bluuebunny/crossref_metadata_2025 huggingface dataset:
369. Tissue Based Species Level Molecular Identification of Schistosoma haematobium in Appendiceal Tissue
Authors: Haddad Fadi A , Nutman Thomas , Feldman Daniela Osowiecki , Correa Manuela , Armas Octavio , Haddad Victoria , Klion Amy , Issa Yazan Al
Published: December 2022

Background

Appendiceal involvement in schistosomiasis is rare, but it has been reported for the 3 major species commonly infecting humans (S. haematobium, S. mansoni, and S. japonicum). Often the diagnosis is made histologically following appendectomy. However, many times the eggs found in the appendiceal tissue are calcified or degraded to a degree that a species level diagnosis cannot be made morphologically.

Case presentation: A 37-year-old Somali female patient presented with chronic abdominal pain. An appendectomy was performed due to the finding of appendicitis on an abdominal CT. A biopsy sent to pathology showed calcified eggs consistent with Schistosoma (Figure 1), but a species could not be defined. Serum Schistosoma IgG was negative.

Eggs of Schistosoma Species Figure 1:Miscroscopy of degraded eggs of Schistosoma species.

Methods

The biopsy was then sent to the Laboratory of Parasitic Diseases at the National Institutes of Health (NIH) for qPCR and molecular indentification. DNA was extracted from two unstained biopsy slides using standard techniques for formalin-fixed, paraffin embedded tissue and subjected to qPCR using S. heaematobium- or S.mansoni-specific primers/probes.

Results

The patient sample only amplified (Ct value -32) with the S. haematobium-specific primers/probes and not with the S. mansoni-specific primers/probes (no amplification). For both qPCR reactions, positive controls were positive and negative controls showed no amplification.

Conclusion

Tissue-based parasite identification of S. haematobium DNA provides a definitive species assignment for the causative agent presumably driving the appendiceal inflammation. This technique further allows species-based therapeutics, should it be necessary.

Disclosures

All Authors: No reported disclosures.
373. Development of multiplex loop-mediated isothermal amplification (LAMP) based on a microfluidic chip for detection of HSV-1 and 2 and VZV.
Authors: Ihira Masaru , Natsuhara Daigo , Enya Yasuko , Higashimoto Yuki , Kozawa Kei , Kawamura Yoshiki , Sugiura Kazumitsu , Shibata Takayuki , Yoshikawa Tetsushi
Published: December 2022

Background

In the era of universal varicella vaccination, point-of-care testing for herpes simplex viruses 1 and 2 (HSV-1, HSV-2) and varicella-zoster virus (VZV) is becoming more important because of the increase in the number of breakthrough varicella cases. The Loop-mediated isothermal amplification (LAMP) method is a reliable method for rapid diagnostic tests for infectious diseases. Meanwhile, microfluidics technology is revolutionary in total system miniaturization, including facile parallelization through multiplexing and process-reduced reagent volumes. It is easy to create miniaturized chips containing multiple chambers according to the needs. In this study, we sought to develop multiplex LAMP for the detection of HSV-1, HSV-2, and VZV DNA using in-house microfluidic chips.

Methods

The polydimethylsiloxane-based chip consists of microfluidic channels and 5 reaction chambers. The specific primers were pre-spotted and dried in each chamber. The condition of LAMPs and each specific primer were described previously. The sensitivity of microfluidic LAMPs was confirmed using plasmids that contain the target sequences. In order to assess the reliability of clinical use, 35 swab samples (without DNA extraction) collected from patients with vesicular skin lesions were used. The result of microfluidic multiplex LAMP was compared with conventional LAMPs and real-time PCRs.

Results

Detection limits of HSV-1 and 2 and VZV LAMP-based on a microfluidic chip were 500 copies per reaction. Among 35 swab samples, HSV-1, HSV-2, and VZV DNA were detected in 10 (28.6%), 4 (11.4%), and 12 (34.3%) samples, respectively. The results of microfluidic LAMPs were completely consistent with the results of conventional LAMPs. HSV-1 DNA was detected in one LAMP negative sample by real-time PCR. One HSV-1 LAMP positive sample was negative in real-time PCR. If real-time PCR was used as a standard, sensitivity of HSV-1, HSV-2, and VZV LAMPs based on microfluidic chip were 90%, 100%, and 100%, and the specificity of three methods were 96%, 100% and 100%, respectively.

Conclusion

Multiplex LAMP, based on a microfluidic chip that detects three alpha herpesviruses, may be useful in laboratory diagnosis of patients with vesicular skin lesions.

Disclosures

All Authors: No reported disclosures.
376. Testing for Cytomegalovirus Viremia in People with HIV/AIDS- An Opportunity for Diagnostic Stewardship
Authors: Savenka Tatsiana , Saccente Michael
Published: December 2022

Background

Guidelines recommend against testing for cytomegalovirus (CMV) viremia as a screening tool for CMV end-organ disease (EOD) in people with HIV/AIDS (PWHA) due to low positive predictive value. Additionally, a negative result does not exclude EOD. In this study, we aim to assess the clinical utility of plasma CMV quantitative PCR (qPCR) for the diagnosis of CMV EOD and to determine if positive results lead to further testing for EOD or earlier initiation of anti-CMV therapy.

Methods

We retrospectively identified PWHA who had a plasma CMV qPCR result or who were diagnosed with CMV EOD between 2014-2021. qPCR results that were undetectable or less than the minimum quantifiable value (300 IU/mL) were considered negative and results >300 IU/mL were considered positive. EOD was confirmed via tissue biopsy, ophthalmic exam, or cerebrospinal fluid analysis. We compared CMV qPCR results for participants with proven EOD and those without proven EOD. For participants diagnosed with CMV EOD, we evaluated if a positive qPCR prompted further workup for EOD diagnosis or triggered anti-CMV therapy.

