bluuebunny/crossref_metadata_2025 huggingface dataset:
337. Diagnostic Yield and Impact on Antimicrobial Management of 16s rRNA Testing on Clinical Specimens
Authors: Eamsakulrat Pruke , Phuphuakrat Angsana , Santanirand Pitak
Published: December 2022

Background

16s rRNA gene sequencing has an advantage over traditional bacterial culture in situations where bacteria are difficult to culture, unculturable, or have previously been exposed to antimicrobial. The study on its applicability to direct clinical specimens is still limited. We studied the value of 16s rRNA gene sequencing from direct clinical specimens on antimicrobial management.

Methods

Inpatient adults whose attending physician requested 16s rRNA gene sequencing and corresponding bacterial culture from a direct clinical specimen were prospectively included between January and December 2021. Diagnostic yield and the impact of 16s rRNA gene sequencing on antimicrobial management were investigated.

Results

A total of 434 specimens from 374 patients were requested. All patients had a complete follow-up and had a definitive final diagnosis. The sensitivity and specificity of 16s rRNA gene sequencing were 38.3% and 93.9%, respectively. The agreement between 16s rRNA gene sequencing and conventional culture among specimens obtained from bacterial infection cases was 83.8% (the κ coefficient 0.664, p< 0.001). Among bacterial infection cases, the proportion of 16s rRNA gene sequencing positive/culture-positive was 32.4% (82 specimens), and the proportion of sequencing positive/culture-negative was 5.9% (15 specimens). The impact on antimicrobial management occurred in 10 (2.3%) specimens, which all resulted in the continuation of antibiotics. An impact on antimicrobial management was highest in the skin and soft tissue infection, followed by bone and joint infection. In contrast, CAP/HAP/VAP was less likely to benefit from this test. Long turnaround time was the limitation of the test in this study, the median (interquartile range) was 11 (9-13) days in the 16s rRNA gene sequencing positive group, and 2 (1-4) days in the 16s rRNA gene sequencing negative group.

Conclusion

The overall diagnostic yield of 16s rRNA gene sequencing in bacterial infection cases was fair. 16s rRNA gene sequencing was useful in selected cases, but it cannot replace traditional culture. The negative result did not exclude bacterial infection. Restrictions on test requests may improve test utilization in this setting.

Disclosures

All Authors: No reported disclosures.
340. GeneXpert Ultra for Diagnosis of Central Nervous System Tuberculosis in the High Tuberculosis Prevalence Country - A Prospective Study from India
Authors: Naguthevar Santhanam , Kumar Deepak , Sharma Shivang , ID D M , Bohra Gopal Krishna , Meena Durga Shankar , Midha Naresh Kumar , Kombade Sarika P , Jain Vidhi , Garg M K , Singh Kuldeep
Published: December 2022

Background

Early diagnosis and initiation of antitubercular treatment are vital steps to reducing the impact of TB in high burden countries. The molecular method like GeneXpert has significantly improved the diagnosis of TB. GeneXpert Ultra is more sensitive to the diagnosis and helps in paucibacillary samples like cerebrospinal fluid (CSF). This study aims to provide its utility in diagnosis of central nervous system tuberculosis (CNS TB) in high TB burden geography.

Methods

This prospective observational study included the suspected cases of CNS TB with age ≥12 years. Patients who presented with ≥ 5 days history of CNS symptoms suggestive of tuberculosis with a lancet score of ≥ 6 on combination of clinical, CSF and imaging criteria were included in the study. Patients diagnosed with aetiology other than tuberculosis for CNS disease were excluded. CSF was analysed for GeneXpert Ultra and mycobacterial culture. The sensitivity, specificity, positive predictive value (PPV), and Negative predictive value (NPV) of GeneXpert Ultra were analysed in comparison with culture results.

Results

A total of 107 patients with mean age of 33.2±18.5 years were analysed. CSF mycobacterial culture was positive in 45.8% (n=49) of patients. However, Mycobacterial tuberculosis via GeneXpert Ultra was detected in 57.9% (n=62) of patients. Sensitivity, specificity, PPV and NPV for GeneXpert Ultra were found 83.7%, 63.8%, 20.4% and 97.2% respectively. According to the lancet score, 70.1% (n=75) and 29.9% (n=32) of patients had probable and possible CNS TB, respectively. Among them, definitive CNS TB were diagnosed in 65.3% (n=49) and 65.6% (n=21) patients with probable and possible CNS TB, respectively.

Conclusion

GeneXpert Ultra has an excellent sensitivity and negative predictive value for the diagnosis of CNS TB in CSF samples. Even with possible CNS TB according to the lancet score, it is better to consider antitubercular treatment in a high TB burden country.

Disclosures

All Authors: No reported disclosures.
344. VersaTrek versus Virtuo Blood Culture System’s Effect on Diagnostic Test Utilization and Patient Outcomes, a Quasi-Experimental Study
Authors: Dillon William P , Khan Naoshin , Nachawati Dana , Alangaden George J , Samuel Linoj , Ramesh Mayur
Published: December 2022

Background

Prior studies evaluating the sensitivity blood cultures utilizing the Virtuo blood culture system versus the VersaTREK blood culture system have suggested increased sensitivity with the Virtuo system. Studies evaluating if this increased sensitivity effects patient outcomes are lacking. This study evaluates the effect of replacing the VersaTREK system with the Virtuo system on morbidity and mortality in patients with Staphylococcus aureus bacteremia.

