bluuebunny/crossref_metadata_2025_split huggingface dataset:
511. The cefazolin (CZ) and piperacillin-tazobactam (TZP) inoculum effects (IEs) are persistent amongst serial isolates of methicillin-sensitive Staphylococcus aureus (MSSA) derived from the sputum of persons with cystic fibrosis (pwCF) despite variation in other phenotypes.
Authors: Svishchuk Julianna , Waddell Barbara Jean M , Lee Sicheng , Rabin Harvey , Lisboa Luiz , Gregson Daniel , Surette Michael , Parkins Michael 
Published: December 2022

Abstract

Background
Phenotypic diversity among chronically infecting pathogens within the airways of pwCF is increasingly recognized, limiting susceptibility testing-directed decision-making (Somayaji, 2019, JCF). While it is an important outcome determinant in infection (Miller, 2018, OFID), the IE has generally only been studied in acute infection models. Herein, we sought to establish if variation in the presence of the IE to beta-lactams exists among CF-derived MSSA.

Methods
Single sputum cultures from 10 pwCF with chronic MSSA infection of ≥ 10 years in duration were collected, and 10 unique colonies from each were selected and confirmed as MSSA for a total of 100 isolates. Individual isolates were subjected to susceptibility testing at standard (SI: 105 CFU/mL) and high inoculum (HI: 107 CFU/mL) against CZ and TZP and assessed for protease (PRO) and hyaluronidase (HA) production in triplicate. The presence of the IE was defined if a ≥ 4-fold difference in MIC between SI and HI existed. All 100 strains were typed using pulsed-field gel electrophoresis.

Results
Patients included had a median age of 30.5 years, forced vital capacity of 93%, forced expiratory volume in one second of 66% predicted, and a BMI of 21.5 kg/m2. Median sputum MSSA burden was 106 CFU/ml. The IE was overall more common with TZP than CZ: 47% vs 33%, respectively. Median MIC50 for CZ increased between SI and HI: 0.5 to 1µg/mL, and TZP: 2 to 4µg/mL (p&lt; 0.0001 for both). The most prevalent pulsotypes identified corresponded to multilocus sequence types (ST)-5 (20%), ST-30 (15%), and ST-1 (5%), where ST-30 isolates were more likely to exhibit the CZ and TZP IE (p&lt; 0.0001 for both). Eight out of 10 patients had all isolates belonging to the same pulsogroup. Of patients infected with a single strain, discordance between IE phenotype was not noted, though PRO and HA production varied. Among these patients, the standard deviation of zone clearance diameter ranged from 0-0.9cm (mean range: 0-1.4cm) and 0-1.8cm (mean range: 0-7.2cm), respectively, between individual isolates.

Conclusion
Phenotypic diversity in chronic MSSA exists within the airways of pwCF. However, we observed the IE for CZ and TZP to be strain dependent, without variable penetrance.

Disclosures
All Authors: No reported disclosures.
516. Delivery Mode and Intrapartum Antibiotics Affect the Gut Mycobiome in Newborn Infants and Young Children
Authors: Turunen Jenni , Paalanne Niko , Reunanen Justus , Tapiainen Terhi , Tejesvi Mysore V 
Published: December 2022

Abstract

Background
The gut mycobiome may have important effects on health. Yet, there is limited data on the mycobiome. Previously, we have shown that antibiotic exposure at birth markedly alters the gut bacteriome in children. As fungi and bacteria may have important interactions in the gut microbiome, we hypothesized that perinatal antibiotics may influence the composition of the gut mycobiome.

Methods
For the study, 434 fecal samples were collected at birth, 6 months, and 18 months of age. We extracted DNA from samples using DNeasy PowerSoil Pro kit. We sequenced the ITS2 gene and analyzed the results using QIIME2. The taxonomy was assigned using UNITE database.

