Citations

Abstract Background Minocycline is a second-generation tetracycline with a broad antimicrobial spectrum. It is often used in chronic suppression of musculoskeletal infections, given activity against gram positive organisms. Efficacy of Minocycline against gram negative skin and soft tissue infection has not previously been defined. In this study, we review in vitro minocycline efficacy against isolates from skin, muscle, and bone sources.Fig 1.Organisms isolated Methods We conducted a retrospective review of all minocycline susceptibility testing performed on musculoskeletal GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We describe the isolates broken down by site of culture and organism isolated. Then, we calculated the overall susceptibility of these isolates to Minocycline and susceptibility of the most common 6 organisms isolated.Fig 2.Sites of gram negative isolation Results During the study timeframe, we identified 13,567 gram negative isolates from musculoskeletal sites. Of 330 species identified, 19 were identified in at least 100 isolates (fig 1). Of 36 unique sites, 19 sites were each identified in at least 100 isolates (fig 2). 1920 isolates were tested for susceptibility to minocycline. Of these, 1584 (82.5%) were susceptible to minocycline. Of the most common organisms identified and tested for minocycline susceptibility, 99% of Stenotrophomonas maltophilia, 83% of Enterobacter cloacae, 80% of Escherichia coli, 68% of Acinetobacter baumanii, 1% of Proteus mirabilis, 53% of Klebsiella pneumoniae, 65% of Serratia marcescens isolates were susceptible to minocycline (fig 3). Pseudomonas aeruginosa isolates were not tested, due to innate resistance.Fig 3.Minocycline susceptibility compared to key organisms Conclusion A majority of skin and soft tissue cultures positive for Gram negative isolates were below the waist line. Of these, we reported organisms most commonly found. Minocycline showed in vitro activity against some commonly isolated gram negative organisms, especially E.coli, Acinetobacter, and Stenotrophomonas. Further research is needed into the efficacy of minocycline in gram negative skin and soft tissue infections, but it may represent a viable oral option, especially in the end of life. Disclosures All Authors: No reported disclosures

Abstract Background Mycobacterium abscessus complex (MABC) is a difficult-to-treat infection due to antibiotic resistance. Our study aimed to assess omadacycline’s (OMC) clinical and microbiological outcomes for the treatment of pulmonary MABC. Methods A retrospective study was carried out across 12 US medical institutions from 1/2018-4/2023 to examine the clinical outcomes, and tolerability of OMC treatment for pulmonary MABC. Patients aged ≥ 18 years who were treated with OMC for ≥ 3 months were included. The primary outcome was clinical success at 3, 6, and 12 months. The secondary outcomes were sputum culture conversion rate, adverse effects, and clinical success by subspecies and macrolide susceptibility. Results Thirty-five patients were included in this analysis. Most patients were female (74.3%) and Caucasian (74.3%), with a median (IQR) age of 61 years (51–70). Subspeciation was performed for 22 isolates with predominant M. abscessus subspecies (77.3%). Moreover, coinfection with other NTM species was present in 28.6% of cases where Mycobacterium avium complex was present in 8 cultures. Sixty-eight percent of the MABC isolates were confirmed to be macrolide resistance; half (12/24, 50.0%) were evident by the presence of functional erm gene, while the other half by antimicrobial susceptibility (Table 3). Of the remaining isolates, 14% were macrolide-susceptible, while no information was reported in 17%. The median (IQR) treatment duration of OMC was 8 months (3.9 – 15.7). The most commonly co-administered antibiotics were intravenous amikacin, imipenem/cilastatin, inhaled amikacin and clofazimine with the same percentage (42.9%) (Table 1). Overall, MABC clinical success was observed in 71.4%, 89.7%, and 90.9% in 3-, 6- and 12 months, respectively (Table 3). Adverse effects reported in 34.3%. The most common side effects were gastrointestinal intolerance (25.7%) and hepatoxicity (11.4%), which led to drug discontinuation in 22.9%. Conclusion OMC treatment showed clinical success in > 70% of patients with pulmonary MABC including patients with macrolide resistant strains for more than 3 months. However, larger studies are needed to validate the outcomes beyond 12 months. Disclosures Kaylee E. Caniff, PharmD, BCIDP, T2Biosystems: Honoraria Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker

Abstract Background The introduction of shotgun metagenomic sequencing (sMGS) methods that identify the presence of microbial cell-free DNA (mcfDNA) in peripheral blood have shown promising results in various populations of patients. There is a pressing need to evaluate its application for osteoarticular infections (OAIs) in real-world setting. Baseline characteristics of the patients with suspected osteo-articular infections, including demographics, clinical characteristics, diagnosis, and KT results. Methods We retrospectively collected data on 73 adult patients who presented to the Mayo Clinic with suspected OAIs between 2019 and 2023, and for whom mcfDNA sMGS (Karius®, KT) testing was part of their diagnostic workup. We collected data on comorbidities, diagnostics, microbiological workout and its concordance with the KT. The primary objective was to evaluate its clinical impact on OAI diagnoses and management distinguishing into four categories: (1) KT was able to confirm an established diagnosis, (2) KT supported non-ID diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information. Relevant microbiologic studies of patients with unsuspected diagnoses established by the KT (N=5) Results In our cohort KT was performed in 73 patients (Table 1). Among the infected individuals, KT yielded positive results in 22/43 (51.2%) cases. Out of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, while in five (22.7%) cases, the KT established an unsuspected diagnosis, improving the diagnostic power from 11/43 (25.6%) to 16/43 (37.2%) (Table 2). Moreover, yielded a negative result in 19/26 (73.1%) patients with non-infectious diagnosis (Figure 1). Native Vertebral Osteomyelitis (NVO) diagnosis (p < 0.001) or OAIs with concomitant presence of endocarditis or endovascular infection (p = 0.005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result (Table 3). Overall, KT influenced antibiotic therapy in six cases (8.2%). Table 3 Factors associated with diagnostic certainty categories Conclusion This is the first retrospective study aiming to assess the real-world usefulness of the KT on the clinical management of patients with OAIs, with a special focus on NVO. It underscores KT's real-world application in cases where traditional diagnostic methods fall short. In highly complex OAIs cases, KT added 11.6% to the diagnostic power by establishing unsuspected diagnosis in 5 of 43 infective patients. Patients with NVO or OAIs with concomitant endocarditis or endovascular infections particularly benefited from KT testing. Figure 1 Distribution of KT results and their respective outcome according to the final diagnosis of suspected OAIs cases. Disclosures All Authors: No reported disclosures

Abstract Background Characterization of transplant transmitted infections associated with drowned organ donors and the recipients is not well delineated, posing challenges for optimal management and prophylaxis strategies. Broader organ sharing may pose additional considerations due to pathogen variation. Methods We reviewed 22 potential donor disease transmission events (PDDTEs) from drowned donors reported to the Organ Procurement and Transplantation Network (OPTN) ad hoc Disease Transmission Advisory Committee (DTAC) from 2017-2022 to estimate the incidence of PDDTEs among all US drowned organ donors and identify the most common pathogens in this setting. We also characterized donor/recipient epidemiology, infection timing and risk factors, and recipient survival. Results From 2017-2022, drowning was the mechanism of death in 777/74,232 (1.0%) of all US organ donors, from whom 2500 organs were transplanted. Among the 22 PDDTEs, there were 70 organ recipients. The median donor age was 17.5 years (range 1-70 years) and lung recipients accounted for 5/70 organ recipients. All PDDTE reports were submitted due to recipient disease, and index cases occurred 2-19 days post-transplant. 7/22 (7/777 drowned donors, 0.9%) PDDTEs were associated with pathogens consistent with plausible waterborne transmission, of which 4 were due to invasive molds (Zygomycetes and Scedosporium) and 3 were due to bacteria (Pseudomonas and Legionella). Of the 21 organ recipients from these 7 donors, 8 had proven or probable infections. 6/8 recipients had severe infection with 3 deaths, all from invasive mold infections. There were no identifiable infection risk factors related to drowning water source, donor immersion time, or geographic region. However, donor/recipient regional discordance occurred in 5/21 recipients, demonstrating the trend in broader organ sharing. Conclusion Though rare, organ recipients are at risk for transplant transmitted infection from drowned donors, particularly invasive mold infections. All infections occurred within the first month after transplant with high associated mortality. Though optimal management and prophylaxis strategies in these scenarios remain uncertain, post-transplant vigilance for early infection is paramount. Disclosures Helen S. Te, MD, CVS Caremark: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Anil J. Trindade, MD, CareDx, Inc.: Advisor/Consultant|CareDx, Inc.: Grant/Research Support|TFF Pharmaceuticals: Advisor/Consultant|Veloxis Pharmaceuticals, Inc.: Grant/Research Support

