Suspicion Of Infection Research Articles

Evaluation of the diagnostic utility of metagenomic next-generation sequencing testing for pathogen identification in infected hosts: a retrospective cohort study.

Metagenomic next-generation sequencing (mNGS) testing identifies thousands of potential pathogens in a single blood test, though data on its real-world diagnostic utility are lacking. Determine the diagnostic utility of mNGS testing in practice and factors associated with high clinical utility. Retrospective cohort study of mNGS tests ordered from June 2018 through May 2020 at a community teaching hospital. Tests were included if ordered for diagnostic purposes in patients with probable or high clinical suspicion of infection. Exclusions included patient expiration, hospice care, or transfer outside of the institution. Utility criteria were established a priori by the research team. Two investigators independently reviewed each test and categorized it to either high or low diagnostic utility. Reviewer discordance was referred to a third investigator. The stepwise multiple regression method was used to identify clinical factors associated with high diagnostic utility. Among 96 individual tests from 82 unique patients, 80 tests met the inclusion criteria for analysis. At least one potential pathogen was identified in 58% of tests. Among 112 pathogens identified, there were 74 bacteria, 25 viruses, 12 fungi, and 1 protozoon. In all, 46 tests (57.5%) were determined to be of high diagnostic utility. Positive mNGS tests were identified in 36 (78.3%) and 11 (32.4%) of high and low diagnostic utility tests, respectively (p < 0.001). Antimicrobials were changed after receiving test results in 31 (67.4%) of high utility tests and 4 (11.8%) of low utility tests (p < 0.0001). In the multiple regression model, a positive test [odds ratio (OR) = 10.9; 95% confidence interval (CI), 3.2-44.4] and consultation with the company medical director (OR = 3.6; 95% CI, 1.1-13.7) remained significantly associated with high diagnostic utility. mNGS testing resulted in high clinical utility in most cases. Positive mNGS tests were associated with high diagnostic utility. Consultation with the Karius® medical director is recommended to maximize utility.

Relationship of Troponin I in Septic Patients Without Cardiac Disease

Background: Septic shock, marked by high morbidity and mortality, entails multiple organ dysfunction. Troponin I (TnI), linked to cardiac injury, rises in septic patient’s sans prior cardiac disease, hinting at myocardial involvement. Methods: A prospective analysis was conducted on n=280 samples collected from patients hospitalized between March and February of 2023, who presented with clinical suspicion of infection. TnI levels were measured upon admission, and patient demographics, clinical characteristics, and outcomes were recorded. Results: Among the patients, 45% exhibited elevated TnI levels upon ICU admission. Of these, 65% progressed to severe sepsis or septic shock during their hospital stay. Additionally, 30% of patients with elevated TnI levels experienced adverse outcomes, including increased mortality and prolonged hospitalization. The mean TnI level in septic patients without known cardiac disease was 0.78 ng/mL (standard deviation: 0.32 ng/mL). Elevated TnI levels showed a significant association with sepsis severity, as evidenced by higher Sequential Organ Failure Assessment (SOFA) scores (p &lt; 0.05), increased in-hospital mortality (p &lt; 0.01), and longer ICU stays (p &lt; 0.05). Conclusions: Elevated TnI levels in septic patients without cardiac disease suggest myocardial involvement in sepsis. TnI's association with adverse outcomes highlights its potential as a prognostic marker, warranting further research for clinical implications.

Early Prediction of Bloodstream Infection with Complete Blood Count Parameters: an Ex-Vivo Human Whole Blood Model.

