bluuebunny/crossref_metadata_2025 huggingface dataset:
511. Risk Factors for Seeking Medical Care Following Nirmatrelvir-Ritonavir (Paxlovid) Treatment For COVID-19
Authors: Bhargava Ashish , Szpunar Susan M , Sharma Mamta , Saravolatz Louis
Published: November 2023

Background

In December 2021, the FDA issued an emergency use authorization (EUA) for nirmatrelvir-ritonavir (Paxlovid). This was based on the randomized placebo-controlled trial data from the EPIC-HR study which showed that high-risk non-hospitalized patients given Paxlovid had an 88.9% reduction in the relative risk of progression to hospitalization or death by Day 28 in coronavirus disease 2019 (COVID-19). We aimed to study the risk factors for seeking medical care following Paxlovid treatment.

Methods

In this historical cohort study, we assessed risk factors for high-risk non-hospitalized patients treated with Paxlovid from January 1, 2022, to December 31, 2022, at outpatient facilities associated with Ascension St. John Hospital. Our outcome variable was the composite of subsequent evaluation in the Emergency Department (ED) or inpatient admission within four weeks of their Paxlovid treatment. Data were analyzed using SPSS v. 29.0. The study was approved by the IRB.

Results

Of 371 patients who received Paxlovid treatment, the mean (SD) age was 59.4 (±13.8) years; 63.9 % (237) were female, and 77.7% (282) white. The mean body mass index (BMI) of the cohort was 31.3 ± 7.8 kg/m2. The incidence of the composite event was 6.7% (25/371). The risk of the composite event was higher in patients with a history of myocardial infarction (MI) (28 % vs 9.3%), congestive heart failure (CHF) (12 % vs 2.3%), chronic lung diseases (CLD) (48 % vs 26.4%) and diabetes mellitus (DM) with complication (24% vs 4.1%), respectively. Alcohol users were less likely to seek medical care following Paxlovid (40 % vs 63.7%, respectively). There were no differences in BMI, tobacco use or vaccination rates between the groups. In multivariable logistic regression, factors associated with seeking medical care post-Paxlovid were female sex (OR 4.6; 95% CI 1.4-15.3; p= 0.013), alcohol use (OR 0.4; 95% CI 0.2-0.9; p= 0.039), MI (OR 4.0; 95% CI 1.4-11.8; p=0.011), DM with complications (OR 6.9; 95% CI 2.0-23.3; p= 0.002), CLD (OR=3.9, 95% CI 1.1-13.5; p=0.03), at the time of Paxlovid treatments.

Conclusion

Independent risk factors for seeking medical care following Paxlovid treatment for COVID-19 were MI, CHF, CLD, and DM with complications while alcohol users were less likely to seek medical care following the Paxlovid treatment.

Disclosures

All Authors: No reported disclosures
528. Matched Retrospective Study, Comparing Molnupiravir to Nirmatrelvir-Ritonavir (Paxlovid) in the Treatment of Mild-Moderate COVID-19 in Immunocompromised Cancer Patients
Authors: Haddad Andrea , Moussa Mohammad , Hachem Ray Y , Jiang Ying , Dagher Hiba , Chaftari Patrick , Chaftari Anne-Marie , Raad Issam I
Published: November 2023

Background

Paxlovid has been shown to reduce the risk of progression (hospitalization/death) by 88% as compared to placebo, while molnupiravir reduced that risk by 31%. However, these two agents have not been compared in the same study patient population. We therefore conducted a matched controlled study, comparing molnupiravir to paxlovid in terms of safety (adverse events and drug-drug interactions) and efficacy (progression and rebound events) in the treatment of mild-moderate COVID-19 in immunocompromised cancer patients.

Methods

This is a single center, retrospective study that included 240 cancer patients diagnosed with COVID-19 in 2022. Patients who received molnupiravir were matched to those who received paxlovid on a 1:2 ratio, based on age group (18-64 years vs. ≥ 65) and type of cancer (lung cancer, hematologic malignancy, or other solid tumors). We collected patient demographics, comorbidities, malignancy history and treatment, vaccination status, as well as post-treatment progression and safety information. We used margins of 10% with 95% confidence intervals to determine the equivalence of outcomes.

Results

As shown in table 1, the two groups had comparable demographics, underlying malignancies, and most comorbidities, however smoking history, underlying CKD, and CAD were more common in the molnupiravir group. Similarly presenting symptoms were comparable, but cough, dyspnea and sore throat were more prevalent in the molnupiravir group.

By multivariate analysis, 3 factors were independently associated with progression: hypertension, cough on presentation and failure to complete the 5-day course of antiviral therapy - P < 0.037. However, multivariate analysis failed to show any difference between the 2 groups in terms of progression to severe/disease and rebound events with equivalent margins within 10%.

Patients who received paxlovid however were significantly more prone to drug-drug interactions/adverse events (28% vs. 0 - P < 0.0001).

Comparing patients treated with molnuprivir versus those treated with paxlovid

Conclusion

In the treatment of mild to moderate COVID-19 in cancer patients, molnupiravir was comparable to paxlovid in preventing progression to severe disease/death and rebound events, with a superior safety profile.

