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The field of transplant infectious diseases is rapidly evolving, presenting a challenge for clinical practice and trainee education. Here we describe the construction of transplantid.net, a free online library, crowdsourced and continuously updated for the dual purpose of point-of-care evidence-based management and teaching.

Altered mental status in immunosuppressed patients has a wide differential of potential etiologies. In this case, a 27-year-old male presented with encephalopathy, nausea, vomiting, and fevers. His medical history was significant for acute myeloid leukemia in remission after allogenic hematopoietic stem cell transplant 17 months prior complicated by graft versus host disease affecting his skin treated with sirolimus. A lumbar puncture was performed with a lymphocytic pleocytosis, mildly elevated protein, and negative gram stain and bacterial and fungal cultures. His examination deteriorated and he became comatose with loss of pupillary and corneal reflexes. An MRI of his brain demonstrated T2/FLAIR signal abnormality involving the bilateral basal ganglia, mesial temporal lobes, and entire brainstem along with bilateral temporal parenchymal and leptomeningeal enhancement. Ultimately, diagnosis was made via metagenomic polymerase chain reaction sequencing from his cerebrospinal fluid. This case highlights diagnostic challenges in immunosuppressed patients as antibodies against the causative antigen were negative (potentially related to decreased antibody production in the setting of immunosuppression).

Introduction: Catheter-associated urinary tract infection (CAUTI) is one of the most common nosocomial infections in hospitals, accounting for 36% of all health care-associated infections. Areas covered: We aimed to address the potential impact of antimicrobial coating of catheter materials for the prevention of CAUTI and to analyze the progress made in this field. We conducted literature searches in the PubMed, Embase, and Cochrane Library databases, and found 578 articles. Data from 60 articles in either the preclinical or clinical stage were analyzed in this expert review. Expert opinion: The literature review revealed many promising methods for preventing CAUTI. Recent studies have suggested the combination of silver-based products and antibiotics, owing to their synergistic effect, to help address the problem of antibiotic resistance. Other coating materials that have been tested include nitric oxide, chlorhexidine, antimicrobial peptides, enzymes, and bacteriophages. Because of heterogeneity among studies, it is difficult to reliably comment on the clinical efficacy of different coating materials. Future research should focus on double-blind randomized clinical trials for evaluating the role of these potential coating agents.

Background Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments. Methods We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs). Results The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection. Conclusions This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.

Chimeric antigen receptor T cell (CAR T) therapy has changed the treatment landscape of relapsed/refractory lymphoid malignancies. With an expanding pool of post–CAR T cell therapy survivors, prevention and management of late toxicities is emerging as an important component of survivorship care. This review summarizes the current state of evidence on late toxicities after CAR T cell therapy in lymphoid malignancies. Late effects that are well described in clinical trials and observational studies include hypogammaglobulinemia, prolonged cytopenias, late infections, neurologic and neuropsychiatric effects, immune-related late effects, and subsequent malignancies. Hypogammaglobulinemia is the most common late effect in the setting of CD19-directed CAR T cell therapy, which necessitates immunoglobulin replacement. Common determinants of late toxicities are age, underlying tumor type, previous therapy, CAR construct, and acute toxicities. Among currently approved indications, the incidence of hypogammaglobulinemia and prolonged cytopenia is higher in patients with acute lymphoblastic leukemia compared with patients with aggressive non-Hodgkin lymphoma. Patient-reported physical and mental quality of life in long-term survivors is comparable to that in the general population, albeit with limited data thus far. This review provides an overview of the incidence, known risk factors, and strategies for prevention and management of late toxicities in this population. Further research is needed to characterize the trajectory of late effects from population-based registries and long-term follow-up of ongoing clinical trials.