Results

We identified 138 PWHA with a CMV qPCR result and 17 PWHA with CMV EOD. Participant characteristics are shown in Table 1. Among participants with a qPCR result, 27 (19.6%) were positive; 13 (9.42%) of those with a qPCR results had EOD. 4 participants with EOD did not have qPCR. Participants with a positive qPCR were 4.55 (95% CI 2.63-7.90) times more likely to have EOD than those with a negative result. Table 2 shows qPCR results among participants with and without EOD. Table 3 shows the performance of qPCR for the diagnosis of EOD. 9 (69.2%) of 13 participants with EOD had a positive qPCR. 7 of them were diagnosed with EOD and started on treatment before the qPCR resulted. In 1 case, the qPCR resulted as positive on the same day ophthalmology diagnosed CMV retinitis. In only 1 case did a positive qPCR result and initiation of therapy precede the diagnosis of EOD.

Conclusion

Contrary to guidelines, clinicians often order plasma CMV qPCR on PWHA. Although PWHA who have CMV EOD are more likely to a have a positive qPCR than those without EOD, our data confirm CMV qPCR should not be used as a screening tool for EOD. Instead, clinical assessment should guide diagnostic investigation.

Disclosures

All Authors: No reported disclosures.
381. Antibiotic Spectrum Index and Risk of Clostridioides difficile Infection
Authors: Ray Michael J , Tucker Kendall J , Furuno Jon P , Lofgren Eric , Strnad Luke , Gerber Jeffrey S , McGregor Jessina C
Published: December 2022

Background

Antibiotic therapy is a known risk factor for Clostridioides difficile infection (CDI) and evidence suggests the magnitude of risk varies by spectrum of antibiotic activity and days of therapy (DOT). We quantified the risk of hospital-associated (HA) CDI associated with antibiotic therapy considering spectrum of activity and DOT.

Methods

We performed a retrospective cohort study of adult (≥18 years) inpatient encounters at a 576-bed academic medical center in Portland, OR between January 2018 and February 2020. We excluded patients with hospital stays under 4 days and those known to have recurrent (CDI in the previous 12 weeks) or community-acquired (CDI diagnosis within first 3 days of hospitalization) CDI. The primary exposure of antibiotic utilization was measured using the Antibiotic Spectrum Index (ASI), where spectrum-based weights are applied to each agent and DOT over the time at risk, summed over the encounter, and divided by the number of antibiotic days. The primary outcome was HA-CDI. We estimated the independent association between aggregate ASI and HA-CDI using multivariable logistic regression.

Results

Among 37,629 inpatient encounters, 68% patients received at least one antibiotic. We identified 159 cases of non-recurrent HA-CDI, which corresponds to 4.8 cases per 10,000 patient-days. Compared to those without HA-CDI, those with HA-CDI had a greater median number of distinct antibiotics prescribed (4 vs 1), greater median days of antibiotic therapy (22 vs 2), a greater median time at-risk (9 vs 6 days), and greater median Elixhauser Comorbidity Index (9 vs 4) (Kruskal-Wallis p-value < 0.0001 for all comparisons). There were no significant differences by age or sex. Patients with HA-CDI had a greater mean ASI per antibiotic day than those without (5.2 vs 3.2, Student’s t-test p < 0.0001). After adjusting for time at-risk and Elixhauser Comorbidity Index, each one-unit of ASI per antibiotic day was associated with 1.29 times increased odds of developing HA-CDI (Odds Ratio = 1.29, 95% Confidence Interval: 1.21 to 1.37).

Conclusion

The Antibiotic Spectrum Index was strongly associated with HA-CDI. ASI may be a useful tool for quantifying the risk of CDI according to the specific antibiotic therapy received among hospitalized patients.

Disclosures

All Authors: No reported disclosures.
390. Eravacycline combination therapy for severe, recurrent, or fulminant Clostridioides difficile infection
Authors: Morrison Austin R , Kwiatkowski Shaina , Ramesh Mayur , Kenney Rachel M
Published: December 2022

Background

Eravacycline (ERV) is a fluorocycline with in vitro activity against Clostridioides difficile infection (CDI). The purpose of this study was to evaluate the usage of ERV in the management of CDI.

Methods

IRB-approved, retrospective case series in a health system that added ERV to formulary in 9/2019. All patients between 9/2019 and 2/2020 treated with adjunctive ERV for > 24 hours for severe, recurrent, or fulminant CDI were included. Exclusion criteria: pregnant, age < 18 years. Primary outcome: all-cause mortality at 30 days (d) from start of ERV. Secondary outcomes: clinical cure, colectomy, and recurrence within 30 d. Data was reported using descriptive statistics and measures of central tendency.

Results

14 patients included: severe (4, 29%), recurrent (4, 29%), and fulminant CDI (6, 43%) (table 1). Infectious diseases consult: 14/14, median time to consult 1 (1, 2) d. Surgery consult: 1 severe and 5 fulminant CDI cases, median time to consult 1 (1, 3) d. Prior to ERV initiation, 10 patients were on oral vancomycin (PO VAN) and intravenous metronidazole (IV MTZ), one was on PO VAN, two were on IV MTZ, and one was on no CDI therapy. After ERV was initiated, six patients were on ERV, PO VAN, and IV MTZ combination and eight patients were on ERV and PO VAN concurrently. The reason for using ERV was fulminant CDI (6, 42.8%), severe CDI (4, 29%), unable to tolerate other CDI medications (3, 21%), refractory CDI (3, 21%), and recurrent CDI (1, 7%). Time to eravacycline initiation 1.5 d (1, 3.75) with median duration of 6 d (4.5, 7.75). 30-day all-cause mortality 2 (14%), all were in-hospital; 1 (7%) hospice. Clinical cure occurred in 12 (86%). Two (14%) required colectomy; one received surgery on the same day of CDI diagnosis and ERV initiation and the other had surgery 4 days before ERV initiation. Two patients with recurrent CDI received fecal microbiota transplant outpatient, one of which also received bezlotoxumab. Zero recurrences and one readmission within 30 d. Table 1.Patient demographics, severity, and clinical outcomes

Conclusion

ERV appears to be a potential adjunctive therapy for severe, recurrent, or fulminant CDI. Prospective studies are needed to further investigate the safety and efficacy of ERV in serious CDI.

