Search

Background Sotrovimab is an anti-spike neutralization monoclonal antibody developed to reduce the risk of coronavirus disease 2019 (COVID-19) progression and advancement to hospitalization in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancy and the predictive factors of hospitalization. Methods We performed an observational study of 156 consecutive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19–related hospitalization(s) compared to those who did not. Results Among the 156 study patients, 17 (11%) were hospitalized, of whom 4 were readmitted for COVID-19–related complications; 3 deaths were attributed to COVID-19. Results from multivariable logistic regression show that significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted odds ratio [aOR], 5.59 [95% confidence interval {CI}, 1.73–18.12]; P = .004) and with relapse/refractory disease (aOR, 5.69 [95% CI, 1.69–19.16]; P = .005). Additionally, whole genome sequencing of severe acute respiratory syndrome coronavirus 2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treated with sotrovimab. Conclusions While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in patients with hematologic malignancy when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy.

Clostridioides difficile (C. difficile), a leading cause of nosocomial infection, produces toxins that damage the colonic epithelium and results in colitis that varies from mild to fulminant. Variation in disease severity is poorly understood and has been attributed to host factors (age, immune competence and intestinal microbiome composition) and/or virulence differences betweenC. difficilestrains, with some, such as the epidemic BI/NAP1/027 (MLST1) strain, being associated with greater virulence. We tested 23 MLST1(ST1)C. difficileclinical isolates for virulence in antibiotic-treated C57BL/6 mice. All isolates encoded a complete Tcd pathogenicity locus and achieved similar colonization densities in mice. Disease severity varied, however, with 5 isolates causing lethal infections, 16 isolates causing a range of moderate infections and 2 isolates resulting in no detectable disease. The avirulent ST1 isolates did not cause disease in highly susceptible Myd88-/-or germ-free mice. Genomic analysis of the avirulent isolates revealed a 69 base-pair deletion in the N-terminus of thecdtRgene, which encodes a response regulator for binary toxin (CDT) expression. Genetic deletion of the 69 base-paircdtRsequence in the highly virulent ST1 R20291C. difficilestrain rendered it avirulent and reduced toxin gene transcription in cecal contents. Our study demonstrates that a natural deletion withincdtRattenuates virulence in the epidemic ST1C. difficilestrain without reducing colonization and persistence in the gut. Distinguishing strains on the basis ofcdtRmay enhance the specificity of diagnostic tests forC. difficilecolitis.

Mutations in the viral genome of SARS-CoV-2 can impact the performance of molecular diagnostic assays. In some cases, such as S gene target failure, the impact can serve as a unique indicator of a particular SARS-CoV-2 variant and provide a method for rapid detection. Here we describe partial ORF1ab gene target failure (pOGTF) on the cobas® SARS-CoV-2 assays, defined by a ≥2 thermocycles delay in detection of the ORF1ab gene compared to the E gene. We demonstrate that pOGTF is 97% sensitive and 99% specific for SARS-CoV-2 lineage BA.2.12.1, an emerging variant in the United States with spike L452Q and S704L mutations that may impact transmission, infectivity, and/or immune evasion. Increasing rates of pOGTF closely mirrored rates of BA.2.12.1 sequences uploaded to public databases, and, importantly increasing local rates of pOGTF also mirrored increasing overall test positivity. Use of pOGTF as a proxy for BA.2.12.1 provides faster tracking of the variant than whole-genome sequencing and can benefit laboratories without sequencing capabilities.

In this retrospective study of 105 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–infected cancer patients with longitudinal nasopharyngeal sampling, the duration of viral shedding and time to attain cycle threshold >30 was longer in patients with hematologic malignancy than in those with solid tumors. These findings have important public health implications.

To describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance.In a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness.Among the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic.Study demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.

Diagnosis and management of bacterial pneumonia still relies on bacterial culture and antimicrobial susceptibility testing. The Unyvero Lower Respiratory Tract panel (LRT) is a multiplex molecular assay that provides results within approximately 4.5 hours. This study evaluated the analytical performance of the LRT on bronchoalveolar lavage (BAL) fluids and bronchial washings (BW) in a cancer patient population and retrospectively determined clinical impact on therapy. Sensitivity and specificity of LRT on BAL and BW compared with bacterial culture and susceptibilities were calculated. Chart reviews were performed to determine whether antibiotic management would have changed based on the LRT results. A total of 113 BAL and 123 BW respiratory samples from 191 patients were included. The overall sensitivity and specificity were 91.7% (95% CI, 77.5%-98.3%) and 92.0% (95% CI, 87.3%-95.4%), respectively. Staphylococcus aureus was the most common target detected (n = 21) with 89.5% (95% CI, 66.8%-98.7%) sensitivity and 98.2% (95% CI, 95.4%-99.5%) specificity. Based on availability of LRT results, 4.8% of patients could have been de-escalated faster. The LRT demonstrated an overall high accuracy for the detection of common bacteria associated with pneumonia. In this cancer inpatient cohort, treatment adjustment based on LRT results would have occurred in a small number of cases. Larger studies are necessary to understand the real-world impact within specific high-risk populations.

