1201. Diphtheria in Veterans Health Administration (VHA), 2000-2021

Background Diphtheria is caused by Corynebacterium diphtheriae and can cause respiratory or skin infections. Transmission occurs primarily person-to-person via respiratory tract and rarely from skin lesions or fomites. In the Veterans Health Administration (VHA), we perform surveillance for nationally notifiable diseases such as diphtheria. In early 2021, there were 4 alerts for C. diphtheriae. Therefore, we investigated diphtheria prevalence in VHA over the last 20 years. Methods Isolates of C. diphtheriae were identified from VHA data sources from 1/1/2000-2/28/2021. Patient demographics, co-morbidities, microbiologic data, treatment, outcomes, and vaccination status were obtained via electronic medical record (EMR) review. Results 33 C. diphtheriae isolates were identified representing 32 unique individuals. 17 isolates were identified from 2000-2015 and 16 were identified from 2016-2021. Isolates were from cutaneous (16), blood (10), urine (4), pulmonary (2), and throat (1) specimens. In 11 individuals, clinical significance was unclear (no antibiotics given, note mentioned that it was being considered a contaminant - i.e., isolate may have been incorrectly labeled as “C. diphtheriae” instead of “diphtheroid”). Only 3 isolates had toxin testing documented. One C. diphtheriae biovar gravis blood isolate was associated with sepsis without another source identified. The throat isolate was a nontoxigenic strain. No cutaneous isolates underwent susceptibility testing, but all 15 individuals received antibiotics (1 patient had 2 isolates). 11 had additional organisms identified in addition to C. diphtheriae. Table 1 describes demographics, co-morbidities, and vaccination status of cutaneous cases. Only 1 case (in 2021) had EMR documentation of local public health department reporting. Table 1. Characteristics of Unique Individuals with Cutaneous Diphtheria Isolates in VHA, 2000-2021 Conclusion Nearly as many isolates have been identified in the last 5.5 years compared to the previous 15 years which may be related to more robust molecular identification methods available in VHA. Most C. diphtheriae isolated was from cutaneous sources that were acute in onset. About 33% were identified as C. diphtheriae but were not treated. EMR documentation of toxin production and public health department reporting was lacking. Disclosures All Authors: No reported disclosures

Antibiotic Susceptibility, Virulome and Clinical Outcomes in European Infants with Bloodstream Infections Caused by Enterobacterales

Mortality in neonates with Gram-negative bloodstream infections has remained unacceptably high. Very few data are available on the impact of resistance profiles, virulence factors, appropriateness of empirical treatment and clinical characteristics on patients’ mortality. A survival analysis to investigate 28-day mortality probability and predictors was performed including (I) infants <90 days (II) with an available Enterobacterales blood isolate with (III) clinical, treatment and 28-day outcome data. Eighty-seven patients were included. Overall, 299 virulence genes were identified among all the pathogens. Escherichia coli had significantly more virulence genes identified compared with other species. A strong positive correlation between the number of resistance and virulence genes carried by each isolate was found. The cumulative probability of death obtained by the Kaplan-Meier survival analysis was 19.5%. In the descriptive analysis, early age at onset, gestational age at onset, culture positive for E. coli and number of classes of virulence genes carried by each isolate were significantly associated with mortality. By Cox multivariate regression, none of the investigated variables was significant. This pilot study has demonstrated the feasibility of investigating the association between neonatal sepsis mortality and the causative Enterobacterales isolates virulome. This relationship needs further exploration in larger studies, ideally including host immunopathological response, in order to develop a tailor-made therapeutic strategy.

Deceiving Phenotypic Susceptibility Results on a Klebsiella pneumoniae Blood Isolate Carrying Plasmid-Mediated AmpC Gene blaDHA-1

