Challener, Douglas

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.

Abstract Background In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection. Methods All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations. Results A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0–6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia. Conclusions Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality.

Abstract Case reports of patients infected with COVID-19 and influenza virus (“flurona”) have raised questions around the prevalence and severity of coinfection. Using data from HHS Protect Public Data Hub, NCBI Virus, and CDC FluView, we analyzed trends in SARS-CoV-2 and influenza hospitalized coinfection cases and strain prevalences. We also characterized coinfection cases across the Mayo Clinic Enterprise from January 2020 to April 2022. We compared expected and observed coinfection case counts across different waves of the pandemic and assessed symptoms and outcomes of coinfection and COVID-19 monoinfection cases after propensity score matching on clinically relevant baseline characteristics. From both the Mayo Clinic and nationwide datasets, the observed coinfection rate for SARS-CoV-2 and influenza has been higher during the Omicron era (2021 December 14 to 2022 April 2) compared to previous waves, but no higher than expected assuming infection rates are independent. At the Mayo Clinic, only 120 coinfection cases were observed among 197,364 SARS-CoV-2 cases. Coinfected patients were relatively young (mean age: 26.7 years) and had fewer serious comorbidities compared to monoinfected patients. While there were no significant differences in 30-day hospitalization, ICU admission, or mortality rates between coinfected and matched COVID-19 monoinfection cases, coinfection cases reported higher rates of symptoms including congestion, cough, fever/chills, headache, myalgia/arthralgia, pharyngitis, and rhinitis. While most coinfection cases observed at the Mayo Clinic occurred among relatively healthy individuals, further observation is needed to assess outcomes among subpopulations with risk factors for severe COVID-19 such as older age, obesity, and immunocompromised status.

Abstract As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.

Abstract 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.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID pos ; n = 2,317) versus COVID-19-negative (COVID neg ; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID pos over COVID neg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID pos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

AbstractHistoplasma capsulatum is an endemic fungus that most oftenly causes a self‐limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra‐pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper‐erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.