Methods

This quasi-experimental study was performed at Henry Ford Health System in Southeast Michigan. We analyzed all patients with positive blood cultures for Staphylococcus aureus between 3/1/18 and 9/30/18 (VersaTREK system) and 3/1/19 and 9/30/19 (Virtuo system). The VersaTREK arm had 267 patients and the Virtuo arm 404. Patients transferred to or from outside facilities with ongoing bacteremia were excluded. Primary outcomes were differences in length of stay, mortality at 14, 30, and 90 days from completion of therapy, and hospitalization for recurrence of bacteremia within 30 days. Secondary outcomes were differences in length of therapy, rates of diagnostic imaging tests to assess for persistent foci of infection or an unknown source of persistent bacteremia, and length of bacteremia. Data were analyzed using SPSS for Macintosh using Pearson’s chi-square test and Student’s t-test. A p < 0.05 was considered statistically significant.

Results

Demographics of the study populations were equal however, the Charlson Comorbidity Index for VersaTREK arm compared to Virtuo (3.5 to 3.1) trended toward significance (p=0.05) (Table 1). There was no difference in length of bacteremia, lengths of antibiotic therapy, CT scans, or echocardiograms performed. More MRIs were performed in the Virtuo arm (p=< 0.001) (Table 2). There was no difference in recurrence of bacteremia, patient death due to bacteremia, length of hospital stay, or 30 day readmission for recurrence of bacteremia (Table 3).

Conclusion

This is the first study to evaluate how increased sensitivity of a blood culture system effects patient outcomes. Our results suggest that Staphylococcus aureus bacteremia may be over treated in blood cultures systems that are highly sensitive. Further prospective studies are needed to explore this further.

Disclosures

All Authors: No reported disclosures.
348. Cell-free plasma next-generation sequencing assists in the evaluation of invasive mold infection in patients with COVID-19: a case series
Authors: David Joshua , Kolipakkam Bharadhwaj , Morales Megan M , Vissichelli Nicole C
Published: December 2022

Background

Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-β-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19.

Methods

We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality.

Results

Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients’ serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13).

Conclusion

In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19.

Disclosures

Megan M. Morales, MD, Karius: Paid speaker.
351. Epidemiology and antifungal susceptibilities of clinically significant filamentous fungi from a tertiary hospital in Singapore from 2018 – 2021
Authors: Huang Wenjie , Tan Mei Gie , Tan Yen Ee
Published: December 2022

Background

Filamentous fungi infections are associated with significant morbidity. Although an increase in antifungal resistance has been reported globally, no data pertaining to Singapore is available. This study investigates the species distribution and antifungal susceptibility profiles of molds isolated from a tertiary hospital in Singapore.

Methods

A retrospective review of fungal cultures with antifungal susceptibility results reported in the laboratory information system from 2018 to 2021 was conducted. Unique isolates per patient were included. Molds were identified primarily by morphology. Molecular studies were used as an adjunct where required. Susceptibility testing was performed via broth microdilution (Sensititre YeastOne) and gradient diffusion (Liofilchem) methods.

Results

125 isolates were analyzed (Table 1). The most common molds recovered were Aspergillus, Fusarium and Mucorales. Aspergillus and Mucorales frequently involved the respiratory tract and skin and soft tissue (SSTI) whereas Fusarium was isolated from SSTI and blood.

Amphotericin B had moderate activity against all molds, with only 11 out of 88 isolates (12.5%) being non-wild type (Table 2). The echinocandins exhibited good activity against Aspergillus and other hyaline molds but not Fusarium and Mucorales. The triazoles were most useful against Aspergillus, with posaconazole demonstrating the lowest geometric mean of 0.067. Fusarium had high MICs when tested against the azoles. Posaconazole was the azole of choice for Mucorales.

Six Aspergillus isolates (all A. fumigatus) were non-wild type when tested against voriconazole, with a MIC >1. Of these six isolates, three were also non-wild type for amphotericin B, with a MIC >2. In particular, one Aspergillus fumigatus complex isolate demonstrated resistance across all tested azoles and sequencing revealed Cyp51 mutations.

Conclusion

Aspergillus species is the most prevalent clinically significant mold in our hospital. Although triazoles and echinocandins exhibit good activity, 13.33% of Aspergillus isolates were non-wild type for amphotericin B. Given the detection of these non-wild type Aspergillus species, susceptibility testing may be indicated in seriously ill patients to aid clinicians in selecting antifungal therapy.

Disclosures

All Authors: No reported disclosures.
355. Outcome of patients with non-COVID-19 related Aspergillosis during the COVID-19 pandemic
Authors: Roman-Montes Carla M , Guzman-Pérez Adriana , Student Medical , Martinez-Gamboa Rosa Areli , Gonzalez Maria Fernanda , Díaz-Lomelí Paulette G , Cervantes Axel , Ponce-de-leon Luis Alfredo , Sifuentes-Osornio José , Rangel-Cordero Andrea
Published: December 2022

Background

In March 2020 our Institution was designated a COVID-19 unit, since the start of 2021 conventional medical attention has been reinstalled and it became a hybrid hospital. Our objective was to compare the outcome of patients with Invasive Aspergillosis (IA) without COVID-19 during the COVID-19 pandemic, compared with past controls from a historical cohort, and describe their clinical characteristics. As a secondary objective, we described the characteristics of other Invasive Fungal Infections (IFI) in a similar patient group.

