bluuebunny/crossref_metadata_2025 huggingface dataset:
2781. The Use of Aminoglycosides for Treatment of Urinary Tract Infections in Pediatric Patients, a Carbapenem-Sparing Approach
Authors: Legaspi Jamie , Mongkolrattanothai Kanokporn , Edward Priya , Orbach Regina
Published: November 2023

Background

Urinary tract infections (UTIs) caused by antimicrobial-resistant pathogens have been increasingly reported. Aminoglycosides are known to be effective therapy for UTIs, however their use is not common due to a fear of nephrotoxicity. Overuse of broad-spectrum antimicrobial agents, particularly carbapenems can lead to colonization with carbapenem-resistant pathogens resulting in more difficult-to-treat infections. We aim to evaluate the use of aminoglycosides for UTI therapy in pediatric patients to assess the clinical outcome.

Methods

A retrospective chart review was performed to evaluate all orders of aminoglycosides for the indication of UTI from 2020-2022 at Children’s Hospital Los Angeles. Demographic data, bacterial pathogen, kidney function before and during treatment, and clinical outcomes were collected and analyzed. We also evaluated the resistance patterns of bacterial pathogens, and whether they met our institutional criteria of a multi-drug resistant organism (MDRO). Patients were excluded if they received ≤ 48hrs of treatment with an aminoglycoside or if they did not have a gram-negative pathogen identified on urine culture.

Results

A total of 61 patient encounters included an aminoglycoside order for treatment of UTI during the review period. 45 out of 61 encounters had a positive urinary culture that met our institutional criteria for an MDRO. Among patients receiving aminoglycosides, we observed 4 cases of elevated sCr that met our definition of AKI. The 2 cases with the greatest creatine increase (3-4 x baseline), were also currently receiving empiric vancomycin treatment. No patients had a documented treatment failure requiring change or escalation in therapy, or lack of resolution of fever. Four cases had a recurrence within 30 days after discharge. Three out of the four patients with recurrence had pre-existing anatomical abnormalities of the urinary tract that put them at increased risk for recurrent infection.

Conclusion

Overall, extended interval aminoglycoside therapy was effective and well-tolerated for the treatment of urinary tract infections in our pediatric patient population. For cases of multi-drug resistant urinary pathogens, aminoglycosides represent a reasonable alternative to broader spectrum options such as carbapenems.

Disclosures

All Authors: No reported disclosures
2793. Clinical Outcomes of Combination Therapy with Daptomycin and Ceftaroline for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection
Authors: Chapin Ryan W , McCoy Christopher , Donohoe Kendall , Patel Dimple
Published: November 2023

Background

IDSA MRSA Treatment Guidelines recommend vancomycin or daptomycin as first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI). Limited data and few recommendations exist regarding combination treatment for MRSA BSI outside of prosthetic valve endocarditis (PVE). The alternative treatment option of combining daptomycin with ceftaroline for its synergistic mechanism possibly through β-lactam-induced reduction in cell wall cross-linking has been pursued. This regimen is less feasible for home administration and more information on when to de-escalate to monotherapy after blood culture clearance is needed. This study evaluated clinical outcomes for patients with MRSA BSI who received combination therapy with daptomycin and ceftaroline.

Methods

This was a single-center, retrospective study evaluating hospitalized patients mostly with persistent MRSA BSI from 1/2019 to 7/2022 who received a combination of daptomycin and ceftaroline. Patients with a diagnosis of pneumonia, PVE or polymicrobial bacteremia were excluded. The primary endpoint assessed in-hospital mortality for patients on combination therapy. Secondary endpoints included readmission within 90 days, reoccurrence of bacteremia within 30 days, length of stay and adverse drug reactions during treatment.

Results

Of 73 patients screened, 14 patients were included with the primary reason for exclusion being diagnosis of PVE. Notably, half of the patients had a history of IVDU, with the majority of patients (71%) being started on initial therapy with vancomycin. Blood culture clearance occurred within 3 days of starting the combination for 11 of 14 patients. Only 4/14 patients received combination therapy for > 14 days, in which one patient died on a total duration of 26 days.

Conclusion

This study demonstrated a variable duration of combination therapy for MRSA BSI in low-risk patients. The in-hospital mortality rate observed was low. All had microbiological cure. However, further exploration is needed to determine the optimal time for de-escalation after blood culture clearance. Future studies could contribute to creating stewardship efforts to de-escalate patients for MRSA BSI.

Disclosures

All Authors: No reported disclosures
2822. Impact of Restrictive Urinalysis Reflex to Culture Criteria at a Large Community Hospital
Authors: Caveness Christian F , Orvin Alison , Bouchard Jeannette
Published: November 2023

Background

Treatment of asymptomatic bacteriuria (ASB) is a common, but often unnecessary, practice. Some data suggest increased rates of positive urine cultures (UC) lead to ASB treatment. The objective of this study was to determine the impact of restrictive urinalysis reflex to culture (UARC) criteria on rate of UCs ordered and ASB treatment. Previous UARC criteria were any of the following: leukocyte esterase trace or greater, positive nitrites, or white blood cells (WBC) > 10 cells/high powered field (HPF). On March 15, 2023, the criteria were modified to only WBC > 10 cells/HPF.

