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Background Candidemia is a common hospital acquired infection that is associated with significant morbidity and mortality. The optimal strategy for diagnosis remains unknown. Methods We evaluated 2 distinct diagnostic strategies in hospitalized patients with suspicion of Candida bloodstream infection, namely strategy #1 that included simultaneous blood cultures and T2Candida and strategy #2 that included blood cultures, T2Candida testing and Beta-D-glucan (BDG). We examined the consistency with which each diagnostic algorithm led to changes in antifungal prescribing, the overall rate of antifungal utilization and patients’ clinical outcomes. Flow Chart. Figure 1. Results Among 96 patients tested with strategy #1, 3 had a positive result. Of those 100% completed a 14-day antifungal course for candidemia or were on antifungals until hospital discharge. Of the 29 out 120 patients that tested positive with strategy #2, 55.2% received a complete 14-day course or were on antifungals until hospital discharge. The percentage of completed treatment increased to 75.0% and 80.0% when the threshold for BDG positivity was increased at 200 pg/ml and 500 pg/ml respectively. We observed a significant difference in the overall antifungal utilization with 268.5 days of antifungals per 1,000 patient days for strategy #1, as opposed to 371.9 days of antifungals for strategy #2, a 38.5% increase. Negative tests at both diagnostic strategies led to a similar rate of antifungal discontinuation 3 days after testing (36.8% and 37.0% for strategy #1 and #2 respectively). We did not find significant benefits in death and/or subsequent diagnosis of candidemia between the 2 diagnostic strategies. Sensitivity analyses performed based on indication for testing and severity of illness did not significantly alter results. Table 1.Characteristics of patients tested for suspicion of candidemia with the 2 diagnostic strategies. Figure 2. Duration of antifungal therapy among patients with positive BDG at different thresholds A. BDG Figure 3. Percentage of patients who were taken off antifungals within 3 days of testing for different BDG thresholds, BDG Conclusion In summary, the addition of BDG in diagnostic algorithms for candidemia was interpreted variably by clinicians, was associated with a significant increase in antifungal utilization, and it did not appear to lead to measured clinical benefits for patients. Diagnostic strategies of common and serious infections that incorporate non-culture diagnostics need to be evaluated for added benefit. Table 2.Antifungal utilization among patients tested for suspicion of candidemia with the 2 diagnostic strategies. Table 3. Outcomes among patients tested for suspicion of candidemia with the two different diagnostic strategies. Disclosures All Authors: No reported disclosures.

Objectives: We evaluated the value of BioFire® FilmArray® pneumonia panel in establishing a microbiological diagnosis of pneumonia. We evaluated opportunities for antimicrobial optimization from its use. Methods: We included adult patients with pneumonia between May 2019 and January 2020. The pneumonia panel was used on high-quality sputum specimens, and the results were prospectively compared with sputum cultures and other tests performed according to standard of care. Results: Seventy patients were included, sixty-nine of whom completed a 5-day antimicrobial course for pneumonia, and 14.3% died during hospitalization. There was a trend of higher rate of microbiological diagnosis among the patients with culture submitted before antimicrobial administration (9/15 vs. 20/55; p = 0.09). The panel increased the microbiological diagnosis from 29/70 to 59/70 (p < 0.001) patients. The per isolate analysis revealed an increase in the isolation of Haemophilus influenzae (p = 0.002) and Streptococcus pneumoniae (p = 0.05). On review of empiric antimicrobials, there was potential for antimicrobial optimization in 56/70 patients, including 9 bacteria among 9 patients, which were not covered by empiric treatment and another 70 antimicrobials in 49 patients that could have been stopped. Conclusions: Incorporation of the pneumonia panel in the diagnostic work-up of pneumonia substantially increased the rate of microbiological diagnosis and revealed abundant opportunities for antimicrobial optimization.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Background Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. Methods This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients’ outcomes. Results We evaluated 910 patients, 121 (13.3%) of whom were PUAT positive. No difference in baseline characteristics, including severity of illness, was observed between groups. Initial de-escalation occurred in 82.9% and 81.2% of PUAT-positive and -negative patients, respectively (P = .749). Median time to de-escalation was shorter in the PUAT-positive group (1 [interquartile range {IQR}, 0–2] day vs 1 [IQR, 1–2] day, P = .01). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%, P = .026) without difference in methicillin-resistant Staphylococcus aureus (MRSA) agent discontinuation (or antipseudomonal de-escalation). Among the PUAT-positive group, unadjusted analysis demonstrated shorter median length of stay in patients who were de-escalated compared to those who were not (6 [IQR, 4–10] vs 8 [IQR, 7–12] days, P = .0005), without difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission. Conclusions We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.

