True Pathogens Research Articles

P-1608. No Targets, No Problem: Evaluation of Patients with Bloodstream Infections without a Molecular Target Detected by a Rapid Diagnostic Assay

Abstract Background Early identification and management of sepsis is essential in improving patient outcomes. Blood culture rapid diagnostic testing (RDT) allows for early targeting of antimicrobial therapy, particularly when paired with antimicrobial stewardship (AMS) intervention. Hospitalized patients with positive blood cultures are reviewed daily by AMS pharmacists in our health-system, regardless of the RDT result. Limited data exist on the impact of AMS assessment in patients with a positive blood culture with an organism that is not a target identified by RDT. The objective of this study is to describe the microbiology and antimicrobial management of patients with a positive blood culture, but no molecular target detected (NMTD) on the BioFire® Blood Culture Identification 2 (BCID2) panel. Methods This retrospective review evaluated patients within the Atrium Health Greater Charlotte Market who had ≥ 1 positive blood culture with a BCID2 result of NMTD from January to May of 2023. The primary endpoint was to identify the most common organisms recovered by standard of care methods following a NMTD result. Secondary endpoints were evaluated in hospitalized patients and included change in antimicrobials in response to the Gram stain result and percentage of patients on active therapy at organism identification and/or susceptibility testing. Data were analyzed using descriptive statistics. Results 160 organisms were identified in 149 patients with a BCID2 result of NMTD. The most common organisms identified were Micrococcus luteus (14.3%), Corynebacterium spp. (9.4%), non-fragilis Bacteroides spp. (8.1%), Clostridium spp. (7.5%), and Fusobacterium spp. (4.4%) (Table 1). Contamination was suspected in 34% of patients; however, when the organism was considered a true pathogen by the treating provider, the most common infection sources were intra-abdominal (26%) and skin/skin structure (12%). Antibiotics were modified after the Gram stain or NMTD results in 38% of patients, and 79/85 (93%) of patients were on active therapy at organism identification or susceptibility testing if considered a true infection. Conclusion Even when RDT fails to yield a molecular target, AMS review of patients with positive blood cultures may ensure adequate antimicrobial therapy Disclosures All Authors: No reported disclosures

P-2093. A 30-year Descriptive Analysis of Mycobacterium szulgai Infections

Abstract Background Mycobacteirum Szulgai is a non-tuberculous mycobacterium known to cause human disease. Descriptions in the literature are limited to case reports and a larger case series from the Netherlands. Guidelines from the American Thoracic Society recommend that M. szulgai should always be considered pathogenic and that treatment should be based on in-vitro susceptibilities. Demographics and patient characteristics Methods We embarked on a retrospective study of adults ( >18 years) with M. szulgai infection at the Mayo Clinic sites in Arizona, Minnesota, and Florida. We queried the Mayo Clinic Database using two different search methods, (Advanced Text Explorer and the Mayo Data Explorer) using the terms ‘Mycobacterium Szulgai,’ ‘Mycobacteria Szulgai’,’ M. Szulgai’ and ‘Szulgai.’ Medical records from 1994 to 2023 were reviewed. Diagnostic studies Results Initial search yielded 43 patients. Twenty-seven patients were excluded (incomplete records or prior history of infection treated elsewhere). For our cohort of 16 patients, the mean age was 65 years [IRQ 57-74 years], 13 of those were caucasian. Five patients [31%] were immunosuppressed. Thirteen patients [81%] developed pulmonary infection, 5[31%] had extra pulmonary infection (2[12%] with disseminated disease and 3[19%] with extra-pulmonary disease without primary pulmonary infection). Only 8 [50%] patients received specific therapy. All treated patients met ATS criteria for NTM infections, while 3 [19%] untreated patient met criteria. Only 4 [25%] patient received therapy based on susceptibilities. The most common regimen was a combination of rifampin, ethambutol and macrolide in 5[31%] of the patients. Seven patients [47%] were cured, 4[27%] had ongoing symptoms, 1[7%] had relapse and 1 [7%] is currently receiving therapy. There were 2[ 13%] deaths in the untreated group and none from the treated group. One patient was lost to follow up. Treatment and outcomes Conclusion Our findings echo published literature and ATS recommendations that M. szulgai should be regarded as a true pathogen that necessitates targeted therapy. Disclosures All Authors: No reported disclosures

