bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1993. Nirmatrelvir/Ritonavir in Immunocompromised Hosts: Use and Outcomes from a Cancer Center
Authors: Drucker Darra , Kassamali-Escobar Zahra , Tverdek Frank , Liu Catherine , Rosen Emily A
Published: January 2025

Background

Prolonged viral replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised (IC) hosts has raised questions about whether treatment duration with nirmatrelvir/ritonavir (nirmatrelvir/r) should be longer than the authorized 5-day course. Data describing nirmatrelvir/r treatment outcomes are limited in the IC population. The primary objective of this study was to assess the efficacy of a nirmatrelvir/r 5-day course as treatment for coronavirus disease 2019 (COVID-19) in IC patients.

Methods

A retrospective chart review was conducted at Fred Hutchinson Cancer Center (FHCC) of patients ≥ 18 years old with an active hematologic malignancy who received nirmatrelvir/r under Emergency Use Authorization between 12/22/21 - 5/25/23. Patients with an active oncology treatment plan within 3 months (before or after) their nirmatrelvir/r prescription date were included. Patients who received nirmatrelvir/r under Investigational New Drug authorization were excluded. The primary outcome was a composite of all-cause mortality or COVID-19 related hospitalization within 30 days of nirmatrelvir/r. A secondary outcome, persistent COVID-19 infection, was defined as a positive SARS-CoV-2 polymerase chain reaction test 30-90 days after initial positive test.

Results

Among 928 patients who received nirmatrelvir/r at FHCC, 399 patients were included. Median age was 63 years, 55% of patients were male, and lymphoma was the most common malignancy, 48% (Table 1). Thirty-day all-cause mortality or COVID-19 related hospitalization occurred in 39/399 (9.8%) of patients. Thirteen patients (3.3%) had persistent COVID-19 infection; 8 had persistent symptoms and 5 required additional treatment. Early discontinuation of nirmatrelvir/r due to adverse effects, most commonly gastrointestinal, occurred in 11 (2.8%) patients (Table 2).

Conclusion

Incidence of the primary outcome was higher in our population compared to rates in nirmatrelvir/r phase 3 trial data and driven by hospitalization rather than all-cause mortality. Persistent infection requiring further treatment occurred in only 1.3% of patients. Additional studies are needed to define optimal treatment duration, including potential indications for use > 5 days in IC hosts.

Disclosures

Frank Tverdek, PharmD, Merck: Advisor/Consultant Catherine Liu, MD, Pfizer: Grant/Research Support
P-1997. Real-world Effectiveness of Tixagevimab/cilgavimab for COVID-19 Pre-exposure Prophylaxis in Solid Organ Transplant Recipients during the BA.2.75 and BQ.1 Omicron Variant Period: A matched Case-control Dtudy
Authors: Rojanakit Gun , Kiertiburanakul Sasisopin , Boongird Sarinya , Sutharattanapong Napan , Kantachuvesiri Surasak , Yingchoncharoen Teerapat , Sobhonslidsuk Abhasnee , Bruminhent Jackrapong
Published: January 2025

Background

Solid organ transplant recipients (SOTRs) develop poor immunogenicity after SARS-CoV-2 immunization. The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab (T/C) has been shown to reduce the risk of COVID-19 among this vulnerable population. We assessed the effectiveness and safety of T/C pre-exposure prophylaxis (PrEP) for COVID-19 protection after transplantation.

Methods

We conducted a matched case-control study at a single transplant center during the Omicron lineages BA.2.75 and BQ.1 period (August 2022 to February 2023). T/C doses of 150/150 mg were provided from August 2022 until February 2023, and doses of 300/300 mg were administered thereafter (December 2022 to February 2023). All patients were followed for up to 6 months, and adverse events (AEs) from T/C were assessed.

Results

A total of 143 SOTRs were included, with 115 and 28 SOTRs in the T/C and control groups, respectively. Transplants included kidney (n=108), liver (n=28), and heart (n=9). Over 6 months, 18 (15.7%) in T/C developed COVID-19, with onset at median 3 months. All had mild infections without respiratory failure. Mild and reversible adverse events (AEs) were reported in 25.2% of cases. No rejection occurred. Non-significantly lower COVID-19 within 3 months during BA.2.75 Omicron (8.7% vs. 17.9% in control; p=0.128; effectiveness: 51.4%). At 6 months (BQ.1 Omicron), COVID-19 incidence was 15.7% in T/C vs. 17.9% in control (p=0.667; effectiveness: 12.3%). The occurrence of COVID-19 was not significantly different after adjustment for the number of vaccine doses, history of prior COVID-19, or the dose of T/C.

Conclusion

The effectiveness of T/C tends to be protective against susceptible strains, although the severity of breakthrough infections tends to be mild. Short-term safety as PrEP appears tolerable. TCTR20220801004.

Disclosures

All Authors: No reported disclosures
P-7. A study of influenza vaccination response in disabled stroke patients
Authors: Pakngao Achiraya , Suwatcharangoon Sureerat , Ngamjanyaporn Pintip , Boonnak Kobporn , Suangtamai Tanitta , Rotjanapan Porpon
Published: January 2025

Background

To date, no clinical study has confirmed the clinical efficacy of routine annual vaccination in stroke patients. The primary objective was to study the immunologic response to influenza vaccination between functional-dependence (FD) and functional-independence (FI) ischemic stroke patients.

Median hemagglutination titers at T0 and T1

Methods

A prospective observational study was conducted between 2023 and 2024 at Ramathibodi Hospital. Old ischemic stroke patients were screened for eligibility. Enrolled patients received standard doses of inactivated trivalent influenza vaccine. Data on patient demographics were retrieved. Blood samples were collected for hemagglutination inhibition (HAI) before and 4-8 weeks after vaccination to determine seroprotection and seroconversion rates.

