Abad, Cybéle Lara R.

AbstractBackgroundGeographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation, and outcomes of 5 endemic mycoses in SOT recipients.MethodsMultiple databases were reviewed from inception through May 2023 using key words for endemic fungi (eg, coccidioidomycosis or Coccidioides, histoplasmosis or Histoplasma, etc). We included adult SOT recipients and publications in English or with English translation.ResultsAmong 16 cohort studies that reported on blastomycosis (n = 3), coccidioidomycosis (n = 5), histoplasmosis (n = 4), and various endemic mycoses (n = 4), the incidence rates varied, as follows: coccidioidomycosis, 1.2%–5.8%; blastomycosis, 0.14%–0.99%; and histoplasmosis, 0.4%–1.1%. There were 204 reports describing 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis cases. The majority of patients were male (176 of 261 [67.4%]). Transplanted allografts were mostly kidney (192 of 268 [71.6%]), followed by liver (n = 39 [14.6%]), heart (n = 18 [6.7%]), lung (n = 13 [4.9%]), and combined kidney-liver and kidney-pancreas (n = 6 [2.7%]). In all 5 endemic mycoses, most patients presented with fever (162 of 232 [69.8%]) and disseminated disease (179 of 268 [66.8%]). Cytopenias were frequently reported for histoplasmosis (71 of 91 [78.0%]), coccidioidomycosis (8 of 11 [72.7%]) and talaromycosis (7 of 8 [87.5%]). Graft loss was reported in 12 of 136 patients (8.8%). Death from all-causes was reported in 71 of 267 (26.6%); half of the deaths (n = 34 [50%]) were related to the underlying mycoses.ConclusionsEndemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high all-cause mortality rate, including many deaths that were attributed to endemic mycoses.

AbstractBackgroundDonor‐derived endemic mycoses are infrequently reported. We summarized the clinical characteristics and outcomes of these infections to provide guidance to transplant clinicians.MethodsMultiple databases were reviewed from inception through May 31, 2023 using endemic fungi as key words (e.g., Coccidioides, histoplasma, blastomyces, talaromyces, paracoccidioides). Only donor‐derived infections (DDI) were included.ResultsTwenty‐four cases of DDI were identified from 18 published reports; these included 16 coccidioidomycosis, seven histoplasmosis, and one talaromycosis. No cases of blastomycosis and paracoccidiodomycosis were published. The majority were male (17/24,70.8%). Half of the cases were probable (12/24, 50%), seven were possible (29.2%), and only five were proven DDI (20.8%). Donor‐derived coccidioidomycosis were observed in kidney (n = 11), lung (n = 6), liver (n = 3), heart (n = 2) and combined SOT recipients (1 KP, 1 KL) at a median time of .9 (range .2–35) months after transplantation. For histoplasmosis, the majority were kidney recipients (6 of 7 cases) at a median onset of 8 (range .4–48) months after transplantation. The single reported possible donor‐derived talaromycosis occurred in a man whose organ donor had at‐risk travel to Southeast Asia. Collectively, the majority of donors had high‐risk exposure to Coccidioides (9/11) or Histoplasma sp. (6/6). Most donor‐derived endemic mycoses were disseminated (18/24, 75%), and mortality was reported in almost half of recipients (11/24, 45.8%).ConclusionDonor‐derived endemic mycoses are often disseminated and are associated with high mortality. A detailed evaluation of donors for the potential of an undiagnosed fungal infection prior to organ donation is essential to mitigate the risk of these devastating infections.

AbstractBackgroundEndemic mycoses after hematopoietic stem cell transplantation (HSCT) are rarely reported. We aimed to comprehensively review the clinical presentation and outcomes of endemic mycoses in this immunocompromised population.MethodsMultiple databases were reviewed from inception through May 31, 2023 using endemic fungi as keywords (e.g., coccidioides, histoplasma, blastomyces, talaromyces, and paracoccidioides). Only hematopoietic transplants were included.ResultsThere were 16 publications on endemic mycoses after HSCT that reported nine unique cases of histoplasmosis, seven coccidioidomycosis, and two talaromycosis. No cases of paracoccidioides and blastomycoses were identified. Fifteen cases were allogeneic hematopoietic transplant recipients and three were autologous. Many were male (14/18, 77.8%) and overall median age was 50 (range 21–75) years. Among the 16 patients with coccidiodomycosis or histoplasmosis, fever, cytopenias and disseminated disease were the most common clinical presentations, with median onset of 8 or 12 months after HSCT, respectively. Likewise, the two HSCT patients with talaromycosis presented with disseminated disease at 12 and 48 months after transplantation. The vast majority were not on effective azole prophylaxis at the time of presentation, and many had recent intensification of immunosuppression. Nine of 18 patients died (50%), and all deaths occurred among patients with disseminated endemic mycoses.ConclusionEndemic mycoses among HSCT are uncommon. Onset was late, after discontinuation of azole prophylaxis, or was associated with intensification of immunosuppression. Disseminated disease was a common presentation, manifested by fever and cytopenias. Attributable mortality was high, and emphasizes the need for a high index of clinical suspicion so that prompt diagnosis and treatment is provided. image

