Leama Ajaka’s research while affiliated with The Ohio State University and other places

Background: Candida auris is an emerging threat to hospitalized patients and invasive disease is associated with high mortality. This study describes clinical and microbiological characteristics of nine patients identified with C. auris at Ohio State Wexner Medical Center discovered through active surveillance or clinical investigation and uses whole genome sequencing (WGS) to compare isolates. Methods: In November 2022, an active C. auris surveillance program was implemented to screen patients admitted to high-risk units (intensive care units and progressive care units). Bilateral axilla and groin swabs were obtained upon unit admission and, if positive, were submitted for C. auris polymerase chain reaction (PCR) with culture and sensitivity testing. Patients with a positive screening or clinical isolate from November 2022 to November 2023 underwent chart review for clinical characteristics, microbiologic data, and index admission information. For each isolate, DNA was extracted and WGS was performed. Core single nucleotide polymorphism (SNP) variation identified from the sequence data was used to infer genetic relationships among the isolates. Results: Nine patients were identified between November 2022 and November 2023. The clinical and microbiologic characteristics are summarized in Table 1. All patients were hospitalized at various acute care facilities across the state at least once in the preceding 12 months. C. auris was determined to be present on admission for 6 patients. For 5 of these patients, it was their first interaction with our healthcare system. Three patients were not in contact isolation for >3 days before C. auris was identified. Unit wide point-prevalence screening was completed in these cases and no evidence of transmission was found. WGS showed eight of the nine isolates were related with 28 or less core SNP differences between isolates (Figure 1). One isolate (8) was genetically distinct with >45000 core SNP differences. Five isolates were highly related with a range of 4-15 SNP differences. No temporal or spatial overlap at our institution was identified among these five patients. Conclusions: The active surveillance program identified several patients colonized with C. auris in addition to those found through clinical testing. Multiple risk factors for C. auris were identified with high patient mortality (67%). Majority of the isolates were closely related without association with a known outbreak or epidemiologic link, suggesting a possible diffuse common reservoir. Next steps with surveillance in acute care and long-term care facilities will be critical for early detection to halt transmission of this organism.

Background: Whole genome sequencing (WGS) is a relatively new method for analyzing outbreaks and modes of transmission, particularly for multidrug resistant bacteria. This study sought to investigate clusters of patients with genetically related Vancomycin-Resistant Enterococcus spp. (VRE) bacteremia for shared hospital environmental exposures. Methods: All VRE blood culture isolates from patients from July 1, 2021 to June 30, 2022 underwent Illumina WGS. Core single nucleotide polymorphisms (SNPs) were identified, and multi-locus sequence typing (MLST) was performed across the VRE isolates. Clusters were defined as isolates with 15 or fewer core genome SNPs and were investigated for potential transmission routes. For each cluster, patients were evaluated in the 12 weeks before and after the first VRE isolate for shared hospital environmental exposures (hospital unit, patient rooms, procedural rooms, and radiology suites). Hospital units were comprised of patient rooms located geographically together on the same floor of the hospital. Results: A total of 82 VRE isolates underwent WGS. Thirty-eight (46%) clustered genetically with at least one other isolate. Clusters included 2 to 15 patients per group and represented 10 distinct MLST subgroups (Figure 1). Nine hundred and thirty-nine hospital environmental exposures were identified across the 38 patients. For each cluster, there was a total of 341 (36.3%) shared exposures. Shared environmental exposures occurred in radiology suites (35, 38.5%), patient rooms (32, 35.6%) and procedural rooms (23, 25.6%). Of the patients who shared the same hospital unit, 10 (31.3%) had the same patient room with 7 (70%) of them being in the emergency department (ED). Overall, the ED represented 7 (21.9%) of the shared hospital units. Each cluster had at least one shared hospital environmental exposure found. Conclusions: Use of WGS can help investigate outbreak clusters of resistant organisms such as VRE. In this study, nearly half of all VRE blood isolates were able to be segregated into clusters with at least one other isolate. Although VRE colonization of hospital rooms is well described, patient rooms represented the smallest proportion of shared hospital environmental exposures. This study thus suggests other environmental transmission routes such as radiology suites and procedural rooms warrant closer investigation.

