bluuebunny/crossref_metadata_2025 huggingface dataset:
453. Distribution of cycle threshold values and the associated factors of SARS-CoV-2 omicron variant in a community setting in Japan
Authors: Mutoh Yoshikazu , Umemura Takumi , Ichihara Toshihiko
Published: November 2023

Background

Little is known regarding the viral dynamics of omicron variant, although the number of severe cases of COVID-19 has decreased due to the expansion of vaccines and emerging of omicron variant. Therefore, we investigated the distribution of cycle threshold (Ct) values and related characteristics in this study.

Distribution of cycle threshold values of SARS-Cov-2 PCR by symptoms

Methods

Patients who tested positive for SARS-CoV-2 using PCR test at Tosei General Hospital between April 2022 and March 2023 were retrospectively analyzed. SARS-CoV-2 was detected using nasopharyngeal swab or saliva via Xpress SARS-CoV-2 assay (Cepheid, Sunnyvale, USA) and Cobas 8800 system (Roche). Age, sex, days since onset, symptoms, comorbidities, prognosis, and vaccination status were collected for each patient. The date of onset was estimated from the contact history of asymptomatic patients.

Results

Of 605 patients, mean age was 51.0 (±26.0) years, 323 were men (53.4 %), 77 (12.7 %) were asymptomatic, and 360 (59.5 %) had more than three times of vaccination. The most frequent comorbidity was chronic pulmonary diseases in 83 (13.7%) patients, followed by diabetes in 61 (10.1%), chronic heart diseases in 61 (10.1%), and malignancy in 55 (9.1%). The distribution of Ct value was 27.8 (IQR: 21.5–34.8) for within 5 days of onset, 27.5 (IQR: 22.5–34.0) for 6–14 days of onset, 35.6 (IQR: 30.4-40.7) for 15 days or later of onset. More than 38.6% (68/176) of the cases diagnosed at symptom onset showed a Ct value of >32.

Among 494 patients diagnosed within 5 days of onset, symptomatic patients showed significantly lower median Ct values than those of not (27.19 vs 32.54; P value < 0.001). However, in multivariable analysis, age, disease severity, vaccination status, and comorbidities were not associated with Ct values.

Conclusion

Ct values of SARS-CoV-2 omicron variant might be able to estimate the onset of disease onset. Conversely, certain number of cases revealed high Ct values from the early phase of infection. Physicians should focus on the interpretation of Ct values for infection prevention and control.

Disclosures

All Authors: No reported disclosures
476. Increased Depression and Anxiety Associated with COVID-19 among Recipients of HIV Healthcare Services at Sexual Health Clinic in NYC
Authors: Huang Simian , Zucker Jason , Castor Delivette , Carnevale Caroline , LaSota Elijah , Klein Joshua , Kim Tae Yoon , Quigee Daniela , Theodore Deborah , Gordon Peter , Cohall Alwyn , Meyers Kathrine , Sobieszczyk Magdalena E
Published: November 2023

Background

The COVID-19 epidemic disrupted routine healthcare services and affected mental health. Within Stick2PrEP, a suite of studies aimed at increasing pre-exposure prophylaxis (PrEP) uptake and healthcare engagement among men who have sex with men (MSM) and trans women (TW) in New York City, participants enrolled from November 2018 to February 2020 (Stick2PrEP2) and, after pandemic onset, from May 2021 onward (Stick2PrEP3). To understand the impact of the pandemic on the mental health of MSM/TW, we compared Stick2PrEP2 and Stick2PrEP3 participants' self-reports of depression and anxiety.

Methods

All participants in the two studies completed a baseline enrollment questionnaire that surveyed demographics, sexual behaviors, depression, anxiety, and intimate partner violence. We compared baseline characteristics of Stick2PrEP3 vs Stick2PrEP3 among participants enrolled between November 2018 and April 2022 using relevant statistics (e.g., Pearson's Chi-squared test or Wilcoxon rank sum test).

Results

We analyzed 345 participants, 141 in Stick2PrEP2 and 204 in Stick2PrEP3. Participants were similar in age, self-identified gender, race/ethnicity, income, rates of adverse childhood events, HIV and sexually transmitted infection (STI) risk scores, and PrEP adherence norms. More participants were on Medicaid or uninsured in Stick2PrEP3 (p< 0.001). Additionally, both PHQ9 (2 vs. 4, p< 0.001) and GAD7 (2 vs. 4, p=0.002) scores were significantly higher in Stick2PrEP3. More participants reported experience of intimate partner violence (24% vs. 45%, p=0.002) in Stick2PrEP3, but had higher PrEP engagement (INDEX score >45, 66% vs. 86%, p< 0.001).

Demographic information of participants in Stick2PrEP2 and Stick2PrEP3.

Results of different measurements from the enrollment survey that each participant completed.

Conclusion

The baseline results suggest that depression and anxiety levels were lower before COVID-19 among MSM and TW. The experiences during the COVID-19 pandemic may have contributed to increased depression and anxiety levels which may be multifactorial and modified by disruption in PrEP services. Further investigation is crucial to uncover the link between COVID-19, mental health, and health services delivery for people at risk of HIV acquisition.