Despite the advanced laboratory technologies available today, blood culture is the gold standard method in the diagnosis of bloodstream infections. Automated blood culture devices give blood culture results for laboratories approximately in 2 - 3 days up to 7 days. Moreover, some microorganisms like nonreproducible bacteria, fungi or viruses cannot be produced in culture. Among all samples taken for blood culture on suspicion of infection approximately 10% are determined as positive whereas the false positive rate due to contamination is 5%. Especially in life-threatening severe conditions such as sepsis early diagnosis and prompt treatment are crucial. Based on this the aim of this study is to investigate complete blood count parameters as potential early markers in Escherichia coli, Staphylococcus aureus and Candida albicans bloodstream infections using an ex vivo whole blood model. Blood samples collected from healthy donors (n = 10) were treated with suspensions containing a certain concentration of microorganisms (107 CFU/mL for both E. coli ATCC 25922 and S. aureus ATCC 29213, 106 CFU/mL for C. albicans ATCC 14053). After bacteremia and candidemia were induced, complete blood count parameters were analyzed hourly in the samples until the end of the 4th hour with a Mindray BC-6800 hematology analyzer. Statistical analysis was performed by Tukey-Kramer post-hoc multiple comparison test and statistical significance was accepted as p < 0.05. When platelet derived parameter baseline values were compared to hourly values in E. coli and S. aureus induced whole blood samples, it was found that the decrease in PLT, P-LCC and the increase in IPF% was significant from the first hour whereas the increase in IMG% was found to be significant only from the 3rd hour onward. In the experiments with C. albicans, it was observed that the increase in IPF% and IMG% was significant from the 2nd and 3rd hour onward, respectively. There was no relationship between MPV, P-LCR, and NLR baseline and hourly results in any microorganism induced model. IPF% can guide clinicians in the early diagnosis and management of treatment of infections caused by S. aureus, E. coli, and C. albicans.

Imaging of MSK infections in the ER.

Musculoskeletal infections in the ER are not an uncommon presentation. The clinical context is critical in determining the suspicion for infection and degree of tissue involvement which can involve all layers from the skin to bones. The location, extent, and severity of clinically suspected infection directly relate to the type of imaging performed. Uncomplicated cellulitis typically does not require any imaging. Localized and superficial infections can mostly be evaluated with ultrasound. If there is a diffuse site (an entire extremity) or suspected deeper involvement (muscle/deep fascia), then CT is accurate in diagnosing, widely available, and performed quickly. With potential osseous involvement, MRI is the gold standard for diagnosing acute osteomyelitis; however, it has the drawbacks of longer scan times, artifacts including patient motion, and limited availability.

Pediatric central nervous system infections in the Amazon: clinical and laboratory profiles.

Central nervous system (CNS) infections are important causes of mortality and morbidity in children, and they are related to severe problems such as hearing loss, neurological sequelae, and death. The objective was to describe clinical and laboratory exam profiles of children who were diagnosed with CNS infections. We conducted a cross-sectional study based on medical records, which included pediatric patients aged from 3 months to 15 years, with a clinical suspicion of CNS infection between January 2014 to December 2019. The pathogens were confirmed in cerebrospinal fluid (CSF) samples using Gram staining, cell culture, molecular diagnostics (PCR and qPCR), and serology. Out of the 689 enrolled patients, 108 (15.6%) had laboratory-confirmed infections in CSF. The most common bacterial pathogens isolated from the culture were Neisseria meningitidis serogroup C in 19, Streptococcus pneumoniae in 11, and Haemophilus influenzae in seven samples. The viruses identified were Enterovirus, Cytomegalovirus, Varicella-zoster virus, Epstein-Barr virus, and arbovirus. No patient was found to be positive for Herpes simplex virus 1 and 2. Patients with viral infections showed altered levels of consciousness (p = 0.001) when compared to bacterial infections. This study shows the presence of important vaccine-preventable pathogens, and different families of viruses causing CNS infections in the pediatric patients of Manaus.

Prevalence, Risk Factors, Treatment, Outcome, and Diagnosis of COVID-19-Associated Pulmonary Aspergillosis Using a Serum Galactomannan Assay

Background: Coronavirus-associated pulmonary aspergillosis (CAPA) is defined as invasive pulmonary aspergillosis (IPA) occurring in patients with COVID-19 infection. Objectives: This study aimed to identify CAPA patients and describe their clinical-epidemiological characteristics in Ahvaz, Iran, from the third to the fifth COVID-19 waves. Methods: The serum galactomannan (GM) antigen assay was used to detect CAPA in 257 COVID-19 hospitalized patients according to the EORTC/MSGERC (European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium) 2020 criteria. The demographic and clinical data, host risk factors, lung radiographic imaging, laboratory findings, antifungal agents used, and the outcomes of the patients were extracted in cases that were available. All findings were statistically analyzed. Results: Of the 257 patients, 114 (44.35%) were positive for GM levels (CAPA cases). The demographic and clinical information of 51 cases showed that diabetes mellitus (25.5%) was the most common underlying condition, followed by oropharyngeal candidiasis (22%) and hypertension (21.6%). In both surviving and deceased patients, the frequency of CAPA in older ages was statistically significant (r = 0.519; P &lt; 0.0001). In surviving individuals, GM had a significant relationship with age (r = 0.520; P = 0.032), blood glucose (BS; r = 0.497; P = 0.043), diagnosis of hyperglycemia during hospitalization (P = 0.039), and diabetes mellitus (P = 0.039). In deceased patients, the frequency of CAPA in older ages was statistically significant (r = 0.503; P = 0.002). Galactomannan had a significant association with the variables of age (r = 0.503; P = 0.002) and suspicion of fungal infection (P = 0.003). Conclusions: The prevalence of CAPA was high in critically ill patients with COVID-19. Diabetes mellitus, hyperglycemia, and old age are the main factors that predispose COVID-19 patients to IPA.