Disclosures

All Authors: No reported disclosures.
398. Post-Infectious Irritable Bowel Syndrome in Patients Referred to a Complicated Clostridioides difficile Clinic
Authors: Pham Natalie , Jones Marieke , Costa Deiziane , Shin Jae , Behm Brian , Warren Cirle A
Published: December 2022

Background

Recurrence of Clostridioides difficile infection (CDI) occurs in up to 20-30% after an initial episode and up to more than half of patients with previous infection. C. difficile has also been associated with post-infectious irritable bowel syndrome (PI-IBS) following the resolution of an acute infection, complicating assessment of gastrointestinal symptoms post-CDI. The prevalence and risk factors for post-CDI IBS are not as well-defined as PI-IBS secondary to other pathogens.

Methods

In this study, we examined the electronic medical record of 67 consecutive patients referred to a Complicated C. Difficile Clinic from March 2020 to July 2021 for consideration of fecal microbiota transplantation.

Results

Patients were referred by primary care providers (54%), gastroenterologists (16%), hospital admitting team (19%) or others (10%). Mean age was 64 (21-93) and 51 patients (76%) were female. In 25 out of the 67 patients (37%), treatment was prescribed without documentation of a positive C. difficile assay. We found that 32.8% of patients referred to the clinic for recurrent CDI had symptoms consistent with post-CDI IBS. Patients with post-CDI IBS were generally younger in age (P = 0.03), had fewer medical comorbidities (P = < 0.001), and more often had history of anxiety (P = 0.03) than patients with a diagnosis of CDI.

Conclusion

Our findings suggest that post-CDI IBS is prevalent, can be misdiagnosed as CDI recurrence, and may lead to inappropriate use of anti-C. difficile agents or interventions.

Disclosures

All Authors: No reported disclosures.
406. Vancomycin Activity against Clostridioides difficile Over Three Decades in Chicago
Authors: Skinner Andrew M , Petrella Laurica A , Young Kim Do , Serna-Perez Fidel , Johnson Stuart
Published: December 2022

Background

In 2017, the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiologist of America (SHEA) updated the C. difficile (CD) treatment guidelines recommending vancomycin as the preferred therapy for C. difficile infections (CDI). We assessed the in vitro vancomycin minimum inhibitory concentration (MIC) against CD across three decades to determine if the vancomycin MIC had increased since these guidelines were published.

Methods

We performed antimicrobial agar dilution susceptibility testing on 89 clinically relevant CD isolates collected within Chicagoland area. These isolates were selected from 3 separate timeframes: 2005 – 2007, 2013 – 2015, and 2021. Isolates were selected based on the prevalence of restriction endonuclease analysis (REA) strain types within each time cohort. Treatment response to vancomycin was reviewed for patients from the 2021 cohort if CD isolates had a vancomycin MIC of ≥ 16 μg/ml.

Results

The in vitro vancomycin geometric mean MIC against all 89 CD isolates was 2.53 μg/ml with a MIC50 of 2 μg/ml and MIC90 of 4 μg/ml. Comparing the 3 timeframes, the geometric mean vancomycin MICs from 2005-2007, 2013-2015, and 2021 were 2.35, 2.27, and 2.91, respectively (p=0.11). Comparison of the isolates collected from 2005 – 2015 to 2021, the in vitro vancomycin geometric mean MICs were 2.31 and 2.91, respectively (p = 0.037). REA group BI was the most common strain group to have an increased in vitro vancomycin MIC within the 2021 cohort as 4 of the 5 isolates tested had a MIC of 16 μg/ml. All 4 of the patients infected with these strains with an elevated vancomycin MICs were treated vancomycin. All 4 patients had a resolution of symptoms on vancomycin and 2 suffered from a recurrent infection within ≤4 weeks of completing vancomycin.

Conclusion

The vancomycin MIC against CD has trended upwards slightly over the past 20 years. The most notable change occurred between 2015 and 2021. We hypothesize that this increase is due to increased use of oral vancomycin for the treatment of CDI. However, these data indicate that most isolates still have a MIC of ≤4 μg/ml and an elevated MIC does not appear to impact clinical outcomes. Further study is required to determine if this upward trend in vancomycin MIC continues and if this could have any potential clinical implications.

Disclosures

Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
413. Cost effectiveness of rectal screening for ESBL producing organism in preventing urosepsis following transrectal prostate biopsy
Authors: Hines Laena , Munsiff Sonal , Obrien Jeanne
Published: December 2022

Background

Urosepsis following transrectal ultrasound guided prostate biopsy (TRUS PB) occurs in 0.3-3.1% of patients. Our center gives ciprofloxacin and ceftriaxone prophylaxis. With rise in urinary pathogens resistant to fluoroquinolones or producing extended spectrum beta lactam (ESBL+), prophylactic regimen might need changing. Studies have highlighted cost effectiveness of rectal screening for ESBL+ organism prior to TRUS PB to determine target antibiotic. We compare our center’s incidence of urosepsis admissions following TRUS PB to the expected rate and calculate cost-effectiveness of pre-procedure screening to prevent urosepsis admissions.