Results

As per the interim analysis, 198 patients were enrolled, and 161 individuals have completed the HAI analysis. The mean ages (±SD) of the control (C), FI, and FD groups were 69.4±7.4 years, 71.4±8.6, and 75.9±8.3, respectively (p< 0.001). The FD group had significantly higher baseline IFN-α2, IFN-γ, IL-6, IL-12p, and IL-18 levels than the FI and C groups.

      Before (T0) and after (T1) vaccination, the proportion of participants with HAI titers >1:40 on the A/Sydney (H1N1) strain in the FI group was significantly higher than in the FD group (p=0.031 and 0.003 at T0 and T1, respectively) similarly to the A/Darwin (H3/N2) and the B/Austria strains and individuals achieved titer >1:160 (p=0.046 at T1). The C group displayed the highest seroconversion rates compared to the FI and the FD groups at 34.2%, 25.4%, and 19.4% (p=0.033). There were three probable and 23 possible influenza infections three months after enrollment. Twenty-two of 198 patients developed mild adverse events associated with influenza vaccination.

Conclusion

The FI group achieved higher seroprotection and seroconversion rates than the FD group. The possible associated factors were higher levels of pro-inflammatory cytokines at baseline, resulting in better vaccination responses in the FI group. Therefore, the FD group may require a different influenza vaccination strategy to achieve more appropriate immune responses.

Disclosures

All Authors: No reported disclosures
P-2054. Effectiveness of a Single COVID-19 mRNA Vaccine Dose in Individuals Previously Infected with SARS-CoV-2: A Systematic Review
Authors: Volkman Hannah R , Nguyen Jennifer L , Mustapha Mustapha M , Yang Jingyan , Jodar Luis , McLaughlin John M
Published: January 2025

Background

Based on the high levels of population immunity to SARS-CoV-2 from prior infection in many countries, in fall 2023 the US Food and Drug Administration, European Medicines Agency, and World Health Organization authorized/recommended a single mRNA XBB.1.5-adapted vaccine dose for unvaccinated individuals aged ≥ 5y.

Methods

This systematic literature review evaluated the vaccine effectiveness (VE) of a single COVID-19 mRNA dose (BNT162b2 or mRNA-1273) in individuals previously infected with SARS-CoV-2 compared to those with differing histories of prior infection and vaccination (PROSPERO ID: CRD42023453257). We searched MEDLINE and Embase for VE studies published from January 1, 2021–October 4, 2023. Data were synthesized following Synthesis Without Meta-Analysis guidelines. Bias was assessed using the Newcastle-Ottawa Scale. VE estimates were reported as a range of point estimates per clinical endpoint and meta-analyses were not performed due to heterogeneity.

Results

Of 1,661 initial results, 18 studies were eligible for inclusion. Among those previously infected, a single mRNA dose (compared to being unvaccinated) increased protection by 8–71% against infection (related to Omicron BA.1, BA.4/5, or XBB), 39–67% against symptomatic infection (BA.1, BA.2, or BA.4/5), and 25–60% against hospitalization or hospitalization or death (BA.1). The protection provided by a single dose among those previously infected was comparable to the VE provided by two doses, and was higher than VE following two doses without prior infection. No studies were identified that reported single-dose VE for adapted vaccines (BA.1 or BA.4/5 bivalent or XBB.1.5-adapted formulations), immunocompromised populations, or children aged < 5y.

Conclusion

Our results suggest that a single dose of COVID-19 vaccine provides similar protection to that conferred by a two-dose series for immunocompetent individuals aged ≥ 5y in the current setting of high pre-existing SARS-CoV-2 immunity. These findings support current recommendations for one dose of COVID-19 vaccines regardless of vaccination status to be given in advance of the viral respiratory season with considerations for additional doses for certain special populations including young children, older adults, and the immunocompromised.

Disclosures

Hannah R. Volkman, PhD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Jennifer L Nguyen, ScD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Mustapha M. Mustapha, MD, PhD, MPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Jingyan Yang, MHS, DrPH, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) Luis Jodar, PhD, Pfizer Inc: Employment|Pfizer Inc: Stocks/Bonds (Public Company) John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-2070. SARS-CoV-2 Vaccination Rates Among a Cohort of Pediatric Solid Organ Transplant Recipients
Authors: Reis Christopher , Ristagno Elizabeth H , Madigan Theresa
Published: January 2025

Background

SARS-CoV-2 vaccination has been shown to prevent severe disease and subsequent secondary infections in immunocompromised patients. This study assessed the rate of SARS-CoV-2 vaccinations among pediatric solid organ transplant (SOT) recipients at a single transplant center.Figure 1.SARS-CoV-2 vaccination status among pediatric solid organ transplant recipients for all ages and by age group.

Methods

We retrospectively reviewed medical records of pediatric recipients of heart, kidney, and liver transplants at Mayo Clinic, Rochester, MN between January 2011 and December 2023. All SARS-CoV-2 vaccine doses administered on or before April 1, 2024 were recorded. Up-to-date (UTD) status was based on current CDC recommendations for immunocompromised patients for each age group. Deceased patients, those no longer following at Mayo Clinic and whose vaccine records were unavailable were excluded. We also assessed whether patients had been seen by an ID physician in the year prior to collection stop date.