Dermatology practice updates in mycobacterial disease.

Atypical mycobacterial infections are commonly acquired through exposure to water, and tuberculosis remains highly endemic in many parts of the world. In this era of global connection, travel, and immigration, it is more important than ever to maintain a high index of suspicion for infection from cutaneous tuberculosis and atypical mycobacteria. Epidemics related to surgical procedures have been related to inadequate sterilization, as almost 50% of public water supplies harbor mycobacteria. Improved diagnostic techniques for these microbes, including Auramine-Rhodamine staining and rapid detection of mycobacteria and drug susceptibilities through PCR and MALDI-TOF, have improved detection and treatment outcomes. Given an increasing number of patients on immunosuppressive therapies, clinicians must remain vigilant.

Diagnostic accuracy of procalcitonin for bacteremia in the emergency department: a systematic review

Obtaining blood cultures (HC) is performed in 15% of the patients treated with suspicion of infection in the Hospital Emergency Services (ED) with a variable diagnostic yield (2-20%). The 30-day mortality of patients with bacteremia is two or three times higher than the rest with the same process. Procalcitonin (PCT) is a biomarker that has been used as a tool to help predict bacteremia in HEDs. The main objective of this systematic review is to investigate the diagnostic accuracy of PCT in predicting true bacteraemia in adult patients treated with clinical suspicion of infection in the ED, as well as to identify a specific PCT value as the most relevant from the clinical decision diagnostic point of view that can be recommended for decision making. A systematic review was performed following the PRISMA guidelines in the PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials.gov databases from January 2010 to May 31, 2023 without language restrictions and using a combination of MESH terms: "Bacteremia/ Bacteraemia/ Blood Stream Infection", "Procalcitonin", "Emergencies/ Emergency/ Emergency Department" and "Adults". Observational cohort studies and partially an systematic review were included. No meta-analysis techniques were performed, but the results were compared narratively. A total of 1,372 articles were identified, of which 20 that met the inclusion criteria were finally analyzed. The included studies represent a total of 18,120 processed HC with 2,877 bacteraemias (15.88%). Ten studies were rated as high, 9 moderate and 1 low quality. The AUC-COR of all the studies ranges from 0.68 (95% CI: 0.59-0.77) to 0.98 (95% CI: 0.97-0.99). The PCT value >0.5 ng/ml is the most widely used and proposed in up to ten of the works included in this systematic review, whose estimated mean yield is an AUC-COR of 0.833. If only the results of the 6 high-quality studies using a cut-off point (PC) >0.5 ng/mL PCT are taken into account, the estimated mean AUC-COR result is 0.89 with Se of 77.6% and It is 78%. PCT has a considerable diagnostic accuracy of bacteraemia in patients treated in EDs for different infectious processes. The CP>0.5 ng/ml has been positioned as the most suitable for predicting the existence of bacteraemia and can be used to reasonably rule it out.

Congenital herpes simplex with ophthalmic and multisystem features: a case report

BackgroundNeonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement.Case presentationA preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition.DiscussionNeonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics.ConclusionsIn the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.

Performance of clinical metagenomics in France: a prospective observational study