Coronavirus disease 2019 (COVID-19) reverse-transcription polymerase chain reaction employee testing was implemented across New York University Langone Health. Over 8 weeks, 14 764 employees were tested; 33% of symptomatic employees, 8% of asymptomatic employees reporting COVID-19 exposure, and 3% of employees returning to work were positive. Positivity rates declined over time, possibly reflecting the importance of community transmission and efficacy of personal protective equipment.

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS‐CoV‐2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)‐confirmed coronavirus disease 2019 (COVID‐19). Serum samples were collected 1–59 days post‐onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR‐confirmed COVID‐19 and samples collected during convalescence, 35–57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS‐CoV‐2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection., Highlights IgA was the predominant immunoglobulin detected in early COVID‐19 disease.IgA levels were highest in patients with a severe and critical illness.IgG antibodies remained detectable in almost 90% of samples collected up to 2 months after infection.

Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, and 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates.

Understanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Recent studies showed that serum from convalescent patients can display variable neutralization capacities. Still, it remains unclear whether there are specific signatures that can be used to predict neutralization. Here, we performed a detailed analysis of sera from a cohort of 101 recovered healthcare workers and we addressed their SARS-CoV-2 antibody response by ELISA against SARS-CoV-2 Spike receptor binding domain and nucleoprotein. Both ELISA methods detected sustained levels of serum IgG against both antigens. Yet, the majority of individuals from our cohort generated antibodies with low neutralization capacity and only 6% showed high neutralizing titers against both authentic SARS-CoV-2 virus and the Spike pseudotyped virus. Interestingly, higher neutralizing sera correlate with detection of -IgG, IgM and IgA antibodies against both antigens, while individuals with positive IgG alone showed poor neutralization response. These results suggest that having a broader repertoire of antibodies may contribute to more potent SARS-CoV-2 neutralization. Altogether, our work provides a cross sectional snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides preliminary evidence that possessing multiple antibody isotypes can play an important role in predicting SARS-CoV-2 neutralization.

Background The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Methods We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. A linear mixed-effects regression analysis was performed. Results Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p < 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms. Flow chart A graph of the Cycle Threshold (Ct) values of the of Cepheid Xpert® Xpress SARS-CoV-2 assay measured on repeat screening of the 42 included patients. Graph of the fitted SOFA scores based on the Cycle Threshold values per patient. Conclusion Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. Disclosures All Authors: No reported disclosures

Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2, as reflected by the Cycle threshold (Ct) value of the RT-PCR, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients’ clinical status. Among 457 patients with COVID-19 pneumonia between 3/31/2020-4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2–3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID‐19. However, there have been no reports of status epilepticus after recovery from COVID‐19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID‐19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS‐CoV‐2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID‐19.

Introduction It is common among microbiology laboratories to blind the Clostridioides difficile (C. difficile) BioFire FilmArray GI Panel result in fear of overdiagnosis. Methods We examined the rate of missed community-onset C. difficile infection (CDI) diagnosis and associated outcomes. Adult patients with FilmArray GI Panel positive for C. difficile on hospital admission who lacked dedicated C. difficile testing were included. Results Among 144 adults with a FilmArray Panel positive for C. difficile, 18 did not have concurrent dedicated C. difficile testing. Eight patients were categorized as possible, 5 as probable and 4 as definite cases of missed CDI diagnosis. We observed associated delays in initiation of appropriate therapy, intensive care unit admissions, hospital readmissions, colorectal surgery and death/discharge to hospice. Five out of 17 lacked risk factors for CDI. Conclusion The practice of concealing C. difficile FilmArray GI Panel results needs to be reconsidered in patients presenting with community-onset colitis.

Understanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Here, we determine the ability of sera from 101 recovered healthcare workers to neutralize both authentic SARS-CoV-2 and SARS-CoV-2 pseudotyped virus and address their antibody titers against SARS-CoV-2 nucleoprotein and spike receptor-binding domain. Interestingly, the majority of individuals have low neutralization capacity and only 6% of the healthcare workers showed high neutralizing titers against both authentic SARS-CoV-2 virus and the pseudotyped virus. We found the antibody response to SARS-CoV-2 infection generates antigen-specific isotypes as well as a diverse combination of antibody isotypes, with high titers of IgG, IgM and IgA against both antigens correlating with neutralization capacity. Importantly, we found that neutralization correlated with antibody titers as quantified by ELISA. This suggests that an ELISA assay can be used to determine seroneutralization potential. Altogether, our work provides a snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides evidence that possessing multiple antibody isotypes may play an important role in SARS-CoV-2 neutralization.

