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.

Clinical evaluation of the APAS® Independence: Automated imaging and interpretation of urine cultures using artificial intelligence with composite reference standard discrepant resolution.

BACKGROUND: This study reports the outcome of the first evaluation of the APAS® Independence for automated reading and preliminary interpretation of urine cultures in the routine clinical microbiology laboratory. In a 2-stage evaluation involving 3000 urine samples, two objectives were assessed; 1) the sensitivity and specificity of the APAS® Independence compared to microbiologists using colony enumeration as the primary determinant, and 2) the variability between microbiologists in enumerating bacterial cultures using traditional culture reading techniques, performed independently to APAS® Independence interpretation. METHODS: Routine urine samples received into the laboratory were processed and culture plates were interpreted by standard methodology and with the APAS® Independence. Results were compared using typical discrepant result resolution and with a composite reference standard, which provided an alternative assessment of performance. RESULTS: The significant growth sensitivity of the APAS® Independence was determined to be 0.919 with a 95% confidence interval of (0.879, 0.948), and the growth specificity was 0.877 with a 95% confidence interval of (0.827, 0.916). Variability between microbiologists was demonstrated with microbiologist bi-plate enumerations in agreement with the consensus 88.6% of the time. CONCLUSION: The APAS® Independence appears to offer microbiology laboratories a mechanism to standardise the processing and assessment of urine cultures whilst augmenting the skills of specialist microbiology staff.

Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak.

BACKGROUND: Until recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks. METHODS: All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. RESULTS: Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012 and 2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation. CONCLUSION: A real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase-producing Enterobacteriaceae surveillance and management.

Self-induced Elizabethkingia meningoseptica endophthalmitis: a case report.

INTRODUCTION: Endophthalmitis is a sight-threatening condition defined as any inflammation of the internal ocular spaces. It is classified as either endogenous or exogenous depending on the route of infection. Exogenous endophthalmitis results from direct inoculation as a complication of intra-ocular surgery, penetrating ocular trauma, intra-ocular foreign bodies, corneal ulceration and following a breach of ocular barriers from a periocular infection. We report a rare case of exogenous endophthalmitis with both unusual etiology and microbiology. CASE PRESENTATION: A 41-year-old Caucasian man with a history of depressive illness presented to our eye department with painful acute visual loss on a background history of chronic uveitis. Ocular examination revealed a dense fibrinous panuveitis with a suspicion of a focal lesion in the posterior segment. Microbiological sampling from his anterior chamber and posterior segment revealed a culture of Elizabethkingia meningoseptica. On closer questioning, he volunteered the occurrence of multiple episodes of deliberate needle ocular penetration. Following vitrectomy for associated retinal detachment, a final Snellen visual acuity of 6/60 was obtained. CONCLUSIONS: Elizabethkingia meningoseptica endophthalmitis is a rare condition, and visual results to date are poor.

Bacteremia due to three Bacillus species in a case of Munchausen's syndrome.

We report on a case of recurrent bacteremia due to three Bacillus spp. in an immunocompetent patient with no history of intravenous drug use. The source of the organisms was postulated to be a self-injected compound containing Bacillus spores, given the patient's past history of psychiatric illness and self-destructive behavior.