Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near‐drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant‐related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near‐drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near‐drowning events. Attention to aseptic technique during organ recovery and processing is re‐emphasized. Two patients developed renal mucormycosis following transplantation of kidneys from the same donor, a near‐drowning victim in a motor vehicle crash. Genotypically, indistinguishable strains of Apophysomyces elegans were recovered from both recipients. We investigated the source of the infection including review of medical records, environmental sampling at possible locations of contamination and query for additional cases at other centers. Histopathology of the explanted kidneys revealed extensive vascular invasion by aseptate, fungal hyphae with relative sparing of the renal capsules suggesting a vascular route of contamination. Disseminated infection in the donor could not be definitively established. A. elegans was not recovered from the same lots of reagents used for organ recovery or environmental samples and no other organ transplant‐related cases were identified. This investigation suggests either isolated contamination of the organs during recovery or undiagnosed disseminated donor infection following a near‐drowning event. Although no changes to current organ recovery or transplant procedures are recommended, public health officials and transplant physicians should consider the possibility of mucormycosis transmitted via organs in the future, particularly for near‐drowning events. Attention to aseptic technique during organ recovery and processing is re‐emphasized.
Abstract Background Initial antifungal (AF) regimens (AFR) for Invasive Aspergillosis (IA) are often changed due to treatment failure, intolerability, or drug-drug interactions. We compared outcomes among IA patients who did and did not change their initial IA AFR.Table 1.Adjusted Baseline Characteristics of Patients Who Changed or Did Not Change Their IA Antifungal Regimen*CCI=Charlson comorbidity index; COPD=chronic obstructive pulmonary disease; IA= invasive Aspergillosis; SD=standard deviation*The following covariates were used to calculate propensity scores for Inverse probability of treatment weighting: age group, geographic region, payer type, year of index, asthma, autoimmune conditions, bacteremia, COPD, pneumonia, immunodeficiencies, myelodysplastic syndrome, transplant history, immunosuppressants, cancer, neutropenia, and total healthcare costs.||All covariates were well balanced as indicated by an SMD <0.1 except corticosteroids which was marginally imbalanced with an SMD of 0.108†Solid organ or hematopoietic cell transplant#Partial years data available in IQVIA New Data Warehouse⁋Azathioprine, cyclophosphamide, cyclosporine, methotrexate, mycophenolate, tacrolimus, voclosporin Methods This retrospective cohort study identified US adults with an index hospitalization for IA (ICD-10: B44.0, B44.1, B44.7) between Oct 2015 and Nov 2022 in IQVIA’s New Data Warehouse (pharmacy, outpatient and hospital claims). Patients were placed into two cohorts based on whether they changed AFRs, defined as starting a new AFR with or without discontinuing initial therapy at any subsequent point. Inverse probability of treatment weighting minimized confounding due to baseline differences between patients who changed vs. did not change their AFR. Inpatient length of stay (LOS), all-cause costs (in 2023 US$) and all-cause mortality in IA patients who did and did not change their initial AFR were reported as medians with interquartile ranges (IQR) or frequencies and compared.Table 2.Adjusted* Outcomes of Patients Who Changed or Did Not Change Their IA Antifungal RegimenLOS=length of stay; IA= invasive Aspergillosis; ICU=intensive care unit; IQR=interquartile range; SD=standard deviation*Inverse probability of treatment weighted Results Among 1,192 IA patients, 707 (59.3%) changed their initial AFR (Table 1). Most patients started therapy on an -azole (87% among those who changed vs 95% in those who did not change regimens). Duration of initial AFR for those who did and did not change their regimen was a median of 5 days (IQR=7) vs. 11 days (IQR=24), respectively. Hospital and ICU LOS were longer in the AFR change than the no change cohort (Table 2). Median costs associated with the index hospitalization, including pharmacy costs, were also significantly higher for those who changed AFR compared with those who did not. No statistical difference was seen in inpatient mortality during the index hospitalization between cohorts. Conclusion In this large contemporary cohort of patients with IA, most patients changed AFRs, with many doing so within 1-2 weeks of treatment initiation. Changing regimens was associated with significantly longer hospital and ICU LOS as well as higher inpatient costs. Further study is needed to understand reasons for changing AFRs and to understand changes that might be avoided. New and improved AFs that reduce the need for regimen changes offer the opportunity to reduce the economic and clinical burden associated with changing AFRs. Disclosures Barbara D. Alexander, MD, Basilea: Advisor/Consultant|F2G: Advisor/Consultant|F2G: Grant/Research Support|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Scynexis: Grant/Research Support|TFF Pharmaceuticals: Advisor/Consultant Mark Bresnik, MD, F2G Ltd: Employee Ruthwik Anupindi, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Lia Pizzicato, MPH, F2G Ltd: Grant/Research Support|IQVIA: Employee Mitchell DeKoven, PhD, F2G Ltd: Grant/Research Support|IQVIA: Employee Belinda Lovelace, PharmD, MS, MJ, F2G, Inc.: Employee Craig I. Coleman, PharmD, F2G Ltd: Advisor/Consultant|F2G Ltd: Grant/Research Support Melissa D. Johnson, PharmD MHS AAHIVP, Biomeme: Licensed Technology|Scynexis, Inc: Grant/Research Support|UpToDate: Author Royalties
Invasive fungal infections are occurring with increasing frequency secondary to medical advances in the areas of transplantation, cancer management and autoimmune diseases. Unfortunately, the currently available antifungal armamentarium does not meet the increasing needs of managing infection in these complex patient populations. Posaconazole, a new triazole antifungal agent, is being investigated for its role in treating serious infections due to yeasts and molds. This new drug offers an expanded spectrum of activity over other members of its class. In addition to potent activity against fluconazole-resistant Candida and refractory cases of aspergillosis, posaconazole demonstrates activity against Zygomycetes. Posaconazole is a well-tolerated agent that offers a diminished toxicity profile compared with other currently marketed systemic antifungal agents. Clinical success rates thus far have been promising, although the exact role of this agent in treating and preventing invasive fungal infections is yet to be determined.
ABSTRACT A 30-year-old man died with Pandoraea pnomenusa sepsis after lung transplantation. Pandoraea species are gram-negative rods, closely related to, and commonly misidentified as, Burkholderia cepacia complex or Ralstonia species. Heretofore considered soil bacteria and colonizers that infect patients with chronic lung diseases, Pandoraea species can produce severe infections.
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