably, Staphylococcus capitis accounted for the majority of these daptomycin-resistant (DAP-R) CoNS. To further investigate the mechanisms of daptomycin resistance in CoNS, daptomycin-susceptible clinical strains of S. capitis and Staphylococcus epidermidis underwent in vitro daptomycin exposure to generate DAP-R CoNS mutants. Unlike that seen with Staphylococcus aureus, alteration of cell surface charge was not observed in the DAP-R CoNS strains, but biofilm formation was compromised. Whole-genome sequencing analysis of the DAP-R CoNS strains identified single nucleotide polymorphisms (SNPs) in walKR, the essential two-component regulatory system controlling cell wall biogenesis. PCR and sequencing of walK and walR from 17 DAP-R CoNS clinical isolates identified seven nonsynonymous mutations. The results were confirmed by the recreation of the walK SNP in S. epidermidis, which resulted in reduced susceptibility to daptomycin and vancomycin. This study highlights the significance of CoNS in evolving daptomycin resistance and showed that walKR is shared among the staphylococcal species and is involved in antibiotic resistance development. Notably, we did not observe mutations in genes responsible for phospholipid biosynthesis or an altered cell surface charge, suggesting that reduced daptomycin susceptibility in CoNS may emerge in a fashion distinct from that in S. aureus.

Nocardiosis: 7-year experience at an Australian tertiary hospital.

BACKGROUND: Nocardiosis has historically been reported in immunocompromised patients, but Australian epidemiological and antimicrobial susceptibility data are limited. AIM: To describe the epidemiology, diagnosis and initial treatment of nocardiosis in an Australian tertiary hospital over 7 years. METHODS: In this retrospective study, all positive cultures for Nocardia species from any site isolated at the Alfred Hospital, Melbourne, between 1 January 2010 and 31 December 2016 were identified, and corresponding laboratory data and medical records reviewed. RESULTS: Sixty-eight non-duplicate isolates were identified from 67 patients. Common predisposing factors were chronic lung disease (38/67; 57%), organ, particularly lung, transplantation (13/67; 19%) and solid organ malignancy (6/67; 9%); 12% (8/67) of patients had no identifiable systemic risk factors. Seventy-nine percent (53/67) of patients had pulmonary nocardiosis only. Nocardia nova was the most commonly isolated species (20/68; 29%). In 48% (32/67) of patients, Nocardia species were isolated only on specific mycobacterial media. All tested species were susceptible to sulfamethoxazole-trimethoprim and amikacin, with the majority (58/63; 92%) susceptible to imipenem. All-cause mortality rates at 6 and 12 months where data were available were 15% (10/66 patients) and 22% (14/64 patients) respectively. CONCLUSION: In the largest Australian series in 25 years, nocardiosis predominantly affected patients with chronic lung disease or impaired cell-mediated immunity. A significant proportion of organisms from pulmonary sites were isolated on mycobacterial culture media only, suggesting that its use may improve yield. Isolates remain highly susceptible to sulfamethoxazole-trimethoprim, amikacin and imipenem, while other agents should be used only after confirmation of in vitro susceptibility.

Mathematical modelling of vancomycin-resistant enterococci transmission during passive surveillance and active surveillance with contact isolation highlights the need to identify and address the source of acquisition.

BACKGROUND: Clinical studies and mathematical simulation suggest that active surveillance with contact isolation is associated with reduced vancomycin-resistant enterococci (VRE) prevalence compared to passive surveillance. Models using pre- and post-intervention data that account for the imperfect observation and serial dependence of VRE transmission events can better estimate the effectiveness of active surveillance and subsequent contact isolation; however, such analyses have not been performed. METHODS: A mathematical model was fitted to surveillance data collected pre- and post-implementation of active surveillance with contact isolation in the haematology-oncology ward. We developed a Hidden Markov Model to describe undetected and observed VRE colonisation/infection status based on the detection activities in the ward. Bayesian inference was used to estimate transmission rates. The effectiveness of active surveillance was assumed to be via increased detection and subsequent contact isolation of VRE positive patients. RESULTS: We estimated that 31% (95% credible interval: 0.33-85%) of the VRE transmissions were due to cross-transmission between patients. The ratio of transmission rates from patients with contact isolation versus those without contact isolation was 0.33 (95% credible interval: 0.050-1.22). CONCLUSIONS: The majority of the VRE acquisitions in the haematology-oncology ward was estimated to be due to background rates of VRE, rather than within ward patient to patient acquisition. The credible interval for cross-transmission was wide which results in a large degree of uncertainty in the estimates. Factors that could account for background VRE acquisition include endogenous acquisition from antibiotic selection pressure and VRE in the environment. Contact isolation was not significantly associated with reduced VRE transmission in settings where the majority of VRE acquisition was due to background acquisition, emphasising the need to identify and address the source of acquisition. As the credible interval for the ratio of VRE transmission in contact isolated versus non-contact isolated patients crossed 1, there is a probability that the transmission rate in contact isolation was not lower. Our finding highlights the need to optimise infection control measures other than active surveillance for VRE and subsequent contact isolation to reduce VRE transmission. Such measures could include antimicrobial stewardship, environmental cleaning, and hand hygiene.