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2., The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real-time reverse transcription-PCR (RT-PCR) platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. The two platforms demonstrate comparable performances; however, the run times for each assay are 3.5 h and 45 min, respectively. In search for a platform with a shorter turnaround time, we sought to evaluate the recently released Abbott ID Now COVID-19 assay, which is capable of producing positive results in as little as 5 min. We present here the results of comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID Now COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID Now. Regardless of method of collection and sample type, Abbott ID Now COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

RationaleThe Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.ObjectivesWe explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.MethodsA retrospective cohort study among adult patients admitted to the hospital between March 31st to April 10th, 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) ≥35), intermediate (25MeasurementsA composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI).Main ResultsOf 457 patients with COVID-19 pneumonia from March 31st to April 10th, 2020, 316 met inclusion criteria. Included patients were followed for a median of 25days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (pConclusionsOur findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.

The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.

Background Limited data support the use of pneumococcal urinary antigen testing (PUAT) for patients admitted with community-acquired pneumonia (CAP) as a stewardship tool to curtail the use of broad-spectrum antimicrobials. At NYULH, CAP guidelines and admission order set were developed to standardize diagnostic testing, including PUAT. In this study we describe patients with positive versus negative PUAT and evaluate de-escalation and patients’ outcomes. Methods This was a retrospective study of adults admitted with diagnosis of CAP between January-December 2019 who had a PUAT performed. The primary outcome was incidence and timing of de-escalation of antimicrobials following PUAT result. Among patients with a positive PUAT we compared hospital length of stay (LOS), incidence of Clostridioides difficile infection (CDI), infection-related readmission within 30 days, and in-hospital mortality among those who were de-escalated versus those who were not de-escalated/required escalation. Results We evaluated 910 patients, of which 121 (13.3%) were PUAT positive. No difference in baseline characteristics, including severity of illness as represented by the Pneumonia Severity Index (97 [IQR 76-117] vs 89 [IQR 67-115], p=0.083) and Charlson Comorbidity Index, were observed between PUAT positive and negative groups. Time to PUAT testing occurred shortly after presentation to the hospital in both cohorts (16h [IQR 16-27] vs 13h [IQR 8-22], p=0.140). Initial de-escalation occurred in 97/117 (82.9%) and 629/775 (81.2%) of PUAT positive and negative patients, respectively (p = 0.749). Median time to de-escalation was shorter in the PUAT positive cohort (1 [IQR 0-2] vs 1 [IQR 1-2] day, p = 0.01). Among the PUAT positive group, hospital LOS stay was shorter in patients who were de-escalated compared to those who were not de-escalated/required escalation (6 days [IQR 4-10] vs 8 days [IQR 7-12], p=0.0005) with no difference in the incidence of CDI (2 [2.1%] vs 1 [3.7%], p=0.535), in-hospital mortality (4 [4.3%] vs 3 [11.1%], p=0.185), or 30-day infection-related readmission (2 [2.1%] vs 1 [3.7%], p=0.535). Conclusion PUAT positivity resulted in quicker time to targeted therapy for CAP. Among patients with a positive PUAT, initial de-escalation of antimicrobials did not lead to worse patient outcomes. Disclosures All Authors: No reported disclosures

A 39-year-old man presented to the Bellevue Hospital emergency department in November with 1 week of fevers and cough. On the previous day, he had been assaulted, developing right buttock and thigh pain. His medical history was notable for alcohol use disorder treated with the opioid antagonist

Background SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes. Methods We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) ≥35) intermediate (25< Ct< 35) and high (Ct ≤25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints. Results Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21–28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p< 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses. Flow Chart Prediction of Outcomes Based on Genomic Load Prediction of Outcomes Based on Genomic Load and Pneumonia Severity Index Conclusion High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic. Disclosures All Authors: No reported disclosures