Disclosures

All Authors: No reported disclosures
482. Long-Term Outcomes of Coronavirus disease 2019 and Risk Factors for Prolonged SARS-CoV-2 Infection in Lymphoma Patients: Multicenter, Retrospective Cohort Study
Authors: Lee Jung Ah , Han Min , Ahn Sangmin , Lee Yongseop , Yeom Joon-sup , Choi Jun Yong , Ku Nam Su , Jeong Su Jin , Kim Jung Ho , Kim Jin Seok , Chung Haerim , Cho Hyunsoo , Kim Yu Ri , Ahn Jin Young
Published: November 2023

Background

In lymphoma patients, SARS-CoV-2 is often detected continuously even after a sufficient amount of time has passed since being confirmed with COVID-19. We aim to describe the long-term outcomes of COVID-19 and identify the risk factors for prolonged SARS-CoV-2 infection in lymphoma patients.

Methods

A multicenter retrospective cohort study was conducted on patients receiving treatment for lymphoma at three tertiary hospitals in South Korea who were quarantined after being diagnosed with COVID-19 by polymerase chain reaction (PCR) testing or antigen test from August 2021 to July 2022. Prolonged COVID-19 is defined as a case where PCR remains positive even after 30 days of COVID-19 confirmation or when COVID-19 pneumonia occurs or worsens after 30 days of COVID-19 confirmation.

Results

A total of 77 lymphoma patients with COVID-19 were studied. Among them, 24 (31%) patients were classified as prolonged COVID-19 and seven patients (9.1%) died within 90 days after the diagnosis of COVID-19. (Table 1) Prolonged COVID-19 was more frequently identified in follicular lymphoma patients with a history of bendamustine and rituximab (BR) treatment (22.6% vs. 50.0%, p=0.016), especially those who maintained rituximab maintenance treatment after BR treatment (11.3% vs. 37.5%, p=0.012). (Table 2) At the time of initial COVID-19 diagnosis, the 'prolonged COVID-19 group' did not show clinically significant differences compared to the non-prolonged COVID group. (Table 3) Multivariable analysis showed that BR treatment followed by rituximab maintenance is one of the risk factors for persistent PCR positivity (OR 3.375, 95% CI 1.104-10.317, p=0.033), delayed or persistent pneumonia (OR 8.833, 95% CI 2.527-30.879, p=0.001), and COVID-19 related admission after quarantine period (OR 11.1, 95% CI 2.758-44.678, p=0.001). Prolonged COVID-19 had an impact on the delay of cancer treatment but did not increase the risk of 90-day or 180-day mortality significantly. (Table 4)

Conclusion

In this study, patients with lymphoma who have received certain treatments may have a higher risk of developing COVID-19 pneumonia due to prolonged infection. Further study is needed to understand the immune responses in this patient group and find treatment methods.

Disclosures

All Authors: No reported disclosures
495. De novo emergence of resistance mutations during treatment of SARSCoV-2 infection in immunocompromised patients
Authors: Johnson Katherine , Soave Rosemary , Wang Wei , Albert Joshua , Kodiyanplakkal Rosy Priya , Salpietro Maria , Jing-Mei Hsu , Diel Diego G , Ghedin Elodie , Salvatore Mirella
Published: November 2023

Background

Vaccination and therapeutic strategies for COVID-19 are constantly hindered by the rapid emergence of new viral variants less sensitive to antibodies or antivirals. Emerging evidence points to prolonged replication in the immunocompromised host as a key factor contributing to emergence of viral genomic mutations. We analyzed viral evolution and emergence of intra-host variants in response to treatments including antivirals and monoclonal antibodies in immunocompromised subjects with hematological malignancies infected with SARS-CoV2.

Methods

From April 2020 to August 2022, we collected 245 nasopharyngeal samples from 92 patients including longitudinal samples of 31 subjects with persistent infection (detection of SARS-CoV-2 RNA ≥30 days regardless of symptomatology). The number of samples per subject ranged from 1-14. To identify SARS-CoV-2 mutations, we performed whole genome sequencing using an amplicon-based approach and the Illumina NextSeq platform. Only samples that had 75% genome covered at 5x read depth were included in the analysis.

Results

After quality control filtering, 21 subjects had at least 2 samples available for longitudinal analyses. Ten of them had no consensus changes during infection (compared to the first sample collected), and 11 had at least 1 change. The spike protein was the most likely location for a consensus change (9 patients), followed by consensus changes in nsp3, nsp12, nsp13, N, ORF8, and nsp4. Mutations tended to appear mostly following treatment, with an increased number of changes apparently associated with worse outcome. After treatment, 3 patients developed mutations in the RNA-dependent RNA polymerase (nsp12) that are known to be associated with remdesivir resistance. One Paxlovid treated patient developed a nsp5 protease mutation potentially associated with resistance. Another patient developed a spike mutation associated with resistance to sotrovimab.

Conclusion

Our results underscore the need for augmented efforts to study intra-host evolution in the immunocompromised host, identify and isolate viruses resistant to treatment(s) and identify host determinants associated with accelerated resistance. These results are important for implementing optimal treatment strategies and to inform infection control measures.

Disclosures

All Authors: No reported disclosures
499. Level of Cord Blood Anti-SARs-CoV-2 Antibodies in Infants Born During 2021-2023 to The Mothers Who Had Received COVID-19 Vaccination During Pregnancy
Authors: Sojisirikul Nophathai , Lapphra Keswadee , Chokephaibulkit Kulkanya
Published: November 2023

Background

Maternal antibodies against SARS-CoV-2 actively transfer across placenta providing passive immunity to neonates. However, levels of cord blood anti-SARS-CoV2 antibodies and protective effects are still unclear. The objectives of the study was to investigate level of cord blood SARs-CoV-2 antibody of infants born to the mothers who received at least 1 dose of COVID-19 vaccine during pregnancy or within 3 months before pregnancy, as well as having SARS-CoV-2 infection during pregnancy.

