bluuebunny/crossref_metadata_2025_split huggingface dataset:
92. Incidence of Adenovirus Respiratory Infection and Coinfection in a Longitudinal Birth Cohort
Authors: Gailani Adam E , Teoh Zheyi , Conrey Shannon C , Burke Rachel M , Cline Allison R , Killerby Marie E , Lu Xiaoyan , Mattison Claire , McNeal Monica , Morrow Ardythe L , Payne Daniel C , Staat Mary A 
Published: December 2022

Abstract

Background
Adenoviruses (AdVs) are a common cause of acute respiratory illness (ARI) in children and are often detected with other viruses (coinfection). However, the community incidence of AdV infections is poorly understood due to a lack of prospective studies outside the hospital setting. Here, we aim to characterize respiratory AdV infections and coinfections in a prospective birth cohort of children.

Methods
The PREVAIL cohort is a CDC-funded, 2-year birth cohort, conducted from 2017–2020 in Cincinnati, OH. ARI was defined as the presence of cough or fever identified with weekly maternal text surveys and medical chart review. Mid-turbinate nasal swabs were collected weekly. Swabs were tested using Luminex Respiratory Pathogen Panel. AdV infection was defined as a swab positive for AdV and included subsequent positives &lt; 30 days apart. Coinfection was defined as detection of any other virus(es) during an AdV infection. Children who submitted at least 70% of weekly samples were included in our analysis.

Results
101 children met inclusion criteria, representing 165 child-years. 137 distinct AdV infections were identified (incidence 0.84 infections per child year), with 98 (97%) children having ≥1 AdV infection. Only 40% (n=55) of AdV infections were symptomatic. Of those with symptomatic infections, 51% (n=28) sought medical care, with 42% (n=23) presenting to a primary care provider and 9% (n=5) resulting in an ED visit or hospital admission. Coinfections were detected in 67% (n=92) of AdV infections, with 45% (n=62) coinfected with 1 virus, 19% (n=26) with 2 viruses, and 3% (n=4) with ≥3 viruses. 77% of coinfections (n=71) were rhino/enterovirus. The number of coinfections or the specific coinfection virus was not associated with an increase in symptom prevalence or symptom severity (all p &gt; 0.05).
Viral Coinfection Frequency with Adenovirus Infection in the PREVAIL Cohort.
Adenovirus Infection and Coinfection in the PREVAIL Cohort.

Conclusion
In this cohort of healthy children, AdVs were a common cause of respiratory infection. Most infections were asymptomatic or resulted in mild symptoms. Two-thirds of AdV infections involved viral coinfections, but coinfection was not associated with more frequent or severe symptoms. Our findings suggest studies that only include symptomatic or hospitalized patients may overestimate AdVs disease severity.

Disclosures
All Authors: No reported disclosures.
737. Oral Antibiotic Stepdown Therapy for Uncomplicated Streptococcal
Authors: Loomis Jordan M , Mang Norman S , Ortwine Jessica , Prokesch Bonnie C , Wei Wenjing 
Published: December 2022

Abstract

Background
Streptococcus species are known pathogens in bloodstream infections (BSIs). Traditionally, BSIs are managed with intravenous (IV) antibiotics, however there is growing literature supporting oral (PO) antibiotics in BSIs as well as other invasive infections. Advantages to PO therapies include shortened hospital stay, reduced treatment costs, and avoidance of line-related complications. Currently, there is a paucity of data supporting the use of PO antibiotics in streptococcal BSIs.

Methods
This retrospective cohort study evaluated patients with streptococcal bacteremia between September 2019 to September 2021. Patients 18 and older were included if they had at least one positive blood culture for any Streptococcus species and excluded if BSI was polymicrobial, or treatment was for complicated BSI, identified by receipt of targeted therapy for ≥ 16 days, or source being endocarditis, osteomyelitis, or meningitis. Clinical outcomes were compared between patients who completed treatment with IV antibiotics verses those who completed with an PO stepdown regimen. The primary endpoint was clinical failure, which was a composite endpoint defined as BSI recurrence with the same pathogen and infection-related readmission within 30 days from completion of antibiotics.

Results
A total of 158 patients were included, with 77 (49%) receiving a full course of IV antibiotics and 81 (51%) receiving an PO antibiotic stepdown regimen. Clinical failure was not different between the IV antibiotics group versus the PO stepdown group, respectively (16% vs. 15%, odds ratio [OR] = 0.94; 95% confidence interval [CI], 0.40 to 2.25). No differences were observed in 30-day all-cause mortality. Patients that received PO antibiotic stepdown therapy had a significantly shorter hospital length of stay by 6 days (6 versus 12 days, p&lt; 0.01).