Results

The study included 136 patients: 48 kidney, 58 heart and 30 liver transplant recipients; 52.9% were male. Two patients subsequently received organs of a different type. Mean age was 16.1 years. Since authorization in 2020, 90 patients (66.2%) received at least one SARS-CoV-2 vaccine. This varied by age group, with 72.8% of > =12 year olds, 40.0% of 5-11 year olds and 62.5% of under 5 year olds (p = 0.007 [Figure 1]). Seventy-three patients (53.7%) completed at least three doses. Based on current recommendations that include the 2023-2024 formulation, 30 patients (22.0%) were UTD. This did not differ between age groups (p = 0.717) or by transplanted organ type (p = 0.21). Patients that saw ID were significantly more likely to be UTD (p = 0.001). Among partially immunized patients, 95% (n = 57) needed one additional dose to be UTD.

Conclusion

Despite simplified guidelines with fewer doses needed, a third of pediatric SOT recipients remain unvaccinated against SARS-CoV-2 and only 22% are UTD based on current recommendations. The proportion of unvaccinated patients was highest in the 5-11 year old age group and lowest in the oldest. Those that recently saw ID were significantly more likely to be UTD. Our data suggest that continued care provided by ID physicians may increase vaccine uptake, but reasons for undervaccination and strategies to counteract this should be further explored within this vulnerable population.

Disclosures

All Authors: No reported disclosures
P-2074. Evaluation of Adherence and Access to Booster COVID-19 Vaccination in Persons with HIV
Authors: Krishna Tara , Swaminathan Shobha
Published: January 2025

Background

COVID-19 disproportionately effects minority communities. Completion of the primary COVID-19 vaccination series (≥ 2 doses) is recommended for all American adults by the Centers for Disease Control and Prevention. A population with high mortality and morbidity related to COVID-19 is persons with HIV (PWH). The Infectious Diseases Practice (IDP) at University Hospital (UH) has been providing care to PWH for over 30 years, and it was one of the designated COVID-19 vaccination centers early in the pandemic. We compared rates of PWH who receive COVID-19 vaccine (incomplete: < 2, complete: ≥ 2) amongst different demographic factors to better understand subgroups that can benefit from additional messaging to promote vaccine uptake.

Methods

A retrospective chart review study was conducted at the IDP at UH, Newark. Adult PWH (18-88 years old) who had an office visit to the clinic between January 2021-December 2022 were included. Demographic variables and COVID vaccine count were collected.

Results

The IDP identified PWH (mean age 52, 75.4% Black, 20.4% Hispanic, 39.5% women) who had either complete (n=1085) or incomplete (n=815) primary vaccine schedules for COVID-19. The most common HIV risk factors were heterosexual contact (52.8%), homosexual contact (28.16%), and injection drug use (8.58%). 54% of patients had a CD4+ count > 499, 87.08% of patients had an HbA1c < 6.4, and 72.68% of patients had an HIV viral load that was undetectable.

Notably, PWH who completed the primary vaccination series were more likely to be undetectable (80.6%) years compared to PWH who did not complete their vaccination series (62.1%). Furthermore, PWH who completed the primary vaccination series were more likely to have an HbA1c< 6.4 (83.1%) compared to PWH who did not complete their vaccination series (77.9%). PWH who completed the primary vaccination series were more likely to have a CD4 count > 499 (54.4%) compared to PWH who did not complete their vaccination series (44.4%).

Conclusion

Patients most at risk of not completing the primary COVID-19 vaccine schedule include PWH who are virally uncontrolled, persons with diabetes, or have a low CD4+ count. This indicates medical adherence should be targeted in such populations to improve their healthcare outcomes.

Disclosures

Shobha Swaminathan, MD, Viiv Healthcare: Advisor/Consultant
P-2077. Carbapenemase Resistance Detection by Direct Xpert Carba-R Assay on Flagged Blood Cultures
Authors: Didwania Akansha , Bhatt Manasvini , Kodan Parul , Singh Binit Kumar , Perumalla Sowjanya , Mohapatra Sarita , Wig Naveet , Soneja Manish
Published: January 2025

Background

Early detection of carbapenem-resistant gram negative bacilli(CR-GNB) is critical in patients with sepsis. Delay in diagnosis leads to higher mortality. We evaluated the performance of the Xpert® Carba-R assay (Cepheid, Sunnyvale, CA, USA) directly on flagged blood culture samples in patients with sepsis.Fig 1:Workflow

Methods

Patients with suspected sepsis with GNB on flagged blood culture were recruited. Xpert® Carba-R assay was performed directly on the positive sample. Their diagnostic performance was compared with culture and drug susceptibility testing (DST)(VITEK-2) and time to results were noted and compared.Table 1:Organism profile of patients with sepsis (n=57)

Results

In the study, 57 patients were included; Stenotrophomonas maltophila (n=17; 29.8%) was found to be the predominant isolate, which was excluded from analysis (being intrinsically resistant to carbapenems). This was followed by Klebsiella pneumoniae (n=14 ; 24.5%), Acinetobacter baumannii (n=10 ;17.5%), Escherichia coli (n=6;10.5%), Pseudomonas mendonica (n=3; 5.2%), Pseudomonas aeruginosa (n=2;3.5%) and 1 each of Salmonella typhi, Serratia sp., Enterobacter cloacae, Acinetobacter dendrificans, and Enterobacter sp. Xpert® Carba-R positivity was seen in 23/40 isolates (57.5%), and CR GNB was found in 25/40 isolates (62.5%) on routine DST. Discordant results were seen in 6/40 isolates (15%). Overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of Xpert® Carba-R compared to routine DST (Disk diffusion method and VITEK-2) were 84%, 86.6% , 91.3%, 76.47 %, 6.30 and 0.18 respectively. On genomic analysis, most common CR gene expression was co-expression of NDM and OXA-48 [10/23 (43.5%)], followed by NDM [9/23 (39.1%)] and OXA-48 [4/23 (17.4%)]. The median time to obtain Carba-R result was 44 hours compared to 97 hours for detection of carbapenem resistance in routine DST, giving a 53-hour lead time.Table 2:Comparison of direct Xpert® Carba-R and DST ( disc diffusion method and Vitek-2) in various organisms