P-1751. Why do we call in the Blues (and Purples)? Critical Result Reporting of Gram Stains for Gram Positive Cocci in Blood Cultures

Abstract Background Gram positive cocci (GPC) in blood cultures (BLCX) can represent pathogens or contaminants. Many laboratories notify care teams of a positive BLCX with the gram stain as a critical results report (CRR). However, PCR results about 90 minutes later and can provide useful information to distinguish a contaminant from a pathogen. The present study describes healthcare utilization surrounding CRR of gram stain result without the PCR result. Methods Retrospective observational study of patients with positive BLCX. Patients were excluded if their BLCX had yeast, polymicrobial growth, a gram-negative organism, or were < 18 years of age. Clinical and healthcare utilization information was collected using the electronic medical record. We defined the following as “true pathogens” (TP): MRSA, MSSA, Enterococcus, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus pneumoniae. We also defined TP as a coagulase-negative staphylococcus or other Strep species with 2/2 positive BLCX with intraarticular or endovascular hardware present and with 4 SIRS criteria. A “likely contaminant” (LC) was defined as coagulase negative staphylococcus or Strep species (not included in the initial TP definition) with 1-2 BLCX positive, with or without intraarticular or endovascular hardware present, and < 4 SIRS criteria. Results Of 94 patients with BLCX positive for GPC, 54 were categorized as TP, and 40 as LC. 36 (67%) of patients with a TP on BLCX received vancomycin (VAN) before CRR and 19 (35%) received VAN after CRR. 12 (30%) patients with a LC on BLCX received VAN before CRR and 11 (28%) received VAN after CRR. For those not on VAN before CRR and were placed on VAN after the call, 10 (24%) had TP and (28%) had LC identified. Repeat BLCXs were performed in 93% of patients with TP and 83% of patients with LC. Infectious Disease (ID) consults were placed in 63% of TP and 73% for LC. Echocardiograms were performed in 57% for TP and 60% for LC. Conclusion Workup and treatment for GPC identified in BLCX were similar for TP and LC. VAN is being over-utilized for LC which could lead to patient harm. Unnecessary resources are being expended in the workup of LC. Using PCR results instead of the gram stain as the CRR may provide more complete information to providers to inform decision making. Disclosures All Authors: No reported disclosures

P-134. Sarcina ventriculi, pathogen or commensal? Case series and review of the literature

Abstract Background Sarcina, or Clostridium, ventriculi (SV), is a non-motile, gram-positive coccus with anaerobic fermentative properties. Due to its rarity, comprehensive knowledge about it is lacking. This study aims to elucidate its epidemiology and common manifestations. Methods We searched PUBMED and EMBASE utilizing terms as 'Sarcina', 'Ventriculi', and 'Clostridium' with no restrictions. Figure 1 contains the PRISMA diagram for case selection. Results We identified 88 cases and included 2 cases from our institution. The mean age was 48 ranging from 10 months to 89 years with an equal distribution between genders. 21% had Diabetes mellitus type 2 and 50% had baseline GI comorbidity primarily affecting the esophagus or stomach in 27% respectively. 37% were concurrently on antacids and prokinetics. The most common symptoms were abdominal pain (58%), nausea/vomiting (41%), anorexia/weight loss (18%), and diarrhea (12%). Pertinent labs were anemia, leukocytosis, and elevated inflammatory markers. Mural inflammation, ulcers, retained food with distension, pneumatosis, perforation, necrosis, masses, or obstruction were common on radiological and endoscopic workup. Organism was mostly isolated from gastric (73%) and esophageal (18%) tissue using endoscopic and/or surgical procedures (76 and 27%, respectively). It was also isolated from respiratory tissue (3%), anaerobic blood culture (3%), lymph nodes (2%), urine (1%), and cerebral ventricles (1%). Co-infection with candida in 8% and H. Pylori in 4% was noted. 57% received antibiotics, being combination therapy with metronidazole and fluroquinolones, the most therapy used. 77% had successful clinical recovery, 11% expired; the outcome for 12% of patients remains unknown. Antibiotic therapy was used in 67% and 40% of patients who clinically recovered and expired respectively. Conclusion In most cases, SV is a true pathogen responsible for symptoms rather than a commensal; however, larger-scale studies are needed to discern pathophysiology. Most cases present with an underlying GI comorbidity including dysmotility which might predispose to colonization. Metronidazole and fluroquinolones provide optimal clinical response. Disclosures All Authors: No reported disclosures