INTRODUCTION: The aim of our study is to evaluate risk factors associated with the development of C. difficile infection (CDI) in hematopoietic stem cell transplant (HSCT) patients, determine its incidence and report outcomes of CDI in our patient population. METHODS: We performed a retrospective review of medical records of adult HSCT recipients diagnosed between 2013 and 2016 at our center. Logistic regression models were used to determine the relationship between risk factors and the odds of CDI. RESULTS: The overall incidence of CDI in HSCT patients was 9.4%. The incidence of CDI was higher in allogeneic HSCT (20%) versus autologous HSCT (4.8%). No statistically significant differences in age, gender, cancer type, transplant type were found between those who developed CDI and those who did not. However, patients with CDI had a longer length of stay (25 days) and used more antibiotics (30 days prior to and during admission for HSCT) than non-CDI patients (19 days). Only two of 17 patients (11.8%) with CDI experienced recurrence among 180 patients after HSCT. No patient suffered from toxic megacolon or ileus and no patient underwent colectomy. There was no mortality associated with CDI at our center. CONCLUSION: CDI has an incidence rate of 9.4% in HSCT recipients. Established risk factors including age, gender, cancer type, and transplant type were not identified as risk factors in our population. However, longer LOS and use of greater than four lines of antibiotics were observed among those with CDI compared to those without CDI.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Hodgkin lymphoma with symptomatic osseous involvement can have a similar presentation to osteomyelitis. Common findings in symptoms, laboratory workup, and imaging can make it very difficult to distinguish between the two diseases. Excisional biopsy should be pursued if fine-needle biopsy is equivocal and suspicion of lymphoma is high. We report a case of a 40-year-old man who presented with a history of marine animal sting on his neck and later developed erythema in the area, chest pain, constitutional symptoms, adenopathy, and imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted the possibility of lymphoma, and further workup was initiated, which confirmed Hodgkin lymphoma. This case is a good reminder that malignancies and infections can share many common features, and keeping a broad differential diagnosis can be lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help determine the optimal treatment.

Immunocompromised patients undergoing chemotherapy for hematologic malignancy and hematopoietic stem cell transplant (HSCT) recipients are at increased risk of Clostridium difficile (C. difficile) infection (CDI). The recurrence of infection and its associated morbidity and mortality are due to multiple risk factors. Diarrhea is common in HSCT recipients, but the diagnosis of diarrhea caused by CDI is a therapeutic challenge due to frequent Clostridium difficile colonization with diarrhea secondary to non-infectious causes. The high recurrence rate is a significant challenge in the treatment of immunocompromised patients. Close monitoring of the patients, timely diagnosis, preventive measures, treatment with antibiotics, and the removal of offending agents can help in the management and cure of the disease. We review the literature on management and describe a patient with acute lymphoblastic leukemia (ALL) with multiple recurrences of CDI during leukemia therapy and allogeneic stem cell transplantation for leukemia.

Restoration of immune response by highly active antiretroviral therapy (HAART) effectively improved the overall prognosis of HIV infection. However, 25%–31.7% of patients experience paradoxical worsening of pre-existing infections or unmasking of subclinical infections after starting HAART therapy, which is termed as immune reconstitution inflammatory syndrome (IRIS). Acute granulomatous interstitial nephritis as a consequence of IRIS has never been reported with Mycobacteriumkansasiicoinfection. Here, we describe an HIV/AIDS patient coinfected with disseminated M. kansasii infection, who presented with acute kidney injury 4.5 months after initiation of HAART. The diagnostic workup revealed IRIS was the cause of acute kidney injury. Short-term course of prednisone (1 mg/kg/day) along with antimycobacterial and HAART regimen achieved significant improvement.

Background Cytomegalovirus (CMV) infection causes morbidity and mortality in solid-organ transplant recipients. Drug-resistant CMV is an emerging problem with poor survival outcomes and limited therapeutic options. In this study we comprehensively address the issue of drug resistance in CMV when compared with standard therapies, such as ganciclovir (GCV) and foscarnet. Methods We conducted a retrospective review of adult patients diagnosed with CMV after solid-organ transplant at our center between 2013 and 2017, and identified 7 resistant CMV cases. To study risk factors in the published literature, we performed an extensive database search. Results All patients had documented UL97 mutations, and 3 patients harbored both UL97 and UL54 mutations. For cases with increasing viral load or failure to achieve clinical improvement despite optimal therapy, genetic resistance testing was carried out. Patients received GCV and foscarnet combination therapy. As an adjunct, CMV immunoglobulin, cidofovir, and leflunomide were added. Risk factors, including donor+/recipient− serostatus, persistent high viral replication, prolonged therapeutic GCV exposure (>2.5 months), and allograft rejection, were assessed. Conclusion Patients at risk, especially those with D+/R− serostatus, should be judiciously monitored for resistance. Prolonged intravenous GCV exposure increases the risk for development of drug resistance. Therefore, precise guidelines are required for prevention of long-term GCV/VGCV exposure. Investigation regarding interferon-gamma release assay and adoptive transfer of T cells in diagnosed CMV patients is warranted to improve future prophylactic and management strategies against CMV, with a potential to reduce the requirement for available toxic antiviral drugs.

Intractable cerebral Nocardia mexicana in a GvHD patient successfully treated with linezolid

Mucor and Rhizopus cause life-threatening infections primarily involving the lungs and sinuses, which disseminate very rapidly by necrosis and infarction of the contiguous tissues. We present a case of a 64-year-old African American posttransplant patient who presented with a productive cough and weight loss. He had a past surgical history of renal transplant for renal cell carcinoma and was on dual immunosuppressive therapy, that is, mycophenolate and tacrolimus. During his hospital stay, he developed a pneumopericardium due to the direct extension of a lung lesion. The diagnosis was made by radiological imaging and PCR result which was consistent with Mucor species. He was treated with antifungal therapy. The purpose of this report is to highlight the unusual association of mucormycosis with pneumopericardium.