Carbapenem-resistant Klebsiella pneumoniae (CRKP) frequently causes hospital-acquired infections and is associated with high morbidity and mortality. CRKP can have multiple resistance mechanisms and only a few can be routinely detected by commercial molecular or phenotypic assays making surveillance for CRKP particularly challenging. In this report, we identified and characterized an unusual non–carbapenemase-producing CRKP carrying a rare plasmid-borne inducible AmpC gene, blaDHA-1. The isolate was recovered from blood culture of a 67-year-old female presenting with sepsis post bladder surgery and ureteral stent removal. The primary isolate displayed an indeterminate susceptibility pattern for ceftriaxone by broth microdilution, but was susceptible by disk diffusion with one colony growing within the zone of inhibition. The ceftriaxone resistant colony was sub-cultured and had a minimum inhibitory concentration (MIC) of 2 ug/ml for imipenem (intermediate) and a zone size of 18 mm for ertapenem (resistant), but remained susceptible to cefepime and meropenem. Further phenotypic characterization of this sub-cultured isolate showed carbapenemase activity. Whole genome sequencing (WGS) revealed the presence of two subpopulations of a K. pneumoniae (MLST sequence type 11) from the primary blood culture isolate: one pan-susceptible to beta-lactams tested and the other resistant to the 3rd generation cephalosporins and ertapenem. WGS analysis identified the resistant K. pneumoniae harboring IncFIB(K) and IncR plasmids and the presence of plasmid-borne beta-lactam resistance genes blaOXA-1 and blaDHA-1, an inducible AmpC gene. Additional resistance genes against quinolones (aac(6′)-Ib-cr, oqxA, oqB), aminoglycoside (aph(3′)-Ia), sulfonamide (sul1), and tetracycline (tet(A)) were also identified. DHA-1 positive K. pneumoniae have been previously identified outside the US, particularly in Asia and Europe, but limited cases have been reported in the United States and may be underrecognized. Our study highlights the importance of using both extended phenotypic testing and WGS to identify emerging resistance mechanisms in clinical Enterobacterales isolates with unusual antimicrobial resistance patterns.

Antibiograms of intensive care units at an Egyptian tertiary care hospital

Background Intensive care unit (ICU) infection management is a growing challenge, and physicians should have regularly updated antibiograms. The aim of this study was to find out the prevalence of pathogens and to determine their antibiotic susceptibility in different ICUs of an Egyptian tertiary care hospital. This retrospective record-based cross-sectional study was conducted from the first of January to the last of December 2019 with a total of 45,221 diagnostic first-isolate culture/patient obtained from different ICUs in Zagazig University Hospitals. The antibiogram construction was done according to Clinical and Laboratory Standards Institute instructions and a Web-based antibiogram at Stanford University. Results The positive blood isolate was the most prevalent infection site (32.37%) followed by sputum and urine isolates. Gram-negative microorganisms (74.41%) were the most common pathogens, with Klebsiella pneumoniae as the most frequently identified one with an incidence of 33.51% followed by Escherichia coli with 19.3% incidence. Antibiotic sensitivity showed that colistin is the most effective antibiotic with 96.2%, 94.7%, and 89.9% sensitivity for Klebsiella, E. coli, and Acinetobacter, respectively, while carbepenems sensitivity was extremely low, showing 19.5% and 19% imipenem and meropenem sensitivity for Klebsiella, 48% imipenem and 52.7% meropenem sensitivity for E. coli, 20.1% imipenem and 20.3% meropenem sensitivity for Acinetobacter, and 17.3% imipenem and 15.2% meropenem sensitivity for Pseudomonas aeruginosa. Fungal infection in our results represented less than 1%. Conclusion Our study provides a local baseline epidemiological data which describes the extent of the ICU infections problem in this tertiary care hospital. Trial registration ClinicalTrials.gov (NCT04318613)

Flying fox haemolytic fever, description of a new zoonosis caused by “Candidatus Mycoplasma haemohominis”

Background Hemotropic mycoplasmas, previously classified in the genus Eperythrozoon, have been reported as causing human infections in Brazil, China, Japan and Spain. Methods In 2017, we detected DNA from “Candidatus Mycoplasma haemohominis” in the blood of a Melanesian patient from New Caledonia presenting with febrile splenomegaly,weight loss, life-threatening autoimmune haemolytic anemia and hemophagocytosis. The full genome of the bacterium was sequenced from a blood isolate. Subsequently, we tested retrospectively (2011-2017) and prospectively (2018-2019) patients who had been hospitalized with a similar clinico-biological picture. In addition, as these patients had been in contact with frugivorous bats (authorized under conditions for hunting and eating in New Caledonia) we investigated the role of these animals and their biting flies by testing them for hemotropic mycoplasmas. Results Fifteen patients were found to be infected by this hemotropic mycoplasma. Among them, four (27%) died following splenectomy performed for spontaneous spleen rupture, or to cure refractory autoimmune haemolytic anemia. The bacterium was cultivated from the patient's blood. The full genome of the Neocaledonian “Candidatus M. haemohominis” strain differed from that of a recently identified Japanese strain. Forty-six percent of 40 tested Pteropus bats and 100% of collected bat flies Cyclopodia horsfieldi (Nycteribiidae, Diptera) were positive. Human,bat and dipteran strains were highly similar. Conclusions The bacterium being widely distributed in bats, “Candidatus M. haemohominis” should be regarded as a potential cause of severe infections in humans.