Background Vaccine-induced clinical protection against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) variants is an evolving target. There are limited genomic level data on SARS CoV-2 breakthrough infections and vaccine effectiveness (VE) since the global spread of the B.1.617.2 (Delta) variant. Methods In a retrospective study from 1 November 2020 to 31 August 2021, divided as pre-Delta and Delta-dominant periods, laboratory-confirmed SARS CoV-2 infections among healthcare personnel (HCP) at a large tertiary cancer center in New York City were examined to compare the weekly infection rate-ratio in vaccinated, partially vaccinated, and unvaccinated HCP. We describe the clinical and genomic epidemiologic features of post-vaccine infections to assess for selection of variants of concern (VOC)/variants of interest (VOI) in the early post-vaccine period and impact of B.1.617.2 (Delta) variant domination on VE. Results Among 13658 HCP in our cohort, 12379 received at least 1 dose of a messenger RNA (mRNA) vaccine. In the pre-Delta period overall VE was 94.5%. Whole genome sequencing (WGS) of 369 isolates in the pre-Delta period did not reveal a clade bias for VOC/VOI specific to post-vaccine infections. VE in the Delta dominant phase was 75.6%. No hospitalizations occurred among vaccinated HCP in the entire study period, compared to 17 hospitalizations and 1 death among unvaccinated HCP. Conclusions Findings show high VE among HCP in New York City in the pre-Delta phase, with moderate decline in VE post-Delta emergence. SARS CoV-2 clades were similarly distributed among vaccinated and unvaccinated infected HCP without apparent clustering during the pre-Delta period of diverse clade circulation. Strong vaccine protection against hospitalization was maintained through the entire study period.

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). Serum and bronchoalveolar lavage (BAL) fluid samples received for GM EIA testing between March and August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient's medical records assessing for any evidence of a fungal infection. Five hundred thirty-three samples (85 BAL samples and 448 serum samples) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% confidence interval [CI], 72.2 to 100%) and 97.5% (95% CI, 95.5 to 98.4%), respectively. Fourteen of 24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable invasive aspergillosis (IA) was 100% (95% CI, 51.0 to 100%) and 87.5% (95% CI, 55.9 to 99.4%), with a specificity of 95.5% (95% CI, 92.3 to 97.2%) and 96.2% (95% CI, 93.4 to 97.7%), respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI, 1.28 to 69.9%) and 62.5% (95% CI, 30.6 to 86.3%), with a specificity of 98.2% (95% CI, 96.2 to 99.1%) and 99.2% (95% CI, 97.7 to 99.8%), respectively. The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.

The diagnosis of invasive aspergillosis can be challenging in cancer patients. Herein, the analytical and clinical performance of the sōna Aspergillus galactomannan lateral flow assay (GM LFA) was evaluated and its performance compared to that of the Bio-Rad galactomannan enzyme immunoassay (GM EIA). Serum and bronchoalveolar lavage (BAL) fluid samples received for GM EIA testing between March and August 2019 were included. Positive and negative percent agreement (PPA and NPA) were calculated for the GM LFA compared to the GM EIA. Discrepant analysis was performed by review of the patient‘s medical records assessing for any evidence of a fungal infection. Five hundred thirty-three samples (85 BAL samples and 448 serum samples) from 379 patients were included in the study. The overall PPA and NPA were 100% (95% confidence interval [CI], 72.2 to 100%) and 97.5% (95% CI, 95.5 to 98.4%), respectively. Fourteen of 24 samples were positive by LFA only. The sensitivity of the GM LFA for proven and probable invasive aspergillosis (IA) was 100% (95% CI, 51.0 to 100%) and 87.5% (95% CI, 55.9 to 99.4%), with a specificity of 95.5% (95% CI, 92.3 to 97.2%) and 96.2% (95% CI, 93.4 to 97.7%), respectively. The sensitivity of the GM EIA for proven and probable IA was 25% (95% CI, 1.28 to 69.9%) and 62.5% (95% CI, 30.6 to 86.3%), with a specificity of 98.2% (95% CI, 96.2 to 99.1%) and 99.2% (95% CI, 97.7 to 99.8%), respectively. The Aspergillus GM LFA outperformed the Aspergillus GM EIA for the detection of the galactomannan antigen in our patient population. The simplicity and rapid time to results makes the Aspergillus GM LFA easy to implement in a wide range of laboratory settings.

BackgroundThere is limited information on the risk of hospital-acquired coronavirus disease 2019 (COVID-19) among high-risk hospitalized patients after exposure to an infected patient or healthcare worker (HCW) in a nonoutbreak setting.MethodsThis study was conducted at a tertiary care cancer center in New York City from 10 March 2020 until 28 February 2021. In early April 2020, the study institution implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing at admission and retesting every 3 days through the hospital stay. Contact tracing records were reviewed for all exposures to SARS-CoV-2 positive patients and HCWs.ResultsFrom 10 March 2020 to 28 February 2021, 11 348 unique patients who were SARS-CoV-2 polymerase chain reaction (PCR) negative at the time of admission underwent 31 662 postadmission tests during their hospitalization, and 112 tested positive (0.98%). Among these, 49 patients housed in semiprivate rooms during admission resulted in 74 close contacts and 14 secondary infections within 14 days, for an overall attack rate of 18.9%. Among those exposed to a roommate undergoing an aerosol-generating procedure (AGP), the attack rate was 35.7%. Whole genome sequencing (WGS) corroborated transmission in 6/8 evaluated pairs. In addition, three transmission events occurred in 214 patients with significant exposure to 105 COVID-19 positive healthcare workers (1.4%).ConclusionsThe overall risk of hospital-acquired COVID-19 is low for hospitalized cancer patients, even during periods of high community prevalence. However, shared occupancy with an unrecognized case is associated with a high secondary attack rate in exposed roommates.

The Roche Cobas SARS-CoV-2 test recently received an Emergency Use Authorization from the U.S. Food and Drug Administration UA for pooling of up to six nasopharyngeal swab samples (NPS). We evaluated the 6-pool approach on both NPS and saliva samples using 564 samples (20 positive NPS and saliva samples each and 262 negative NPS and saliva samples each). The sensitivity of the Roche SARS-CoV-2 RNA test for pooled NPS samples was 100 % (95 %CI: 83.2-100 %) and the sensitivity for pooled saliva samples was 90 % (95 % CI: 68.3-98.8 %). Given the high throughput of the Roche Cobas 6800, pooling of 6 samples has the potential to significantly increase testing capacity without significant loss in sensitivity.