AbstractBackgroundManagement of multidrug‐resistant (MDR) and rifampin‐resistant (RR) tuberculosis is challenging. Data on transplant recipients is limited. We reviewed published literature to examine treatment choices, outcomes, and adverse effects from MDR‐TB/RR‐TB treatment in transplant recipients.MethodsMultiple databases from inception to 12/2022 were reviewed using the keywords “drug‐resistant TB” or “drug‐resistant tuberculosis” or “multidrug‐resistant TB” or “multidrug‐resistant tuberculosis”. MDR‐TB was defined as resistance to isoniazid (H) and rifampin (R), and RR if resistant to rifampin alone. Cases without patient‐level data and reports which did not describe treatment and/or outcomes for MDR‐TB were excluded.ResultsA total of 12 patients (10 solid organ transplants and two hematopoietic cell transplants) were included. Of these, 11 were MDR‐TB and one was RR‐TB. Seven recipients were male. The median age was 41.5 (range 16–60) years. Pre‐transplant evaluation for the majority (8/12, 66.7%) did not reveal a prior history of TB or TB treatment, but 9/12 were from TB intermediate or high‐burden countries. Seven patients were initially treated with the quadruple first‐line anti‐TB regimen. Those who had early RR confirmation (5/12) via Xpert MTB/RIF assay were initiated on alternative therapies. Final regimens were individualized based on susceptibility profiles and tolerability. Adverse events were reported in seven recipients, including acute kidney injury (n = 3), cytopenias (n = 3), and jaundice (n = 2). Four recipients died, with two deaths attributable to TB. The remaining eight patients who survived had functioning allografts at the last follow‐up.ConclusionsMDR‐TB treatment in transplant recipients is associated with many complications. Xpert MTB/RIF detected RR early and guided early empiric therapy. image

Abstract Background We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation. Methods CINAHL, PUBMED, and OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation. Results Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14–417) and 8.8 (range, 0–208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 [79.6%]), while skin rash (22/108 [20.3%]) and fever (31/103 [30%]) were less common. Peripheral eosinophilia was observed in half of patients (41/77 [53.2%]). Bacteremia (31/59 [52.5%]) was frequently due to Gram‐negative organisms (24/31 [77.4%]). Abnormal chest radiologic findings were reported in half (56/108 [51.9%]). The majority had hyperinfection syndrome (97/108 [89.8%]) while disseminated strongyloidiasis was less common (11/108 [10.2%]). Thirty‐two cases were categorized as donor‐derived infection (DDI), with donors (23/24 [95.8%]) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5–34.3 weeks) after transplantation. Treatment consisted of ivermectin ( n = 26), a benzimidazole ( n = 27), or both drugs ( n = 28). There was high all‐cause mortality (48/107, 44.9%) and a high Strongyloides ‐attributable mortality (32/49, 65.3%). Conclusions Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro‐active screening is needed, to ensure preventive measures are provided to recipients at increased risk.

AbstractBackgroundNeutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation.MethodWe conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation.ResultsA total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D‐index value compared with patients who did not have BSI (4990 vs. 3570, P < .001). As a marker, the performance of the D‐index was similar to that of the duration of profound neutropenia (P = .18) and significantly better than the total duration of neutropenia (P = .001).ConclusionThe D‐index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D‐index and, a more easily calculable indicator, duration of profound neutropenia.

