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Key Points Question Is convalescent plasma therapy associated with improved outcomes of hospitalized patients with COVID-19 and hematologic cancer? Findings In this cohort study of 966 patients with hematologic cancer and COVID-19, after adjustment for potential confounding factors, convalescent plasma treatment was associated with a significantly improved 30-day mortality in the 143 individuals who received it. This association remained significant after propensity score matching. Meaning These findings suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic cancers and COVID-19., Importance COVID-19 is a life-threatening illness for many patients. Prior studies have established hematologic cancers as a risk factor associated with particularly poor outcomes from COVID-19. To our knowledge, no studies have established a beneficial role for anti–COVID-19 interventions in this at-risk population. Convalescent plasma therapy may benefit immunocompromised individuals with COVID-19, including those with hematologic cancers. Objective To evaluate the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic cancers and COVID-19 from a multi-institutional cohort. Design, Setting, and Participants This retrospective cohort study using data from the COVID-19 and Cancer Consortium registry with propensity score matching evaluated patients with hematologic cancers who were hospitalized for COVID-19. Data were collected between March 17, 2020, and January 21, 2021. Exposures Convalescent plasma treatment at any time during hospitalization. Main Outcomes and Measures The main outcome was 30-day all-cause mortality. Cox proportional hazards regression analysis with adjustment for potential confounders was performed. Hazard ratios (HRs) are reported with 95% CIs. Secondary subgroup analyses were conducted on patients with severe COVID-19 who required mechanical ventilatory support and/or intensive care unit admission. Results A total of 966 individuals (mean [SD] age, 65 [15] years; 539 [55.8%] male) were evaluated in this study; 143 convalescent plasma recipients were compared with 823 untreated control patients. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (HR, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity score matching (HR, 0.52; 95% CI, 0.29-0.92). Among the 338 patients admitted to the intensive care unit, mortality was significantly lower in convalescent plasma recipients compared with nonrecipients (HR for propensity score–matched comparison, 0.40; 95% CI, 0.20-0.80). Among the 227 patients who required mechanical ventilatory support, mortality was significantly lower in convalescent plasma recipients compared with nonrecipients (HR for propensity score–matched comparison, 0.32; 95% CI, 0.14-0.72). Conclusions and Relevance The findings of this cohort study suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic cancers and COVID-19., This cohort study evaluated the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic cancers and COVID-19.

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

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.

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.

Clostridioides difficile infection (CDI) is prevalent in pediatric oncology patients, but the transmission risk to peers is unknown. In 224 children with CDI, multilocus sequence typing (MLST) identified only 7 alleged transmission events (18%) originating from children

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.

Cefiderocol is a novel injectable siderophore cephalosporin that hijacks the bacterial iron transport machinery to facilitate cell entry and achieve high periplasmic concentrations. It has broad in vitro activity against gram-negative bacteria, including multidrug-resistant (MDR) organisms such as carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii. It was approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections and nosocomial pneumonia based on clinical trials that demonstrated noninferiority to comparators. In this review, we summarize the available in vitro and clinical data, including recent evidence from 2 phase 3 clinical trials (APEKS-NP and CREDIBLE-CR), and discuss the place of cefiderocol in the clinician’s armamentarium against MDR gram-negative infections.

SummaryConvalescent plasma may benefit immunocompromised individuals with COVID-19, including those with hematologic malignancy. We evaluated the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic malignancy and COVID-19 from a multi-institutional cohort. 143 treated patients were compared to 823 untreated controls. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (hazard ratio, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity-score matching (hazard ratio, 0.52; 95% CI, 0.29-0.92). These findings suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic malignancy and COVID-19.

