bluuebunny/crossref_metadata_2025_split huggingface dataset:
222. Oral Step-Down Therapy for Uncomplicated Enterococcus Bacteremia
Authors: Ni Jessica , Decano Arnold , Zacharioudakis ioannis , Mazo Dana , Dubrovskaya Yanina , Siegfried Justin , Marsh Kassandra 
Published: November 2023

Abstract

Background
The mainstay of therapy for uncomplicated Enterococcal bloodstream infections (BSI) is intravenous (IV) antibiotics which have higher bioavailability than oral (PO) options. This study evaluated clinical outcomes and the safety of early step-down to oral antibiotics in uncomplicated Enterococcus bacteremia.

Methods
This was a retrospective study of adult patients admitted from January 2013 to October 2022 with an initial bacteremia episode and positive blood culture for Enterococcus species who completed treatment with PO or IV antimicrobial therapy. The primary endpoint was clinical cure, defined as no evidence of transition back to IV therapy after starting PO therapy or no need for escalation of definitive IV therapy due to new fever, leukocytosis, or hemodynamic instability. Safety endpoints were C. difficile or adverse drug events leading to discontinuation or change in therapy.

Results
A total of 110 patients were included in the analysis, and 49% received oral step-down therapy (n=54). The most commonly used PO agents were linezolid (59%) and amoxicillin (22%). The severity of illness of the IV and PO groups was assessed by Pitt bacteremia score [1.7 (interquartile range, 0-2.8) vs. 1.3 (IQR, 0-2.0)], Charleston Comorbidity Index [6 (IQR, 4.0-8.0) vs. 5 (IQR, 3.8-6.0)] and ICU admission (35.2% vs. 13.0%; P=0.008). The most commonly identified sources of infection were gastrointestinal (23%) and urinary (23%). No statistical differences were seen between the IV and PO groups in clinical cure (91.1% vs. 98.1%; P=0.111), microbiological cure (98.2% vs. 100%; P=0.509), mortality (1.9% vs. 8.9%; P=0.111), or infectious readmissions at 30-day (5.6% vs. 12.5%; P=0.163) and 90-day (14.8% vs. 19.6%; P=0.384). HLOS was 12.5 days in the IV group and 8.5 days in the PO group (P=0.038). No differences were seen in safety outcomes. The majority of patients in both the IV and PO groups were followed by ID consult (76.8% vs. 81.5%; P=0.356) and Antimicrobial Stewardship (75.0% vs. 77.8%; P=0.453).

Conclusion
Our results suggest that oral antibiotic step-down therapy in uncomplicated Enterococcal BSIs may be a safe alternative to IV therapy in a carefully selected patient population. Larger studies are required to confirm these results.

Disclosures
All Authors: No reported disclosures
223. Clinical Characteristics and Outcomes of Acinetobacter baumannii XDR and Pseudomonas aeruginosa XDR in a Tertiary Referral Medical Center in Mexico
Authors: Ojeda Yuren Alicia Sarahi , Murillo López Maricarmen , Gómez Abrajan Mariana , Salinas Arteaga Gustavo , Rodríguez González José Carlos , González De León María Fernanda Osorno , Domínguez Valdez Sandra Ivet , Ruiz Araceli Acosta , Gónzalez Cardel Ana Maria , Montiel López Luis , Lopez Luis Bruno Ali 
Published: November 2023

Abstract

Background
Highly resistant gram-negative bacteria such as Acinetobacter baumannii (AB) Complex and Pseudomonas aeruginosa (PA) have developed into Extremely Drug-Resistant organisms (XDR). This study aims to identify the clinical characteristics and outcomes of bacteremia caused by non-fermenting bacilli (Acinetobacter baumanni and Pseudomonas Aeruginosa) XDR in a Mexican population of a tertiary medical center in Mexico.

Methods
From January 2019 to December 2021, the results of positive bloodstream cultures for AB XDR and PA XDR were collected from the microbiology laboratory. The electronic records of these patients were obtained, and the variables associated with their clinical characteristics and outcomes were extracted for their analytical description.

Results
A total sample of 49 patients was gathered, from which 26 were men (53%) and 23 (46%) were women, with an average age of 55 years. 71% of patients were admitted to the critical care units. The average Charlson Index was 3.01. 12% had an immunosuppressive condition, 24% had presented a previous hospitalization last year, and 38% had received a previous antibiotic regimen. The length of stay from the AB group had an average of 29 days compared with 46 days in the PA group. The persistence of bacteremia with AB was an average of 11 days versus 22 days with PA. Only 16% of these patients were treated with colistin. The Pitt Index at the time of the first positive culture had an average of 7.56 points in the AB XDR group with 73% mortality, compared to a PA XDR Pitt Index score of 2.4 points and a 42% mortality.