Methods

Prospective observational study was conducted in Bangkok between March 2022 to March 2023. Cord blood samples were tested for anti-receptor binding protein IgG (anti-RBD IgG). Medical records were review for history of SARS-CoV-2 infections in the mothers.

Results

A total of 154 neonates were enrolled. The highest cord blood geometric mean concentration (GMC) of anti-RBD IgG was observed in infants who was born from the mother who received COVID-19 vaccine and were diagnosed with COVID-19 during pregnancy (n= 28; anti-RBD IgG: 7684.8 [95% confidential interval (CI) 4215.9-14007.8] AU/ml), while the lowest GMC was found in the infants born from mothers who received COVID-19 vaccination before pregnancy and did not have COVID-19 during pregnancy (n=18, anti-RBD IgG 1453.5 [95% CI 648.1-3259.6 AU/ml]. Maternal SARs-CoV-2 infection during pregnancy had a significant association with anti-RBD IgG levels (P=0.03).

Figure of Anti-RBD IgG comparison at birth

Conclusion

Vaccinating and having SARs-CoV-2 infection during pregnancy induced several folds higher antibody level in cord blood that could effectively provide protection in infants.

Disclosures

All Authors: No reported disclosures
523. Efficacy and Safety of Nirmatrelvir/Ritonavir for COVID-19 in Adolescents
Authors: Lee Kiriam Escobar , Lee Philip J , Anosike Brenda I
Published: November 2023

Background

Nirmatrelvir/ritonavir (n/r) is a currently 1 of 2 oral medications FDA-approved for treatment of COVID-19 in patients ≥ 12 years of age AND ≥ 40 kg. To date, dosing recommendations for adolescents are extrapolated primarily from adult studies. We conducted a retrospective study at a large pediatric academic center to evaluate the efficacy and safety of n/r in adolescent patients.

Methods

Retrospective electronic chart review of adolescents ages 12-18 years diagnosed with COVID-19 between 1/1/2022 to 3/31/2022. We included those with laboratory confirmed COVID-19 by either PCR or rapid antigen, treated with n/r within 5 days of symptom onset. The primary endpoint was COVID-related hospital admissions, ER and/or outpatient visits within 30 days after completion of n/r. Our secondary endpoint was COVID-related adverse event(s) due to n/r.

Results

A total of 91 unique patients were prescribed n/r therapy; 1 was prescribed twice. All but 2 were ordered in the outpatient setting. 34.1% (29/85) had a BMI ≥ 30 kg/m2. Thirty-eight (41.8%) and 25 (27.5%) patients received 2 and 3 COVID-19 vaccines, respectively. Asthma (26/91, 28.6%) was the most common underlying condition; (16/91, 16.6%) were immunocompromised. Median time from initial COVID-19 positivity to n/r prescription was 0 days (range: 0-4). 2.2 % (2/90) of those who received outpatient prescriptions returned to the ER with COVID-19 like symptoms within 30 days. Another 2 different patients who were prescribed n/r inpatient expired at 28 and 48 days after completion of therapy. Only 2.2% (2) experienced an adverse event after completion of n/r. (Table 1)

Demographic and outcome information of adolescent patients treated with nirmatrelvir/ritonavir for COVID-19 infection at a large pediatric academic medical center.

Conclusion

Though limited, this single center study demonstrated low rates of COVID-related hospital admissions, ER and/or other outpatient visits as well as adverse events suggesting that n/r may be a safe and well tolerated by most adolescents diagnosed with COVID-19. Larger/prospective pediatric studies are still needed.

Disclosures

All Authors: No reported disclosures
526. Treatment Inconsistencies of Patients Hospitalized with COVID-19 during Four Waves in Almaty, Kazakhstan, 2020-2021
Authors: Gazezova Saya , Horth Roberta , Smagul Manar , Kasabekova Lena , Usmanov Shokhruh , ZIKRIYAROVA S A N A M , Nabirova Dilyara
Published: November 2023

Background

Clinical management guidelines were continually changing during the COVID-19 pandemic to reflect best available evidence for a novel virus. In Kazakhstan, the treatment guidelines have been modified 16 times since the pandemic began. We assessed compliance with guidelines during four waves of COVID-19 in Kazakhstan.

Methods

We conducted a cross-sectional study among people hospitalized with COVID-19 in an infectious disease hospital in Almaty during 4 waves: T1 (June 1-August 30, 2020); T2 (October 1-31 December 2020); T3 (April 1-May 31, 2021); and T4 (July 1-October 26, 2021). Changes in COVID-19 diagnostic and treatment guidelines published during these periods were studied. We abstracted data from patient electronic medical records.

Results

Seven of 16 COVID-19 diagnostic and treatment guidelines adopted in Kazakhstan were updated during this time. In T1, all people with COVID-19 including those with asymptomatic and mild disease. Antibiotics were recommended only for bacterial infections in T1-T4. Glucocorticosteroids were recommended only to patients with severe disease in T1-T4. Anticoagulants were recommended prophylactically in T1-T3 but only empirically in T4. Of 1,146 COVID-19 patients hospitalized, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Mean age was 57 years (range 18-96 years) and 59% were female. In T1-T4 respectively: Antibiotics were given to 78%, 64%, 71%, and 67% of patients with no documentation of bacterial infections; glucocorticosteroids were given to 36%, 31%, 33%, and 28% of patients with non-severe disease; non-COVID-19-specific antivirals were given to 28%, 10%, 4%, and 8% of patients; and anticoagulants given to 18%, 24%, 6%, and 7% of patients with mild disease.