Methods

Retrospective and descriptive study. The information was obtained from the electronic file. For IFI diagnosis, the EORTC/MSG criteria for proven and probable infection were considered, including the AspiCU modified criteria. The main outcome was death at 6 weeks, time from symptom onset to diagnosis/treatment, and having received antifungal treatment as secondary outcomes. Outcomes were compared to historical IA controls (2:1) from a pre-COVID-19 cohort. The study was approved by the local research and ethics committee.

Results

From March 2020 to December 2021, 50 IFIs were diagnosed in non-COVID-19 patients, of which 27 (54%) were Invasive Aspergillosis, 10 (20%) Cryptococcosis, 8(16%) histoplasmosis, 4 (8%) mucormycosis, and 1 (2%) Fusariosis. The median age was 44 years (IQR 33-58) and 67% were men. Forty three percent (22/51) had immunosuppression and 35% (18/51) had hematological malignancy, the median time from symptom onset to IFI diagnosis was 30 days (IQR 11-90) and 38% died within 6 weeks. During the pandemic, in Invasive Aspergillosis non COVID-19 patients, the median number of days from symptom onset to start antifungal was 21 (IQR 6-68) vs 5 (IQR 3-10) of IA historic controls (p=0.0005), 81.5% (22/27) vs 93% (50/54) received antifungal treatment (OR 0.88 , 95% CI 0.72-1.0,p=0.13), and IA cases had a mortality of 44% (12/27) vs 41% (22/54) in the historical cohort (p=0.75). We show the IA characteristics in Table 1. Table 1.Clinical characteristics of Patients with Invasive aspergillosis without COVID-19 during COVID-19 pandemic vs historic controlsFigure 1.Invasive fungal infections in non-COVID-19 patients during COVID-19 pandemicFigure 2.Invasive aspergillosis diagnosis methods in non-COVID-19 patients during COVID-19 pandemic

GM: Galactomannan antigen

Conclusion

During the COVID-19 pandemic, patients with IA withouth COVID-19 were diagnosed significantly later. Also, a trend towards increased mortality and lower proportion of antifungal treatment was observed. It is likely a consequence of hospital reconversion during the start of the pandemic.

Disclosures

All Authors: No reported disclosures.
356. Risk Assessment of Pneumocystis jirovecii Pneumonia among Hospitalized Patients with Hypoxic Respiratory Failure - A Proposed Multivariable Calculator Based on Previous Prednisone Equivalent Dose
Authors: Barahona Lilian Vargas , Sillau Stefan , Molina Kyle C , Pedraza-Arévalo Laura C , Scherger Sias , Chastain Daniel B , Shapiro Leland , Franco-Paredes Carlos , Hawkins Kellie , Henao-Martínez Andrés F
Published: December 2022

Background

Corticosteroids increase the risk of Pneumocystis jirovecii pneumonia (PJP). It is unknown how much corticosteroid dose exposure would modify the risk of PJP in different populations. We aim to develop a PJP risk calculator based on the previous dose of corticosteroids and modulated by additional clinical factors.

Methods

A multicenter retrospective case-control study was performed on patients tested for PJP within the UCHealth system from 2000 to 2021. We developed a model for estimating PJP risk based on previous prednisone equivalent daily dose (PEDD) and adjustable for additional clinical variables. PJP was fit to a generalized additive model (GAM), with a spline for prednisone dose and additive covariates for demographics and risk factors. We used a multicenter federated network to calibrate the model to estimate the PJP prevalence among hospitalized patients with hypoxic respiratory failure.

Results

We had a complete sample of 199 patients, 104 cases with PJP, and 95 controls. Patients with HIV (OR: 19 CI: 6.3-60.8, p< 0.0001), diabetes (OR: 4.1 CI: 1.2-14.8, p< 0.0288), and autoimmune disease (OR: 5.2 CI: 1.4-19.2, p< 0.0139) were more likely to have PJP. Patients with preexisting lung disease (OR: 0.3 CI: 0.1-0.6, p< 0.0041) and on PJP prophylaxis (OR: 0.06 CI: 0.02-0.2, p< 0.0001) were less likely to have PJP. 36.8% of controls and 49% of cases were on steroids with a mean PEDD of 15 mg/day and 20.4 mg/day, respectively. We found a prevalence of PJP of 0.126% among hospitalized patients with hypoxic respiratory failure. The developed model can estimate the PJP risk based on a previous PEDD in 32 different clinical combinations: e.g., a PEDD of 20 mg/day would give a calculated annual PJP risk of approximately 1.74% (95% CI: [0.39, 7.42]) if a patient has autoimmune disease only but 6.29% (95% CI: [1.34, 24.91]) if a patient has HIV only (Figure 1). Figure 1.Predicted probability of PJP based on previous prednisone dose among hospitalized patients with hypoxic respiratory failure for three different clinical scenarios

Conclusion

Previous corticosteroid dose alone is inadequate to inform of an increased risk of PJP. A multivariable calculator incorporating the absence or presence of additional traditional risk factors could optimally stratify the PJP risk. Future directions include validating the findings in external cohorts and modeling PJP risk in the ambulatory setting to inform the need for PJP prophylaxis.