Results
At birth, newborn infants had a low-biomass gut mycobiome, which developed over time until the age of 18 months. At the genus level, there was a transition from Candida to Trichosporon and Saccharomyces at 6 and 18 months respectively. Unidentified fungi were found in greater numbers in 18-month stool samples than in earlier samples. Alpha and beta diversity analyses showed statistically significant differences depending on the age of infants.
Both delivery mode and intrapartum antibiotics were associated with significant differences in the gut mycobiome composition. Infants born vaginally had mycobiome with abundant Candida at birth and their mycobiome progressed towards composition dominated by Trichosporon and Saccharomyces. Samples from infants born via C-section had more Malassezia, Hyalotiella and Saccharomyces.
Vaginally delivered infants exposed to antibiotics at birth had more Candida sp. in the gut mycobiome than those unexposed to antibiotics. By 18 months of age, half of the fungi in no intrapartum antibiotic group were unidentified fungi, but more than half of the fungi in the intrapartum antibiotic group were of genus Trichosporon.Figure 1.Taxonomic figures of each sample type. Taxa have been drawn from phylum (innermost level) to species (outermost level).
Figure 2. Taxonomic figures of each sample type are based on the delivery mode. Taxa have been drawn from phylum (innermost level) to species (outermost level).
Figure 3. Taxonomic figures of each vaginal delivery sample are based on the usage of intrapartum antibiotics. Taxa have been drawn from phylum (innermost level) to species (outermost level).

Conclusion
In this prospective cohort study, the gut mycobiome composition of newborn infants and young children was markedly influenced both by delivery mode and exposure to antibiotics at birth. The effects were observed from birth until 18 months of age.

Disclosures
All Authors: No reported disclosures.
523. A Rapid, Objective Measure of the Host Response May Help Guide Efficient and Judicious ED Care for Sepsis
Authors: O’Neal Hollis R , Sheybani Roya , Tse Henry T , Shah Ajay M , Thomas Christopher B 
Published: December 2022

Abstract

Background
Most cases of sepsis present to Emergency Departments (ED’s). Current guidelines stress ED clinicians to intervene before adequate, objective diagnostic and prognostic data are available, resulting in a ‘one size fits all’ strategy. This causes excessive use of broad-spectrum antibiotics and limited resources. The IntelliSep test is an investigational, in vitro host response test that quantifies the state of immune activation by measuring the biophysical properties of leukocytes. The test is performed on EDTA-anticoagulated blood and results in under 10 minutes. The result, the Intellisep Index (ISI), ranges 0.1-10.0, stratified into three interpretation bands of increasing disease severity risk: Green, Yellow, and Red.
This study assesses the Intellisep Index (ISI) as a potential aid for risk stratification and resource allocation for the treatment of patients presenting to the emergency department with possible sepsis.

Methods
Adult patients presenting to the ED with signs or suspicion of infection were prospectively enrolled at multiple US sites (Apr. – Sept. 2019). Patients were followed by retrospective chart review for outcome information and Sepsis-3 adjudication. Treating clinicians were blinded to ISI results.

Results
290 study patients (sepsis prevalence 17.5%) were stratified by the ISI as 160 (55%) Green, 70 (24%) Yellow, and 60 (21%) Red. The diagnostic odds ratio for sepsis was 20.5 (8.2 - 36.0, 95% CI) between the Red and Green Bands. Subjects in the Green Band had significantly lower mortality (p &lt; .01) and severity of illness, as measured by APACHE II (p &lt; .01), SOFA (p &lt; .001), ICU admission (p &lt; .001) and hospital length of stay among survivors (p &lt; .001). However, 16 (10%) subjects in the Green Band received antipseudomonal and / or anti-MRSA antibiotics in the ED; only two of these subjects were septic (both survived without needing ICU care with 0 and 6-day hospital stays). Conversely, 12 septic subjects in the Red Band did not receive broad-spectrum anti-MRSA antibiotics in the ED, with an average hospital length of stay of 8 days and one fatality.

Conclusion
The ISI, a rapid, quantitative measure of immune activation, may offer ED clinicians an aid for rapid risk stratification of patients presenting with suspicion of infection and guide appropriate treatment.

Disclosures
Roya Sheybani, PhD, Cytovale: Employee|Cytovale: Stocks/Bonds Henry T. Tse, PhD, Cytovale: Stocks/Bonds Ajay M. Shah, PhD, Cytovale Inc: Board Member|Cytovale Inc: Ownership Interest|Cytovale Inc: Stocks/Bonds.
537. First Week Post-Operative C-Reactive Protein Kinetics Show Different Patterns of Association with Infection Depending on the Type of Surgery
Authors: van Boekel Anna M , van der meijden Siri L , Geerts Bart F , Arbous Sesmu M , de Boer Mark G 
Published: December 2022

Abstract

Background
C-reactive protein (CRP) is a nonspecific marker of inflammation and due to surgery alone CRP levels are increased post-operatively. Although multiple studies investigated the potential of post-operative CRP levels to predict post-operative infection, its discriminative capacity remained unclear. We aimed to describe the kinetics of CRP for post-operative patients with- and without a post-operative infection for different types of surgery in the first seven post-operative days.

