Kasule, Sabirah N

Abstract Background Management of disseminated Nocardia (NC) infection in transplant recipients requires prolonged antimicrobial therapy. Treatment can be particularly challenging if NC is resistant to standard agents. Drug toxicities can further limit options. We present a series of transplant patients with multi-drug resistant, disseminated NC infection complicated by serious adverse reactions to sequential antimicrobials. Methods This is a prospective review monitoring response to treatment of disseminated NC as well as adverse events to therapies. Results The first case is a 66-year old heart transplant patient who presented with fever and cough. Investigations revealed N. otitidiscaviarum lung lesion and multiple brain abscesses. Trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid were started empirically. NC was fully susceptible to linezolid only, and intermediate to quinolones and tobramycin. Linezolid was switched to ciprofloxacin due to ongoing cytopenia, and dose of TMP-SMX was reduced due to renal insufficiency. Repeat brain MRI showed enlarging abscesses; regimen was changed to linezolid and moxifloxacin. Severe peripheral neuropathy led to linezolid discontinuation and initiation of high-dose doxycycline plus moxifloxacin. One year into therapy, he presented with a large aortic dissection. His long-term quinolone therapy was felt to be contributory. He underwent aortic stent placement and remains on doxycycline monotherapy. The second case is a 74-year old female renal transplant patient who presented with fevers. A perinephric abscess was found which grew N. farcinica resistant to floroquinolones and clarithromycin, and intermediate to doxycycline. Further imaging also revealed pulmonary and brain involvement. TMP-SMX was started but soon switched to linezolid due to acute kidney injury. One month later she presented with severe thrombocytopenia and subdural hematoma thought to be secondary to linezolid. She died despite surgery. Conclusion This series illustrates challenges encountered in the treatment of disseminated NC infection in transplant recipients. Multidrug resistant NC coupled with serious toxicities of therapies often severely limits treatment options. Counseling patients and closely monitoring for adverse events is essential. Disclosures All Authors: No reported disclosures

AbstractCoccidioidomycosis is an infection caused by the geographically restricted dimorphic fungus, Coccidioides. Coccidioidomycosis occurs endemically in the southwestern and western United States, mainly in focused regions of Arizona and California where the incidence is highest, and in Central and South America. Patients with impaired immunity, especially those with impaired cellular immunity, are at higher risk of severe and disseminated disease. In this review, we describe the fungal ecology and mycology, epidemiology, pathophysiology, and normal immune defenses to Coccidioides as well as address current concepts in diagnosis, treatment, and continued care of patients with pulmonary coccidioidomycosis. We also present and answer our most frequently asked questions regarding patients with primary pulmonary coccidioidomycosis.

Abstract Background There is growing interest in the use of rapid blood culture identification (BCID) in antimicrobial stewardship programs (ASPs). Although many studies have looked at its clinical and economic utility, its comparative utility in gram-positive and gram-negative blood stream infections (BSIs) has not been as well characterized. Methods The study was a quasi-experimental retrospective study at the Mayo Clinic in Phoenix, Arizona. All adult patients with positive blood cultures before BCID implementation (June 2015 to December 2015) and after BCID implementation (June 2016 to December 2016) were included. The outcomes of interest included time to first appropriate antibiotic escalation, time to first appropriate antibiotic de-escalation, time to organism identification, length of stay, infectious diseases consultation, discharge disposition, and in-hospital mortality. Results In total, 203 patients were included in this study. There was a significant difference in the time to organism identification between the pre- and post-BCID cohorts (27.1 hours vs 3.3 hours, P < .0001). BCID did not significantly reduce the time to first appropriate antimicrobial escalation or de-escalation for either gram-positive BSIs (GP-BSIs) or gram-negative BSIs (GN-BSIs). Providers were more likely to escalate antimicrobial therapy in GP-BSIs after gram stain and more likely to de-escalate therapy in GN-BSIs after susceptibilities. Although there were no significant differences in changes in antimicrobial therapy for organism identification by BCID vs traditional methods, more than one-quarter of providers (28.1%) made changes after organism identification. There were no differences in hospital length of stay or in-hospital mortality comparing pre- vs post-BCID. Conclusions Although BCID significantly reduced the time to identification for both GP-BSIs and GN-BSIs, BCID did not reduce the time to first appropriate antimicrobial escalation and de-escalation.