Background New York City (NYC) experienced a surge of coronavirus disease 2019 (COVID-19) cases in March and April 2020. Since then, universal polymerase chain reaction (PCR)–based surveillance testing and personal protective equipment (PPE) measures are in wide use in procedural settings. There is limited published experience on the utility and sustainability of PCR-based surveillance testing in areas with receding and consistently low community COVID-19 rates. Methods The study was conducted at a tertiary care cancer center in NYC from 22 March to 22 August 2020. Asymptomatic patients underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing before surgeries, interventional radiology procedures, and endoscopy. Contact tracing in procedural areas was done if a patient with an initial negative screen retested positive within 48 hours of the procedure. Results From March 22 until August 22, 2020, 11 540 unique patients underwent 14 233 tests before surgeries or procedures at Memorial Sloan Kettering Cancer Center. Overall, 65 patients were positive, with a peak rate of 4.3% that fell below 0.3% after April 2020. Among the 65 positive cases, 3 were presymptomatic and 38 were asymptomatic. Among asymptomatic test-positive patients, 76% had PCR cycle threshold >30 at first detection. Five patients tested newly positive in the immediate postoperative period, exposing 82 employees with 1 case of probable transmission (1.2%). Conclusions The prevalence of SARS-CoV-2 infection identified on preprocedural surveillance was low in our study, which was conducted in an area with limited community spread at the later stage of the study. Universal PPE is protective in procedural settings. Optimal and flexible diagnostic strategies are needed to accomplish and sustain the goals of comprehensive preprocedure surveillance testing.

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.

Background The global struggle against antibiotic resistance requires antimicrobial stewardship (AMS). Massive open online courses (MOOCs) offer health professionals unprecedented access to high-quality instructional material on AMS; the question is how apprehensible it is to non-native English speakers. Furthermore, to better understand how education interventions promote change towards rational antibiotic prescribing, leading institutions call for studies integrating behavioural science. Research from lower- and middle-income countries is particularly needed. Objectives To measure the knowledge improvement from an AMS MOOC, the influence of language, course satisfaction and subsequent effect on intention to change antibiotic prescribing behaviour. Methods Fifty-five physicians from Macedonia completed the MOOC. Pre- and post-course knowledge test scores were compared using a one-sample t-test. The effect of a language barrier was assessed using self-reported English level. Scores were compared with participants’ intention to change behaviour in clinical practice. Results Scores significantly improved from 77.8% to 82.2%. Participants with a higher English level improved most, while the low-level group showed no significant improvement. Physicians reported a high or very high intention to change behaviour. This was independent of knowledge improvements. Conclusions First, lower self-reported English proficiency hindered knowledge acquisition from a MOOC platform. AMS programmes should commit to bridge this barrier so as to enable a global spread of education in AMS. Second, factors underlying the physicians’ intentions to engage in AMS appear to be more complex than simple knowledge improvements. This suggests that less time-consuming interventions could be as effective.

Two distinct clusters of gastroenteritis due to Salmonellae and Entamoeba histolytica (EH) were identified using a multiplex gastrointestinal pathogen panel (GPP) at a tertiary-care cancer center. Despite temporo-spatial overlap, our investigation did not corroborate transmission or true infection. In clinical practice, GPPs may render false-positive results.Infect Control Hosp Epidemiol 2018;867–870

Obtaining central venous access is one of the most commonly performed procedures in hospital settings. Multiple devices such as peripherally inserted central venous catheters, tunneled central venous catheters (eg, Hohn catheter, Hickman catheter, C. R. Bard, Inc, Salt Lake City UT), and implantable ports are available for this purpose. The device selected for central venous access depends on the clinical indication, duration of the treatment, and associated comorbidities. It is important for health care providers to familiarize themselves with the types of central venous catheters available, including information about their indications, contraindications, and potential complications, especially the management of catheters in the setting of catheter-related bloodstream infections. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Purpose of review Antimicrobial stewardship is the primary intervention in the battle against antimicrobial resistance, but clinicians do not always apply many key antimicrobial stewardship principles to patients with significant immune defects due to lack of data and fear of bad outcomes. We review evidence regarding the application of stewardship principles to immunocompromised patients, with a focus on solid organ and hematopoietic stem cell transplant recipients. Recent findings Antimicrobial stewardship programs (ASPs), targeting immunocompromised patient populations such as oncology and transplant, are gaining traction. Emerging literature suggests that several stewardship interventions can be adapted to immunocompromised hosts and improve antimicrobial utilization, but data supporting improved outcomes is very limited. Summary The application of antimicrobial stewardship principles to immunocompromised patients is feasible, necessary, and urgent. As antimicrobial stewardship programs gain momentum across a diverse range of healthcare settings more immunocompromised patients will fall under their purview. It is imperative that centers applying antimicrobial stewardship principles share their experience and establish collaborative research efforts to advance our knowledge base in applying antimicrobial stewardship initiatives to immunocompromised host populations, both in terms of programmatic success and patient outcomes.

