Bacterial Infections In Patients Research Articles

Qualitative Immunoglobulin Deficiency Causes Bacterial Infections in Patients with STAT1 Gain-of-Function Mutations.

STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy. Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity. All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts. STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels.

Evaluation of mucosal-associated invariant T-cells as a potential biomarker to predict infection risk in liver cirrhosis.

Infection is a serious complication in patients with cirrhosis. Mucosal-associated invariant T (MAIT) cells are involved in the immune defense against infections and known to be impaired in several chronic conditions, including cirrhosis. Here, we evaluated if MAIT cell levels in peripheral blood are associated with risk of bacterial infections in patients with cirrhosis. Patients with cirrhosis seen at the Karolinska University Hospital, Stockholm, Sweden, between 2016 and 2019 were included. Levels of MAIT cells in peripheral blood were determined using flow cytometry. Baseline and follow-up data after at least two years of follow-up were collected by chart review for the primary outcome (bacterial infection) and secondary outcomes (decompensation and death). Competing risk and Cox regression were performed. We included 106 patients with cirrhosis. The median MAIT cells fraction in the circulation was 0.8% in cirrhosis compared to 6.1% in healthy controls. In contrast to our hypothesis, we found an association in the adjusted analysis between relatively preserved MAIT cell levels, and a slightly higher risk to develop bacterial infections (adjusted subdistribution hazard ratio (aSHR) 1.15 (95%CI = 1.01-1.31). However, MAIT cell levels were not associated with the risk of hepatic decompensation (aSHR 1.19 (95%CI = 0.91-1.56)) nor with death (adjusted hazard ratio 1.10 (95%CI = 0.97-1.22)). Relatively preserved MAIT cell levels in blood of patients with cirrhosis were associated with a somewhat higher risk of bacterial infections. The clinical relevance of this might not be strong. MAIT cells might however be an interesting biomarker to explore in future studies.

Characterization of genes related to the efflux pump and porin in multidrug-resistant Escherichia coli strains isolated from patients with COVID-19 after secondary infection

BackgroundEscherichia coli (E. coli) is a multidrug resistant opportunistic pathogen that can cause secondary bacterial infections in patients with COVID-19. This study aimed to determine the antimicrobial resistance profile of E. coli as a secondary bacterial infection in patients with COVID-19 and to assess the prevalence and characterization of genes related to efflux pumps and porin.MethodsA total of 50 nonduplicate E. coli isolates were collected as secondary bacterial infections in COVID-19 patients. The isolates were cultured from sputum samples. Confirmation and antibiotic susceptibility testing were conducted by Vitek 2. PCR was used to assess the prevalence of the efflux pump and porin-related genes in the isolates. The phenotypic and genotypic evolution of antibiotic resistance genes related to the efflux pump was evaluated.ResultsThe E. coli isolates demonstrated high resistance to ampicillin (100%), cefixime (62%), cefepime (62%), amoxicillin-clavulanic acid (60%), cefuroxime (60%), and ceftriaxone (58%). The susceptibility of E. coli to ertapenem was greatest (92%), followed by imipenem (88%), meropenem (86%), tigecycline (80%), and levofloxacin (76%). Regarding efflux pump gene combinations, there was a significant association between the acrA gene and increased resistance to levofloxacin, between the acrB gene and decreased resistance to meropenem and increased resistance to levofloxacin, and between the ompF and ompC genes and increased resistance to gentamicin.ConclusionsThe antibiotics ertapenem, imipenem, meropenem, tigecycline, and levofloxacin were effective against E. coli in patients with COVID-19. Genes encoding efflux pumps and porins, such as acrA, acrB, and outer membrane porins, were highly distributed among all the isolates. Efflux pump inhibitors could be alternative antibiotics for restoring tetracycline activity in E. coli isolates.