Treatment of hospitalized COVID-19 patients inconsistent with national treatment guidelines, Almaty, Kazakhstan, 2020-2021

T1: June 1-August 30, 2020; T2: October 1-31 December 2020; T3: April 1-May 31, 2021; T4: July 1-October 26, 2021

Conclusion

We identified inconsistencies with patient treatment and national guidelines. Inappropriate use of antibiotics and non-specific antivirals can result in adverse treatment outcomes and rise in resistance. Improved communication with additional training is needed when guidelines are updated.

Disclosures

All Authors: No reported disclosures
530. Population Pharmacokinetic Analysis of Ensitrelvir, an Inhibitor of 3C-like (3CL) Protease of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for patients with SARS-Cov-2 Infection
Authors: Ishibashi Toru , Nomura Luna , Shimizu Ryosuke , Kubota Ryuji
Published: November 2023

Background

Ensitrelvir is a novel oral inhibitor of 3CL protease of SARS-CoV-2, which is essential for viral replication. Ensitrelvir which is administered at once daily for 5 days with 375 mg on Day 1 followed by 125 mg, was approved in Japan for the treatment SARS-CoV-2 infection under the Emergency Regulatory Approval System in November 2022. The aim of this study is to build a population pharmacokinetic (PK) model to assess covariates on ensitrelvir PK.

Methods

A population PK analysis was performed using a total of 8034 plasma ensitrelvir concentrations from 2060 healthy participants in Phase 1 studies and patients in Phase 2/3 study. A 2-compartment model with first order absorption was used as a structural PK model for a base model. The effects of covariates were evaluated including age, body weight (BWT), AST, ALT, albumin, total bilirubin, creatinine clearance, GFR, sex, race, health status, formulation, food conditions and so on. The exposures (individual post-hoc maximum concentration [Cmax], area under the time-concentration [AUC] and plasma concentration at 24 hours post-dose [C24]) in the patients were estimated with an empirical Bayesian approach based on the final model to assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship between SARS-CoV-2 viral RNA load and exposures.

Results

The population PK model well described the plasma ensitrelvir concentration data. The effects of BWT on clearance and volume of distribution, food conditions and formulation on absorption rate constant were found to be significant covariates. The anti-viral effect did not change in the range of ensitrelvir exposure in Phase 2/3 study, while the efficacy of ensitrelvir was demonstrated by significant reduction of viral RNA compared with placebo.

Conclusion

The population PK model was developed based on the plasma ensitrelvir concentration data from participants including patients infected with SARS-CoV-2 and the BWT was the most important covariate on ensitrelvir PK. The expected exposures for anti-viral effect at the clinical dose were obtained regardless BWT. The population PK model would be useful for understanding PK characteristics of ensitrelvir and the PK/PD results supported that the clinical dose of 375/125 mg is appropriate for treatment of SARS-CoV-2 infection.

Disclosures

All Authors: No reported disclosures
536. Development of post acute sequelae of SARS-Cov-2 infection (long Covid) in outpatient receiving monoclonal antibodies
Authors: Neto Amelia , Kak Vivek
Published: November 2023

Background

The development of post-acute sequelae of SARS-Cov-2 infection (long COVID), is a complex condition defined as a persistence of symptoms at least 3 months after initial infection. Although the etiology of long COVID is poorly understood, studies suggest it is related to immune dysregulation following infection. The development of long COVID is unclear with studies suggesting it can occur in up to 15% of individuals, however most of this data focuses on hospitalized patients. We examined the occurrence of long COVID in patients who received the monoclonal antibody (mAb) treatment at an outpatient infusion center.

Methods

We performed a study of high-risk symptomatic COVID patients who received the mAb treatment at an OP center from April 2021-22. Patients who received the mAb treatment were characterized based on the following criteria: age > 65, BMI > 25, or comorbidity. A follow up closed-ended survey was used to determine if patients experienced any of the following long COVID symptoms: fatigue, exertion intolerance, persistent cough or chest pain, dyspnea, brain fog, headaches, issues sleeping, myalgia, or loss of smell/taste.

Results

We called 1100 patients, yielding 615 responses, of which 57.7% (n = 355) fully recovered, while 42.3% (n = 260) reported experiencing long COVID. From the subset of individuals who experienced long COVID, 4.6% (n = 12) were hospitalized. In addition, 50% (n = 129) of long COVID patients reported having 3 or more symptoms, with fatigue, brain fog, and loss of smell/taste being the most prevalent. The characteristics and outcomes of patients who received the mAb treatment are shown in Table 1.

Conclusion

Long COVID was documented in almost half of high-risk symptomatic patients suggesting a higher incidence compared to the literature, despite a low hospitalization rate. Female sex, unvaccinated patients and those who received the mAb later were more likely to develop long COVID. Patients given steroids on/before the date of their mAb also had more long COVID. Predictors of long COVID based on our data includes female sex, vaccination status, and the administration/timing of immune modulators. Modulation of the immune system is likely important in controlling the development of long COVID. These results need to be validated in larger cohorts.

Disclosures

All Authors: No reported disclosures
544. Outpatient Remdesivir Use at a Stand Alone Children's Hospital
Authors: Rodriguez Brittany , Stimes Grant T , Hilliard Tanya J , Satter Lisa Forbes , Munoz Flor M
Published: November 2023

Background

When remdesivir was approved for non-hospitalized, high-risk patients with mild to moderate COVID-19, Texas Children’s Hospital (TCH) implemented an outpatient clinic for eligible patients to receive remdesivir infusions. There are limited data evaluating the use of outpatient remdesivir in pediatric patients. We describe the clinical characteristics and outcomes of the patients treated with outpatient remdesivir at TCH.