Emerging Resistance Mechanisms in Gram-Positive Bacteria Isolated From Septicemia Cases in ICUs: A Focus on Genotypic Insights.

Background Bloodstream infections (BSIs) are associated with high morbidity and mortality, especially in intensive care unit (ICU) settings. The most common Gram-positive pathogens, methicillin-resistantStaphylococcus aureus (MRSA) and coagulase-negative Staphylococci (CoNS), are likely to cause BSIs. The phenotypic and genotypic characteristics of multidrug-resistant (MDR)Staphylococcal species isolated from patients admitted to the ICUwith septicemia were evaluated for better treatment outcomes. Materials and methods A cross-sectional study was conducted at Sree Balaji Medical College and Hospital over two years (July 2022 to June 2024). Blood samplesin blood culture bottles received in the laboratory from ICU patients with suspected sepsis were included in this study. The BacT/ALERT® 3D system (bioMérieux, France) was used to assess the bacterial growth. TheVITEK®2 system (bioMérieux, France) and conventional methods were used to identify Gram-positive isolates. Antibiotic susceptibility was determined by the Kirby-Bauer disc diffusion method, and polymerase chain reaction (PCR) was used to detect genes like mecA, icaA, and icaD genes. Results Out of 274 blood samples, eight (2.9%) were contaminants, and 121 (44.2%) were culture-positive as true pathogens. Eighty-seven (71.9%) Gram-positive isolates were identified from the positive blood cultures, of whichCoNS was predominant (51, 58.6%), followed by Staphylococcus aureus(25, 28.7%). Methicillin resistance was observed in 10 (13.1%) Staphylococcusaureus and 14 (18.4%) CoNS isolates. PCR detected the mecA gene in 20 (83.3%) methicillin-resistant isolates and biofilm-related genes icaD in 64 (84.2%) and icaA in 58 (76.3%). Vancomycin and teicoplanin showed high effectiveness. Conclusions This study has emphasized the importance of molecular screening for the mecA, icaA, and icaD genes in framing antibiotic regimens. The findings emphasize the efficacy of vancomycin, teicoplanin, and linezolid in combating MDR Staphylococcus infections in ICUs of hospitals and demonstrate the importance of antibiotic stewardship.

The natural history of cerebral infundibula: A retrospective cohort study.

Debate exists regarding the true pathogenicity of cerebral infundibula (CI). Pre-aneurysmal lesions and benign anatomical variants have both been proposed. In this study, we present the largest single cohort series on the natural history of CI. Retrospective review of prospective surveillance of 420 CI was undertaken in a single tertiary cerebrovascular centre. All CI diagnosed by a neuroradiologist, diagnosed on either a Magnetic resonance angiography (MRA), Computed tomography angiography (CTA) or Digital subtraction angiography (DSA) were eligible for inclusion. Imaging and demographic characteristics were recorded at baseline. CI growth and aneurysm transformation were the outcomes of interest. Groupwise comparison was conducted via Fischer exact testing. Kaplan Meir curves and Cox proportional hazard ratios were used to assess variables of interest with respect to time on surveillance. 402 patients with 420 CI were surveyed over 2418 infundibula-years. Eleven CI (2.62%) grew on surveillance, and three (0.7%) transformed into aneurysms. Median time to growth was 85 months (36-263) and median time to aneurysm transformation was 112 months (96-142). Of the CI that grew, male sex and CI >2 mm at diagnosis were significant predictors of growth (all p<0.05). Of the CI that grew in surveillance, 2/11 (18.2%) transformed into aneurysms (p=0.001). Aneurysm transformation occurred at a rate of 1.27 per 1000 infundibula years. CI growth on surveillance (p= 0.00016) and size at diagnosis (p=0.038) remained significant predictors of aneurysm transformation on Kaplan Meir curves. The transformation of a CI to an aneurysm occurs at a low rate. A history of growth on surveillance imaging represents significant risk for aneurysm transformation.