Methods
We conducted a single center cohort study in adult patients undergoing surgery between 2011 and 2021 with the use of whole digital case file extraction (big data). All patients that had either an infectious complication registered, non-prophylactic antibiotics prescribed and/or an infection related surgical re-intervention within 7 days after having undergone surgery, were labelled as having an infection. We analyzed the CRP kinetics in the first seven post-operative days for all these patients.

Results
A total of 39.985 individual patients were included of which 12.002 patients had at least one CRP measurement and 4.014 patients had an infection in the first seven post-operative days. CRP was measured in 66% of the patients with an infection and in 26% of the patients without an infection. In all patients CRP increased during the first two post-operative days regardless of infection status (Figure 1). In cardiothoracic, orthopedic, ear-nose-throat, general and urological surgery CRP decreased after day 2 or 3 in all patients but the absolute CRP value remained higher in the following days in patients with an infection compared to patients without an infection. In gynecological and oral surgery CRP decreased on day 3 in patients without an infection but not before day 4 in patients with an infection. CRP was not discriminative in neurosurgical or plastic surgery patients (Figure 2).
CRP kinetics in the first seven post-operative days for patients with- and without an infection
CRP kinetics for different subspecialties in the first seven post-operative days
CTS = cardiothoracic surgery; ENT = ear-nose-throat surgery; GEN = general surgery; GYN = gynecological surgery; NEUR = neurosurgery; ORAL = oral surgery; ORT = orthopedic surgery; PLA = plastic surgery; URO = urological surgery.

Conclusion
In the first 2 post-operative days CRP increases in both patients with- and without an infection which is probably due to the surgical procedure itself. After the second post-operative day differences in CRP kinetics develop between patients with- and without an infection, but how they differ depends, among other factors, on the type of surgery.

Disclosures
Siri L. van der meijden, MSc, Healthplus.ai: Employee Bart F. Geerts, MD. PhD., Healthplus.ai: Board Member.
538. Human neutrophil gelatinase-associated protein (N-gal) and proinflammatory cytokines as biomarkers of disease severity in children with Hemolyitic Uremic Syndrom (HUS) and Shigatoxin-producing E.coli (STEC) infection.
Authors: Toledano Analía , Caratozzolo Ana , Lanfranchi Romina , Martinez Mayra , Chacoff Marian , Talarico Laura , Contrini María M , Lopez Eduardo Luis 
Published: December 2022

Abstract

Background
Hemolytic Uremic Syndrome (HUS) is a complication of Shigatoxin-producing E.coli (STEC) infection which presents a characteristic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Preliminary in vitro and experimental animal studies demonstrated that Shigatoxins (STXs) induce the secretion of proinflammatory cytokines. Human neutrophil gelatinase-associated protein (N-gal) has been reported as a marker of acute kidney injury. Dosing serum levels of IL-8, TNF-α, IL-6, IL-1β and N-gal in children with STEC-associated infection and HUS would allow to establish the role of these cytokines as biomarkers of renal injury and severity

Methods
Prospective study during 2017 – 2020 was performed; three groups of patients &lt; 18 years were included: bloody diarrhea (BD), HUS requiring dialysis (HUSD) and HUS and no dialysis requirement (HUSND), all of them with presence of STX in stool. Blood samples were collected at diagnosis (t1) and at 7 days (t2). An immunoassay was used for detection of TNF-α, IL-1β, IL-6, and IL-8 (Bio-Plex Pro Human®, BioRad). An immunoassay (Anti-Lipocalin-2) was used for N-gal detection

Results
Forty-nine children were admitted; 22 (49%) were male. Median age was 24 (IQR 13-36) months. Fourteen patients with BD, 24 patients with HUS: 12 HUSD and 12 HUSND. Eleven healthy children (HC) were included. At diagnosis, higher IL-8 values were found in HUSD vs. BD (p=0.0004), HUSND (0.003) and HC (p= 0.0043). Higher TNF-α values were detected in HUSD vs. BD (P= 0.0001), HUSND (p= 0.0011) and HC (p= 0.0002). Higher TNF-α values were found in patients with BD vs HC (p= 0.0055). HUSD exhibited higher IL-6 values as compared with BD (p= 0.0145) and HC (0.0106). N-gal concentrations were higher in HUSD vs. BD (P= 0.0120), HUSND (P= 0.0166) and HC (p= 0.0049). A decrease in IL-8 was observed in HUSD between t1 and t2 (p=0.0357). (Figure 1)