Conclusion

Xpert® Carba-R was found to have a good diagnostic performance for detection of carbapenem resistance when performed directly on positive blood culture samples with substantial time advantage over conventional methods.Fig 2:Distribution of Carbapenem resistant genes*Two discordant sampleCRO- Carbapenem resistant organismCSO- Carbapenem sensitive organism

Disclosures

All Authors: No reported disclosures
P-2079. A Retrospective Analysis of the Reproducibility of Discordant Fourth-Generation Quantiferon Tests
Authors: Burra Arun , Graber Christopher J , Goetz Matthew B , Ikuta Kevin
Published: January 2025

Background

Interferon-gamma release assays (IGRAs) are used for tuberculosis (TB) screening. The Quantiferon-TB Gold Plus (QFT-Plus) assesses T-cell reactivity to two distinct sets of TB antigens; the test is considered positive if either assay returns positive. Many studies suggest retesting patients with low level positivity prior to proceeding with TB treatment given high rates of reversion in this group. The significance and reproducibility of when TB antigen minus nil (TB Ag-Nil) in one assay is positive and the other is negative (i.e., a discordant result) is unknown.

Methods

We reviewed 26,474 QFT-Plus tests completed for any purpose between 2018 and 2024 at an academic VA medical center. Excluding indeterminate tests, we noted the frequency and (where follow-up tests were available) reproducibility of discordant results. Based on a literature review on the reproducibility of prior generation tests, we defined levels of positivity: “low+” TB Ag-Nil as 0.35-0.69 IU/mL, “mid+” 0.7-0.99 IU/mL, and ”high+” ≥1 IU/mL. For statistical analysis, we performed univariate logistic regression assessing the probability of follow up QFT testing returning negative (reversion) in a discordant result compared to a concordant low+ result.

Results

During the study period, 449 QFT-Plus test results were discordant, representing 26% of all positive QFT-Plus tests (Table 1). Among all discordant tests with follow-up available, 70% (103/148) reverted to negative while 49% (43/88) of repeated concordant low+ tests reverted. Discordant tests were more likely to revert than were concordant low+ tests (OR 2.40, 95% CI 1.39-4.15, p=0.002). 71% (79/111), 58% (11/19), and 72% (13/18) of repeat tests were negative with an initial discordant test that was low+, mid+, or high+, respectively (Table 1). Most discordant results were low+ (Figure 1).

Conclusion

Upon retesting, discordant QFT-Plus tests most often revert. The level of positivity in discordant tests does not appear to correspond with the likelihood of reversion. We found that the rates of reversion for discordant tests were significantly higher than for concordant lowly positive tests, suggesting a role for retesting patients with discordant results — regardless of the actual test values — prior to decision making around TB treatment in some settings.

Disclosures

All Authors: No reported disclosures
P-2083. Validation of the Modified Rapid Test for detection of the Cefazolin Inoculum Effect (CzIE) in bloodstream isolates of Methicillin-Susceptible Staphylococcus aureus (MSSA) from North and Latin America
Authors: Carvajal Lina Paola , Rincon Sandra , Panesso Diana , Gomez Villegas Sara I , Singh Kavindra , Jacques-Palaz Karen , Malikzad Husna , Dziadula Jacob , Dingle Tanis C , Butler-Wu Susan , Miller William R , Arias Cesar A , Reyes Jinnethe
Published: January 2025

Background

S. aureus is a major human pathogen and a leading cause of bloodstream infections (BSI). Cefazolin is frequently used for severe deep-seated MSSA infections, as in general it displays similar efficacy and a more favorable side effect profile as compared to isoxazolyl-penicillins. In some studies, the CzIE has been associated with therapeutic failures and mortality in MSSA BSI treated with cefazolin, however, current laboratory testing methods are unable to detect the CzIE. The aim of this study was to conduct a blinded evaluation of a modified colorimetric rapid test to detect the CzIE in MSSA isolated from BSI in North and Latin-America.

Methods

99 MSSA recovered from BSI in North America (2019; n=69) and Latin-America (2011-2019; n=30), and previously characterized for the presence of the CzIE (71 CzIE + and 28 CzIE -) using gold-standard broth microdilution at high inoculum (breakpoint >= 16 ug/mL) were included. In a central laboratory in Colombia, a modified rapid colorimetric test (rCT) was performed according to a published protocol with modification that included the use of ampicillin (AMP) discs placed in 1 mL of BHI-broth for induction of β-lactamase expression. The researchers were blinded to the results of the gold standard test to detect CzIE. Diagnostic performance metrics were calculated and typing of BlaZ was performed using whole genome sequence data.

Results

Compared to the gold standard, the modified test showed a sensitivity and specificity of 97% and 86%, respectively, and overall accuracy of 94%. The predominant BlaZ β-lactamase types in the 99 MSSA were type C (70%) and type A (27%). When analyzing the performance of the rCT by BlaZ type, in isolates with type C enzyme the modified rapid test had a sensitivity of 96% and specificity of 82% with an accuracy of 91%. In isolates with BlaZ type A, the sensitivity and specificity of the rCT were 100%.

Conclusion

The modified rapid colorimetric test detected the CzIE in bloodstream MSSA from different geographic areas with a global accuracy of 94%. Notably, the accuracy of the test for BlaZ type A isolates was 100% and for BlaZ type C isolates was 91%. Further, the use of AMP discs proved to be a practical, time-saving modification that did not impair accuracy of the test.

Disclosures

William R. Miller, M.D., Merck: Grant/Research Support|UptoDate: Royalties
P-2084. Construction of dominant peptide librarys of Mycobacterium tuberculosis-specific antigens and validation of their immunogenicity
Authors: Li Yuanchun , Ge Qiping , Gao Mengqiu , Liu Xiaoqing , Zhang Lifan
Published: January 2025

Background

Current immunological methods cannot accurately distinguish active tuberculosis (ATB) and latent tuberculosis infection (LTBI). The combination of latency-associated antigens with virulence antigens of Mtb enhances the discriminatory diagnostic ability. This study aims to screen and integrate dominant peptide segments of virulence factors and latency-associated antigens, verify their immunogenicity.

Methods

ATB patients and LTBI healthy healthcare workers were enrolled, and PBMCs were isolated. Peptide pools of ESAT-6, CFP-10, Rv1733c and Rv2028c were used as stimuli. The frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 were measured using the FluoroSpot assay. Dominant peptide segments for library construction were screened based on the cytokine secretion characteristics of ATB and LTBI. Clinical T-SPOT.TB-positive patients were included for the verification of the immunogenicity of the newly combined peptide library.

Results

Significant differences were found in the frequencies of specific T cells secreting IFN-γ, secreting IL-2, and dual-secreting IFN-γ and IL-2 between the ATB group and the LTBI group (p< 0.05) after stimulation with peptide pools from ESAT-6 and CFP-10, integrating six dominant peptide pools into the virulence antigen dominant peptide library. Similarly, six peptide pools from Rv1733c and Rv2028c were integrated into another dominant peptide library. The newly constructed library showed no significant differences (p >0.05) in the frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 compared to ESAT-6 combined with CFP-10, and the correlation coefficients were 0.947, 0.763, and 0.993, respectively. Similarly, the newly constructed latency-associated antigen library also showed no significant differences (p >0.05) in the frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 compared to Rv1733c combined with Rv2028c, and the correlation coefficients were 0.674, 0.562, and 0.692, respectively.

Conclusion

The newly constructed librarys retain good immunogenicity and can be further used clinically to evaluate the accuracy of ATB and LTBI differential diagnosis.

Disclosures

All Authors: No reported disclosures
P-2088. Correlation of pediatric blood culture transport time and time-to-positivity since microbiology service centralization
Authors: Yeung Eugene
Published: January 2025

Background

Guidance from Clinical & Laboratory Standards Institute (CLSI) and Infectious Diseases Society of America (IDSA) both recommend that transport of blood culture specimens from collection to laboratory accession should take less than 2 hours to preserve the specimen quality, such as positivity rate and time-to-positivity (TTP). This recommendation could be impractical in Canada as many diagnostic microbiology laboratories are moving towards centralization, in which microbiology services are relocated from individual laboratories to regional sites, where resources and personnel are consolidated. This is especially crucial for the pediatric population as different published guidelines are available on the required pediatric blood culture volume, which could affect their positivity rate and TTP.

Methods

The current study investigated the blood culture transport time and TTP for Children’s Hospital of Eastern Ontario (CHEO), a tertiary pediatric hospital, situated about 700 meters away from Eastern Ontario Regional Laboratory Association (EORLA) microbiology laboratory, which has consolidated the microbiology services for 18 hospitals in Eastern Ontario since 2010’s. All first positive blood cultures from patients at CHEO from 1 November 2019 to 31 October 2020 were included. TTP was defined as the time from collection to a positive signal from the automated incubators. Two-tailed Spearman’s correlation was used to determine the association between transport time and TTP.

Results

A mean transport time of 2.95 hours and a mean TTP of 31.8 hours were calculated from the 268 episodes of first positive blood culture from patients in a year (mean patient age 6.27 years). Only 82 specimens were transported to the laboratory in less than 2 hours. A weak but statistically significant correlation (rs = 0.17, p = 0.0047.) was observed between transport time and TTP.

Conclusion

Even for a hospital within walking distance of a regional microbiology laboratory, the blood culture transport time was unable to meet the guidance recommendation, associated with delay in TTP. Centralization of microbiology services could affect the quality of critical clinical specimens. Remedial actions, such as molecular testing, could be considered to salvage specimens if they are crucial for diagnoses.

Disclosures

All Authors: No reported disclosures
P-17. Worldwide Impact of Increased Recombinant Zoster Vaccine Coverage on the Burden of Herpes Zoster, based on 11-year Clinical Trial Follow-up Data, in Adults Aged ≥50 Years
Authors: Curran Desmond , Matthews Sean , Giannelos Nikolaos
Published: January 2025

Background

Herpes zoster (HZ) is a viral disease impacting patients quality of life due to pain and rash. It is a vaccine-preventable disease with approximately 15 million cases observed annually in individuals ≥50 years of age (YOA) worldwide. Recombinant zoster vaccine (RZV) has proven effective in protecting against HZ infection. This is the first study evaluating the potential increased (incremental) public health benefits - in terms of HZ cases averted - of vaccinating adults ≥50 YOA worldwide with RZV.Table 1:Number of Herpes Zoster cases avoided by region as a function of increasing vaccine coverage and second dose completion levels*Incremental coverage: impact observed due to increased coverage of X%

Methods

A previously published static multi-cohort Markov model with an annual cycle length, and a lifetime horizon was used, which incorporated the following inputs : population estimates, and age-gender specific mortality rates from the latest (2022) United Nations data, depicting populations on December 31, 2023; HZ incidence rates from a recent (2021) meta-regression analysis of HZ burden across the globe (Asia, Europe, Northern America, and Oceania); RZV efficacy modelled based on 11-year clinical trial follow-up data [NCT02723773].Table 2:Number needed to vaccinate to prevent Herpes Zoster cases by age and region as a function of increasing vaccine second dose completion levelsYOA, years of age.

Results

Assuming a 70% second-dose completion rate in the general population ≥50 YOA worldwide, absolute increases in uptake of RZV by 5% would reduce the number of expected cases by >10 million over the remaining lifetime of vaccinated individuals (see Table 1). Numbers needed to vaccinate (NNV) to avert 1 HZ case by age group worldwide varied from 9 in 50-59 YOA to 18 in ≥80 YOA, and 10 overall in ≥50 YOA (see Table 2). Variations observed by region and age reflected varying inputs, i.e. population demographics, HZ incidence rates, life expectancy and vaccine efficacy.

Conclusion

Even with a relatively modest increase of coverage rates worldwide, RZV is projected to prevent millions of HZ cases due to the long term protection it affords. Lower NNVs are observed in younger vaccinated cohorts, irrespective of region, outlining the relative merits of age of vaccination.

Funding: GSK

Disclosures

Desmond Curran, PhD, GSK: employee|GSK: Stocks/Bonds (Public Company) Sean Matthews, MSc, GSK: Advisor/Consultant Nikolaos Giannelos, PhD, GSK: Employee|GSK: Stocks/Bonds (Private Company)
P-2096. Reverse Blot Hybridization Assay for Simultaneous Multi-drug Resistance Detection of Helicobacter pylori
Authors: Lee Kyoung Hwa , Lee Eun Hwa , Han Sang Hoon , Song Young Goo , Lee Hye Young
Published: January 2025

Background

Helicobacter pylori (H. pylori) the eradication is important for cancer prevention. Amoxicillin and clarithromycin, the initial treatments of H. pylori, have been shown increasing resistance, suggesting alternative levofloxacin or tetracycline based treatment option. However, theses resistance rate is also increasing by nearly 18-37%, thus, early recognition of multi-drug resistance is critical for efficient treatment success.

Methods

The novel diagnostic kit is needed that can simultaneously detect multi-drug resistance (Table 1). A total of 311 clinical H. pylori isolates were obtained from the gastric endoscopic biopsy in Gangnam Severance Hospital, Seoul, Republic of Korea. The phenotypic drug susceptibility test (pDST) was performed (Table 2), compared with the reverse blot hybridization assay (REBA) tests, and whole genome sequencing was done for the inconsistency.

Results

The overall sensitivity about clarithromycin, tetracycline, and levofloxacin are 95.5%, 16.7%, and 55.8%, respectively. The specificity showed much improved detection rate, 96.3%, 92.7%, and 81.8%, respectively (Table 3). Clarithromycin resistance was not significantly different from the performance of the other previously developed kits, and no specific novel mutation sites were discovered other than already known resistance genes. However, novel mutations at A926G, A926T, A926C, A928C, and A934G of tetracycline resistance were discovered. Tetracycline-susceptible clinical H. pylori isolates (n = 100) were sequenced at the target region, and these novel mutations were not present. A926G, A926T, A926C showed low-level resistance, with MIC range from 0.36 µg/mL to 1 µg/mL, and the A928C mutation was found in high-level tetracycline resistance (MIC > 2 µg/mL). Among 102 quinolone-resistant H. pylori isolates, 45 H. pylori isolates showed mismatched with REBA, they had specific sequence (Table 4).

Conclusion

Detection of resistance against H. pylori is important in selecting treatment options, therefore, we found novel mutation of tetracycline which can be new target lesion. By simultaneously targeting and detecting various resistance genes, efficiency in antibiotic selection, shortened treatment duration, and reduced medical costs can be expected.

Disclosures

All Authors: No reported disclosures
P-2097. Genomic basis of Oxacillin- and Cefoxitin-Susceptible PBP2a-Positive Staphylococcus aureus
Authors: Tao Lili
Published: January 2025

Background

Methicillin-resistance Staphylococcus aureus (MRSA) is resistant to all ß-lactam antibiotics except for the fifth-generation cephalosporin drug, ceftaroline. The mecA gene, which encodes an alternative penicillin-binding protein, PBP2a, is responsible for the high-level resistance to methicillin. However, mecA positive, oxacillin- and cefoxitin susceptible MRSA has been reported, with limited understanding of the genomic basis behind this contradictory phenomenon. Here, we studied the molecular base of a “stealth” MRSA from clinical specimen.

Methods

A MRSA isolate was routinely isolated from a deep wound specimen, which was positive for PBP2a by lateral flow assay but negative for cefoxitin screen test and susceptible to oxacillin (MIC of 0.5 ug/ml) by VITEK 2 AST-GP75 card. It was also susceptible to cefoxitin using disk diffusion method (diameter of 26 mm). The “stealth” MRSA isolate was sequenced on illumina NovaSeq 6000 platform using 150 bp paired end sequencing. Bacteria genome was assembled and annotated using pipelines on BV-BRC (https://www.bv-brc.org/).

Results

Genomic sequencing revealed a point mutation (G to A) in the mecA gene resulting in a Gly599Ser substitution located in the transpeptidase domain of PBP2a, which is close to the active site of Ser403 on the 3D structure of the protein. Additionally, an insertion in the methicillin resistance regulatory sensor-transducer mecR1 gene was identified, resulting in a frameshift mutation, and predicted to cause premature termination. However, the sequence of frame shift mutation in mecR1 has been described and was not associated with reversed cefoxitin susceptibility. Therefore, the point mutation in mecA gene is most likely responsible for loss of function of PBP2a, and lead to susceptible cefoxitin and oxacillin results despite a positive PBP2a reaction.

Conclusion

Whole genome sequencing is valuable to understand the genomic basis of unusual phenotypic testing results. The reversion of “stealth” MRSA strain to a high-level oxacillin- and cefoxitin-resistant strain has been reported, which highlights the importance of considering tests for mecA or PBP2a in routine laboratory practice to avoid the risk of missing such strains.

Disclosures

All Authors: No reported disclosures
P-2099. A Novel Anaerobic Activity Index to define the “anti-anaerobic” spectrum of antimicrobials
Authors: Mackow Natalie A , Aronoff David M , Young Vincent B , Bartelt Luther A , van Duin David
Published: January 2025

Background

While necessary for the treatment of anaerobic infections, use of antibiotics with anaerobic activity may be associated with poor patient outcomes including graft-versus host disease after bone marrow transplant and mortality in critically ill patients. However, we lack a uniform method to assess the relative anaerobic activity of antibiotics and have poor definitions of what it means for antimicrobials to be “anti-anaerobic”.

Methods

A PubMed search using terms “microbial sensitivity test”, “anti-bacterial agents” and “bacteria, anaerobic” yielded 575 papers published between January 2013-2024 (Figure 1). Papers with < 100 isolates, non-human isolates, or without antimicrobial susceptibility testing (AST) were excluded. AST for an average of 17,709 anaerobic clinical isolates per antimicrobial from 56 publications were summarized. Anaerobes were categorized into 11 groups based on the literature (Table 1). For 16 commonly used antibiotics, values of 0, 1, or 2 were awarded for each group of anaerobes for average published susceptibility of ≤ 10%, 11-89.4%, and ≥ 89.5%, respectively, and tallied to create a composite score (0-22, Score A). Three alternative scores were created based on different susceptibility cutoffs (Scores B-D; Table 2).Table 1:Groups of anaerobes for which antimicrobial susceptibility was scored

Results

In Anaerobic Activity Index Score A, scores ranged from 11 for moxifloxacin to 22 for tigecycline, meropenem, and imipenem (Table 2). Anaerobic Activity Index scores were plotted against the Antibiotic Spectrum Coverage (ASC), a previously published antibiotic “broad” spectrum score (Figure 2). Varying susceptibility thresholds affected estimated anaerobic activity for some antibiotics, including clindamycin and vancomycin, but overall, there was good agreement across all scores (A-D). Moxifloxacin had the lowest overall scores due to high rates of resistance across all groups of anaerobes.

Conclusion

Antibiotic broad-spectrum scores have been proposed, but no valid score exists and no score assessing anaerobic activity has been developed. An Anaerobic Activity Index may improve the definition of “anti-anaerobic” antimicrobials for clinical care and research. Further studies are needed to validate this index as a potential tool to evaluate the effect of anaerobic antibiotic exposure on clinical outcomes.

Disclosures

Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support
P-2102. Performance of the VITEK®2 Advanced Expert System (AES) as a Rapid Aid for Reporting Antimicrobial Susceptibility Testing in Pseudomonas aeruginosa and Acinetobacter spp
Authors: Hackel Meredith , Bailey-Person Mary
Published: January 2025

Background

The VITEK®2 Advanced Expert System (AES) is an automated antibiotic susceptibility testing (AST) system which provides rapid AST data by interpreting and checking each MIC against a database of phenotypes and MIC distributions and infers a resistance mechanism. AES provides a level of confidence for auto-releasing reports of green (consistent), yellow (consistent with correction), and red (inconsistent, MIC pattern not matching any phenotype). This study evaluated VITEK®2 AES reports compared to broth microdilution (BMD) on a set of Pseudomonas aeruginosa (PA) and Acinetobacter spp. (ABC).

Methods

A total 148 PA and 150 ABC were tested. Susceptibility was tested by VITEK®2 (N802 and XN15 AST cards) and CLSI reference BMD against 13 antimicrobials for PA and 17 antimicrobials for ABC applying 2021 CLSI breakpoints. Molecular characterization of isolates was based on WGS or PCR of β-lactamase genes. Permeability and gene expression were not evaluated.

Results

Among 143 ABC, AES reports were green for 131 (91.6%), and yellow for 12 (8.4%) isolates. Green reports agreed with BMD for 131 isolates (100%) and could have been automatically reported without further review. Among yellow reports, AES corrections were acceptable for 11 isolates (91.7%). Among 40 carbapenem-producing ABC, AES reports were green for 39 isolates (97.5%) and yellow for one isolate (2.5%). Green reports agreed with BMD for 37 isolates (94.9%) and could have been automatically reported. Of 148 PA, AES reports were green for 125 (84.5%), yellow for 18 (12.2%), and red for 5 (3.4%) isolates. Of 112 PA with molecular data, 64 (57.1%), 38 (33.9%), 6 (5.4%), 3 (2.7%), and one (0.9%) contained genes for intrinsic β-lactamases only (WT), MBL, GES carbapenemase, KPC, and ESBL genes only, respectively. Overall, the AES accurately reported phenotypes for 97/112 PA (86.6%). Among the MBL-positive PA, 37/38 (97.4%) were reported as green and all showed AES phenotype agreement with the genotype. Among the WT PA, 51/64 (79.7%) were reported as green and 82.4% showed AES phenotype agreement with the genotype.