Disclosures

Issam I. Raad, Distinguished Professor, Novel Anti-Infective Technologies, LLC: Technology License
540. A Dose-Comparison Study of Methylprednisolone on Mortality in COVID-19 Patients Require Oxygen in A Tertiary Hospital in Thailand
Authors: Piyapan Pattraporn , Masamhisak Viranpat
Published: November 2023

Background

Dexamethasone 6 mg IV for 10 days or an equivalent dose of another corticosteroid like methylprednisolone (MP) is recommended for severe COVID-19 patients. A higher dose has been reported as beneficial for severe patients. We aimed to compare the effect of < 3 and ≥ 3 mg/kg/day (MKD) of MP in patients who require conventional oxygen therapy or high-flow nasal cannula

Methods

A retrospective study was conducted between June and October 2022 in Bhumibol Adulyadej Hospital by reviewing the medical record of COVID-19 patients requiring conventional oxygen therapy or high-flow nasal cannula. The patients were divided into two groups by the dosing of MP to ≥ 3 MKD and < 3 MKD to compare baseline characteristics, treatment, and clinical course. Multivariate logistic regression was used to identify factors associated with mortality.

Results

There are 197 patients included in the study: 100 from ≥ 3 MKD group and 97 from < 3 MKD group. The mean daily dose of MP was 4.16 (± 0.93) and 2.25 (± 0.55) MKD. There were no statistical differences between the baseline characteristic of the two groups except enoxaparin prophylaxis were more used and LDH were higher in ≥ 3 MKD group. Mortality at 28 days was 26% in ≥ 3 MKD group vs 8.2% in < 3 MKD group (adjusted odd ratio, 3.52 [95% CI, 1.44-8.62]; P = 0.006). Age > 65 is also an independent factor associated with mortality (P = < 0.001). Bacteremia occurred in 10% VS 2% of ≥ 3 and < 3 MKD groups, respectively (odd ratio, 0.19 [95% CI, 0.04-0.89]; P = 0.02).

Conclusion

During the fourth wave of the COVID-19 pandemic with the Delta variant in Thailand, we found patients requiring conventional oxygen therapy or high-flow nasal cannula who received a higher dose of MP (≥ 3 MKD) were associated with significant 28-day mortality.

Disclosures

All Authors: No reported disclosures
547. Molnupiravir and Nirmatrelvir/Ritonavir Effectiveness in Reducing the Risk for COVID-19 Disease Progression and Death
Authors: Paraskevis Dimitrios , Gkova Mary , Mellou Kassiani , Mellou Kassiani , Gkolfinopoulou Kassiani , Kostaki Evangelia Georgia , Loukides Stylianos , Kotanidou Anastasia , Skoutelis Athanasios , Thiraios Eleftherios , Saroglou George , Zografopoulos Dimitrios , Mossialos Elias , Zaoutis Theoklis , Gaga Mina , Antoniadou Anastasia , Tsiodras Sotirios
Published: November 2023

Background

Molnupiravir (M) and Nirmatrelvir/Ritonavir (N/R) have been authorized for use in COVID-19 patients at high risk for severe disease. We aimed to evaluate the effectiveness of M and N/R in highly vulnerable SARS-CoV-2 patients using a retrospective cohort study design.

Methods

The study population consisted of SARS-CoV-2 infected non-hospitalized patients in Greece, aged 65 years or older, that received M between February 2 and March 25, 2022 and N/R between March 26 and July 20, 2022. The impact of each drug was determined via comparisons with age-matched control groups of SARS-CoV-2-positive patients who did not receive oral antiviral therapy, using as outcome (i) hospital admission with COVID-19 within 10 days after tested positive, and (ii) death from COVID-19 within 35 days from positive test.

Results

Overall, 4,240 M and 13,861 N/R recipients were enrolled. Administration of M significantly reduced the risk of hospitalization (Odds Ratio [OR] = 0.40, p < 0.001) and death (OR = 0.31, p < 0.001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of N/R also resulted in significant reductions in the risk of hospitalization (OR = 0.31, p < 0.001) and death (OR = 0.28, p < 0.001). Similar to M, the impact of N/R was more substantial among elderly patients and in those with high levels of drug adherence.

Conclusion

N/R and M use prevented hospital admissions and death in a large real-world study of highly vulnerable patient populations.

Disclosures

All Authors: No reported disclosures
560. Circulating Pneumocystis jirovecii Genotypes in Central-Eastern Canada
Authors: Roy Valerie , Desjardins Anne , Dufresne Simon F , Marchand-Senécal Xavier , Carignan Alex , Dufresne Philippe J
Published: November 2023

Background

Genotyping allows description of Pneumocystis jirovecii (Pjp) heterogenous population structure and clusters linked to nosocomial transmission. It may also reveal mutations associated with resistance to antimicrobials. Recently, a multilocus sequence typing (MLST) scheme by Pasic et al. (2020) has been adopted by International Society for Human & Animal Mycology (ISHAM) as the typing method of choice for this fungus.

Methods

We analyzed Pjp specimens submitted to the Laboratoire de santé publique du Québec for genotyping between February 2013 and March 2023. The loci genotyped were those used in the Pasic et al. scheme (mt26s, CYB, SOD, B-TUB) with the addition of dihydropteroate synthase (DHPS).

Results

296 specimens from Central-Eastern Canada were genotyped: 266 from Quebec, 29 from Ontario, 1 from New Brunswick. Most specimens were submitted as part of outbreak investigations. 187 complete (161 unique and 26 mixed) and 109 incomplete genotypes were obtained. Among specimens with complete and unique genotypes, 87 isolates matched with 23 previously known sequence-types (ST), according to ISHAM MLST scheme. Twenty-four new ST with currently known alleles were described. We also identified 36 isolates with previously undescribed alleles which resulted in 21 new distinct ST. MLST typing allowed epidemiological description of 9 outbreaks. Out of 243 specimens for which DHPS amplification was possible, only one showed a mutation (DHPS 57) previously linked to trimethoprim-sulfamethoxazole resistance. This contrasts with high prevalence of mutant strains seen in some countries. ST-52 was the most prevalent with 32 isolates (20% of strains with complete and unique genotypes) and was involved in 3 outbreaks. A specific CYB mutation (G369T) conferring resistance to atovaquone was uncovered in 18 ST-52 isolates, all associated with an outbreak in one hospital.