Methods

This was a pre-post study evaluating UARCs ordered in the emergency department or inpatient units from March 1 to March 31, 2022 (pre-intervention) and March 16 to April 15, 2023 (post-intervention). The primary outcome was the proportion of reflex UCs prevented. Secondary outcomes included the frequency of repeat UARCs and stand-alone UCs ordered after an initial negative UARC, the incidence of patients with gram-negative rod (GNR) bacteremia within 7 days of a negative UARC, and the rate of ASB treatment in a sample of patients with positive UCs after UARC.

Results

In the pre-intervention, 4761 UARCs were ordered compared to 5420 in the post-intervention; 1806 (37.9%) and 1160 (21.4%) reflexed to UCs, leading to a 43.5% reduction in UCs. The rate of repeat UARCs, stand-alone UCs, and rates of GNR bacteremia with a negative UARC were numerically similar between groups. In the sample of pre-intervention patients (n = 100), 70 were women, median age was 74 years old (IQR 61-82), and median Charlson comorbidity index (CCI) was 5 (IQR 2-6). In total, 83 patients with positive UCs were treated, 43 (51.5%) were asymptomatic. In the post-intervention (n=68), 54 (79.4%) were women, median age was 80 (IQR 64-85), and median CCI was 5 (IQR 4-6). Fifty-five (80.9%) patients were treated, 24 (43.6%) were asymptomatic.

Conclusion

The change in UARC criteria led to a 43.5% relative reduction in UCs. A similar number of patients in the post-intervention and the pre-intervention had GNR bacteremia without a reflex UC. ASB treatment rate was lower in the post-intervention; more studies are needed to determine the true effect of restrictive UARC criteria on ASB treatment.

Disclosures

All Authors: No reported disclosures
2827. A mixed-methods analysis of provider-documented and patient-reported urinary tract infection symptoms among Veterans with neurogenic bladder
Authors: Fitzpatrick Margaret A , Wirth Marissa , Solanki Pooja , Suda Katie , Burns Stephen , Weaver Frances , Collins Eileen , Safdar Nasia , Evans Charlesnika T
Published: November 2023

Background

Urinary tract infections (UTI) are common in patients with neurogenic bladder (NB). Non-specific symptoms are frequent in this population, and may lead to inappropriate UTI diagnosis in patients who have asymptomatic bacteriuria. Characterization of patient-reported symptoms can inform interventions to promote appropriate UTI diagnosis.

Methods

Mixed methods study of adults with NB due to spinal cord injury/disorder (SCI/D), multiple sclerosis (MS), or Parkinson’s Disease (PD) and encounters with a UTI diagnosis (via ICD10). Provider-documented symptoms were collected from chart review of 198 encounters at 4 Veterans Affairs medical centers (VAMCs) between 2017-2018. Eleven virtual focus group discussions (FGDs) were conducted between May 2021 and May 2022 with patients from the chart review cohort with a UTI encounter in the prior year. Discussions were recorded, transcribed, and coded. Thematic analysis identified key concepts about symptoms and informed comparisons to provider-documented data from chart review.

Results

Provider-documented (n=198 encounters; SCI/D 51%, MS 20%, PD 28%) and patient-reported (n=23 FGD participants; SCI/D 78%; MS 18.5%) symptoms are in Table 1. Similar to providers, most patients noted urine changes as UTI symptoms (“cloudy” and “smelly” urine). Only 12% of encounters had provider-documented altered mental status, but this was commonly described in FGDs (“brain fog”). Only 25% of encounters had provider-documented dysuria or pelvic pain, but this was also frequently noted in FGDs (“sitting on a stick”). Several patients felt providers ignored their symptoms, particularly when they did not have fever, which may affect provider documentation. Nearly all patients noted diminished quality of life from UTI symptoms, such as difficulty engaging in social activities and psychosocial impacts from worsened mobility and functioning.

Conclusion

Both providers and patients attributed non-specific symptoms like urine changes to UTI, but there was discordance in recognition and reporting of other UTI symptoms. Optimizing care for patients with NB could involve patient and provider education on alternate sources of non-specific symptoms, interventions to improve communication about symptoms, and better assessment of quality of life impacts.

Disclosures

All Authors: No reported disclosures
2889. One vs Three Weekly Doses of Benzathine Penicillin G for Treatment of Early Syphilis in Persons with and without HIV: A Multicenter Randomized Controlled Trial (RCT)
Authors: Hook Edward W , Workowski Kimberly , Dionne Jodie A , McNeil Candice J , Taylor Stephanie N , Teresa Batteiger , Dombrowski Julia C , Mayer Kenneth H , Seña Arlene C , Wiesenfeld Harold C , Perlowski Charlotte , Newman Lori , Zhu Chunming , Mejia-Galvis Jorge E
Published: November 2023

Background

Syphilis rates in the United Stated (U.S.) have increased steadily for over a decade. Despite over 75 years as the drug of choice for syphilis treatment, controversy persists on optimal duration of therapy with benzathine penicillin G (BPG) for persons with early(primary, secondary, and early latent) syphilis, particularly for persons co-infected with HIV. Given the ongoing national shortages of BPG, optimizing duration of therapy is an urgent concern.

Methods

We conducted a multicenter RCT comparing a single intramuscular (IM) injection of BPG, 2.4 million units to BPG administered for three successive weeks for treatment of early syphilis in persons with and without HIV. The primary outcome of the study was a > 4-fold decline in RPR titer measured at 6 months. Intention to treat (ITT) and per protocol analyses were performed and were similar. ITT analyses are presented here.