Disclosures

All Authors: No reported disclosures.
362. Association of Eosinophilia with Parasites in Rhode Island Refugees, 2015 - 2020
Authors: Teferi Maranatha , Osorio Marcela , Marin Benjamin Gallo , Ding Ann , Michelow Ian C
Published: December 2022

Background

There are sparse data reporting the rates of potentially pathogenic parasites in asymptomatic, newly arrived refugees to the United States. Untreated parasitic infections can have significant health consequences including anemia, malnutrition, infertility, urinary tract malignancy, and death, among others. Eosinophilia may serve as a biomarker for certain parasites, but its reliability is debated. We hypothesized that detection of eosinophilia in refugees to Rhode Island would be useful for guiding management in this vulnerable population.

Methods

A retrospective chart review was performed on all adult and pediatric refugees who had their initial refugee intake clinic visit at Lifespan’s Center for Primary Care Refugee Clinic, Hasbro Children Hospital’s Refugee Clinic, or Medicine-Pediatrics Refugee Clinic, all in Rhode Island, from January 2015 to December 2020. Patients who had delayed intakes or were originally evaluated in other states were not eligible. Data were systematically collated in RedCap and descriptive statistics were performed.

Results

Charts of 955 refugees were reviewed retrospectively, of which 143 did not meet eligibility criteria and were excluded. Overall, 505 (62.2%) patients were from Africa, 242 (29.8%) from Asia, 32 (3.9%) from the Americas, 32 (3.9%) from Europe, and 1 (0.1%) from Australia. Among the 812 individuals included, 147 (18.1%) patients had eosinophil counts > 500/uL, of whom 113 (76.9%) had mild (450-1499/uL), 30 (20.4%) had moderate (1500-4999/uL), and 4 (2.7%) had severe eosinophilia (⪰ 5000/uL). The majority of patients with or without eosinophilia originated from Africa.

Prevalence of symptoms (Table 1) ranged from 0% (bloody stools) to 17.6% (abdominal pain). Overall, > 50% of refugees tested positive for a parasite by various methods (Table 2). Serology did not distinguish between acute or past infection. One patient (0.7%) was diagnosed with Plasmodium falciparum malaria. Table 1.Symptoms at Initial Encounter Among Patients With Eosinophilia (n=68)Table 2.Lab Values Among Patients with Eosinophilia (n=147)

Conclusion

Eosinophilia was common in both adult and pediatric asymptomatic refugees in Rhode Island who had parasites detected by various tests. Therefore, we conclude that routine testing for eosinophilia may inform treatment of potentially dangerous parasites in the absence of symptoms.

Disclosures

All Authors: No reported disclosures.
363. Autoimmune Sensory Neural Hearing Loss Apparently Triggered by Neurocysticercosis
Authors: Davies Evan , Arabshahi Alidad , Lateef Hamza A
Published: December 2022

Background

Meniere’s disease (MD) occurs when an abnormal amount of fluid causes increased pressure in the inner ear or labyrinth. People with Meniere's can experience symptoms including vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Various triggers for MD have been recognized and range from smoking and alcohol consumption to recent viral illness, allergies and anxiety. We present the case of a 37 year old Hispanic male, who presented with dizziness and tinnitus, which progressed to include left sided sensorineural hearing loss and he was diagnosed with Meniere’s Disease, later found to be triggered by Neurocystercercosis.

Methods

Case report based on chart review.

Results

The patient's laboratory work up was positive for anti-HSP antibody and he had an abnormal electrocochleography, left greater than right. His vestibulonystagmogram was positive for both central and peripheral findings and bithermal caloric irrigations suggested abnormal peripheral function with a 57% weakness in the left ear.

The patient was also referred to rheumatology and neurology. Neurodiagnostic work up included an MRI which revealed a post inflammatory calcification in the right parietal lobe and patient was presumed to have neurocystercercosis. He was treated with steroids, betahistine, and a low salt diet for his MD.

Conclusion

To our knowledge, this is the first reported case in the literature of Meniere’s disease that may have been triggered by or concurrent with neurocysticercosis. This highlights the importance of a thorough work up to look for neurologic comorbidity for patients presenting with Meniere’s disease.

Neurocystercercosis is typically seen developing countries and is caused by the larval form of the parasite Taenia solium infecting the central nervous system. It commonly presents with seizures and such a manifestation associated with Meniere’s disease has not been previously reported.

Disclosures

All Authors: No reported disclosures.
368. Successful treatment of resistant visceral leishmania with repeated trial of Liposomal Amphotericin B- A Case Report
Authors: Mendiratta Ayushi , Adhikari Ramesh , Jagirdhar Gowthami Sai Kogilathota , Tirupathi Raghavendra , Kashyap Rahul , Sagar Vinay
Published: December 2022

Background

Although visceral leishmaniasis is endemic in various parts of India, management is still a challenge due to multiple drug resistance. Here we describe a case of a 50 years old female who was diagnosed with visceral leishmaniasis at a tertiary care hospital in northern parts of India and was managed with a repeated trial of liposomal Amphotericin B.

