Chesdachai, Supavit

The prevalence of invasive candidiasis caused by non-Candida albicans has rapidly increased. Candida glabrata (Nakaseomyces glabrata) is an important pathogen associated with substantial mortality. Our study examined the antifungal temporal susceptibility of C. glabrata and cross-resistance/non-wild-type patterns with other azoles and echinocandins. Laboratory data of all adult patients with C. glabrata isolated from clinical specimens at the Mayo Clinic, Rochester, from 2012 to 2022 were collected. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used. We obtained 1046 C. glabrata isolates from 877 patients. Using CLSI and EUCAST breakpoints, 187 (17.9%) isolates and 256 (24.5%) isolates were fluconazole-resistant, respectively. Focusing on C. glabrata bloodstream infections, fluconazole-resistance ranged from 16 to 22%. Among those 187 fluconazole-resistant isolates, 187 (100%) and 184 (98.4%) isolates were also voriconazole and posaconazole non-wild-type, respectively, with 97 (51.9%) isolates deemed non-wild type for itraconazole. The fluconazole susceptibility pattern has not changed over the past decade. The proportion of fluconazole-resistant C. glabrata is relatively high, which could be due to the complexity of patients and fluconazole exposure. Itraconazole appears to be a compelling step-down therapy for fluconazole-resistant C. glabrata, given the high proportion of wild-type isolates. Further research to examine clinical outcomes is warranted.

Abstract Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000–4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered.

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.

Abstract Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups.

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

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010–2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5–647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87–17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18–5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

Abstract Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.

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 Introduction During the early phase of the coronavirus disease 2019 (COVID‐19), remdesivir was only approved for hospitalized patients. Our institution developed hospital‐based, outpatient infusion centers for selected hospitalized patients with COVID‐19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods Retrospective study of all hospitalized adult patients with COVID‐19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results Among 3029 hospitalized patients who received treatment with remdesivir for COVID‐19, the majority (89.5%) completed the recommended 5‐day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06–0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27–2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5‐day course of remdesivir (aOR 2.07, 95% CI 1.45–2.95, p < 0.001). Conclusions This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5‐day course of remdesivir.

Beta-hemolytic streptococci are common causes of bloodstream infection (BSI). There is emerging data regarding oral antibiotics for BSI but limited for beta-hemolytic streptococcal BSI.