Background: Whole-genome sequencing (WGS) has a high discriminatory power in confirming outbreaks. Outbreak investigation models that categorize the possibility of an outbreak based on the degree of genetic relatedness of isolates are highly dependent on the single-nucleotide polymorphism (SNP) threshold used. Methods: NYU Langone Medical center is a 725-bed academic center that has implemented WGS of methicillin-resistant Staphylococcus aureus (MRSA) isolates since 2016. Patients admitted to a medical or intensive care unit were screened on admission and transfer. The first surveillance and clinical MRSA isolate during each hospitalization was sequenced. We conducted a retrospective analysis to identify strong epidemiologic links among patients involved in genetically related clusters. We used different SNP thresholds to define genetic relatedness to identify the optimal threshold that should prompt an outbreak investigation. We considered strong hospital epidemiologic links sharing the same room or unit or having resided in the same room or unit within 7 days. A pairwise analysis was conducted to compare the epidemiologic links among patients involved in genetically related clusters. Results: Among 1,070 isolates, our analysis focused on 777 belonging to USA100 and USA300 clones. For USA100 isolates, we identified 8, 14, and 20 clusters comprising of 16, 29, and 42 patients when the threshold for genetic relatedness was set at 20, 40, and 60 SNP differences, respectively. Patients identified in a cluster yielded a strong hospital epidemiologic link in 62.5%, 87.5%, and 91.7% of cases (Fig. 1). For USA300 isolates, SNP differences of 10, 20, and 30 were used, identifying 20, 34, and 40 clusters of 43, 79, and 127 patients. The expansion of the threshold from 10 to 30 resulted in a decrease of the percentage of pairwise analyses with a strong hospital epidemiologic link from 57.7% to 13.6% by increasing 13-fold the number of analyses that were conducted to identify only 3 times more cases with strong epidemiologic links (Fig. 2). Conclusions: The results of our study indicate that SNPs thresholds determined by intrapatient variability of MRSA isolates might need to be tailored to the individual setting to guide infection control interventions because optimal thresholds might vary depending on characteristics of the population, MRSA isolates, and screening practices. Establishing conservative thresholds might allow the identification and quantification over time of the locations (eg, rooms or units) where transmission is occurring as well as the investigation of the clusters without strong epidemiologic links that might be valuable in elucidating unrecognized routes of transmission.Funding: NoneDisclosures: None

Background: Contaminated surfaces within patient rooms and on shared equipment is a major driver of healthcare-acquired infections (HAIs). The emergence of Candida auris in the New York City metropolitan area, a multidrug-resistant fungus with extended environmental viability, has made a standardized assessment of cleaning protocols even more urgent for our multihospital academic health system. We therefore sought to create an environmental surveillance protocol to detect C. auris and to assess patient room contamination after discharge cleaning by different chemicals and methods, including touch-free application using an electrostatic sprayer. Surfaces disinfected using touch-free methods may not appear disinfected when assessed by fluorescent tracer dye or ATP bioluminescent assay. Methods: We focused on surfaces within the patient zone which are touched by the patient or healthcare personnel prior to contact with the patient. Our protocol sampled the over-bed table, call button, oxygen meter, privacy curtain, and bed frame using nylon-flocked swabs dipped in nonbacteriostatic sterile saline. We swabbed a 36-cm2 surface area on each sample location shortly after the room was disinfected, immediately inoculated the swab on a blood agar 5% TSA plate, and then incubated the plate for 24 hours at 36°C. The contamination with common environmental bacteria was calculated as CFU per plate over swabbed surface area and a cutoff of 2.5 CFU/cm2 was used to determine whether a surface passed inspection. Limited data exist on acceptable microbial limits for healthcare settings, but the aforementioned cutoff has been used in food preparation. Results: Over a year-long period, terminal cleaning had an overall fail rate of 6.5% for 413 surfaces swabbed. We used the protocol to compare the normal application of either peracetic acid/hydrogen peroxide or bleach using microfiber cloths to a new method using sodium dichloroisocyanurate (NaDCC) applied with microfiber cloths and electrostatic sprayers. The normal protocol had a fail rate of 9%, and NaDCC had a failure rate of 2.5%. The oxygen meter had the highest normal method failure rate (18.2%), whereas the curtain had the highest NaDCC method failure rate (11%). In addition, we swabbed 7 rooms previously occupied by C. auris–colonized patients for C. auris contamination of environmental surfaces, including the mobile medical equipment of the 4 patient care units that contained these rooms. We did not find any C. auris, and we continue data collection. Conclusions: A systematic environmental surveillance system is critical for healthcare systems to assess touch-free disinfection and identify MDRO contamination of surfaces.Funding: NoneDisclosures: None

Background:Staphylococcus aureus–colonized hospitalized patients are at risk for invasive infection and can transmit S. aureus to other patients in the absence of symptoms. Infection isolation precautions do not reduce the risk of infection in colonized patients and are untenable in health systems with high rates of S. aureus colonization. Objective: We implemented an inpatient S. aureus screening and targeted decolonization program across hospital campuses to reduce transmission and invasive infection. We screen and decolonize for methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) because MSSA makes up more than half of all S. aureus isolated from clinical cultures in our health system. Methods: All medicine, pediatrics, and transplant patients receive S. aureus nares culture at admission and upon change in level of care for medicine, and at admission and weekly for pediatrics and transplant patients. All S. aureus–colonized patients receive decolonization with nasal mupirocin ointment and chlorhexidine baths. Two implementation frameworks guide our processes for S. aureus screening and decolonization: the Consolidated Framework for Implementation Research, to evaluate factors affecting implementation at different levels of the health system, and the Dynamic Sustainability Framework, to account for iterative changes as the hospital setting and patient population change over time. Implementation interventions focus on education of patients and bedside nurses who perform S. aureus screening and decolonization; utilization of the electronic health record to identify patients for screening and/or decolonization and avoid human error; and introduction of a clinical nurse specialist to oversee the program and to provide iterative feedback. Results: At baseline, 21% of patients had S. aureus colonization, 20% of which was MRSA, and the MRSA bloodstream infection rate was 0.06 per 1,000 patient days. After program implementation, there was no change in S. aureus colonization and the MRSA bloodstream infection rate fell to 0.04 per 1,000 patient days. Screening compliance improved from 39% (N = 1,805) of eligible patients in the 6-month period before the introduction of the clinical nurse specialist to 52% (N = 2,024) after the introduction of the clinical nurse specialist. In the same periods, decolonization increased from 18.6% to 41% of eligible patients. Conclusions: We used 2 implementation frameworks to design our S. aureus screening and decolonization program and to make iterative changes to the program as it evolved to include new patient populations and different hospital settings. This resulted in a large-scale, sustainable, health system program for S. aureus control that avoids reliance on infection isolation precautions.Funding: NoneDisclosures: None