Conclusion

This is the first multicenter study to describe circulating genotypes of Pjp in Central-Eastern Canada. It represents the largest genotyping assembly performed according to the recent ISHAM MLST scheme. We described 45 new ST to be added to ISHAM’s 52 current genotypes. Our study highlights the usefulness of MLST typing in Pjp outbreak investigation and identification of potentially resistant isolates.

Disclosures

Simon F. Dufresne, MD, AvirPharma Inc.: Grant/Research Support|Merck Canada Inc.: Grant/Research Support Alex Carignan, MD, MSc, GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: Honoraria|Moderna: Advisor/Consultant|Moderna: Honoraria|Orimed Pharma: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria
570. Impact of a Blood Culture Direct Identification Procedure on Time to Identification for Gram-Negative Organisms and Antimicrobial Management in Bloodstream Infections
Authors: Coppinger Corwin , Cubillos Ashley L
Published: November 2023

Background

Multiplex polymerase chain reaction (PCR) and microarray diagnostic methods for rapid identification (ID) in Gram-negative bloodstream infections (GNBSI) remain unavailable in many healthcare facilities. Use of other methods such as matrix-associated laser desorption/ionization time-of-flight (MALDI-TOF) along with rapid sample preparation from positive blood cultures, may decrease time to ID and targeted antimicrobial therapy in BSI. This study compares time to ID and final susceptibilities of Gram-negative bacteria (GNB) in positive blood cultures using a rapid MALDI-TOF direct ID process versus conventional culture methods, as well as impact on antimicrobial therapy in GNBSI.

Methods

This retrospective cohort included patients ≥18 years of age who had a positive blood culture with a GNB from January 1 through December 31, 2022, at a hospital serviced by the microbiology lab at Banner University Medical Center Phoenix (conventional ID) or Banner University Medical Center Tucson (direct ID). Direct ID consisted of using MALDI-TOF for immediate ID of a centrifuged sample from a GNB-positive blood culture bottle. The primary outcome was time to GNB ID between the two groups. Secondary outcomes included time from positive blood culture to susceptibility reporting, definitive antibiotic regimen, and hospital discharge. Statistical analysis performed with Wilcoxon Rank-Sum testing for continuous data, and Chi square testing for nominal data.

Results

A total of 254 patients were evaluated, with 100 included in each group. Median time to bacterial ID in the direct group vs. conventional group was 6.1 hr vs 29.2 hr (P< 0.0001). No differences in secondary outcomes, including times to final susceptibility (54.0 hr vs 60.9 hr, P=0.73), definitive antibiotic regimen (49.5 hr vs 44.9 hr, P=0.42), and hospital discharge (132.5 hr vs. 124.4 hr, P=0.85) were noted, though this study may have been unable to detect differences in such outcomes due to variance in organism resistance patterns and clinical practice between facilities.

Conclusion

Direct MALDI-TOF ID significantly decreases time to organism identification in GNBSI compared with conventional methods. Utilization of direct ID plus antimicrobial stewardship interventions in GNBSI is an area of opportunity.

Disclosures

All Authors: No reported disclosures
580. Changes in Serotype Distribution of Invasive Pneumococcal Infections in South Korea Before and After the COVID-19 Outbreak
Authors: Kang Da Yun , Kim Ye Eun , Yun Ki Wook , Choi Eun Hwa
Published: November 2023

Background

The introduction of extended-valency pneumococcal conjugate vaccine (PCV) since 2014 has changed the serotype distribution in South Korea. The COVID-19 pandemic in 2020 has changed the epidemiology of several infectious diseases significantly, involving the invasive pneumococcal disease (IPD).

Methods

This study obtained sterile body fluid samples of IPD in patients under 19 years old from January 2014 to April 2023 in South Korea, involved in multihospital-based surveillance system. Serotype distribution and multilocus sequence typing were performed for each sample. Vaccine serotypes (VTs) and nonvaccine serotypes (NVTs) were classified. The characteristics of IPD were compared between the pre-COVID-19 period (January 2014 to December 2019) and post-COVID-19 period (January 2021 to April 2023).

Results

A total of 230 isolates of Streptococcus pneumoniae from sterile body fluid samples were obtained. Among those, VTs accounted for 14.3% of cases (19A, 8.3%; 19F, 3.0%; and 6A, 1.3%), NVTs for 83.9% (10A, 23.0%; 15A, 9.1%; 15C, 7.8%; 15B, 6.1%; 23B, 6.1%), and four cases (1.7%) were nontypeable. Serotype 10A decreased to 14.6% in the post-COVID-19 period, which was the most common serotype in the pre-COVID-19 period (25.4%). Among the NVTs, isolates of serotype 6D, 7C, 11A, 12F, 13, 20, 22F, 33F, 37, and 38 were not found in the post-COVID-19 period, although they accounted for 18.5% in the pre-COVID-19 period. Meanwhile, serotypes 6C, 15B/C, and 23B increased from 0.6%, 12.7%, and 2.9% in the pre-COVID-19 period to 8.3%, 18.8%, and 16.7% in the post-COVID-19 period, respectively. All the serotype 6C isolates found in the post-COVID-19 period were sequence type 13556. 66.7% of serotype 15B/C and 87.5% of serotype 23B in the post-COVID-19 period showed clonal complex 166.