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

Summary Background Cases of Clostridiodes difficile infection (CDI) diagnosed after hospital discharge account for a substantial proportion of new infections. It is unclear whether post-discharge infections originate from hospital-based transmission. Methods This was a Retrospective cohort study at a tertiary-care cancer center (non-outbreak setting). For all laboratory-identified cases of CDI in 2015–2016, patients with post-discharge (PD) CDI within eight weeks of their hospital stay were included in the study. Isolates from PD-CDI cases and their CDI-positive unit-based contacts were first genotyped by multilocus sequence typing (MLST). Common strains were further examined by core genome sequencing (CGS) to evaluate transmission links. Results Of 173 cases examined by MLST, 50% of PD cases matched previous unit contacts. Next, 34 isolates, including 16 PD cases and their 18-unit contacts were examined by CGS. None were ≤3 single-nucleotide variants apart. Seventy percent of PD cases had in-hospital antibiotic exposure before CDI onset in the community. Conclusion Our study results suggest that symptomatic CDI cases are not a substantial source of transmission to PD cases. Frequent antibiotic exposure in post-discharge CDI cases is an important target for surveillance and stewardship efforts.

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

Access to rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for controlling the current global pandemic of coronavirus disease 2019. In this study, the use of oral rinses (ORs) and posterior oropharyngeal saliva as an alternative to swab collection methods from symptomatic and asymptomatic health care workers for the detection of SARS-CoV-2 RNA by RT-PCR was evaluated. For saliva samples, the overall agreement with oropharyngeal swabs was 93% (Ƙ = 0.84), with a sensitivity of 96.7% (95% CI, 83.3%–99.8%). The agreement between saliva and nasopharyngeal swabs was 97.7% (Ƙ = 0.93), with a sensitivity of 94.1% (95% CI, 73.0%–99.7%). ORs were compared with nasopharyngeal swabs only, with an overall agreement of 85.7% (Ƙ = 0.65), and a sensitivity of 63% (95% CI, 46.6%–77.8%). The agreement between a laboratory-developed test based on the CDC RT-PCR and two commercial assays, the Xpert Xpress SARS-CoV-2 and the Cobas SARS-CoV-2, was also evaluated. The overall agreement was >90%. Finally, SARS-CoV-2 RNA in saliva samples was shown to be stable, with no changes in viral loads over 24 hours at both room temperature and 4°C. Although the dilution of SARS-CoV-2 in ORs precluded its acceptability as a sample type, posterior oropharyngeal saliva was an acceptable alternative sample type for SARS-CoV-2 RNA detection.

OBJECTIVESIn this study, we sought to evaluate the performance of the Xpert MTB/RIF (Cepheid) assay for the detection of Mycobacterium tuberculosis (MTB) complex DNA on fresh and formalin-fixed, paraffin-embedded (FFPE) tissue specimens from oncology patients in an area with a low prevalence of tuberculosis. We also aimed to retrospectively assess the potential impact of Xpert MTB/RIF on the duration of airborne infection isolation (AII).SETTINGA 473-bed, tertiary-care cancer center in New York City.DESIGNA total of 203 tissue samples (101 FFPE and 102 fresh) were tested using Xpert MTB/RIF, including 133 pulmonary tissue samples (65.5%) and 70 extrapulmonary tissue samples (34.5%). Acid-fast bacilli (AFB) culture was used as the diagnostic gold standard. The limit of detection (LOD) and reproducibility were also evaluated for both samples types using contrived specimens. The potential impact of the Xpert MTB PCR assay on tissue samples from AII patients on AII duration was retrospectively assessed.RESULTSUsing the Xpert MTB/RIF for fresh tissue specimens, the sensitivity was 50% (95% CI, 1.3%–98.7%) and the specificity was 99% (95% CI, 94.5%–99.9%). For FFPE tissue specimens, the sensitivity was 100% (95% CI, 63.1%–100%) and the specificity was 98.3% (95% CI, 95.5%–100%. The LOD was 103 colony-forming units (CFU)/mL for both fresh and FFPE tissue specimens, and the Xpert MTB/RIF was 100% reproducible at concentrations 10 times that of the LOD. With an expected turnaround time of 24 hours, the Xpert MTB PCR could decrease the duration of AII from a median of 8 days to a median of 1 day.CONCLUSIONSThe Xpert MTB/RIF assay offers a valid option for ruling out Mycobacterium tuberculosis complex (MTBC) on tissue samples from oncology patients and for minimizing AII resource utilization.Infect Control Hosp Epidemiol 2018;39:462–466