Metagenomic next-generation sequencing (mNGS) allows untargeted identification of a broad range of pathogens, including rare or novel microorganisms. Despite the recognition of mNGS as a valuable diagnostic tool for infections, the most relevant indications for this innovative strategy remain poorly defined. We aimed to assess the determinants of positivity and clinical utility of mNGS. In this observational study, we prospectively performed short-read shotgun metagenomics analysis as a second-line test (in cases of negative first-line test or when the symptoms were not fully explained by initial positive results) or as a first-line test in life-threatening situations requiring urgent non-targeted pathogen identification at the Necker-Enfants Malades Hospital (Paris, France). All sample types, clinical indications, and patient populations were included. Samples were accompanied by a mandatory form completed by the senior clinician or pathologist, on which the clinical level of suspected infection (defined as high or low) was indicated. We assessed the variables (gender, age, immune status, initial suspicion of infection, indication, and sample type) associated with mNGS pathogen detection using odds ratios (ORs) from multivariate logistic regression. Additional investigations were carried out using specific PCR or culture techniques, to confirm positive mNGS results, or when infectious suspicion was particularly high despite a negative mNGS result. Between Oct 29, 2019, and Nov 7, 2022, we analysed 742 samples collected from 523 patients. The initial suspicion of infection was either high (n=470, 63%) or low (n=272, 37%). Causative or possibly causative pathogens were detected in 117 (25%) samples from patients with high initial suspicion of infection, versus nine (3%) samples analysed to rule out infection (OR 9·1, 95% CI 4·6-20·4; p<0·0001). We showed that mNGS had higher odds of detecting a causative or possibly causative pathogenic virus on CNS biopsies than CSF samples (4·1, 1·7-10·7; p=0·0025) and in samples from immunodeficient compared with immunocompetent individuals (2·4, 1·4-4·1; p=0·0013). Concordance with conventional confirmatory tests results was 103 (97%) of 106, when mNGS detected causative or possibly causative pathogens. Altogether, among 231 samples investigated by both mNGS and subsequent specific tests, discordant results were found in 69 (30%) samples, of which 58 (84%) were mNGS positive and specific tests negative, and 11 (16%) mNGS negative and specific tests positive. Major determinants of pathogen detection by mNGS are immune status and initial level of suspicion of infection. These findings will contribute, along with future studies, to refining the positioning of mNGS in diagnostic and treatment decision-making algorithms. Necker-Enfants Malades Hospital and Institut Pasteur. For the French translation of the abstract see Supplementary Materials section.

Pharmacogenetics and Pharmacokinetics of Posaconazole in Patients with Acute Myeloid Leukemia: Useful Tools for Antifungal Stewardship

DISCUSSION INTRODUCTION Antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy is usually recommended [1]. Few studies described the clinical impact of suboptimal posaconazole plasma concentrations during prophylaxis, which may be associated with a higher risk of invasive fungal infections (IFI) and a strong impact on clinical outcome [2]. ENDPOINT: The primary endpoint of this study was to evaluate weekly posaconazole Cthrough plasma concentration in AML patients treated with induction chemotherapy. Since polymorphisms of genes encoding enzymes, transporters and transcription factors were also analyzed a possible association amongst plasma exposure, genetic polymorphisms, risk of breakthrough infection and clinical outcam was evaluated . MATERIALS AND METODS: This was a prospective, single center study at “City of Health and Science”, Molinette Hospital in Turin, Italy. Adult Patients with AML undergoing induction chemotherapy admitted to Haematological wards, were enrolled between March 2023 and July 2023. Antifungal prophylaxis with oral posaconazole, 300mg bid the first day and 300 mg qd thereafter was given. Biological samples (plasma for posaconazole quantificatication and whole blood for genetics) were obtained for each patient after loading dose and then posaconazole C trough were evaluated weekly (at 7, 14, 21 and 28 days). The Following genes were evaluated: UGT1A1, UGT1A3, ABCB1, ABCG2, ABCC2, ABCB11, SLCO1B1, SLCO1B3, SLC22A6, PXR, CAR, VDR, CYP27B1, CYP24A1, GC. The mortality was assessed at day 28 from hospital admission. Invasive fungal disease (IFD) was defined as the occurence of a proven or probable IFD according to the European Organization for Research and Treatment of Cancer/National insitute of Allergy and Infection Diseases Micoses Study Group Criteria (EORTC/MSG) revised definitions [3]. Furthermore, according to the clinical suspicion of breakthrough infection, the switch from prophylaxis to antifungal therapy was also recorded as well as antifungal restaging before treatment change. RESULTS: Twenty patients were included: 9 were women (45%) with a median age of 67 years old (±10.5) and a median Charlson Comorbidity Index of 5 (±1.3). Mean posaconazole C through plasma concentrations are reported in Table 1 and were in range for all the different timepoints. According to EORTC criteria, two patients (10%) had a probable IFI on day 14, and antifungal therapy with liposomal amphotericin B was started [3]. One of those patients had low C trough value at time of suspected breaktrough infection (T 14; 0.2 microg/L 9). The 28 day mortality was 10%, due to the haematological underlying disease. Regarding pharmacogenetic analysis, posaconazole C trough at day 7 and 14 was associated with ABCB1 1236 polymorphism with p=0.022 and p=0.038, respectively. Furthermore, VDR ApaI (p=0.010), VDR TaqI (p=0.023), VDR BsmI (p=0.042), ABCB11 (p=0.023) and UGT1A3 023 (p=0.023) genetic variants were reported in patients with probable IFI. There is a potential impact of the use of posaconazole plasma levels monitoring and associated pharmacogenetics to evaluate the risk of underexposure during antifungal prophylaxis, but also at antifungal restaging before treatment switch. These useful tools may help clinicians to identify patients with a higher risk for under-effective plasma concentrations of posaconazole and can be used to improve antifungal stewardship approach in this setting. The utility of such approaches should also be evaluated in azole-to-azole strategies BIBLIOGRAPHY Olivia White et al. Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia. J Oncol Pharm Pract 2023 May 15;10781552231175825. doi: 10.1177/10781552231175825.Tang LA et al. Risk factors for subtherapeutic levels of posaconazole tablet. J Antimicrob Chemother. 2017 Oct 1;72(10):2902-2905. doi: 10.1093/jac/dkx228. PMID: 29091205Peter Donnelly et al. Revision and update of the Consensus definition of Invasive Fungal Disease from the European Organization for Research adn Treatment of Cancer and the Mycoses study Group Education and Research Consortium. Clin Infect Dis 2020 Sep 12;71(6):1367-1376. doi: 10.1093/cid/ciz1008.