Clostridioides difficile infection (CDI) is prevalent in pediatric oncology patients, but the transmission risk to peers is unknown. In 224 children with CDI, multilocus sequence typing (MLST) identified only 7 alleged transmission events (18%) originating from children

Despite successful vaccination programs, pertussis remains endemic in the United States, and increasing incidence has been reported. We used national surveillance data to describe pertussis epidemiology, including patient demographic characteristics, geographic distribution, and temporal trends.We included cases reported through the National Notifiable Diseases Surveillance System between 1 January 2000 and 31 December 2016. Differences in case characteristics were compared using Pearson χ2. Average annual incidence (cases per 100 000 population) was calculated overall and by age (1 year, 1-6 years, 7-10 years, 11-18 years, 19-39 years, 30-64 years, and ≥65 years) and geographic subgroup. Annual percent change was estimated using negative bionomial regression.During 2000-2016, 339 420 pertussis cases were reported. The majority were in white (88.2%) and non-Hispanic (81.3%) persons, 9.9% were hospitalized, and 0.1% were fatal; however, differences existed by age. Infants had the highest incidence (75.3/100 000 population), accounting for 88.8% of deaths. Incidence increased significantly over time (P = .0019), increases were observed for all groups except persons aged1 year and 19-64 years. Elevated case counts among persons aged 7-10 and 11-18 years coincided with the aging of acellular-primed cohorts. Incidence varied by geographic region, with some similarities in disease cyclicity.Increasing baseline incidence and changing age distribution of pertussis suggest a central role of the transition to acellular vaccines in the US disease resurgence. Continued monitoring of national data is important to evaluate and optimize pertussis prevention and control strategies.

An evidence-based triage plan for cellular therapy distribution is critical in the face of emerging constraints on healthcare resources. We evaluated the impact of treatment delays related to COVID-19 on patients scheduled to undergo hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy at our center. Data were collected in real time between March 19 and May 11, 2020, for patients who were delayed to cellular therapy. We evaluated the proportion of delayed patients who ultimately received cellular therapy, reasons for not proceeding to cellular therapy, and changes in disease and health status during delay. A total of 85 patients were delayed, including 42 patients planned for autologous HCT, 36 patients planned for allogeneic HCT, and 7 patients planned for CAR-T therapy. Fifty-six of these patients (66%) since received planned therapy. Five patients died during the delay. The most common reason for not proceeding to autologous HCT was good disease control in patients with plasma cell dyscrasias (75%). The most common reason for not proceeding to allogeneic HCT was progression of disease (42%). All patients with acute leukemia who progressed had measurable residual disease (MRD) at the time of delay, whereas no patient without MRD at the time of delay progressed. Six patients (86%) ultimately received CAR-T therapy, including 3 patients who progressed during the delay. For patients with high-risk disease such as acute leukemia, and particularly those with MRD at the time of planned HCT, treatment delay can result in devastating outcomes and should be avoided if at all possible.

Oncolytic viral immunotherapy is an emerging treatment modality for cancer that exploits in vivo replication and other viral properties to enhance immune killing of malignant cells. The potential for horizontal transmission of native or engineered oncolytic viruses creates several unique infection control challenges. In 2015, talimogene laherparepvec (TVEC) became the first agent in this class to gain FDA approval for treatment of melanoma, and several others are being developed. Although some data on the transmissibility of TVEC are available from clinical studies, the aftermarket or real-world experience remains limited. We conducted a PUBMED-based search of the medical literature focusing on the safety and risk of TVEC transmission to close contacts including healthcare workers. The findings are summarized in this review and are intended to provide infection preventionists with practical guidance on handling issues related to administration and care of patients receiving TVEC. Additionally, we describe the current mechanism for evaluating the risk related to similar new agents entering clinical trials at our institution. Development of standarized approaches for the safe administration and precautions for ongoing care, especially in immunocompromised patients, are essential to support the broad adoption of this novel therapy.

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.