Conclusion
Interleukin 8, IL-6, and N-gal may be considered as potential serological markers of renal damage and dialysis requirement. TNF-α concentrations are already increased in BD without HUS complications

Disclosures
All Authors: No reported disclosures.
547. Risk factors that can predict adrenal insufficiency in fever of unknown origin
Authors: Go Ji Won , Lee Seung Eun , Park Jung Hwan , Pai Hyunjoo , Kim Dong Sun , Kim Bongyoung 
Published: December 2022

Abstract

Background
Adrenal insufficiency is one of the causes of fever of unknown origin (FUO), however, it is often mistaken for an infectious disease, leading to unnecessary antibiotic use. The purpose of this study is to find out risk factors that can predict adrenal insufficiency in FUO patients so that set a target to recommend the adrenocorticotropic hormone (ACTH) stimulation test.

Methods
This study was conducted retrospectively in a tertiary hospital with 846 beds in South Korea. All adult inpatients (age ≥ 19 years) who have requested a consult with the department of infectious disease (ID) for FUO between 1 July, 2019 and 30 June, 2020 were included in the study. Among them, those who underwent an ACTH stimulation test and had a fever of 37.8°C or higher within 48 hours of the ACTH stimulation test were finally included in the study subjects.

Results
A total of 202 FUO patients were enrolled and 61 (30.1%) were finally diagnosed with adrenal insufficiency. Patient with adrenal insufficiency had higher charlson comorbidity index score than others (2.36±1.88 vs. 1.85±2.06, P=0.016). In addition, higher proportion of patients who used immunosuppressant (31.1% vs. 6.4%, P&lt; 0.001) and/or corticosteroid (19.7% vs. 3.5%, P&lt; 0.001) within 3 months were observed in adrenal insufficiency group. Patients with adrenal insufficiency tended to show hypotension (21.3% vs. 10.6%, P=0.044), lower white blood cell count [10^3/uL] (9.27±6.30 vs. 10.54±5.82, P=0.025), lower hemoglobin (4.38±9.96 vs. 1.70±2.10, P=0.023), lower albumin (8.25±0.94 vs. 8.49±0.60, P=0.009), and higher creatinine (1.39±1.61 vs. 1.05±1.57, P=0.044) than those without adrenal insufficiency. In a multivariate analysis, use of immunosuppressant within 3 months (OR 6.06, 95% CI 1.82–20.13, P = 0.003), use of corticosteroid within 3 months (OR 8.23, 95% CI 1.35–50.17, P = 0.022), sodium ≥ 136.7 (OR 3.43, 95% CI 1.49–7.88, P = 0.004), and calcium ≥ 8.4 (OR 0.31, 95% CI 0.14-0.71, P = 0.005) were proven to be factors that can predict adrenal insufficiency in FUO patients.

Conclusion
When FUO patients have a history of immunosuppressant/corticosteroid use within 3 months, and/or shows sodium ≥ 136.7, or calcium &lt; 8.4 at initial laboratory test, performing ACTH stimulation test is recommended.

Disclosures
All Authors: No reported disclosures.
589. Clinical Outcomes of Twice versus Thrice daily Metronidazole Dosing for Bacteroides Bloodstream Infections
Authors: Shah Sunish , Adams Kathleen , Topal Jeffrey E , McManus Dayna , Clarke Lloyd , Nguyen Minh-Hong , Shields Ryan K 
Published: December 2022

Abstract

Background
The optimal metronidazole dose for the treatment of Bacteroides spp. has not been defined. The purpose of this study was to evaluate the utility of a twice (BID), rather than thrice (TID) daily metronidazole dosing strategy among patients with bacteremia due to Bacteroides spp.

Methods
Adult, hospitalized patients with bacteremia secondary to Bacteroides spp. between October 2010 and June 2021 were assessed across 11 hospitals. The primary endpoint was clinical failure which was a composite of all-cause 30-day mortality, escalation of antimicrobial therapy, 30-day readmission or recurrence due to an anaerobic infection, positive repeat blood cultures for Bacteroides spp., or failure to resolve leukocytosis or fever.