Background: COVID-19 is associated with a wide spectrum of neurologic manifestations, which can emerge weeks to months after the initial infection. Cancer patients are at a heightened risk of severe infections due to their immunocompromised status. Leading hypotheses predict that SARS-CoV-2 neuroinvasion or neurologic toxicity from the systemic cytokine storm may account for neurologic dysfunction. Methods: We prospectively evaluated cancer patients with confirmed SARS-CoV-2 infection and subsequent neurologic manifestations at an NCI-designated cancer center. Evaluations included neurologic examinations, brain imaging, electroencephalogram, and cerebrospinal fluid (CSF) analysis for SARS-CoV-2 detection by RT-PCR for viral RNA and ELISA for nucleocapsid (N) and spike (S2) proteins. Additional proteomic analysis compared the CSF of patients with COVID-19 (CoV+) to cancer- and brain metastasis-matched COVID-19-negative controls (CoV-), and to patients with other cancer-associated neuroinflammatory conditions, including immune effector cell-associated neurotoxicity syndrome (ICANS) and autoimmune encephalitis. Results: Between May and July 2020, we evaluated 18 COVID-19-positive cancer patients with a wide range of solid tumor and hematologic malignancies. Thirteen (72.2%) of our patients received tumor-directed treatment within 30 days of SARS-CoV-2 infection. Neurologic diagnoses include protracted critical care delirium (N=10), limbic encephalitis (N=4), refractory headaches (N=2), rhombencephalitis (N=1), and large-territory infarctions (N=1). A median delay of 19 days (range 0-77) existed between onset of respiratory symptoms and neurologic manifestations. Among 13 patients who underwent CSF analysis, there was no evidence of SARS-CoV-2 neuroinvasion by RT-PCR in the CSF (N=13) or by N and S2 protein detection (N=10). Targeted proteomic analysis detected a significant accumulation of IL-6 and -8, IFN-gamma, CXCL-1, -6, -9, -10, and -11, CCL-8 and -20, MMP-10 and 4E-BP1 in the CSF of CoV+ patients (N=10) relative to matched CoV- controls (pooled, p=0.029). Combined analysis of these 12 inflammatory mediators revealed CoV+ cytokine levels approaching that of ICANS. CSF MMP-10, a marker of neurodegeneration, correlated with neurologic dysfunction by Karnofsky performance status (p=0.011) and by disability rating scale (p=0.086) at the time of lumbar puncture. Conclusion: A durable accumulation of IFN-gamma-mediated cytokines is detected in the CSF of cancer patients with neurologic manifestations of COVID-19, in the absence of detectable neuroinvasion. We hypothesize that cytokine-mediated neuroinflammation is responsible for the prolonged neurologic sequela of COVID-19. Our findings suggest a potential role for anti-inflammatory treatments in the management of such patients. Citation Format: Jessica A. Wilcox, Jan Remsik, N. Esther Babady, Tracy A. McMillen, Behroze A. Vachha, Neil A. Halpern, Vikram Dhawan, Marc Rosenblum, Christine A. Iacobuzio-Donahue, Edward K. Avila, Bianca Santomasso, Adrienne Boire. An inflammatory leptomeningeal signature in cancer patients with neurologic manifestations of COVID-19 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 703.

Background Diagnosis of Adenovirus infections in transplant patients may be accomplished using either plasma or stool samples. IVD-cleared multiplexed gastrointestinal (GI) PCR panels offer an option for rapid testing of stool samples but most only target Adenovirus (HAdV) types F40/41. Objectives Given the potential significance of a positive adenovirus test in an immunocompromised patient, we sought to determine the frequency of type 40/41 in our patient population and the utility of a readily available multiplexed, FDA-cleared GI Panel for the detection of adenovirus infections. Study design A total of 215 specimens from immunocompromised patients mostly with hematologic malignancy or transplant recipients were evaluated including 107 plasma samples, 85 stool samples and 23 respiratory samples. Genotyping was performed successfully on 122 specimens. Results The most common type detected in all samples including stools was Adenovirus C/2. In a subset of patients with multiple specimen types tested, similar types were detected in all samples. Conclusions Although Adenovirus F40/41 is the most common enteric type, Adenovirus C/2 was the most common type identified in stools and subsequently plasma samples of our patient population. Implementation of assays that have wide reactivity for most adenovirus types is essential for optimal diagnostic yield.

Rapid and accurate identification of human papillomavirus (HPV) is important for both clinical management and population screening. Analytic validation of Atila AmpFire Multiplex HPV assays on formalin-fixed, paraffin-embedded (FFPE) cervix/vulva and oropharynx diagnostic tissue samples was performed. The AmpFire assay incorporates a novel isothermal multiplex amplification coupled with real-time fluorescent detection to detect and genotype 15 high-risk (HR) HPV genotypes. Limits of detection determined by plasmids cloned with HPV genotype-specific sequences were 2 copies/reaction for HPV16, HPV18, and some HR HPV genotypes, and 20 copies/reaction for the remaining HR HPV genotypes. The performance of the AmpFire assays in clinical samples was evaluated using 214 FFPE specimens. The AmpFire assay failed in one clinical specimen for an invalid rate of 0.5%. The AmpFire assay detected HPV in clinical samples with positive percent agreements of 100.0% for HPV16, 100.0% for HPV18, and 94.7% for non-16/18 HR HPV, and 100% negative percent agreements for HPV16, HPV18, and non-16/18 HR HPV. Qualitative detection agreement was obtained in the reproducibility study. In summary, the Atila AmpFire HPV assay demonstrated excellent analytic sensitivity and specificity for detection and genotyping of 15 HR HPV genotypes. Assay parameters of simple specimen processing, small sample size requirement, rapid turnaround time, and being near instrument-free render it well suited for HPV detection and genotyping in FFPE specimens.

The Aries Bordetella assay (Aries BA) (Luminex Corporation) recently received FDA clearance for the detection and differentiation of Bordetella pertussis and Bordetella parapertussis nucleic acids in nasopharyngeal swab (NPS) samples. The objective of this study was to evaluate the performance of the Aries BA in comparison to that of the BioFire FilmArray respiratory panel (RP). The Aries BA was evaluated using retrospective, remnant nasopharyngeal swabs (NPS), previously tested by FilmArray RP. Performance characteristics evaluated included positive percent agreement (PPA) and negative percent agreement (NPA) with the FilmArray RP. Discordant analysis was performed using bidirectional sequencing. A time and motion study was performed to compare the laboratory workflow of the two tests. Three hundred samples were included in the study. There were no samples positive for B. parapertussis The PPA and NPA of the Aries BA were 61.1% (95% confidence interval [CI], 35.8 to 82.7%) and 100% (95% CI, 98.7 to 100%). Discordant results included five Bordetella bronchiseptica results that were incorrectly identified as B. pertussis by the FilmArray RP and one false-negative result for both the Aries BA and the FilmArray RP. The overall agreement between the Aries BA and FilmArray RP for the detection of B. pertussis was considered good at 97.7% with a kappa value of 0.71 (95% CI, 0.51 to 0.9). The Aries BA offers a new diagnostic option for the rapid and targeted approach to the diagnosis of pertussis. Unlike the FilmArray RP, the Aries BA did not cross-react with B. bronchiseptica in our study, although a larger sample set should be tested to confirm this finding.