Influenza A as a True Zoonotic Pathogen: Transmission through Reservoir Hosts

Influenza A virus (IAV) represents a considerable global health threat due to its rapid mutation rates and broad host range, facilitating cross-species transmission and enabling the virus to evade immune defenses. This review explores the molecular mechanisms underlying IAV's pathogenicity, focusing on its zoonotic potential through reservoir hosts, such as wild birds and swine. The virus's ability to undergo antigenic shift and drift allows it to continually adapt to new hosts and environments, posing challenges for control and treatment. Current antiviral therapies are limited by the emergence of resistant strains, underscoring the necessity for innovative vaccine development and treatment strategies. By examining IAV's molecular evolution, immune evasion tactics, and transmission dynamics, this review highlights the critical need for enhanced surveillance, improved therapeutic options, and international cooperation to mitigate future outbreaks. A deeper understanding of these processes is essential to inform public health efforts and combat the persistent threat of IAV.

Epidemiology and clinical characteristics of Aeromonas-associated gastroenteritis in Northern Israel: Insights and implications for public health

The role of Aeromonas spp. in gastroenteritis is controversial due to varied clinical presentations and variable prevalence in asymptomatic. This study, conducted in Northern Israel, aimed to compare positivity rate and demographic characteristics of patients with Aeromonas-associated gastroenteritis (AAG) to asymptomatic, and examine the role of Aeromonas in AAG by comparing clinical and epidemiological characteristics between AAG and Campylobacter-associated gastroenteritis (CAG) patients.Results showed that 4.24%-4.81% of AAG patients had Aeromonas spp. in stools as a sole pathogen in 2020-2022, compared to 4.9% of asymptomatic. Analysis of 243 CAG patients versus 70 AAG patients revealed significantly less diarrhea, fever, abdominal pain, and muscle pain in AAG patients. Multivariate analysis identified higher Ct values, recent restaurant dining, and prolonged diarrhea as predictive factors for AAG versus CAG.In conclusion, similar positivity rates of Aeromonas spp. in symptomatic and asymptomatic making the distinction between true pathogen versus commensal bacteria difficult, unlike CAG.

Hands-On And Mobile App-Based Training Of Second Phase MBBS Students Regarding Blood Sample Collection For Routine Tests And Culture

Background Aseptic measures during blood sampling should be strictly enforced as identification of the true pathogen can act as life-saving measure in patients. Contamination during collection can produce erroneous results which can lead to unnecessary antibiotic usage. Thus, adequate training must be imparted so that the MBBS students can learn the correct technique and develop appropriate skills. This pre-post interventional study thus assessed the students’ and faculties’perception on venous blood sampling through hands on exercises on a simulated model and learning through digital module among MBBS students. Methodology The knowledge of the students was assessed through a questionnaire while practical skills through OSPE using a pre-validated checklist in the pre-intervention phase. The intervention comprised of students being trained in small batches regarding blood sample collection on a mannequin followed by biomedical waste disposal and spillage management. A digital intervention module for self-directed learning was shared with the students to reinforce their learning. This was followed by post interventional assessment of theoretical knowledge and practical skills. Results Paired sample t-test showed a statistically significant improvement in the knowledge scores and OSPE skills in the post-intervention phase. About 91% students opined that they were well trained. All the faculty opined that this training was immensely useful to students for future practical applications. Conclusion The current study demonstrated effectiveness of intervention among the medical students under the new curriculum through hands-on and digital module-based training on accurate blood sampling procedure.