Background Oncolytic viral immunotherapy is an emerging cancer treatment, but the infectious complications are not well described outside of clinical trials. Genetically engineered replication competent herpes simplex virus (HSV-1), commercially known as IMLGYIC® (AmGen) or talimogene laherparepvec (TVEC) was the first FDA approved agent in this class and is used for the local intralesional treatment (of unresectable melanoma. TVEC is derived from a wild-type(WT) strain of HSV-1 (JS—1), which is modified to attenuate off-target effects and promote selective proliferation within cancer cells. Despite these changes local and systemic infection with HSV have been reported from trials and is the subject of an FDA mandated post-marketing review. Here we review the infectious complications of the first cohort of patients treated at our institution post-FDA approval. Methods Demographic and clinical information for 52 adult patients treated for unresectable melanoma with TVEC following FDA approval in 2015 was extracted from the EMR for the period October 1, 2015–June 30, 2018. EMR and microbiologic data were reviewed for evidence of local site reaction and disseminated infection. Results No cases of disseminated HSV infection were identified during the study period. Of cutaneous reactions, none were documented as greater than severity grade 2, based on standard adverse event reporting criteria. 3 (50%) grade 1–2 cutaneous reactions were deemed probable or definitely related to TVEC and described as pruritis or rash. 12 (23%) patients had any microbiologically confirmed infection identified following TVEC therapy; 6 were bacterial (3 UTI, 1BSI, 2 wound). 8 episodes of viral infections occurred (5 respiratory and 3 GI). A single patient was noted to have localized HSV dermal lesions more than one year after the final TVEC. Conclusion No local or disseminated HSV infections were encountered in the study cohort. Bacterial skin and soft-tissue infection were uncommon. Most other infections were unrelated to TVEC therapy. Real-world review of the use of an HSV-derived oncolytic viral vector therapy mimics reported infectious complications from clinical trials. Disclosures All authors: No reported disclosures.

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.

Antibiotic treatment can deplete the commensal bacteria of a patient’s gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

Background Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI after engraftment. Methods Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample. Bacterial taxa with protective effects against development of CDI were identified by means of linear discriminant analysis effect size analysis and then further assessed with clinical predictors of CDI using survival analysis. Results A total of 234 allo-HSCT recipients were studied; postengraftment CDI developed in 53 (22.6%). Within the composition of the microbiota, the presence of 3 distinct bacterial taxa was correlated with protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae. Colonization with these groups at engraftment was associated with a 60% lower risk of CDI, independent of clinical factors. Conclusions Colonization with these 3 bacterial groups is associated with a lower risk of CDI. These groups have been shown to be vital components of the intestinal microbiota. Targeted efforts to maintain them may help minimize the risk of CDI in this at-risk population.

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.

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and 93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.

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 The utility of active surveillance and contact isolation of VRE colonized individuals has not been established in non-outbreak and hyperendemic settings. The practice is onerous and resource intensive, with a hospital wide impact on patient flow. There is growing body of evidence suggesting that routine isolation of VRE colonized patients may not be beneficial. At MSKCC, VRE colonization rates in BMT and ICU units are ~ 33%, individuals with colonization only account for 80 % of all new VRE cases. Active surveillance had not shown any significant reduction in incident VRE. The objective of this study was to analyze the first year after discontinuation of active surveillance and routine contact precautions for VRE in the ICU. Outcomes assessed were house wide VRE BSI rate, unit specific BSI rates, and VRE-related nosocomial outbreaks. VRE-specific isolation days were simultaneously monitored. Methods Beginning in September 2015, we discontinued active VRE surveillance and isolation of colonized individuals in our 20 bed ICU, followed a year later by our 25-bed transplant unit. VRE BSI rates were observed for a 12-month period following these changes. Results The baseline house wide VRE BSI rate was 0.31/1,000 patient days. After discontinuation of practice in ICU, the ICU rate remained unchanged over the following 12 months (pre: 0.88/1,000 patient days vs. post: 0.77/1,000 patient days; P value = 0.83). No significant difference was seen in house wide or unit specific rates after the policy was subsequently implemented in the BMT unit (Figure 1). No VRE-related outbreaks were detected. There was a 50% absolute reduction in isolation days for VRE between the pre- and post-intervention periods. Figure 1 Conclusion Discontinuation of active surveillance and contact isolation of colonized individuals did not result in an increase in incidence of VRE BSI rates in a hyperendemic setting. A reduction in isolation beds facilitated patient flow, especially access to critical care services. 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.

