Pneumocystis jirovecii in solid organ transplant recipients: updates in epidemiology, diagnosis, treatment, and prevention.

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.

A cluster of six respiratory cultures positive for Mycobacterium xenopi -Clinical characteristics and genomic characterization.

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.

Association Between Clostridium innocuum and Antibiotic-Associated Diarrhea in Adults and Children: A Cross-sectional Study and Comparative Genomics Analysis.

BACKGROUND: A recent study from Taiwan suggested that Clostridium innocuum may be an unrecognized cause of antibiotic-associated diarrhea (AAD) and clinically indistinguishable from Clostridioides difficile infection. Our objective was to compare C. innocuum prevalence and strain between those with AAD and asymptomatic controls. METHODS: In this cross-sectional study, we collected stool from 200 individuals with AAD and 100 asymptomatic controls. We evaluated the association between AAD and C. innocuum in stool using anaerobic culture and quantitative polymerase chain reaction (qPCR). To identify strain-specific associations with AAD, we performed whole-genome sequencing of C. innocuum isolates using Illumina MiSeq and constructed comparative genomics analyses. RESULTS: C. innocuum was isolated from stool of 126/300 (42%) subjects and more frequently from asymptomatic controls than AAD subjects (50/100 [50%] vs 76/200 [38%], respectively; P = .047). C. innocuum isolation frequency was not associated with AAD in either the adult or pediatric subgroups. C. innocuum and C. difficile were frequently co-prevalent in individuals with and without diarrhea. There were no phylogenetic differences or accessory genome associations between C. innocuum isolates from AAD subjects and asymptomatic controls. CONCLUSIONS: C. innocuum was frequently isolated and at a greater frequency in asymptomatic controls than those with AAD. We did not identify strain lineages or accessory genomic elements associated with AAD. These data highlight that differentiating C. innocuum-associated diarrhea from asymptomatic colonization, and differentiating diarrhea caused by C. difficile from C. innocuum, are clinical microbiology challenges that require additional investigation to identify host-specific factors and/or biomarkers that distinguish these conditions.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

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.

Disparities in COVID-19 Monoclonal Antibody Delivery: a Retrospective Cohort Study.

BACKGROUND: Disparities in access to anti-SARS-CoV-2 monoclonal antibodies have not been well characterized. OBJECTIVE: We sought to explore the impact of race/ethnicity as a social construct on monoclonal antibody delivery. DESIGN/PATIENTS: Following implementation of a centralized infusion program at a large academic healthcare system, we reviewed a random sample of high-risk ambulatory adult patients with COVID-19 referred for monoclonal antibody therapy. MAIN MEASURES: We examined the relationship between treatment delivery, race/ethnicity, and other demographics using descriptive statistics, binary logistic regression, and spatial analysis. KEY RESULTS: There was no significant difference in racial composition between patients who did (n = 25) and patients who did not (n = 378) decline treatment (p = 0.638). Of patients who did not decline treatment, 64.8% identified as White, 14.8% as Hispanic/Latinx, and 11.1% as Black. Only 44.6% of Hispanic/Latinx and 31.0% of Black patients received treatment compared to 64.1% of White patients (OR 0.45, 95% CI 0.25-0.81, p = 0.008, and OR 0.25, 95% CI 0.12-0.50, p < 0.001, respectively). In multivariable analysis including age, race, insurance status, non-English primary language, county Social Vulnerability Index, illness severity, and total number of comorbidities, associations between receiving treatment and Hispanic/Latinx or Black race were no longer statistically significant (AOR 1.32, 95% CI 0.69-2.53, p = 0.400, and AOR 1.34, 95% CI 0.64-2.80, p = 0.439, respectively). However, patients who were uninsured or whose primary language was not English were less likely to receive treatment (AOR 0.16, 95% CI 0.03-0.88, p = 0.035, and AOR 0.37, 95% CI 0.15-0.90, p = 0.028, respectively). Spatial analysis suggested decreased monoclonal antibody delivery to Cook County patients residing in socially vulnerable communities. CONCLUSIONS: High-risk ambulatory patients with COVID-19 who identified as Hispanic/Latinx or Black were less likely to receive monoclonal antibody therapy in univariate analysis, a finding not explained by patient refusal. Multivariable and spatial analyses suggested insurance status, language, and social vulnerability contributed to racial disparities.

Risk Factors Associated With Nephrotoxicity During Outpatient Intravenous Vancomycin Administration.