741. Assessing the Concordance of MRSA Carriage Screening with MRSA Infections

Abstract Background There is a lack of research on MRSA surveillance in children. This study focused on children with confirmed MRSA infections to determine the utility of MRSA screens in guiding empiric anti-MRSA treatment for children without history of MRSA infection. We examined the concordance of screens to assess for differences by infection type, and used statistical analysis to determine significant contributors to concordance. Methods Pediatric hospital patients admitted from 2002-2022 were included. Subjects had MRSA infections subsequent to a MRSA surveillance screen performed in the preceding year. Statistical analysis, namely multivariable and binomial regression, identified associations between MRSA screens and infections. Number needed to treat analysis calculated the utility of re-screening. Results Among 246 subjects, 39.0% had concordant screens. 151 (61.4%) screens were obtained in the two weeks preceding infection. Sensitivity for bacteremia was 50.0% (n=42), for ET/respiratory 44.4% (n=81), for SSTI 29.4% (n=102). For children under 6 months of age, sensitivity was 35.9% (n=78). Multivariable analysis significantly associated days since MRSA screening and decreasing likelihood of concordance. Binomial regression modeled the probability of concordance to drop below 50.0% for all infections after four days, after six days for bacteremia specifically, and twelve days for ET/respiratory infections. Probability of Concordance Over Time The probability of MRSA screening concordance over time based upon binomial prediction modeling. Each line represents the probability of concordance on a given day subsequent to MRSA screening. Number Needed to Treat (test) Analysis A theoretical control arm of patients receiving no re-screening is compared to a theoretical treatment arm receiving re-screening. Each column represents the number needed to re-screen (for a given number of days) to predict one MRSA infection. Absolute risk reduction is overlaid. Conclusion The concordance of screens was far lower than NPV found in past studies. Bacteremia concorded at 50.0%, ET/respiratory infections 44.4%, SSTI 29.4%. The number of days elapsed since MRSA screening proved the only significant covariate. When that covariate modeled the probability of screening concordance with infection, 7 days represented when the probability of concordance fell to or dropped below 50.0% for infection types. Only patients with a known MRSA infection were included in our study, and concordance of screens was far lower than NPV found in past studies; previous results may have been impacted by low prevalence to inform high NPV. We suggest that negative MRSA screens should not invalidate reasonable suspicion for MRSA infection in patients with high pre-test probabilities for infection. Re-screening patients may optimize concordance. Disclosures All Authors: No reported disclosures

Case Series: Mixed Infectious Keratitis by Pythium insidiosum and Fungal Species.