Polymicrobial consortia in the pathogenesis of biofilm vaginosis visualized by FISH. Historic review outlining the basic principles of the polymicrobial infection theory

The manuscript disputes the exclusive mono-infectious way of thinking, which presumes that for every infection only one pathogen is responsible and sufficient, when infectious vectors, close contact and reduced immunity meet. In situations involving heavily colonized anatomical sites such an approach often ends in insoluble contradictions. Upon critical reflection and evaluation of 20 years research on spatial organization of vaginal microbiota it is apparent, that in some situations, pathogens may act and operate in permanent, structurally organized consortia, whereas its individual components may be innocuous and innocent, failing to express any pathogenic effect. In these cases, consortia are the true pathogens responsible for many infectious conditions, which usually remain unrecognized as long as improperly diagnosed.The structure of such consortia can be unraveled using ribosomal fluorescence in situ hybridization (FISH). FISH methodology, that not only offers an ex vivo opportunity to recognize bacterial species, but provides unique physical insight into their specific role in the pathogenesis of polymicrobial infections. Ribosomal FISH technique applied to both, women with bacterial vaginosis (BV) and their male partners, has added significantly to our understanding of the pathogenesis of this condition and contributed to appreciating the mechanisms of polymicrobial, community-based infection, potentially leading to therapeutic advances.

Evolution of Life Cycles of Nematodes Parasitizing Woody Plants As a Result of Ecological and Phylogenetic Co-Adaptations with Hosts and Vectors.

Fundamental aspects in the evolution of nematodes parasitizing woody plants are reviewed. (1)Nematode faunal lists of natural refugia are useful to predict the risks of opportunistic pathogens becoming true pathogens in the forest and park communities. (2) Nematode composition in natural refugia gives a chance to identify nematode antagonists of insect vectors of dangerous fungal and nematode infections, which can be potentially used as the biological agents for woody plants' protection. (3) Dauers in the ancestors of wood-inhabiting nematodes played a role as a survival stage in the detritus decomposition succession, and they later acquired the functions of dispersal and adaptations for transmission using insect vectors. (4)When inspecting wilted trees, it is necessary to use dauers for diagnostics, as sexually mature nematodes may be absent in tree tissues. (5) Plant parasitic nematodes originated from members of the detritus food web and retained a detritivorous phase in the life cycle as a part of the propagative generation. (6) Vectors in the life cycles of plant parasitic nematodes are inherited from the ancestral detritivorous nematode associations, rather than inserted in the dixenic life cycle of the 'nematode-fungus-plant' association. (7) Despite the significant difference in the duration of the nematode-tree and nematode-vector phases of the life cycle, the actual parasitic nematode specificity is dual: firstly to the vector and secondly to the natural host plant (as demonstrated in phytotests excluding a vector).

Coagulase-negative Staphylococci – A True Pathogen in Bloodstream Infections and their Resistance Patterns in a Tertiary Care Hospital

Coagulase-negative staphylococci (CoNS) are primary skin commensals that have long been considered contaminants even when grown in blood cultures. This group of organisms has been recently recognized as a potential causative pathogen of septicemia. This increase has been attributed to the increased use of intravascular and prosthetic devices. Hence, we aimed to estimate the prevalence of CoNS as a true pathogen in adult and pediatric blood cultures along with their antibiotic susceptibility patterns. A total of 1076 adult and 611 pediatric blood cultures were subjected to an automated BacT/ALERT continuous monitoring system. Isolated CoNS were considered true pathogens if they met the diagnostic, clinical, and laboratory criteria. Antimicrobial susceptibility testing for pathogenic CoNS was carried out using the Kirby-Bauer disk diffusion method and interpreted as per CLSI 2021. CoNS were considered true pathogens in 23 (42.5%) of 54 adults and 12 (41.3%) of 29 pediatric CoNS isolated from blood cultures. Methicillin-resistant CoNS was detected in 66% and 70% of adult and pediatric cultures, respectively. All the CoNS isolates were sensitive to vancomycin and linezolid. Coagulase-negative staphylococci (CoNS) can either be a contaminant or a true pathogen, whose discrimination based on clinical and laboratory indices plays a pivotal role in the management of patients with sepsis.