Methods

Patients that were referred to receive outpatient remdesivir from June 7, 2022 to April 5, 2023 were included. Information collected includes demographics, comorbidities, refusal reason, adverse events, emergency center (EC) visit or admission within 14 days after final dose, and EC visit or admission within 14 days of referral if patients did not receive remdesivir. Chi-square was used to determine differences between the groups.

Results

There were 187 patients referred during the study period. The median age of all referred patients was 8.8 years (IQR 4.84-12.96 years). The median time from reported symptom onset to dose 1 of remdesivir was 2 days (IQR 1-4 days). The comorbidities of all patients are listed in Figure 1. Out of the 182 patients, 69 patients (37.9%) received remdesivir, 10 patients (5.5%) were admitted prior to receiving their first dose, and 107 (58.8%) were not treated. The most common refusal reason was improvement between the referral and treatment evaluation visit (Figure 2). Among those treated, 8 patients (11.6%) visited the EC resulting in 7 admissions (10.1%) within 14 days of their last dose of remdesivir, while 7 patients (6.5%) that were referred but did not receive remdesivir visited the EC resulting in 3 admissions (2.8%) within 14 days of their referral being placed (p=0.04). More serious underlying conditions (e.g. immunosuppression, chronic lung disease, etc.) were more common among treated patients vs. untreated patients (p=0.00002).

Conclusion

Outpatient remdesivir was well tolerated among pediatric patients. In our series, the majority of high- risk patients receiving outpatient remdesivir treatment did not require subsequent EC visit or hospitalization. More robust data are needed to determine the clinical efficacy of this treatment for pediatric patients in the outpatient setting.

Disclosures

Lisa Forbes Satter, MD, ADMA: Advisor/Consultant|CsL Behring: Advisor/Consultant|Grifols: Advisor/Consultant|incyte: Advisor/Consultant|Pharming: Advisor/Consultant|Takeda: Advisor/Consultant Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB
558. Cost-effectiveness of Introducing Metagenomic Next-generation Sequencing (mNGS) for the Diagnosis of Suspected Respiratory Infections Patients in China
Authors: Peng Siyang , Liang Rui , Mao Sheng , Tang Wen , Tang Mi , Ai Yaping , Wang Junfeng , Hong Guanqi , Qu Shuli
Published: November 2023

Background

Early identification of respiratory pathogens is crucial for favorable clinical outcomes. Metagenomic next-generation sequencing (mNGS) offers an alternative approach to identify pathogens in complex clinical samples. This study aimed to assess the cost-effectiveness of using mNGS in combination with traditional methods in diagnosing suspected respiratory infections patients.

Methods

A decision tree model was developed to illustrate the clinical pathway for patients with suspected respiratory infections in China. Two strategies were compared, one utilizing mNGS combined with traditional pathogen detection methods, and the other relying solely on traditional methods including bronchoalveolar lavage fluid microbial culture, smear microscopy, and serological tests. The study was conducted from the Chinese healthcare system perspective. Survival outcome, life years outcome and cost outcomes were captured over a lifetime horizon. Model inputs, including cost (specimen collection cost, diagnosis cost, imaging examination cost, drug cost and inpatient bed cost), treatment efficacy, mortality, sensitivity and specificity of different testing strategies, were derived from published literature and experts’ interviews. Uncertainty was assessed by sensitivity analyses.

Results

The base case analysis suggested that, compared with traditional pathogen detection methods, mNGS combined with traditional methods resulted in longer life-year (average 0.18 life-year gain) and lower cost (average saving of 3,069 CNY (453 USD)), among all patients tested. The life-years gain was primarily driven by the more accurate diagnosis and the consequent administration of more effective etiological treatment. The cost saving was largely driven by the reduction of drug costs which resulted from precision medicine-based treatment, instead of empirical treatment. The probabilistic sensitivity analysis confirmed the robustness of the model.

Conclusion

Compared to traditional methods only, mNGS combined with traditional methods is a cost-effectiveness method for improving patient clinical outcomes while reducing healthcare costs.

Disclosures

All Authors: No reported disclosures
559. Results of the implementation of a molecular pneumonia panel at a hospital in the Dominican Republic: expanding the scope of detection and management
Authors: Guzman-Marte Anel E , Rojas-Fermin Rita A , Hernandez-Landa Ricardo Ernesto , Reyes-Batista Ledis , Camilo Glennys S
Published: November 2023

Background

Lower respiratory tract infections (LRTIs) have been associated to significant morbidity and mortality. Conventional microbiology methods often fail to identify the etiological agent due to lack of sensitivity or viral or fastidious pathogens. Pneumonia molecular diagnostics is able to expand the scope of pathogens detected, therefore, we describe our experience in the incorporation of this method, the difference in etiological identification and clinical decision making.

Methods

We performed a retrospective cohort study of 75 patients with Filmarray pneumonia panel from November 2020 to September 2022. We described demographics, co-morbid conditions, outcomes and correlation with standard cultures in patients who were admitted with LRTI at the Hospital General de la Plaza de la Salud, a 289-bed tertiary teaching hospital in the Dominican Republic.