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection., Graphical abstract, Remsik et al. analyze the cerebrospinal fluid of cancer patients with neurologic symptoms of COVID-19 and detect unique markers of inflammation and neurodegeneration, present weeks after initial SARS-CoV-2 infection. Cytokine storming, both systemically and intracranially, likely contribute to neurologic dysfunction, indicating a potential therapeutic target for investigation.

ObjectiveTo determine the effectiveness of ultraviolet (UV) environmental disinfection system on rates of hospital-acquired vancomycin-resistant enterococcus (VRE) and Clostridium difficile.DesignUsing active surveillance and an interrupted time-series design, hospital-acquired acquisition of VRE and C. difficile on a bone marrow transplant (BMT) unit were examined before and after implementation of terminal disinfection with UV on all rooms regardless of isolation status of patients. The main outcomes were hospital-based acquisition measured through (1) active surveillance: admission, weekly, and discharge screening for VRE and toxigenic C. difficile (TCD) and (2) clinical surveillance: incidence of VRE and CDI on the unit.SettingBone marrow transplant unit at a tertiary-care cancer center.ParticipantsStem cell transplant (SCT) recipients.InterventionTerminal disinfection of all rooms with UV regardless of isolation status of patients.ResultsDuring the 20-month study period, 579 patients had 704 admissions to the BMT unit, and 2,160 surveillance tests were performed. No change in level or trend in the incidence of VRE (trend incidence rate ratio [IRR], 0.96; 95% confidence interval [CI], 0.81–1.14; level IRR, 1.34; 95% CI, 0.37–1.18) or C. difficile (trend IRR, 1.08; 95% CI, 0.89–1.31; level IRR, 0.51; 95% CI, 0.13–2.11) was observed after the intervention.ConclusionsUtilization of UV disinfection to supplement routine terminal cleaning of rooms was not effective in reducing hospital-acquired VRE and C. difficile among SCT recipients.

This multicenter study was designed to assess the accuracy and reproducibility of the Vitek MS v3.0 matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry system for identification of Mycobacterium and Nocardia species compared to DNA sequencing. A total of 963 clinical isolates representing 51 taxa were evaluated. In all, 663 isolates were correctly identified to the species level (69%), with another 231 (24%) correctly identified to the complex or group level. Fifty-five isolates (6%) could not be identified despite repeat testing. All of the tuberculous mycobacteria (45/45; 100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly identified at least to the group or complex level. However, not all species or subspecies within the M. tuberculosis , M. abscessus , and M. avium complexes and within the M. fortuitum and M. mucogenicum groups could be differentiated. Among the 312 Nocardia isolates tested, 236 (76%) were correctly identified to the species level, with an additional 44 (14%) correctly identified to the complex level. Species within the N. nova and N. transvalensis complexes could not always be differentiated. Eleven percent of the isolates (103/963) underwent repeat testing in order to get a final result. Identification of a representative set of Mycobacterium and Nocardia species was highly reproducible, with 297 of 300 (99%) replicates correctly identified using multiple kit lots, instruments, analysts, and sites. These findings demonstrate that the system is robust and has utility for the routine identification of mycobacteria and Nocardia in clinical practice.

The accuracy and robustness of the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) system was evaluated by identifying mycobacteria from automated liquid-medium systems using patient samples. This is the first report to demonstrate that proteins within the liquid medium, its supplements, and decontamination reagents for nonsterile patient samples do not generate misidentification or false-positive results by use of the Vitek MS v3.0 system. Prior to testing with patient samples, a seeded-culture study was conducted to challenge the accuracy of the Vitek MS system at identifying mycobacteria from liquid medium by mimicking a clinical workflow. Seventy-seven Mycobacterium strains representing 21 species, seeded in simulated sputum, were decontaminated, inoculated into BacT/Alert MP liquid culture medium, incubated until positivity, and identified using the Vitek MS system. A total of 383 liquid cultures were tested, of which 379 (99%) were identified correctly to the species/complex/group level, 4 (1%) gave a "no-identification" result, and no misidentifications were observed. Following the simulated-sputum study, a total of 73 smear-positive liquid-medium cultures detected using BD BBL MGIT and VersaTREK Myco liquid media were identified by the Vitek MS system. Sixty-four cultures (87.7%) were correctly identified to the species/complex/group level; 7 (9.6%) resulted in no identification; and 2 (2.7%) were misidentified at the species level. These results indicate that the Vitek MS v3.0 system is an accurate tool for routine diagnostics of Mycobacterium species isolated from liquid cultures.

