Neuroinvasive West Nile virus infection in solid organ transplant recipients.

BACKGROUND: Literature on the natural course of neuroinvasive West Nile virus (WNV) infection in solid organ transplant (SOT) recipients is sparse. In the setting of a 2021 WNV outbreak in Arizona, we reviewed our institution's experience with neuroinvasive WNV infection in patients with SOT. METHODS: We retrospectively identified SOT recipients treated for neuroinvasive WNV at Mayo Clinic in Arizona from 2007 through 2021. Clinical manifestations, disease course, and outcomes were analyzed. RESULTS: Among 24 SOT recipients with WNV infection identified during the study period, 13 infections occurred in 2021. Most patients had gastrointestinal tract symptoms and fever at disease presentation. Five patients had cognitive impairment, and 14 initially or eventually had acute flaccid paralysis. Clinically significant deterioration occurred at a median of 4 (range, 1-11) days after hospital admission. Seventeen patients (71%) were transferred to the intensive care unit, with 15 requiring mechanical ventilation. Initial cerebrospinal fluid analysis mainly demonstrated a neutrophil-predominant pleocytosis. Almost all patients (n = 23) were treated with intravenous immunoglobulin alone or in combination with interferon alfa-2b. Sixteen patients had clinical improvement, 4 of whom recovered completely. Six patients died during hospitalization due to complications of neuroinvasive WNV infection. Two patients were discharged to hospice without clinical recovery. The overall 30-day mortality rate was 36%. CONCLUSION: Despite advances in supportive care, neuroinvasive WNV infection is associated with substantial morbidity and mortality in SOT recipients. Flaccid paralysis is an indicator of poor prognosis.

Coccidioidomycosis in Patients Treated With Ruxolitinib.

We report 8 cases of coccidioidomycosis associated with ruxolitinib treatment. Among 135 patients living in the coccidioidal-endemic region receiving ruxolitinib, 5 cases were diagnosed after starting and 4 had extrathoracic dissemination. Periodic serological screening while on ruxolitinib is warranted for patients residing in the coccidioidal-endemic region.

A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients.

BACKGROUND: Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. METHODS: Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/µL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. RESULTS: From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, -0.33 log10 copies/mL; 95% confidence interval [CI] -.64 to -.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22-1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. CONCLUSIONS: Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. CLINICAL TRIALS REGISTRATION: NCT02254408; EUDRA-CT#2014-002474-36.

Clostridioides difficile therapeutics: guidelines and beyond.

Clostridioides difficile infection (CDI) has become an increasingly common infection both within and outside of the hospital setting. The management of this infection has been evolving as we learn more about the role of the human microbiota in protecting us from this gastrointestinal opportunist. For many years the focus of treatment had been on eradication of the vegetative, toxin-producing form of the organism, with little regard for its collateral impact on the host's microbiota or risk of recurrence. With the marked increase in C. difficile disease, and, particularly, recurrent disease in the last decade, new guidelines are more focused on targeting and reducing collateral damage to the colonic microbiota. Immune-based strategies that manipulate the microbiota and provide a humoral response to toxins have now become mainstream. Newer strategies are needed to look beyond simply resolving the primary episode but are focused on delayed outcomes such as cure at 90 days, reduced morbidity and mortality, and patient quality of life. The purpose of this review is to familiarize readers with the most recent evidence-based guidelines for C. difficile management, and to describe the role of newer antimicrobials, immunological-, and microbiota-based therapeutics to prevent recurrence and improve the outcomes of people with CDI.

Why Does Clostridium difficile Infection Recur?

Clostridium (or Clostridioides) difficile infection affects more than 500,000 people annually in the United States, one-third of whom have recurrent symptoms. The evolution of C difficile as a resilient pathogen has to do with its ability to persist in the environment and in the host, leading to recurrence and environmental spread. Understanding the mechanisms by which this microbe interacts with the environment, the host, and the gut microbiota are critical to solving this problem. This article presents a brief clinical vignette; discusses the current state of understanding of colonization, transmission, and recurrence; and considers the role the host plays in eliminating this infection. The understanding of these mechanisms and application of osteopathic principles has the potential to improve patient outcomes.

A case of Verruconis gallopava infection in a heart transplant recipient successfully treated with posaconazole.

Verruconis gallopava is an environmental dematiaceous fungus that is recognized increasingly as a cause of human disease, especially for immunocompromised persons. Infection can range from superficial and localized lesions to pulmonary involvement and disseminated disease, including central nervous system abscesses. Optimal therapy is undefined. We report a patient post cardiac transplant who had pulmonary infection with V gallopava and was treated successfully with posaconazole.

Mini-Fecal Microbiota Transplantation for Treatment of Clostridium difficile Proctitis Following Total Colectomy.

Rarely, in fulminant Clostridium difficile infection (CDI), the rectal stump is persistently infected following total abdominal colectomy. We report cure of a septic patient with proctitis by fecal microbiota transplant via rectal swabs (mini-FMT). This novel procedure offers a management option for recurrent CDI following total abdominal colectomy.

St. Louis encephalitis virus possibly transmitted through blood transfusion-Arizona, 2015.

BACKGROUND: St. Louis encephalitis virus is a mosquito-borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source. STUDY DESIGN AND METHODS: The patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito-borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection. RESULTS: The patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus-infected mosquito pools were identified around the patient's residence. CONCLUSION: This investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified.

Vancomycin Taper and Risk of Failure of Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection.

We retrospectively analyzed a cohort of 109 subjects treated for recurrent Clostridium difficile infection with fecal microbiota transplantation (FMT) at a tertiary referral center between 2011 and 2014 to determine risk factors for FMT failure. In a multivariate analysis, failure to use an oral vancomycin taper preceding FMT was associated with a significant risk of FMT failure (odds ratio, 0.15; 95% confidence interval, .007-.40).

Integrative Medicine Preferences Among Coccidioidomycosis (Valley Fever) Patients.

OBJECTIVES: To understand the extent and modalities of integrative medicine strategies that patients with coccidioidomycosis (valley fever) have incorporated into their treatment regimens. DESIGN: A direct patient survey was distributed, with 100 unique responses, at a single infectious diseases clinic at an academic medical center in Arizona. Eligible patients, defined as those with confirmed coccidioidomycosis or currently under evaluation, were polled on their personal use of 36 integrative medicine modalities. Patients were also asked to indicate their level of fatigue on a 10-point scale in an attempt to correlate levels of fatigue to use of specific integrative medicine modalities. RESULTS: Of the patients surveyed, 64% had used at least one integrative medicine modality, and 53% used two or more, along with conventional medical therapy. The top three modalities were nutrition (39%), massage (27%), and breathing exercises (26%). The mean reported fatigue level was 4.7 on a 10-point scale, with a standard deviation of 3.0. There was no statistically significant association between use of a specific modality and reported level of fatigue. CONCLUSIONS: Nearly two thirds of patients (64%) surveyed had used at least one integrative medicine modality throughout the course of their therapy. Clinicians are probably unaware of the extent to which many patients, including this population, have embraced integrative medicine. Awareness of patients' goal and preferences is valuable in shared clinical decision making.

Plasma cell pleocytosis in cerebrospinal fluid in patients with West Nile virus encephalitis.

We describe 4 patients with West Nile virus encephalitis who all displayed previously unreported plasma cell pleocytosis of the cerebrospinal fluid (CSF). Three patients recovered but had varying degrees of mild neurologic disability on discharge from the hospital, and 1 patient died. The finding of significant numbers of plasma cells in CSF may serve as a useful early diagnostic clue for West Nile virus encephalitis.