Search

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence.Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools.Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available.Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy.Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Spontaneous bacterial peritonitis (SBP) is a feared complication of ascites that affects 10%-30% of hospitalized patients with cirrhosis with an associated mortality rate of approximately 20%.1-3 Although efforts have been undertaken to encourage prompt evaluation and treatment of SBP, outcomes have generally remained dismal.3 There is significant interest in identifying factors that can reliably predict mortality among individuals with SBP.

Background Coronavirus disease 2019 (COVID-19) has strained healthcare systems with patient hospitalizations and deaths. Anti-spike monoclonal antibodies, including bamlanivimab, have demonstrated reduction in hospitalization rates in clinical trials, yet real-world evidence is lacking. Methods We conducted a retrospective case-control study across a single healthcare system of nonhospitalized patients, age 18 years or older, with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, risk factors for severe COVID-19, and referrals for bamlanivimab via emergency use authorization. Cases were defined as patients who received bamlanivimab; contemporary controls had a referral order placed but did not receive bamlanivimab. The primary outcome was 30-day hospitalization rate from initial positive SARS-CoV-2 polymerase chain reaction (PCR). Descriptive statistics, including χ 2 and Mann-Whitney U test, were performed. Multivariable logistic regression was used for adjusted analysis to evaluate independent associations with 30-day hospitalization. Results Between 30 November 2020 and 19 January 2021, 218 patients received bamlanivimab (cases), and 185 were referred but did not receive drug (controls). Thirty-day hospitalization rate was significantly lower among patients who received bamlanivimab (7.3% vs 20.0%, risk ratio [RR] 0.37, 95% confidence interval [CI]: .21–.64, P < .001), and the number needed to treat was 8. On logistic regression, odds of hospitalization were increased in patients not receiving bamlanivimab and with a higher number of pre-specified comorbidities (odds ratio [OR] 4.19 ,95% CI: 1.31–2.16, P < .001; OR 1.68, 95% CI: 2.12–8.30, P < .001, respectively). Conclusions Ambulatory patients with COVID-19 who received bamlanivimab had a lower 30-day hospitalization than control patients in real-world experience. We identified receipt of bamlanivimab and fewer comorbidities as protective factors against hospitalization. Bamlanivimab’s role in preventing hospitalization associated with coronavirus disease 2019 (COVID-19) remains unclear. In a real-world, retrospective study of 403 high-risk, ambulatory patients with COVID-19, receipt of bamlanivimab compared to no monoclonal antibody therapy was associated with lower 30-day hospitalization.

Background We present a yet to be described association of SARS-CoV-2 infection with Kikuchi-Fujimoto disease. Case presentation A 32-year-old physician with history of SARS-CoV-2 infection presented to the emergency department with 2 weeks of fever, chills, and right sided cervical lymphadenopathy. He was treated empirically for presumed folliculitis with worsening of symptoms leading to repeat presentation to the emergency department. Extensive workup was unrevealing of an infectious cause and needle biopsy of the lesion was unrevealing. An excisional lymph node biopsy revealed follicular hyperplasia with necrotic foci showing abundance of histiocytes at the edge of necrosis with CD8 predominance of T-cells. Final diagnosis was deemed to be Kikuchi-Fujimoto disease. Antibiotic therapy was discontinued, and the patient’s symptoms resolved with steroid therapy and expectant management. Conclusions This is the first report of a patient developing Kikuchi-Fujimoto disease following SARS-CoV-2 infection. Clinicians should be aware of Kikuchi-Fujimoto disease as a possibility when approaching patients with hyper-inflammatory states who present with cervical lymphadenopathy.