Objectives Clostridium difficile infection (CDI) is a toxin-mediated disease. Oncology patients are at increased risk for developing CDI. Diagnosis of CDI by PCR has led to misclassification of some C. difficile carriers as CDI cases. We determined if an optimized C. difficile PCR cycle threshold value (C T ) could reliably predict presence of free toxin, and in turn improve the utility of PCR in detecting clinically relevant CDI in oncology patients. Methods 183 consecutive patients positive for C. difficile by the Xpert C. difficile were additionally tested using the cell culture cytotoxicity neutralization assay (CYT) and enzyme immunoassays (EIA). C T values at diagnosis and relevant clinical information were recorded. Receiver operating characteristic (ROC) curve was used to assess predictive validity and to find optimal C T for CYT positive cases. Severity of CDI was assessed by blinded charts review. Results Using CYT as the reference, ROC-derived Youden cut-off C T of 28.0 predicted 77% cytotoxin positive cases, and 91% and 100% of severe and complicated CDI episodes respectively. The median C T values for non-severe, severe, and complicated CDI episodes were 28.0, 24.5 and 22.5 respectively (p = 0.005). Conclusions Lower C T value of the Xpert C. difficile PCR was associated with the presence of toxin and increased CDI severity. C T values may be beneficial in interpreting positive C. difficile PCR results.

Background The Society for Healthcare Epidemiology of America (SHEA) recommends that surveillance for healthcare facility-onset C. difficile infections (HO CDI) be conducted to detect elevated rates or outbreaks of CDI and stratify data by hospital unit when possible to facilitate detection of clusters. At Memorical Sloan Kettering Cancer Center, strain typing of isolates using multi-locus sequence typing (MLST) is performed routinely and in real time to inform control efforts. Genotyping can conclusively establish or debunk transmission events based on routine surveillance. Management of C. difficile outbreaks is time and resource intensive. Methods A retrospective analysis was conducted to identify all nosocomial C. difficile cases between July 2013 and July 2018. Based on Memorial Sloan Kettering’s baseline surveillance data, a cluster of C. difficile was defined as three or more hospital-acquired cases (as defined by NHSN) on the same inpatient unit within a 7-day period. Data were analyzed to quantify the number of clusters observed and determine genetic relatedness among cases to detect an outbreak. Results A total of 1,116 HO CDI cases occurred during the 5-year time period. Annual nosocomial rates of CDI remained stable (P = 0.052). Eighty clusters were identified; 63 clusters had 3 cases within each cluster, 16 were each made up of 4 cases, and 1 cluster consisted of 5 cases. Two clusters had strain typing concordance amongst all 3 cases; strain type 42 and strain type 1. Among all the epidemiologically linked clusters over the 5-year period, only 2.5% were genetically linked suggestive of true outbreaks. Conclusion The majority of HO-CDI clusters detected on clinical surveillance are non-clonal. Genotyping should be routinely used to corroborate clusters identified on microbiological surveillance before costly outbreak control interventions are deployed. Disclosures All authors: No reported disclosures.

Background Device-related infections account for a fourth of all HAIs. Hepatic artery infusion pump (HAIP) devices are used to deliver chemotherapy directly into the hepatic artery. This device is used primarily in patients with colorectal cancer for the management of unresectable hepatic metastases. We describe the infection rates and outbreak management of MRSA-related infections in newly placed HAIPs. Methods In December 2018, a cluster of 3 MRSA cases was identified within 15–26 days of HAIP insertion. From January 1, 2017 to December 31, 2018, patients with culture proven SSIs within 30 days of HAIP placement were identified through the infection control database to establish baseline rates. Procedural denominator data were found by querying CPT procedure codes. EMR was reviewed to extract clinical characteristics. In response to the cluster, healthcare personnel (HCP) were screened for MRSA by PCR and environmental cultures performed. PFGE and whole-genome sequencing (WGS) was performed to compare isolates recovered in culture and SNP analysis performed using the BioNumerics software v7.6. Results IIn December 2018, 3/15 patients with HAIP procedures developed MRSA infections within 30 days of the procedures (post-op days: 15,16,26). The baseline 30 day SSI rate for HAIP in 2017 was 1.3% (2/160). No infections, prior to the cluster, in 2017–18 were MRSA related. All patients were male, with a median age of 49 years (range: 45–54). Sixty HCP who provided direct care during the peri and early post-operative period for the 3 cases were screened for MRSA carriage; 2/60 (3.3%) were positive. All 56 environmental cultures were negative for MRSA. WGS of the 3 patient samples showed 2/3 samples were identical (1 SNP difference); confirming common source transmission. Only one HCP isolate was available for WGS and shown to be unrelated to the two patient isolates. Both employees underwent decolonization. Review of HAIP handling did not reveal obvious lapses, but mask use and strict hand hygiene were enforced with HCPs. No further infections have been identified in the 76 procedures since the cluster. Conclusion WGS confirmed common source transmission between two newly placed HAIP although the definitive source could not be identified. Surveillance and prevention efforts should extend to all types of vascular access devices. Disclosures All authors: No reported disclosures.

Background Observational studies have identified same room occupancy with a hospital-onset Clostridium difficile infection (HO-CDI) case as a risk factor for subsequent CDI diagnosis. Despite this, the risk remains poorly characterized in endemic settings. Furthermore, genotyping techniques have not been applied to examine concordance between infecting strains in index patients and exposed roommates who eventually develop CDI. The study seeks to quantify transmission of C. difficile from an index case to their roommates and identify if concordance was present among strain types by the application of multi-locus sequence typing (MLST). Methods Laboratory-identified cases of hospital onset C. difficile infection (CDI) from October 1, 2017 through March 31, 2018, were included in the study. Patients with HO-CDI are placed in private room once diagnosis is established. Roommates who were in the same room as cases for at least 24 hours prior to diagnosis, regardless of duration of overlap, were identified through of the hospital patient tracking database to establish spatial link. Next, all exposed roommates who developed CDI within 3 months after exposure (defined as date of CDI diagnosis of index case) were identified. Strain types of linked cases was examined by MLST. Results During the 6-month period, 279 cases of CDI were diagnosed. Of these cases, 156 were hospitalized at the time of diagnosis including 83 (53%) in a room with shared occupancy. These 83 patients had 109 roommates that met exposure criteria. Four (3.7%) roommates developed CDI over a 90-day follow-up period. None of the examined pairs were genetically concordant. Conclusion Indirect patient to patient transmission of C. difficile from newly diagnosed CDI cases to roommates is not common despite the spatial proximity with shared occupancy. Disclosures All authors: No reported disclosures.