Genetic diversity of Anaplasma phagocytophilum was assessed in specimens from 16 infected patients and 16 infected Ixodes scapularis ticks. A region immediately downstream of the 16S rRNA gene, which included the gene encoding SdhC, was sequenced. For the A. phagocytophilum strains from patients no sequence differences were detected in this region. In contrast, significantly fewer ticks had a sequence encoding SdhC that was identical to that of the human strains (11/16 vs. 16/16, p = 0.04). This variation is consistent with the premise that not all A. phagocytophilum strains present in nature are able to cause clinical illness in humans. A strain referred to as A. phagocytophilumVariant-1 that is regarded as non-pathogenic for humans was previously described using a different typing method. Data from the current study suggest that both typing methods are identifying the same non-pathogenic strains.

Background Pneumonia is a leading cause of hospitalization and mortality. Due to the low yield of available diagnostic tests, ATS/IDSA pneumonia guidelines recommend a microbiologic work-up only for hospitalized patients with severe pneumonia. Methods From 5/2019 to 1/2020, we selected adult patients with clinical and radiographic findings highly suggestive of pneumonia. The BioFire® FilmArray® pneumonia panel was performed on sputum specimens that met quality microbiologic criteria and the results were compared to those of sputum cultures and other tests sent per standard of care. A limit of 105 copies/mL was used for positivity in semi-quantitative bacterial targets. The empiric antimicrobial regimen was reviewed to quantify the potential for antimicrobial optimization. Results Seventy patients were included in the analysis. Median age was 70 (IQR 53.5–81.75), and the majority (43 patients, 61.4%) were classified as Class IV and V using the pneumonia severity index, indicating severe cases of pneumonia. Sixty-nine patients completed at least a 5-day course for pneumonia and 14.3% died during their hospitalization. The fifteen patients (21.4%) that submitted a sputum culture before the initiation of antimicrobial therapy, had a trend towards a positive sputum culture (60% (9/15) vs 36.4% (20/55)) (p=0.09). The BioFire® FilmArray® pneumonia Panel increased the number of patients who received a microbiologic diagnosis from 29 (41%) to 59 (84.3%) (p< 0.001). The per isolate analysis revealed significantly more targets detected for Haemophilus influenzae (p=0.002) and Streptococcus pneumoniae (p=0.05). On review of empiric antimicrobial treatment, there was possibility for antimicrobial optimization in 80% of patients, including 9 cases of pathogens (4 MRSA, 3 Legionella pneumophila, 2 CTX-M gram-negative rods) where the pathogens were not covered and another 70 antimicrobials in 49 patients that could be stopped. Flow chart Bacterial Pathogens Detected in Standard of Care Alone Testing and with the Addition of Pneumonia Panel. Potential for Antimicrobial Optimization Using the Pneumonia Panel Conclusion Incorporation of the pneumonia panel in the diagnostic work-up of patients hospitalized with pneumonia substantially increased the rate of microbiologic diagnosis and had the potential to guide appropriate antimicrobial therapy. Future studies to quantify the effects on clinical outcomes and cost-effectiveness from tailored therapy are needed. Disclosures All Authors: No reported disclosures

In the United States, laboratories frequently offer multiple different assays for testing of cerebrospinal fluid (CSF) samples to provide laboratory support for the diagnosis of central nervous system Lyme disease (CNSLD). Often included among these diagnostic tests are the same enzyme immunoassays and immunoblots that are routinely used to detect the presence of antibodies to Borrelia burgdorferi in serum. However, performing these assays on CSF alone may yield positive results simply from passive diffusion of serum antibodies into the CSF. In addition, such tests are only U.S. Food and Drug Administration cleared and well validated for testing serum, not CSF. When performed using CSF, positive results from these assays do not establish the presence of intrathecal antibody production to B. burgdorferi and therefore should not be offered. The preferred test to detect intrathecal production of antibodies to B. burgdorferi is the antibody index assay, which corrects for passive diffusion of serum antibodies into CSF and requires testing of paired serum and CSF collected at approximately the same time. However, this assay also has limitations and should only be used to establish a diagnosis of CNSLD in conjunction with patient exposure history, clinical presentation, and other laboratory findings.