Introduction: Patients with HIV have an elevated risk of cardiovascular disease (CVD) that may be partially driven by inflammation and residual immune dysfunction despite treatment with antiretroviral therapy (ART). Coronary microvascular dysfunction (CMD) is an important pathophysiological link between inflammation, immune dysfunction, and CVD and may provide mechanistic insight into CVD risk among HIV+ patients. Methods: We recruited 3 groups of adults aged 40-80 years free of CVD: HIV with evidence of prior/current immunocompromise (n=17), HIV without immunocompromise (n=19), and HIV- controls. All HIV+ participants were on ART and had suppressed viral loads. All controls were on HIV pre-exposure prophylaxis (PrEP). Immunocompromise was defined as nadir CD4 count Results: Of 51 individuals who underwent CFR testing, median (IQR) age was 54 (46-58) and 92% were male. CFR was 3.71 (2.90-4.72) in controls, 3.49 (2.52-4.20) in HIV+/ immunocompromise-, and 2.35 (2.12-2.92) in HIV+/ immunocompromise+ (p=0.002). CMD was present in 7% of controls, 21% of HIV+/immunocompromise-, and 53% of HIV+/immunocompromise+ (p= 0.01). Compared with controls, HIV+/immunocompromise+ was significantly associated with lower CFR after multivariable adjustment ( Table ). Conclusions: HIV+ patients with current/prior immunocompromise free of CVD had high prevalence of CMD and had significantly lower CFR compared with controls on PrEP. Future studies should investigate CMD as a possible target for CVD prevention in HIV+ patients, particularly those with a prior or current immunocompromised state.

Tocilizumab, an interleukin-6 receptor antagonist, has been used to treat critically ill patients with coronavirus disease-2019. We present the case of a previously immunocompetent man with coronavirus disease-2019 who developed invasive pulmonary aspergillosis after treatment with tocilizumab, illustrating the importance of considering opportunistic infections when providing immune modulating therapy.

Background & aimsSpontaneous Bacterial Peritonitis (SBP) is an infection in patients with cirrhosis and carries significant mortality. The management of SBP is evolving with the rise of multidrug resistant organisms. Our aim was to perform a retrospective analysis to determine if identification of bacteria in culture could aid in prognosis and provide information regarding optimal treatment.MethodsWe analyzed our 10-year experience of SBP in a single academic center (Northwestern Memorial Hospital). We obtained information regarding SBP prophylaxis, culture data and resistance patterns of bacteria, choice/duration of inpatient antibiotics, and key laboratory measurements and determined outcomes including mortality, hospital duration, and ICU stay.ResultsPatients with SBP had a 17.8% mortality and had culture positive SBP 34.4% of the time. Antimicrobial resistance was seen in 21.3% of cases and trended towards worsening mortality, with worsened mortality associated with first line use of piperacillin-tazobactam (p = 0.0001). Patients on SBP prophylaxis who developed SBP had improved mortality (pConclusionsOur results show that SBP continues to be a morbid and deadly condition and identification of an organism is key in treatment. The standard initial antibiotic for SBP may need to be modified to reflect emerging resistant pathogens and gram-positive organisms. Further, antibiotic prophylaxis should be utilized only in select cases to prevent development of resistance.

BackgroundCOVID-19 is associated with hypercoagulability and an increased incidence of thrombosis. We evaluated the clinical outcomes of adults hospitalized with COVID-19 who either continued therapeutic anticoagulants previously prescribed or who were newly started on anticoagulants during hospitalization.MethodsWe performed an observational study of adult inpatients’ with COVID-19 at 10 hospitals affiliated with Northwestern Medicine in the Chicagoland area from March 9 to June 26, 2020. We evaluated clinical outcomes of subjects with COVID-19 who were continued on their outpatient therapeutic anticoagulation during hospitalization and those who were newly started on these medications compared to those who were on prophylactic doses of these medications based on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement. The primary outcome was overall death while secondary outcomes were critical illness (WHO score ≥5), need for mechanical ventilation, and death among those subjects who first had critical illness adjusted for age, sex, race, body mass index (BMI), Charlson score, glucose on admission, and use of antiplatelet agents.Results1,716 subjects with COVID-19 were included in the analysis. 171 subjects (10.0%) were continued on their outpatient therapeutic anticoagulation and 201(11.7%) were started on new therapeutic anticoagulation during hospitalization. In subjects continued on home therapeutic anticoagulation, there were no differences in overall death, critical illness, mechanical ventilation, or death among subjects with critical illness compared to subjects on prophylactic anticoagulation. Subjects receiving new therapeutic anticoagulation for COVID-19 were more likely to die (OR 5.93; 95% CI 3.71-9.47), have critical illness (OR 14.51; 95% CI 7.43-28.31), need mechanical ventilation (OR 11.22; 95% CI 6.67-18.86), and die after first having critical illness. (OR 5.51; 95% CI 2.80 −10.87).ConclusionsContinuation of outpatient prescribed anticoagulant was not associated with improved clinical outcomes. Therapeutic anticoagulation for COVID-19 in absence of other indications was associated with worse clinical outcomes.