This case series is the first to illustrate mixed infection from Pythium sp. and fungal species in corneal ulcer. This case series aimed to alert all toward the possibility of both Pythium sp. and fungal species infection in case of nonresponding corneal ulcer treated with either antifungals or antipythium drugs alone. Increased suspicion of mixed infection in case of nonresponding fungal/ Pythium keratitis may facilitate early and prompt management. Six patients presented with signs of either fungal or Pythium keratitis. They underwent ophthalmological examinations, smear examinations, cultures, and polymerase chain reaction (PCR). Therapeutic penetrating keratoplasty was performed in cases where symptoms worsened after treatment with either antifungal or antipythium drugs. The half corneal button (HCB) was shared for histopathological and microbiological examinations. In the first case, smear examination from corneal scraping (CS) revealed Pythium -like filaments, which were confirmed with PCR; however, Aspergillus nidulans grew in culture. In the second case, iodine-potassium iodide (IKI) staining was positive for Pythium ; however, PCR was positive for both Pythium and fungus, which was further confirmed by DNA sequencing. In the third case, IKI staining and HCB were positive for Pythium ; however, PCR was positive for fungus, which was identified as Candida saitoana with DNA sequencing. In the fourth case, Pythium grew in the CS culture; however, Candida sp. grew in the HCB culture. In the fifth case, Cladosporium sp. grew in culture from CS; however, Pythium insidiosum grew from the anterior chamber exudate after therapeutic penetrating keratoplasty. In the sixth case, smear examination revealed septate fungal filaments, and Cladosporium sp. grew in culture; however, HCB on histopathological examination showed features of Pythium keratitis. In unresponsive cases of Pythium or fungal keratitis, diagnostic modalities such as IKI and PCR should be implemented as a routine practice, in addition to smears and cultures.

2718. Prevalence of Infections Following Anti-CD30 Targeted Chimeric Antigen Receptor T-cell Therapy for Relapsed and Refractory Lymphoma

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies. Clinical trials have demonstrated anti-CD30 CAR T-cell efficacy in patients with CD30+ malignancies such as Hodgkin lymphoma, but little is known about post-treatment infections. Understanding infections in this context is necessary to inform antimicrobial prophylaxis and treatment guidelines. The purpose of this project was to provide the first known characterization of infections in patients who received anti-CD30 CAR T-cell therapy. Methods Ours was a retrospective cohort study of adult patients receiving anti-CD30 CAR-T cells between 2016 and 2021. For the year following therapy, we tracked viral, bacterial, and fungal infections with both a microbiological confirmation or strong clinical suspicion of infection. Results 62 patients received anti-CD30 CAR T-cell therapy during the study period. The median age was 40.9 years, 35.5% were female, 79.0% were of European ancestry, and 93.5% were Not Hispanic or Latino. 77.4% of patients’ primary malignancy was Hodgkin’s lymphoma. 56.5% received Fludarabine and Bendamustine as the preparatory regimen (Table I). Five patients were lost to follow-up and were not included in infection analysis. Overall, there were 37 infectious events in 25 patients (25/57, 43.9%). 43.2% of infections happened within 30 days, 35.1% within 31-90 days, and 21.6% within 90 days to one year. Viral infections were the most common overall (48.6%) and within each time period (Table II). The most common pathogen was Varicella Zoster (10.8%); none of these patients were on valacyclovir prophylaxis at the time of infection. The lung was the most common site of infection overall (29.7%) (Figure 1). Death due to infection was seen in one patient during the study period. Table showing the demographic characteristics of the study cohort including age, gender, race, ethnicity, malignancy, and preparatory regimen. Table capturing infection characteristics including total infections, patients with an infection, and microbiology of the infections overall and broken down by time period.Figure 1.Infectious Organisms and Site of Infection Two bar charts with the top bar chart demonstrating the frequency of each infectious organism and the bottom bar chart demonstrating the frequency of each infection site. Conclusion Infections following anti-CD30 CAR T-cell therapy are most common within 30 days following therapy though risk persists through one-year post-therapy. Viral infections were the most prevalent which differs from reports with anti-CD19 CAR T-cell therapy in which bacterial infections were most common. These results may inform future antimicrobial guidelines for patients receiving these therapies. Disclosures Manish K. Saha, MD, Novavax: Stocks/Bonds Melody Smith, MD, MS, BMS: Advisor/Consultant

Seasonality of Microbiology of Combat-Related Wounds and Wound Infections in Afghanistan.