Methods

All patients with CPT billing code 55700 (biopsy, prostate; needle or punch, single or multiple, any approach) from January 2020 through January 2021 were identified retrospectively. Charts were queried for emergency department or urgent care visits and hospital admissions within two weeks of TRUS PB and admissions reviewed for evidence of urosepsis and ESBL+ cultures. Hospitalization cost was compared to the extrapolated cost of doing pre-procedural rectal swabs. Cost of rectal swab and culture was estimated at $39.02 per swab, and identification and susceptibility at $67 per isolate.

Results

33 of 1593 patients presented to our institution within 2 weeks of TRUS PB over a 13 month period. 3 were admitted for urosepsis post TRUS PB (2 with ESBL+ infection, 1 with no growth on culture), 12 had ED visits relating to their TRUS PB without urosepsis, (2 due to UTI with other organisms) and 18 visits were unrelated to TRUS PB. Our urosepsis admission rate was 0.19% (for ESBL+ 0.13%). Cost of the 3 hospitalizations was $37,910.92 ($27,063.76 for 2 ESBL+ infections). Rectal swabs would in theory have prevented 2 admissions. Cost of swab and culture would be $62,158.86. 50% of the swabs would need further testing to identify ESBL+ organism, for an additional cost of $53,365.50.

Conclusion

Given lower than expected urosepsis admission rates at our institution after TRUS PB, pre-procedure rectal swabs would not be cost effective, especially since some admissions may be unavoidable. The cost analysis is an underestimate as a visit some days prior to procedure would be scheduled and the staff resource utilization to collect the swab is not accounted for.

Disclosures

All Authors: No reported disclosures.
420. ­­Impact of Intensified Prevention Measures On Rates of Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii In Endemic Setting
Authors: Ben-David Debby , Cohen Yael , Yakovov Malka , Raviv Lili , Esmansky Ekaterina , Mazo Eduard , Belichkov Julia , Tasher Diana , Schwartz Orana , Maor Yasmin
Published: December 2022

Background

During the last decade, hospital-acquired carbapenem-resistant Acinetobacter baumannii (HA-CRAB) have become endemic in acute care facilities in Israel. Despite the increasing rates CRAB carriage among hospitalized patients in endemic settings, the role of active surveillance cultures (ASC) is still debated. The aim of the study was to evaluate the impact of different components of control measures conducted in an endemic acute care hospital

Methods

The study consisted of a 12-month baseline period (1 January 2019–31 December 2019; period 1), 12-month 1st intervention period (1 January 2020- December 2020; period 2); 6-month 2nd intervention period (1 January 2021-30 June 2021; period 3) and a 9-month follow-up period (1 June 2021–31 March 2022; period 4). During period 1, basic infection-control measures were implemented including contact precautions for CRAB carriers. During period 2, all CRAB carries were cohorted in a single ward and managed by dedicated health care workers. Enhanced environmental cleaning was conducted by a dedicated team. During periods 3 and 4, high-risk patients were screened on admission; weekly cultures were obtained in high-risk units. The incidence density rate (IDR) of HA-CRAB was defined as the per-patient number of first CRAB isolate from clinical specimens. Incidence rates ratios (IRR) were compared between the study periods.

Results

During the baseline period, IDR of HA-CRAB was 4.9/10,000 patient days (PD). During period 2, no significant decrease was observed (IDR 3.9/10,000 PD, IRR 0.7 95% CI 0.49-1.16, p=0.15). In response to ongoing transmission in several wards, ASC program was initiated in January 2021. IDR during period 3 was 5.3/10,000 PD (IRR 1.1, 95% CI 0.74- 1.56, p=0.64). Since January 2021, 2.1% (78/3799) were found to be colonized on admission and 5.5% (100/1809) were detected by weekly screening. Among the 291 patients who were detected with CRAB during this period, 70.9% were identified by ASC. During period 4, IDR was 3.1/10,000 PD (IRR 0.60, 95% CI 0.40-0.88, p=0.007).

Conclusion

The comprehensive intervention that combined intensiﬁed control measures with routine ASC was effective in reducing the incidence of HA-CRAB in endemic setting.

Disclosures

Yasmin Maor, MD, MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Honoraria.
421. In vitro and in vivo synergistic antimicrobial activities of the combinations of meropenem, colistin, tigecycline, and ceftolozane/tazobactam against carbapenem-resistant Klebsiella pneumoniae
Authors: Yoon Young Kyung , Kim Jeong Yeon , Suh Jin Woong , Sohn Jang Wook
Published: December 2022

Background

The aim of this study was to evaluate the in vitro and in vivo activities of various antimicrobial combinations against carbapenem-resistant Klebsiella pneumoniae (CRKP).

Methods

The in vitro activity of six two-drug combinations against CRKP isolates collected from the rectal swab samples of patients with intestinal CRKP colonization was evaluated using the checkerboard method and time-kill assay to identify potential synergistic and bactericidal two-drug combinations against CRKP isolates. The in vivo efficacy of the combinations of colistin, meropenem and ceftolozane/tazobactam (C/T) as therapeutic options, was assessed in a mouse model of intraperitoneal CRKP sepsis. Antimicrobial susceptibility and genotypes of carbapenem-resistance were also analyzed.

Results

A total of 5 clinical isolates of CRKP were collected from nonduplicate patients with CRKP infection. Of 5 CRKP isolates, 4 carried the blaKPC-2-type carbapenem-hydrolyzing enzymes except 1 blaNDM-1-type. Antimicrobial susceptibility rates were tigecycline 80%, colistin 40%, and C/T 0%, respectively. The checkerboard assay showed that in vitro synergistic activity against CRKP isolates was 90% for the meropenem-tigecycline combinations and 20% for colistin-C/T combinations. None of the various combinations of the six antibiotics showed a synergistic effect in the time-kill assay. However, the meropenem-colistin (100%) and colistin-C/T (100%) combinations showed bactericidal effects in the time-kill assay (using an antibiotic concentration of 1× MIC) (Table). The survival rates of the mice was 80% (4/5) at 48 h in the treated group using low dose combinations of colistin (10 mg/kg) and C/T (25 mg/kg), unlike both antibiotics, which were 60% in a monotherapy with the same dose (Figure).