SummaryWhat is known and objective Neurotoxicity is a side effect of acyclovir. We report the first case, to our knowledge, whereby Bayesian-informed clearance estimates supported a therapeutic intervention for acyclovir-associated neurotoxicity. Case summary A 62-year-old male with the diagnosis of disseminated zoster was being treated with intravenous (IV) acyclovir when he developed symptoms of acute neurotoxicity. Acyclovir had been dose-adjusted for renal dysfunction according to traditional creatinine clearance estimates; however, as the patient was also on vancomycin, Bayesian estimates of vancomycin clearances were performed, which revealed a 2-fold lower creatinine clearance. In response to the Bayesian estimates, acyclovir was discontinued, and improvements in mentation were noted within 24 hours. What is new and conclusion Alternate approaches to estimate renal function beyond Cockcroft-Gault, such as a Bayesian approach used in our patient, should be considered when population estimates are likely to be inaccurate and potentially dangerous to the patient.

Purpose of review This review will focus on the epidemiology and cause of diarrheal illness in solid organ transplant and stem-cell transplant population recipients with a specific focus on the role of advanced multiplex technology in the diagnosis of diarrhea within this patient population. Recent findings A wide range of infectious and noninfectious causes of diarrhea have been described in immunocompromised patients. The most common infections noted are Clostridioides difficile, norovirus, and cytomegalovirus, whereas immunosuppressive drugs and mucositis are the most common noninfectious causes of diarrhea. Historically, diagnostic evaluation has been limited to an array of single pathogen assays. Newer multiplex assays have become available that allow rapid, sensitive detection of a wide range of pathogens in a single assay. These assays have improved the number of patients with a diagnosed pathogen but may identify colonizing pathogens that are not pathogenic. Studies are needed to inform the discrimination and optimal use of these newer assays. Summary Diarrhea is a common complication in immunocompromised patients and is associated with greater morbidity and rare mortality. New diagnostics facilitate detection of recognized pathogens and may allow for improved outcomes through the use of pathogen-targeted therapy.

These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of diarrhea in the pre- and post-transplant period. Diarrhea in an organ transplant recipient may result in significant morbidity including dehydration, increased toxicity of medications, and rejection. Transplant recipients are affected by a wide range of etiologies of diarrhea with the most common causes being Clostridioides (formerly Clostridium) difficile infection, cytomegalovirus, and norovirus. Other bacterial, viral, and parasitic causes can result in diarrhea but are far less common. Further, noninfectious causes including medication toxicity, inflammatory bowel disease, post-transplant lymphoproliferative disease, and malignancy can also result in diarrhea in the transplant population. Management of diarrhea in this population is directed at the cause of the diarrhea, instituting therapy where appropriate and maintaining proper hydration. Identification of the cause to the diarrhea needs to be timely and focused.