Battlefield-related wound infections are a significant source of morbidity among combat casualties. Seasonality of these infections was demonstrated in previous conflicts (e.g., Korea) but has not been described with trauma-related health care-associated infections from the war in Afghanistan. The study population included military personnel wounded in Afghanistan (2009-2014) medevac'd to Landstuhl Regional Medical Center and transitioned to participating military hospitals in the United States with clinical suspicion of wound infections and wound cultures collected ≤7 days post-injury. Analysis was limited to the first wound culture from individuals. Infecting isolates were collected from skin and soft-tissue infections, osteomyelitis, and burn soft-tissue infections. Data were analyzed by season (winter [ December 1-February 28/29], spring [March 1-May 31], summer [June 1-August 31], and fall [September 1-November 30]). Among 316 patients, 297 (94.0%) sustained blast injuries with a median injury severity score and days from injury to initial culture of 33 and 3.5, respectively. Although all patients had a clinical suspicion of a wound infection, a diagnosis was confirmed in 198 (63%) patients. Gram-negative bacilli (59.5% of 316) were more commonly isolated from wound cultures in summer (68.1%) and fall (67.1%) versus winter (43.9%) and spring (45.1%; P < .001). Multidrug-resistant (MDR) Gram-negative bacilli (21.8%) were more common in summer (21.8%) and fall (30.6%) versus winter (7.3%) and spring (19.7%; P = .028). Findings were similar for infecting Gram-negative bacilli (72.7% of 198)-summer (79.5%) and fall (83.6%; P = .001)-and infecting MDR Gram-negative bacilli (27.3% of 198)-summer (25.6%) and fall (41.8%; P = .015). Infecting anaerobes were more common in winter (40%) compared to fall (11%; P = .036). Gram-positive organisms were not significantly different by season. Gram-negative bacilli, including infecting MDR Gram-negative bacilli, were more commonly recovered in summer/fall months from service members injured in Afghanistan. This may have implications for empiric antibiotic coverage during these months.

Surge of lower respiratory tract group A streptococcal infections in England in winter 2022: epidemiology and clinical profile

BackgroundFollowing low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response. MethodsWe undertook a case-series analysis using multiple routine data sources, exempted from ethics approval or patient consent. We identified iGAS cases in England in children younger than 15 years with an LRTI reported between Oct 1 and Dec 21, 2022, using UKHSA laboratory surveillance data (GAS detected in LRT specimens) and notifications by clinicians and Health Protection Teams (HPTs). Symptoms, diagnoses, health-care interactions, and outcome (death or recovery) data were obtained from HPT case management notes, the National Child Mortality Database, and the NHS Digital Emergency Care Dataset. FindingsWe identified 147 cases of LRTI iGAS in children across England (77 [52%] male, 70 [48%] female; median age 4 years [IQR 2–6]). Predominant ethnicities were White (74 [65%] of 113 with known ethnicity) and Asian (18 [16%] of 113). Most reported symptoms were fever (90 [75%] of 120 children with ≥1 symptom) and cough (60 [50%] of 120), and 71 (48%) of all 147 children had a diagnosed respiratory viral coinfection (most commonly hMPV and RSV). 127 (86%) of children attended an emergency department, 31% (n=36/114 with onset date) at least twice within 21 days after symptom onset. 37 (25%) of 147 children died, with a median time from symptom onset to death of 4 days (IQR 3–7). Of 32 children with sample dates, 16 (84%) were tested for GAS on or after the day they died. Over half of deaths (21 [57%] of 37 deaths) occurred in the community after rapid deterioration, of whom 18 had previous contact with health-care services documented. InterpretationThe UK saw an unusual rise in iGAS LRTIs in children in late 2022. One in four cases died, over half in the community. Non-specific symptoms, viral symptoms, or positive virology might have lowered suspicion of bacterial infection. Although the use of multiple available data sources expedited the analysis, varying data completeness limited interpretation. Our study highlights the need for earlier detection and identification of effective measures to prevent death. FundingNone.