Comparison of checkerboard assay and time-kill assay

Comparison of checkerboard assay and time-kill assay associated with the bactericidal activity of two-drug combinations (1 × MIC) against each carbapenem-resistant Klebsiella pneumoniae isolate

In vivo survival tests for antimicrobial combinations

Comparison of the survival rates of the mice in the treated group using antimicrobial combinations

Conclusion

In conclusion, the present in vivo study demonstrated that the low-dose combination of colistin and C/T may be a promising alternative to nephrotoxic high-dose colistin alone for treating CRKP infections. However, it was difficult to predict this possibility in in vitro tests, and even there is great discordance of antimicrobial synergistic activities between the checkerboard microdilution and time-kill assays.

Disclosures

All Authors: No reported disclosures.
423. Molecular Epidemiology of ESBL E. coli Over a 2 Year Period in Worcester Massachusetts USA
Authors: Hathaway Nicholas J , Ward Doyle V , Ellison Richard T
Published: December 2022

Background

Extended-spectrum beta-lactamase (ESBL) producing Escherichia coli are an increasing health burden contributing to a pandemic of resistant bacteria.

Methods

To better understand the population genomics of ESBL E. coli, 129 phenotypically identified ESBL isolates collected between 2017-04 to 2018-11 from a single academic medical center underwent whole genome sequencing with the presence of antibiotic resistance genes identified by screening against the CARD database. The odds of phenotypic resistance to beta-lactam agents were calculated for each known resistance gene. A novel approach based on k-mer-enrichment among antibiotic resistance gene groups was developed to predict genes associated with phenotypic resistance.

Results

Genomic analysis revealed that 60% of the ESBL isolates collected were pandemic strain ST131. All isolates contained at least 1 gene in the beta-lactamase family with a median of 3 different beta-lactamase genes being present. Ninety-five percent of isolates contained a CTX-M gene with 52% CTX-M-15, 43% CTX-M-27, 5% other CTX-M; 24% had OXA and 34% had TEM. The presence of CTX-M-15 significantly increased the odds of resistance to ampicillin-sulbactam (95% confidence interval 5.9-116.5, p-value < 1e-7), ceftazidime (4.2-25.9, p< 1e-6) and cefepime (3.6-20.1, p< 1e-5) but not to piperacillin-tazobactam (0.9-6.3, p 1). CTX-M-27 decreased the odds of resistance to these 4 beta-lactams (0.003-0.07, p< 1e-13; 0.04-0.3, p< 1e-05; 0.06-0.4, p< 0.001; 0.03-0.6, p 0.11). TEM-1 significantly increased the odds for ampicillin-sulbactam resistance (3.8-1036.7, p< 1e-3) but not for other beta-lactams. Our de novo sequence approach was able to identify the known genes listed above and also identified a 683 bp open reading frame with unknown function that had increased odds of resistance to piperacillin-tazobactam resistance (2.1-43.6, p< 1e-3). This 683 bp open reading frame did not share any homology with known beta-lactamases.

Conclusion

The majority of phenotypic ESBL isolates contain multiple beta-lactamase genes. The presence of CTX-M-15 appears to increase the odds of resistance to key beta-lactam agents. Our novel k-mer-enrichment approach identified a novel marker of piperacillin-tazobactam resistance.

Disclosures

All Authors: No reported disclosures.
424. Risk Factors for Infection or Colonization with Piperacillin-tazobactam (TZP) Resistant P. aeruginosa (PSA) with Increasing Degrees of β-lactam Resistance
Authors: Vita Angelina Jessica A , Rice Seth , Albin Owen , Patel Twisha S , Styron Charles N , Kaye Keith S , Pogue Jason M
Published: December 2022

Background

Resistance to β-lactams amongst PSA is common with roughly 20% of isolates demonstrating resistance to TZP. This can lead to delays in the time to appropriate empiric therapy. While rapid diagnostics can identify PSA at earlier time points, they fail to detect common β-lactam resistance mechanisms in this pathogen. Though risk factors for TZP resistance (TZP-R) amongst PSA have been identified, co-resistance amongst traditional anti-PSA β-lactams is common, so decisions to turn to other traditional anti-PSA or novel agents in the presence of such predictors are unclear. This study aims to find predictors unique to varying degrees of β-lactam resistance amongst TZP-R PSA to inform these decisions.

Methods

This was a retrospective case-case-case-control study of all non-cystic fibrosis patients with PSA isolated from a culture from 2015-2021 at Michigan Medicine. Four study groups were created based on the susceptibility profile of PSA: TZP susceptible (TZP-S), resistance to TZP only (TZP-R ONLY), resistance to TZP in addition to 1 or 2 other traditional anti-PSA β-lactams (TZP-R PLUS), and resistance to all traditional anti-PSA β-lactams (pan β-lactam resistance, PBR). Bivariate and multivariate analyses were performed to compare each degree of TZP resistance to the TZP-S group. Results were then compared across models to assess uniqueness to a given resistant phenotype.

Results

2365 patients were included, and results of the multivariate analyses are listed in the table. The sole predictor of TZP-R ONLY was recent ceftriaxone or cefotaxime use. Independent predictors unique to TZP-R PLUS were community acquired infection, recent ICU residence, and recent exposure to TZP or aztreonam. Most risk factors identified were either unique to PBR or shared between PBR and TZP-R PLUS including history of PSA, history of TZP-R PSA, and recent exposure to multiple antibiotics.