OBJECTIVETo determine the role of unit-based transmission that accounts for cases of early Clostridium difficile infection (CDI) during hospitalization for allogeneic stem cell transplant.SETTINGStem cell transplant unit at a tertiary care cancer center.METHODSSerially collected stool from patients admitted for transplant was screened for toxigenic C. difficile through the hospital stay and genotyping was performed by multilocus sequence typing. In addition, isolates retrieved from cases of CDI that occurred in other patients hospitalized on the same unit were similarly characterized. Transmission links were established by time-space clustering of cases and carriers of shared toxigenic C. difficile strains.RESULTSDuring the 27-month period, 1,099 samples from 264 patients were screened, 69 of which had evidence of toxigenic C. difficile; 52 patients developed CDI and 17 were nonsymptomatic carriers. For the 52 cases, 41 had evidence of toxigenic C. difficile on the first study sample obtained within a week of admission, among which 22 were positive within the first 48 hours. A total of 24 sequence types were isolated from this group; 1 patient had infection with the NAP1 strain. A total of 11 patients had microbiologic evidence of acquisition; donor source could be established in half of these cases.CONCLUSIONSMost cases of CDI after stem cell transplant represent delayed onset disease in nonsymptomatic carriers. Transmission on stem cell transplant unit was confirmed in 19% of early CDI cases in our cohort with a probable donor source established in half of the cases.Infect. Control Hosp. Epidemiol. 2015;37(1):8–15

SUMMARYNorovirus, an RNA virus of the familyCaliciviridae, is a human enteric pathogen that causes substantial morbidity across both health care and community settings. Several factors enhance the transmissibility of norovirus, including the small inoculum required to produce infection (

The continuing emergence of infections due to multidrug resistant bacteria is a serious public health problem. Klebsiella pneumoniae, which commonly acquires resistance encoded on mobile genetic elements, including ones that encode carbapenemases, is a prime example. K. pneumoniae carrying such genetic material, including both blaKPC and genes encoding metallo-β-lactamases, have spread globally. Many carbapenemase-producing K. pneumoniae are resistant to multiple antibiotic classes beyond β-lactams, including tetracyclines, aminoglycosides, and fluoroquinolones. The optimal treatment, if any, for infections due to these organisms is unclear but, paradoxically, appears to often require the inclusion of an optimally administered carbapenem.

Microbial whole-genome sequencing (WGS) is poised to transform many of the currently used approaches in medical microbiology. Recent reports on the application of WGS to understand genetic evolution and reconstruct transmission pathways have provided valuable information that will influence infection control practices. While this technology holds great promise, obstacles to full implementation remain. Two articles in this issue of the Journal of Clinical Microbiology ( S. Octavia, Q. Wang, M. M. Tanaka, S. Kaur, V. Sintchenko, and R. Lan , J Clin Microbiol 53:1063–1071, 2015, doi: 10.1128/JCM.03235-14 , and S. J. Salipante, D. J. SenGupta, L. A. Cummings, T. A. Land, D. R. Hoogestraat, and B. T. Cookson , J Clin Microbiol 53:1072–1079, 2015, doi: 10.1128/JCM.03385-14 ) describe the breadth of application of WGS to the field of clinical epidemiology.

Background Transmission of healthcare-associated Clostridium difficile infection (HA-CDI) has been shown to occur directly or indirectly through a contaminated environment. At a tertiary-care cancer center, HA-CDI rates were higher for pediatric units than for other general oncology units. To address the problem, a multidisciplinary team, including Infection Control, Nursing, and Environmental Services (EVS), was convened and identified refusals and room clutter as barriers to proper cleaning of rooms on the unit. Aim: The aim of this study seeks to reduce HA-CDI in the inpatient pediatrics setting through environmental and educational interventions. Methods In the first phase of the study from February to April 2016, a baseline assessment of prevalent environmental disinfection practices was made among Nursing, EVS, Physicians, and Patient Representatives. Based on this feedback, the following were implemented during Phase 2, from June through October 2016: 1) Unit-wide disinfection with bleach twice a day including common and high traffic areas; 2) Initiation of a “preferred time for cleaning” program to engage families; 3) Enhanced visitor and family education on PPE use; 4) Creation of a communication plan in case of refusal to clean rooms; and 5) Dedicated use of diaper scales. Results During the first phase of the study, the following barriers to cleaning were identified: 1) High refusal rate as cleaning was perceived as inconvenient by families due to timing; 2) Common perception among EVS staff that multiple requests for cleaning the room may appear intrusive to the families; 3) Excessive clutter in the room; 4) Lack of education regarding PPE use; and 5) Shared equipment for diapers. To overcome these barriers, several interventions as outlined in methods were implemented. In Phase 2, there were 0 cases of HA-CDI identified in pediatric patients starting in July through October, 2016. Conclusion Control of CDI on pediatric units poses unique challenges. Engagement of key stakeholders is essential to identify and meet these challenges and to devise effective strategies that will ultimately lead to reduced hospital-based transmission of CDI. Disclosures All authors: No reported disclosures.