Abstract Background Acute pancreatitis, a prevalent gastrointestinal condition, frequently necessitates hospitalization and is associated with potential adverse in-hospital outcomes. Recent data showed the detrimental effects of COVID-19 infection on acute pancreatitis, particularly in patients with severe COVID-19 infections. However, limited information exists on the specific impacts of COVID-19 infection in patients hospitalized for acute pancreatitis. Methods We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted due to acute pancreatitis. Participants aged 18 and above were identified using relevant ICD-10 CM codes. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Statistical significance was established at a P value of 0.05. Results We identified 252,435 patients with a primary discharge diagnosis of acute pancreatitis. The mean age was 50.1 years; 48.6% were female. Caucasians accounted for 41%, followed by Hispanics. Of these, 1.05% (2,675/252,435) had a concurrent diagnosis of COVID-19 infection. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 3.71; 95% CI 2.01, 6.84, P < 0.001), prolonged length of stay (β LOS 1.05; 95% CI 0.46, 1.64, P < 0.001), increased hospitalization charge ( β charge 9,327; 95% CI 820, 17834, P < 0.001), and acute respiratory failure (aOR 2.49; 95% CI 1.75, 3.53, P < 0.001), We observed non-significant, but increased, risks of shock, acute kidney injury (AKI), pancreatic pseudocyst, acute respiratory distress syndrome (ARDS), and mechanical ventilation in COVID-19 positive patients. Conclusion In conclusion, our study underscores that COVID-19 infection is associated with higher in-hospital mortality, prolonged hospital stays, and increased incidence of acute respiratory failure in patients diagnosed with acute pancreatitis. Future longitudinal studies are warranted to comprehensively assess the long-term health sequelae in this population. Disclosures All Authors: No reported disclosures

Abstract Background Morbidity from bacteremia may be exacerbated by inadequate initial antibiotic therapy. This concern however may lead to hesitance to de-escalate while awaiting pathogen identification and susceptibility results. We performed a randomized controlled trial evaluating the impact of a strategy for rapid pathogen and resistance detection directly from positive blood culture bottles (BCBs) using a rapid multiplex PCR (rmPCR) complemented with a rapid phenotypic screen (RPS) for extended-spectrum beta-lactamases and carbapenemases in a setting with moderate to high levels of antimicrobial resistance where routine direct-from-BCB disk diffusion susceptibility testing was in place Methods Patients with positive BCBs were randomized to 2 arms: 1) Standard BCB processing (including direct from BCB disk diffusion susceptibility testing - control, n=419) with antimicrobial stewardship (AS); or 2) rmPCR/RPS with AS (rmPCR/RPS, n=425). The primary outcome was time from positive blood culture result to prescription of an effective or optimal antibiotic regimen. An effective antibiotic regimen was defined as one active against the detected pathogen(s); an optimal antibiotic regimen was defined as an effective regimen which was also the most narrow spectrum and targeted one, as recommended by institutional guidelines. Mortality was analyzed as a secondary outcome. Results True bacteremia was identified in 658 patients (n=329 in both arms); 597 were monomicrobial (405 with aerobic or facultative anaerobic Gram negatives rods [AGNR]) and 61 polymicrobial (41 harboring AGNR). Time from BCB Gram stain to prescription of an effective antibiotic was 9.9 versus 3.2 hours in the control and rmPCR/RPS groups, respectively (p=0.58) and time from Gram stain to prescription of an optimal antibiotic regimen was 41.6 versus 29.4 hours in the two groups, respectively (p < 0.001). 14-day mortality was 7.6% versus 4.3% (p = 0.069) and 30-day mortality was 11.2% versus 8.8% (p=0.30) in the two groups, respectively. Conclusion Compared to control methods which included direct-from-BCB disk diffusion susceptibility testing, an intervention comprising rmPCR/RPS with AS applied to positive blood cultures improved time to optimal therapy but not time to effective therapy or mortality. Disclosures Shawn Vasoo, MBBS, MRCP, D(ABP), D(ABIM) (Inf Dis), FRCPath, bioMerieux: In-kind, for this study|Rosco Diagnostica: In-kind, for this study Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria Paul Tambyah, MBBS (S'pore), Diplomate, American Board of Internal Medicine and Infectious Diseases, Moderna: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support