Results

A total of 249 persons with early syphilis were enrolled at 10 participating sites. Most (97%) participants were were categorized as male sex, black race (62%), and 153 (64%) were living with HIV. The syphilis stage distribution was 19% primary, 47% secondary, and 33% early latent and did not differ significantly by HIV status. Serologic response (> 4-fold decline in RPR titer) at 6 months was 76% (95% Confidence Interval (CI) 0.68-0.82) in the single dose group and did not differ significantly from the three-dose group (70%, 95% CI 0.61-0.77). There were no treatment failures (> 4-fold increase in RPR titer). Among persons with and without HIV there was no significant difference in RPR response at 6 months: 76% in the single-dose group vs. 71% in the 3-dose group (95% CI 0.05-0.17). Most participants experienced mild to moderate local injection site pain and tenderness.

Conclusion

Treatment of persons with early syphilis with more than a single dose of 2.4 million units of BPG offers no therapeutic benefit irrespective of HIV infection status and was associated with increased rates of injection site discomfort.

Disclosures

Edward W. Hook, III, FIDSA, GARPD (Global Antibiotic Resistance Program: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|VISBY Diagnostics: Advisor/Consultant Candice J. McNeil, MD, MPH, BARDA/GSK: Grant/Research Support|Becton Dickinson: Grant/Research Support|Cepheid: Grant/Research Support|Gilead: Grant/Research Support|Hologic: Grant/Research Support|Lupin: study product Julia C. Dombrowski, MD, MPH, Hologic: Grant/Research Support|Mayne Pharmaceuticals: Grant/Research Support
181. COVID-19 Infection is a Key Factor in Mortality for Staphylococcus aureus and Candida sp. Bloodstream Infections: an Evaluation of Outcomes before and during the COVID-19 Pandemic
Authors: Cosimi Reese , Daragjati Florian , Ghosh Subhangi , Perez Moreno Ana Cristina , Miller Collin , Saake Karl , Fakih Mohamad G
Published: November 2023

Background

Staphylococcus aureus and Candida sp. bloodstream infections (BSI) are associated with considerable mortality. The COVID-19 pandemic presented new challenges in the acute care setting which may affect outcomes in high-risk populations.

Methods

Retrospective cross-sectional analysis across a large healthcare system of all admitted patients aged 18 years or older with S. aureus or Candida sp. BSI between pre-pandemic (January 2017-February 2020) and pandemic (March 2020- February 2023). The primary clinical outcome was all-cause mortality. Secondary outcomes include length of stay (LOS) and 30-day readmission. Data was stratified across the pre-pandemic and pandemic period, COVID-19 positive and negative patients, and community and hospital-onset BSI.

Results

A total of 17,730 patients were included in the analysis. Baseline characteristics were similar between pre-pandemic and pandemic groups aside from higher hospital-onset infection rates in the pandemic COVID-19 positive population [Table 1]. No significant differences were found in mortality between COVID-19 negative groups [Table 2]. Concomitant COVID-19 infection was associated with increased mortality in both the S. aureus and Candida sp. BSI patients.

Conclusion

While patients with concomitant COVID-19 infection had a substantially higher mortality compared to those without infection, the mortality in patients with S. aureus and Candida sp. community-onset and hospital-onset BSI did not change during the pandemic compared to pre-pandemic for patients without concomitant COVID-19 infection.

Disclosures

Reese Cosimi, PharmD, Allergen: Advisor/Consultant
187. Risk Factors and Outcomes of Patients with Serratia Bacteremia at an Academic Medical Center
Authors: Doktor Katherine L , King Madeline , Martirosyan Diana , Moore Scott R , Fraimow Henry S
Published: November 2023

Background

The majority of reported Serratia infective endocarditis (SIE) in recent years are healthcare-associated. At our urban institution with a high prevalence of people who inject drugs (PWID), we noted an increasing number of Serratia bacteremias (SB) and SIE over the past decade. Our study describes patient factors associated with SB and SIE.

Methods

We evaluated charts of patients with SB at our institution between 2010 and 2022 to determine risk factors and clinical outcomes.

Results

There were 157 episodes of SB in 153 patients. The majority were male (57%), white (57%) with a mean age 53. The most common source of infection was catheter- line-associated infection (CLABSI) (27%), followed by primary bacteremia (19%). Twenty-six % were PWID with younger mean age (41 years). PWID had lower mortality than non-PWID (23% vs 44%, p=0.023). Sixty-nine (46%) were admitted to the intensive care unit (ICU) with significantly higher mortality associated with ICU admission (48% vs 8%, p=0.015).

Echocardiograms were performed in 59% (93/157) of SB episodes and 14% had SIE (13/93). Most SIE (69%) occurred after 2017 with 89% in PWID (8/9). The most common comorbidity with SIE was injection drug use (IDU) (69%). All non-IDU SIE were CLABSI-related; 75% had hemodialysis catheters. Tricuspid valves were infected in 46%. Sixty-two % of those with SIE had septic emboli. Most SIE (69%) required ICU admission. Overall mortality was 31%.