Background Polymerase chain reaction (PCR) based diagnostic testing for the detection of toxigenic Clostridium difficile infection (CDI) does not distinguish between carriers and patients with true CDI. As a result, CDI is over-diagnosed in hospitalized patients with diarrhea. Unnecessary testing generates false positives and several downstream sequelae. Aim: The aim of this study was to reduce unnecessary testing for CDI through an electronic alert, targeted education, and implementation of evidence-based laboratory testing policy. Methods In order to quickly identify laxative induced diarrhea and avoid CDI testing, an electronic alert was created in the electronic medical record (EMR) system. The alert was built on a logic that identified patients who had received laxatives within 48 hours of a CDI PCR test order. The alert additionally provided the rationale for avoiding testing in patients on laxatives and guidance on appropriate testing for CDI. The following steps were taken simultaneously to complement these efforts: 1) Infection Control conducted hospital-wide education for licensed independent practitioners on a CDI testing algorithm 2) Laboratory based policy was instated to reject all formed stools (Bristol Stool Chart types 1 through 4) for CDI testing. Results In the 6 month pre-intervention period, there were 29 CDI tests per 1000 patient-days. In the post-intervention period, CDI tests decreased to 19 per 1000 patient-days, a 35% decrease (P < 0.0001). The decline in testing has been sustained for 7 months. The following observations were also made: 1) HAI rate reduction of 28%; 2) decrease in oral vancomycin use. Conclusion Decreasing inappropriate testing has several distinct advantages, including reducing excessive and unnecessary antibiotic use, avoiding misclassification of carriers as CDI cases, normalizing healthcare-associated CDI rates, and diminishing healthcare costs associated with preventable tests. Laboratories that use PCR only testing for CDI diagnosis should follow stringent policies to ensure that only patients with high pretest probability are tested. EMR systems are a useful and effective resource to achieve this for patients with laxative induced diarrhea. Disclosures All authors: No reported disclosures.

Background Patients undergoing treatment for hematologic malignancy are at a higher risk for developing Clostridium difficile infection (CDI). We sought to determine the epidemiology of toxigenic C. difficile (TCD) carriage and CDI incidence among patients undergoing with newly diagnosed or relapsed acute leukemia. Methods Serial stool samples were collected from 92 patients with new or relapsed acute leukemia admitted at Memorial Sloan Kettering Cancer Center between August 26, 2011 to January 22, 2013. Only the first hospitalization during this time period was included. Screening was performed by toxigenic culture and polymerase chain reaction for tcdB gene regardless of symptoms of diarrhea. Genotyping was done by Multi Locus Sequence Typing (MLST). Acquisition of TCD, development of CDI, and associated clinical variables were recorded. Results A total of 92 patients were enrolled in the study. The mean age was 54.3 (median 57.5, range 21–86), 51 were male (55%). The majority (86, 93%) had newly diagnosed acute leukemia and 7% had relapsed disease. 60 patients (65%) had recent healthcare-related exposure, among these were 35 (38%) patients newly referred another facility. The most common chemotherapy regimen was Daunorubicin + Cytarabine in 71 subjects (77%). Systemic antibiotics of any duration during the same hospitalization were used in 89 patients (97%). Median length of stay (LOS) was 30.5 days (range 6–140 days). Among the 92 subjects, 17 developed CDI within 90 days (18%), 12 (71%) had CDI during the index admission. Five among these 12 had known TCD colonization, genotyping of colonizing and CDI strains from the same patients were identical for all patients. CDI in subsequent hospitalizations occurred in 5 patients, 4/5 were new acquisitions. One patient with TCD colonization never developed CDI. 53 subjects (58%) underwent stem cell transplant at a median time of 4 months (range 2–19 months), 8 (15%) developed CDI within 30 days of the transplant admission. Conclusion CDI is exceedingly common among patients with acute leukemia. Acquisition of TCD and CDI occurs early in the treatment course. Approximately half of infections occur in patients with known TCD colonization. Extended LOS and high antibiotic usage are contributors to the high burden of CDI among this population. Disclosures All authors: No reported disclosures.

Background The aim of this study was to evaluate the change in strain-type distribution after eliminating testing of formed and laxative induced diarrheal stool. Methods Beginning in July 2013, all Clostridium difficile-positive stool samples by Cepheid’s GeneXpert were routinely typed using Multi-Locus Sequence Typing (MLST). MLST was performed as previously described (1). After implementation of rejection policy and re-education of staff, strain type (ST) distribution among tested samples were analyzed and compared with historic data. Results After evaluation of our historical typing data the 10 most frequent ST were identified. Diagnostic stewardship led to 40.0% reduction in testing volume, the positivity rate increased from 12.0% to 12.6%. The frequency distribution of threemost prevalent strain types (MLST-2, 8, and 42) declined by 38%, 60%, and 42%, respectively. The absolute number of epidemic strains, ST-1 and ST-11, remained unchanged and the frequency distribution increased from 9.6% to 14.0%. No clonal outbreaks were detected during this time. Conclusion Implementation of diagnostic stewardship led to a reduction in recovery of endemic strains without substantial impact on detection of hypervirulent or epidemic strains. Disclosures All authors: No reported disclosures.