A reconstructed genome-scale metabolic model of Helicobacter pylori for predicting putative drug targets in clarithromycin and rifampicin resistance conditions.

Helicobacter pylori is considered a true human pathogen for which rising drug resistance constitutes a drastic concern globally. The present study aimed to reconstruct a genome-scale metabolic model (GSMM) to decipher the metabolic capability of H. pylori strains in response to clarithromycin and rifampicin along with identification of novel drug targets. The iIT341 model of H. pylori was updated based on genome annotation data, and biochemical knowledge from literature and databases. Context-specific models were generated by integrating the transcriptomic data of clarithromycin and rifampicin resistance into the model. Flux balance analysis was employed for identifying essential genes in each strain, which were further prioritized upon being nonhomologs to humans, virulence factor analysis, druggability, and broad-spectrum analysis. Additionally, metabolic differences between sensitive and resistant strains were also investigated based on flux variability analysis and pathway enrichment analysis of transcriptomic data. The reconstructed GSMM was named as HpM485 model. Pathway enrichment and flux variability analyses demonstrated reduced activity in the ribosomal pathway in both clarithromycin- and rifampicin-resistant strains. Also, a significant decrease was detected in the activity of metabolic pathways of clarithromycin-resistant strain. Moreover, 23 and 16 essential genes were exclusively detected in clarithromycin- and rifampicin-resistant strains, respectively. Based on prioritization analysis, cyclopropane fatty acid synthase and phosphoenolpyruvate synthase were identified as putative drug targets in clarithromycin- and rifampicin-resistant strains, respectively. We present a robust and reliable metabolic model of H. pylori. This model can predict novel drug targets to combat drug resistance and explore the metabolic capability of H. pylori in various conditions.

Corynebacterium striatum: A True Pathogen in Chronic Contiguous Osteomyelitis.

All patients were cured after successful completion of an antibiotic course with a resolution of infection. Cure was defined as granulation of the infected wound and resolution of clinical symptoms at outpatient follow-up between 6 and 8 weeks. This series emphasizes that C. striatum is often a true pathogen in the setting of CCO. When isolated in polymicrobial infections, a targeted antibiotic therapy towards this pathogen along with other causative pathogens accompanied by surgical intervention is typically required for a successful cure of CCO.

The Yield of One vs. Two Blood Cultures in Children: Under-Detection and Over-Testing.

We aimed to determine whether obtaining two blood cultures (BCs) instead of one improved the detection of bloodstream infections (BSIs) in children. For this descriptive study, we used surveillance data collected in 2019-2021 from all Israeli hospitals serving children. The sample included 178,702 culturing episodes. One BC was taken in 90.1% of all episodes and 98.2% of episodes in the emergency department. A true pathogen was detected in 1687/160,964 (1.0%) of single-culture episodes and 1567/17,738 (8.9%) of two-culture episodes (p < 0.001). The yield was significantly different even when considering only the first BC in two-culture episodes: 1.0% vs. 7.5%. Among 1576 two-culture episodes that were positive for a true pathogen, the pathogen was detected only in the second culture in 252 (16.0%). We estimated that if a second culture had been taken in all episodes, an additional 343 BSIs by a true pathogen would have been detected. Among 1086 two-culture episodes with commensal bacteria, the second BC was sterile in 530 (48.8%), suggesting contamination. A commensal was isolated in 3094/4781 (64.7%) positive single-culture episodes, which could represent BSI or contamination. The yield of a single BC bottle was low, reflecting both lower sensitivity of a single bottle and the taking of single bottles in patients with a low probability of BSI.