Conclusion
Our results suggest that clinical cure with an PO stepdown regimen for uncomplicated streptococcal BSIs is comparable to IV antibiotics. The benefit of comparable efficacy in the setting of reduced length of stay and avoidance of central line placement for outpatient IV antibiotics should be considered when making treatment plans for patients with uncomplicated streptococcal BSIs.

Disclosures
All Authors: No reported disclosures.
752. Decreased Echinocandin Resistance among Candida glabrata over an Eleven-Year Period at a University Hospital
Authors: Raabe Nathan , Zhao Yanan , Paderu Padmaja , Shields Ryan K , Clancy Cornelius J , Nguyen Minh-Hong 
Published: December 2022

Abstract

Background
Invasive candidiasis (IC) is associated with significant morbidity and mortality. Echinocandins (ECH; caspofungin (CAS), micafungin (MFG), anidulafungin (AFG)) are first line therapy for IC. ECH resistance has emerged widely, most commonly among Candida glabrata. At some centers, &gt; 10% of C. glabrata are ECH resistant. We reported ECH resistance in 8% of C. glabrata at our hospital from 2008–2014, which prompted stewardship strategies to limit prolonged ECH treatment courses. We evaluated trends of ECH resistance from Jan 2010-Dec 2020 among C. glabrata clinical isolates, and assayed isolates for FKS hot spot (HS) mutations.

Methods
We mined electronic medical records for ECH MIC data against C. glabrata clinical isolates at UPMC. We defined ECH resistance using Clinical and Laboratory Standards Institute clinical breakpoints. Isolates resistant to any ECH underwent FKS Sanger sequencing. Statistical analysis was performed using Stata.

Results
Overall CAS, AFG and MFG resistance rates among 516 isolates were 4%, 3%, and 2.5%, respectively. There was no significant difference in resistance rates between blood and non-blood sites (Table 1). There was a significant decrease in MFG resistance over the 12-year period (Fig 1). Time series regression analysis showed a decrease in rate of MFG resistance of 0.73% per year (p=.007). Trends for decreases in AFG and CAS resistance rates were also noted (p=.1 and p=.17). Similar analyses showed annual decreases in MFG MICs (0.019 μg/mL per year; p=.07). The average percentage of AFG resistant isolates was significantly lower in 2017–2020 than in 2012–2016 (p=.04); similar trends were evident for MFG (p=.07) and CAS (p=.08) (Fig 2). Sanger sequencing of FKS1/2 was performed for 27 isolates resistant to ≥1 ECH. Mutations were found in 44% (12/27) of isolates: 5 mutations in HS1 FKS1, 1 in HS2 FKS1, 5 in HS1 FKS2 and 1 in HS2 FKS2. Using both CAS and AFG MICs was most predictive of FKS mutations (Fig. 3).

Conclusion
ECH resistance among C. glabrata stabilized or decreased over 11-years at our hospital, in keeping with stewardship interventions to reduce prolonged use of ECHs. These results demonstrate that it is feasible to conserve ECH susceptibility.

Disclosures
Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham & Associates: Advisor/Consultant Minh-Hong Nguyen, MD, QPX: Grant/Research Support.
779. PIDS Featured Oral Abstract: High Beta Lactam Exposure in Neonates with Bloodstream Infection Associated with Intestinal Dysbiosis and Enterococcus spp. Abundance in the Gut Microbiome
Authors: Hendricks Hope , Weitkamp Jörn-Hendrik , Pakala Suman , Rajagopala Seesandra , Banerjee Ritu 
Published: December 2022

Abstract

Background
To characterize how antibiotic exposure impacts development and durability of intestinal dysbiosis and the acquisition of antibiotic resistance genes (ARGs) in the intestinal flora of premature infants in the Neonatal Intensive Care Unit (NICU), we established an infant gut microbiome biorepository (IGMB).

Methods
We performed prospective weekly stool collection in NICU patients meeting the following criteria: birthweight &lt; 2000 g, postnatal age &lt; 2 months and no diagnoses of congenital gut malformation or cyanotic heart disease. Cases were infants with bloodstream infections (BSI), defined as bacterial growth from blood culture; controls were infants with &lt; 5 days of antibiotic exposure, no BSI nor necrotizing enterocolitis. We performed metagenomic analysis on 5–6 serial stool samples from each of the 10 cases and 10 controls (n= 100 stools). We used Wilcoxon rank sum tests for pairwise comparisons.