Clinical Blood Isolates from Hemodialysis Patients: Distribution of Organisms and Antimicrobial Resistance, 2007–2014

Background: Given the morbidity and mortality associated with bloodstream infections in hemodialysis patients, understanding the microbiology is essential to optimizing treatment in this high-risk population.Objectives: To conduct a retrospective surveillance study of clinical blood isolates from adult hemodialysis patients, and to predict the microbiological coverage of empiric therapies for bloodstream infections in this population.Methods: Clinical blood isolate data were collected from the 4 main outpatient hemodialysis units in Winnipeg, Manitoba, from 2007 to 2014. The distribution of organisms and antimicrobial susceptibilities were characterized. When appropriate, changes over time were tested using time series analysis. Study data were used to predict and compare the microbiological coverage of various empiric therapies for bloodstream infections in hemodialysis patients.Results: The estimated annual number of patients receiving chronic hemodialysis increased steadily over the study period (p < 0.001), whereas the number of blood isolates increased initially, then decreased significantly, from 180 in 2011 to 93 in 2014 (p = 0.04). Gram-positive bacteria represented 72.6% (743/1024) of isolates, including Staphylococcus aureus (36.9%, 378/1024) and coagulase-negative staphylococci (23.1%, 237/1024). Only 26.1% (267/1024) of the isolates were gram-negative bacteria, the majority Enterobacteriaceae. The overall rate of methicillin resistance in S. aureus was 17.5%, and although annual rates were variable, there was a significant increase over time (p = 0.04). Antibiotic resistance in gram-negative bacteria was relatively low, except in Escherichia coli, where 13.5% and 16.2% of isolates were resistant to ceftriaxone and ciprofloxacin, respectively. Empiric therapy with vancomycin plus an agent for gram-negative coverage was predicted to cover 98.8% to 99.7% of blood isolates from hemodialysis patients, whereas cefazolin plus an agent for gram-negative coverage would cover only 67.5% to 68.4%.Conclusions: In an era of increasing antimicrobial resistance, data such as these and ongoing surveillance are essential components of antimicrobial stewardship in the hemodialysis population.Keywords: hemodialysis, microbiology, surveillance, resistance, antimicrobial stewardshipRÉSUMÉ Contexte : Étant donné la morbidité et la mortalité associées aux infections du sang parmi les patients en hémodialyse, la compréhension de la microbiologie est essentielle à l’optimisation du traitement de cette population exposée à un risque élevé.Objectifs : Mener une étude de surveillance rétrospective des isolats de sang cliniques des patients adultes en hémodialyse et prédire la couverture microbiologique des thérapies empiriques contre les infections du sang dans cette population.Méthodes : Les données relatives aux isolats de sang cliniques ont été recueillies dans les quatre unités ambulatoires principales d’hémodialyse à Winnipeg (Manitoba), entre 2007 et 2014. La caractérisation a porté sur la distribution des organismes et les susceptibilités aux antimicrobiens. L’évolution dans le temps a été testée au besoin à l’aide d’une analyse chronologique. Les données de l’étude ont permis de prédire et de comparer la couverture microbiologique de diverses thérapies empiriques contre les infections du sang pour les patients en hémodialyse.Résultats : On estime que le nombre annuel de patients recevant une hémodialyse chronique a augmenté régulièrement au cours de la période de l’étude (p < 0,001); le nombre d’isolats de sang a tout d’abord augmenté, puis il a grandement diminué : de 180 en 2011, il est passé à 93 en 2014 (p = 0,04). Les bactéries à Gram positif représentaient 72,6 % (743/1024) des isolats, y compris les Staphylococcus aureus (36,9 %, 378/1024) et les staphylocoques à coagulase négative (23,1 %, 237/1024). Seulement 26,1 % (267/1024) des isolats étaient des bactéries à Gram négatif, la majorité desquelles étant des Enterobacteriaceae. Le taux général de résistance à la méticilline de S. aureus était de 17,5 %, et bien que les taux annuels étaient variables, une augmentation importante a été observée avec le temps (p = 0,04). La résistance aux antibiotiques des bactéries à Gram négatif était relativement faible, sauf Escherichia coli, où respectivement 13,5 % et 16,2 % des isolats étaient résistants à la ceftriaxone et à la ciprofloxacine. On prévoyait que la thérapie empirique à la vancomycine associée à un agent pour la couverture à Gram positif couvrirait de 98,8 % à 99,7 % des isolats de sang des patients en hémodialyse, tandis que la céfazoline associée à un agent de la couverture à Gram négatif ne couvrirait que 67,5 % à 68,4 %.Conclusions : À une époque qui se caractérise par une augmentation de la résistance aux antimicrobiens, des données comme celles-ci et celles portant sur la surveillance continue sont des composantes essentielles de la bonne gestion de l’utilisation des antimicrobiens pour les patients adultes en hémodialyse.Mots-clés : hémodialyse, microbiologie, surveillance, résistance, gestion de l’utilisation des antimicrobiens

