Mycoplasma hominis infections in solid organ transplant recipients: Clinical characteristics, treatment outcomes, and comparison of phenotypic and genotypic susceptibility profiles.

BACKGROUND: Mycoplasma hominis can cause significant infections after solid organ transplantation (SOT). Treatment should be guided by susceptibility testing, but conventional lab methods are laborious with prolonged turnaround time (TAT). This case series compares the phenotypic and genotypic susceptibility profiles of M. hominis isolates identified from SOT patients. METHODS: This is a single-center retrospective study evaluating SOT recipients with confirmed M. hominis infections. Patients' demographic, clinical, microbiological, and radiographic data were collected. Culture of M. hominis isolates was performed according to current Clinical and Laboratory Standards Institute guidelines. Phenotypic susceptibility testing was performed by University of Alabama Diagnostic Mycoplasma Laboratory. Whole genome sequencing (WGS) was performed followed by bioinformatic analysis of known genetic determinants of resistance. RESULTS: Seven SOT recipients with M. hominis infections were identified. Two out of seven (28.5%) patients had resistance detected by phenotypic susceptibility testing (Case 5 to levofloxacin and Case 7 to tetracycline). Genomic analyses confirmed the presence of mutations in the parC and parE topoisomerase genes at positions conferring to fluoroquinolone resistance in the isolate from Case 5, while the tetracycline-resistant isolate from Case 7 harbored the tetM gene. The median TAT from the date of specimen collection was 24 days for phenotypic susceptibility testing and 14 days for genotypic susceptibility testing. All seven patients received antimicrobials directed toward M. hominis and recovered with complete resolution of infection. CONCLUSIONS: WGS may offer a novel and more rapid methodology for M. hominis susceptibility testing to help optimize antimicrobial usage, but more data are needed.

Pre-Cardiac Dental Treatment Does Not Increase the Risk of Adverse Events.

PURPOSE: Elimination of dental sources of infection prior to cardiovascular surgery (CVS) is performed to reduce perioperative infection and complications. This study aims to evaluate if preoperative dental intervention is associated with increased risk of adverse events. METHODS: A retrospective medical record review of inpatient consultations (n = 1513) completed by the Hospital Dentistry Service at University of California Los Angeles Medical Center from January 2011 to December 2020 was performed. Seven hundred thirty-eight consults met the inclusion criteria and were divided into 4 groups: Group A were patients that were dentally unhealthy and received surgical dental intervention (n = 265), Group B were patients that were dentally unhealthy and underwent non-surgical dental treatment (n = 14), Group C were patients that were dentally unhealthy and did not receive the recommended dental treatment (n = 29), and Group D were patients that were dentally healthy requiring no intervention (n = 430). They were evaluated for major adverse events in 3 categories: dental complications, medical adverse events and death. RESULTS: Dental complications were only experienced in Group A, all of which were bleeding. Only 2 patients were found to have major bleeding, which was more likely due to anticoagulation and CVS rather than dental extractions. There was no significant difference in the number of medical adverse events or number of deaths during the postoperative period between groups. CONCLUSIONS: The results of this study suggest that elimination of oral infection prior to CVS does not increase the risk of morbidity or mortality.

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series.

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.

Fungal Infections Complicating Lung Transplantation.

Lung transplantation is an increasingly utilized modality for treating advanced lung disease. However, lung transplant recipients (LTRs) experience high rates of infection-related mortality and, compared with other solid organ transplant recipients, are at increased risk of infectious complications given the intensity of immunosuppression employed, the presence of airway abnormalities after surgery and exposure of the allograft to the environment. Fungal infections, particularly mold infections, are problematic after transplantation as they are often associated with limited treatment options and poor outcomes. We describe the non-Candida fungal infections occurring in LTRs, including their epidemiology, clinical features, and treatment.

Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation.