Conclusion
The infections of these pathogens were more prevalent in patients greater than 50 years of age with similar distribution between sexes. Hospitalization in critical care units and immunosuppressive conditions were frequent characteristics of the patients. However, despite the diagnosis of XDR by blood cultures, few patients received colistimethate or another antibiotic with corroborated susceptibility, probably contributing to their complications. Finally, an increase in the length of stay after a positive blood culture is observed in the outcomes, being lower in AB XDR baumannii infections but with higher mortality than PA XDR infections.

Disclosures
Luis Montiel López, Medical Doctor, Merck: Speaker|Novartis: Speaker
228. Increased Incidence of Invasive Haemophilus influenzae Infections in Adults in Central Massachusetts
Authors: Qadri Qadija H , Ellison Richard T , Ward Doyle V , Yoon Jungwon 
Published: November 2023

Abstract

Background
Since the advent of the Haemophilus influenzae B vaccine, the incidence of infections due to this pathogen has substantially decreased, although occasional cases of severe infections due to other serotypes are observed. Routine surveillance at an academic medical center in central Massachusetts identified an apparent increase in the incidence of community-acquired bacteremic H. influenzae infections in adult patients and further investigation was undertaken.

Methods
A retrospective review was performed of all patients with positive blood or cerebrospinal fluid cultures for H. influenzae hospitalized at UMass Memorial Medical Center between January 1, 2008 and March 31, 2023. Available blood culture isolates of H. influenzae from recent bacteremic cases underwent whole genome sequencing (WGS).

Results
There was a notable increase in the quarterly incidence of H. influenzae cases seen in the last quarter of 2022 (3 cases) and first quarter of 2023 (8 cases) as compared to the period from 2008 through the third quarter of 2022 (0.7 cases) [figure 1]. The 11 cases involved 2 children and 9 adults with the median age of adults 66 years. All cases were bacteremic with 8 associated with pneumonia and 1 with pharyngitis, with 2 other infections. Underlying conditions included emphysema, cancer, diabetes, Crohn's disease and others; 2 patients died. There was no apparent geographic clustering. Three isolates were available for WGS with two being in serotype F clade (HiF) and one a non-typeable clade. The two HiF isolates had 1210 SNV differences suggesting the same genomic clade, but not related by recent transmission.

Conclusion
A notable increase in invasive H. influenzae infections has been seen in our institution. The majority of the most recent cases have been in adults, and about 72% of the 11 cases were in association with pneumonia. Of the case fatalities, one was taking an IL-1 inhibitor, and another with cancer. Potential etiologies could be the emergence of a new and more invasive H. influenzae strain, as well as changes in either the host immunity to this pathogen or the upper respiratory tract microbiome in relation to the recent COVID pandemic and the effect of social isolation and increased use of face masks.

Disclosures
All Authors: No reported disclosures
229. Predictive markers for bacteremia in patients receiving extracorporeal membrane oxygenation (ECMO) support
Authors: Hendrix Curtis , Radcliffe Christopher , Tantawy Hossam , Roberts Scott C 
Published: November 2023

Abstract

Background
Patients receiving extracorporeal membrane oxygenation (ECMO) support are critically ill, which can confound the usual metrics clinician use to diagnose bacteremia. The best methods to detect bacteremia in patients receiving ECMO support are unknown, and we sought to evaluate the accuracy of various metrics used in determining bacteremia.

Methods
A retrospective review of patients receiving ECMO support at Yale New Haven Hospital from April 2020 to September 2021 who had blood cultures obtained for any reason was performed. Reasons for blood culture and metrics associated with bacteremia, including white blood cell count (WBC), maximum daily temperature, and procalcitonin, were evaluated for each blood culture event. If patients became bacteremic, only the first positive blood cultures were included in the analysis. Receiver operator curves for each metric were performed to generate areas under the curve (AUC) for assessing diagnostic accuracy.

Results
60 patients who required ECMO support had 132 blood cultures performed, 22 (16.7%) with bacteremia and 110 (83.3%) without. In blood cultures with bacteremia compared to those without, there was no difference in WBC count (17.4 vs 17.9, p = 0.825), maximum daily temperature (37.1 vs 36.9 C, p = 0.572), or procalcitonin (2.0 vs 2.2, p = 0.776) on the day of culture. The most predictive reason for obtaining blood cultures with confirmed bacteremia was hemodynamic instability (AUC 0.668), followed by temperature dysregulation (AUC 0.623). Reasons for obtaining blood cultures minimally associated with bacteremia included adding ice to the ECMO circuit (AUC 0.527), leukocytosis (AUC 0.523), respiratory decompensation (AUC 0.500), surveillance culturing (AUC 0.432), and other reasons not specified but per clinician discretion (AUC 0.386).

