The performance of bronchoalveolar lavage Aspergillus PCR testing in solid organ transplant recipients with invasive pulmonary aspergillosis.

BACKGROUND: Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients. METHODS: We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria. RESULTS: Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%-93%), and the specificity was 98% (95% CI 93%-99%). CONCLUSION: BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test.

Coccidioides species antifungal susceptibility testing: Experience from a large healthcare system in the endemic region.

The clinical utility of Coccidioides species antifungal susceptibility testing (AST) remains unclear. This study describes the clinical course of eight patients with severe or chronic coccidioidomycosis and subsequent Coccidioides AST. We present the clinical manifestations, antifungal treatment regimens, and clinical outcomes for these patients.

The role of antifungal susceptibility in the management of coccidioidomycosis remains unknown. This report presents cases of complex coccidioidomycosis where clinicians elected to conduct antifungal susceptibility testing as part of the treatment approach.

Diagnostic Approach to Coccidioidomycosis in Solid Organ Transplant Recipients.

Coccidioidomycosis is a fungal infection endemic in the southwestern United States, Mexico, and parts of Central and South America. While coccidioidomycosis is associated with mostly mild infections in the general population, it can lead to devastating infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Early and accurate diagnosis is important in achieving better clinical outcomes in immunocompromised patients. However, the diagnosis of coccidioidomycosis in SOT recipients can be challenging due to the limitations of diagnostic methods including cultures, serology, and other tests in providing a timely and accurate diagnosis. In this review, we will discuss the available diagnostic modalities and approaches when evaluating SOT recipients with coccidioidomycosis, from the use of conventional culture methods to serologic and molecular testing. Additionally, we will discuss the role of early diagnosis in assisting with the administration of effective antifungal therapy to reduce infectious complications. Finally, we will discuss ways to improve the performance of coccidioidomycosis diagnostic methods in SOT recipients with an option for a combined testing approach.

Lack of effectiveness of Bebtelovimab monoclonal antibody among high-risk patients with SARS-Cov-2 Omicron during BA.2, BA.2.12.1 and BA.5 subvariants dominated era.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N = 1,091) compared to propensity score (PS) matched control (N = 1,091). The primary composite outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary composite outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p = 0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (<65 years or ≥65), and immunocompromised status (patients with HIV/AIDS or solid organ transplants or malignancy including lymphoproliferative disorder). The number needed to treat (1/0.026-0.022) with BEB MAb was 250 to avoid one hospitalization and/or death over 30 days. The BEB MAb use lacked efficacy in patients with SARS-CoV-2 Omicron subvariants (mainly BA.2, BA.2.12.1, and BA.5) in the Banner Healthcare System in the Southwestern United States.

Pneumocystis jiroveci Pneumonia: A Review of Management in Human Immunodeficiency Virus (HIV) and Non-HIV Immunocompromised Patients.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection that was mainly associated with pneumonia in patients with advanced human immunodeficiency virus (HIV) disease. There has been a decline in Pneumocystis jirovecii pneumonia incidence in HIV since the introduction of antiretroviral medications. However, its incidence is increasing in non-HIV immunocompromised patients including those with solid organ transplantation, hematopoietic stem cell transplantation, solid organ tumors, autoimmune deficiencies, and primary immunodeficiency disorders. We aim to review and summarize the etiology, epidemiology, clinical presentation, diagnosis, and management of Pneumocystis jirovecii pneumonia in HIV, and non-HIV patients. HIV patients usually have mild-to-severe symptoms, while non-HIV patients present with a rapidly progressing disease. Induced sputum or bronchoalveolar lavage fluid can be used to make a definitive diagnosis of Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is considered to be the first-line drug for treatment and has proven to be highly effective for Pneumocystis jirovecii pneumonia prophylaxis in both HIV and non-HIV patients. Pentamidine, atovaquone, clindamycin, and primaquine are used as second-line agents. While several diagnostic tests, treatments, and prophylactic regimes are available at our disposal, there is need for more research to prevent and manage this disease more effectively.