Multivariate Models for TZP-R ONLY, TZP-R PLUS, and PBR

Conclusion

This analysis demonstrates that previously identified risk factors for TZP-R P. aeruginosa are predictors of PSA with greater degrees of resistance. Given these findings, consideration needs to be given to escalation to novel agents in the presence of risk factors at the time of PSA isolation, rather than to other traditional anti-PSA β-lactams.

Disclosures

Owen Albin, MD, Charles River Laboratory: Advisor/Consultant|Cipla Pharmaceuticals: Advisor/Consultant|Shionogi Inc: Advisor/Consultant Keith S. Kaye, MD, GSK: Advisor/Consultant|merck: Advisor/Consultant|merck: Stocks/Bonds|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant jason M. Pogue, PharmD, consultant to Venatorx, Merck, Shionogi, QPex Biopharma, Utility, GSK, and Entasis.: Advisor/Consultant.
435. Investigation of the cause of low measles seroprevalence among young healthcare workers in South Korea
Authors: Joo Jiyeon , Chung Hyemin , Kim Sun-Kyung , Kim Eun Ok , Kim Min Jae , Jung Jiwon , Kim Sung-Han
Published: December 2022

Background

After a large measles outbreak in 2000∼2001, national measles vaccination program was implemented in Korea, and more than 95% of people born after 1985 have been vaccinated with 2-dose MMR. But sporadic outbreaks have continued to occur mainly in adults in their 20’s and 30’s in 2014 and 2019. Although low prevalence in young adults have been reported, there are limited data regarding the cause of low seropositivity (positive vaccine failure vs. secondary vaccine failure). We aimed to evaluate the cause of low seroprevalence of measles.

Methods

This study was performed in a 2743-bed tertiary-care hospital in South Korea. At 1-month after MMR vaccination in healthcare workers (HCWs) who were seronegative for measles, we performed measles antibody test(enzyme immunoassay), IgM/IgG index ratio, and avidity test.

Results

Of the 1,698 new HCWs in 2020 and, 1,686 in 2021, 54 HCWs with negative measles IgG at their entering at our hospital were enrolled in this study. Of these, 36(67%) were female, and the median age was 25 (IQR, 24-27) years. Of 43 HCWs who measured IgM/IgG index 1 month after MMR vaccination, 38 HCWs had IgM/IgG index of less than 1 and remaining 5 had negative IgG results (seroconversion rate of 88%). All 54 healthcare workers who performed avidity test showed high avidity index Measles vaccination record in KCDA showed that 45 had documented vaccination record during their childhood (of these, 11 received MMR vaccine again during their adult age) and remaining 9 had no documented vaccination record during their childhood. Of these 9 healthcare workers without record in their childhood, 3 had a history of vaccination at adult. Analyzing 48 healthcare workers with vaccination record, they received MMR vaccination median 18 years (IQR, 7-20) before. Therefore, at least 48 received at least 2 dose MMR vaccination, and 11 received at least 3 dose MMR vaccination.

Conclusion

Secondary vaccine failure may be the reason for vaccine failure in young adults in Korea. Therefore, HCWs with negative measles antibody who were born after 1985 may receive 1 dose booster vaccination rather than 2 dose vaccination.

Disclosures

All Authors: No reported disclosures.
438. An Observational Study Evaluating the Seroprotection of HepB-alum Vaccine and HepB-CpG Vaccine in Adults Living with HIV
Authors: Reilly-Evans Brenna , Dudzik Beatrix , Costlow David J , Hartmann Carlos , Khalsa Ann M , Kassis Christelle , Zmarlicka Monika
Published: December 2022

Background

Hepatitis B virus (HBV) vaccine seroprotection rates with conventional aluminum adjuvanted recombinant HBV vaccines (HepB-alum) among people with HIV (PWH) are varied. HepB-CpG, a novel adjuvanted recombinant HBV vaccine, has shown higher seroprotection rates in immunocompetent patients but is not well studied in PWH. There are no published studies comparing seroprotection rates between HepB-alum and HepB-CpG in PWH. The purpose of this study was to evaluate and compare the seroprotection incidence of HepB-CpG versus HepB-alum in adults at least 18 years of age with HIV.

Methods

This retrospective, observational, cohort study screened for inclusion adults diagnosed with HIV who received a 3-dose series of HepB-alum or a 2-dose series of HepB-CpG between January 1, 2015 through December 31, 2021 at a community health center in Phoenix, Arizona. Patients who had a confirmed diagnosis of HIV and a hepatitis B surface antibody < 10 IU/L at the time of the first vaccine dose were included until an adequate sample size was achieved. The primary outcome was to compare seroconversion incidence of HepB-CpG and HepB-alum in PWH. Secondary outcomes included identifying factors associated with an increased likelihood of response to HBV vaccination. Seroconversion incidence data was analyzed using Fisher’s exact test using BlueSky Statistics.

Results

A total of 121 patients were included in this study, 59 in the HepB-alum cohort and 61 in the HepB-CpG cohort. In the HepB-alum cohort, 57.6% (34/59) achieved seroconversion, compared to 93.4% (57/61) in the HepB-CpG group (p < 0.001). Univariate comparisons of comorbidities among the vaccine cohorts found no significant differences in sex, body mass index, diabetic status, kidney/liver disease, CD4 count, HIV viral load, or active/prior history of substance use.

Conclusion

Among PWH at a single community health center, HepB-CpG provided a statistically higher incidence of seroprotection against HBV compared to HepB-alum. The higher seroprotection rate for HepB-CpG versus HepB-alum patients is not due to differences in group demographics or reported comorbidities.

