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Abstract: 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 < .001); odds of infection were high with ALC ≤ 500 × 106 cells (OR 18.7, P < .01). Conclusion: Pneumocystis jirovecii pneumonia is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis. [ABSTRACT FROM AUTHOR]

There is an increased risk of infection in patients with cancer that results in higher morbidity and mortality. Several risk factors can predispose these patients to infectious complications. Some such factors include immunocompromised states like neutropenia, allogeneic hematopoietic cell transplantation, and graft-versus-host disease, while others include immunosuppressive agents like corticosteroids, purine analogs, monoclonal antibodies, and other emerging cancer therapeutics like CAR T-cell therapy. The NCCN Guidelines for the Prevention and Treatment of Cancer-Related Infections address infection concerns that may be observed in these immunocompromised populations and 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 paper highlights 2 recently updated sections of the guidelines, namely, infection concerns related to CAR T-cell therapy and antimicrobial prophylaxis recommendations, including vaccination, in patients at high-risk for infections.

Purpose of Review: This review highlights the epidemiology of Pneumocystis jirovecii pneumonia in solid organ transplant recipients, advancements in the diagnostic landscape, and updates in treatment and prevention., Recent Findings: The increasing use of immune-depleting agents in the context of solid organ transplantation has given rise to P. jirovecii pneumonia in this population. The use of prophylaxis has dramatically reduced risk of infection; however, late-onset infections occur after cessation of prophylaxis and in the setting of lymphopenia, advancing patient age, acute allograft rejection, and cytomegalovirus infection. Diagnosis requires respiratory specimens, with PCR detection of Pneumocystis replacing traditional staining methods. Quantitative PCR may be a useful adjunct to differentiate between infection and colonization. Metagenomic next-generation sequencing is gaining attention as a noninvasive diagnostic tool. Trimethoprim-sulfamethoxazole remains the drug of choice for treatment and prevention of Pneumocystis pneumonia. Novel antifungal agents are under investigation., Summary: P. jirovecii is a fungal opportunistic pathogen that remains a cause of significant morbidity and mortality in solid organ transplant recipients. Early detection and timely treatment remain the pillars of management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mycobacterium xenopi is a slow growing non-tuberculous mycobacterium (NTM) isolated from water systems and has been associated with pseudo-outbreaks and pulmonary infections in humans. We observed a cluster of six respiratory cultures positive for M. xenopi within a six-month period at our institution, approximately double our normal isolation rate of this organism. Only three of the six cases met clinical, radiographic, and microbiologic criteria for NTM infection. An investigation led by our hospital's Healthcare Epidemiology and Infection Program found no epidemiologic link between the six patients. Three isolates underwent whole-genome sequencing (WGS) and phylogenetic analysis confirmed they were non-clonal. In vitro susceptibility data found the isolates were sensitive to macrolides, moxifloxacin, and rifabutin. Our findings suggest that isolation of M. xenopi from pulmonary specimens may be increasing, further defines the genomic population structure of this potentially emerging infection, and establishes WGS as a useful tool for outbreak investigation strain typing., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

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.

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2016 by the National Comprehensive Cancer Network.)

Purpose of Review: 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 Findings: 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., Summary: 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.

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.

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.

Viral infections are some of the most frequent complications in patients with hematologic malignancies are viral infections. Infections caused by cytomegalovirus, herpes simplex virus, varicella zoster virus, hepatitis B virus and influenza virus are associated with high morbidity and mortality in this vulnerable population. Fortunately, a growing number of antiviral medications and vaccines are allowing for more effective prophylaxis against these pathogens. This article reviews the epidemiology and prophylactic strategies available for these opportunistic viral pathogens.

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.