Methods

Case Discussion: The patient presented in the outpatient department with recurrent fever, mild intermittent abdominal discomfort associated with generalized weakness for the past one month. On per abdomen examination the patient had splenomegaly with spleen palpable 8 cm below the left costal margin. Blood investigations were suggestive of pancytopenia (leukocyte of 1800/cumm, Hemoglobin 7 g/dl, Platelet count: 80,000/cumm) along with severe neutropenia (Absolute neutrophil count: 400/cumm) . The CT abdomen showed massive splenomegaly (23 cm) with mild hepatomegaly . Leishmania Immunoglobulin G was positive. Bone marrow biopsy revealed hyperproliferative marrow with plasmacytosis (12-15%). Bone marrow Leishman-Donovan bodies were negative. Serum immunofixation was negative for M spike and serum light chain assay was also negative. She was managed with liposomal Amphotericin B (3mg/kg) for 7 days and was subsequently discharged. After 3 months, the patient again presented with continuous fever, lethargy, running nose, palpitations. Her blood work-up revealed severe pancytopenia again. She was tested for Leishmania anti- rk39 antibody, which was positive. She was given a repeat trial of Liposomal Amphotericin B with a different regimen-3 mg/kg dose on Day 1 to 5, followed by 6th dose on Day 14, followed by 7th dose on Day 21, as per the FDA approved regimen. Patient recovered well. The most recent total leukocyte counts eventually improved to 4800 with normal differential count. Platelets increased to 180,000, Hemoglobin was around 10.8g/dl and spleen was non palpable on physical examination.

Results

Treatment of leishmania can become complicated due to resistance to various drugs especially when a single agent is being given.

Conclusion

But in resource limited countries different regimens of liposomal amphotericin B can be tried which might be helpful due to speedy clinical recovery and cost effectiveness.

Disclosures

All Authors: No reported disclosures.
380. A molecular epidemiological exploration of reduced vancomycin susceptibility in Clostridioides difficile
Authors: Eubank Taryn A , Dureja Chetna , Hurdle Julian G , Garey Kevin W , Gonzales-Luna Anne J
Published: December 2022

Background

Use of vancomycin to treat Clostridioides difficile infection (CDI) has increased following recent IDSA/SHEA treatment guideline updates, applying a selection pressure for resistance development. We previously demonstrated acquired mutations in VanSR two-component system led to constitutive vanG expression and improved in vitro C. difficile survival in physiologic vancomycin concentrations. We aim to describe the molecular epidemiology of reduced vancomycin susceptibility in clinical isolates during a period of high vancomycin use.

Methods

A cohort study was performed including adult patients hospitalized with CDI in two health systems (14 hospitals) in the Houston Area between 2017-2021. (Stool transport) C. difficile were ribotyped by fluorescent PCR and susceptibility tested by agar dilution in accordance with CLSI standards. Reduced vancomycin susceptibility was defined by minimum inhibitory concentrations (MICs) >2 mg/L. Sanger sequencing was conducted on a subgroup of isolates to identify VanSR mutations. Analysis using Chi square was performed using IBM SPSS Statistics (v 28.0.1.0).

Results

A total of 36% (165/465) of isolates exhibited reduced vancomycin susceptibility (MIC50 = 2 mg/L, MIC90 = 4 mg/L, range 0.5-16 mg/L), of which 348 were ribotyped. A significantly higher proportion of ribotype (RT) 027 isolates demonstrated reduced vancomycin susceptibility (83%) compared to other common ribotypes (30%); p< 0.001). No differences based on collection year (p=0.3) or healthcare system (p=0.08) were observed. Overall, 11% (7/56) of isolates exhibiting mutations in VanS (n=1), VanR (n=5), or both (n=1). VanSR mutations were present in 47% (7/15) of those with MICs >2mg/L vs 0% (0/41) of those with MICs ≤2 mg/L (p< 0.001).

Conclusion

A high proportion of clinical C. difficile isolates exhibited elevated MICs to vancomycin, which was most common in RT027 isolates. Mutations in the vanG regulator, VanSR, correlated with elevated MICs in a subgroup of isolates. Future research is needed to expand upon molecular mechanisms and clinical implications of reduced vancomycin susceptibility.

Disclosures

Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.
392. Guideline adaptation of fidaxomicin as first-line therapy for Clostridioides difficile infection in institutions across the United States
Authors: Basir Angela , Bradley Nicole , Lee Yuman
Published: December 2022

Background

In 2021, Clostridioides difficile infection (CDI) treatment guidelines were updated to recommend fidaxomicin over oral vancomycin as first-line therapy in initial and recurrent CDI episodes. Prior to this update, fidaxomicin use in management of CDI was limited, as cheaper alternatives were recommended as first-line therapy. The purpose of this study was to assess the guideline adaptation of fidaxomicin as first-line therapy in CDI management in institutions across the United States (US) and to identify barriers to its use.

Methods

An electronic survey was distributed to members of the American Society of Health-System Pharmacists in April 2022. Baseline demographics, current practices, and barriers to fidaxomicin use were collected. Results were analyzed using descriptive statistics. Fisher’s Exact Test was used to compare categorical variables.

Results

Based on 63 responses, majority of institutions (41/63, 65%) did not recommend use of fidaxomicin as first-line therapy for CDI. While most hospitals reported having institution specific CDI guidelines (48/63, 76%), over half of institutions with CDI guidelines still recommended oral vancomycin as first-line therapy (26/48, 54%). None of the institutions without CDI guidelines (0/15, 0%) recommended use of fidaxomicin as first-line therapy and majority of them (12/15, 80%) did not have fidaxomicin on formulary or restricted its use to ID services. Recommendation of fidaxomicin as first-line therapy was significantly higher in institutions with CDI guidelines versus those without (46% vs 0%, Fisher’s Exact 0.0006, p< 0.05).