Introduction Cardiobacterium valvarum is a HACEK organism known for causing infective endocarditis (IE); there are no reported cases implicating this bacterium in left ventricular assist device (LVAD) infections in the English literature. Case Report A 59 year old gentleman with sarcoidosis, systolic heart failure (EF 15%), BiV-ICD (implanted 11/2015) and LVAD (Heartware implanted 10/2017) presented with fever and cough. He experienced worsening lower extremity edema and abdominal girth one week prior to admission. In the emergency room his temperature was 39.5°C and had mild erythema without drainage at his drive line exit site (DLES). Labs were notable for WBC of 15.5 × 103/μL and lactic acid of 2.2 mmol/L. Blood cultures were obtained and the patient received piperacillin-tazobactam and vancomycin. TTE and CT imaging of chest and abdomen demonstrated no significant findings. The initial blood culture became positive with gram-negative bacilli after 3.5 days and were identified as C. valvarum 28 days after initial presentation. He completed a two-week course of ertapenem and transitioned to cephalexin 500 mg BID as secondary prophylaxis. Erythema at the DLES improved and heart failure symptoms resolved. The patient remained on this regimen until transplant, 348 days from positive culture. The organisms classified in the HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella spp., and Kingella spp.) group are known for being fastidious causes of IE; they are not traditionally associated with pump, line, or pocket infections in VAD patients. The most common gram-negative bacterial infections associated with VADs and their components are P. aeruginosa and enteric organisms. This patient's case was treated as a VAD-related blood stream infection. Because Cardiobacterium spp. are oral commensals, DLES as the source was less likely. As noted in the IE guidelines, the presence of a HACEK organism without an identifiable source should be considered IE unless proven otherwise, even if there are no other stigmata of IE. Thus, despite only one culture growing C. valvarum, there was a high suspicion for the components of the VAD being seeded, resulting in antibiotic suppression until transplantation. Summary In the presence of a VAD, HACEK organism found in the bloodstream should be treated as a pump infection unless proven otherwise.

Injection drug use (IDU) is a complicated social and medical issue. Infectious diseases often affect morbidity and mortality in people who inject drugs and can complicate the management of comorbid medical and psychiatric conditions. The major complications of IDU include viral and bacterial infections, namely HIV, hepatitis B virus, hepatitis C virus, and bacteremia/endocarditis. These infections, as well as the other medical and psychiatric conditions associated with IDU, complicate treatment, management, and societal prevention of substance use. There are various resources and recommendations that clinicians should track when treating patients who inject drugs; these patients require a multidisciplinary team to manage their challenging medical care. [ Psychiatr Ann . 2017;47(1):33–37.]

Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

Background Ganciclovir-resistant cytomegalovirus (GCV-R CMV) is an emerging challenge among solid organ transplant (SOT) recipients. The literature suggests that about 1% of abdominal transplant recipients develop GCV-R CMV infection. The epidemiology and outcome of GCV-R CMV in SOT recipients who have received alemtuzumab induction is not well described. Methods After Institutional Review Board approval, a single-center, retrospective review of 2148 abdominal SOT recipients between January 2006 and July 2011 at our institution (n = 2148) was conducted to identify patients with proven or empirically treated GCV-R CMV. Descriptive statistics on collected demographics, clinical course, and therapeutic outcomes were performed. Results Of 116 SOT recipient treated for CMV, 14 patients (12.1% of cases; 0.65% of all SOT patients) had proven or suspected GCV-R CMV. Eight (50%) developed GCV-R CMV while receiving valganciclovir (valGCV) prophylaxis. The remainder developed late-onset disease, after having completed an average 212 days (range 83–353) of prophylaxis. Resistance was clinically suspected an average of 103 days (range 10–455) after CMV infection was initially identified; 10 patients had confirmed genotypic resistance. Foscarnet therapy was associated with resolution of CMV in 13. Conclusion Suboptimal dosing of valGCV is associated with development of GCV-R CMV. Our observed rate of GCV-R CMV in alemtuzumab-induced patients is similar to rates seen to historical data for other induction agents.