Disclosures

Carlos Hartmann, MD, Viiv Pharmaceuticals: Speaker.
440. Assessing Motivators and Barriers in Anal Cancer Screening for People with HIV
Authors: Geba Maria C , Kalluri Divya , Cardenas Benjamin , Mitchell Emma , Flickinger Tabor , Dillingham Rebecca , Thomas Tania A
Published: December 2022

Background

There is a rising prevalence of anal cancer in people with HIV (PWH) with recent evidence showing efficacy of screening procedures in preventing progression to anal cancer. A recent retrospective cohort study in our Ryan White HIV/AIDS Program (RWHAP) clinic evaluating engagement and retention in anal cancer screening services identified a significant gap in engagement in care among those eligible. This highlighted a need to identify and address barriers to engagement in screening services.

Methods

Semi-structured qualitative interviews were performed on people eligible for anal cancer screening in the RWHAP clinic at the University of Virginia. Participants were at least 35 years old and receiving HIV care in the clinic. Recruitment was carried out by convenience sampling via internal clinic advertising and a tailored mobile app. Interviews were constructed using the health belief model and themes explored included perceived risks, benefits, and barriers to screening, as well as self-efficacy and cues to action.

Results

Prominent barriers to engaging in anal cancer screening services included lack of awareness about screening procedures and stigma associated with sexual practices and sexual orientation. Notable motivators to engaging in screening services were education and familiarity with cancer prevention as well as trust in RWHAP clinic providers and staff.

Conclusion

Our findings highlight the importance of eliciting patient perspectives as a critical and powerful tool when evaluating and improving on a screening program’s performance. There is a resounding need to promote awareness of anal cancer screening among PWH in order to empower those at risk to seek effective preventative services. Raising awareness will involve careful and thoughtful messaging to de-stigmatize and normalize anal cancer screening in PWH.

Disclosures

Rebecca Dillingham, MD, MPH, WHT, INC: Advisor/Consultant.
445. High HCV Treatment Success among People Living with HIV - Kyrgyzstan, 2018-2021
Authors: Kyzy Nasyat Kemelbek , Horth Roberta , Karagulova Aida , Alaverdyan Sevak , Mergenova Gaukhar , Otorbaeva Dinara , Nabirova Dilyara
Published: December 2022

Background

People living with HIV (PLHIV) with viral hepatitis C (HCV) co-infection have higher risk of liver failure and mortality. Globally, >2 million people globally have HIV/HCV co-infections. Central Asia is one of the regions most affected by HCV. Since 2018, Kyrgystan has provided HCV treatment free of charge to 427 PLHIV. We analyzed factors associated with HCV treatment success among PLHIV in Kyrgystan.

Methods

We conducted retrospective cohort survey among PLHIV > 18 years old on HIV antiretroviral treatment that completed viral hepatitis C treatment before September 2021. We defined treatment success as having RNA PCR < 15 IU/mL post-treatment and negative DNA PCR 12 and 24 weeks post-treatment. We abstracted demographic, clinical, and laboratory data from the national registry and interviewed consenting participants using structured questionnaires. We used logistic regression to identify factors associated with treatment success.

Results

Of 302 participants, 81% were ≥ 40 years old, 79% were male, 72% had ever injected drugs, 53% had ever been incarcerated, and 15% were on methadone. Treatment outcomes were classified as success among 86%. Reluctance to seek healthcare services due to fear of HIV status disclosure was reported by 39% of participants and was associated with reduced odds of treatment success (adjusted odds ratio [AOR]: 0.4, 95% CI: 0.2-1.0). Participants receiving SMS counseling (64%) had increased odds of treatment success (AOR: 2.4, 95% CI: 1.2-5.4) as did those who followed an HCV diet (AOR: 31, 95% CI: 1.4-6.8). Participants with an opportunistic infection (32%) and or HIV stage 3 or 4 (49%) also had decreased odds of treatment success (AOR: 0.3, 95% CI: 0.1-1.3; and AOR: 0.1, 95% CI: 0.01-0.5, respectively). Initiation of care in 2020 (COVID-19 pandemic beginning) was also associated with reduced odds (AOR: 0.3, 95% CI: 0.1-1.0).

Conclusion

Our study found high HCV treatment success in a difficult-to-treat population including during the COVID-19 pandemic. Programs that reduce stigma towards people living with HIV, promote early engagement in care, and provide SMS-based counseling could help increase treatment success for PLHIV in groups at higher risk for non-retention in care.

Disclosures

All Authors: No reported disclosures.
447. Improvement of Anal Pap Collection Documentation and Adequacy in PLWHIV in Infectious Diseases Clinic
Authors: Villa-Chan Frederico , Pryor Zachary , Wark Kellie , Kubat Ryan C , Newman Jessica
Published: December 2022

Background

Anal Pap smear is an essential screening tool for high-risk human papillomavirus (hrHPV)-associated anal squamous cell carcinoma (ASCC), particularly in people living with HIV (PLWHIV). Currently, there is no consensus regarding time interval or protocols for screening of anal hrHPV-associated cancer. Limited reports suggest self-collected specimens have similar cytology sensitivity compared to physician-collected samples.

Methods

We utilized a Quality Improvement project (QIP) to assess validity of self-collected anal swab specimens (SCS) for screening of hrHPV-related anal lesions versus physician-collected specimens (PCS) over 3 months. The protocol was implemented in an Infectious Diseases clinic by patients and physicians during routine visits. Patients learned about the QIP via educational handout and were offered self- or physician-collection.

Results

A total of 60 patients participated. Seventy-five percent opted for self-collection and 35/45 (78%) SCS were adequate for interpretation, compared to 10/15 (67%) PCS. Fisher exact test value was 0.49, indicating no significant difference between groups (at p< .05). In total, 77% of patients completed the satisfaction survey. Only 13% reported preference for physician-performed procedure, while 63% felt that a self-collection option made them more likely to complete the Pap. A limitation to this project is the Hawthorne effect, as participants were aware of the QIP and that validity of the samples depended on appropriate sample collection. There was also a relatively small sample size of self-collected specimens (n=45).