Urinary tract infections (UTIs) are the most common healthcare-acquired infections, and are associated with high morbidity and mortality. Worldwide use of antibiotics has led to a significant rise in resistant uropathogens emanating from both hospitals and communities. The huge concern of multidrug resistance (MDR) has led the Food and Drug Administration (FDA) to encourage drug companies to invest in the development of new antibiotics. Area covered: In this review we summarized data on already approved antibiotics, and selected emerging therapies that are currently in phase II and III trials with emphasis on complicated urinary tract infections (cUTIs). We performed our search using PubMed, ClinicalTrials.gov, Google Scholar and Pharmaprojects. Expert opinion: Efficacious antimicrobials are needed to overcome MDR organisms. There are several dugs in initial and later stages of development, but most of them lack full spectrum of activity against some Gram-negative organisms, particularly against MDR Pseudomonas aeruginosa. Better understanding of the pathogenesis of UTI and genetic engineering of pathogens can provide new drugs to combat resistance in the future.

A 72-year-old man with a history of blastoid variant stage IV relapsed refractory mantle cell lymphoma presented with new central nervous system (CNS) symptoms. Brain imaging was positive for rim-enhancing lesions along with a mitral valve mass on the echocardiogram. It was a challenge to establish the exact aetiology of these lesions in this patient. He was empirically treated with chemotherapy on the presumption that the brain lesions were secondary to progressive malignancy. However, brain biopsy was negative for malignancy and blood cultures were found positive for Nocardia kroppenstedtii sp nov. He subsequently improved with antibiotic therapy. Disseminated Nocardia can present with multiorgan involvement. Clinical and microbiological diagnosis can be challenging. Antimicrobial treatment-related side effects require close monitoring, and dosage changes or therapy adjustments may be necessary.

Background Diabetic foot ulcers (DFUs) cause significant morbidity and put great economic burden on patient and healthcare facilities. Infection is the main driving force behind admissions related to DFU. Culture of soft tissue or bone is invaluable in diagnosing infection but is time consuming. Inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) are rapid, simple, and inexpensive laboratory tests that can aid in early diagnosis of diabetic foot infection (DFI) and monitor response to treatment. We did a meta-analysis to compare diagnostic performance of inflammatory markers for detecting DFI. Methods We searched PubMed, Embase, and Cochrane databases from their inception to December 2017. This meta-analysis was performed according to PRISMA guidelines. We included studies based on following inclusion criteria: (1) at least one of the biomarkers (ESR, CRP, PCT) was evaluated; (2) both sensitivity and specificity were measured as outcomes; and (3) sufficient data were available to construct 2 × 2 contingency table. We used bivariate random effect regression model to pool the sensitivity and specificity of the targeted biomarkers. Results A comprehensive literature search identified a total of 73 studies. Twelve studies met our inclusion criteria. Number of studies reporting data on each individual biomarker was as follows: 11 for ESR, seven for CRP, and five for PCT. Pooled sensitivity and specificity for ESR were calculated to be 0.84 (95% CI 0.76–0.89) and 0.82 (95% CI 0.73–0.89) with area under receiver operating characteristic curve (AUROC) of 0.90 (95% CI 0.87–0.92). Pooled sensitivity and specificity for CRP were found to be 0.64 (95% CI 0.46–0.80) and 0.87 (95% CI 0.75–0.93) with AUROC of 0.85 (95% CI0.82–0.88). Pooled sensitivity and specificity for PCT were 0.74 (95% CI 0.62–0.83) with AUROC of 0.84 (95% CI 0.81–0.87). Conclusion ESR could be beneficial in ruling out infection in persons who have low suspicion of disease. For those who have high suspicion of disease, PCT could be helpful in ruling in infection. Clinicians should avoid ordering both ESR and CRP because role of CRP is limited. All inflammatory markers need standardization of threshold levels for detecting infection. Disclosures All authors: No reported disclosures.

Background Nocardiosis is a life-threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%-3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors. Methods We performed a retrospective review study on 54 SOT patients diagnosed with Nocardia between 1997 and 2016 at our center. To explore the association of various risk factors with both the development of disseminated disease and mortality, a series of Fisher's exact tests was used. Findings Incidence of nocardiosis in SOT patients was 2.65%. Fisher's exact tests revealed no association between development of disseminated disease and the following variables: transplant rejection (P = 1), elevated tacrolimus levels (P = .4), and CMV viremia (P = .06). Also, we did not find any association between mortality and the variables we evaluated: type of transplant, transplant rejection, renal failure, disseminated nocardia, and patient's age. Overall mortality and 1-year mortality were 17% and 11%. Interpretation Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).