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age

Background Although blood cultures are the clinical diagnostic standard for candidemia, their delay in results and low sensitivity has lead to increasing the use of alternate tests and diagnostic algorithms. The T2Candida magnetic resonance assay (T2C) results in a few hours, but concomitant cultures are also needed. We compared results from the T2C with β-d-glucan (BDG), blood cultures (BCx) and the Candida Sepsis Score (CSc) in diagnosis and management of candidemia. Methods This retrospective observational study included patients from July 2017 to December 2018 who had a T2C as well as BCx. Positive (+) and negative (–) results of BCx and BDG within 24 hours (24 h) of T2C were recorded, with clinical data to determine CSc at the time of T2C (recent surgery, severe sepsis, parenteral nutrition, multifocal candida colonization). Results There were 648 T2Cs done over the study period. Only the first +T2C for patients with multiple T2Cs on admission was included. There were 41 patients with +T2, in which 31 had a 24hBCx. Two patients were of pediatric age. There were 7 neutropenic, 1 post-transplant, and 27 intensive care (ICU) patients. Reasons for ordering T2C included sepsis and persistent fevers. In 18 (44%) patients, antifungals were given prior to the T2C. Eight among 31 24hBCx were positive for concordant Candida spp. (26%). Six of these 8 patients were on antifungal therapy when T2C was sent. Seventeen patients had a 24hBDG, with 7 positive (41%). Overall mean CSc in 27 ICU patients with +T2C was 2.2 ± 0.8, and 40% of adult non-neutropenic ICU patients had a CSc of 3 or above. A central line was present in 26 patients, and was removed in 16 after +T2. In 213 patients with −T2C who had 24hBCx, only 1 BCx was positive, from a PICC line in a 2-year-old patient. Seven of the 41 patients with +T2C were treated for deep-seated candidiasis with 6 weeks antifungal therapy or longer; others received 1 to 4 weeks. Thirteen patients died while on antifungal therapy. Conclusion T2Candida was used for diagnosis and management of candidemia in patients who had concomitant blood culture positive in 26%, β-d-glucan positive in 41%, and ICU Candida sepsis score 3 or above in 40% patients. It did not miss candidemia in adults, compared with blood culture within 24 hours. Positive T2Candida helped expedite source control e.g line removal. Disclosures All authors: No reported disclosures.

Health-care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are pathogen-specific. We describe a system, FilmArray®Trend, for rapid disease reporting that is syndrome-based but pathogen-specific. Results from a multiplex molecular diagnostic test are sent directly to a cloud database.www.syndromictrends.compresents these data in near real-time. Trend preserves patient privacy by removing or obfuscating patient identifiers. We summarize the respiratory pathogen results, for 20 organisms from 344,000 patient samples acquired as standard of care testing over the last four years from 20 clinical laboratories in the United States. The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks and adenovirus and bacterial pathogens show constant detection over the year. Interestingly, the rate of pathogen co-detections, on average 7.7%, matches predictions based on the relative abundance of organisms present.

The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae , we identified three clinical isolates, CN1, CR14, and NY9, carrying both bla CTX-M and bla KPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, bla CTX-M and bla KPC were carried on two different plasmids. In contrast, CN1 had one copy of bla KPC-2 and three copies of bla CTX-M-15 integrated in the chromosome, for which the bla CTX-M-15 genes were linked to an insertion sequence, IS Ecp1 , whereas the bla KPC-2 gene was in the context of a Tn 4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn 4401a-bla KPC-2 -prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)- cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR- cas in K. pneumoniae strains and suggested that the evolving CRISPR- cas , with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of bla CTX-M and bla KPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae . Additionally, the implications from this study also raise concerns for the application of a CRISPR- cas strategy against antimicrobial resistance.

The diagnosis of Lyme disease is a controversial topic. Most practitioners and scientists recognize that Lyme disease is associated with certain objective clinical manifestations supported by laboratory evidence of infection with Borrelia burgdorferi sensu lato (the etiologic agent). There are others, however, who believe that patients with Lyme disease may have a wide variety of entirely nonspecific symptoms without any objective clinical manifestation and that laboratory evidence of infection by B. burgdorferi is not required to support the diagnosis. In reality, this perspective is not evidence based and would inevitably lead to innumerable misdiagnoses, given the high frequency of medically unexplained symptoms, such as fatigue and musculoskeletal pains, in the general population. Although those espousing this viewpoint do not believe that a positive laboratory test is required, nevertheless, they often seek out and promote alternative, unapproved testing methods that frequently provide false-positive results to justify their diagnosis. Herein, we provide a brief overview of Lyme disease testing, emphasizing current usage and limitations. We also discuss the use of nonvalidated procedures and the prospects for a reduction in such testing practices in the future.