Results
208 patients were included; 68 received metronidazole 500mg BID and 140 patients received metronidazole 500mg TID (Figure). Patient age, Charlson comorbidity index, and Pitt Bacteremia score were similar among patients receiving BID vs TID dosing (Table 1). On balance, patients who received BID dosing were more likely to receive oral metronidazole and had shorter lengths of hospitalization prior to bacteremia. Overall, there was no significant difference between rates of clinical failure or other outcomes between patients who received BID versus TID metronidazole dosing (Table 2). In the multivariate model, neither the use of TID dosing (OR = 0.74; 95% CI = 0.33–1.65; P=0.457), time to treatment initiation (OR = 1; 95% CI = 0.81–1.22; P=0.968), days of initial non-metronidazole anaerobic therapy (OR = 0.91; 95% CI = 0.59–1.34; P=0.646), pre-infection length of stay (OR = 1.02; 95% CI = 0.99–1.05; P=0.106), admission prior to 2016 (OR = 1.09; 95% CI = 0.49–2.39; P=0.829), or initial oral metronidazole use (OR = 0.45; 95% CI = 0.18–1.03; P=0.066) were significantly associated with clinical failure. Figure 1:Inclusion and exclusion
Non-metronidazole anaerobic coverage consisted of a beta-lactam/beta-lactamase inhibitor, cefoxitin, or a carbapenem Table 1:Demographics and baseline characteristicsTable 2:Clinical outcomes*Patients were considered to have escalated antimicrobial therapy if, in the setting of ongoing signs of infections, antimicrobial therapy was either broadened or the frequency of metronidazole was increased from twice daily to thrice daily.

Conclusion
In the largest study to date of patients with Bacteroides spp. bacteremia treated with metronidazole, there was no significant difference between BID and TID metronidazole dosing strategies. In the absence of a clear benefit, metronidazole 500mg BID is a reasonable dosing strategy in lieu 500mg TID for infections due to Bacteroides spp.

Disclosures
Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.
601. Characterizing Modifiable Risk Factors for Liposomal Amphotericin B (L-AMB) Nephrotoxicity
Authors: Bialick Kate , Leu Teresa , Liu Catherine , Tverdek Frank P 
Published: December 2022

Abstract

Background
Liposomal amphotericin B (L-AMB) is a broad spectrum anti-fungal utilized in the treatment of serious fungal infections. Despite its liposomal formulation aimed at reducing toxicity, it is still associated with relatively high rates of nephrotoxicity. Few studies have attempted to assess the effectiveness of mitigation strategies to lower the risk of L-AMB-associated nephrotoxicity.

Methods
The purpose of this study is to characterize the time course of nephrotoxicity secondary to L-AMB, evaluate modifiable risk factors for L-AMB-related nephrotoxicity, and identify potential interventions to minimize nephrotoxicity. A retrospective chart review of inpatients who received L-AMB: Oct 1, 2020 through Jan 31, 2022 at the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). The primary objective was to identify the incidence and onset of L-AMB related nephrotoxicity. Eligible patients ≥18 years old with a history of hematologic malignancy, solid organ transplant, or bone marrow transplant were included. Univariable associations were evaluated with either Chi-square or T-test.

Results
A total of 132 patients were reviewed with 77 patient courses included. The baseline characteristics are depicted in TABLE 1. The mean dose of L-AMB was 4.9 mg/kg with an average treatment duration of 8.2 days. Nephrotoxicity occurred in 33.8 % of patients with median onset of 3 days. IV hydration occurred in 88.5 and 68% of patients pre and post, respectively. Patients had at least one concomitant nephrotoxin (87 %) with an average of 2. Comparing those patients with nephrotoxicity and those without, age and L-AMB duration, were associated with nephrotoxicity. Table 1- Baseline CharacteristicsTable 2- Nephrotoxicity Risk Factors

Conclusion
L-AMB nephrotoxicity occurred at a relatively high rate in this patient population despite high utilization of toxicity mitigating strategies such as IV hydration. Nephrotoxicity was associated with longer durations of therapy. Further investigation is necessary to determine alternative strategies for nephrotoxicity prevention.

Disclosures
All Authors: No reported disclosures.