Approximately 92% (58/63) of respondents reported at least 1 barrier to using fidaxomicin, with 39.6% (25/63) reporting 2 or more barriers to use. Barriers identified were cost (55/63, 87.3%), lack of formulary inclusion (14/63, 22.2%), lack of provider familiarity (13/63, 20.6%) and inability of patients to afford upon discharge (7/63, 11.1%).

Conclusion

Majority of institutions do not currently recommend use of fidaxomicin as first-line therapy for CDI despite the recent guideline updates. Institutions with CDI treatment guidelines were more likely to recommend use fidaxomicin as first-line therapy. Cost and lack of formulary inclusion were cited as the most frequent barriers to fidaxomicin use.

Disclosures

All Authors: No reported disclosures.
400. Rehospitalization of Patients for Recurrent Clostridioides difficile Infection
Authors: Drwiega Emily , Johnson Stuart , Skinner Andrew M
Published: December 2022

Background

Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality, especially in patients with recurrent episodes and those requiring re-hospitalization. Decreasing recurrent CDI (rCDI) and re-hospitalization for rCDI are important outcomes. The purpose of our study was to evaluate the impact of specialty care from an infectious disease (ID) or gastroenterology (GI) provider, either during the admission of the primary episode or in a follow-up appointment within 30 days.

Methods

This was a single-center, retrospective, chart review at a tertiary medical center. All hospitalized patients with a positive stool test for C. difficile (CD) (GI panel PCR, FilmArray, Biofire, or CD PCR, Xpert CD assay, Cepheid) with or without an ICD-10 code Enterocolitis due to CD (A04.7, A04.71, A04.72) from January 2018 through December 2018 were reviewed. Demographic and clinical data at the time of diagnosis and up to 90 days after discharge were collected.

Results

Our criteria identified 602 patients. We excluded 27 patients who died while hospitalized and 104 patients classified as colonized from analysis. Most patients (410/471, 87%) were determined to have a primary CDI episode. After discharge, 57 (14%) patients developed rCDI and 40 patients (10%) died within 90 days of discharge. Among those with rCDI, 40% (23/57) of patients had to be re-hospitalized due to their recurrence. Those re-hospitalized for rCDI developed their recurrence sooner (40% within 45 days, p < 0.005) compared to patients with rCDI that were not re-hospitalized (Figure). ID/GI evaluated 173 of 471 (37%) patients during the index hospitalization or on hospital follow-up. Among patients evaluated by ID/GI, 10.4% had rCDI compared to the 13.8% with no ID/GI intervention. (p=NS). Only 3.5% (6/173) of patients evaluated by ID/GI were re-hospitalized vs 5.7% (17/298) of patients without ID/GI evaluation. (p=NS)

Time to CDI recurrence in re-hospitalized patients

Conclusion

In our study, 40% of patients who had rCDI had to be readmitted for their rCDI. Recurrence occurred significantly earlier in patients who were re-hospitalized. Patients evaluated by ID or GI had a decreased rate of re-hospitalization. Inpatient consultation and timely follow up of hospitalized CDI patients should be studied prospectively to determine the impact on rCDI re-hospitalization.

Disclosures

Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
402. Risk Factors for the Development of Clostridioides difficile Infection in Patients Colonized with Clostridioides difficile
Authors: Clement Josh , Barlingay Gauri , Donnelley Monica , Crabtree Scott
Published: December 2022

Background

Asymptomatic patients colonized with Clostridioides difficile are at risk of progressing to C. difficile infection (CDI), but the risk factors associated with progression are poorly defined. The objectives of this study were to identify the prevalence and risk factors to progression of hospital-onset CDI (HO-CDI) among colonized patients.

Methods

This was a retrospective cohort study conducted at a large academic medical center. Patients were included if they were ≥ 18 years of age and colonized with C. difficile, detected via polymerase chain reaction (PCR) on a rectal swab collected on admission from 2017 to 2020. Patients were excluded if they had prior CDI, CDI symptoms on admission, neutropenia, prior rectal surgery, or were hospitalized for less than 24 hours. CDI toxin positive patients were matched 1:3 to CDI negative patients using PCR colonization test date. The primary endpoints were the prevalence of HO-CDI and the risk factors for progression to HO-CDI. Descriptive analyses were used to describe the population and univariate analysis was used to determine risk factors associated with HO-CDI.

Results

A total of 2,150 patients were colonized with C. difficile; 109 CDI toxin positive patients were matched to 327 CDI toxin negative patients. 134 patients were included and 3.2% (69/2150) developed HO-CDI. The median age was 64 and 68 patients (50.7%) were male. Malignancy (OR 2.89, 95% CI: 1.24-6.75; P = 0.01), hospitalization within one month (OR 2.2, 95% CI: 1.1-4.38; P = 0.03), antibiotic use within one month (OR 3.23, 95% CI: 1.59-6.56; P = 0.001), antibiotic use within three months (OR 2.16, 95% CI: 1.07-4.35; P = 0.03), intensive care unit (ICU) admission (OR 5.14, 95% CI: 2.47-10.73; P < 0.0001), immunosuppressant use (OR 3.33, 95% CI: 1.14-9.78; P = 0.03), and use of a third generation cephalosporin within three months (OR 4.5, 95% CI: 1.12-18.13; P = 0.03) were associated with HO-CDI.