Results
From July 2021 to May 2022, 265 infants contributed 1,300 stool samples to the IGMB. In 7 of 8 BSI cases the causative pathogen was identified in the pre-BSI stool sample. Two more BSI cases did not have a pre-BSI stool sample. Microbiome species α-diversity increased with advancing postnatal age in controls but not in cases (Fig. 1). Among 6 cases with high beta lactam exposure ( &gt;14 cumulative days by last stool collection), 3 had notable increases in the relative abundance of Enterococcus spp. (Fig. 2). Controls did not have similar trends in Enterococcus spp., but did have higher relative abundance of facultative anaerobes including Bifidobacterium, Lactobacillus, and Veillonella spp. (Fig. 3). Antibiotic resistance gene (ARG) abundance did not differ significantly between cases and controls.

Conclusion
Compared to controls, neonates with BSI have increased antibiotic intensity throughout their NICU admissions, reduction of microbial species diversity and overabundance of specific organisms in their gut microbiomes. We observed increased Enterococcus spp. prevalence with higher beta lactam exposure. ARG abundance did not differ between cases and controls. The clinical implications of this microbiome dysbiosis warrant further study.

Disclosures
Jörn-Hendrik Weitkamp, MD, Roche Diagnostics: Advisor/Consultant.
782. Infectious Complications of Lung Transplant for COVID-Associated Lung Injury (CALI)
Authors: Osborn Rebecca , Ison Michael G , Alamri Maha M 
Published: December 2022

Abstract

Background
More than 200 orthotopic lung transplants (OLT) have been performed in the United States for patients (pts) with severe CALI. While some outcomes have been reported to generally be good, we conducted this study to describe the infectious outcomes.

Methods
After IRB approval, a retrospective case review was conducted of pts at Northwestern Memorial Hospital who had undergone OLT for CALI between June 1, 2020 and January 31, 2022. Data was collected from our Enterprise Data Warehouse and primary chart review to describe pts demographics and epidemiology of infectious complications.

Results
35 OLTs were included (33 bilateral, 2 single lung; see Table 1). In the two weeks prior to transplant, 65.7% of pts were treated for bacterial, fungal, or mycobacterial infections (Table 2). Post-transplant, 32 (91.4%) of OLTs developed infections (Table 2), with most (28, 80%) developing pneumonia within 30 days of transplant. Five (14.3%) pts had airway complications, 7 (20%) pts required hemodialysis, and 3 (8.6%) pts died within one year of follow-up.

Conclusion
Infections remain a significant cause of morbidity post-OLT for CALI. Enhanced immunosuppression, long ICU stays post-tx, high rates of primary graft dysfunction and deconditioning likely contributed to this high rate of infection. A matched control group is being collected to compare these outcomes to other OLT pts.

Disclosures
Michael G. Ison, MD MS, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support.
792. Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Nasal Swab for Invasive MRSA Infection in Critically Ill Pediatric Patients: A Promising Tool for Antimicrobial Stewardship
Authors: Crawford Lexi M , Hamdy Rana F , Pertsovskaya Vera , Zhang Anqing 
Published: December 2022

Abstract

Background
Patients admitted to the pediatric intensive care unit (PICU) are frequently evaluated for bacterial infections and initiated on antibiotic regimens that include a MRSA-active agent even though invasive MRSA infections are rare in this population. The MRSA PCR nasal swab (MRSA-PCR) is a non-invasive test for MRSA colonization that has been shown within adult ICUs to have a high negative predictive value (NPV), making it a potentially valuable tool for antimicrobial stewardship. This study evaluated the performance of the MRSA-PCR in predicting invasive MRSA infection in critically ill pediatric patients.

Methods
A retrospective cohort study was performed in a 44-bed PICU from January 2013 to December 2018 when it was protocol for all admissions to be screened with a MRSA-PCR. Patients who had both a MRSA-PCR and cultures obtained to evaluate for invasive infection within seven days were included in the study. Invasive MRSA infection was defined by the isolation of MRSA from clinical cultures along with infectious signs and symptoms. A random sample comprising 55% of the patient population was evaluated. We calculated sensitivity, specificity, positive predictive value (PPV) and NPV of the MRSA-PCR for confirmed invasive MRSA infection.