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Investigation Few Biomarkers for Pantoea Infection with Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) is a disease known as systemic lupus erythematosus. SLE is an autoimmune condition in which the immune system attacks the body’s own tissues, leading to extensive tissue damage and inflammation in other organs. One of the most frequent causes of death and morbidity in SLE patients is infection. Patients with SLE may contract a genus of gram-negative bacteria called Pantoea. This study aims to find biomarkers for Pantoea infection in SLE patients in Iraq’s Najaf Governorate. Methods: About 60 individuals with systemic lupus erythematosus from Al-Sader Medical City in Al-Najaf Province had blood samples taken at a specialized rheumatology and nephrology center between September 2022 and February 2023. Some bio-markers has been evaluated. Results: The results of microbiological analyses indicate that 26/60 samples contain bacteria. Pantoea was discovered in 3 (11.6%) of the 26 specimens. Despite SLE, increased autoantibody levels in patients. The results of this analysis indicate a significant decrease in Hb, WBC, and platelet levels. In contrast to the control group, the serum levels of CD69, IL-21, and IL-35 increased significantly. Conclusion: Pantoea produces elevated diagnostic and immunological parameters in SLE patients. Consequently, it is necessary to conduct assays to identify bacterial infections in patients, with a significant increase in CD69, IL-21, and IL-35 in the event that SLE patients are infected with bacteria.

Microbiological profile of long COVID and associated clinical and radiological findings: a prospective cross-sectional study.

To study the frequency of microbiological etiology of respiratory infections in patients with long COVID and their associated clinical and radiological findings. Nasopharyngeal swabs and sputum specimens were collected from 97 patients with respiratory illness stemming from long COVID. The specimens were assessed for their microbiological profile (bacteria and virus) and their association with the overall clinical and radiological picture. In total, 23 (24%) patients with long COVID had viral infection (n = 12), bacterial infection (n = 9), or coinfection (n = 2). Microorganisms were detected at significantly higher rates in hospitalized patients, patients with moderate COVID-19, and patients with asthma (P < .05). Tachycardia (65%) was the most common symptom at presentation. A statistically significant number of patients with long COVID who had viral infection presented with cough and myalgia; and a statistically significant number of patients with long COVID who had bacterial infection presented with productive coughing (P < .05). Post-COVID fibrotic changes were found in 61% of cohort patients (31/51). A decreasing trend of respiratory pathogens (enveloped viruses and bacteria) was found in long COVID. An analysis including a larger group of viral- or bacterial-infected patients with long COVID is needed to obtain high-level evidence on the presenting symptoms (cough, myalgia) and their association with the underlying comorbidities and severity.

THE CORRELATION BETWEEN TYPE 2 DIABETES MELLITUS WITH BACTERIAL INFECTION IN COVID-19 PATIENTS ADMITTED TO INTENSIVE CARE UNIT AT CENTRAL GENERAL HOSPITAL PROF. DR. I.G.N.G. NGOERAH DENPASAR IN 2021-2022

Type 2 Diabetes Mellitus (T2DM) has a detrimental impact on the immune system, resulting in a decrease in the body's immune response, making patients highly susceptible to bacterial infections. Patients with T2DM, especially those treated in the Intensive Care Unit (ICU) of a hospital, face an increased risk of infection. The emergence of COVID-19, which also infects T2DM patients, further diminishes the immune system's function in these patients. Consequently, individuals with both T2DM and COVID-19 are at a heightened risk of developing secondary infections, commonly referred to as Hospital-Acquired Infections.This research aims to explore the relationship between T2DM, assessed through blood sugar levels, and the occurrence of bacterial infections in COVID-19 patients treated in the ICU of Prof. Dr. I.G.N.G. Ngoerah Central Hospital from 2021 to 2022. The research design employed is quantitative analytical correlational study using a cross-sectional approach, with a sample size of 98 patients collected from the Medical Records and Hospital Management System of Prof. Dr. I.G.N.G. Ngoerah Central Hospital in Denpasar. This study found that there is a significant correlation between patient’s infection profile with random blood glucose levels with an Odds Ratio (OR) of 1.15 (95% CI: 1.04 – 1.27; p = 0.013). Additionally, a significant relationship was observed between the severity of COVID-19 and bacterial infections in patients, with an Odds Ratio of 1.12 (95% CI: 1.01 – 1.26; p = 0.04).&#x0D; Keywords : T2DM, ICU, Hospital-Acquired Infection

Host transcriptomics and machine learning for secondary bacterial infections in patients with COVID-19: a prospective, observational cohort study