Results

Amongst the 75 patients, 56.6% were male and the average age was 51 years old. The most common comorbidities were diabetes mellitus (81.6%), hypertension (40.8%) and nephropathy (10.5%). The panels had a positivity rate of 74.6% (56/75) versus a 35% (14/40) seen in cultures. The most frequent microbial targets detected were S. aureus (18%), P. aeruginosa (14,3%) and K. pneumoniae group (10%) and at least one antimicrobial resistance gene was detected in 50% (28/56), distributed as MecA/C and MREJ (35%), CTX-M (38%), KPC (10%), NDM (10%), VIM (8%), IMP (8%) and OXA-48 like (3%). A positive culture was most likely to occur when the number of copies/mL in the panel was ≥ 10˄5 (p-value < 0.001). A viral target was detected in 21 patients (28%) alone or coinfecting with a bacterial agent.

Conclusion

Not only did the pneumonia panels allow an earlier detection of the etiological agent, but they also identified more pathogens compared to cultures. This enabled targeted management by reducing the unnecessary use of antimicrobials as well as activating infection control measures when necessary (i.e Influenza). The results seen in this study, along with the expanded scope of pathogens detected, will definitely serve as an update into our current LRTI hospital guidelines.

Disclosures

All Authors: No reported disclosures
565. Antimicrobial susceptibility profiles of Acinetobacter species in blood: 10-year experience from a major United States reference laboratory
Authors: Bisono Garcia Bismarck S , Ranganath Nischal , Streck Nicholas , Schuetz Audrey N , Shah Aditya
Published: November 2023

Background

Antimicrobial resistance (AMR) is a threat to healthcare, and infections with antimicrobial resistant organisms carry significant morbidity and mortality. Owing to high rates of AMR, the Centers for Disease Control and Prevention listed Acinetobacter baumannii as a top priority pathogen for research and development of new antimicrobial agents. Antimicrobial susceptibility testing is challenging for this organism, and susceptibility profiles are variable, leading to need of a potential guidance document with assistance in selecting effective empiric therapeutic regimens.

Methods

We retrospectively reviewed the microbiology and antimicrobial susceptibility testing (AST) results for Acinetobacter spp. from blood culture isolates submitted to Mayo Clinic Laboratories from December 2012 to 2022. AST was performed using agar dilution and interpretations following Clinical & Laboratory Standards Institute (CLSI) guidelines. Isolates were identified by MALDI mass spectrometry and/or 16S sequencing, as available (Figure 1).Figure 1:Isolate identification

Isolate identification description. Isolates were analyzed based on this classification used in out laboratory.

Results

804 blood culture isolates were included. A. baumannii/calcoaceticus complex (27%) was most frequently isolated, followed by A. lwoffii (22%), and showed the highest resistance across all antimicrobials (73% susceptible or below) (Figure 2). A. baumannii/calcoaceticus complex showed rising resistance rates over time from 2012 to 2022 for meropenem, minocycline and ampicillin-sulbactam (Figure 3). Cefiderocol non-susceptible rate was 35% for A. baumannii/calcoaceticus complex.Figure 2:Antimicrobial susceptibility profiles for Acinetobacter spp.

Description of susceptibility profiles for Acinetobacter spp. isolates, based on the classification used by our laboratory. Antimicrobials are presented at the top and isolates on the left. Number of isolates analyzed are presented in the table with the percentage of the isolates susceptible to each antibiotic class in parenthesis.Figure 3:Acinetobacter baumannii/calcoaceticus complex isolates and resistance, trend

Trend of isolates per year and resistance percentage to meropenem, colistin, minocycline and amp-sulb. Number of isolates per year at the base of each bar; percentage of resistance for antimicrobials expressed on lines. Amp-sulb = ampicillin-sulbactam.

Conclusion

A. baumannii/calcoaceticus complex showed high levels of resistance ( >75%) across multiple antimicrobials and increasing rates of resistance over time from 2012 to 2022. A high number of cefiderocol non-susceptible organisms is also concerning (Figure 2).

Disclosures

Audrey N. Schuetz, MD, Merck: Advisor/Consultant
569. Utility of Repeat Molecular Diagnostic Testing in the Laboratory Diagnosis of Pulmonary Tuberculosis
Authors: Chia Jonathan
Published: November 2023

Background

Molecular diagnostic methods are commonly used to supplement microscopy and culture in the rapid diagnosis of pulmonary tuberculosis (TB). While international guidelines recommend the collection of multiple sputum samples for microscopy and culture due to their low sensitivity, the utility of performing multiple molecular tests is less well-defined. A retrospective analysis of molecular diagnostic testing in a high pre-test probability population was conducted to determine the impact of repeated testing on achieving diagnosis.

Methods

A review of 10406 requests for Mycobacterium tuberculosis polymerase chain reaction (PCR) testing, originating from the TB contact screening and treatment clinic of a national Infectious Diseases specialist centre, was conducted for the period of 1 Jan - 31 Dec 2022. 5336 patients with valid test results were identified. (Table 1)

PCR testing was performed using the Xpert® MTB/RIF (Cepheid) PCR assay, either in the clinic as a point-of-care test, or in the hospital’s microbiology laboratory. Acid-fast microscopy was performed in the microbiology laboratory using a combination of fluorochrome and Ziehl-Neelsen staining, while cultures were referred to a Biosafety Level 3 laboratory at another institution for culture and susceptibility testing using the Mycobacteria Growth Indicator Tube (MGIT) system.Table 1:PCR testing ordered by a tuberculosis contact screening and treatment clinic in 2022

Results

Out of 5336 patients identified, 4540 (85.0%) had 2 or more PCR tests performed within the first month of their initial encounter.