The Impact of Nirmatrelvir-Ritonavir in Reducing Hospitalizations Among High-Risk Patients With SARS-CoV-2 During the Omicron Predominant Era.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality in high-risk populations. Several therapeutics have been developed to reduce the risk of complications related to COVID-19, hospitalizations, and death. In several studies, nirmatrelvir-ritonavir (NR) was reported to reduce the risk of hospitalizations and death. We aimed to evaluate the efficacy of NR in preventing hospitalizations and death during the Omicron predominant period. METHODS: We retrospectively evaluated patients from June 1, 2022, through September 24, 2022. There were a total of 25,939 documented COVID-19 cases. Using propensity matching, we matched 5754 patients treated with NR with untreated patients. RESULTS: Postmatching, the median age of the NR-treated group was 58 years (interquartile range, 43-70 years) and 42% were vaccinated. Postmatching composite outcome of the 30-day hospitalization and mortality in the NR-treated group were 0.9% (95% confidence interval [CI]: 0.7%-1.2%) versus 2.1% (95% CI: 1.8%-2.5%) in the matched control group, with a difference of -1.2 (-1.7, -0.8), P value <.01. The difference rates (NR vs. control) in 30-day all-cause hospitalizations and mortality were -1.2% (95% CI: -1.6% to -0.7%, P value <.01) and -0.1% (95% CI: -0.2% to 0.0%, P value = 0.29), respectively. We found similar finding across different age groups (≥65 vs. <65) and the vaccinated group. CONCLUSION: We report a significant benefit with the use of NR in reducing hospitalizations among various high-risk COVID-19 groups during the Omicron BA.5 predominant period.

Effect of coccidioidomycosis prophylaxis in selecting non-Candida albicans species amongst solid organ transplant recipients in Arizona.

BACKGROUND: Invasive candidiasis carries an increased risk of morbidity and mortality. The rates of non-albicans Candida species (NAC) infections are on the rise secondary to frequent azole antifungal use. NAC incidence and risk amongst solid organ transplant (SOT) recipients in Arizona receiving prolonged azole course for coccidioidomycosis prophylaxis have not been well elucidated. METHODS: We retrospectively evaluated SOT recipients hospitalised between 2017 and 2021 with a positive Candida spp. culture. RESULTS: There were 66 SOT recipients with 74 hospitalisations and 79 Candida spp. isolates. The median age was 59 (IQR 45-66), 68% were male, 58% were non-Hispanic White, and the most common SOT 38/74 (51%) was a liver transplant. Median time from transplant to the identification of any NAC (infection or colonisation) was significantly shorter, 8 months (IQR 3-78) vs 128 months (IQR 10-282) for Candida albicans isolates, p = .03. Prior use of azoles was significantly higher in NAC-associated post-transplant colonisation and invasive disease hospitalisations (83%) than in those with C. albicans (17%), p < .001. There were 59 hospitalisations with invasive disease, with the majority having NAC isolates of 49 (83%). CONCLUSION: The universal azole prophylaxis has reduced the incidence of coccidioidomycosis complications amongst SOT recipients in Arizona; however, there is an increased risk of developing NAC colonisation and infections, which can complicate the care of the SOT recipients with invasive candidiasis. Future studies are needed to investigate methods of reducing the risk of NAC infections whilst preventing coccidioidomycosis amongst SOT recipients.

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab-Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among immunocompromised patients. Tixagevimab-cilgavimab (Tix-Cil) is a combination of 2 monoclonal antibodies approved for the prevention of COVID-19 complications in this high-risk group. METHODS: We retrospectively reviewed the charts of patients who received Tix-Cil during the Omicron variant period (January 17 to April 23, 2022), with a follow-up period until May 24, 2022. We collected data about patient underlying comorbidities and post Tix-Cil COVID-19 infections, deaths, and hospitalizations. RESULTS: There were 463 patients with a median age of 68 years, of which 51% were male, 79% White, 13.2% Hispanic, 1.7% Black/African American, and 5.8% identified as Other. A total of 18% had undergone a solid organ transplantation or hematopoietic stem cell transplantation. Only 6/98 (6.1%) had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by polymerase chain reaction (PCR) at a median 48 days (interquartile range [IQR] 27.5, 69) follow-up. Forty-two patients (9.1%) were hospitalized, and 4 (0.9%) died, but none were attributed to COVID-19 or Tix-Cil. One hospitalized patient had an incidental, asymptomatic, positive SARS-CoV 2 by PCR. The median days from Tix-Cil administration to non-COVID-19-related hospitalization and death were 30 (IQR 17, 55) and 53 (IQR 18, 91), respectively. CONCLUSION: Tix-Cil provides protection against COVID-19 complications in immunocompromised patients with suboptimal immune responses to vaccines.

The Utility of (1→3)-ß-D-Glucan Testing in the Diagnosis of Coccidioidomycosis in Hospitalized Immunocompromised Patients.