Conclusion

The COVID-19 pandemic has resulted in a shift in the predominant serotypes of invasive pneumococcal infections, with an increase in serotypes 6C, 15B/C, and 23B, which seems to be related with a certain clonal expansion. Notably, the cross-protection conferred by the PCV against serotype 6A appears to be insufficient for serotype 6C.

Disclosures

All Authors: No reported disclosures
586. Characterizing the Clinical Outcomes of Patients with Positive Blood Cultures Not Identified by Rapid Diagnostics
Authors: McLeod Caleb C , Tan Karen K , Abdul-Mutkabbir Jacinda
Published: November 2023

Background

Rapid diagnostics tools (RDTs) have improved clinical outcomes by prompt identification of pathogens in blood cultures, leading to the initiation of directed empiric antibiotic therapy. However, several organisms are unidentified by RDTs, which may delay appropriate antimicrobial therapy and increase mortality risks. Studies characterizing these off-panel organisms are limited, and guidance for antimicrobial therapy is unavailable. We sought to characterize the off-panel organisms encountered in blood cultures and provide important insights into the pathogens that may be missed by RDTs to improve the clinical management of bacteremia.

Methods

This was a retrospective study conducted from 8/2018 to 5/2021 at an academic medical center in Loma Linda, California. All adult patients with blood cultures processed on the Verigene (RDT) platform were screened for inclusion. Patients were included if Verigene was unable to detect a target organism. Species identification and antimicrobial susceptibility were performed with MicroScan WalkAway or sent to a reference laboratory if unidentifiable by MicroScan. Patient demographics, comorbidities, suspected source of infection, discharge disposition, and readmissions were determined by chart review.

Results

Out of 1,071 blood cultures screened, 80 (47 Gram-positive [GP] and 33 Gram-negative [GN] isolates were not identified by Verigene. While not significant, patients with off-panel GN bacteremia were older (65.5 vs 58 years, p=0.074) and had longer durations of stay (11 vs 9 days, p=0.149) than patients with unidentified GP isolates. Patients with off-panel GN isolates were also more likely to have a comorbid malignancy than those with off-panel GP isolates (42% vs 26%, p=0.112) and more likely to present with severe sepsis (89% vs 79%, p =0.376), though these differences were not significant. Cefepime and piperacillin/tazobactam were reliable agents for GN isolates (11/13, 18/21), and vancomycin retained activity against unidentified GP isolates.

Conclusion

Patients with GN organisms not identified by RDTs are more likely to present with severe sepsis and less likely to survive hospital discharge than those with unidentified GP organisms. Further research is needed to guide antimicrobial therapy for off-panel results.

Disclosures

Jacinda Abdul-Mutkabbir, PharmD,MPH, Entasis Therapeutics: Advisor/Consultant|Entasis Therapeutics: Honoraria|shionogi: Advisor/Consultant|shionogi: Honoraria
597. False Positive Carbapenemase Test in Carbapenem Resistant Acinetobacter baumannii
Authors: Tao Lili , Bentley Emily , Russo Carmella , Khan Ayesha , Rhoads Daniel D , Humphries Romney
Published: November 2023

Background

The detection of carbapenemases in carbapenem resistance gram negative organisms is necessary for appropriate antibiotic treatment and infection prevention. Lateral flow testing for the most common carbapenemases, KPC, NDM, VIM, IMP and OXA-48 is FDA-cleared for use in Enterobacterales and Pseudomonas aeruginosa. We evaluated use this assay for the detection of carbapenemases in carbapenem-resistant Acinetobacter baumannii (CRAB), which yielded false positives for the IMP carbapenemase.

Methods

CRAB (n=22) isolated from routine clinical cultures at two sites were evaluated. Isolates were tested by the NG-Test CARBA 5 (NG Biotech, Guipry, France). Phenotypic metallo-β-lactamase testing was performed using meropenem-EDTA disk and imipenem-EDTA disk method, including positive controls (NCTC 13476, Escherichia coli, IMP+; BAA 2146, Klebsiella pneumoniae, NDM+) and negative controls (BAA 1706, K. pneumoniae, negative for carbapenemase, BAA 1705, K. pneumoniae, KPC+). The absence of blaIMP was further confirmed by whole genome sequencing (WGS) using MiSeq (Illumina, CA). The identification of antibiotic resistance genes using WGS data was performed using BV-BRC pipelines (https://www.bv-brc.org).

Results

Of 22 isolates, 14 (66.7%) tested positive for IMP using NG-Test CARBA 5. No other carbapenemases were detected in these isolates by the lateral flow assay. Metallo-β-lactamase activity was not detected in any of the CRAB isolates. WGS and antibiotic resistance gene identification using Comprehensive Antibiotic Resistance Database (CARD) and National Database of Antibiotic Resistant Organisms failed to identify any blaIMP or other metallo-β-lactamase genes in the CRAB isolates. Β-lactamase genes detected by WGS in CRAB isolates were listed in Table 1.

Conclusion

Positive IMPs detected by NG-Test CARBA 5 in CRAB isolates were most likely false positive results. Further confirmative tests may be indicated for the off-label use of NG-Test CARBA 5.

Disclosures

Daniel D. Rhoads, MD, Hardy Diagnostics: Grant/Research Support Romney Humphries, PhD, D(ABMM), M(ASCP), Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Ventorx: Advisor/Consultant
599. Rapid Molecular Identification of Staphylococcus aureus and Methicillin Resistance in Blood Isolates Leads to Improved Patient Outcomes
Authors: Volk Cecilia , Meyer Ethan , Jacobs Deanna , Rose Warren
Published: November 2023

Background

Staphylococcus aureus bacteremia (SaB) is a common infection with a high mortality rate. Optimal therapy for SaB depends on susceptibility, and the use of anti-staphylococcal beta-lactams (ASBL) for MSSA bacteremia leads to lower mortality rates compared to vancomycin. For this reason, rapid susceptibility results, such as molecular detection using the Cepheid Xpert MRSA/SA Blood Culture PCR system, are important for patient management. At our institution, providers have varying levels of confidence in this assay, with some preferring to wait for traditional susceptibility results (AST) before narrowing therapy. This study aimed to both assess concordance between PCR results and AST and determine if waiting for AST leads to differences in patient outcomes.