Background: Many studies have described an association between intravenous vancomycin and nephrotoxicity; however, the majority have evaluated incidence and risk factors among hospitalized patients. Outpatient administration of intravenous antibiotics is a growing practice and presents its own set of unique challenges. Objective: The aim of this study was to identify risk factors for vancomycin-associated nephrotoxicity in the outpatient setting. Methods: A case-control study of patients who received intravenous vancomycin through an Outpatient Parenteral Antimicrobial Therapy (OPAT) program was conducted. Patients were identified who developed an acute kidney injury (AKI) during treatment. The primary outcome was the incidence of AKI during treatment. Results: A total of 37 out of 130 patients (28.5%) met the criteria for AKI. AKI was more likely to occur in patients with a longer duration of therapy, higher maximum trough concentration, co-administration of a fluoroquinolone or metronidazole, and those who received another potentially nephrotoxic medication. Co-administration of a fluoroquinolone (OR = 5.96, P = 0.009, [CI: 1.59, 24.38]), any nephrotoxic medication (OR = 11.17, P < 0.001, [CI 3.14, 51.23]), and a higher maximum vancomycin trough (OR = 1.29, P < 0.001, [CI 1.17, 1.44]) were all indicative of a higher odds of an AKI. Conclusion: In this cohort, vancomycin-associated nephrotoxicity was common during outpatient intravenous antibiotic therapy. Co-administration of a fluoroquinolone, any nephrotoxic medication, and a higher maximum vancomycin trough were associated with AKI development. Further study is needed to determine how this impacts long-term clinical outcomes and what measures can be taken to reduce nephrotoxicity risk.

Real-World Experience of Bamlanivimab for Coronavirus Disease 2019 (COVID-19): A Case-Control Study.

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.

Changes in Ascitic Fluid Polymorphonuclear Cell Count After Antibiotics Are Associated With Mortality in Spontaneous Bacterial Peritonitis.

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.

Kikuchi-Fujimoto disease presenting in a patient with SARS-CoV-2: a case report.

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.

Invasive pulmonary aspergillosis after treatment with tocilizumab in a patient with COVID-19 ARDS: a case report.

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.

Mortality, critical illness, and mechanical ventilation among hospitalized patients with COVID-19 on therapeutic anticoagulants.

Background: COVID-19 is associated with hypercoagulability and increased incidence of thrombosis. We compared the clinical outcomes of adults hospitalized with COVID-19 who were on therapeutic anticoagulants to those on prophylactic anticoagulation. Materials and methods: We performed an observational study of adult inpatients' with COVID-19 from March 9 to June 26, 2020. We compared patients who were continued on their outpatient prescribed therapeutic anticoagulation and those who were newly started on therapeutic anticoagulation for COVID-19 (without other indication) to those who were on prophylactic doses. The primary outcome was overall death while secondary outcomes were critical illness (World Health Organization Ordinal Scale for Clinical Improvement score ≥5), mechanical ventilation, and death among patients who first had critical illness. We adjusted for age, sex, race, body mass index (BMI), Charlson score, glucose on admission, and use of antiplatelet agents. Results: Of 1716 inpatients with COVID-19, 171 patients were continued on their therapeutic anticoagulation and 78 were started on new therapeutic anticoagulation for COVID-19. In patients continued on home therapeutic anticoagulation, there were no differences in overall death, critical illness, mechanical ventilation, or death among patients with critical illness compared to patients on prophylactic anticoagulation. In patients receiving new therapeutic anticoagulation for COVID-19, there was increased death (OR 5.93; 95% CI 3.71-9.47), critical illness (OR 14.51; 95% CI 7.43-28.31), need mechanical ventilation (OR 11.22; 95% CI 6.67-18.86), and death after first having critical illness (OR 5.51; 95% CI 2.80-10.87). Conclusions: Therapeutic anticoagulation for inpatients with COVID-19 was not associated with improved outcomes.

A retrospective analysis of cases of Spontaneous Bacterial Peritonitis in cirrhosis patients.

BACKGROUND & AIMS: Spontaneous 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. METHODS: We 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. RESULTS: Patients 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 (p<0.0001) unless there was a positive culture, in which case patients had worsened mortality (p = 0.019). Patient with a higher PMN counts after repeat paracentesis had higher mortality (p = 0.02). CONCLUSIONS: Our 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.

Newer approaches in diagnosis of diarrhea in immunocompromised patients.

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.

Diagnosis and management of diarrhea in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

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.