RATIONALE: Pseudomonas aeruginosa is the most commonly isolated gram-negative bacterium after lung transplantation and has been shown to up-regulate glutamic acid-leucine-arginine-positive (ELR(+)) CXC chemokines associated with bronchiolitis obliterans syndrome (BOS), but the effect of pseudomonas on BOS and death has not been well defined. OBJECTIVES: To determine if the influence of pseudomonas isolation and ELR(+) CXC chemokines on the subsequent development of BOS and the occurrence of death is time dependent. METHODS: A three-state model was developed to assess the likelihood of transitioning from lung transplant (state 1) to BOS (state 2), from transplant (state 1) to death (state 3), and from BOS (state 2) to death (state 3). This Cox semi-Markovian approach determines state survival rates and cause-specific hazards for movement from one state to another. MEASUREMENTS AND MAIN RESULTS: The likelihood of transition from transplant to BOS was increased by acute rejection, CXCL5, and the interaction between pseudomonas and CXCL1. The pseudomonas effect in this transition was due to infection rather than colonization. Movement from transplant to death was facilitated by pseudomonas infection and single lung transplant. Transition from BOS to death was affected by the length of time in state 1 and by the interactions between any pseudomonas isolation and CXCL5 and aspergillus, either independently or in combination. CONCLUSIONS: Our model demonstrates that common post-transplantation events drive movement from one post-transplantation state to another and influence outcomes differently depending upon when after transplantation they occur. Pseudomonas and the ELR(+) CXC chemokines may interact to negatively influence lung transplant outcomes.

A retrospective chart review evaluating pre-operative dental extractions on patients with end-stage heart failure undergoing advanced surgical cardiac therapies.

OBJECTIVES: End-stage heart failure patients are functionally compromised by multiple physiologic mechanisms, placing them at increased risk of peri- and post-operative complications. This study aimed to evaluate if dental treatment performed before advanced cardiac interventions, including orthotopic heart transplant and mechanical circulatory support, increases the risk of adverse events. STUDY DESIGN: A retrospective chart review spanning January 2011 to December 2020 was performed. Inpatients with end-stage heart disease were evaluated by the hospital dentistry service at UCLA Ronald Reagan Medical Center. Three hundred and five consults met the inclusion criteria. The patients were divided into 2 groups: those who underwent dental treatment and those who did not require dental treatment. The wait time from dental consultation to cardiac intervention (days), dental complications, medical adverse events, and deaths were evaluated. RESULTS: Dental complications were only experienced in the form of intraoral bleeding. There was no significant difference in the number of medical adverse events or deaths between groups. CONCLUSIONS: The elimination of oral infection before advanced cardiac interventions does not increase the risk of morbidity or mortality.

Transmission of Trypanosoma cruzi by heart transplantation.

BACKGROUND: Trypanosoma cruzi infection (i.e., Chagas disease) is an unusual complication that can occur after solid-organ transplantation and that can result in severe illness or death. In 2006, there were 2 heart transplant recipients in Los Angeles, California, reported to have acute trypanosomiasis during the same month. We conducted an investigation to determine the source of these infections. METHODS: We reviewed the medical, organ procurement, and donor transfusion and transplantation records of these 2 heart transplant recipients. The 2 heart transplant recipients were interviewed regarding any kind of natural exposure and were screened for parasites by obtaining blood and other tissue samples for buffy coat, culture, and polymerase chain reaction. Serum samples from the heart transplant recipients, organ donors, and blood donors were tested for T. cruzi antibodies by use of immunofluorescence assay and radioimmunoprecipitation assay. Tissue samples from the organ donors were examined by use of polymerase chain reaction and immunohistochemical staining. Other recipients of organs from the same donors were monitored for T. cruzi infection by use of polymerase chain reaction and immunofluorescence assay. RESULTS: Both heart transplant recipients had no apparent risk factors for preexisting T. cruzi infection. Both were seronegative but tested positive for the parasite, indicating recent infection. Both recipients died despite medical treatment. The organ donors tested positive for T. cruzi antibodies by use of radioimmunoprecipitation assay; the blood donors were seronegative. Six other patients had received a liver or kidney from these organ donors. None showed evidence of T. cruzi infection. CONCLUSIONS: To our knowledge, this is the first report of T. cruzi transmission associated with heart transplantation. Clinicians and public health authorities should be aware that manifestations of Chagas disease can occur after transplantation, requiring rapid evaluation, diagnosis, and treatment.

Successful Treatment of Scedosporium Sinusitis in Two Lung Transplant Recipients: Review of the Literature and Recommendations for Management.

