Todd P McCarty

Phaeohyphomycosis in transplant recipients: Results from the Transplant Associated Infection Surveillance Network (TRANSNET)

Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P = <.001). The most frequent pathogen was Alternaria species (32%). Disseminated disease was found in 55.4%. Cutaneous infection was more common in SOT (53.3% vs 23.1%; P = .021), while pulmonary disease was more common in SCT (57.7 vs. 26.7; P = .019). Voriconazole (44.6%) and amphotericin B preparations (37.5%) were the most common antifungal therapies. Overall mortality was 25% and was higher in SCT than in SOT (42% vs 10%; P = <.001). A wide variety of organisms encompass phaeohyphomycosis contributing to varying types of infection in transplant recipients. Site of infection, time to disease, and mortality varies significantly between SCT and SOT recipients. Lipid formulations of amphotericin B and voriconazole were the most common antifungals used to treat this disorder.

Cytomegalovirus appendicitis in solid organ transplant patients, two cases and a review

Cytomegalovirus (CMV) disease is a common complication following solid organ transplantation with a variety of gastrointestinal (GI) tract manifestations. CMV appendicitis, however, is a rare complication in a solid organ transplant patient, having been reported only once previously. We have recently seen two cases in solid organ transplant recipients at our institution, one a liver recipient and the other a heart recipient. Both patients underwent surgical resection. Pathologic evaluation of both resected appendices as well as polymerase chain reaction (PCR) amplification for CMV from the serum revealed the virus as the etiology. Both patients received induction intravenous ganciclovir followed by oral valganciclovir and have done well post-operatively. Tissue-invasive CMV disease should be considered in the differential diagnosis for solid organ transplant patients with symptoms suggesting acute or chronic appendicitis. Both PCR testing as well as pathologic review of tissue specimens should be considered to ensure accurate diagnosis and management.

Echinocandin resistance among Candida isolates at an academic medical centre 2005–15: analysis of trends and outcomes

Objectives To identify the frequency of micafungin resistance among clinically significant isolates of Candida stored at our institution from 2005 to 2015. Chart review of patients with resistant isolates then informed the clinical setting and outcomes associated with these infections. Methods Clinical Candida isolates had been stored at -80°C in Brucella broth with 20% glycerol from 2005. Isolates were tested using broth microdilution to determine micafungin MICs. All Candida glabrata isolates and all isolates demonstrating decreased susceptibility to micafungin were screened for FKS mutations using a Luminex assay. Results In total, 3876 Candida isolates were tested for micafungin resistance, including 832 C. glabrata isolates. Of those, 33 isolates from 31 patients were found to have either decreased susceptibility to micafungin and/or an FKS mutation. C. glabrata accounted for the majority of these isolates. While bloodstream infections were found to have a very high mortality rate, isolates from other sites were uncommonly associated with 30-day mortality. Overall resistance rates were very low. Conclusions Echinocandin resistance in C. glabrata has been increasingly reported but rates at our institution remain very low. We hypothesize that a focus on antifungal stewardship may have led to these observations. Knowledge of local resistance patterns is key to appropriate empirical treatment strategies.

Improvement of gram-negative susceptibility to fluoroquinolones after implementation of a pre-authorization policy for fluoroquinolone use: A decade-long experience

OBJECTIVE Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance. DESIGN Retrospective cohort. SETTING Large academic medical center. METHODS We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998-2005) and the postimplementation period (2006-2016). RESULTS Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005-1.072), E. cloacae (RR, 1.028; 95% CI, 1.013-1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006-1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996-1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975-0.987). CONCLUSIONS A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.

Impact of Infectious Disease Consultation on Clinical Management and Mortality in Patients with Candidemia

Candidemia has a high attributable mortality. The objective of this study was to determine the impact of infectious disease consultation on mortality and clinical outcomes in candidemia. Infectious disease consultation was associated with better adherence to guidelines and improved survival, even in patients with high Acute Physiology and Chronic Health Evaluation II scores.

Impact of an Antimicrobial Stewardship Program Led OPAT Program on Clinical Complications and Frequency of Hospital Readmissions

Abstract Background Treatment of serious bacterial infections with Outpatient Parenteral Antibiotic Therapy (OPAT) has provided patients (patients) the opportunity to complete treatment safely and effectively, while avoiding complications, and prolonged hospitalization. Despite the benefits, considerable risks with drug-related and central venous catheter (CVC)-related complications exist. We sought to improve clinical outcomes of our program by implementing intensive monitoring in partnership with our antimicrobial stewardship program (ASP) with a goal of decreasing the frequency of complications as well as hospital readmission rates and lengths of stay (LOS). Methods A retrospective study was conducted including all patients discharged from the Birmingham VA Medical Center on OPAT from January 1, 2015 to December 31, 2016. The start date coincides with ASP development of a physician and pharmacist led OPAT program, working closely with home health agencies. Data collection included baseline demographics, antibiotic indication, antibiotic therapy received, and laboratory monitoring. Clinical outcomes included frequency and types of drug-related complications, CVC complications, hospital admission rate due to complications, and hospital days avoided. Results In the study period, 299 patients were discharged on OPAT. They were 96.9% male, and the average age was 64 (Table 1). The average number of hospital days avoided was 32.1. The most common indication was osteomyelitis (Table 1). There were 82 complications in 78 (26%) patients, almost half were acute kidney injury, defined as a rise in serum creatinine requiring a change in antibiotic dosing (Table 2). These led to 25 hospitalizations (32% of patients with complications, 8.3% overall) with another 5 patients being hospitalized for unrelated reasons. Conclusion Our medical center instituted an ASP led practice of closely monitoring and directing care with the local home health agencies due to concerns about patient safety. In doing so, we have realized a low rate of complications and an ability to manage the majority while remaining as an outpatient, with the exceptions of CVC-related complications and encephalopathy. Our data supports the center’s efforts and choice to dedicate resources to improving this increasingly popular treatment. Disclosures All authors: No reported disclosures.

