McHugh, Jack

Artificial intelligence (AI) has emerged as a promising adjunct in the diagnosis and management of infective endocarditis (IE), a disease characterized by diagnostic complexity and significant morbidity. Machine learning (ML) models such as SABIER and SYSUPMIE have demonstrated strong predictive accuracy for early IE diagnosis, embolic risk stratification, and postoperative mortality, surpassing traditional clinical scoring systems. In imaging, AI-enhanced echocardiography and advanced modalities like FDG-PET/CT offer improved sensitivity, specificity, and reduced inter-observer variability, potentially transforming clinical decision making. Additionally, AI-powered microbiological techniques, including MALDI-TOF mass spectrometry combined with ML and neural network-based metagenomic classifiers, show promise in rapidly identifying pathogens and predicting antimicrobial resistance. Despite encouraging early results, widespread adoption faces barriers, including data limitations, interpretability issues, ethical concerns, and the need for robust validation. Future directions include leveraging generative AI as clinical consultative tools, provided their capabilities and limitations are carefully managed. Ultimately, collaborative efforts addressing these challenges could transform IE care, enhancing diagnostic accuracy, clinical outcomes, and patient safety.

ABSTRACT The prevalence of invasive candidiasis caused by non- albicans Candida species is increasing. Candida guilliermondii is an infrequent cause of candidemia but has been associated with decreased susceptibility to triazoles. Clinical data related to the infection with C. guilliermondii are sparse. Our study evaluated the antifungal susceptibility testing (AST) for C. guilliermondii isolates submitted to a reference laboratory over a 12-year period (2012–2023). AST patterns were examined using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiological cutoff values (ECVs) and breakpoints. Where isolates were identified from patients treated at our institution, retrospective chart review was performed to describe patient risk factors, treatment approaches, and outcomes associated with C. guilliermondii fungemia. One hundred twelve blood culture isolates of C. guilliermondii were identified, and clinical data were available for 21 fungemic patients. A significant number of isolates (9.8–20.5%) were observed to be non-wild type for various triazoles. All isolates were susceptible to micafungin. A majority (76.2%) of cases of C. guilliermondii fungemia treated at our tertiary care center were hospital-acquired, and two-thirds of patients were immunocompromised at the time of diagnosis. Ten of the 21 patients died within 60 days of fungemia, although mortality was directly or partially attributed to C. guilliermondii fungemia in only four cases (19.0%). Echinocandins may be used for empiric therapy for C. guilliermondii until the results of AST are available. Further research is required to determine appropriate clinical breakpoints for triazoles. IMPORTANCE Our study addresses a significant knowledge gap in the clinical management of this non- Candida albicans species. Our retrospective review includes comprehensive AST data for 112 Candida guilliermondii isolates, which is the largest number of isolates reported from the United States to date. Susceptibility data are supplemented by clinical outcomes, where isolates were identified for patients treated at Mayo Clinic. Key findings from our study include the observation that a notable proportion of C. guilliermondii isolates exhibit non-wild-type profiles for various triazoles. Importantly, all isolates remained susceptible to echinocandins, suggesting their efficacy as first-line therapy in the absence of timely susceptibility results. Furthermore, our study highlights the high mortality associated with C. guilliermondii fungemia in immunocompromised patients, emphasizing the urgent need for optimized treatment strategies.

Abstract We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.

Abstract Background Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain, and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. Methods We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012 to 2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. Results Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (P < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (P = .244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (odds ratio [OR] = 2.12; 95% confidence interval [CI] = 1.24–3.64; P = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. Conclusions In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Abstract Background Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24–3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

Blood culture-negative infective endocarditis (BCNE) is a challenging condition associated with significant morbidity and mortality. This review discusses the epidemiology, microbiology, diagnosis, and treatment of BCNE considering advancements in molecular diagnostics and increased access to cardiac surgery. BCNE can be categorized into bacterial endocarditis with sterilized blood cultures due to previous antibiotic treatment, endocarditis caused by fastidious microorganisms, and true BCNE caused by intracellular organisms that cannot be cultured using traditional techniques. Non-infectious causes such as nonbacterial thrombotic endocarditis should also be considered. Diagnostic approaches involve thorough patient history; blood and serum testing, including appropriate handling of blood cultures; serological testing; and molecular techniques such as targeted and shotgun metagenomic sequencing. Where available, evaluation of explanted cardiac tissue through histopathology and molecular techniques is crucial. The therapy for BCNE depends on the likely causative agent and the presence of prosthetic material, with surgical intervention often required.

Abstract Background Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62–2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37–4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

AbstractBackgroundSpecific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.MethodsWe performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.ResultsNine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart‐kidney (N = 1), liver‐kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152–283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX) and all patients received TMP‐SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow‐up of 1.96 (IQR 0.90–6.33) years. Two patients died during follow‐up, both without evidence of nocardiosis.ConclusionsThis study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP‐SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis. image

Postdural puncture headache is a frequently encountered complication following procedures such as lumbar puncture, neuraxial anesthesia, or intrathecal drug delivery device implantation. It classically presents as a painful orthostatic headache that is exacerbated when a patient is upright. For treatment, patients are often started on conservative options such as hydration, caffeine, bedrest, and NSAID analgesics; however, certain patients who fail these therapies may require intervention with an epidural blood patch. The epidural blood patch remains the gold standard for treating refractory postdural puncture headache. Contraindications to epidural blood patch include severe coagulopathy, patient refusal, or infection at the intended site of entry. There are no clear consensus recommendations regarding patients with a hematological malignancy and potential risk that autologous blood may seed malignant cells into the neuraxis. In this case report, we present a patient with acute myeloid leukemia who developed a postdural puncture headache after receiving subarachnoid administration of antineoplastics. The patient was refractory to conservative therapy, prompting multidisciplinary consultation and discussion with the patient about the risks and benefits of proceeding with an epidural blood patch. Ultimately, the patient elected to proceed with the offered epidural blood patch which led to complete resolution of his painful headaches and did not cause any spread of malignant cells into his neuraxis or cerebral spinal fluid.