Conclusion

Progression to HO-CDI was uncommon among colonized patients at our institution. This data suggests that in hospitalized patients colonized with C. difficile, malignancy, hospitalization within one month, antibiotic use within one or three months, ICU admission, receipt of immunosuppressants, and use of a third generation cephalosporin within three months are associated with HO-CDI.

Disclosures

All Authors: No reported disclosures.
429. Identifying Barriers to Compliance with a Universal Inpatient Protocol for Staphylococcus aureus Nasal Decolonization with Povidone-Iodine
Authors: Talbot Thomas R , Harris Bryan D , DeVault Mary , Stern Rebecca A
Published: December 2022

Background

Intranasal povidone-iodine (PI) is a recommended strategy for universal decolonization in high-risk patients (ICU and those with central venous or midline catheters) to reduce hospital-associated Staphylococcal infections. Few studies have evaluated implementation challenges and barriers to successful performance of inpatient intranasal decolonization programs.

Methods

We surveyed adult acute care unit nurses at an academic medical center in March 2022, approximately 14 months after implementation of a universal decolonization standard operating procedure (SOP). The anonymous, voluntary REDCap® survey evaluated domains focused on patient identification, education, training, resources, application, and patient acceptance using Likert scale ratings.

Results

Among 248 respondents, most were new to nursing (54.4% with 0-4 years of experience) and worked in non-ICU units (61.5%). Only 60.5% reported receiving training on how to perform intranasal PI (hands-on 48.6%, computer/electronic module 25.7%, both 20.9%). Nurses who received training indicated moderate to strong confidence in their ability to perform intranasal PI decolonization (89.2%). A majority cited a good understanding of the rationale for use and identified patients appropriately. Low rates were reported for performing decolonization per the SOP (49%), with barriers including inadequate supplies (35.1%), lack of a readily available copy of the SOP (69%), difficulty swabbing with nasal devices in place (41.5%) and time constraints from other patient duties. Nurses perceived that only 49.2% of patients had a moderate or strong understanding of why PI decolonization was performed, and most were unwilling to undergo intranasal PI (59.1%). Other issues included tracking PI application within the electronic medical record (EMR), limited nurse knowledge of PI effectiveness, patient refusal despite education, and overall frontline personnel burnout.

Conclusion

Gaps in nursing and patient education should be prioritized during and after implementation to improve fidelity, particularly with frontline burnout from COVID-19. Streamlined tracking and ordering of PI on the EMR may ease nursing workflow.

Disclosures

Thomas R. Talbot, III, MD, MPH, OmniSolve: Board Member.
436. Paid sick leave among U.S. healthcare personnel, April 2021
Authors: de Perio Marie , Srivastav Anup , Razzaghi Hilda , Laney Anthony , Black Carla
Published: December 2022

Background

Healthcare personnel (HCP) are at risk for acquiring and transmitting coronavirus disease 2019 (COVID-19), influenza, and other respiratory infections in the workplace. An important strategy to prevent workplace transmission, paid sick leave benefits allow workers to stay home and visit a healthcare provider when ill. Our objectives were to quantify the percentage of HCP reporting paid sick leave, identify differences across occupations and settings, and determine factors associated with having paid sick leave.

Methods

In a national nonprobability Internet panel survey of HCP in April 2021, respondents were asked, “Does your employer offer paid sick leave?” We weighted responses to the U.S. HCP population by age, sex, race/ethnicity, work setting, and census region. We calculated the weighted percentage of HCP who reported paid sick leave by occupation, healthcare setting, and type of employment. Using multivariable logistic regression, we identified factors associated with having paid sick leave (i.e. an adjusted prevalence ratio (aPR) with a 95% confidence interval that excludes 1).

Results

In April 2021, 71.4% of 1,652 responding HCP reported having paid sick leave, a slight increase from 68.1% in April 2020. The percentage of HCP reporting paid sick leave varied by occupation, ranging from 54.3% (physicians) to 88.8% (nurse practitioners/physician assistants), and by work setting, ranging from 59.7% (“other” clinical settings) to 82.4% (hospitals). In multivariable analyses, factors associated with having paid sick leave included age between 30–44 years (aPR:1.20) and 45–59 years (aPR:1.22) and male sex (aPR:1.19). HCP working as physicians (aPR:0.74), as contract employees (aPR:0.71), and those working in the Midwest (aPR:0.78) and South (aPR:0.87) regions and in rural settings (aPR:0.86) were less likely to report having paid sick leave.

Conclusion

The majority of HCP from all occupational groups and healthcare settings reported having paid sick leave. However, differences by age, sex, occupation, type of work arrangement, and region exist and highlight disparities. Increasing HCP access to paid sick leave may decrease presenteeism and subsequent transmission of infectious diseases in healthcare settings.

Disclosures

All Authors: No reported disclosures.
437. A Single-Center Experience of Solid versus Hematologic Malignancies in People Living with HIV
Authors: Daoud Nour A , Bhuiyan Mohammad Alfrad Nobel , Koppada Satya , Alam Mohammad , Malek Alexandre E
Published: December 2022

Background

People living with HIV (PLWH) have an increased risk of cancer, including AIDS-defining and non-AIDS-defining malignancies. Some of the contributing factors are related to the high-risk lifestyle choices, but the introduction of HAART has reduced the incidence of AIDS-defining cancers.