Only 2% (3/153) of patients with SB developed antibiotic resistance on therapy. Clinical worsening or failure occurred in 20% (32/157). Only 5% (7/157) had microbiologic recurrence within 30 days. 32% of discharged patients re-presented to the hospital within 30 days. Almost all deaths (92%) occurred during initial admission.

Conclusion

Patients with SB were quite ill with a high rate of in-hospital mortality; over half of the patients had antibiotic exposures prior to developing SB or presented within 90 days of a prior hospitalization. The majority of SB were line-associated, including all episodes of non-IDU SIE. IDU was the second most common comorbidity and PWID with SB had a higher rate of SIE, with most IDU-associated SIE diagnosed after 2017. This aligns with other recent studies documenting the increased prevalence of SB, especially in PWID.

Disclosures

Madeline King, PharmD, La Jolla: Advisor/Consultant|Shionogi: Advisor/Consultant
205. The increasing trend of penicillin resistance in Streptococcus suis clinical isolates during the past 5 years in a tertiary hospital in Thailand
Authors: Kiatkangwanchon Natthapol , Wongjarit Kanphai , Nilgate Sumanee , Chatsuwan Tanittha , Suankratay Chusana
Published: November 2023

Background

Streptococcus suis, an emerging zoonotic pathogen, is able to cause a wide spectrum of infections including primary bacteremia, meningitis, endocarditis, and other localized infections. Due to the increasing and widespread use of antibiotics in pig industry in Thailand, will contribute to the emergence of antimicrobial resistance to infection caused by S. suis. We aimed to determine the in vitro susceptibility of S. suis clinical isolates, in accompanying with the treatment outcomes.

Methods

A retrospective study was carried out on all patients with S. suis bacteremia at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from 2017 to 2022. S. suis identification was analyzed by conventional biochemical tests, the API-20 STREP system (bioMérieux, Marcy-l'Étoile, France), or MALDI-TOF MS. In vitro susceptibility test of penicillin, cefotaxime, meropenem, and vancomycin was carried out by E-test according to CLSI recommendation.

Results

There were 32 patients with 17 (53.1%) male and median age of 57 (IQR: 50-65) years. Comorbidities were diabetes (10 patients, 31.3%) and cancer (4, 12.5%). 12 (37.5%) patients had a history of consumption of undercooked pork products. Regarding clinical syndrome, there were 15 (46.9%), 6 (18.8%), 6 (18.8%), and 3 (9.4%) patients with primary bacteremia, infective endocarditis, meningitis, and septic arthritis/spondylodiscitis, respectively. The median length of stay was 13 (IQR: 5-16) days. The most common empirically used antibiotic was ceftriaxone (26 patients, 81.3%), followed by meropenem (3, 9.4%), and ampicillin (2, 6.2%). De-escalation treatment to penicillin G sodium was performed in 11 (34.4%) patients. Of 29 patients with available outcomes, there were 19 (65.5%), 6 (20.7%), and 3 (10.3%) patients with complete recovery, hearing loss, and mortality, respectively.

In vitro susceptibility results are shown in Tables 1 and 2.Table 1.The minimum inhibitory concentration (MIC) distribution for Streptococcus suis blood isolates.Table 2.MIC50, MIC90, MIC ranges, and susceptibility according to 2023 CLSI clinical breakpoints for Streptococcus suis blood isolates.

Conclusion

S. suis bacteremic patients still had favorable outcomes despite the emergence of penicillin resistance. All isolates were susceptible to meropenem and vancomycin, and most were susceptible to cefotaxime. However, only 28.1% was still susceptible to penicillin. Third-generation cephalosporin should be the first agent for empirical treatment in patients with suspected S. suis bacteremia.

Disclosures

All Authors: No reported disclosures
219. Clinical Outcomes of Early vs Late Oral Stepdown Therapy in the Management of Uncomplicated Gram-Negative Bacteremia
Authors: Michael Amanda , Vyas Nikunj M , DeRose Joseph
Published: November 2023

Background

Current studies show that oral stepdown antibiotics are safe and effective for patients with gram-negative bacteremia (GNB), but evidence is lacking in appropriate time from IV to oral stepdown therapy. The purpose of this study was to evaluate clinical outcomes in early (EPOS) vs late (LPOS) oral stepdown therapy in patients with GNB.

Methods

This was an IRB-approved retrospective chart review including patients in a three hospital community health system. Patients were included in this study if they were ≥ 18 years old, hospitalized for ≥ 24 hours with a positive blood culture with E. coli, Klebsiella spp., and/or Proteus spp. and transitioned to oral antibiotics prior to discharge. Exclusion criteria included complicated bacteremia and any patients who were pregnant or immunocompromised. The primary endpoint of the study was to evaluate the achievement of clinical cure at the end of therapy (CC) in EPOS (≤ 96 hours) vs LPOS ( > 96 hours) groups. A subgroup analysis included achievement of microbiological cure (MC). The secondary endpoint evaluated the length of stay (LOS) and duration of IV (DIV) and duration of PO (DPO) antibiotics.