Coccidioidomycosis is a fungal infection endemic to the Southwestern United States which is associated with high morbidity and mortality in immunocompromised hosts. Serology is the main diagnostic tool, although less sensitive among immunocompromised hosts. (1→3)-ß-D-glucan (BDG) is a non-specific fungal diagnostic test that may identify suspected coccidioidomycosis and other invasive fungal infections. We retrospectively investigated the utility of BDG between 2017 and 2021 in immunocompromised hosts with positive Coccidioides spp. cultures at our institutions. During the study period, there were 368 patients with positive cultures for Coccidioides spp.; among those, 28 patients were immunocompromised hosts, had both Coccidioides serology and BDG results available, and met other inclusion and exclusion criteria. Half of the patients had positive Coccidioides serology, and 57% had a positive BDG ≥ 80 pg/mL. Twenty-three (82%) had at least one positive test during their hospitalization. Among immunocompromised hosts with suspicion for coccidioidomycosis, the combination of Coccidioides serology and BDG can be useful in the initial work up and the timely administration of appropriate antifungal therapy. However, both tests failed to diagnose many cases, underscoring the need for better diagnostic techniques for identifying coccidioidomycosis in this population.

Effectiveness of Casirivimab-Imdevimab Monoclonal Antibody Treatment Among High-Risk Patients With Severe Acute Respiratory Syndrome Coronavirus 2 B.1.617.2 (Delta Variant) Infection.

Background: Real-world data on the effectiveness of neutralizing casirivimab-imdevimab monoclonal antibody (Cas-Imd mAb) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among high-risk patients may inform the response to future SARS-CoV-2 variants. Methods: This study covers an observational retrospective data analysis in Banner Health Care System sites, mainly in Arizona. During the study period, the prevalence of SARS-CoV-2 Delta variant was between 95% and 100%. Of 29 635 patients who tested positive for coronavirus disease 2019 (COVID-19) between 1 August 2021 and 30 October 2021, in the Banner Health Care System, the study cohort was split into 4213 adult patients who received Cas-Imd mAb (1200 mg) treatment compared to a PS-matched 4213 untreated patients. The primary outcomes were the incidence of all-cause hospitalization, intensive care unit (ICU) admission, and mortality within 30 days of Cas-Imd mAb administration or Delta variant infection. Results: Compared to the PS-matched untreated cohort, the Cas-Imd mAb cohort had significantly lower all-cause hospitalization (4.2% vs 17.6%; difference in percentages, -13.4 [95% confidence interval {CI}, -14.7 to -12.0]; P < .001), ICU admission (0.3% vs 2.8%; difference, -2.4 [95% CI, -3.0 to -1.9]; P < .001), and mortality (0.2% vs 2.0%; difference, -1.8 [95% CI, -2.3 to -1.3]; P < .001) within 30 days. The Cas-Imd mAb treatment was associated with lower rate of hospitalization (hazard ratio [HR], 0.22 [95% CI, .19-.26]; P < .001) and mortality (HR, 0.11 [95% CI, .06-.21]; P < .001). Conclusions: Cas-Imd mAb treatment was associated with a lower hospitalization rate, ICU admission, and mortality within 30 days among patients infected with the SARS-CoV-2 Delta variant.

A Comparative Analysis of Mucormycosis in Immunosuppressed Hosts Including Patients with Uncontrolled Diabetes in the Southwest United States.

BACKGROUND: Mucormycosis (zygomycosis) is an invasive fungal infection that carries a high risk of morbidity and mortality. Uncontrolled diabetes mellitus and other immunocompromising conditions are risk factors for mucormycosis development. We here describe the differences in characteristics and outcomes of mucormycosis among solid organ transplant, hematological malignancy, and diabetes mellitus groups at our institution. METHODS: We conducted a retrospective chart review over the period of 2009-2020, with identifying patients using the International Classification of Diseases, Ninth and Tenth Revisions. Clinical, laboratory, and outcome data were collected. RESULTS: There were 28 patients identified: 7 solid organ transplant, 3 hematological malignancy, and 18 diabetes mellitus patients were included in the study. Three solid organ transplant patients experienced an episode of rejection, and another 3 had cytomegalovirus infection prior to presenting with mucormycosis. Four of seven solid organ transplant patients had a history of diabetes mellitus, but the median hemoglobin A1C was lower than in the diabetes mellitus group (6.3 vs 11.5; P = .006). The mortality rate difference between solid organ transplant and diabetes mellitus was not statistically significant: 2/7 (28.57%) vs 5/18 (27.78%); P = .66. Patients with bilateral disease (pulmonary or sinus) had significantly higher mortality (80% vs 13%, P = .008). There was no difference in mortality outcomes among the different types of antifungal therapies administered. CONCLUSION: A multispecialty approach is imperative in mucormycosis therapy. While the underlying risk factors were different, the outcomes were comparable for the solid organ transplant and diabetes mellitus groups. Future larger and longitudinal studies are recommended.