Optimizing treatment of mild to moderate ulcerative colitis: CU-forum Delphi consensus

Background and objectiveUlcerative colitis (UC) clinical guidelines include the best available evidence, although not all clinical situations are answered, so their management can be controversial. The aim of this study is to identify the situations of mild to moderate UC susceptible to controversy and to evaluate the degree of agreement or disagreement with specific proposals. MethodsInflammatory bowel disease (IBD) expert discussion meetings were used to identify criteria, attitudes and opinions regarding the management of UC. A Delphi questionnaire was then developed with 60 items regarding antibiotics, salicylates and probiotics; local, systemic and topical corticosteroids; and immunosuppressants. ResultsConsensus was reached in 44 statements (73.3%); 32 in agreement (53.3%) and 12 in disagreement (20.0%). Some of them were: it is not necessary the systematic use of antibiotics despite the severity of the outbreak, being reserved when there is suspicion of infection or systemic toxicity; when faced with a mild-moderate outbreak of UC and in patients who do not respond to aminosalicylates, it is appropriate to use a dose of beclomethasone of 10 mg/day for one month and 5 mg/day for another month; it is advised that the dose of azathioprine be administered in a single dose. ConclusionsIBD experts agree on most of the proposals identified for managing mild to moderate UC and there is a need for scientific evidence in some specific situations where expert opinion may be helpful.

Diffuse Cardiac Uptake Misdiagnosed as Cardiac Amyloidosis in Bone Scan.

In this presented case, a 77-year-old woman with an implanted prosthesis and ongoing knee pain underwent a bone scan using 99mTc-hydroxydiphosphonate (HDP) in suspicion for bone infection. An incidental finding from this scan revealed diffuse cardiac uptake, necessitating further diagnostic procedures to exclude the possibility of cardiac amyloidosis. In the subsequent 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scan and SPECT images, no perceptible cardiac uptake was observed at all. Upon retrospective review of the patient's medical records, she received 1000 mg of ferric carboxymaltose for iron-deficient anemia the day before the 99mTc-HDP bone scan. Therefore, it was assumed that the diffuse and temporary cardiac activity was due to the transient iron overload. We present and share these bone scan images in order to avoid possible future misinterpretation of cardiac amyloidosis.

Outbreak of nosocomial sepsis in NICU by multidrug-resistant Klebsiella pneumoniae: Diagnostic challenges

Purpose: Nosocomial infections are a serious problem in neonatal intensive care units (NICU) – they are one of the main causes of morbidity and mortality among preterm newborns. Material/methods: We present a prospective clinical-epidemiological study of an outbreak of 7 cases of culture-proven multidrug-resistant (MDR) Klebsiella pneumoniae late onset sepsis in a period of 2 months in a tertiary level NICU in Pleven, Bulgaria. The risk factors, early clinical presentation, laboratory changes, course of infection, treatment, and outcome were evaluated. Results: Three of our patients were term infants, the other four patients were preterm aged from 25 to 36 gestational weeks. The most possible routs of transmission of the infection were: venous lines, mechanical ventilation, tube feeding. Аll of the mentioned were present in one extremely immature patient. Early clinical signs included skin color changes, abnormal muscle tone, respiratory failure. Laboratory tests taken at the time of onset revealed leucopenia and/or thrombocytopenia in a half of the cases and usually C-reactive protein remained normal, but in all cases the I/T ratio increased significantly. The clinical course varied from fulminant deterioration to easily controlled condition. Treatment with Meropenem was started at the time of clinical suspicion of infection, according to the antibiogram of the first cases. No fatal outcome was observed. Conclusion: Main causes for the outbreak of hospital acquired infection were overcrowding of the NICU, admission of patients from lower-level hospitals, insufficient working staff, especially midwifes. The early diagnosis and proper antimicrobial treatment were crucial for the favorable outcome.

Tick-Borne Encephalitis in a 6-Year-Old Patient: A Case Report.

Background: Tick-Borne Encephalitis virus (TBEV) is a positive-sense single-stranded RNA virus belonging to the Flaviviridae family. TBEV transmission typically occurs through infected Ixodes tick bite or by consumption of unpasteurised milk from infected cattle. Case report: We report the clinical, neuroimaging, electroencephalogram (EEG), and laboratory (microbiological tests and spinal tap) data of a 6- year-old boy with Tick-borne encephalitis. Our patient presented with a biphasic course, initially with a myositis-like picture on his first admission to the emergency department, and after a few days with an encephalitic picture, resulting in a second hospitalization. EEG showed focal slow activity, while his brain magnetic resonance imaging (MRI) showed a signal abnormality, which completely resolved on repeat MRI after 3 months. Conclusion: To our knowledge, this is the youngest patient presenting with myositis in the first phase of Tick-borne encephalitis (TBE). In the presence of a biphasic clinical course, with previous myositis, aspecific MRI changes in the thalamic and midbrain regions and an EEG documenting slowed bioelectrical activity should prompt suspicion of TBEV infection.