Results

Total of 50 patients were included in the primary analysis, with 30 patients in the EPOS group and 20 patients in the LPOS group. The median age and gender stratification between both groups were similar. CC (93.3% vs 100%) and MC (86.7% vs 95%) were similar amongst patients in the EPOS and LPOS groups, respectively. As seen in Table 1, DIV was shorter in the EPOS group (3.27 vs 6.2 days, P=0.0001) and DPO was longer in the EPOS (6.83 vs 4.75 days, P=0.007). Patients in the EPOS group had trends toward shorter LOS compared to the LPOS group (6.67 vs 8.1 days, P=0.08). Patient is the EPOS group were more likely to receive oral cephalosporins compared to LPOS patients (83.3% vs 45%, P=0.006) as seen in figure 1, patients in the LPOS group were more likely to receive amoxicillin/clavulanate than the EPOS patients (30% vs 6.7%, P=0.04).

Conclusion

EPOS may be a viable approach to uncomplicated gram-negative bacteremia with a lot of practical benefits. EPOS may lead to decreased DIV therapy and potentially decreased LOS. Additionally, EPOS with cephalosporins may be considered in most patients with uncomplicated bacteremia with a urinary source.

Disclosures

All Authors: No reported disclosures
221. Performance of risk scores in predicting infective endocarditis Staphylococcus aureus bacteremia in a prospective Asian cohort
Authors: Nicholas Ngiam Jinghao , CY Koh Matthew , GW Goh Wilson , Meng Tham Sai , Archuleta Sophia , Fisher Dale , Chai Louis , Tambyah Paul
Published: November 2023

Background

Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB). This helps to guide clinical management, including the need for transoesophageal echocardiography (TEE).

Methods

We prospectively studied 634 patients admitted with SAB. Baseline clinical characteristics and laboratory results recorded, and patients were followed up prospectively. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under receiver operating characteristic (AUC) curves were constructed to compare the performance of each score.

Results

Of the 634 patients examined, 36 (5.7%) had IE. These patients were slightly younger (51.6±20.1 vs 59.2±18.0 years, p=0.015), but tended to have community acquisition of bacteraemia (41.7% vs 17.9%, p< 0.001), intravenous drug use (30.6% vs 2.7%, p< 0.001), pre-existing structural heart disease (11.1% vs 2.7%, p=0.005), and persistent bacteraemia beyond 72 hours (19.4% vs 6.0%, p=0.002). There was no significant difference in mortality (8.3% vs 5.7%, p=0.459). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of < 3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (< 4) and Day 5 (< 2) (94.3% and 96.6% respectively).

Receiver operating curves comparing performance of each risk score in predicting IE in patients with SABScore Proportion of cohort Sensitivity (%) Specificity (%) Positive predictive value (%) Negative predictive value (%) PREDICT Day 1 ≥4 4/634 (0.6%) 0.0 99.3 0.0 94.3 PREDICT Day 5 ≥2 192/634 (30.2%) 58.3 71.4 10.9 96.6 VIRSTA ≥3 149/634 (23.5%) 66.7 79.1 16.1 97.5

Comparing performance of each risk score at specified cut-offs in predicting IE in patients with SAB

Conclusion

Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 required TEE, and a score of < 3 would have a negative predictive value of 97.5%.

Disclosures

All Authors: No reported disclosures
231. Blood Neutrophil to Lymphocyte Ratio Is Associated with Mortality And Readmission in Gram Negative Bacteremia
Authors: Roldgaard Marcus , Benfield Thomas , Tingsgård Sandra
Published: November 2023

Background

Neutrophil-Lymphocyte Ratio (NLR) in blood has been shown to be able to predict bacteremia in emergency departments and an association with mortality has been shown in patients with sepsis in intensive care units. Its potential in relation to mortality and readmission in gram negative bacteremia (GNB) is unknown.

Methods

Retrospective cohort study of patients with GNB from 2018 through 2022 from four different hospitals in the greater Copenhagen area. Exclusion criteria were immunosuppression and missing NLR values on the day of blood culture. The association between NLR levels and 90-day all-cause mortality were analyzed using logistic regression models, while the association between NLR levels and 60-day readmission was analyzed using the logit link interpretation of the cumulative incidence function. Associations were expressed as odds ratios with 95% confidence intervals.

Results

The study included 1763 patients. The median age was 76.8 years and 51.3% were female. The median NLR was 17.3. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli was the most frequent pathogen. Significant differences in median NLR were found between age groups, pathogens, and patients with/without hypertension, liver disease, COPD, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days.

The odds ratio for all-cause 90-day mortality per NLR increase by one was 1.008 (1.003-1.013, p:0.002) and for 60-day readmission, it was 1.006 (1.001-1.012, p:0.02) per NLR increase by one, corresponding to odds ratios of 1.15 (1.04-1.27, p: 0.009) and 1.11(1.01-1.23, p: 0.04) per doubling of NLR respectively. NLR was not associated with outcome when stratified for UTI and gastrointestinal infection. Discriminatory ability for mortality was limited and comparable for NLR, neutrophil and lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.58 (0.55-0.62), 0.60 (0.55-0.62) and 0.60 (0.57-0.64).

Forest plot depicting adjusted odds ratios and 95% confidence intervals for 90-day mortality and 60-day readmission

Cumulative incidence curves for 60-days readmission and mortality divided by quartiles of blood neutrophil to lymphocyte ratio

Kaplan-Meier curve of the survival probability divided by quartiles of blood neutrophil to lymphocyte ratio

Conclusion

Blood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with gram negative bacteremia. However, the ratio has limited ability in predicting mortality or readmission.