Methods

All patients diagnosed with SaB at a single US academic medical center during 2019-2022 were included in a retrospective analysis. Data regarding blood culture results, administered antibiotics, and all-cause mortality was collected. For MSSA, optimized therapy was defined as an ASBL (oxacillin or cefazolin).

Results

A total of 288 patients with SaB were included (22.2% MRSA). Three isolates had discordant PCR and AST, all reported an MSSA isolate as MRSA. For MRSA, the positive-predictive value was 95.5% and negative-predictive value was 100%. The average time between PCR and AST results was 38.3 hours. Amongst 220 patients with MSSA bacteremia, 28 never received optimized therapy due to early mortality or other infections/conditions. Of the remaining 192 patients, 137 started an ASBL based on PCR results. The average time from culture draw to optimized therapy was 28.9 hours. Fifty-five patients did not receive ASBL until after AST was available, which increased the time to optimized therapy to 72.7 hours. This delay in therapy led to a significant increase in 30-day mortality rate (21.8% vs 10.2%, P=0.0337).

Conclusion

The Cepheid Xpert MRSA/SA Blood Culture had reliable results that led to a faster time to optimized therapy. Lower mortality was observed when providers opted to start an ASBL based on MSSA PCR results instead of waiting for AST. The mortality benefit of rapid PCR testing in SaB appears to stem from earlier initiation of ASBL therapy for MSSA in addition to improving optimization of MRSA therapies.

Disclosures

Warren Rose, PharmD, MPH, Basilea: Honoraria|Ferring: Honoraria|Merck: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Honoraria
602. Usefulness of the DSTM Method in the Era of Drug Resistance
Authors: Yamagishi Yuka , Nakayama Norihisa , Doke Akito , Iwame Saya , Nishida Yoshie , Tokuhiro Shinji , Yokoyama Akihito , Mikamo Hiroshige
Published: November 2023

Background

Rapid drug susceptibility testing is required as a measure against drug-resistant bacteria. The usefulness of the drug susceptibility testing microfluidic device (DSTM) method, which evaluates drug susceptibility based on morphological changes of bacteria in microfluidic channels, has been reported. We reported that this method can be used as a rapid screening method for ESBL and MBL. In this study, we confirmed the applicability of AmpC to this method. We have also demonstrated the usefulness of this method in directly testing blood cultures with a simple pretreatment. We evaluated blood cultures using this protocol and confirmed its usefulness in a clinical setting.

Methods

We evaluated the ability of DSTM to screen for 84 ESBLs, 24 MBLs, and 43 AmpC strains from clinical isolates with confirmed drug resistance and 156 strains not producing the above enzymes. Furthermore, blood cultures were evaluated using DSTM, and its efficacy was confirmed in clinical practice. A total of 178 specimens that tested positive in the blood culture bottle and were detected as Gram-negative rods by MALDI TOF-MS were evaluated. The specimens were pretreated by two centrifugation procedures to remove blood cell components and evaluated by the DSTM method. For confirmation, resistance genes were evaluated by PCR.

Results

Sensitivity and specificity of ESBL were 95% and 100%, respectively; MBL were 96% and 98%, respectively; AmpC were 58% and 98%, respectively. It was found that the detection methods for chromosomal and plasmid AmpC need to be optimized for each. All specimens evaluated successfully removed blood cell components. Numbers of ESBLs were 21 from E, coli and K. pneumoniae complex and MBLs were 2 from M. odoratimimus using DSTM. 4 specimens containing Proteus mirabilis (CTX-M-2) from one patient were false negative for ESBL because those were insensitive to CVA. There were no false positives in the all strains.

Conclusion

As with ESBL and MBL, AmpC could be detected by using morphological changes of the bacteria as an indicator. The pretreatment method for blood culture-positive specimens can confirm the production of β-lactamase within 3.5 hours after a positive blood culture, and is expected to be applied to bacteremia.

Disclosures

Hiroshige Mikamo, M.D, Ph.D, Asahi Kasei Pharma Corporation: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Pfizer Inc.: Grant/Research Support|Pfizer R&D Japan: Honoraria|Sumitomo Pharma Co., Ltd.: Grant/Research Support|Sumitomo Pharma Co., Ltd.: Honoraria
607. Candidemia: Role of T2Candida® compared to Bact/Alert Virtuo blood culture system in a real-world setting
Authors: Birk Navina K , Soman Sana , Kapur Nandita , Pochhareddy Vedanth , Dillon William P , Veve Michael , Samuel Linoj , Ramesh Mayur , Alangaden George J
Published: November 2023

Background

Candidemia is the most common cause of invasive fungal infections with mortality rates up to 60%. The current standard for diagnosis of candidemia is traditional blood cultures (BC) but it has low sensitivity. The need for rapid identification of candidemia has led to the development of non-culture-based diagnostic platforms. T2Candida® (T2) is an FDA approved direct from blood PCR test. T2 detects 5 candida species (C. albicans/C. tropicalis, C. parapsilosis, & C. krusei/C. glabrata) with a turnaround time of three to five hours. T2 is used at our institution for the diagnosis of candidemia in the intensive care units (ICU) if prior blood cultures are negative. Patients with positive T2 results are managed the same as patients with positive BC. In February 2019, our health system switched from the VersaTREK™ to a more sensitive Bact/Alert Virtuo BC system. Our objective was to assess the impact of the new Virtuo system on the diagnosis of candidemia compared to T2 in a real-world setting.

