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Background Recent advances in shotgun metagenomic sequencing (sMGS) for detecting microbial cell-free DNA (mcfDNA) in peripheral blood have shown promise across various patient populations. This study evaluates the application of sMGS for diagnosing osteoarticular infections (OAIs), a condition with significant diagnostic challenges. Methods We conducted a retrospective analysis on 73 patients suspected of OAIs at the Mayo Clinic from 2019 to 2023, incorporating mcfDNA sMGS (Karius test [KT]) into their diagnostic evaluation. We categorized the clinical impact of KT on OAI diagnoses and management into 4 distinct outcomes. (1) KT was able to confirm an established diagnosis, (2) KT supported noninfectious diseases diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Results In our cohort, KT was performed in 73 patients. Among the infected individuals, KT yielded positive results in 22 of 43 (51.2%) cases. Of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, whereas in 5 (22.7%) cases, the KT established an unsuspected diagnosis. Native vertebral osteomyelitis diagnosis (P <.001) or OAIs with concomitant presence of endocarditis or endovascular infection (P =.005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result. Conclusions In complex OAIs, KT enhanced diagnostic accuracy by 11.6%, proving especially beneficial in diagnosing native vertebral osteomyelitis and infections with concurrent endocarditis or endovascular complications. Our findings underscore the utility of KT in the diagnostic workflow for challenging OAI cases, potentially altering clinical management for a significant subset of patients. [ABSTRACT FROM AUTHOR]

Background We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10–15 hours) from the initial and 21 hours (17–29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)–infected patients had significantly shorter STTPs (P <.001) and lower TTP ratios (P <.001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P =.002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3–5.6]; P =.01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Introduction: Gram‐negative bacillary bloodstream infection (GN‐BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow‐up blood cultures (FUBCs) for GN‐BSI in this population, particularly in the setting of neutropenia, is poorly defined. Methods: We conducted a single‐center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN‐BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs. Results: Of 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug‐resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22–8.72) and vascular catheter source (OR 4.82; CI 1.76–13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all‐cause mortality (16.7% vs. 16.6%; p =.942) and microbiologic relapse (11.1% vs. 6.0%; p =.401) within 90‐days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy. Conclusion: Positive FUBCs were infrequent in neutropenic patients with GN‐BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram‐negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN‐BSI in patients with underlying immune compromise. [ABSTRACT FROM AUTHOR]

Background Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes. Methods A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases. Results Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%). Conclusions To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease. [ABSTRACT FROM AUTHOR]

Dermatomyositis is a rare inflammatory myopathy that is often related to lung cancer. In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2017 and July 2021. A total of 689 patients with lung cancer were included in this study, 97 of whom had small cell lung cancer and 592 had non-small cell lung cancer. We identified a single patient (60-year-old female) who presented with signs and symptoms of dermatomyositis, which was later confirmed to be associated with lung cancer as a paraneoplastic syndrome. Both our study and a recent review of the literature illustrate the temporal link between dermatomyositis and lung cancer, as well as reinforce the need for heightened cancer screenings in DM patients. [ABSTRACT FROM AUTHOR]

Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P  < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P  < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P  = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality. [ABSTRACT FROM AUTHOR]

Background Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, "PREDICT," that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. Methods We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. Results Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke's criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. Conclusions We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system. [ABSTRACT FROM AUTHOR]

Background Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. Methods We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. Results A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2–31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P  < .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. Conclusion 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections. [ABSTRACT FROM AUTHOR]

Background Capnocytopha ga is a gram-negative, facultative anaerobe. Human infection is rare but can lead to devastating outcomes. Capnocytophaga canimorsus can cause sepsis following an animal bite, whereas human-oral–associated Capnocytophaga infections were reported in immunocompromised patients. Current data on these infections are not robust. Our goal is to provide a contemporary description of a unique characteristic of Capnocytophaga infections. Methods We performed a retrospective review of all patients with Capnocytophaga infection from January 2010 to August 2020 at 3 main hospitals of Mayo Clinic in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. We collected baseline demographic data, clinical characteristics, microbiological data, and outcomes of C. canimorsus and human-oral–associated Capnocytophaga infection. Results Among 82 patients with Capnocytophaga infection, 46 patients (56.0%) had bacteremia. The most common species identified in this group was C. sputigena (57.9%), followed by C. canimorsus (34.8%). Patients with human-oral–associated Capnocytophaga bacteremia were often immunocompromised, presented with neutropenic fever, and had worse 6-month all-cause mortality compared to C. canimorsus bacteremia (36.4% vs 6.2%, P  = .03). They also had a higher β-lactamase production rate (36.4% vs 0.0%, P  = .02). Among patients without bacteremia, the main clinical syndrome was polymicrobial head and neck infections (47.2%). Conclusions Human-oral–associated Capnocytophaga bacteremia occurs primarily in immunocompromised patients, particularly those with hematologic malignancy. In contrast, C. canimorsus bacteremia is more likely to present with community-onset infection related to zoonotic exposure. Human-oral–associated Capnocytophaga infection without bacteremia is frequently isolated in polymicrobial infection; this phenomenon's significance is yet to be fully understood. [ABSTRACT FROM AUTHOR]

Cefazolin is commonly used as an alternative to antistaphylococcal penicillins (ASPs) in treating methicillin-susceptible Staphylococcus aureus (MSSA) infections; however, no study has compared these agents in MSSA spinal epidural abscess (SEA). We describe our experience in managing MSSA SEA and compare the clinical efficacy of cefazolin with ASPs. This retrospective multicenter study reviewed 79 adult patients diagnosed with SEA between January 2006 and July 2020 using data collected from electronic health records and clinical microbiology laboratory databases. Forty-five patients received cefazolin, while 34 received ASPs. The total antibiotic duration was longer in the ASPs group but not statistically significant. There were no significant differences in treatment failure at week 6 vs week 12, 30-day vs overall mortality, or in 90-day recurrence rates between the treatment groups. Cefazolin was equally as effective as ASPs, and our findings suggest that it can be an alternative to ASPs in the treatment of MSSA SEA. [ABSTRACT FROM AUTHOR]

In an effort to "flatten the curve" of SARS-CoV-2, society is urged to practice social distancing. However, the management of other disease states may require some patients to undergo outpatient parenteral antimicrobial therapy (OPAT). Practical considerations for OPAT management during an infectious pandemic are reviewed. These include shortening durations of therapy, utilizing the oral route, avoiding medications requiring therapeutic drug monitoring, selecting antimicrobials with long durations, decreasing frequency of laboratory blood draws, and performing tele-health visits. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 24-year-old with rash. Topics include red, painful, and nonpruritic rash had appeared on her upper and lower extremities; her physical examination that revealed multiple tender violaceous nodules; and confirmation of Erythema induratum related to extrapulmonary tuberculosis infection.

Background Mycobacterium marinum is a slow-growing, non-tuberculous mycobacterium responsible for skin and soft-tissue infections (SSTIs), tenosynovitis, and osteomyelitis (OM). We conducted a retrospective study describing the risk, clinical course, and outcome of M. marinum infection. Methods Adult patients with culture-confirmed M. marinum infections were identified from the mycology laboratory at Mayo Clinic, Rochester from January 1998 to December 2018. M. marinum infection was defined as uncomplicated (limited to SST) and complicated (tenosynovitis, OM, or disseminated). Results Forty-six cases of culture-confirmed infection with M. marinum were included (Table 1). Only 16 cases (35%) reported a water exposure and 22 (48%) involved finger and/or hand trauma. The median time to diagnosis was 3.6 months. Most patients (76%) presented with uncomplicated M. marinum infection with skin lesions mainly localized in the upper limb (Table 2). QuantiFERON and PPD were positive in 4 (8%) and 2 (4%) cases, respectively. Granulomatous inflammation and positive special stains were noted in 34 (74%) and 11 (24%) cases, respectively. Cases with complicated M. marinum infection had a longer duration of symptoms and length of treatment (P < 0.05) (Table 3). Prior to diagnosis, 63% of patients received at least one antibiotic for bacterial SSTIs. More than 50% of the patients diagnosed with M. marinum received a one drug regimen and 8% did not initiate therapy. Median treatment duration was 4.4 months. Twenty-six cases (56%) had susceptibilities performed and treatment modifications were made in 10 cases (38%). From the patients that started therapy, 73% completed therapy and 33% were lost to follow up. Cured was achieved in 87% of cases that completed therapy, 2 cases (6%) had a recurrence, and only one patient with active malignancy had a positive blood culture and died. Twelve (44%) and 10 cases (37%) were cured with one and two-drug regimens, respectively. Conclusion Most patients with M. marinum infection present as an uncomplicated infection in the upper limb. Classical exposure was only suspected in a third of the cases. Patients with complicated M. marinum infection had a prolonged duration of symptoms and lengthy treatment. Most patients were successfully treated with a one and two-drug regimen. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Q fever is a zoonotic disease caused by Coxiella burnetii. Primary infection can progress to persistent infection irrespective of initial symptomatology. Our aim is to describe the clinical features, treatment, risk of progression, use of prophylaxis, and outcomes of Coxiella burnetii infection at our institution. Methods We did a retrospective review of all adult patients with positive Coxiella burnetii serology at Mayo Clinic, Rochester from 1st January 2012 to 31st December 2018. Centers for Disease Control and Prevention (CDC) case definition and classification were used to group the patients into confirmed and probable acute Q fever, and confirmed and probable chronic/persistent Q fever. Data on demographics, clinical presentation, comorbid conditions, exposure history, risk factors associated with progression, serology, treatment and outcomes were collected. Results We found 266 patients with positive titres of Coxiella IgG or IgM greater than 1:16, of which 49 patients met the CDC case definition for Q fever. Median age at presentation was 62 years. 45/49 (91. 8%) were men, while 4/49 (8%) were women. 20/49 (40. 8%) patients presented with acute Q fever of which 5 (25%) patients progressed to persistent infection. 29/49 (59%) patients presented with persistent Q fever of which 4 patients could recall symptoms suggestive of acute Q fever. The most common presentation of acute Q fever was acute febrile illness (65%). Endocarditis (11/29) was the most common presentation of chronic/persistent Q fever. Of the 5 patients with acute Q fever that progressed to persistent infection, 3/5(60%) progressed despite being on doxycycline and hydroxychloroquine. 8/29 patients with persistent Q fever had serological resolution at last follow-up. 2/4(50%) deaths were attributable to Q fever. Conclusion Minority of the patients tested met the case definition. 25% of patients with acute disease progressed to chronic Q fever out of which 60%(3/5) progressed despite prophylaxis. Endocarditis and vascular infections were the most common chronic cases. Interestingly we found 4 cases of MPGN in association with Q fever. Prosthetic valves are the most important risk factors for progression (P = 0.02). Serological cure often lags behind clinical cure (27% vs. 68% in persistent infection)(Table 4). Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]