Background: Multidrug-resistant organisms (MDROs) are increasingly implicated in nosocomial outbreaks worldwide. We evaluated whole-genome sequencing (WGS) as an adjunctive epidemiological tool to identify infection clusters and MDRO transmission in the healthcare setting. Methods: Clinical isolates of carbapenem-resistant Enterobacterales (CRE) from July 1, 2021, to June 30, 2022, underwent Illumina WGS. Assembled genomes were taxonomically classified with GTDB-Tk software and were typed using multilocus sequence typing (MLST). Average nucleotide identity (ANI) was calculated between genomes. Numbers of differences among core single-nucleotide polymorphisms (SNPs) were calculated for pairs within taxonomic groups, and the data were evaluated in the context of patient dates and locations of care obtained from the electronic medical record. Results: In total, 39 CRE isolates underwent WGS (Fig. 1). Klebsiella pneumoniae represented the largest number of isolates (n = 18). Using MLST, 2 distinct groups of K. pneumoniae were identified (ST307 and ST258) with 5 and 4 isolates, respectively (Fig. 2). Within ST307, SNP differences ranged between 8 and 115. 3 isolates (CRE8, CRE10, and CRE12) were collected within 4 weeks of each other and had ≤26 pairwise SNP differences. Notably, CRE8 and CRE10 were located on the same unit at the same time and used the same MRI scanner on the same day. CRE35 had >95 SNP differences and was admitted 8 months prior to others in ST307 but had surgery in the same OR as CRE8. Within ST258, pairwise comparison of samples revealed 139–588 SNP differences. CRE21, CRE31, and CRE33 had SNP differences of ≤150. These patients were in the same hospital room (CRE33 and CRE21) and unit (CRE31 and CRE33), but they did not overlap temporally. CRE37 had >580 SNP differences, with no overlap in hospitalization dates or locations with other patients. Conclusions: Two closely related K. pneumoniae isolate populations were identified using WGS. Strong temporal and spatial commonalities were identified among isolates with few SNP differences. Isolate pairs with intermediate SNP differences shared spatial commonalities, suggesting possible indirect transmission between patients. No common exposures were identified for pairs with large numbers of SNP differences. WGS is an evolving tool to detect outbreak clonal populations of MDRO not identified through traditional epidemiologic techniques. WGS can provide insight into transmission patterns and the role of environmental contamination in propagating these nosocomial infections. More studies are needed to define the role and clinical significance of isolates with intermediate SNP differences in transmission of these pathogens between hosts and the healthcare environment. Disclosures: None

Background Although Enterococcus species can colonize and cause infection in multiple body sites, it is considered a rare cause of pneumonia (PNA). The study objective was to describe clinical outcomes in immunocompromised patients with PNA and Enterococcus in respiratory cultures to better elucidate the pathogenic role played by Enterococci. Methods A retrospective, descriptive observational study was conducted on immunocompromised patients with Enterococcus spp on lower respiratory culture from January 1, 2015 to September 22, 2021 with clinical PNA. Data was collected on patient demographics, microbiologic details including bacteremia, other potential infectious causes of PNA and clinical outcomes. Results 116 cases of immunocompromised patients with PNA and Enterococcus spp on respiratory culture were identified. Two patients also grew Enterococcus spp on pleural fluid and 1 on lung tissue. Vancomycin-resistant Enterococcus grew in 41/116 (35%) cases. Six (5%) patients had a bloodstream infection due to Enterococcus spp and a central line was present in all cases. In 52/116 (45%) cases there was growth of another organism, and 61/116 (53%) cases had an alternative infectious cause for PNA, whether it was a typical respiratory bacterial pathogen, viral illness, or invasive fungal infection. In 55 (47%) cases, there was no alternative infectious cause of PNA identified; 44 (80%) of these patients received an antibiotic active against Enterococcus spp and of these, 30 (68%) were clinically improved after 14 days. Overall mortality was high with 52/116 total cases (45%) in which the patient was alive after 90 days. In 25 cases patients did not receive antibiotic therapy active against Enterococcus and 28% were alive at 90 days. Conclusion Enterococcus spp should be considered a significant pulmonary pathogen in immunocompromised hosts in the appropriate clinical context. At our institution, the majority of immunocompromised patients with a monomicrobial pulmonary infection with Enterococcus were treated with targeted antibiotics. Further studies should evaluate outcomes of and indications for targeted treatment of pleuropulmonary Enterococcus. Disclosures All Authors: No reported disclosures.