Methods

We conducted a retrospective study of PLWH who were diagnosed with cancer between November 2019 and March 2022. We identified 60 patients who had HIV infection prior to the diagnosis (dg) of cancer or concurrently diagnosed with cancer. We evaluated patient’s characteristics, CD4 T cell counts, HIV viral load, adherence to HAART, solid and hematologic (HM) malignancies.

Results

Sixty pts were included in the analysis. The median age was 49.50 (range, 21-76 yrs) and 48 pts (80%) were male. The majority were African Americans (78.3%). Around 75% of pts were smokers, 35% of pts use alcohol, and 33.3% use illicit drugs. Cancer types were non-Hodgkin lymphoma (NHL) (11 pts, 18.3%), skin cancer (8 pts, 13.3%), Kaposi sarcoma (KS) (7 pts, 11.7%), prostate cancer (7 pts, 11.7%), head and neck cancer (5 pts, 8.3%), breast cancer (4 pts, 6.7%), Hodgkin lymphoma, leukemia, and lung cancer with same percentage each (3 pts, 5%), colorectal cancer (2 pts, 3.3%), and miscellaneous solid tumors (7 pts, 11.7%). AIDS-defining cancers were identified in 28.3% of pts. The median time between HIV and cancer dg was 8 years (range, 0-31 yrs). Eight pts (13.3%) were diagnosed with HIV and cancer at the same time [NHL (3 pts), myeloid leukemia (1 pt), and solid tumors different than cervical cancer (4 pts)]. A group of 43 pts (71.7%) had solid tumors were compared with 17 patients (28.3%) had HM. There were no differences between the two groups regarding gender, sexual orientation, smoking history, medical comorbidities, time between HIV and cancer dg. Pts with HM were younger (P-value of 0.05), and the rate of alcohol use was higher in pts with solid tumors (P-value, 0.003). HIV viral load > 200 copies/ml was higher in HM (75%) than solid tumors (44.1%) with P-value of 0.06 and the adherence rate to HAART was higher in pts with solid tumors (67.6%) compared to HM (38.4%) with a P-value of 0.1, prior to cancer dg.

Conclusion

PLWH with HM are more likely to be younger, non-adherent to HAART, and have higher HIV viremia compared to pts with solid tumors.

Disclosures

All Authors: No reported disclosures.
465. A Multifaceted and Multi-Institutional Analysis of the COVID19-Associated Mucormycosis Outbreak in the Delhi Area Indicates the Simultaneous Convergence of Multiple Risk Factors
Authors: Chowdhary Anuradha , Wurster Sebastian , Gupta Nitesh , Mohabir Jason , Tatavarthy Shashidhar , Mittal Vikas , Sharma Brijesh , Jiang Ying , Cuomo Christina , Kontoyiannis Dimiitrios P
Published: December 2022

Background

A major outbreak of COVID19-associated mucormycosis (CAM) in India in spring 2021 aggravated the death toll of COVID19. As the causes of that CAM outbreak remain unclear, we performed a multifaceted study of host, pathogen, environmental, and heath care-related factors in adult CAM patients (pts) in the metropolitan New Delhi area.

Methods

We reviewed the records of all pts diagnosed with culture- or biopsy-proven CAM at 7 hospitals in the New Delhi area (April 1 – June 30, 2021). We used a multivariate logistic regression model to compare clinical characteristics of either all CAM cases (analysis 1, n = 50) or only pts with CAM after moderate or severe COVID19 (analysis 2, n = 31). As controls for both analyses, we used 69 COVID19-hospitalized contemporary pts. Selected hospital fomites were cultured for Mucorales. Additionally, we compared meteorological data and fungal spore concentrations in outdoor air before the CAM outbreak (January-March 2021) and during the outbreak (April-June 2021). Mucorales isolates from CAM pts were identified by MALDI-TOF-MS and ITS sequencing. A subset of 15 isolates underwent whole genome sequencing (WGS).

Results

Risk factors for CAM in both analyses were newly diagnosed diabetes mellitus (odds ratio [OR] 8.26/5.67) and active cancer (OR 5.98/5.68) (Figure 1). Supplemental oxygen for COVID19 was associated with a lower CAM risk in both analyses (OR 0.13/0.17). Another significant CAM risk predictor identified only in analysis 1 was severe COVID19 (WHO score ≥ 6, OR 4.09), while remdesivir therapy (OR 0.40) and ICU admission for COVID19 were protective (OR 0.41) (Figure 1). No Mucorales were cultured from hospital fomites. The CAM incidence peak coincided with a significant uptick in environmental spore concentrations but was not linked to specific meteorological factors. Rhizopus was the predominant Mucorales genus (64%) identified by MALDI-TOF-MS and ITS sequencing; WGS found no clonal population of isolates but detected 2 cases of the rare pathogen Lichtheimia ornata. Figure 1

Conclusion

An intersection of host, environmental, pathogen and healthcare-related factors might have contributed to the emergence of CAM. Surrogates of access to advanced treatment of COVID19 were associated with lower CAM risk.

Disclosures

Dimiitrios P. Kontoyiannis, MD, ScD, PhD (hon), AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant.