bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001) and T2 positivity 34 (9.8%) vs. Virtuo BC positivity 8 (2.3%) (p &lt; 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

Abstract

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 ( &gt; 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