443 patients (8.3%) tested PCR-positive in total. 385 tested positive on their first test; further tests after the first identified another 58 cases. Compared to cumulative culture results, the sensitivity and specificity of the first PCR test performed in the target population was 65.2% and 98.3% respectively, with a negative predictive value (NPV) of 96.8%. Repeat PCR testing increased sensitivity to 69.3% and NPV to 97.5%. (Tables 2 and 3) 74 initially-negative patients would need to be retested to identify an additional PCR-positive case, with potential costs of SGD $14,504 per case ($196 per test).Table 2:Comparison of single PCR test performance against cumulative mycobacterial culturePPV = Positive Predictive Value NPV = Negative Predictive ValueTable 3:Comparison of repeated PCR test performance against cumulative mycobacterial culturePPV = Positive Predictive Value NPV = Negative Predictive Value

Conclusion

For purposes of resource allocation, rationalisation of repeat testing in the diagnosis of pulmonary TB should be considered as an alternative to routine retesting, even in a high-risk population.

Disclosures

All Authors: No reported disclosures
571. Development of a Multiplexed PCR Assay for the Detection and Differentiation of Non-Tuberculosis Mycobacteria (NTM)
Authors: Cowden Scott , Grantham James , Davidson Jerod , Lute Emily , Nutt Jamie , Bixler Ellis , Kleiboecker Steve
Published: November 2023

Background

Current NTM diagnostics rely on a combination of testing modalities including clinical presentation, radiology, and culture. NTM cultures often have extended turnaround times. Additionally, the importance of discriminating etiological agents in the Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAbC) due to increasing drug resistance is now recognized. Here we describe the development of real-time PCR assays targeting members of the MAC and MAbC responsible for NTM infections. The objective was to develop a rapid diagnostic assay for the detection of pathogenic NTM directly from patient blood and sputum.

Methods

The MAC qPCR assay design allows for non-specific yet inclusive detection of M. avium subsp. avium, hominissuis, paratuberculosis, and sylvaticum, M. intracellulare, M. intracellulare subsp. chimaera and M. colombiense. The MAbC assay allows for inclusive and differential detection of M. abscessus subsp. abscessus, bolletii and massiliense. MAC and MAbC designs were screened to identify candidates and were then multiplexed with an internal control assay. Performance was evaluated in spiked whole blood and sputum.

DNA was extracted using the MagMAX™ DNA Multi-Sample Ultra 2.0 Kit and KingFisher™ Flex system (Thermo Fisher). Amplification was performed using TaqMan™ Fast Advanced Master Mix (Thermo Fisher) and the Applied Biosystems™ 7500 Fast instrument.

Results

Linear regression of plasmid standards for assays targeting MAbC-specific gene targets produced R2 values >0.99 and slopes ranging from -3.39 to -3.35 (97-99% efficiency). Linear regression of standards for assays targeting MAC-specific gene targets produced R2 values >0.99 and slopes ranging from -3.47 to -3.35 (94-98% efficiency). Assay specificity was determined by challenging the assays with NTM’s outside of each respective complex as well as other common bacterial pathogens.

Conclusion

Development of NTM PCR assays to detect and differentiate slow growing Mycobacteria aids in rapid diagnosis and provides insight into selection of appropriate antibiotic therapies. The assays described here exhibit excellent linearity, specificity, inclusivity and with additional development will provide a reliable means of detecting and differentiating relevant NTM species.

Disclosures

Scott Cowden, MS, MB ASCP(CM), Eurofins Viracor: Employee James Grantham, n/a, Eurofins Viracor: Employee Jerod Davidson, n/a, Eurofins Viracor: Employee Emily Lute, n/a, Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee
573. Creation of a Statewide Ambulatory Urinary Antibiogram and Evaluation of Regional and Temporal Variation in Antibiotic Susceptibility
Authors: Curanovic Dusica , Chin Jacinta , Garcia Chris , Wright Catherine , Stainback Rita , Martin Melissa , Naccache Samia , Smith Kristen , Engler Howard , Flett Kelly
Published: November 2023

Background

Empiric antibiotic selection in outpatient care often relies on inpatient antibiograms which may not accurately reflect ambulatory susceptibility rates. To address this, Novant Health (NH) and Labcorp analyzed urine culture results from North Carolina (NC) to create an ambulatory antibiogram and assess temporal and regional differences.

Methods

Cross-sectional study of urine culture data collected 1/1/20-12/31/21 from ambulatory sites in NC. Testing and antibiogram preparation were performed at Labcorp (Burlington, NC) based on CLSI guidelines (M100 S28). Pediatric and adult data were compiled separately. NH and state-wide data were analyzed using the chi-square or Fisher exact test with Bonferroni correction for multiple comparisons.

Results

In 2021, Escherichia coli was the most common isolate for NH (n=18937 adult, n=624 pediatric) and state-wide (n=87,226 adult; n=2696 pediatric). E. coli was ≥ 80% susceptible to all tested antibiotics except ampicillin; Klebsiella pneumoniae was ≥ 80% susceptible to all except nitrofurantoin; and Proteus mirabilis/penneri was ≥ 80% susceptible to all antibiotics tested. Susceptibility rates were similar between NH and state-wide data except for lower susceptibility to ceftriaxone (94% vs 95%; p< .001). Compared to 2020, state-wide adult E. coli isolates from 2021 had increased susceptibility for amoxicillin/clavulanic acid (86% vs 85%), ampicillin (60% vs 59%), cephalosporins (84-93% vs 82-92%), and quinolones (87% vs 86%) (p< .001 all). NH isolates did not show significant changes. Susceptibility rates by region were similar, except for lower susceptibility to cefuroxime among adult E. coli isolates in the Triad region relative to state-wide (82% vs 84%; p< .001). No significant temporal or regional differences in susceptibility were observed for K. pneumoniae, Proteus spp., P. aeruginosa, and among pediatric samples.