Viral respiratory tract infections are frequently complicated by secondary bacterial infections. This studyaimed to use machine learning to predict the risk of bacterial superinfection in SARS-CoV-2-positive individuals. In this prospective, multicentre, observational cohort study done in nine centres in six countries (Australia, Indonesia, Singapore, Italy, Czechia, and France) blood samples and RNA sequencing were used to develop a robust model of predicting secondary bacterial infections in the respiratory tract of patients with COVID-19. Eligible participants were older than 18 years, had known or suspected COVID-19, and symptoms of a recent respiratory infection. A control cohort of participants without COVID-19 who were older than 18 years and with no infection symptoms was also recruited from one Australian centre. In the pre-analysis phase, data were filtered to include only individuals with complete blood transcriptomics and patient data (ie, age, sex, location, and WHO severity score at the time of sample collection). The dataset was then divided randomly (4:1) into a training set (80%) and a test set (20%). Gene expression data in the training set and control cohort were used for differential expression analysis. Differentially expressed genes, along with WHO severity score, location, age, and sex, were used for feature selection with least absolute shrinkage and selection operator (LASSO) in the training set. For LASSO analysis, samples were excluded if gene expression data were not obtained at study admission, no longitudinal clinical information was available, a bacterial infection at the time of study admission was present, or a fungal infection in the absence of a bacterial infection was detected. LASSO regression was performed using three subsets of predictor variables: patient data alone, gene expression data alone, or a combination of patient data and gene expression data. The accuracy of the resultant models was tested on data from the test set. Between March, 2020, and October, 2021, we recruited 536 SARS-CoV-2-positive individuals and between June, 2013, and January, 2020, we recruited 74 participants into the control cohort. After prefiltering analysis and other exclusions, samples from 158 individuals were analysed in the training set and 47 in the test set. The expression of seven host genes (DAPP1, CST3, FGL2, GCH1, CIITA, UPP1, and RN7SL1) in the blood at the time of study admission was identified by LASSO as predictive of the risk of developing a secondary bacterial infection of the respiratory tract more than 24 h after study admission. Specifically, the expression of these genes in combination with a patient's WHO severity score at the time of study enrolment resulted in an area under the curve of 0·98 (95% CI 0·89-1·00), a true positive rate (sensitivity) of 1·00 (95% CI 1·00-1·00), and a true negative rate (specificity) of 0·94 (95% CI 0·89-1·00) in the test cohort. The combination of patient data and host transcriptomics at hospital admission identified all seven individuals in the training and test sets who developed a bacterial infection of the respiratory tract 5-9 days after hospital admission. These data raise the possibility that host transcriptomics at the time of clinical presentation, together with machine learning, can forward predict the risk of secondary bacterial infections and allow for the more targeted use of antibiotics in viral infection. Snow Medical Research Foundation, the National Health and Medical Research Council, the Jack Ma Foundation, the Helmholtz-Association, the A2 Milk Company, National Institute of Allergy and Infectious Disease, and the Fondazione AIRC Associazione Italiana per la Ricerca contro il Cancro.

Bacterial infections in patients with COVID-19: the impact of procalcitonin testing on antibiotics prescription in the real world

BackgroundBacterial infections are not prevalent among patients hospitalized with COVID-19, while unnecessary prescription of antibiotics was commonly observed. This study aimed to determine the impact of procalcitonin testing on antibiotics prescription in the real-world setting.MethodsWe performed a territory-wide retrospective cohort study involving all laboratory-confirmed patients hospitalized in public hospitals in Hong Kong in 2020 with COVID-19. We determined the prevalence of bacterial co-infections (documented infections within 72 h of admission) and secondary bacterial infections (infections after 72 h of admission) and antibiotics consumption, and the correlation between procalcitonin testing and antibiotics prescription.ResultsThe cohort included 8666 patients, with mean age 45.3 ± 19.9 years, 48.5% male, and comorbidities in 26.9%. Among 2688 patients with bacterial cultures performed, 147 (5.5%) had bacterial co-infections, and 222 (8.3%) had secondary bacterial infections. Antibiotics were prescribed for 2773 (32.0%) patients during the hospital admission. Procalcitonin tests were performed for 2543 (29.3%) patients. More patients with procalcitonin testing received antibiotics (65.9% vs. 17.9%, p < 0.001). Procalcitonin testing was associated with 5-fold increased risk of antibiotics prescription after adjusting for confounding variables. At hospital level, procalcitonin testing correlated with antibiotics prescription. Patients with procalcitonin level < 0.5 ng/mL had a lower probability of antibiotics initiation and shorter duration of antibiotics therapy.ConclusionsProcalcitonin testing was not associated with lower prescription of antibiotics. Patients with low procalcitonin level had lower antibiotics exposure, supporting the use of procalcitonin to exclude bacterial infections aiding early stopping of antibiotics among patients hospitalized with COVID-19.

Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis.

Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.

Prevalence of extended-spectrum beta-lactamases producing isolates obtained from patients of pediatric critical care unit in a tertiary care hospital

Background: Over the past decades, antibiotic-resistant Gram-negative bacteria commonly Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae have increased significantly. These microorganisms have great clinical importance because they increase hospital stay of the patients in the intensive care unit (ICU) leading to high morbidity and mortality. Because of their role in increasing morbidity and mortality, this study was performed to isolate extended-spectrum beta-lactamase (ESBL) producing Gram-negative bacilli screened by phenotypical method and further projected into molecular characterization by polymerase chain reaction. Aims and Objectives: The aims and objectives are to isolate the Gram-negative multidrug-resistant strains from clinically suspected bacterial infections in patients of neonatal, sick newborn, and pediatric ICU and to study antibiotic sensitivity pattern of isolated Gram-negative multidrug-resistant strains with special reference to molecular characterization. Materials and Methods: A total of 100 Gram-negative bacilli were isolated. Screening of ESBL positivity was done by double-disk synergy test (combined disc test method). Their antibiogram profile was interpreted. With the use of designed primers, 26 ESBL isolates each of E. coli and Klebsiella spp. were processed for molecular analysis of beta-lactamase family genes TEM and CTX-M. Results: Within the 100 samples, majority of the isolates (45%) were Klebsiella spp. and 40% was E. coli isolates. Highest ESBL-producing organisms were observed within E. coli (65%). Prevalence bla-TEM gene was highest followed by bla-CTX-M. These ESBL-producing organisms were found to be resistant to multiple classes of antibiotics. With extensive ESBL surveillance and proper usage of antibiotics, this threatening rise of antibiotic resistance can be mitigated. Conclusion: Gram-negative isolates showed high resistance to commonly used antibiotics. Significant proportions of them were MDR strains. Such high antibiotic resistance is associated with significant morbidity and mortality among pediatric population. MDR along with possession of ESBL associated resistance genes among Gram-negative bacilli pose a serious problem in therapeutic management of patients. Our study signifies that there is a high probability of Gram- negative bacilli to be multi-drug resistant and ESBL positive and earliest detection of such cases should be made.

Clinical Utility of the Serum Amyloid A Test for the Diagnosis of Bacterial Infections in Patients Visiting the Emergency Room

Clinical Utility of the Serum Amyloid A Test for the Diagnosis of Bacterial Infections in Patients Visiting the Emergency Room

Levofloxacin to Prevent Bacterial Infection in Patients with Acute Myeloid Leukemia Treated By Azacitidine and Venetoclax: A Study from the Dataml Registry