Background Cryptococcus has a worldwide distribution, with C. neoformans and C. gattii being two of the most common species causing disease. Despite advances in therapy, disseminated infection often results in significant morbidity and mortality. Methods We conducted a single center retrospective cohort study over a twenty-year period spanning from January 2000 through May 2020 to determine epidemiology and outcomes of non-HIV-associated cryptococcosis at Northwestern Memorial Hospital. Cases were identified by positive culture data or positive cryptococcal antigen in the serum or cerebrospinal fluid (CSF). Epidemiology of risk factors, morbidity, and mortality was evaluated. Results 81 cases were identified of which, 67 had Cryptococcus spp isolated from culture and the remaining patients diagnosed by cryptococcal antigen and/or histopathology. The cohort was primarily Caucasian (56.8%, n=46) and male gender (67.9%, n=55), with a median age of 59.5 (IQR: 52.75-66.25) years old. Common predisposing conditions were diabetes (37%, n=30), chronic kidney disease (34.6%, n=28), and liver disease (28.4%, n=23). Solid organ transplant recipients and use of immunosuppression accounted for, respectively, 32.1% (n=26) and 29.6% (n=24) of the cohort. Sites of infection include lung (65.4%. n=53), central nervous system (33.3%, n=27), blood (30.9%, n=25), peritoneum (6.2%, n=5), musculoskeletal (2.5%, n=2), and prostate (1.2%, n=1). Mean opening pressure on lumbar puncture was 25.3 mmHg (range: 9 -52 mmHg). In hospital mortality at time of diagnosis was 27.2% (n=22), and mortality at 12 months post diagnosis was 51.9% (n=42). Conclusion At our center, those with cryptococcosis commonly had risk factors such as immunosuppression either secondary to solid organ transplant or otherwise. Morbidity and mortality remain high. Disclosures Sudhir Penugonda, MD, MPH, AbbVie, Inc. (Employee, Other Financial or Material Support, ownership and/or investment interests) Michael Angarone, DO, Abbvie (Other Financial or Material Support, Data Safety Monitoring Board)Allergan (Speaker’s Bureau)

Diarrhea is a common complaint in the solid organ transplant recipient. Unlike the immune-competent patient, diarrhea in an organ transplant recipient may result in dehydration, increased toxicity of medications, and rejection. There is a wide range of causes for diarrhea in transplant recipients, but the most common causes are Clostridium difficile infection, cytomegalovirus, and norovirus. This review will focus on new epidemiology data as to the cause of diarrhea in the transplant population.Recent data have identified C. difficile, cytomegalovirus, and norovirus as important causes of diarrhea in this population, and management should be focused on these causes. Newer diagnostic platforms (such as PCR) are being evaluated, which may help in identification of the cause of diarrhea.New epidemiologic data and new testing techniques offer an opportunity for research into better testing strategies for transplant patients with diarrhea. These newer testing strategies may offer better insight into the cause of diarrhea and more appropriate treatment for this illness.

BACKGROUND Although the research is limited, treatment guidelines recommend lifelong suppressive azole therapy for disseminated endemic fungal infection (EFI) after solid organ transplantation (SOT). Suppressive azole therapy may prevent EFI recurrence at the risk of hepatotoxicity and drug interactions. We present real-world safety and effectiveness data of chronic suppressive azole therapy for EFI in SOT recipients over a 10-year period at a single comprehensive transplant center. METHODS A retrospective analysis was conducted of SOT recipients diagnosed with EFI from January 1, 2005, to May 1, 2015. Chronic suppressive azole therapy was defined as treatment for more than 12 months after diagnosis. Effectiveness of suppression was defined as preventing EFI reactivation. Safety endpoints included adverse reactions and drug interactions. RESULTS Over a 10-year period, 28 SOT recipients were diagnosed with EFI: 16 histoplasmosis, 9 blastomycosis, and 3 coccidioidomycosis. Eighteen (64%) patients were treated with chronic suppressive azole therapy for a median length of 36 months (range 15-90). One patient had an adverse drug interaction requiring azole discontinuation. There were no episodes of azole-related hepatotoxicity, toxicity from antirejection medication, or EFI reactivation. CONCLUSIONS Chronic suppressive azole therapy was safe and effective in preventing reactivation of EFI in SOT recipients.