Background It is common practice among microbiology laboratories in the United States to blind the BioFire FilmArray GI Panel results for Clostridioides (Clostridium) difficile (C. difficile) in fear of over-diagnosis of C. difficile infection (CDI). Methods We conducted a retrospective cohort study in 2 tertiary academic centers in New York to examine the rate of missed CDI diagnosis and the associated adverse outcomes from blinding the BioFire FilmArray GI Panel results for C. difficile. Of note, in one of the two included hospitals the list of daily positives is reviewed by an Infectious Diseases attending to determine whether cases have been tested for CDI and if not if they meet criteria for CDI. Adult patients with FilmArray GI Panel positive for C. difficile on admission to the hospital who lacked dedicated testing for C. difficile were included in the analysis and were stratified as possible, probable and definite cases of missed CDI diagnosis. Results Among the 144 adult patients with a FilmArray GI Panel test positive for C. difficile within 48 hours of hospital admission, 18 did not have a concurrent dedicated C. difficile testing. Eight patients were categorized as possible cases of missed CDI diagnosis, 5 as probable and 4 as definite, for a total of 17 cases of at least possibly missed CDI diagnosis. One case was considered to represent C. difficile colonization rather than infection for a rate of 6.9% of CDI over-diagnosis based on the FilmArray GI Panel results. Missed CDI diagnoses were associated with a delay in initiation of appropriate therapy, admission to the intensive care unit, hospital re-admission, colorectal surgery and death/discharge to hospice. Five out of 17 cases of missed CDI diagnosis (29.4%) lacked traditional risk factors for CDI. Conclusion In conclusion, the practice of concealing FilmArray GI Panel results for C. difficile may lead to a higher rate of missed CDI diagnosis than over-diagnosis and might need to be re-considered at least in patients with community-onset colitis of unknown etiology on presentation to the hospital. Disclosures All authors: No reported disclosures.

Lyme disease is transmitted by the bite of certain Ixodes ticks, which can also transmit Anaplasma phagocytophilum , the cause of human granulocytic anaplasmosis (HGA). Although culture can be used to identify patients infected with A. phagocytophilum and is the microbiologic gold standard, few studies have evaluated culture-confirmed patients with HGA. We conducted a prospective study in which blood culture was used to detect HGA infection in patients with a compatible clinical illness. Early Lyme disease was defined by the presence of erythema migrans. The epidemiologic, clinical, and laboratory features of 44 patients with culture-confirmed HGA were compared with those of a convenience sample of 62 patients with early Lyme disease. Coinfected patients were excluded. Patients with HGA had more symptoms ( P = 0.003) and had a higher body temperature on presentation ( P < 0.001) than patients with early Lyme disease. HGA patients were also more likely to have a headache, dizziness, myalgias, abdominal pain, anorexia, leukopenia, lymphopenia, thrombocytopenia, or elevated liver enzymes. A direct correlation between the number of symptoms and the duration of illness at time of presentation (rho = 0.389, P = 0.009) was observed for HGA patients but not for patients with Lyme disease. In conclusion, although there are overlapping features, culture-confirmed HGA is a more severe illness than early Lyme disease.

For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice.

Background. Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more symptoms than patients with Lyme disease alone. Methods. Blood culture and serology were used to detect HGA infection in patients with early Lyme disease who presented with erythema migrans. The rate of coinfection was determined using different definitions. The clinical and laboratory features of Lyme-HGA coinfection were compared with that of the individual infections. Results. Among 311 patients with erythema migrans, the frequency of coinfection with HGA varied from 2.3% to 10.0%, depending on the definition used (P< .001). Only 1 of 4 groups with presumed coinfection had significantly more symptoms than patients with Lyme disease alone P< .05. High fever and cytopenia were less common in Lyme-HGA coinfection than in patients with HGA alone. Conclusion. The results of this study indicate that how HGA is defined in patients with early Lyme disease has an impact on the apparent rate of coinfection and the severity of illness. The findings also suggest that HGA may be less severe than is usually believed, suggesting the existence of referral bias in testing patients preferentially who present with high fever or cytopenia.