Introduction: Antibioprophylaxis in patients with cancer and neutropenia is controversial and is not a broadly recommended intervention in management of patients with hematological malignancies. Previous study showed that prophylactic treatment with levofloxacin (LEVO) is an effective and well-tolerated strategy to prevent febrile episodes and other relevant infection-related outcomes in patients with cancer and neutropenia, including acute leukemia ( Bucaneve et al., NEJM 2005). However, impact on microbial resistance discouraged the widespread use of this strategy., Venetoclax (VEN) and azacitidine (AZA) combination was recently approved in newly diagnosed patients with AML who are ineligible for intensive chemotherapy. VEN-AZA allowed higher rates of complete remission and longer overall survival but twice the incidence of febrile neutropenia compared to AZA alone making primary antibioprophylaxis a relevant question, especially in patients who are treated as outpatients or discharged after the seven days of AZA treatment. Methods: We retrospectively selected AML patients who received VEN-AZA treatment from the Toulouse-Bordeaux DATAML registry. The two centers have similar management protocols, but patients in Toulouse (but not in Bordeaux) receive antibacterial prophylaxis with LEVO 500 mg/day from day 11 during the neutropenia period following the 1 st course of VEN-AZA, until neutrophil recovery (&amp;gt;0.5 G/l). We included ≥ 18-year-old non-APL de novo or secondary AML receiving VEN-AZA treatment between June 2015 and May 2023, excluding patients that deceased before day 11 VEN-AZA or who were receiving antibiotherapy before start of VEN-AZA. The primary endpoint was the incidence of febrile neutropenia during the first course of VEN-AZA. Secondary endpoints included clinically documented infections, microbiologically documented infections, and safety data. Results: The population included 264 patients, 71 received LEVO as primary antibioprophylaxis during 1 st course of VEN-AZA and 193 received no prophylaxis [antibiotherapy in case of febrile neutropenia, i.e. standard of care (SOC)]. The median age was 69 (range 20-87) years, 55.3% of patients were male, 48.5% of patients received VEN-AZA as front-line treatment and others 51.5% ≥ 2 nd line of treatment. Febrile neutropenia occurred in 32.4% of patients who received LEVO prophylaxis leading to a hospitalization of 100% of patient with antibiotherapy for a median of 10 days (range 2-45), as compared with 38.9% of those in SOC group leading to hospitalization of 73.3% of patient with antibiotherapy for a median of 10 days (range 1-31), (23 of 71 vs. 75 of 193; relative risk, 0.90; IC95% 0.74-1.10; P=0.33). Delay from day 1 VEN-AZA to febrile neutropenia was 23 (range 10-38) and 18 (range 7-44) days in LEVO and SOC groups (p=0.008), respectively. The LEVO group had a significantly lower rate of clinically documented infections (26.1% vs 52.0%, relative risk, 0.65; IC95% 0.46-0.91; P=0.03) (Figure 1A), but similar microbiologically documented infections (30.4% vs 32.0%) (Figure 1B). It is noteworthy that among patients receiving LEVO prophylaxis, no urinary tract infections were reported. The rate of lung infections was considerably reduced (5% vs 25%) as well as gram-negative bacterial infections (50% vs 74%), consistent with LEVO's broad spectrum, including non-fermenting micro-organisms. Anaerobia infections could be due to the lack of activity of LEVO on this bacterial spectrum. There was no difference in frequency of intensive care unit (ICU) hospitalization (1.4% vs 5.2%, P=0.29). No selection of extended spectrum beta-lactamase bacteria nor burden of fluoroquinolone resistance has been detected. Clostridium difficile colitis has been detected in 2 patients, both in SOC group. No adverse musculoskeletal events have been observed. Conclusion: A short course of levofloxacin as primary prophylaxis in AML patients treated with VEN-AZA was well tolerated, seemed to have no impact on microbial resistance and was associated with a lower rate of clinically documented infection but not febrile neutropenia.

2067. Preclinical Characterization of Rationally Designed Microbial Consortia to Prevent Bacterial Infections in Patients with Chronic Liver Disease

Abstract Background In chronic liver disease (CLD), gut microbiome disruption worsens with disease severity and growing evidence suggests it is a key driver of infection risk through a combination of intestinal pathogen expansion from a loss of colonization resistance and dysfunction of the gastrointestinal (GI) barrier. For the SER-147 preclinical program, we evaluated rationally designed cultivated consortia of human commensal bacteria in vitro and in vivo for the ability to reduce the abundance of pathogens commonly observed in patients with CLD, such as Enterococcus and Enterobacteriaceae. Methods Candidate consortia for SER-147 were designed by leveraging genomic data from public observational CLD patient studies and Seres interventional human trial data to include taxa associated with reduced risk of infection and select strains from Seres’ strain library to maximize features associated with decolonizing key pathogens. We developed a novel in vitro gut-ecology model (iGEM) system that propagates human stool-derived microbial communities to evaluate candidate consortia for their ability to reduce titers of vancomycin-resistant Enterococcus faecium (VRE), and both carbapenem-resistant Klebsiella pneumoniae (CR-Kpn) and Escherichia coli (CR-Ec). In vivo, candidate consortia were evaluated for their ability to reduce fecal titers of VRE and CR-Kpn in mouse models of gut pathogen colonization. Results In the iGEM system, following introduction and expansion of select pathogens in the microbial community, intervention with a subset of five unique candidate consortia from the SER-147 program were able to significantly reduce titers of VRE and Cr-Ec compared to controls and in the case of Cr-Kpn, titers were reduced to the limit of detection of the assay (Figure 1). In the in vivo colonization models, oral administration of the same five candidate consortia led to a 1-3 Log10 reduction in VRE and Cr-Kpn fecal titers compared to vehicle-only treated mice (Figure 2).Figure 1.Reduction in abundance of Cr-Kpn, Cr-Ec, and VRE after microbiome intervention in the iGEM system. (A) Human stool-derived microbial communities were passaged anaerobically in 96-well deep well plates, with cultures stamped into fresh deep well plates every 24 hours with different wells representing different treatments and conditions. Individual pathogens were introduced on day 4 of the experiment, followed by a vancomycin pre-treatment from days 5-8. On days 10-16, five unique candidate consortia (DE061, DE456, DE240, DE714, and DE492) were dosed daily as the microbiome intervention. (B, C, D) The titers of Cr-Kpn, Cr-Ec, or VRE were quantified at specific timepoints during the study by plating culture aliquots on selective and differential media. The mean CFU per milliliter of culture was calculated for each arm of the study and plotted on the line graph (N=4 per arm). Error bars represent the standard deviation from the mean. L.O.D., limit of detection.Figure 2:Reduction in abundance of Cr-Kpn and VRE after microbiome intervention in mouse models of gut pathogen colonization. (A) Wild-type C57BL/6 mice underwent antibiotic conditioning prior to pathogen challenge. Following the introduction of pathogen (Day 0) mice were dosed daily vial oral gavage with five unique candidate consortia (DE061, DE456, DE240, DE714, and DE492) as the microbiome intervention or vehicle only for 6 days and fecal titers are monitored for a 3-week period to evaluate pathogen abundance (B,C) The titers of VRE or CR-Kpn were quantified in fecal pellets by plating on selective agar at the indicated time-points. The median (B) CR-Kpn and (C) VRE CFU per gram of feces was calculated for each group and plotted on the line graph (n=9 per group). L.O.D., limit of detection. Conclusion Preclinical assessments in vitro and in vivo support the ability of SER-147 candidate consortia to reduce VRE, CR-Kpn, and CR-Ec abundance in the gut. These results support the potential ability of microbiome therapeutics to reduce the risk of infection in patients with CLD. Disclosures Elizabeth Halvorsen, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Marin Vulić, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Kelsey Barrasso, PhD, Seres Therapeutics: Stocks/Bonds Nicholas Beauchemin, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Jessica Brown, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Nathaniel J. Ennis, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Melissa Mayol, n/a, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Jenna Wurster, PhD, Seres Therapeutics: Paid Employee|Seres Therapeutics: Stocks/Bonds Edward J. O'Brien, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Christopher Ford, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Matthew Henn, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds

371. Clinical Characteristics and Prognoses for Carbapenem-Resistant Bacterial Infections in Patients with Cancer in Japan: A Multicenter Study from the Multi-Drug Resistant Organisms Clinical Research Network (MDRnet)

Abstract Background Carbapenem-resistant bacteria in patients with cancer are concerning due to the high risk of infection and mortality rates; however, the characteristics and prognoses of carbapenem-resistant infections in this population are currently unknown in Japan. We hence investigated the features and outcomes of carbapenem-resistant bacterial infections (CRBI) in patients with cancer in Japan. Methods From April 1, 2019, to March 31, 2022, patients with CRBI who either had cancer or no cancer were prospectively enrolled at eight centers as part of the Multi-Drug Resistant Organisms Clinical Research Network (MDRnet). The primary outcome was the 30-day all-cause mortality rates in patients with and without cancer. Two secondary outcomes were evaluated: 1) composite outcomes including mortality, worsening of clinical course after culture collection, intensive care unit stay, intubation, new dialysis from the date of culture collection to the end of antimicrobial therapy, and readmission within 90 days after discharge; and 2) the length of hospital stay after CRBI excluding death. Results We included a total of 167 patients, with 66 (39.5%) in the cancer group and 101 (60.5%) in the non-cancer group. The 30-day mortality rates in the cancer and non-cancer groups were 18.2% (12/66) and 14.0% (14/101), respectively (p = 0.45), while the composite outcomes in the cancer and non-cancer groups were 56.1% (37/66) and 43.6% (44/101), respectively (p = 0.12). Average duration of hospitalization was not significantly different between the two groups (cancer group, 44.6 days; non-cancer group, 51.0 days; p = 0.55). Propensity score analysis using inverse probability weighting also showed no significant difference in 30-day mortality and average duration of hospitalization (p = 0.22 and 0.98, respectively); however, the composite outcome was significantly higher in the cancer group than in non-cancer controls (odds ratio, 2.41; 95% confidence interval, 1.11–5.21; p = 0.03). Conclusion There was no difference in 30-day mortality rates between the cancer and non-cancer patient groups; however, we found a significant difference in the composite outcome. Patients with cancer who had CRBI experienced a worse clinical course that non-cancer patients. Disclosures Masahiro Suzuki, PhD, KANTO Chemical co., inc.: Grant/Research Support Yasufumi Matsumara, MD, PhD, Beckman Coulter: Grant/Research Support|Presicion System Science: Grant/Research Support|Toyobo: Grant/Research Support David van Duin, MD, PhD, Entasis: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Union: Advisor/Consultant|Utility: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Advisor/Consultant|FujiFilm: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria Sho Saito, MD, PhD, Shionogi &amp; Company, Limited: Grant/Research Support