The modulatory effect of Lactobacillus gasseri ATCC 33323 on autophagy induced by extracellular vesicles of Helicobacter pylori in gastric epithelial cells in vitro

Helicobacter pylori has been recognized as a true pathogen, which is associated with various gastroduodenal diseases, and gastric adenocarcinoma. The crosstalk between H. pylori virulence factors and host autophagy remains challenging. H. pylori can produce extracellular vesicles (EVs) that contribute to gastric inflammation and malignancy. Some probiotic strains have been documented to modulate cell autophagy process. This study was aimed to investigate the modulatory effect of cell-free supernatant (CFS) obtained from Lactobacillus gasseri ATCC 33323 on autophagy induced by H. pylori-derived EVs. EVs were isolated from two clinical H. pylori strains (BY-1 and OC824), and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The viability of AGS cells was assessed after exposure to different concentrations of H. pylori EVs, and L. gasseri CFS. Based on MTT assay and Annexin V-FITC/PI staining, 50 μg/ml of H. pylori EVs and 10 % v/v of L. gasseri CFS were used for further cell treatment experiments. Autophagy was examined using acridin orange (AO) staining, RT-qPCR analysis for autophagy mediators (LC3B, ATG5, ATG12, ATG16L1, BECN1, MTOR, and NOD1), and western blotting for LC3B expression. H. pylori EVs were detected to range in size from 50 to 200 nm. EVs of both H. pylori strains and L. gasseri CFS showed no significant effect on cell viability as compared to untreated cells. H. pylori EVs promoted the development of acidic vesicular organelles and the expression of autophagy-related genes (LC3B, ATG5, ATG12, ATG16L1, BECN1, and NOD1), and decreased the expression of MTOR in AGS cells at 12 and 24 h time periods. In addition, the production of LC3B was increased following 12 h of treatment in AGS cells. In contrast, L. gasseri CFS effectively inhibited EVs-induced autophagy, as evidenced by reduced acidic vesicular organelle formation and modulation of autophagy markers. Our study indicated that L. gasseri CFS can effectively suppress H. pylori EV-induced autophagy in AGS cells. Further investigations are required to decipher the mechanism of action L. gasseri CFS and its metabolites on autophagy inhibition induced by H. pylori.

Evolution of life cycles of nematodes parasitizing woody plants as a result of ecological and phylogenetic co-adaptations with hosts and vectors

Fundamental aspects in the evolution of nematodes parasitizing woody plants are reviewed. 1) Nematode faunal lists of natural refigia are useful to predict the risks of opportunistic pathogens becoming true pathogens in the forest and park communities. 2) Nematode composition in natural refugia gives a chance to identify nematode antagonists of insect vectors of dangerous fungal and nematode infections, which can be potentially used as of the biological agents for woody plants’ protection. 3) Dauers of the ancestors of wood-inhabiting nematodes played a role as a survival stage in the detritus decomposition succession, and they later acquired the functions of dispersion and adaptations for transmission using insect vectors. 4) When inspecting wilted trees, it is necessary to use dauers for diagnostics, as sexually mature nematodes may absent in tree tissues. 5) Plant parasitic nematodes originated from members of the detritus food web and retained a detritivorous phase in the life cycle as a part of the propagative generation. 6) Vectors in the life cycles of plant parasitic nematodes are inherited from the ancestral detritivorous nematode associations, rather than inserted in the dixenic life cycle of the ‘nematode-fungus-plant’ association. 7) Despite the significant difference in the duration of the nematode-tree and nematode-vector phases of the life cycle, the actual parasitic nematode specificity is twofold: firstly to the vector and secondly to the natural host plant (as demonstrated in phytotests excluding a vector).