Methods

All T2 and concurrent BC results were retrospectively collected from January 2018 to January 2019 (VersaTREK™ cohort) and March 2019 to March 2020 (Virtuo cohort) in our quaternary care facility in metro Detroit. Only patients with presumed candidemia were included (ICU patients with sepsis, recent exposure to anti-bacterial agents, and negative BC for candida in the past 7 days). Demographic data and the results of T2 and concurrent BC (obtained within 48 hours of T2) were analyzed for the presence or absence of candida. Indeterminate T2 results were excluded. Descriptive statistics were utilized to report the results.

Results

A total of 522 and 348 T2 tests performed with concurrent BC through VersaTREK™ and Virtuo systems respectively were included for analysis. In this ICU cohort with presumed candidemia, T2 remained superior: T2 positivity 45 (8.6%) vs. VersaTREK™ BC positivity 14 (2.7%) (p < 0.001) and T2 positivity 34 (9.8%) vs. Virtuo BC positivity 8 (2.3%) (p < 0.001) (Figure 1). The Virtuo cohort had overall fewer T2 tests performed. This may be because the more sensitive Virtuo system could have detected more cases of candidemia than VersaTREK™ obviating the need for T2 test.

Conclusion

T2 may still have a role in the early diagnosis of candidemia despite the use of newer sensitive blood culture systems.

Disclosures

Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support
608. Systematic Fungal Biomarker Testing in Lung Transplant Recipients : Retrospective Analysis to Optimize Their Use
Authors: Boutin Catherine-Audrey , Ison Michael
Published: November 2023

Background

Serial galactomannan (GM), 1,3-β-d-glucan (BDG) and Pneumocystis jirovecii (PJ) testing after lung transplantation are resource consuming and have low PPV for invasive fungal infections (IFI) in asymptomatic recipients.

Methods

We aim to document the added-value of mentioned reflex screenings tests in diagnosing IFI among lung transplant recipients. After IRB approval, we retrospectively collected all blood and BAL GM, BDG and PJ PCR results from patients transplanted at one large academic center from January 2015 – July 20, 2022. Manual chart review was then used to inform clinical likelihood of infection.

Results

During the study period, 236 lung transplant patients were cared for by our program. Of these, 561 BAL and 56 serum GM tests were ordered. Twenty-five (4.1%) were positive ( > 1), all from BAL. Fungal cultures were requested for most BAL GM (301/343; 87.8%) and were positive for mold in 11 incidences (11/343; 3.2%). Only one was considered involved in a clinical IFI. Out of the duplicates in same BAL specimen a discrepancy in results were seen in 3.4% (7/207). 172 BDG tests were performed of which 25.6% (44/172) were positive. Among the 13 patients with serial BDG during a unique hospitalization, a mean of 2.3 tests were performed. None of the negative test repeated during the same stay became positive. Among patients with IA diagnoses and BDG testing, 5 BDG were positive (5/19; 26.3%). Three cases of IA had a positive BDG while having a negative BAL GM but had positive cultures for Aspergillus spp. Of the 737 BAL specimens, 577 (78.3%) had PJ testing (DFA (n=497) or PCR (n=83), or both (n=3)). None were positive. Among hospitalized patients, mean duration of stay was 31.2 d at time of testing and many had repeated testing (mean 1.8 tests). Additional results will be provided with the final analysis.

Conclusion

BAL GM should be performed with fungal cultures and duplicates on same BAL probably have little additional benefit. BDG confers no added-value over BAL GM combined with cultures for the diagnosis of IA and likely can be deferred in most cases. There is limited value for systematic PJ testing on surveillance BAL of stable recipients with prophylaxis. There is especially limited diagnostic value in repeating a negative BDG or PJ testing during a stay.

Disclosures

All Authors: No reported disclosures
613. The Clinical Spectrum of Curvularia Species: A 20-year Experience at 2 Tertiary Care Hospitals
Authors: Little Jessica S , Nussbaum Eliezer Zachary , Braidt Joseph , Kanjilal Sanjat , Hammond Sarah P
Published: November 2023

Background

Curvularia species are dematiaceous environmental molds that rarely cause disease in humans. Infections may be superficial or invasive and can present as disseminated infection or localized infection including keratitis, invasive fungal sinusitis (IFS), and skin and soft tissue infection (SSTI). Non-pathogenic colonization is also common. The frequency and spectrum of infection has not been well characterized.

Methods

This was a retrospective study of all Curvularia infections at two institutions in Boston, MA between January 1, 2002 and January 1, 2023. Infections were identified using microbiologic culture databases and a research patient data registry. Clinical information was collected. This study was approved by the Massachusetts General Brigham IRB; research was conducted in accordance with the Declaration of Helsinki.

Results

Curvularia species were identified from clinical specimens in 36 patients: 28 pathogenic infections and 8 cases of non-pathogenic colonization. Clinical characteristics of the pathogenic infections are described in Table 1. Of those with infection, 5 were invasive (2 disseminated; 3 localized) and occurred only in immunocompromised hosts (hematologic malignancy n=4, heart transplant n=1). Local invasive disease was characterized by SSTI (n=2) and IFS (n=1). There were 6 SSTI or wound infections without correlative pathology demonstrating tissue invasive disease (3 treated with triazoles; 3 not treated). All cases were identified by culture except one case identified by 28s ribosomal DNA PCR testing. Polymicrobial infection was common with > 50% of pathogenic infections exhibiting cultures with additional bacterial and/or fungal organisms. Antifungal susceptibility testing was performed in most invasive infections; results are shown in Table 2. Invasive infections were treated with both single and dual-agent antifungal regimens (posaconazole n=3; voriconazole and terbinafine n=1; voriconazole and liposomal amphotericin n=1).