Background: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. Objective: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. Methods: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. Results: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. Conclusions: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

Since the year 2000, linezolid has been used in the United States to treat infections caused by antimicrobial-resistant Gram-positive cocci. At present, linezolid-resistant (Lin r ) Staphylococcus aureus and Staphylococcus epidermidis strains are rare and the diversity of their genetic backgrounds is unknown. We performed sequence-based strain typing and resistance gene characterization of 46 Lin r isolates that were collected from local and national sources between the years 2004 and 2007. Resistance was found to occur in at least three clonal complexes (CCs; lineages) of S. aureus and in at least four subclusters of a predominant, phylogenetically unstable CC of S. epidermidis . New candidate resistance mutations in 23S rRNA and the L4 riboprotein were identified among the S. epidermidis isolates. These findings suggest that linezolid resistance has emerged independently in multiple clones of S. aureus and with a variety of ribosomal mutations in multiple clones of S. epidermidis .

Background Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection. Methods Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed. Results With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity. Conclusions Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity.

Lyme disease, relapsing fever, and leptospirosis are infections caused by spirochetes, a phylogenetically ancient and distinct group of microorganisms among the prokaryotes.

We describe the clinical and laboratory manifestations and pregnancy outcomes of 6 women who received a diagnosis of human granulocytic ehrlichiosis during pregnancy. Human granulocytic ehrlichiosis did not seem to present in a fulminant fashion, and all treated patients had excellent responses to rifampin or doxycycline therapy. Perinatal transmission was documented in 1 neonate, who responded well to treatment. There do not appear to be any long-term adverse sequelae in children born from these pregnancies (mean follow-up duration, 21 months).

Introduction This session was designed to teach OB-GYN and pathology residents the concepts behind regulatory requirements for laboratory testing in clinical settings. Point-of-care (POC) testing and provider-performed microscopy (PPM) are procedures done frequently in the ambulatory and in-patient setting, but residents are not exposed to the rule set and regulations behind them. Pathology residents do not regularly interact with clinical residents and may not understand the clinical environment in which POC testing and PPM are occurring. We utilized a case-based approach to teach the concepts, as well as skills stations to teach hands-on tasks. Methods The 2-hour session began with a 10-minute introduction and orientation of participants to the flow of events and to setting rules and expectations. Three case-based discussions occurred, each taking 30 minutes. One of the participants read a case aloud, the case was discussed by the group, and residents were asked to answer a series of questions. OB-GYN and pathology attending physicians participated as facilitators in the discussion. After the discussion was complete, OB-GYN and pathology residents paired up to perform a hands-on skill station corresponding to each case. The session concluded with the participants making remarks on take home messages and filling out feedback forms on the session. Results We carried out this session with our own OB-GYN and pathology residents at New York University in October 2014. It was well received, generating robust discussion. Residents expressed improved understanding of the POC testing and PPM, regulatory requirements (including policies and procedures), quality control, certification and maintenance of competency, result interpretation, knowledge of supervision, and ability to perform POC testing and PPM as demonstrated by each resident in the hands-on skills stations. Participants also made several suggestions on how to utilize this session in the future, for example, to include elements such as the hands-on portion in the intern boot camp. Discussion As a result of this session, residents are now able to understand and perform POC testing and PPM.

Human granulocytic anaplasmosis (HGA) is a potentially fatal tick-borne infection caused by Anaplasma phagocytophilum. Treatment options are limited for this entity, with doxycycline being the drug of choice. Certain fluoroquinolones such as levofloxacin are active against A. phagocytophilum in vitro. We report a hospitalized patient with HGA who improved coincident with a 13-day course of levofloxacin therapy, but clinically and microbiologically relapsed 15 days after completion of treatment. Relapse of infection after levofloxacin therapy was reproduced in a severe combined immune-deficient (SCID) mouse infection model. Quinolone therapy should not be considered curative of HGA.

The Bmp proteins are a paralogous family of chromosomally encoded Borrelia burgdorferi lipoproteins. They have similar predicted immunogenicities and similar electrophoretic mobilities by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. P39 reactivity against Borrelia burgdorferi lysate in immunoblots of Lyme disease patients has long been identified with reactivity to BmpA, but responses to other Bmp proteins have not been examined. To determine if patients with Lyme disease developed such responses, immunoglobulin G (IgG) anti-Bmp reactivity in patient and control sera was studied by using soluble recombinant Bmp (rBmp) proteins expressed in Escherichia coli . Although some patient sera contained IgG immunoblot and immunodot reactivities against all four Bmp proteins, analysis of IgG anti-Bmp fine specificity by a competitive enzyme-linked immunosorbent assay with graded doses of soluble homologous and heterologous rBmp proteins showed that only the responses to BmpA, BmpB, and BmpD were specific. This suggests that at least three of the four Bmp proteins are expressed by B. burgdorferi in infected patients and that specific antibodies to them are likely to be present in the P39 band in some patients.