Restoration of immune response by highly active antiretroviral therapy (HAART) effectively improved the overall prognosis of HIV infection. However, 25%–31.7% of patients experience paradoxical worsening of pre-existing infections or unmasking of subclinical infections after starting HAART therapy, which is termed as immune reconstitution inflammatory syndrome (IRIS). Acute granulomatous interstitial nephritis as a consequence of IRIS has never been reported with Mycobacteriumkansasiicoinfection. Here, we describe an HIV/AIDS patient coinfected with disseminated M. kansasii infection, who presented with acute kidney injury 4.5 months after initiation of HAART. The diagnostic workup revealed IRIS was the cause of acute kidney injury. Short-term course of prednisone (1 mg/kg/day) along with antimycobacterial and HAART regimen achieved significant improvement.

A 70-year-old man with history of heart transplant performed in 1986, presented with altered mental status. CT scan of brain showed ring-enhancing lesions, raising suspicion for metastatic malignancy. Work-up revealed bilateral adrenal masses, biopsy showed granulomatous changes consistent with histoplasmosis. The possibility of histoplasmosis was less likely as the patient had no prior history of symptomatic disease and had lived in the endemic area 30 years prior to presentation. Brain biopsy confirmed central nervous system involvement. Amphotericin B was initiated for disseminated disease but his hospital course was complicated by renal failure and new liver hypodensities on follow-up imaging. Acute progressive disseminated histoplasmosis can manifest after decades of initial exposure and should always be in differential diagnosis even in non-endemic areas for prompt diagnosis and better clinical outcome.

Background C. difficile infection (CDI) is the most common cause of nosocomial infections in U.S. and leading cause of gastroenteritis associated death. Incidence of CDI in hematopoietic stem cell transplant (HSCT) patients has been reported between 5.7% to 24.7% during first year after HSCT. Literature review reveals many risk factors i.e., allogenic-HSCT, extremes of age, myeloablative conditioning, prior vancomycin resistance (VRE) colonization, pre-transplant C. difficile colonization, severe mucositis, graft vs. host disease (GVHD), duration and type of antibiotics used, immunosuppression, proton pump inhibitor use and NAP1 C. difficile strain. Methods To study incidence and different variables for CDI, we performed a retrospective review of medical records of adult patients who underwent HSCT between 2013 and 2016 at our center. REDCap database was used to record key variables related to each patient’s HSCT and CDI, keeping in mind HIPPA guidelines. Categorical data were summed up as percentages and counts and numeric data as means, medians, standard deviations and ranges. Results A total of 181 HSCT recipients were included. Incidence of CDI was 10% (18 Patients). Cohort’s most common underlying malignancy was multiple myeloma (35.4%). 70% had autologous HSCT and 30% had allogenic HSCT. Among allogenic transplants, 53% had matched unrelated donor. Peripheral blood was the most common stem cell source (93%). Most common myeloablative conditioning regimen was melphalan (70%). 27% patients were on PPIs. 4% had PEG/NG tube placed and 12% were on TPN. 10% had diabetes mellitus. 5 patients had previous episodes of CDI. 69% developed mucositis. 5% patients developed acute GVHD. 6% had VRE colonization while 66% had no documentation for VRE. Out of positive CDI cases, 17% were NAP1 positive. No episode of ileus or mega colon was documented. Most common treatment regimen were metronidazole 500 mg per orally every 8 hourly (65%) and vancomycin 125 mg per orally four times a day (58.8%). Conclusion This single-center study demonstrates that CDI has 10% incidence in patients undergoing HSCT. Risk factors include neutropenia, high dose chemotherapy, mucosal damage and provision of broad spectrum antibiotic prophylaxis. Data on CDI prophylaxis in these patients is emerging and randomized prospective trials are needed. Disclosures All authors: No reported disclosures.

Candida albicans is a common human pathogen. Occasionally, it can cause peritonitis in immunocompromised and postsurgical patients. We report a case of a male patient who presented with abdominal pain and distention. He had a history of end-stage liver disease secondary to alcoholism. His peritoneal fluid culture revealed C albicans, and (1–3)-β-d glucan (BDG) level was elevated. His hospital course was complicated by sepsis and renal failure. He was treated with antifungals for spontaneous fungal peritonitis. Fungal peritonitis should be suspected in patients with chronic liver disease particularly with elevated BDG levels.