Conclusion

Invasive Curvularia infections are rare but mainly occur the immunocompromised, and here manifested as disseminated disease, IFS, and SSTI. Coinfection is common. Non-invasive infections are more frequent (82%) and occur in normal hosts.

Disclosures

Sanjat Kanjilal, MD, MPH, GSK: Advisor/Consultant|Pattern biosciences: Advisor/Consultant|Roche: Honoraria|Uptodate: Royalties Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant
619. Fungal Species Causing Eumycetoma and Chromoblastomycosis in a Commercial Laboratory, United States
Authors: Smith Dallas J , Gold Jeremy A W , Lockhart Shawn R , Benedict Kaitlin
Published: November 2023

Background

The World Health Organization (WHO) designates the implantation mycoses eumycetoma and chromoblastomycosis as Neglected Tropical Diseases. These infections usually develop after traumatic skin inoculation and primarily occur in resource-limited countries in tropical or subtropical areas. They are difficult to diagnose, may require prolonged antifungal therapy and surgery if not diagnosed early, and cause substantial stigma and morbidity. Understanding the organisms causing these diseases and their epidemiology might help inform best clinical practices in the United States.

Methods

We analyzed Labcorp (a major U.S. commercial laboratory) data sent to CDC’s National Syndromic Surveillance Program. We identified results from cultures ordered during 3/1/2019–3/1/2023 involving fungi known to cause eumycetoma and chromoblastomycosis. Nail and scalp specimens were excluded. We examined patient demographic characteristics, ordering clinical specialty, and species.

Results

We identified 33 eumycetoma and 119 chromoblastomycosis results. For eumycetoma, most patients were aged ≥ 50 years (mean=56, interquartile range 42-69), male (64%), and diagnosed in the South census region (52%). Dermatology ordered 21%; family practitioners ordered 18%. Scedosporium apiospermum species complex was the most common species (94%). Another species identified was Exophiala jeanselmei. For chromoblastomycosis, 31% of results were from patients 45–64 years old; 29% were ≥ 65. Most were male (53%), and results were evenly distributed among the Northeast (33%), South (34%), and West (31%) census regions. Most cultures were ordered by dermatologists (70%). Fifty-two percent of results were Aureobasidium pullulans, 24% were Exophiala (undetermined species), and 12% were Exophiala dermatitidis. Phialophora verrucosa, Fonsecaea pedrosoi, Exophiala jeanselmei, and Exophiala xenobiotica accounted for the other 13%.

Conclusion

Although rare, clinicians should be aware that eumycetoma and chromoblastomycosis can occur in U.S. patients seeking treatment for subcutaneous skin infections. Identifying the epidemiology of causative organisms can inform evidence-based practices for diagnosis and treatment.

Disclosures

All Authors: No reported disclosures
641. Limited Utility of Epstein-Barr Virus (EBV) Surveillance for Predicting Post-Transplant Lymphoproliferative Disorder in EBV Seropositive Adult Lung Transplant Recipients
Authors: Heldman Madeleine R , Chang Yeh-Chung , Saullo Jennifer , Baker Arthur W , Maziarz Eileen K , Tam Patrick C , Messina Julia A , Reynolds John M , Wolfe Cameron R , Alexander Barbara D
Published: November 2023

Background

Post-transplant lymphoproliferative disorder (PTLD), which is often driven by Epstein-Barr virus (EBV), causes significant morbidity and mortality in lung transplant recipients (LTRs). EBV viremia surveillance with reduction of immunosuppression at certain viral load thresholds is a common strategy used to prevent PTLD or mitigate progression of PTLD in pre-clinical stages, but the utility of EBV surveillance in adult seropositive LTRs is poorly understood.

Methods

In a retrospective cohort study of EBV seropositive adults who underwent lung transplant at a single academic center between 1/1/2019-12/31/2020, we compared peak whole blood EBV viral load (VL) among samples collected from 1) LTRs who developed PTLD, before PTLD symptom onset, 2) LTRs who developed PTLD, after PTLD symptom onset and 3) LTRs who did not develop PTLD. LTRs without any recorded EBV VLs were excluded. Patients were followed through 1/31/2023 (maximum 49 months post-transplant). Center protocol recommended quantitative EBV PCRs every 3 months between 3-18 months post-transplant, and as clinically indicated thereafter. Reduction of immunosuppression and evaluation for PTLD was at the discretion of clinicians.

Results

Two-hundred twenty-nine LTRs with a total of 1095 EBV PCRs were included (40% female, median age 65 years at transplant, Table 1). Six (2.6%) LTRs developed biopsy-proven PTLD 8-35 months post-transplant (median 17 months); 5/6 PTLDs were EBV+. Clinical symptoms, rather than an asymptomatic high EBV VL, triggered evaluation for PTLD in all 6 cases. Only one of six LTRs with PTLD had an EBV VL above the assay’s lower limit of quantification before PTLD symptom onset (Figure 1A); among the other 5 LTRs, median time between most recent negative EBV PCR and PTLD symptom onset was 125 days (range 35-216). Peak EBV VL in LTRs with PTLD was significantly higher after PTLD symptom onset than in the asymptomatic period (p=0.016), but peak EBV VL was similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD (p=0.62, Figure 1B).