Conclusion
Hemodynamic instability as the reason for obtaining blood cultures was the most predictive of bacteremia in patients on ECMO support, while leukocytosis, temperature change, and surveillance cultures were less well associated. There was no difference in WBC counts, maximum daily temperature, and procalcitonin in patients with bacteremia versus those without. Optimizing clinical criteria to determine bacteremia in patients on ECMO remains challenging and warrants further study.

Disclosures
All Authors: No reported disclosures
235. Investigation of the relationship between the number of positive blood cultures and patient prognosis
Authors: Sekiya Satoru , Hasegawa Ryo , Shibutani Koko , Lee Mihye , Mori Nobuyoshi 
Published: November 2023

Abstract

Background
The relationship between the number of positive blood cultures (NPBCs) and clinical outcomes has not been well-studied. The purpose of this study was to assess the impact of NPBCs (one set or two) on clinical outcomes.

Methods
We conducted a retrospective study comparing the clinical features of two sets of positive blood cultures (NPBCs=2) and one set of positive blood culture (NPBCs=1) in adult patients with bacteremia and fungemia from 2004 to 2021 at a tertiary hospital in Tokyo, Japan. We focused on four pathogens commonly encountered in clinical practice, including Staphylococcus aureus (S. aureus), Streptococci, gram-negative rods (GNR) (Enterobacterales and Pseudomonas aeruginosa), and Candida species, as the true causative pathogens in bacteremia and fungemia. The primary outcome was in-hospital mortality, and secondary outcomes were ICU admission and use of vasopressor drugs.

Results
In univariate analysis, NPBCs=2 for S. aureus was associated with vasopressor use, and NPBCs=2 for Streptococci was linked to a higher rate of ICU admission. However, these differences were not significant in multivariate analysis. Interestingly, NPBCs=2 for S. aureus had a positive impact on in-hospital mortality compared with NPBCs=1 (OR 0.574, 95%CI 0.376–0.877, p &lt; 0.05). NPBCs for Candida species did not affect clinical outcomes. Furthermore, NPBCs=2 for GNR was associated with vasopressor use (OR 1.62, 95%CI 1.27–2.07, p &lt; 0.05) in both univariate and multivariate analysis. We performed logistic regression analysis using the five items with the highest clinical significance: NPBCs=2, serum Cr &gt; 1.2 mg/dL, Hb &lt; 12 g/dL, heart rate &gt; 90 beats/min, and platelet count &lt; 150,000/μL. Based on the β coefficient, we assigned scores to each item and created a STAT-2 (S: Serum Cr, T: Thrombocytopenia, A: Anemia, T: Tachycardia, 2: NPBCs=2) score for the use of hypertensive drugs for GNR. The receiver operating characteristic (ROC) curve for the STAT-2 score with a cutoff of 6 points or higher had an area under the curve (AUC) of 0.763. The specificity was 90.8%, with a positive likelihood ratio of 4.13 (95% CI 3.40-5.02).

Conclusion
Our study suggests that NPBCs can predict clinical outcomes in patients with certain pathogenic infections.

Disclosures
All Authors: No reported disclosures
237. Elizabethkingia species: An Emerging Cause of Healthcare-Associated Bloodstream Infection Among Immunocompromised Hosts
Authors: Stewart Adam , Laupland Kevin , Edwards Felicity , Paterson David , Harris Patrick N A 
Published: November 2023

Abstract

Background
Elizabethkingia species are environmental opportunistic pathogens that are a rare but potentially severe cause of bloodstream infection (BSI). The objective of this study was to determine the incidence, risk factors, and outcomes of Elizabethkingia species BSI in a large Australian population.

Methods
Retrospective, laboratory-based surveillance was conducted among residents of Queensland, Australia (population approximately 5 million) over a twenty-year study period. All microbiological data was collected from a government-funded, centralised laboratory service. Clinical and outcome information was obtained from statewide databases.