Results
Of the 4,410 patients reviewed, 1,961 patients met inclusion criteria (45% female, mean age 7.4 yrs. [birth-19.9 yrs.]). MRSA-PCR was positive in 13.5% of patients. Invasive MRSA infection was identified in 25 patients (2 blood, 19 respiratory, 2 soft tissue, 1 pleural fluid, and 1 urine culture) equaling 1.2% of encounters and an incidence rate of 1.1 case per 1,000 patient days. The MRSA-PCR demonstrated a PPV of 8.7% and a NPV of 99.8% (see table).

Conclusion
The MRSA-PCR has a poor PPV but a very high NPV for invasive MRSA infection in critically ill pediatric patients, a result that is congruent with what has been reported in the adult literature. The high NPV of the MRSA-PCR in this vulnerable patient population makes it a potentially powerful tool for antimicrobial stewardship. Creation of protocols to guide antimicrobial selection based on MRSA-PCR results may lead to a significant reduction in unnecessary antibiotic exposure, drug level monitoring, and patient risk of renal injury or adverse reactions.

Disclosures
All Authors: No reported disclosures.
793. Procalcitonin-guided Antibiotic Stewardship Oversight Reduces Antibiotic Use and Adverse Outcomes for Patients Admitted with Pneumonia, Results from a Real-world Randomized Controlled Trial in US Hospitals
Authors: Mansour Michael 
Published: December 2022

Abstract

Background
ProSAVE (NCT04158804) is the first prospective interventional RCT to address the effect of procalcitonin (PCT)-guidance in the setting of antimicrobial stewardship (ASP) oversight on clinical outcomes and antibiotics usage for patients admitted with pneumonia.

Methods
Analysis of the pilot cohort from a multicenter trial was conducted enrolling subjects admitted with pneumonia at three clinical sites (academic and community hospitals). Subjects meeting eligibility criteria were randomized 1:1 between the standard of care (SoC) versus PCT-guided ASP oversight (PCT arm); subjects were monitored daily by chart review for up to 30 days. An FDA-approved PCT algorithm was used to guide antimicrobial usage.
95 patients were enrolled as ITT of which 60 patients were assigned per-protocol who were adherent to the PCT algorithm (30 in SoC and 30 in the PCT arm). Primary study endpoints were antimicrobial usage and composite safety comprising readmission, death, intubation, septic shock, renal failure, and pneumonia complications such as empyema and abscess up to day 30.

Results
Baseline subject characteristics were similar between both arms; median age 73y (IQR: 62–86, heart disease (43% SoC vs. 40% PCT arm), and diabetes (23% SoC vs. 29% PCT arm). Early antimicrobial cessation by day 4 of hospitalization was achieved more often in the PCT arm as compared to SoC (ITT: SoC n=5, 11% vs. PCT arm n=14, 29%, p=0.045). In addition, antimicrobial prescription at discharge was lower in the intervention arm (ITT: SoC n=24, 51% vs. PCT arm n=15, 31%, p=0.08; similar and statistically significant efficacy for PP) (Fig 1, panel A). A substantial statistically significant improvement of safety was observed in the PCT arm compared to SoC (reduction by 18.3% (95%-CI: 2.3% – 36.3%) from 23.3% (11.9% – 41.1%, SoC) to 3.3% (0.8% – 16.7%, PCT arm) in PP, similar in ITT) (Fig 1, panel B). Readmission was the main driver for fewer safety events in the intervention arm (SoC 50% vs. PCT arm 33%).

Conclusion
In this pilot cohort of ProSAVE, the introduction of PCT-guided, ASP intervention to medical teams proved to be a successful aid for resourceful antibiotic management decisions resulting in shorter antibiotic durations and significantly lower adverse event rates.

Disclosures
Michael Mansour, MD, PhD, ThermoFisher Scientific: Grant/Research Support.
796. HIV transmission clusters among people who inject drugs in North Carolina, 2010 to 2021
Authors: Panichsillapakit Theppharit , Enders Kimberly , Greifinger Annalea C , Zhou Shuntai , Frost Simon , DPhil M A , Swanstrom Ronald , Eron Joseph J , Mobley Victoria , Samoff Erika , Dennis Ann 
Published: December 2022

Abstract

Background
The marked increase in injecting drug use (IDU) in the past decade presents concern for increased HIV transmission among people who inject drugs (PWID) and explosive outbreaks. Among statewide HIV molecular surveillance, we assessed demographic, clinical, and reported behavioral risk factors associated with HIV clusters involving PWID in North Carolina (NC).