Survey results

Final result from surveys answered by patients that participated in the project.

Conclusion

Survey analysis showed increased patient satisfaction and similar adequacy of samples collected. While the project was not powered to demonstrate an increase in acceptance of anal Paps, increased satisfaction could lead to improvement over time with a simple and inexpensive workflow adjustment. Additionally, with expansion of telehealth, self-collected anal Paps may increase opportunities to complete screening at times physicians are not available. Studies with larger populations, in multiple institutions and with varying educational handouts/instruction methods may provide better data to corroborate recommendations regarding best practices for screening for ASCC.

Disclosures

All Authors: No reported disclosures.
466. All-Cause Mortality in Patients with Invasive Candidiasis or Candidemia from an Interim Analysis of a Phase 3 Open-label Study (FURI)
Authors: Prattes Juergen , King Thomas , Azie Nkechi , Angulo David A
Published: December 2022

Background

There are limited oral antifungal treatment options for patients with high-mortality fungal infections such as candidemia or invasive candidiasis who fail available antifungals or have infection caused by resistant fungi. Ibrexafungerp is a broad-spectrum glucan synthase inhibitor with activity against Candida spp., including azole- and echinocandin-resistant strains. A Phase 3 open-label study of ibrexafungerp (FURI; NCT03059992) is ongoing for patients intolerant of, or invasive fungal disease refractory to, standard antifungal therapy. We present an interim analysis of all-cause mortality (ACM) through 30 d post-treatment for patients with candidemia or invasive candidiasis (IC) who completed therapy up until Oct 2020.

Methods

FURI patients are eligible for enrollment with proven/probable severe mucocutaneous candidiasis or IC, or candidemia, with documented evidence of failure, intolerance, or toxicity related to an approved standard-of-care antifungal treatment; or patients who cannot receive oral antifungals (e.g., due to susceptibility), and continued IV antifungal therapy is clinically undesirable/unfeasible. Patients were followed through 30 d post-treatment for ACM.

Results

Out of the 74 patients who completed therapy in the FURI study through October 2020, 39 (52.7%) had IC or candidemia and received ibrexafungerp. The most common infections in this group were candidemia (28.2%), intra-abdominal infection (28.2%), and bone infection (20.5%).

Survival at ≥ 30 d post-treatment was 92.3%. Three patients (7.7%) died within 30 d post ibrexafungerp, a 4th died at 31 d, and a 5th died at 56 d. The mean age of the expired patients was 54 yr. Three patients had candidemia (2 with C. parapsilosis and 1 with C. albicans), and 2 had intra-abdominal candidiasis, (both with C. glabrata). The average time on ibrexafungerp was 16.6 d. The mean time to death post-treatment for these patients was 22 d (median 8 d). In each case, the deaths were due to causes other than the underlying fungal disease.

Conclusion

Analysis of all-cause mortality in these patients from the FURI study indicates that oral ibrexafungerp provides a favorable therapeutic response in patients with challenging fungal disease and limited treatment options.

Disclosures

Thomas King, MS MPH, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds Nkechi Azie, MD MBA FIDSA, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds David A. Angulo, MD, SCYNEXIS, Inc.: employee|SCYNEXIS, Inc.: Stocks/Bonds.
471. Comparison of Outcomes for Obese and Non-Obese Patients Receiving Micafungin 100 mg Daily for Candidemia
Authors: Diaz Jonathan , Denzer Rose , Hand Elizabeth O , Foster Dana , Yap Alexander , Hughes Darrel W
Published: December 2022

Background

Echinocandins, such as micafungin, are first-line agents for the treatment of candidemia. Researchers have questioned the adequacy of the standard 100 mg dose for all patients, as certain characteristics such as obesity can significantly alter the pharmacokinetics of this agent. Prior data have shown obese patients may be less likely to achieve the pharmacodynamic targets shown to be associated with clinical success. The purpose of this study is to compare clinical outcomes for obese and non-obese patients receiving standard dosing of micafungin.

Methods

This is a multi-center, retrospective study conducted at two large academic hospitals. All adults admitted with a positive blood culture for Candida spp. between January 1st 2017 and December 31st 2021 were reviewed for inclusion. Patients who received > 1 dose of micafungin were designated as either obese (BMI ≥ 30 kg/m2) or non-obese (BMI < 30 kg/m2). Patients who received combination antifungal therapy or had subsequent episodes of candidemia were excluded.

Results

One hundred and eighty-five of 248 patients were included. Fifty-six (30.3%) patients were obese and 129 (69.7%) were non-obese. Most were critically ill (55.1%), middle-aged (median 60 years), Hispanic or Latino (52.7%) and male (57.8%). Patients received micafungin 100 mg IV daily for a median of 6 (IQR 3-11.5) days. Obese patients had a higher Charlson Comorbidity Index of 4.5 (IQR 3-6.8) compared to 4 (IQR 2-6) in non-obese patients. Critically ill obese and non-obese patients had median Sequential Organ Failure Assessment scores of 10 (IQR 6.75-11.5) and 9 (IQR 4-12), respectively. Clinical and microbiologic failure at day 14 were numerically higher in obese patients ([44.6% vs 32.3%; p = 0.13] and [19.6% vs 10.1%; p = 0.10], respectively), while in-hospital and 30-day mortality were significantly higher in the obese population ([39.3% vs 22.5%; p = 0.03] and [44.6% vs 27.1%; p = 0.03], respectively).

Conclusion

Obese patients treated for candidemia with micafungin 100 mg IV daily had a significantly higher in-hospital and 30-day mortality. Clinical and microbiological failure followed a similar trend, without meeting statistical significance. Additional studies are warranted to determine whether higher doses of micafungin may improve outcomes in obese patients.

Disclosures

All Authors: No reported disclosures.