Candida auris in the US Department of Veterans’ Affairs (VA)

Background:Candida auris is an emerging pathogen with high mortality and challenges in detection. C. auris healthcare-associated infections are now being reported worldwide. Most isolates are resistant to fluconazole, and some show resistance to all 3 classes of antifungals. Herein, we describe C. auris surveillance in the VA. Methods: Cultures were identified using VA data sources for C. auris isolates and surveillance cultures (axilla and groin) performed January 1, 2010, through October 15, 2019. Chart reviews were performed for patients with C. auris, including isolate susceptibilities and antifungal treatment. Results: Overall, 6 C. auris isolates from 3 patients at 2 VA hospitals (located in the Midwest and Northeast) were identified. From a single patient, 3 urine isolates were identified June–July 2018, and they were susceptible to all antifungals tested (voriconazole, posaconazole, micafungin, itraconazole, flucytosine, caspofungin, anidulafungin, amphotericin B, and fluconazole). No antifungal treatment was received (presumed colonization). C. auris surveillance cultures for 32 additional patients at this facility between July 10, 2018, and July 19, 2018, were negative. From a second patient (admitted November 9, 2018), 2 C. auris blood isolates were identified at the same facility, first on February 3, 2019, and they were susceptible to all antifungals tested (same as above). The infection was deemed healthcare associated, and the patient received 2 weeks of micafungin. On October 11, 2019, C. auris was identified again (susceptibilities as above) and another course of micafungin was started. A third patient from a different VA hospital had a C. auris sputum isolate (September 5, 2018, susceptibilities not reported), which was not treated with antifungals. This patient with tracheostomy had a documented history of C. auris colonization from a non-VA long-term care facility. This VA facility screened 3 additional patients for “rule out C. auris” between July 2018 and March 2019,finalized as C. parapsilosis (1 blood and 1 wound isolate) and C. tropicalis (1 blood isolate). At 2 other VA facilities, 3 patients had C. auris surveillance cultures performed in 2019, which were negative. Additionally, at least 65 isolates of C. haemulonii, which can be difficult to distinguish from C. auris, have been identified from 51 unique individuals at 24 other VA facilities since 2010. Conclusions: Two VA facilities have identified cases of C. auris infection and colonization. Additional awareness is needed because C. auris can be difficult to identify using traditional biochemical methods and may be resistant to standard treatment. According to the CDC, screening of close healthcare contacts should be considered for patients with newly identified C. auris infection or colonization. Early and accurate diagnosis are important for improving outcomes and reducing transmission of this rapidly emerging pathogen.Funding: NoneDisclosures: None

Increasing proportion of vancomycin resistance among enterococcal bacteraemias in Switzerland: a 6-year nation-wide surveillance, 2013 to 2018

Background Vancomycin-resistant enterococci (VRE), mostly Enterococcus faecium, are multidrug-resistant microorganisms that can cause nosocomial infections. VRE has increased throughout many European countries, but data from Switzerland are scarce. Aim The aim of this work was to characterise the epidemiology of enterococcal bacteraemias in Switzerland with a focus on VRE. Methods In this observational study, we retrospectively investigated bacteraemias from 81 healthcare institutions from January 2013 to December 2018 using data from the Swiss Centre for Antibiotic Resistance. Only the first blood isolate with E. faecalis or E. faecium from an individual patient was considered. We analysed the annual incidences of enterococcal bacteraemias and determined the proportion of VRE over time. We also assessed epidemiological factors potentially associated with VRE bacteraemia. Results We identified 5,369 enterococcal bacteraemias, of which 3,196 (59.5%) were due to E. faecalis and 2,173 (40.5%) to E. faecium. The incidence of enterococcal bacteraemias increased by 3.2% per year (95% confidential interval (CI): 1.6–4.8%), predominantly due to a substantial increase in E. faecalis bacteraemic episodes. Vancomycin resistance affected 30 (1.4%) E. faecium and one E. faecalis bacteraemic episodes. Among all E. faecium bacteraemias, the proportion of vancomycin-resistant isolates increased steadily from 2013 to 2018 (2% per year; 95% CI: 1.5–2.9%). No independent epidemiological factor for higher prevalence of vancomycin-resistant E. faecium bacteraemias was identified. Conclusions Vancomycin-resistant E. faecium bacteraemias remain infrequent in Switzerland. However, an important increase was observed between 2013 and 2018, highlighting the need for implementing active surveillance and targeted prevention strategies in the country.

Draft Genome Sequence of an Unusually Multidrug-Resistant Strain of Achromobacter xylosoxidans from a Blood Isolate

ABSTRACT Achromobacter xylosoxidans strain DN2019 was isolated from blood of a septicemia patient. We describe the draft genome and antibiotic susceptibility of this strain.