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) affected 5%-15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim-sulfamethoxazole (TMP-SMX). Guidelines generally recommend 6-12 months of prophylaxis post-SOT, yet optimal duration and robust PJP risk stratification have not been established. METHODS A retrospective, single-center, case-control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed. RESULTS Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed vs 60 controls. PJP occurred on average 6.1 years (range 0.9-13.8) post-SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP-SMX plus steroids (80%). Six patients (40%) required critical care; 3 (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs 48 years, P = .1). In univariate analysis, prior viral infection was more common among cases (67% vs 37%, P = .08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs 1230 × 106 cells/μL, P

Noroviruses are among the most common cause of diarrhea in transplant recipients. The clinical spectrum of norovirus infection after transplant is increasingly being recognized. As substantial morbidity is now associated with norovirus infections in this population; the quest for rapid diagnostic modalities and newer therapies has expanded. Transplant recipients with norovirus infection are at risk for several complications, including protracted illness with malnutrition, organ failure, and chronic viral shedding. This review summarizes the current knowledge on the epidemiology, complications, diagnosis, and treatment of norovirus infection in the transplant setting.

Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.

Background The use of antifungal prophylaxis, targeted or universal, remains controversial and unstudied. The goal of this study is to determine the role of targeted voriconazole prophylaxis (VORI) in prevention of invasive fungal infections (IFI) after heart transplantation (HT). Methods We conducted a single-center, prospective, observational cohort study of 276 HT recipients from June 2005 to April 2017 to characterize the incidence and outcome of IFI following targeted VORI. Starting in June 2013, HT recipients with thymoglobulin (ATG) treatment received VORI for 3 months. Probable/proven IFI were defined by EORTC/MSG criteria. Descriptive frequencies and univariate analyses were performed. Results Mean duration of follow-up post-HT was 1,165 days (0–3,152 days). 149 (54%) and 70 (25%) received basiliximab and thymoglobulin induction, respectively. Thirty-one (11%) received VORI, following use of ATG in the setting of induction (68%) or rejection (32%). VORI was started at median of 6 days (0–1,008 days) post-HT for a mean duration of 97 days (5–251 days). Overall, 23 IFIs occurred in 23 recipients (8%) at mean 283 days post-HT (range 2–1,579 days), including seven Aspergillus (one occurring after VORI completion), seven invasive Candida (five with candidemia), two Rhizopus, one Cunninghamella, two histoplasma, two blastomyces, one Cryptococcus, and one multifocal cutaneous Alternaria. Conclusion Targeted VORI resulted in reduced incidences of both early and overall IFI after HT although this did not reach statistical significance. Since instituting this strategy, we have observed a single case of aspergillosis following VORI discontinuation. Overall and 1-year mortality were not impacted. The use of antifungal prophylaxis following HT requires continued investigation both to determine efficacy and toxicity in this patient population. Disclosures All authors: No reported disclosures.

Background Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation. Methods We performed a prospective cohort study of CMV donor (D) or recipient (R) seropositive heart transplant recipients from 2005 to 2012 who completed VGC prophylaxis, ranging from 3 to 12 months according to serostatus and induction immunosuppression. Univariate and multivariate logistic regression was performed. Results Among 159 heart transplant recipients during the study period, 130 (82%) were eligible for VGC prophylaxis. CMV D/R serostatus was as follows: 24% D+/R-, 30% D+/R+, and 29% D-/R+. 65% and 21% received basiliximab and thymoglobulin induction, respectively, followed by maintenance tacrolimus, mycophenolate mofetil, and prednisone. Twenty-one (16%) recipients suffered CMV infection. There was no association with comorbidities including diabetes mellitus, chronic kidney disease, or mechanical assist devices, nor were there associations with rejection, treatments of rejection, or mortality. When VGC prophylaxis duration was stratified by ≤6 vs ≥12 months, time from heart transplantation to CMV infection was delayed (median 247 vs 452 days, P = .002) but there was no difference in days from VGC discontinuation to onset of CMV infection (median 72 vs 83 days, P = .31). CMV infection occurred most frequently within 6-16 weeks of VGC cessation, and 95% of infections occurred during the 6 months post-prophylaxis period. Conclusions Relative to ≤6 months, ≥12 months of VGC did not reduce incidence of CMV infection and only delayed time to onset. 95% of CMV infection occurs within 6 months after cessation of VGC.