Conclusion

In EBV seropositive adult LTRs , EBV surveillance rarely facilitated PTLD diagnosis and may not be an effective strategy for identifying asymptomatic individuals at high risk for future PTLD.

Disclosures

Arthur W. Baker, MD, MPH, Insmed: Grant/Research Support|Medincell: Advisor/Consultant Eileen K. Maziarz, MD, Karius, Inc: Advisor/Consultant Barbara D. Alexander, MD, F2G Pharmaceuticals: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Leadiaint: Grant/Research Support|Merck: Advisor/Consultant|Scynexis: Grant/Research Support|Thermofisher: Advisor/Consultant
643. Animal Bites Case Surveillance and Rabies Post Exposure Prophylaxis in the Republic of Korea Military, From 2012 to 2019
Authors: Oh Hong Sang , Kim Se-yong , Sung Gyeong-Yong
Published: November 2023

Background

Rabies is a fatal zoonosis on a global scale. In South Korea, no human rabies and animal case has been reported since 2005 and 2014, respectively. Military personnel is frequently exposed to outdoor environment, we hypothesized that their risk of exposure to wild animal is higher than general population. This study aimed to determine the level of rabies risk exposure and the adequacy of treatment by analyzing animal-bitten patients and assessing the status of post-exposure prophylaxis(PEP).

Methods

This study was conducted from January 1, 2012, to December 31, 2019, in 18 military hospitals across the country. The patients with animal bite-related diagnoses were included in the study. The diagnoses were made based on the ICD-10 code related to animal bite. We excluded patients with human bites, insect bites, and snake bites. Cases of repeated visits for additional vaccination were excluded as duplicate cases.

Results

A total of 330 cases of animal bites were included. No human rabies was reported. 297 (90%) were military personnel, with a males (92.1%) and a mean age of 32±11 years. The most frequent site of bite was the hands and fingers (69.7%), followed by the legs (12.4%) and arms (3.9%). Dogs were responsible for 44.8% of bites, followed by cats (38.5%) and mice (5.8%). Empirical antibiotic was administered to 58.5%, while tetanus vaccination was given to 22.1%. In terms of PEP, the matching rate with domestic health authorities’ standards was 62.1%. Category II was the most common criteria for bite injuries (71.5%), according to the World Health Organization(WHO)’s criteria.

Conclusion

Dogs and cats are the most frequently bitten animals, as in previous studies, and hands and fingers, were the most frequently bitten. We postulate that bites occur mainly during contact with animals using hands, suggesting that precaution is necessary. PEP requires immediate medical attention, however 43.7% of patients visited hospitals more than 24 hours after the bite, indicating a need to improve awareness of the disease. PEP was not performed in 15.1% of cases despite meeting domestic standards, and 37.3% in the WHO’s criteria. These emphasize that efforts should be needed to provide appropriate PEP that meets the relevant criteria and minimize unnecessary use of medical resources.

Disclosures

All Authors: No reported disclosures
644. "Impact of heat inactivation and freeze-thaw cycles on detection of influenza A and influenza B antigens and RNA when assessing novel multiplex diagnostic assays"
Authors: Rao Anuradha , Bowers Heather , Sabino Courtney , McLendon Kaleb , Morales Evelyn , Solis Zianya , Greenleaf Morgan , Sullivan Julie , Lai Eric , Damhorst Gregory L , Lam Wilbur A , Bassit Leda
Published: November 2023

Background

Advances in diagnostics since the emergence of COVID-19 has resulted in easy availability of rapid antigen tests (RAT). Building on this, multiplex tests for simultaneous detection of Flu A, Flu B, and SARS-CoV-2 are being evaluated as part of NIH’s Rapid Acceleration of Diagnostics (RADx) program. Critically important for assay development and assessment are viral panels prepared under validated conditions to evaluate new tests. These panels may contain live virus or may be inactivated to promote biosafety. They also may undergo freeze-thaw cycles during storage and transport. We characterized the effect of heat inactivation (HI) on detection of Flu A and B using two RATs, and the effect of freeze-thaw cycles on a point-of-care (PoC) molecular assay already on the market.

Methods

Panels were prepared by serially diluting Flu A or B strains obtained from BEI Resources. Both live and HI panels were prepared. HI was achieved in-house (60°C, 30 minutes). Panels with and without HI were used to assess two RATs by performing triplicate tests and determining limit of detection (LOD) as the lowest TCID50 at which 3 of 3 replicates were positive. Additionally, a molecular-based PoC assay was evaluated by recording cycle threshold (Ct) values before and after freeze-thaw of specimens. All assays were performed according to the manufacturer’s instructions.

Results

Both RATs detected Flu A with similar sensitivity (2-fold increase in LOD) before and after heat inactivation (Figure 1), whereas Flu B was not detected by either RAT after heat inactivation. These results were consistent across both RATs and two strains of each virus. Live Flu A and B were stable and consistently detected up to four freeze-thaw cycles in the molecular assay with minor attrition of Ct values (Figure 2).

Results of LOD characterization for two independent RATs with influenza A and B with and without heat inactivation.

Correlation of Flu A and Flu B Ct values for fresh samples versus after four cycles of freeze thaw measured using a PoC molecular assay.

Conclusion

Pre-treatment and storage of testing material plays a crucial role in the assessment of diagnostic tests used for Flu A and B detection. Loss of reactivity in Flu B antigen tests after inactivation suggests that heating may denature a critical epitope recognized by immunoassays. Selection of live versus HI samples and degradational effects of freeze thaw cycles must be considered by laboratorians and engineers creating or validating diagnostic tests.

Disclosures

All Authors: No reported disclosures