Perinephric abscess in a renal transplant recipient due to Mycoplasma hominis: Case report and review of the literature.

A 42-year-old man presented with nausea, malaise, and pain at his renal graft site 4 months following deceased donor renal transplant. His transplantation had been complicated by urinary leak with delayed wound closure requiring ureteral revision with biologic mesh placement. The initial evaluation in the hospital revealed urinalysis with significant pyuria as well as abdominal CT imaging concerning for abscess formation anterior to the grafted kidney. Interventional radiology (IR) guided drainage of this abscess yielded growth of Enterococcus faecalis treated with intravenous ampicillin/sulbactam. He continued to have pain at his graft site and repeat imaging revealed a persistent abscess despite prolonged antimicrobial therapy. Urine cultures isolated Mycoplasma species. A repeat aspirate of abscess fluid collected and Mycoplasma hominis was identified by molecular test. Patient's symptoms abated and his abscess completely resolved on repeat imaging after completing a course of oral moxifloxacin and doxycycline. His immunosuppression did not require adjustment and the renal graft continued to function well following this therapy. Mycoplasma and Ureaplasma should be considered as a potential etiology for perinephric abscess in renal transplant recipients.

Clinical Outcomes Following the Use of Archived Proviral HIV-1 DNA Genotype to Guide Antiretroviral Therapy Adjustment.

BACKGROUND: Evidence regarding the safety of using proviral HIV-1 DNA genotype (DNA GT) to guide antiretroviral therapy (ART) is limited. We hypothesized that HIV RNA would not increase following ART adjustment guided by DNA GT in a university HIV clinic. METHODS: Data were obtained from electronic medical records of adult persons living with HIV-1 (PWH) who underwent DNA GT testing and changed ART between October 2014 and November 2017. Logistic regression was used to evaluate the effect of ART switch on HIV RNA over time. RESULTS: Eighty-three PWH had DNA GT performed, 66 (80%) switched ART, and 59 had postswitch follow-up. Data were analyzed pre-/postswitch for these 59 PWH (median age, 54 years; 71% LWH ≥10 years; 46% ≥2 previous regimens; 36% recent low-level viremia; 34% unknown medication history). On DNA GT, 58% had ≥1-class ART resistance, 34% ≥2-class, and 10% 3-class. Median follow-up (range) was 337 (34-647) days. There was no change in probability of HIV RNA ≥50 copies/mL over time (P > .05). At baseline, 76% had HIV RNA <50 vs 88% at last postswitch follow-up (P = .092). Protease inhibitor use decreased from 58% to 24% (P < .001). Average daily pills and dosing frequency decreased from 3.48 to 2.05 (P < .001) and 1.39 to 1.09 (P < .001), respectively; ART cost did not change. CONCLUSIONS: DNA GT facilitated changes in ART in a treatment-experienced population without increases in HIV RNA. Decreased pill burden occurred without increased ART cost. Further studies to identify optimal use of DNA GT are needed.

A Single-Center Experience and Literature Review of Management Strategies for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Patients.

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

De novo coccidioidomycosis among solid organ transplant recipients 1 or more years after transplant.

Solid organ transplant recipients who contract coccidioidomycosis are at risk for complicated, protracted, disseminated, and severe disease. To date, no studies have described outcomes for patients who develop coccidioidomycosis only after the first posttransplant year. This study was a joint project of Mayo Clinic Hospital, Phoenix, Arizona, and the University of Arizona/Banner University Medical Center, Tucson, Arizona. We retrospectively reviewed electronic health records for patients with a history of solid organ transplant between January 1, 1998, and October 11, 2014, who developed coccidioidomycosis after the first transplant year. We identified 91 patients. Of those, 37/91 (40.7%) had pulmonary coccidioidomycosis (29/37 [78.4%] were symptomatic); and 5/91 (5.5%) had extrapulmonary disease (all were symptomatic). One patient (1.1%) died. Coccidioidomycosis was evident in 2/91 (2.2%) patients within 3 months of antirejection treatment. Many of the patients (51/91 [56.0%]) had asymptomatic coccidioidomycosis, 27 (27.9%) of whom were followed up closely but did not receive antifungal medication and had no sequelae. Although solid organ recipients taking low-level immunosuppression after the first posttransplant year appeared to have less symptomatic, disseminated, or fatal coccidioidal infection than historical cohorts, this remains an important infection with morbidity and mortality even after the first posttransplant year.