A leading complication of leukemia therapy and stem cell transplantation is opportunistic viral infections. Infections caused by cytomegalovirus, herpes simplex, varicella-zoster, Epstein-Barr, and the community respiratory viruses are associated with significant morbidity and mortality in this highly immunosuppressed population. Fortunately, a growing armamentarium is allowing more effective prophylaxis of these pathogens. This article reviews the epidemiology and prophylactic strategies available for these common opportunistic viral pathogens.

BACKGROUND Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution. METHODS A prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS By univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32-411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%). CONCLUSIONS The cumulative incidence was 10.7%. IFIs were associated with pre- and post-HT vancomycin-resistant Enterococcus colonization and/or infection, post-HT renal replacement therapy, anti-thymocyte globulin induction, and antibody-mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re-operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3-12.1) and 1-year mortality (P

Sexually transmitted infections (STIs) remain a significant burden on public health in the United States. Primary prevention counseling with early diagnosis and treatment remain the best methods to decrease the incidence of STIs. Through significant public heath interventions, the incidence of gonorrhea, Chlamydia, and trichomoniasis is decreasing; however, the incidence of primary and secondary syphilis is increasing. Human papilloma virus remains the most common STI, but new vaccinations have the possibility of having a significant impact on this virus's disease potential. This review discusses the most common STIs in the United States, focusing on clinical presentation, diagnosis, and treatment.

Purpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo-related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18S ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P. lilacinum included violet colonies on malt extract agar, long tapering brush-like phialides, and elliptical conidia attached in chains. P. lilacinum has intrinsic resistance to many antifungal agents including amphotericin B, but voriconazole and posaconazole have good in vitro activity. The patient was treated with voriconazole with subsequent resolution of the papules after 3 months of therapy.

Background Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost-analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. Design A cost-analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. Results Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). Conclusions A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C. difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay. This article is protected by copyright. All rights reserved.

(See the Editorial Commentary by Polage on pages 738–40.) Diarrhea in solid organ transplant (SOT) recipients has been estimated to occur in 22%–52% of patients [1–4]. At one center, gastrointestinal complaints accounted for 31% of presentations to their emergency department with an associated risk of hospitalization [5]. Furthermore, posttransplant diarrhea is associated with allograft loss and increased mortality [2, 6, 7]. The impact of diarrhea on immunosuppressive therapy may, in part, explain this association. Gastrointestinal distress is a recognized side effect of mycophenolate mofetil (MMF) and mycophenolic acid (MPA), which increase tacrolimus exposure [8]. Resulting reductions in immunosuppression increase the risk of acute rejection and ultimately graft failure [9–11]. Despite its significance, the epidemiology of diarrhea in transplant recipients is poorly defined. Previously, infectious causes of diarrhea in general accounted for 13%–19% of diarrheal episodes [2, 6]. The Diarrhea Diagnosis Aid and Clinical Treatment study prospectively investigated the etiology and management of diarrhea in renal transplant recipients and identified a specific infectious etiology in 30 of 108 (28%) patients, with Campylobacter jejuni enteritis and cytomegalovirus (CMV) colitis being the most common [1]. Later studies have found that Clostridium difficile colitis is frequent, but its incidence relative to other pathogens and noninfectious etiologies has not been compared [12–15]. Recommendations for the diagnostic evaluation and management of posttransplant diarrhea are based largely on expert opinion and generally include initial stool culture, stool C. difficile assessment, and blood CMV quantitative viral load, if necessary to be followed by consideration of empiric reduction in immunosuppression, and thereafter colonoscopy [1, 16–18]. Recommendations for additional testing are quite variable and may include fecal testing for leukocytes (or lactoferrin), ova and parasites, Cystoisospora (Isospora) and Cyclospora assessments, Giardia and Cryptosporidium antigen screen or enzyme immunoassay (EIA), and norovirus detection by polymerase chain reaction (PCR). SOT recipients are at increased risk of atypical and typical infections leading to diarrhea, but it is unclear that this immunocompromised state necessarily translates to an increased incidence of all possible etiologies of diarrhea, especially with consideration of endemic and geographic exposures. There may be more optimized testing strategies, for which evidence is required. We hypothesized that the majority of SOT recipients hospitalized with diarrheal illness were attributable to a few etiologies, predominantly C. difficile and norovirus, and that the yield for other studies is low.