Results
During 86 million person-years of surveillance, 112 incident Elizabethkingia species BSI occurred for an annualized age and sex-standardized incidence of 1.4 per million residents. Elizabethkingia species isolates were identified as E. meningoseptica in 104 (93%) and were not speciated in 8 (7%). Fifty-three percent were male, and the median age was 69 years (IQR, 55-80). Almost 80% were hospital onset or healthcare-associated BSI, and the median length of hospital stay being 10 days (IQR, 5-30). Comorbidity was common with a median Charlson Co-morbidity Index of 3 (IQR, 1-4), with 25% having active malignancy. Almost 80% were monomicrobial infections, with the majority having no focus identified. Ninety-day overall case-fatality rate was 23%. In vitro susceptibility to ciprofloxacin, sulfamethoxazole, piperacillin-tazobactam was 75%, 71%, 18%, respectively; all isolates were resistant to vancomycin.

Conclusion
Elizabethkingia species BSI is an important cause of opportunistic infection, particularly among vulnerable hosts. Although uncommon, it is associated with a high case-fatality rate and limited antibiotic treatment options due to intrinsic resistance mechanisms.

Disclosures
David Paterson, AMR Action Fund: Board Member|Entasis: Board Member|Merck: Board Member|Pfizer: Board Member|QPex: Board Member|Venatorx: Board Member Patrick N A Harris, PhD, DTMH, MRCP, FRACP, FRCPA, Merck: Advisor/Consultant|Opgen: Advisor/Consultant|Sandoz: Advisor/Consultant
241. Early switch from intravenous to oral antibiotics in patients with Gram-negative bacteremia – a target trial emulation
Authors: Tingsgård Sandra , Bastrup Israelsen Simone , Østergaard Christian , Benfield Thomas 
Published: November 2023

Abstract

Background
Gram-negative bacteremia is a global health concern, that continues to cause significant morbidity and mortality. Intravenous (IV) antibiotics are typically the first-line treatment; however, it is unclear when it is appropriate to switch to oral antibiotics in order to maintain positive outcomes. An early switch from intravenous to oral antibiotics may have several advantages, including reduced hospital stay, lower healthcare costs, and improved patient quality of life. This study investigates the effectiveness of early switch to oral antibiotics in patients with Gram-negative bacteremia using a target trial framework.

Methods
We outlined the protocol for a target trial to estimate the effect of 1) switching to oral antibiotics within four days after initial blood culture compared with 2) continuing IV antibiotic treatment throughout the treatment course on 90-day all-cause mortality. We then emulated the trial using a cohort of adult patients with Gram-negative bacteremia from 2018 through 2022 admitted to four hospitals in the Capital Region of Denmark. Patients who were immunosuppressed, transitioned to hospice care, had polymicrobial infection, were not clinically stable within four days of blood culture, or did not receive adequate empirical antibiotic treatment were excluded. Inverse probability of treatment weighting was applied to adjust for confounding. Intention-to-treat analysis was performed using pooled logistic regression to estimate absolute risk, risk difference, and risk ratio. 95% confidence intervals (CI) were computed using bootstrapping.

Results
1088 patients were eligible for inclusion in the study. Of these, 582 patients transitioned early to oral antibiotic treatment and 506 patients continued IV treatment. The absolute risk of 90-day all-cause mortality was 11.6% (95% CI 9.4;13.7) for patients switching early to oral antibiotics, and 13.4% (95% CI 11.2; 15.5) for patients continuing IV. The risk difference was -1.8% (95% CI -4.9; 1.3) and the risk ratio was 0.99 (95% CI 0.67; 1.13).

Conclusion
Our findings indicate that an early switch to oral antibiotic treatment within four days may be a safe and effective alternative to continued IV treatment in patients hospitalised with uncomplicated Gram-negative bacteremia.

Disclosures
All Authors: No reported disclosures
242. Evaluation of PBP4 promoter variation and clinical outcomes in patients with Enterococcus faecalis bacteremia
Authors: Atterstrom Rachel , Tran Truc T , Nisar Tariq , Panesso Diana , Singh Kavindra , Streling Ana , Rizvi Samie A , Simar Shelby R , Egge Stephanie , Dinh An , Contreras German , Hanson Blake M , Zervos Marcus , Abbo Lilian M , Shimose Luis , Shelburne Samuel A , Arias Cesar A , Miller William R 
Published: November 2023

Abstract

Background
Penicillin-binding protein 4 (PBP4) is a low affinity PBP that has been associated with decreased susceptibility to penicillins in Enterococcus faecalis (Efs). Changes in the promoter region leading to increased expression of the pbp4 gene contribute to this phenotype. There is limited data on the clinical outcome of patients infected with these strains in the U.S. We investigated the clinical outcomes of patients with Efs bacteremia stratified by PBP4 promoter type and piperacillin MIC.