Background Testing for Clostridium difficile (CD) is not recommended in patients under 2 years old because of CD endemicity in young children and absence of associated disease. These patients may, however, represent a reservoir for CD transmission to other high-risk pediatric patients. We describe the strain relatedness of CD isolates among a cohort of pediatric oncology patients by multilocus sequence type (MLST) and interrogate putative transmission events originating from donors ≤2 years of age with whole-genome sequencing (WGS). Methods Demographic and epidemiologic information was extracted from our infection control database for all laboratory identified CD cases in pediatric patients from October 2014 to December 2017. Patients ≤2 year old were identified as potential CD donors in a temporal–spatial model of transmission based on initial MLST analysis. CD recipients were identified as any patient with overlapping hospitalization within 12 weeks of the donor, regardless of recipient’s age. Donor–recipient pairs were further characterized with WGS to investigate the validity of presumed transmission events by epidemiologic links and MLST. Results During the study period CD infection (CDI) was diagnosed in 179 unique pediatric patients. Thirty-nine were ≤2 years. Overall MLST distribution of strains and frequency among patients ≤2 years is shown in Figure 1. ST-2 and 42 were the dominant strains (32% total). ST-11 was not isolated among ≤2 years group and only two ST-1 were isolated without identification of any related recipient cases. Based on concordant strain type on initial MLST, 27 (69%) patients ≤2 years of age were identified as potential donors to 48 pediatric patients; 40 samples were recoverable for WGS representing seven donors and 33 recipients. Despite the high concordance on MLST, WGS revealed only one pair of related CD isolates among these based on a single nucleotide polymorphism (SNP) difference of 1. Retrospective review revealed that these patients were in adjoining rooms during an overlapping admission but were diagnosed with CDI 7 days apart. Conclusion In a pediatric oncology unit, hospitalized children ≤2 years of age are not a substantial reservoir for hypervirulent or epidemic strains and an infrequent source of transmission to others with spatial proximity. Disclosures All authors: No reported disclosures.

We evaluated the performance characteristics of the FilmArray respiratory panel and the eSensor respiratory viral panel on clinical and spiked lower respiratory tract specimens (LRTS). The overall agreement between the two methods was 89.5% (51/57). The lower limit of detection of both assays for all targets in LRTS was comparable to that for nasopharyngeal swab specimens.

Background The incubation period of C. difficile infection (CDI) is highly variable. Infections may be diagnosed weeks after initial acquisition of bacterial spores. Such cases of CDI have onset in the community after a recent hospitalization, or upon readmission, and are characterized as community-onset healthcare-facility associated (CO-HCFA) by current surveillance methods. Aim: With the application of multi-locus sequence typing (MLST), our study seeks to characterize genetic concordance between CO-HCFA cases and prior unit-based contacts (donors) sharing the same strain type (ST). Methods For all laboratory-identified cases of CDI from January 1, 2015, through December 31, 2016, patients with CDI onset within 8 weeks of hospital discharge were included in the study. Infection control database was queried to identify putative donors using the following criteria: previous unit occupants with CDI who had been discharged from the same unit less than 4 weeks, 4–8 weeks, and 8–12 weeks before admission of CO-HCFA cases. Intensity of exposure was further characterized by same room or same unit occupancy. Analysis was restricted to endemic strains at our institution (ST 1, 2, 3, 8, 11 and 42). Results During the two year period, 1330 cases were diagnosed with a new CDI episode, 425 community-onset (32%), 440 hospital-onset (33%) and 465 CO-HCFA (35%) cases. Among the 314 unique CO-HCFA patients due to endemic strains, there were a total of 92 same unit contacts with a concordant strain type, and 1035 same unit contacts with a discordant strain type. The proportion of concordant same unit occupants did not differ by time between cases (P = 0.8120). Conclusion CO-HCFA cases account for a third of all new cases of CDI. Genotypic concordance as potential donors was observed among 8% of all indirect unit based CDI contacts of CO-HCFA cases. This association did not vary significantly as the interval between potential exposure and CDI onset in CO-HCFA cases increased. Disclosures All authors: No reported disclosures.

Background The Ad Hoc C. difficile surveillance working group defines recurrent C. difficile infection as a second episode occurring >8 weeks after the index case. Due to its high sensitivity, diagnosis of recurrent CDI by PCR is extremely challenging in patients who may have persistent, PCR detectable shedding of toxigenic C. difficile (TCD) for an extended period of time after treatment of the initial CDI episode. CYT, which detects C. difficile toxin antigen, is a cumbersome test to perform but is considered as the current clinical diagnostic gold standard for CDI diagnosis. Aim: To determine the CYT and Toxin A/B EIA positivity among patients with recurrent CDI episodes detected by PCR. We further characterized the performance of diagnostic tests based on whether the recurrent episode was a relapse or reinfection. Methods During a three month study period, CYT and Tox A/B EIA was performed on consecutive stool samples submitted from PCR positive recurrent episodes of CDI. For the purpose of this study, recurrence was defined as a second episode of CDI that occurred within 120 days from the most recent episode. MLST analysis was performed as previously described to characterize relapse and reinfection among the recurrent episodes (2). Results Thirty-five recurrent episodes occurred over the study period. 21/35 [60%] were positive by CYT and 12/35 [34%] by Tox A/B EIA. Among the recurrent CDI episodes, 16 (46%) were genotypical confirmed as relapse with the original infecting strain. Majority of these relapses were positive by CYT (81%) when compared with Tox EIA (43%). Among patients with geno typically confirmed reinfection (n = 8), CYT and EIA positivity was 63 % and 50 % respectively. For the remaining 11 episodes, TCD was not retrievable in culture, CYT and EIA positivity among this group was 27 % and 9 % respectively. Conclusion Forty percent of recurrent CDI episodes detected by PCR could not be confirmed by CYT. EIA missed 66 % of CYT positive recurrent CDI. The performance of CYT and EIA varied among recurrences due to relapse and reinfection. These results have significant implication for reporting of CDI HAI rates. Disclosures All authors: No reported disclosures.