BD Chloraprep™ (“2 % chlorhexidine with 70 % isopropyl alcohol”) versus povidone iodine plus alcohol, for prevention of blood culture contamination at children: An investigator-initiated, open-label, single centre, randomized controlled trial

IntroductionOne of the important problems that lower the diagnostic value of blood culture is contamination with skin organisms. The povidone-iodine, alcohol, and chlorhexidine gluconate alcohol are used for disinfection prior to blood sampling for culture. MethodsThe investigator-initiated, open label, single centre, randomised trial compared blood culture contamination rates between two groups of patients in which using a povidone iodine skin-preparation process with the contamination rate for using “2 % chlorhexidine with 70 % isopropyl alcohol” skin-disinfection. The patients who required sampling for blood cultures were included in the study and study period was from 15 March 2023 to 15 July 2023. ResultsA total of 400 blood cultures were obtained during the study, including 133 in the study group and 267 in the control group. In the total blood cultures, 11.75 % (n = 47) had microorganism isolation. Among them 39 (9.75 %) were contaminants and 8 (2 %) of them were true pathogens. The contaminant microorganisms were as following; 34 coagulase-negative Staphylococci, 3 Micrococcus spp, and 2 Streptococci viridans. The blood culture contamination rate in the study group was 5.3 % (n = 7) and 12.0 % (n = 32) in the control group, and significantly lower in the study group (p = 0.033). There is no significant difference regarding skin related side effects between two groups. ConclusionsThis study, showed that 2 % chlorhexidine gluconate in 70 % isopropyl alcohol is more efficacious in children than 10 % povidone-iodine preparations for disinfecting the skin prior to blood specimen collection for prevention of blood culture contamination.

235. Investigation of the relationship between the number of positive blood cultures and patient prognosis

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 &amp;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 &amp;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 &amp;gt; 1.2 mg/dL, Hb &amp;lt; 12 g/dL, heart rate &amp;gt; 90 beats/min, and platelet count &amp;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

2811. Real-World Experience Utilizing Cefiderocol for Serious Multidrug Resistant Gram-Negative Infections

Abstract Background Cefiderocol is a novel siderophore cephalosporin that demonstrated in vitro activity against carbapenem-resistant Enterobacterales, Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Stenotrophomonas maltophilia. Cefiderocol demonstrated promising efficacy in randomized, clinical trials; however, real-world utilization of cefiderocol is not well characterized. Methods This was a retrospective study of adults who received cefiderocol for ≥72h for serious meropenem-resistant Gram negative infections at our institution between 11/2021 and 12/2022. Patients with all sources of infection were considered for inclusion. Clinical failure was defined as all-cause 90d or in-hospital mortality, or the lack of resolution of signs or symptoms of infection. Microbiological failure was defined as positive cultures growing the index pathogen after ≥7d of initiating therapy or ≤60d of completing therapy. Descriptive statistics were used to compare outcomes by the index pathogen. Results Of 55 patients who received cefiderocol, 35 patients were included. The remaining 20 patients were excluded for receiving &amp;lt; 72h of therapy. The most common infections were pneumonia (n = 17, 48.6%), skin and skin structure infections (n = 6, 17.1%), and osteomyelitis (n = 5, 14.3%) wherein PA (n = 17, 48.6%) and AB (n = 14, 40%) were isolated most frequently. The overall 90d and in-hospital mortality rates were 9 (25.7%) and 11 (31.4%) patients, respectively. Clinical failure, assessed in 34 patients, occurred in 10 (29.4%) patients and was similar between pathogens (p = 0.71). Microbiological failure, assessed in 26 patients, occurred more commonly in infections caused by PA (n = 11/12, 91.7%) compared to all other pathogens (n = 3/14, 21.4%; p &amp;lt; 0.01). Notably, most microbiological failures due to PA were in the setting of pneumonia (n = 6/11, 54.5%). Conclusion Real-world experience demonstrated that most patients receiving cefiderocol for serious Gram-negative infections did well; however, microbiological failure among patients with PA infections may be attributed to the difficulty in differentiating true pathogens and colonizers in respiratory infections. Disclosures All Authors: No reported disclosures