Conclusion

Susceptibility data were largely similar in NH vs. state-wide data, and between regions. Small but statistically significant temporal changes were found in state-wide data. Overall, our results support use of a state-wide antibiogram to inform treatment choices across all regions and within specific healthcare systems.

Disclosures

Dusica Curanovic, PhD, Labcorp: employed by labcorp during study|Labcorp: Stocks/Bonds Chris Garcia, MD, Labcorp: Prior employee|Labcorp: Stocks/Bonds Catherine Wright, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds Rita Stainback, MS, MT (ASCP) SM, DLM, Labcorp: Employee|Labcorp: Stocks/Bonds Melissa Martin, BS, Labcorp: Employee Samia Naccache, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds Kristen Smith, PhD, bioMerieux: Employee|Labcorp: Stocks/Bonds Howard Engler, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds
574. Daily Antibiotic Utilization Prescription Audit in the Infectious disease (ID) and Non-ID Department in Hospitalized Patients: A Prospective Case-Control study in a Teritiary care hospital
Authors: Dorairajan Suresh Kumar , Pavithra G , Hari Nivetha , Angel Jenifer F , Vijayakumar Oviya , Eiphan Kezia V
Published: November 2023

Background

Antimicrobial prescription audits were often carried out to reduce the overuse of antibiotics. Usually, audits were performed over periodical intervals. Daily antibiotics audits were time consuming and labour intensive. Though it"s practically impossible, we tried. However, we conducted this audit over a three-month period as daily audit and the cases were regularly followed. It is the prospective case-control study of antibiotic utilizations from prescriptions on ID and non-ID department.

Methods

This Prospective Case-Control study was conducted in tertiary care hospital in India for a period of 3months (Jan-mar2023). Data regarding demographics, antibiotic therapy, diagnosis, rational antibiotic usage (indications mentioned or not), type of therapy (surgical prophylaxis, definitive and empirical therapy) and 48hrs review of antibiotic prescriptions (escalation, de-escalation, continuation and dis-continuation therapy) of both groups were collected by Pharm-D interns from the medical records and analysed using SPSS version 26.0.

Results

During the study period, 899 subjects’ medical records were audited for antibiotic usage from the prescriptions. The comparative data were shown in table-1.

Conclusion

1/3rd of the cases acquired ID opinion which is significantly less than the non-ID department. Predominantly ID opinion is acquired when culture shows positive results. In most cases, the indications were mentioned only by the ID and not by the non-ID team. Discontinuation (28.1%) and de-escalations (18.7%) done by the ID was found to be significantly higher than non-ID. Based on this, we conclude that ID opinion play a crucial role in selection of antibiotics, both in terms of definitive and empirical choices. This study has certain limitations where, outcomes will be followed further.

Disclosures

All Authors: No reported disclosures
577. Visual Recognition of GAS Pharyngitis Based on a Photographic Image: A Physician Survey
Authors: Hamdy Rana F , Berkowitz Deena , Zhang Anqing , Ansusinha Emily , Dome Jeffrey S , Shekhar Raj
Published: November 2023

Background

Sore throat is one of the most common reasons for an ambulatory pediatric visit in the U.S., and Group A Streptococcus (GAS) pharyngitis is diagnosed in 10-30% of children presenting with pharyngitis. While some prediction rules based on clinical signs and symptoms can reliably identify a low-risk patient, clinical signs or symptoms alone are insufficient in identifying a patient with GAS pharyngitis. The ability to identify GAS from non-GAS pharyngitis from a photographic image has not been previously determined. We conducted a survey to determine clinicians’ ability to identify a GAS vs non-GAS pharyngitis based on a photographic image presented with and without a patient’s clinical data.

Methods

We devised an online electronic survey with photographic images of the posterior pharynx of children presenting with pharyngitis without upper respiratory infection (URI) symptoms who had been evaluated for GAS pharyngitis. The survey included 20 images of the pharynx (10 positive, 10 negative for GAS) with and without clinical data. For each image, participants were asked their prediction for the patient’s GAS test result. We calculated percentage of individual responses correctly identifying GAS vs non-GAS pharyngitis.

Results

102 providers participated in the online survey (23% response rate) and 86 completed all questions in the survey. When counting each response independently, the overall percent of images correctly identified as positive or negative for GAS pharyngitis was 55.9% -- 53% without clinical data, and 59.4% with clinical data (p< 0.001). Among images corresponding to patients who tested positive for GAS pharyngitis, the overall percent correct was 46.6% (38.6% without and 56% with clinical data), and among images corresponding to patients who tested negative for GAS pharyngitis, the percent correct overall was 67.3% (70.5% without and 63.4% with clinical data)(Table 1).

Table 1: Number of responses from clinician’s impression correct by those with GAS pharyngitis and vs. those without GAS pharyngitis

Conclusion

When presented with a photographic image of the pharynx of a patient presenting with pharyngitis, clinician respondents were able to identify just over half of photographic images as GAS vs non-GAS pharyngitis in children presenting with sore throat and without URI symptoms; this increased modestly when accompanied with clinical data.

Disclosures

All Authors: No reported disclosures