BACKGROUND: Scedosporium fungal infection is an emerging disease which is difficult to diagnose and treat. Patients undergoing lung transplant may be colonized prior to transplantation and are at risk for lethal allograft infection after transplantation. OBJECTIVES: To identify and evaluate treatment options. METHODS: This study is a retrospective review of patients treated at a tertiary academic medical center from 2007 to 2017 with positive sinonasal cultures. A review of the literature was also performed to identify additional cases. RESULTS: Two lung transplant patients had a positive culture for Scedosporium. The literature search resulted in 37 citations, which yielded only 2 prior cases of Scedosporium paranasal sinus colonization or infection in lung transplant recipients. Three of the 4 patients had cystic fibrosis. Two of the patients were colonized before initial transplant, while 1 patient was colonized before subsequent transplant. Three of the 4 patients survived, and all 3 had disease isolated to their sinuses and lungs treated with sinus surgery, while the fourth had disseminated disease and did not undergo sinus surgery. All patients were treated with multiple antifungals due to resistance patterns. One surviving patient cleared both sinus and lung cultures in less than 1 month, while the other 2 surviving patients achieved negative cultures after a minimum of 6 months. CONCLUSIONS: Surgery may be especially important in patients with fungal sinus colonization or infection before or after lung transplantation. Chronic sinusitis is an important source for persistent fungal colonization and reinfection of the allograft which could be removed with surgical debridement before causing highly morbid pulmonary disease.

Diagnosis of coccidioidomycosis with use of the Coccidioides antigen enzyme immunoassay.

BACKGROUND: We have previously shown antigenuria in patients with coccidioidomycosis through use of the Histoplasma antigen enzyme immunoassay (EIA), and now we have developed a specific Coccidioides antigen EIA. METHODS: The Coccidioides EIA uses antibodies to Coccidioides galactomannan. The sensitivity of the Coccidioides and Histoplasma EIAs was evaluated in patients with more-severe coccidioidomycosis, and the specificity of these EIAs was evaluated in patients with nonfungal infections, in patients with other endemic mycoses, and in healthy individuals. RESULTS: Among patients in the present study, antigenuria was detected in 70.8% of patients with coccidioidomycosis with use of the Coccidioides EIA and in 58.3% of patients with use of the Histoplasma EIA. Antigenuria was absent in 99.4% of healthy individuals, patients with nonfungal infections, and patients with noninfectious conditions. Cross-reactions with other endemic mycoses were observed in 10.7% of patients. CONCLUSIONS: The Coccidioides EIA has potential to be useful in the rapid diagnosis of more-severe forms of coccidioidomycosis.

Bronchoalveolar immunologic profile of acute human lung transplant allograft rejection.

Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4 and CD8 T cells and their activation status by CD38 expression, natural killer (NK), NK-like T (NT), B, regulatory T, and invariant receptor NK-T cells. Percentages of CD4 were reduced, and CD8 and activation of CD4 T cells correlated with rejection. There were trends for increased NT, reduced NK, and increased B cell percentages with rejection, suggesting potential roles of these cells. Among regulatory cells, the percentages of regulatory T cells decreased and CD4/CD8 invariant NK-T cells increased during rejection, suggesting a proinflammatory profile. A unique BALF lymphocyte profile was associated with rejection and may provide insight into the pathogenesis of allograft rejection.

Clinical phenomapping and outcomes after heart transplantation.

BACKGROUND: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes. METHODS: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013. Multivariate analyses were used to evaluate the association between immunosuppression therapy, biomarkers, and the combined clinical end point of death, allograft loss, retransplantation, and rejection. Data were analyzed by K-means clustering (K = 2) to identify patterns of similar combined immunosuppression management, and percentile slopes were computed to examine the changes in dosages over time. Findings were correlated with clinical parameters, human leucocyte antigen antibody titers, and peripheral blood mononuclear cell gene expression of the AlloMap (CareDx, Inc., Brisbane, CA) test genes. An intragraft, heart tissue gene coexpression network analysis was performed. RESULTS: Unsupervised cluster analysis of immunosuppressive therapies identified 2 groups, 1 characterized by a steeper immunosuppression minimization, associated with a higher likelihood for the combined end point, and the other by a less pronounced change. A time-dependent phenomap suggested that patients in the group with higher event rates had increased human leukocyte antigen class I and II antibody titers, higher expression of the FLT3 AlloMap gene, and lower expression of the MARCH8 and WDR40A AlloMap genes. Intramyocardial biomarker-related coexpression network analysis of the FLT3 gene showed an immune system-related network underlying this biomarker. CONCLUSIONS: Time-dependent precision phenotyping is a mechanistically insightful, data-driven approach to characterize patterns of clinical care and identify ways to improve clinical management and outcomes.