In vitro activity of tebipenem and comparator agents against bacterial pathogens isolated from patients with cancer

Abstract Background Tebipenem is a broad-spectrum orally administered carbapenem antibiotic that could be an alternative to IV carbapenems. The current study evaluated in vitro activity of tebipenem against bacterial isolates recovered from patients with cancer. Methods A total of 611 bacterial pathogens recently isolated from patients with cancer were tested for susceptibility to tebipenem and comparators. CLSI-approved broth microdilution methods were used. MIC50, MIC90, MIC range and percentage susceptibility calculations were made using FDA breakpoints when available. Results Tebipenem had a low MIC90 for most Gram-positive and Enterobacterales isolates. Tebipenem MIC90 ranged from 0.06 to 0.25 mg/L for all tested Enterobacterales. Conclusions Oral tebipenem has promising activity against clinically significant bacterial pathogens isolated from patients with cancer. Further clinical evaluation of tebipenem for the treatment of bacterial infections in patients with cancer is warranted.

Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency

Abstract Background Antibody-deficient patients are at high risk of respiratory tract infections. Many therefore receive antibiotic prophylaxis and have access to antibiotics for self-administration in the event of breakthrough infections, which may increase antimicrobial resistance (AMR). Objectives To understand AMR in the respiratory tract of patients with antibody deficiency. Methods Sputum samples were collected from antibody-deficient patients in a cross-sectional and prospective study; bacteriology culture, 16S rRNA profiling and PCR detecting macrolide resistance genes were performed. Bacterial isolates were identified using MALDI-TOF, antimicrobial susceptibility was determined by disc diffusion and WGS of selected isolates was done using Illumina NextSeq with analysis for resistome and potential cross-transmission. Neutrophil elastase was measured by a ProteaseTag immunoassay. Results Three hundred and forty-three bacterial isolates from sputum of 43 patients were tested. Macrolide and tetracycline resistance were common (82% and 35% of isolates). erm(B) and mef(A) were the most frequent determinants of macrolide resistance. WGS revealed viridans streptococci as the source of AMR genes, of which 23% also carried conjugative plasmids linked with AMR genes and other mobile genetic elements. Phylogenetic analysis of Haemophilus influenzae isolates suggested possible transmission between patients attending clinic. In the prospective study, a negative correlation between sputum neutrophil elastase concentration and Shannon entropy α-diversity (Spearman’s ρ = −0.306, P = 0.005) and a positive relationship with Berger–Parker dominance index (ρ = 0.502, P &amp;lt; 0.001) were found. Similar relationships were noted for the change in elastase concentration between consecutive samples, increases in elastase associating with reduced α-diversity. Conclusions Measures to limit antibiotic usage and spread of AMR should be implemented in immunodeficiency clinics. Sputum neutrophil elastase may be a useful marker to guide use of antibiotics for respiratory infection.

Risk Factors for Post-Operative Multi-Drug-Resistant Organism Bacterial Infection in Patients With Stanford Acute Type A Aortic Dissection.

Background: To explore the risk factors for multi-drug-resistant organism (MDRO) infection in patients with Stanford acute type A aortic dissection (ATAAD). We conducted a retrospective cohort study using the data of post-operative patients with ATAAD in our hospital. Patients and Methods: This study included 82 post-operative patients with ATAAD in the past decade. They were divided into a MDRO group (n = 31) and a non-MDRO group (n = 51) according to whether they had acquired multi-drug-resistant (MDR) bacterial infection. Multivariable logistic regression was used to analyze the risk factors for MDR infections in patients with ATAAD. Results: The incidence of multi-drug-resistant bacterial infection was 37.80%. Seventeen factors, including hospital stay (p = 0.007), utilization of third-generation cephalosporins (p = 0.0068), antibiotic species of exposure (p = 0.0002), leukocyte-depleted red blood cell suspension dosage (p < 0.0001), fresh frozen plasma dosage (p < 0.0001), application of blood purification (p = 0.0493), and the total antibiotic days of exposure (p = 0.0001) diverged between the two groups (all p < 0.05). The logistic regression analysis revealed that the utilization of third-generation cephalosporins (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.01-5.33; p = 0.0478), antibiotic species of exposure (OR, 5.76; 95% CI, 1.45-22.83; p = 0.0128), leukocyte-depleted red blood cell suspension dosage (OR, 12.43; 95% CI, 2.71-57.07; p = 0.0012), and fresh frozen plasma dosage (OR, 5.05; 95% CI, 1.18-21.56; p = 0.0286) were independent variables for MDRO infections. Among the 23 drug-resistant bacteria detected, Acinetobacter baumannii was the main pathogen. Conclusions: Our study shows that the utilization of third-generation cephalosporins, antibiotic species of exposure, leukocyte-depleted red blood cell suspension dosage, and fresh frozen plasma dosage were independent risk factors for post-operative multi-drug-resistant infection in patients with ATAAD. Acinetobacter baumannii occupied the largest share of resistant bacteria that induce infection in post-operative patients with ATAAD.