Abstract Background Prosthetic valves are considered a risk factor for endocarditis however diagnosing prosthetic valve endocarditis (PVE) is complicated by acoustic shadowing on echocardiography. In 2023, the ISCVID published an update to the Duke Criteria (Duke 2023) which intended to increase the sensitivity in diagnosing PVE. The purpose of this study was to examine how TAVR infective endocarditis (TAVR-IE) was diagnosed at our institution 90 Day Mortality Kaplan Meier Curve Methods HERON was utilized to match cases between ACC/STS databases and the EMR at The University of Kansas Health System (TUKHS). Patients with bacteremia occurring after a TAVR were reviewed. Each case was evaluated if they met rejected/possible/definitive endocarditis criteria in the Modified Duke Criteria (Duke 2005) and the Duke 2023 Criteria. To adjudicate the diagnosis, an expert panel reviewed all cases that met definitive endocarditis criteria in any edition of the Duke Criteria. Results A total of 2371 TAVRs were conducted at TUKHS from 2012 to 2023. We identified 146 cases of post procedure bacteremia. We excluded 53 cases leaving 93 in the cohort. Transeophageal echocardiography was utilized in about half of the cases (TTE 73, TEE 45). F-FDG positron emission tomography/CT was done in six patients and Cardiac CT in one patient. Cultures returning with Enterococcus spp (16). viridans group streptococci (15), and Staphylococcus spp. (15) had similar incidence. About half had either atypical organisms (40) on 2005 Duke criteria or polymicrobial growth (7). Definitive criteria were met in 18 and 21 patients for the Duke 2005 and Duke 2023 Criteria respectively. Two cases had minor microbiological criteria upgraded to major in Duke 2023. One case was promoted to definitive endocarditis based on Cardiac CT. Upon adjudication the panel agreed with Duke 2023 Criteria classification. Sensitivity was calculated 85%/100% for Duke 2005 and Duke 2023 Criteria respectively. Kaplan Meier curves calculated no significant difference of 3 month mortality between TAVR patients who had met definitive criteria and those who did not. (Figure #1) Conclusion The 2023 ISCVID Duke Criteria in this study appeared to have superior sensitivity for TAVR-IE when compared to the older Modified Duke Criteria published in 2005. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties). Wissam El Atrouni, MD, ViiV Healthcare: Advisor/Consultant

Abstract Background Acute diverticulitis, a prevalent gastrointestinal condition, frequently necessitates hospitalization and is associated with potential adverse in-hospital outcomes. Recent data showed the detrimental effects of COVID-19 infection on acute diverticulitis, particularly in patients with severe COVID-19 infections. However, limited information exists on the specific impacts of COVID-19 infection in patients hospitalized for acute diverticulitis. Methods We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted due to acute diverticulitis. Participants aged 18 and above were identified using relevant ICD-10 CM codes. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Statistical significance was established at a P value of 0.05. Results We identified 167,170 patients with a primary discharge diagnosis of acute pancreatitis. The mean age was 60.1 years; 56.8% were female. Caucasians accounted for the majority, followed by Hispanics. Of these, 0.90% (1,504/167,170) had a concurrent diagnosis of COVID-19 infection. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 8.43; 95% CI 4.32, 16.42, P < 0.001), prolonged length of stay (β LOS 2.02; 95% CI 1.27, 2.77, P < 0.001) and increased hospitalization charge ( β charge 17,813.27; 95% CI 4,080, 31,546, P < 0.001), We observed non-significant, but increased, risks of shock, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and mechanical ventilation in COVID-19 positive patients. Conclusion In conclusion, our study revealed that COVID-19 infection is associated with higher in-hospital mortality, prolonged hospital stays, and increased hospitalization charges in patients diagnosed with acute diverticulitis. Future longitudinal studies are warranted to comprehensively assess the long-term health sequelae in this population. Disclosures All Authors: No reported disclosures