Diagnosis of coccidioidomycosis by antigen detection using cross-reaction with a Histoplasma antigen.

BACKGROUND: In 2005, patients with coccidioidomycosis were observed to have positive Histoplasma antigen test results. METHODS: We performed a review of the records of patients with coccidioidomycosis who were under our care who underwent testing for Histoplasma antigen to determine the value of this test in the diagnosis of coccidioidomycosis. Many of the patients were immunosuppressed and critically ill. RESULTS: The Histoplasma antigen test had positive results when urine samples from 11 (58%) of 19 patients who had acute or chronic coccidioidomycosis were tested. The sensitivity was highest for patients who had acute coccidioidomycosis, and antigenuria was detected in 11 (79%) of 14 patients. One patient who had chronic coccidioidomycosis but who had a negative result when a urine sample was tested had antigen detected in bronchoalveolar lavage fluid. CONCLUSIONS: Physicians should be alerted that infections with Coccidioides species may cause positive Histoplasma antigen test results. There is potential for the use of this test in the diagnosis of coccidioidomycosis by taking advantage of this observed cross-reactivity. The greatest benefit appears to be in the population of seriously ill patients with acute pneumonia who live in areas that are endemic for Coccidioides infection.

Graft Loss and CLAD-Onset Is Hastened by Viral Pneumonia After Lung Transplantation.

BACKGROUND: Community-acquired respiratory virus (CARV) infections occur frequently after lung transplantation and may adversely impact outcomes. We hypothesized that while asymptomatic carriage would not increase the risk of chronic lung allograft dysfunction (CLAD) and graft loss, severe infection would. METHODS: All lung transplant cases between January 2000 and July 2013 performed at our center were reviewed for respiratory viral samples. Each isolation of virus was classified according to clinical level of severity: asymptomatic, symptomatic without pneumonia, and viral pneumonia. Multivariate Cox modeling was used to assess the impact of CARV isolation on progression to CLAD and graft loss. RESULTS: Four thousand four hundred eight specimens were collected from 563 total patients, with 139 patients producing 324 virus-positive specimens in 245 episodes of CARV infection. Overall, the risk of CLAD was elevated by viral infection (hazard ratio [HR], 1.64; P < 0.01). This risk, however, was due to viral pneumonia alone (HR, 3.94; P < 0.01), without significant impact from symptomatic viral infection (HR, 0.97; P = 0.94) nor from asymptomatic viral infection (HR, 0.99; P = 0.98). The risk of graft loss was not increased by asymptomatic CARV infection (HR, 0.74; P = 0.37) nor symptomatic CARV infection (HR, 1.39; P = 0.41). Viral pneumonia did, however, significantly increase the risk of graft loss (HR, 2.78; P < 0.01). CONCLUSIONS: With respect to CARV, only viral pneumonia increased the risk of both CLAD and graft loss after lung transplantation. In the absence of pneumonia, respiratory viruses had no impact on measured outcomes.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

RATIONALE: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes. OBJECTIVES: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. METHODS: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. MEASUREMENTS AND MAIN RESULTS: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. CONCLUSIONS: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

Cluster of cases of invasive aspergillosis in a transplant intensive care unit: evidence of person-to-person airborne transmission.

In October 1998, a patient developed deep surgical-site and organ-space infection with Aspergillus fumigatus 11 days after undergoing liver retransplantation; subsequently, 2 additional patients in the transplant intensive care unit had invasive pulmonary infection with A. fumigatus diagnosed. It was determined that debriding and dressing wounds infected with Aspergillus species may result in aerosolization of spores and airborne person-to-person transmission.

Leptospirosis, water sports, and chemoprophylaxis.

Recreational activities, such as water sports and adventure travel, are emerging as an important risk factor for leptospirosis, a potentially fatal zoonosis. We report the clinical course of 2 patients who acquired leptospirosis through participation in water sports. Physicians caring for patients who participate in adventure travel involving water sports should be familiar with the risk factors for and diagnosis, prevention, and treatment of leptospirosis.

Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation.

Human beta-defensin-2 (HBD)2 is an antimicrobial peptide that participates in the innate host immune defense. HBD2 is present in bronchoalveolar lavage (BAL) fluid during conditions associated with airway inflammation but not in normal subjects. We measured HBD2 concentrations by semiquantitative Western analysis in BAL of prelung transplant patients (PRE) and postlung-transplant BAL associated with either "quiescent" histopathology (i.e., without acute cellular rejection or infection) (NORMAL POST) or with bronchiolitis obliterans syndrome (BOS). HBD2 levels were not different for PRE (n=9) versus NORMAL POST-transplant BAL specimens (n=22) (204+/-180 vs. 82+/-60 pg/mL; P=NS). The BAL HBD2 concentrations were significantly elevated, however, with BOS (n=8) (1,270+/-430 pg/mL; P<0.001). HBD2 has been previously shown to elicit an adaptive immune response by means of recruitment of immature CD34 dendritic cells and memory (CD4/CD45RO) T lymphocytes through interactions with their chemokine receptor, CCR6. Furthermore, HBD2 with CD14 in human tracheobronchial epithelium can complex with "toll-like receptors" to activate the nuclear factor (NF)-kappaB pathway and therefore promote cytokine gene expression. We therefore speculate that complex interactions between adaptive and innate immunity may contribute to the propagation of airway inflammation in BOS.

Mycobacterium abscessus empyema in a lung transplant recipient.

Non-tuberculous mycobacteria (NTM) have emerged as important pathogens in organ transplant recipients. Because NTM pulmonary infections vary in their clinical and radiographic presentations, heightened clinical suspicion is necessary for accurate diagnosis. We report a case of Mycobacterium abscessus empyema in a lung transplant recipient. Repeated attempts at identifying the organism from a variety of clinical specimens led to the correct diagnosis and treatment.

Corynebacterium jeikeium sepsis after 8-methoxypsolaren photopheresis for cutaneous T-cell lymphoma.

We describe a patient with cutaneous T-cell lymphoma who developed Corynebacterium jeikeium sepsis after experimental treatment with 8-methoxypsolaren. The epidemiology and clinical features of C. jeikeium infection are discussed. The patient was successfully treated with intravenous vancomycin without recurrence.

Seventeen-year experience with 1,083 heart transplants at a single institution.

BACKGROUND: Heart transplantation is the most accepted treatment for end-stage heart disease. A review of 1,083 consecutive transplants (1984 to 2001) was undertaken. METHODS: Adult recipients were divided into quartiles. The last 540 transplants were combined. Three eras were created from these, 1984 to 1991, 1991 to 1995, and 1995 to 2001, with three age groups: 0 to 18 years, 19 to 61 years, and 62 to 74 years. All patients have at least 1 year of follow-up time. End points were survival, rejection, and graft coronary artery disease. RESULTS: There were 1,012 patients. Donor age, graft ischemic time, and the proportion of elderly recipients and nonstandard donor hearts have increased in the current era. Actuarial 60-month survivals of recipients after 1995 were 80.7% (0 to 18 years); 75.3% (19 to 61 years); and 76.2% (>62 years). The current era children and younger adult groups demonstrated improved results when compared with previous eras (p = 0.003 and p = 0.05). Rejection episodes equal to or greater than ISHLT grade 3A per person per year improved to 0.15 in the current era (p < 0.001). During the three eras, older recipients (>62 years) demonstrated fewer episodes of rejection when compared with other adults (0.13 versus 0.58, p = 0.03). Deaths attributed to graft coronary artery disease decreased from 11% to 5% from era 2 to era 3. Regression analysis revealed a mild effect of donor age on survival and graft coronary artery disease (hazard ratio = 1.02, p = 0.001; hazard ratio = 1.039, p < 0.001, respectively). Recipient predictors of graft coronary artery disease were diagnosis of ischemic cardiomyopathy (hazard ratio = 1.6, p = 0.014) and congenital heart disease (hazard ratio = 3.41, p = 0.02). CONCLUSIONS: Improved survival in the current era may be attributed to better organ preservation, improved immunosuppression and control of infection, and less life-threatening graft coronary artery disease.