Co-infection with Neisseria mucosa in a patient with tuberculous otitis media

Tuberculous otitis media (TOM) is a rare manifestation caused by Mycobacterium tuberculosis with low incidence rates among extrapulmonary tuberculosis cases. Diagnosis is often delayed because of the presence of several clinical manifestations and the high prevalence of secondary bacterial infections. Few reports have attributed secondary bacterial infections in patients with TOM to commensal Neisseria. Thus, understanding the pathogenic mechanisms and clinical features of commensal Neisseria is important, considering its recent presentation as an infection-causing pathogen. Neisseria mucosa is a commensal inhabitant in humans and is generally considered non-pathogenic but can cause infection in rare cases. Here, we report an atypical secondary infection caused by Neisseria mucosa in an 81-year-old woman with TOM being treated for pulmonary tuberculosis. Direct purulent otorrhea smear microscopy revealed no acid-fast bacilli using Ziehl-Neelsen staining, whereas the phagocytosis of gram-negative cocci by white blood cells was confirmed using Gram staining. Otorrhea culture revealed the growth of N. mucosa. Subsequently, M. tuberculosis infection in the otorrhea was identified using a culture-based method. Vigilance is critical for the early detection of TOM to prevent further complications. This report raises awareness regarding TOM and provides insight into the pathogenicity of N. mucosa in otitis media.

Demodex Species and Culturable Microorganism Co-Infestations in Patients with Blepharitis.

We aimed to determine the prevalence of Demodex spp. and bacterial infection in patients with blepharitis and also to investigate the relationship between culturable microorganisms and Demodex spp. in this study. The study included patients diagnosed with blepharitis (n = 128) and volunteers without ocular problems (n = 113). Eyelash sampling was performed by epilating eight lashes, which were then tested for Demodex spp. using a light microscope. The examination consisted of assessing the patient's vision with and without ocular correction and tonus in both eyes and a careful examination of the anterior segment of both eyes. Bacterial identification was performed based on morphological, physiological, and biochemical methods. The prevalence of Demodex spp. was 8.0% in patients from the control group and all patients with blepharitis. Isolated forms of Demodex spp. were detected in all infested patients in the control group and in 58% of patients with blepharitis. A total of 35% of patients with blepharitis had from three to nine forms of Demodex spp., and 7% of patients with blepharitis had more than 10 mites in every field of vision. We found a statistically significant relationship between Demodex spp. infestation and the occurrence of eye dryness and sensations of burning and tearing, redness of the conjunctiva, feeling of a foreign body, loss of eyelashes, Meibomian gland dysfunction, and cylindrical dandruff. There were statistically significant relationships between Demodex sp. infestation and the presence of hyperopia, Meibomian cysts, chronic eyelid inflammation, and the use of eyeglasses. There was also a statistically significant relationship between the occurrence of Demodex spp. and seborrheic dermatitis and diabetes mellitus. Culturable microorganisms of the ocular surface were found in 8.7% of participants who were uninfested and in all patients infested with D. folliculorum. We isolated Staphylococcus aureus, Acinetobacter baumannii, Streptococcus pneumoniae, Klebsiella oxytoca, and Bacillus spp. from the conjunctival sac only in patients infested with D. folliculorum. This indicates an increased probability of colonization by pathogenic bacteria in patients with demodicosis. Therefore, patients infested with D. folliculorum should undergo a microbiological examination of conjunctival swabs.