Methods
Persons ≥ 13 years old with HIV-infection residing in NC with ≥ 1 partial pol sequence collected between April 2010 and December 2021 were included in the study. We used an automated cluster analysis pipeline to detect genetic clusters (nextHIV2), defined as ≥ 2 sequences with a pairwise genetic distance &lt; 1.5%. Logistic regression was used to estimate the risk and adjusted odds ratios of the relationship between the demographic factors that were likely associated with HIV clustering. Graphics were generated using the R packages ggplot2 and igraph.

Results
Among 19,641 persons with a sequence, 1,611 were PWID. Of these, 347 (21.5%) PWID were members of 248 clusters involving a total of 2,083 persons (size ranged 2–104). Sixty-four clusters (25%) had ≥2 PWID, whereas 2 (1%) included at least 5 PWID. The most commonly injected drug among cluster members was methamphetamine (19%). Overall, in a univariate analysis, younger age, dual risks of male-to-male sex and IDU, having sex under the influence of drugs, recent IDU (past 12 months), acute HIV infection, higher viral loads and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering PWID individuals (all P&lt; 0.001). In multivariate analyses, only recent IDU and higher CD4 T-cell count at the time of HIV diagnosis were significantly associated with clustering (P&lt; 0.01). In addition, the proportion of PWID in clusters increased from 11.2% in 2010–2013 to 28.5% in 2018–2021 (P&lt; 0.001).
Nodes are colored by their reported PWID in darkred and reported non-PWID in blue.

Conclusion
We detected an increase in HIV genetic clusters among PWID in NC in recent years. Our results support the use of routine local molecular HIV surveillance to identify high priority clusters and offer prevention interventions for specific risk groups to prioritize limited public health resources.

Disclosures
Joseph J. Eron, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant.
799. Unstable Housing, Daily Drug Use, and Transactional Sex are Associated with Viremia in Transgender Individuals Living with HIV
Authors: Garrett Grace , Eyasu Rahwa , Cover Amelia A , Davis Ashley , Harfouch Omar , Ebah Emade , Bijole Phyllis , Gannon Catherine , Wang Vivian , Spikes Michelle , Imani F N U , Jones Miriam , Masur Henry , Kottilil Shyam , Kattakuzhy Sarah , Rosenthal Elana S 
Published: December 2022

Abstract

Background
In the United States, HIV is highly prevalent among transgender individuals, but factors contributing to viremia in this population are poorly understood. We aimed to assess factors associated with HIV viremia among transgender people living with HIV (PLWH).

Methods
PATCH is a longitudinal natural history study of transgender individuals in Washington, DC. Participants complete laboratory assessments, as well as surveys assessing demographics, behaviors, and mental health. Patients whose HIV viral load was &gt;200 copies/mL at screening were considered viremic. Fisher’s exact test was used for statistical analysis.

Results
Of 62 enrolled participants, 35(56%) were HIV+, the majority of whom were prescribed antiretroviral therapy (31, 89%) and had an undetectable viral load (25, 71%). Of PLWH, 35(100%) were assigned male at birth, 34(97%) were Black, and the median age was 37 years. PLWH were predominately stably housed (24, 69%), with 9(26%) reporting daily drug use or more, and 16(46%) reporting transactional sex within a year.
When comparing PLWH who were viremic versus those virally suppressed, viremic PLWH were less likely to be prescribed antiretroviral therapy (60% vs 100%, p=0.004), and more likely to have unstable housing (60% vs 25%, p=0.04), use drugs daily or more in the last month (60% vs 12%, p=0.007), and engage in transactional sex in the last 12 months (80% vs 32%, p=0.02). HIV viral suppression was not significantly associated with number of sexual partners within the last 12 months or always using condoms during any type of sex (p &gt;0.05).

Conclusion
In this cohort of transgender PLWH, we found moderate rates of HIV viremia associated with chaotic life factors such as daily drug use, unstable housing, and engaging in transactional sex. In addition, we found low rates of consistent condom use despite multiple sexual partners, regardless of viral load. Comprehensive care programs that improve access to ART, address substance use disorders and facilitate housing may serve to improve treatment outcomes and reduce risk of HIV transmission in this population.

Disclosures
Shyam Kottilil, MD, PhD, Arbutus Pharmaceuticals: Grant/Research Support|Gilead: Grant/Research Support|Merck: Grant/Research Support|Regeneron Pharmaceuticals: Advisor/Consultant|Silverback Therapeutics: Advisor/Consultant|The Liver Company: Advisor/Consultant|Yufan Biotechnologies: Advisor/Consultant Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support.