Disclosures

All Authors: No reported disclosures
234. Risk Factors for Mortality in Patients with Escherichia coli Bloodstream Infections and Influence of the Antimicrobial Resistance Pattern in a Referral Hospital in Nicaragua
Authors: Sánchez-Delgado Mauricio , Marenco-Avilés Sunaya , Porras-Cortés Guillermo D
Published: November 2023

Background

Escherichia coli is the most frequent etiological agent in bloodstream infections, and mortality has increased because of the increasing rates of bacterial resistance. Every healthcare institution has to characterize the epidemiological trend and recognize determinants for adverse outcomes in patients with bacteremia. The aim of this study was to identify risk factors for mortality and identify the influence of the pattern of bacterial resistance, as well as associated clinical characteristics in patients with E. coli bloodstream infections hospitalized at the Dr. Fernando Vélez Paiz Hospital in Managua, Nicaragua.

Methods

It is a retrospective, cross-sectional, and analytical study. The study period was between January 1st, 2020, and December 31st, 2022. A total of 81 patients with bacteremia due to E. coli were analyzed out of the total number of patients with bloodstream infections (Figure 1). The epidemiological trend, clinical variables, and pattern of antimicrobial resistance were analyzed. Risk factors for mortality were identified, and odds ratios and confidence intervals were calculated.Figure 1.Flowchart of Selection of Patients with E. coli Bloodstream Infections

Results

The prevalence of E. coli bacteremia among all bloodstream infections was 13.3%, with a mortality rate of 37.0%. The mean age of the patients was 54.7 ± 17.2 years old. Regarding comorbidities, 43.2% and 42.0% had hypertension and diabetes, respectively. Genitourinary was the main associated site of infection (58.0%) (Table 1). A high rate of E. coli producing ESBL was identified (64.2%). The resistance to ciprofloxacin and carbapenem was 67.9% and 12.3% respectively. Multi-drug resistance was observed in 28.4% of the strains. (Table 2). A history of steroid use was recorded in 40% of non-survivors versus 9.8% of survivors. Resistance to carbapenems was higher in non-survivors (26.7% vs. 3.9%). The main risk factors for mortality were use of a urinary catheter in ≥60 years old, resistance to carbapenems, and abdominal sepsis as source of infection, among others (Table 3).Table 1.Sites of Infection in Survivors and Non-SurvivorsTable 2.Antimicrobial Resistance Pattern in Survivors and Non-SurvivorsTable 3.Risk Factor for Mortality in Patients with E. coli Bloodstream Infections

Conclusion

The main risk factors for mortality in patients with bloodstream infections due to E. coli were use of urinary catheter in older patients, resistance to carbapenems, bacteremia associated with abdominal sepsis, among others. A high rate of resistance to ciprofloxacin, and beta-lactams was observed.

Disclosures

All Authors: No reported disclosures
239. Comparing Alternative Treatment Options for Stenotrophomonas maltophilia bacteremia
Authors: Teran Nicholas S , Zidaru Andrei , Phe Kady
Published: November 2023

Background

Stenotrophomonas maltophilia can cause nosocomial infections in immunocompromised hosts and patients with indwelling devices or broad-spectrum antibiotic exposure. Treatment of S maltophilia infections poses a challenge due to intrinsic resistance mechanisms, including inducible L1 metallo and L2 cephalosporinase beta-lactamases. Trimethoprim-sulfamethoxazole (SXT) is recognized as the agent of choice for S maltophilia infections. Outcomes with alternative antimicrobials are not well described.

Methods

We conducted a retrospective study of adults with positive blood cultures with S maltophilia who received ≥48h of directed antimicrobials at our institution between 3/2013 and 6/2022. Patients were stratified by their antimicrobial treatment, including levofloxacin, SXT, minocycline, ceftazidime, or combination therapy. The primary outcome was 30d all-cause mortality. Secondary outcomes were microbiological and clinical cure. Microbiological failure was defined as blood cultures growing S maltophilia during or within 7d of discontinuing therapy. Clinical failure was defined as a lack of resolution of signs or symptoms of infection requiring therapy adjustment.

Results

Of 67 patients with positive S maltophilia blood cultures, 53 patients treated with levofloxacin (n = 27), SXT (n = 10), minocycline (n = 8), combination (n = 5) or ceftazidime (n = 3) were included. The remaining 14 patients were excluded for receiving < 48h of therapy. The median Charlson comorbidity index was 4 [IQR 3-6]. The most common source of bacteremia was catheter-related (n = 27). Overall, 30d mortality was 26.4%. There was no significant difference in 30d mortality among patients treated with levofloxacin, SXT, minocycline, combination or ceftazidime (p = 0.23). Interestingly, patients with monomicrobial S maltophilia bacteremia had statistically higher 30d mortality (35.3% versus 11.8%, p < 0.05). Microbiological and clinical cure rates were similar between treatment groups (p = 0.06 and p = 0.16, respectively).

Conclusion

Treatment options for S maltophilia bacteremia resulted in similar 30d mortality; however, findings were limited by the small sample size. Larger, prospective studies are warranted to detect differences in treatment alternatives.