Abstract Background Coccidioidomycosis (cocci) is a fungal infection caused by Coccidioides and a common cause of community acquired pneumonia in endemic regions. Disseminated cocci occurs in ≤ 1% of persons with cocci, and among these, disseminated cutaneous coccidioidomycosis (DCC) is estimated to occur in 15 to 67% of cases, however little data exists to describe its frequency and timing of recurrence. Limited small studies show recurrence rates from 17 to 50% and often do not distinguish skin dissemination from other soft tissues. Our aim was to determine the frequency, timeframe and risk factors for relapsed DCC. Methods Potential cases of disseminated cocci were identified by ICD-10 codes 38.3, 38.7, 38.9 (& ICD-9 equivalents) and keyword-based search of pathology reports from 1/1/2008 - 3/31/2024. We included patients with proven or probable DCC. We excluded patients with primary cutaneous cocci or reactive rash. We performed a retrospective review to identify episodes of recurrence, comorbidities, and antifungal regimen. Results We identified 44 proven and 3 probable cases of DCC (33 males, 14 females), median age 48 years, 66.0% white, 21.3% black, 5.4% Hispanic. 18 (38.3%) were immunosuppressed and 6 (13.6%) had diabetes mellitus. Median follow-up duration was 68 months; 12 (25.5%) patients had ≥1 recurrence, 7 (14.9%) of whom relapsed ≥2 times. Median interval off of antifungals until recurrence was 14 months (range: 1 - 96). 3 (6.4%) patients had recurrence within three months of diagnosis, and 6 (13.0%) and 11 (23.9%) had a recurrence by the 1st and 5th follow-up year, respectively. 21 (87.5%) recurrences were at the same site as a prior occurrence, 4 (18.2%) occurred on antifungal therapy. There were no significant differences in recurrence rates by race or diabetes. Of the 18 immunosuppressed cases, there was 1 (5.6%) recurrence, though 14 (77.8%) continued antifungal therapy throughout follow-up. Conclusion Once antifungal treatment was discontinued, recurrence of disseminated cutaneous cocci was common, and among those whose DCC relapsed, multiple relapses were noted. Longer follow up is needed to better characterize the risk of long-term recurrence. Disclosures All Authors: No reported disclosures

Abstract Background Culture-negative native vertebral osteomyelitis (CN-NVO) is increasingly common, rising from 0.3 to 1.8 cases per 100,000 between 1995 and 2008. The lack of microbial identification complicates optimal treatment and creates prognostic uncertainties. We describe our decade-long clinical experience with CN-NVO, focusing on patient characteristics, treatment, and outcomes. Patient Characteristics Methods We retrospectively analyzed adult patients with radiographic evidence of NVO between January 1, 2011, and July 31, 2021. CN-NVO required clinical indicators such as back pain and fever, elevated inflammatory markers, and negative cultures from at least one spine biopsy. Patients with infected instrumentation were excluded. Diagnostic Evaluation Values represent median, lower quartile, and upper quartile for continuous variables unless otherwise specified, 2 whereas frequencies and percentages are presented for categorical variables. ^ All results returned negative *Biopsies number two and three did not result in additional findings or change clinical management. Results Seventy-two patients were included. Their characteristics are presented in Table 1. Most (77.8%) had received antibiotics within the 4 weeks preceding the biopsy. Disc space enhancement on MRI was the primary finding, with the lumbar spine being the most frequently involved (Table 2). Blood cultures were positive in 39.4% of the patients within 3 months of symptom onset. Streptococcus spp. (n=9, median time between positive culture and diagnosis: 6.5 days [IQR 2.25, 26.75]) and Staphylococcus aureus (n=7, 40 days [IQR 37.5, 51.5]) were most common. Definitive antibiotics were administered in 98.6% of the cases, primarily IV β-lactam + vancomycin. Oral antibiotics (PO) were used in 46.5% of the patients, primarily as step-down therapy (91%) (Table 3). Surgery was required in 8.5% of the patients for abscess drainage or relief of spinal cord compression. Treatment failure occurred in 9.4% of patients, and 37.5% died during the median follow-up of 568.5 days, with two deaths related to the infection. Treatment and Outcomes ^ defined as requiring another course of antibiotics and/or surgery for suspected ongoing infection ¶ Clinical findings include back pain or fevers; laboratory findings indicate abnormal or uptrend in inflammatory marker values # Defined as MRI findings concerning ongoing or worsening infection as per the interpretation of the Radiologist, Infectious Disease physician, and/or Orthopedic Surgeon Conclusion Patients with CN-NVO often require prolonged antibiotic therapy, typically combination regimens, with favorable treatment outcomes. Our treatment failure rate is similar to other studies, although comparability may be limited by heterogeneity in definitions. Mortality rates in the range of 6 and 36% have been reported, with the higher end driven mostly by comorbidities. Enhanced diagnostics and standardized treatment protocols are needed to further improve patient outcomes. Disclosures All Authors: No reported disclosures