Abstract Introduction Patients with hematologic malignancies are at higher risk for infection due to the nature of their immunocompromised status, therapy-related complications, and numerous other factors. Multiple myeloma (MM) is the second most common hematologic malignancy after non-Hodgkin's lymphomas. Current literature on bone and joint infections (BJI) in MM is limited to case reports, and this study aims to identify the frequency and characteristics of BJI in MM. Methods We retrospectively reviewed 4607 patients within the MM database at Mayo Clinic from 1/1/2005 through 1/1/2015. A computerized search of the electronic medical record using diagnosis codes, pathology reports, and free text searches, followed by manual chart review, identified 39 unique patients with BJI as depicted in Figure 1. Results Of the 39 patients with BJI and a diagnosis of multiple myeloma, 28/39 (72%) were male, and median age was 70 years-old (range 39-86). 35/39 (90%) had IgG subtype MM, and 21/39 (54%) were in remission from MM while 4/39 (10%) were neutropenic at the time of BJI. 14/39 (36%) occurred after hematopoietic stem cell transplant, and the median duration from transplant to BJI was 45.0 months (range 1.0-88.7). 11/39 (28%) had chronic kidney disease on chart review, and 8/39 (21%) were on corticosteroids. 32/39 (82%) had prior exposure to chemotherapy, and median duration from most recent chemotherapy to BJI was 32 days (range 0-1559). Septic arthritis (9/39, 23%) and osteomyelitis (9/39, 23%) occurred most frequently followed by prosthetic joint infection (PJI) (8/39, 21%). Pathogens were primarily Gram positive organisms (20/39, 51%), and 7/20 (35%) had polymicrobial infections. All patients received culture-guided induction antimicrobial therapy. 27/39 (69%) underwent surgical intervention. Treatment and outcomes by infection can be seen in Figure 1. Of the 5 (13%) treatment failures (TF), 3 (60%) had PJI while 1 (20%) had osteomyelitis with necrotizing fasciitis, and 1 (20%) had septic arthritis. Median time from diagnosis of BJI to TF was 6.3 months (range 0.0-13.5), and none of the TF were neutropenic at the time of BJI. 26/39 (67%) were alive one year after BJI, and at latest chart review, 8/39 (21%) were alive, of whom 7 were treated successfully. Median overall survival from diagnosis of BJI was 34.3 months for all cases. Conclusions BJI are uncommon in MM, and pathogens are similar to patients without MM, though with polymicrobial infections occurring frequently. Treatment is successful in the majority of cases, but PJI appear to have higher TF rates. However, TF may not necessarily correlate with hematologic status or survival. Figure 1 Flowchart of the multiple myeloma study cohort, BJI, treatment, and outcomes MM = Multiple Myeloma; BJI = Bone and Joint Infection; PJI = Prosthetic Joint Infections; VO = Vertebral Osteomyelitis; I&D = Irrigation & Debridement; Abx = Antibiotic Therapy Alone; DAIR = Debridement and Implant Retention; TF = Treatment Failure; CHF = Congestive Heart Failure Figure 1. Flowchart of the multiple myeloma study cohort, BJI, treatment, and outcomes. / MM = Multiple Myeloma; BJI = Bone and Joint Infection; PJI = Prosthetic Joint Infections; VO = Vertebral Osteomyelitis; I&D = Irrigation & Debridement; Abx = Antibiotic Therapy Alone;. / DAIR = Debridement and Implant Retention; TF = Treatment Failure; CHF = Congestive Heart Failure Disclosures Kapoor: Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding.

Abstract Background Mycobacterium tuberculosis disease may occur after treatment of latent TB infection (LTBI). Prompted by a case of reactivation TB disease in a solid organ transplant (SOT) recipient who received LTBI treatment, we reviewed the literature to examine outcomes, adverse effects, resistance, and treatment choices of tuberculosis after LTBI therapy. Methods MEDLINE and Web of Science from inception to 5/2019 were reviewed using key words “latent tuberculosis infection” and “SOT” or “transplantation.” The search yielded nine cases, 41 cohort studies and six randomized controlled trials (RCT). Results Cohort and RCT demonstrated significant reduction in TB disease among transplanted patients who received LTBI therapy; only 56/2651 (2.1%) SOT patients developed TB after LTBI therapy. Adverse drug reactions occurred in 149/1148 (12.9%) and 73/641 (11.4%) of cohort and RCT patients, respectively. Among liver recipients, 56/266 (21%) developed side effects, of which half (29/56, 51.8%) was INH‐related. There was no reported INH resistance. Conclusions Latent TB infection treatment is efficacious in SOT recipients at risk of TB disease. However, tuberculosis may still occur despite LTBI treatment. Hepatotoxicity associated with LTBI therapy is infrequent, although more commonly observed among liver recipients.