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Background. Solid organ transplant recipients are at risk of severe coccidioidomycosis and are given prophylaxis to mitigate the risk. Patients with seropositive testing typically receive lifelong prophylaxis; currently, this prophylaxis strategy includes patients who are positive only for IgM by enzyme immunoassay (EIA-IgM-only), although this result may be falsely positive. Methods. We conducted a retrospective study at a large-volume transplant center in an endemic coccidioidomycosis region to compare outcomes of non–lung transplant recipients who were seropositive for Coccidioides but discontinued prophylaxis (case patients) to outcomes of patients who continued prophylaxis (controls). Results. No case or control patients developed active coccidioidomycosis during the follow-up period. Before transplant, 62 of 77 case patients (80.5%) had a single positive serologic test, of whom 27 of 62 were EIA-IgM-only positive (43.5%). In contrast, 57 of 77 controls (74.0%) had a single seropositive result (16/57 [28.1%] were EIA-IgM-only). The single EIA-IgM-only result was classified as falsely positive by infectious disease consultants in 20 of 43 patients (46.5%) compared with all other Coccidioides serologic results (13/111 [11.7%], P < 0.001). Lifetime antifungal prophylaxis was felt to be unnecessary for 28 of 43 patients (65.1%) who were EIA-IgM-only versus 31 of 111 patients (27.9%) with other serologic results (P < 0.001). Conclusions. For patients repeatedly positive for EIA-IgM-only and no evidence of seroconversion, compatible clinical illness, or radiographic findings, discontinuing antifungal prophylaxis may be reasonable after the first posttransplant year.

Introduction. The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods. We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results. In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54–3.05); p<0.001. There was no difference in overall survival (HR 0.90, CI 0.49–1.66) or graft survival (HR 1.27, CI 0.74–2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14–4.55; p=0.019) and graft survival (HR 1.98, CI 1.10–3.56; p=0.023) when patients with infection were compared to those without. Conclusions. As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution’s robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis.

Abstract 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. image

Abstract Background Large cohort studies from the Veteran’s Administration support the negative predictive value of the methicillin resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) swabs for skin and soft tissue infection (SSTI). We investigated the use of the nasal MRSA PCR swab to reduce the inappropriate empiric use of vancomycin and piperacillin-tazobactam for SSTI at our institution. Methods Between July and August 2021, we educated Hospital Internal Medicine (HIM) and Internal Medicine Residents (IMR) on the basics of SSTI management and the utility of a negative nasal MRSA PCR swab. Data on empiric use of vancomycin and piperacillin-tazobactam for SSTIs were collected 3/1/2021 to 7/1/2021 (pre-intervention) and 8/30/2021 to 12/29/2021 (post-intervention). We excluded patients who didn’t have an SSTI, weren’t managed by IMR or HIM, and whose empiric antibiotics were for another indication. To account for antibiotics started in the emergency department (ED), a patient was regarded as having received appropriate empiric antibiotics if they were de-escalated in the first 24 hours of being admitted to IMR or HIM. Example of education material. These fliers were distributed to resident rooms following a series of noon conferences Results Pre-intervention there were 106 patient encounters. In 56 of these (52.8%), patients were placed on inappropriate empiric antibiotics. Post-intervention, there were 72 patient encounters. In 23of these (31.9%), patients were placed on inappropriate empiric antibiotic for an absolute risk reduction (ARR) of 20.9% with a statistically significant 95% CI (6.522 - 35.249) and a number needed to treat (NNT) of 4.78. Nasal MRSA PCR testing increased from 40.6% to 56.9%. The ARR among the HIM teams was 21.3% and was statistically significant with a 95% CI (4.24 - 38.394). Their proportion of MRSA testing increased from 41.5% to 50%. The IMR teams had an ARR of 14.8%, which was not statistically significant (95% CI, -11.339 to 40.884). Their MRSA nasal PCR testing increased from 37.5% to 72%. Conclusion Education on SSTI treatment coupled with use of the MRSA nares PCR appeared to improve empiric antibiotic choices. Residents stated that the nasal MRSA PCR facilitated empiric antibiotic choice. Positive ARR was seen in whole and sub-group analyses of physician teams. We theorize that the lack of statistical significance in the IMR group was related to a small sample size. Disclosures All Authors: No reported disclosures.

Introduction: Coccidioidal meningitis (CM) is the most lethal form of disseminated coccidioidomycosis. Current guidelines recommend fluconazole as initial therapy but there has been a paucity of data regarding failure of fluconazole and optimal fluconazole dosage in the treatment of CM. We conducted this study to understand risk factors for fluconazole failure. Methods: We conducted a single-center retrospective chart review of patients diagnosed with coccidioidal meningitis between 1 January 1988 and 15 May 2021. Relevant demographic and clinical variables were collected, along with outcomes including treatment failure and death at any point. Univariate tests were conducted using the chi-squared goodness of fit test and analysis of variance. Results: Among 71 patients who began treatment for CM with fluconazole, 22 (31%) developed worsening meningitis at a median time of 206 days. Longer time from symptom onset to diagnosis of CM was a risk factor for fluconazole failure. Although the absolute failure rate of fluconazole starting dose of 400 mg daily was higher than that of 800 mg daily, the differences did not achieve statistical significance (p = 0.39). Conclusion: Fluconazole failure is not uncommon in the treatment of CM. A dose of 800 mg daily was not superior to a dose of 400 mg daily. All patients on fluconazole for CM require close monitoring.

AbstractIntroductionInfections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection.MethodsThis is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment.ResultsWe identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients.ConclusionsInfections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. image

The COVID-19 pandemic has disrupted medical care worldwide and caused delays in care for many illnesses and procedures unrelated to COVID-19; however, less clear is how it may have affected diagnosis of conditions that present with similar symptoms, such as primary pulmonary coccidioidomycosis (PPC). We conducted an observational cohort study of patients diagnosed with PPC between March 1 and December 1 in 2 years: 2019 (before COVID-19) and in 2020 (after COVID-19) to compare the time from symptom onset to PPC diagnosis. Relevant demographic and clinical variables were collected, and statistical analyses were performed with the χ 2 test, Wilcoxon rank sum test, and Cox proportional hazards regression analysis. During 2019, 83 patients were diagnosed with PPC. During 2020, 113 patients were diagnosed with PPC. For both groups, the median time from symptom onset to diagnosis of PPC was 14 days (P = .13). No significant differences in time to diagnosis existed between the 2 years for location of diagnosis (outpatient clinic, emergency department, or in hospital), for computed tomographic imaging performed before diagnosis, or for number of COVID-19 tests received before PPC diagnosis. In addition, there were no differences in the 2 years between the total number of clinical visits before diagnosis. However, patients in the post-COVID-19 group who had fever were diagnosed with PPC earlier than those without fever (hazard ratio, 1.77; 95% confidence interval, 1.15–2.73; P = .01). Contrary to what we expected, no significant delay in diagnosis of PPC occurred during the COVID-19 pandemic.