Disclosures

All Authors: No reported disclosures
247. Evaluation of the Efficacy and Safety of Cefazolin in Non-Pneumococci Streptococcal Bacteremia
Authors: Wibisono Arya , Rose Dusten T T , Jaso Theresa (Terry)
Published: November 2023

Background

Among the large variation of streptococcal infections, recommended therapies are generally well-defined. There is a lack of efficacy data on alternative therapies, notably in phylogenetic groups that are less studied. The purpose of this study is to quantify the differences in clinical efficacy and safety between recommended antibiotics (penicillins and ceftriaxone) compared to cefazolin for uncomplicated non-pneumococci streptococcal bacteremia.

Methods

This is a multi-center, retrospective cohort study from January 2017 to January 2021. Patients were included if older than 18 years of age and had a non-pneumococci streptococcal isolate recovered on blood cultures. Patients were excluded if they had a polymicrobial bacteremia, diagnosed meningitis or endocarditis, received less than two days of a study drug, or received more than three days of a non-study drug. The primary outcome was treatment failure defined as: 30-day in-hospital all-cause mortality; or the alteration of targeted therapy after at least 48 hours of treatment for (1) concern of clinical failure based on progress notes in the electronic medical record or (2) an adverse drug reaction. Secondary outcomes included 90-day all-cause mortality, intensive care unit length of stay, hospital length of stay, C. difficile infection, adverse events, and 6-month infection related readmissions.

Results

A total of 230 patients were included: 177 in the penicillins/ceftriaxone group and 53 in the cefazolin group. Baseline demographics were balanced between the two groups in regard to age, sex, comorbidity score, infection severity, and infectious disease consultation. The most commonly identified pathogens were S. pyogenes (30.9%), S. agalactiae (26.5%), and S. mitis/oralis (11.7%). Analysis showed no significant difference between treatment failures with recommended antibiotics (6/177, 3.4%) and cefazolin (1/53, 1.9%), p=1.00. No differences were noted in secondary safety outcomes.

Conclusion

Rates of treatment failure with cefazolin were not significantly different compared to recommended antibiotics in the treatment of uncomplicated non-pneumococci streptococcal bacteremia. Cefazolin may be a potential option for treatment in these infections. Further studies are warranted.

Disclosures

All Authors: No reported disclosures
257. Shared antibody sequences reveal novel public clonotypes of antibodies within and between HIV infected and healthy individuals
Authors: Chang Arthur , Hicar Mark D
Published: November 2023

Background

Public clonotypes, antibodies against specific antigens in unrelated individuals that have genetic similarities, have been shown in a variety of infections, including SARS-CoV-2 and HIV. These can be exploited as potential diagnostics and to identify past infections that may be related to post-infectious disorders, such as Kawasaki disease, Multiple Sclerosis or Alzheimer's disease.

Methods

Heavy chain variable sequences were retrieved from public biorepositories (Bioprojects PRJNA486667, PRJNA638224,PRJNA527941) from 270 subjects. These were derived from labeled cohorts: Healthy (116), HIV broadly neutralizing (46), HIV non-broadly-neutralizing (50), HIV-negative (43), and COVID-19 (15). We utilized the Immcantation package of software run on our SUNY Buffalo computational cluster. After PRESTo annotation, duplicate sequences were collapsed and sequences of only single counts were removed. Clonal groups were determined using SCOPer requiring IGHV, IGHJ, and CDR3 amino acid sequence to be perfectly matched. Figures and statistics were generated with immcantation, excel, pandas, and graphpad prism 8.

Results

There were 5.5 million unique heavy chain sequences from 32 million sequences. Defining public clonotypes as completely sharing CDR3 amino acid sequence and having predicted same germline variable, D, and J chains, 6861 (0.12%) shared clones were found. The distributions of CDR3 lengths showed skewing to shorter CDR3s (mean length of 10.5). There were no stringently defined clones noted in all members. Within HIV infected persons the two most shared clones both used VH1-18, JH4, had CDRaa 8, and were immature IGM/D. Three clones were used in near 10% of cases across both non-HIV and HIV datasets with prominent usage of VH 4 family members and were less mutated and IGM/D. There were eight clones solely shared > 10% within non-HIV/non-Covid infected individuals, with the top shared clones all consistent with matured IGG responses with prominent predicted use of VH3-7 and a number of novel CDR3s noted.

Predicted CDR3 length using incantation was compared for cohort of clones that shared predicted V, D, J usage and the exact CDR3 amino acids between individuals. This distribution failed normality testing.

Conclusion

Identification of public clonotypes will show stochastic bias toward shorter CDR3 regions. There were differences between HIV and non-HIV cohorts and a number of novel public clonotypes were found.

Disclosures

Mark D. Hicar, MD/PhD, Pfizer: site investigator for 2 trial
295. Humanized Mice and Convalescent Humans Yield an Antibody Panel against the Highly Immunogenic Decorin Binding Protein A (DbpA) of the Lyme Disease Spirochete, Borrelia Burgdorferi
Authors: Muriuki Beatrice M , Golonka Rachel M , Ma Zepei , Bharadwaj Ravi , Li Qi , Vance David , Willsey Graham G , Lyn Piazza Carol , Rudolph Natalie J , Mantis Nicholas , Wang Yang , Cavacini Lisa
Published: November 2023

Background

Lyme disease is the most commonly diagnosed tick-borne infection, affecting more than 300000 people in the United States annually. The disease is principally caused by the transmission of the spirochete bacteria, by the black-legged (deer) ticks. With a renewed call for interest in a Lyme disease vaccine, antibodies relevance continues due to their efficacy, safety and versatile nature. Humanized mice and humans recovering from the disease have successfully been used to generate therapeutic antibodies against Ebola and SARS-CoV-2 diseases.