Relationship of T2 Candida Panel to Disease Severity, Mortality and Time to Therapy in Patients with Candidemia

Abstract Background Candidemia is a common hospital-acquired infection that is associated with high mortality. Diagnosis via blood cultures (BC) is limited by poor sensitivity (50%) and slow turnaround time (2–5 days). T2Candida (T2C) is a newly available rapid test using magnetic resonance that can detect 5 species of Candida from whole blood in < 6 hours with a sensitivity of 91.1%. Methods We performed a retrospective analysis of all cases of candidemia detected by BC and/or T2C during 2016 at UAB Medical Center. The test was targeted to ICU patients who had higher risk criteria for candidemia. We collected APACHE II scores at the time of BC or T2C test collection as a surrogate for severity of illness. Other outcomes included 30-day mortality and time to initiation of therapy (TTT). Results We identified 139 patients with candidemia, defined as a positive BC (BC+) and/or positive T2C (T2C+). Performance of a single test led to diagnosis in 103 patients (74%). On initial diagnosis if both a BC and T2C were performed within a 24 hour interval, patients were grouped based on the results of both tests. 36 patients (26%) had both tests performed: 8/36 (22%) were concordant (BC+/T2C+) and 28/36 (78%) discordant. 23/28 patients (82%) with discordance were BC-/T2C+ and the remaining 5 were BC+/T2C-. The difference in APACHE II scores and 30-day mortality rate of BC+ patients (13.6, 0.36) and T2C+ patients (16.4, 0.46) were not significant (P-values 0.06 and 0.29, respectively); the difference in TTT between BC+ patients (1.6 day) and T2C+ patients (0.1 day) was statistically significant (P-value < 0.00001). Conclusion T2C demonstrated excellent sensitivity (88.6%) in a ‘real world’ setting focused in the ICU. We observed a significant reduction in TTT associated with the T2C assay, but did not observe an improvement in survival with earlier therapy for candidemia defined as a T2C+. Patients with T2C+ had higher APACHE II scores suggesting biased testing towards sicker patients. We cannot explain the large number of discordant results (BC−/T2C+, BC+/T2C−), but hypothesize that T2C+ may be a more sensitive marker for invasive candidiasis/candidemia. These data strongly endorse the need for a large, prospective, multicenter study exploring the use of T2C vs. standard of care in the diagnosis and management of this disorder. Disclosures P. G. Pappas, T2Candida Panel: Grant Investigator and Scientific Advisor, Grant recipient, Research grant and Research support Merck: Grant Investigator, Grant recipient and Research grant Gilead: Grant Investigator, Grant recipient and Research grant Scynexis: Grant Investigator and Scientific Advisor, Grant recipient and Research grant Cidara: Grant Investigator and Scientific Advisor, Grant recipient and Research grant Astellas: Grant Investigator, Grant recipient and Research grant Viamet: Scientific Advisor, Consulting fee Amplyx: Scientific Advisor, Consulting fee Vical: Scientific Advisor, Consulting fee

Yeast Infections After Solid Organ Transplantation

Invasive infections due to yeast are among the most common infections following solid organ transplantation and account for considerable morbidity and mortality. Infections due to Candida species are most common, accounting for over half of all fungal infections following solid organ transplantation. Cryptococcosis is the next most common yeast infection in organ transplant recipients, and is overall the third most common invasive mycosis in this population. Much of what we know about the management of these infections is extrapolated from observations in the general population or other at-risk populations supplemented by lessons learned specific to solid organ transplantation. As the solid organ transplant population continues to grow larger and live longer, the capacity to prevent, diagnosis, and treat these infections appropriately will become more relevant and challenging.

The Evolving Epidemiology of Sporotrichosis

Sporotrichosis is an uncommon subcutaneous mycosis found throughout the world. Certain tropical and subtropical areas, in particular South America, have regions of hyperendemic disease. Here, we report on the developing genetic diversity of the genus as well as the epidemiology, from the beginnings of the French and South African epidemics through the modern day outbreak in Brazil. The ongoing Brazilian epidemic has led to the discovery of a new species, Sporothrix brasiliensis, and there have been several other clinical and environmental species identified throughout the globe as well. It remains to be seen, however, just what impact this species diversity has on clinical disease.