Conclusion

The use of VITEK®2 AES for the confident release of AST results without additional review could have a positive impact on time savings in the laboratory and aid in antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
P-20. Estimating the Public Health Impact of Pertussis Decennial Booster Vaccination for German Adults
Authors: Soares Victoria G , Waize Maria , Marijic Pavo , Heiseke Alexander , Heinze Daniel , Jamet Nicolas , Shah Hiral , Deeywadaa Pavitra , Jacob Jorge , Oikonomou Stavros , Verelst Frederik , Biundo Eliana
Published: January 2025

Background

Pertussis is a highly contagious respiratory disease affecting both children and adults. Current vaccination strategies primarily target infants, young children, and pregnant women, shifting the disease burden towards adults, with age and comorbidities increasing the risk of severe disease. This study aims to estimate the potential public health impact of decennial booster vaccination in adults in Germany.

Methods

A dynamic transmission model (DTM) was developed to evaluate the public health impact of alternative strategies for pertussis booster vaccination in adults (≥ 18 years) and those at increased risk. Disease transmission dynamics occurred at total population level with high-risk and non-high-risk populations tracked in separate compartments. The DTM was populated with published German data sources for population, vaccination coverage and incidence. Incidence was adjusted with previously published under-reporting rates. The model evaluated the age-stratified incidence and impact on healthcare resource utilization over a 100-year horizon. As base case, a decennial booster strategy for all adults was assessed in replacement of the current recommendation of a single adult (≥ 18 years) booster. Vaccination strategies targeting only high-risk populations were tested in scenario analyses.

Results

Interim results for the decennial booster strategy in adults suggest that administering an incremental 171 million booster doses would prevent over 35 million symptomatic cases, 1.7 million hospitalizations and 215,000 cases with complications, over 100 years. The model predicts that 5 individuals need to be vaccinated to avoid a pertussis case and 100 to avoid hospitalization. At equilibrium, the population overall incidence (symptomatic and asymptomatic) is expected to decrease from around 1,480 cases to 930 cases (-38%) per 100,000 person-years.

Conclusion

Modelling results suggest that implementing adult decennial booster vaccinations can significantly alleviate the burden of pertussis in Germany.

Disclosures

Victoria G. Soares, MBA, GSK: Advisor/consultant Maria Waize, MSc, GSK: Employed by GSK Pavo Marijic, PhD, GSK: Employed by GSK Alexander Heiseke, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Daniel Heinze, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Nicolas Jamet, PharmD, GSK: Employed by GSK Hiral Shah, PhD, GSK: Employee of GSK|GSK: Stocks/Bonds (Public Company) Pavitra Deeywadaa, MBBS, MD, GSK: Employed by GSK|GSK: Stocks/Bonds (Private Company) Frederik Verelst, PhD, GSK: Employed by GSK|GSK: Stocks/Bonds (Public Company) Eliana Biundo, MSc, GSK: Employee|GSK: Stocks/Bonds (Private Company)
P-2126. ‘SPECIFIC’ First-In-Human Clinical Trial of 68Ga-triacetylfusarinine (TAFC) Siderophore PET/CT for Detection of Invasive Aspergillosis
Authors: Sim Beatrice Z , Levy Sidney , Haskali Mohammad , Decristoforo Clemens , Haas Hubertus , Emmerson Brittany , Kamil Usama , Slavin Monica , Hofman Michael , Douglas Abby
Published: January 2025

Background

Invasive Aspergillus spp. infections (IAI) confer high morbidity and mortality in immunocompromised patients. Diagnosis often requires invasive and risky sampling. 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) is useful in diagnosis but is non-specific.

Siderophores are pathogen-specific iron chelators which are a promising radiolabelling target for IAI diagnosis. Aspergillus fumigatus secretes 2 siderophores, fusarinine C and triacetylfusarinine (TAFC), which are upregulated during IAI. Gallium-68 (68Ga)-labelled TAFC is attractive due to its short half life, rapid renal clearance, and low radiation risk. Preclinical mouse studies demonstrate diagnostic potential of 68Ga-TAFC PET/CT with specific visualisation of A. fumigatus infection.Figure 1:68Ga-TAFC-PET/CT in a patient with leukemia and probable pulmonary A. fumigatus IAI. Specific infective uptake of known pulmonary lesions at around blood pool level intensity (SUVmax 3.5, SUVmean 2.3). There was minimal liver and marrow uptake, with progressive washout to 60 minutes.

Methods

We report the first result from a 10 patient pilot trial of 68Ga-TAFC PET/CT for IAI diagnosis (NCT06105411). Inclusion criteria are adults with pulmonary IAI within 2 weeks of diagnosis. Exclusion criteria are pregnant/lactating patients or those within a week of iron infusion.

68Ga-TAFC PET/CT was performed at 15, 62, and 209 minutes after IV 139 MBq 68Ga-TAFC administration. Findings pertinent to IAI and physiologic uptake were analysed.

Results

The patient had probable A. fumigatus IAI in the setting of leukemia. Galactomannan and Aspergillus fumigatus PCR were positive on bronchoalveolar lavage fluid. Empiric antifungal treatment was commenced with fever resolution at 72 hours.

68Ga-TAFC-PET/CT was performed 10 days after treatment start and 4 days after microbiological diagnosis. Blood pool activity (SUVmax at 15/60/209 mins: 4.1/2.7/1.9) was demonstrated with minimal liver, spleen and gastrointestinal tract uptake (SUVmax 2.7), early renal excretion, and no marrow or other organ uptake. There was focal uptake in multiple pulmonary lesions (SUVmax 3.5), similar to blood pool activity, with synchronous washout over time. No adverse effects occurred.

Conclusion

Very low background physiologic biodistribution was seen in the first participant in this study. Focal low grade pulmonary uptake was visualised, likely demonstrating specific activity for A.fumigatus. Trial recruitment continues.

Disclosures

Abby Douglas, MBBS, Gilead Sciences: Honoraria