Methods

Our study used humanized mice and convalescent patients to generate recombinant human antibodies that recognize decorin-binding protein A (DbpA), a lipoprotein that is proposed to function as spirochete adhesin. The mAbs expressed as human IgG-Fc fragments were characterized for reactivity with recombinant DbpA, native DbpA on the surface of live Borrelia burgdorferi, borreliacidal activity in the presence of human complement and, finally subject to epitope mapping using an array of methodologies.

Results

The predominant lineage of humanized mice antibodies utilized VH5-51, VH3-20, VH3-23 and VH3-53 all paired with VK1-33 families. Other common families included VH4-31 paired with VK1-39, VH4-4 and VH4-8 paired with VK-9. The human derived antibody utilized VH3-30 paired with VK1-33. We observed an overlap in the repertoire of kappa chains between humanized mice and human-derived mAbs.

Conclusion

Combining the humanized mice and human platforms enabled the identification of antibodies with a high binding and specificity to DbpA, which have potential prophylactic and therapeutic properties.

Disclosures

All Authors: No reported disclosures
304. Immunoproteasome Inhibition Augments Endoplasmic Reticulum Stress and Enhances Disease During Coronavirus Respiratory Infection
Authors: Steigmann Jacob C , Suttenberg Lauren , Zhou Xiaofeng , Weinberg Jason
Published: November 2023

Background

Inflammation contributes to disease in patients with SARS-CoV-2 infection. The immunoproteasome (IP), an inducible component of the ubiquitin-proteasome system, contributes to the diversity of T cell epitopes generated during infection and production of antiviral and pro-inflammatory cytokines. Like the standard proteasome, the IP degrades damaged and misfolded proteins to minimize proteotoxic cell damage, which may occur via endoplasmic reticulum (ER) stress pathways. IP subunit expression increases in lungs of patients with SARS-CoV-2 infection. We previously demonstrated increased IP activity in mice infected with murine hepatitis strain 1 (MHV-1), a murine coronavirus. However, specific contributions of the IP to coronavirus pathogenesis are not yet defined. We used MHV-1 to test the hypothesis that increased IP activity is a protective host factor during acute coronavirus infection.

Methods

C3H.HeJ mice infected with MHV-1 were treated with vehicle or ONX-0914 (ONX), an IP inhibitor. We monitored weight loss and survival following infection and harvested organs at multiple times. Bone marrow-derived dendritic cells (BMDC) from C3H.HeJ mice were infected with MHV-1 in the presence of ONX. We used qPCR to assay viral load and expression of cytokines (IFN-β, IFN-γ, TNF-α, IL-6, IL-1β) and genes involved in ER stress pathways (CHOP, BiP, Grp94, Calreticulin, GADD34).

Results

IP inhibition enhanced weight loss and mortality following MHV-1 infection but did not substantially affect viral replication. Virus-induced expression of TNF-α and IL-1β was lower in the lungs of ONX-treated mice, while TNF-α expression was higher in livers. Expression of ER stress pathway genes was significantly greater in both lungs and livers of infected, ONX-treated mice compared to controls early in the course of infection. IP inhibition did not affect viral replication in BMDC, but it did enhance expression of IFN-β, TNF-α, and GADD34.

Conclusion

IP inhibition enhanced MHV-1-induced disease but did not affect viral replication. IP inhibition had modest effects on virus-induced inflammation. Increased evidence of ER stress in mice and cells treated with ONX suggests that the IP minimizes harmful proteotoxic stress, particularly in the liver, during acute coronavirus infection.

Disclosures

All Authors: No reported disclosures
310. Yogurt Intake and Colorectal Cancer Incidence Subclassified by Bifidobacterium Status in Tumor
Authors: Ugai Satoko , Ugai Tomotaka , Ogino Shuji
Published: November 2023

Background

Although epidemiological evidence is limited, experimental data indicated a tumor-suppressive effect of yogurt containing Bifidobacterium. We hypothesized that the association between yogurt intake and colorectal cancer incidence differed by Bifidobacterium status in tumor tissue.

Methods

We utilized data from two prospective cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by tumor Bifidobacterium status.

Results

During follow-up of 132,056 individuals, we documented 2,950 incident colorectal cancer cases, including 1,191 with available Bifidobacterium data. The association between yogurt intake and colorectal cancer incidence differed by Bifidobacterium status (Pheterogeneity = 0.03). This differential association became stronger in a subgroup analysis of proximal colon cancer (Pheterogeneity = 0.003). Multivariable hazard ratios in individuals who consumed ≥ 2 servings/week (vs. < 1 serving/month) of yogurt were 0.43 [95% confidence interval (CI), 0.22-0.85] for Bifidobacterium-positive proximal colon cancer, and 1.40 (95% CI, 0.95-2.05) for Bifidobacterium-negative proximal colon cancer.

Conclusion

Yogurt intake was inversely associated with the incidence of Bifidobacterium-positive (but not Bifidobacterium-negative) proximal colon cancer, suggesting an interactive influence of yogurt intake and intestinal microbiota on tumor development.

Disclosures

All Authors: No reported disclosures