Invasive fungal infections (IFI) have become a leading cause of morbidity and mortality in cancer patients. Infections with these organisms are often difficult to diagnose and treat. Appropriate and timely diagnosis requires a high index of suspicion and invasive procedures, including biopsy, to confirm the diagnosis. Treatment may be difficult, secondary to variable susceptibility and difficulty with exact and specific characterization of the fungal pathogen. The pathogens that are seen range from yeasts to invasive molds. Fortunately newer, noninvasive diagnostic techniques are available to aid in the diagnosis and treatments have become better tolerated and more efficacious.

Invasive fungal infections (IFI) have become a leading cause of morbidity and mortality in cancer patients. Infections with these organisms are often difficult to diagnose and treat. Appropriate and timely diagnosis requires a high index of suspicion and invasive procedures, including biopsy, to confirm the diagnosis. Treatment may be difficult, secondary to variable susceptibility and difficulty with exact and specific characterization of the fungal pathogen. The pathogens that are seen range from yeasts to invasive molds. Fortunately newer, noninvasive diagnostic techniques are available to aid in the diagnosis and treatments have become better tolerated and more efficacious.

BACKGROUND Surveillance colonoscopy using random biopsies to detect colitis-associated cancer (CAC) suffers from poor sensitivity. Although chromoendoscopy improves detection, acceptance in the community has been slow. Here, we examine the usefulness of near infrared fluorescence (NIRF) endoscopy to image molecular probes for cathepsin activity in colitis-induced dysplasia. METHODS In patient samples, cathepsin activity was correlated with colitis and dysplasia. In mice, cathepsin activity was detected as fluorescent hydrolysis product of substrate-based probes after injection into Il10(-/-) colitic mice. Fluorescence colonoscopy and colonic whole-mount imaging were performed before complete sectioning and pathology review of resected colons. RESULTS Cathepsin activity was 5-fold and 8-fold higher in dysplasia and CAC, respectively, compared with areas of mild colitis in patient tissue sections. The signal-to-noise ratios for dysplastic lesions seen by endoscopy in Il10(-/-) mice were 5.2 ± 1.3 (P = 0.0001). Lesions with increased NIRF emissions were classified as raised or flat dysplasia, lymphoid tissue, and ulcers. Using images collected by endoscopy, a receiver operating characteristic curve for correctly diagnosing dysplasia was calculated. The area under the curve was 0.927. At a cutoff of 1000 mean fluorescence intensity, the sensitivity and specificity for detecting dysplasia were 100% and 83%, respectively. Analysis revealed that focally enhanced NIRF emissions derived from increased numbers of infiltrating myeloid-derived suppressor cells and macrophages with equivalent cathepsin activity. CONCLUSIONS These studies indicate that cathepsin substrate-based probe imaging correctly identifies dysplastic foci within chronically inflamed colons. Combined white light and NIRF endoscopy presents unique advantages that may increase sensitivity and specificity of surveillance colonoscopy in patients with CAC.