Methods
Index Efs bloodstream isolates from 167 patients were selected from the VENOUS cohort (2016-2021). Whole genome sequencing was performed on all isolates and changes in the promoter region (200 bp upstream of the start codon) were identified, using Efs JH2-2 as reference. β-lactam susceptibility (ampicillin, penicillin, and piperacillin [PIP]) was performed on all isolates by broth microdilution. Clinical outcomes (in-hospital mortality, microbiologic failure, and recurrence) were collected on all patients.

Results
The median age for the cohort was 65 years (IQR: 56-72), and 63.5% were male. The median length of hospitalization was 13 days (IQR: 8-22). The duration of bacteremia was 3 days (IQR: 2-4) and 8.98% of patients had prolonged bacteremia (≥ 7 days). Among 167 isolates, 4 major primary promoter variants were identified: reference JH2-2 (n=66), ΔA88 (n=43), A175C (n=35), and insA192 (n=20). All strains were susceptible to ampicillin and penicillin. A PIP MIC ≥ 16 mg/L (non-susceptible) was found in 74.4% of strains with the ΔA88 promoter, as compared to 22.7% of reference, 17.1% of A175C, and 10% of insA192 (p &lt; 0.001). Clinical outcomes of the 167 patients are shown in Table 1. PIP non-susceptibility was associated with immunocompromise state (49.09% vs 23.85%, p=0.001), history of hematological cancer (40% vs 16.51%, p=0.002), and recurrence (7.27% vs 0.92%, p=0.044). There was no statistical difference in mortality or microbiologic failure.

Conclusion
Isolates with ΔA88 PBP4 promoter variants were associated with PIP non-susceptibility. While in-hospital mortality and microbiologic failure were similar between all patients, those who were infected with a PIP non-susceptible strain were more likely to experience a recurrence.

Disclosures
Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support Lilian M. Abbo, MD, MBA, Ferring: Advisor/Consultant|Pfizer: Advisor/Consultant|Regeneron: Grant/Research Support|Shionogi: Advisor/Consultant William R. Miller, M.D, Merck: Grant/Research Support|UpToDate: Honoraria
244. Predictors and Outcomes of Multi-Drug Resistant Gram-Negative Bacteremia in Patients with Solid Tumours
Authors: Varghese George M , Awada Bassem , Abarca Jorge , Milupi Maniyando , Al Moundhri Mansour 
Published: November 2023

Abstract

Background
Multi-drug resistant Gram-negative bacteraemia (MDR-GNB) is a major concern in cancer patients. However, predictors and outcomes of MDR-GNB bacteraemia in patients with solid tumours are not well defined. The objective of this study was to identify the predictors and outcomes of MDR-GNB bacteraemia in patients with solid tumours.

Methods
This retrospective cohort study was conducted on patients with solid tumours admitted to a tertiary care hospital between January 2022 and December 2022. Demographic, clinical, and microbiological data were collected from electronic medical records. Univariate and multivariate analyses were performed to identify the predictors of MDR bacteraemia. The outcomes of interest included in-hospital 30-day mortality, length of hospital stay, and recurrence of bacteraemia.

Results
Among 1074 patients with solid tumours, a total of 77 episodes of Gram-negative bacteremias occurred in 59 patients (47% male) with a mean age of 57.4 years. Of which 37(48%) had MDR-GNB bacteraemia. The most common source of bacteraemia was biliary (34.2%) followed by central line-associated (21%) and abdomen(21%). Carbapenem resistance was documented in 7(9.1%) of all Gram-negative bacteremias of which 75% were harbouring NDM with or without OXA-48 among enterobacteralis. The predictors of MDR-GNB bacteraemia were prior use of antibiotics (odds ratio [OR] 7.82, 95% [CI] 2.52,24.2) and E.coli bacteremia (OR 6.56, 95% CI 1.26,34.22). The median length of hospital stay was significantly longer in the MDR group compared to the non-MDR group (23 vs. 10.5 days; p= 0.003) and recurrence of bacteremia was significantly more common in the MDR group (35.13% vs. 5.0%; p=&lt; 0.001). The 30-day in-hospital mortality was not significantly different (35.14% vs. 32.5%; p=0.81).

Conclusion
This study identifies prior use of antibiotics and E.coli bacteremias as predictors of MDR-GNB bacteraemia in patients with solid tumours. Patients with MDR-GNB bacteraemia had longer hospital stays, and higher recurrence rates compared to those with non-MDR-GNB bacteremias. This highlights the importance of the judicious use of antibiotics and infection control measures to prevent MDR-GNB bacteraemia in this population.

Disclosures
All Authors: No reported disclosures