Clinical characteristics and treatment strategy of nocardiosis in lung transplant recipients: A single-center experience.

Objective: Nocardia are infrequent pathogens that disproportionately afflict organ transplant recipients. The present study aimed to summarize the clinical manifestations, diagnostic approaches, and treatment strategies of nocardiosis in lung transplant recipients. Methods: This retrospective study reviewed the clinical data of adult lung transplant recipients who were complicated with nocardiosis between January 2018 and December 2021 at the largest lung transplant center in South China. Results: The incidence of nocardiosis was 4.2% (13/316), including 9 cases of pulmonary nocardiosis and 4 disseminated nocardiosis (blood, pulmonary and intracranial). The accuracy in diagnosing nocardiosis was 77.8% by culture and 100% by metagenomic next-generation sequencing (mNGS). Nocardia farcinica was the most common causative pathogen. Trimethoprim-sulfamethoxazole-based combination therapy was administered initially, followed by a single antibiotic as the maintained therapy, lasting for 4-8 months. Conclusions: mNGS is more accurate than culture in diagnosing nocardiosis. Most patients responded well to the antibiotic therapy with combined antibiotics at the initial stage followed by a single antibiotic treatment.

Lung transplantation for anti-MDA5-positive dermatomyositis-associated rapid progressive interstitial lung disease: report of two cases and review of the literature.

Lung transplantation is an ultimate lifesaving treatment for many patients with end-stage lung disease, whereas whether it is an optional intervention for the anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis (DM)-associated rapid progressive interstitial lung disease (RP-ILD) remain controversial. We report two patients diagnosed with anti-MDA5-positive DM-associated RP-ILD, who were both bridging to lung transplant with extracorporeal membrane oxygenation (ECMO) after failing to respond to extensive immunosuppressants. The first patient received full rehabilitation, but the second patient died of DM flare at the early-stage post-lung transplantation. Most of the clinical information was parallel in these two patients except the anti-MDA5 antibody level, which gradually decreased and became negative in the first patient but always hovering in high titers in the second patient, although both of the two patients received standard immunosuppressive regimen for prevention of rejection after lung transplantation. A total of 11 patients with anti-MDA5-positive DM-associated RP-ILD who underwent lung transplantation from the literature were identified. Most patients (10/11, 90.1%) were successfully discharged and without DM flare during the follow-up period post-lung transplantation. Nine of them were followed up more than 1 year, and anti-MDA-5 antibody was reported to be negative in four patients, whereas the others were unavailable. Combined with the case series in the literature, our limited experience suggests that lung transplantation is a promising therapeutic option for end-stage patients with anti-MDA5-positive DM-associated RP-ILD, with ECMO as a bridge to lung transplantation, if necessary. However, clearance or a downtrend of anti-MDA5 antibody may be required pre-transplant to avoid DM flare and recurrent RP-ILD post-transplantation.

The Airway Microbiota Signatures of Infection and Rejection in Lung Transplant Recipients.

Infection and rejection are the two most common complications after lung transplantation (LT) and are associated with increased morbidity and mortality. We aimed to examine the association between the airway microbiota and infection and rejection in lung transplant recipients (LTRs). Here, we collected 181 sputum samples (event-free, n = 47; infection, n = 103; rejection, n = 31) from 59 LTRs, and performed 16S rRNA gene sequencing to analyze the airway microbiota. A significantly different airway microbiota was observed among event-free, infection and rejection recipients, including microbial diversity and community composition. Nineteen differential taxa were identified by linear discriminant analysis (LDA) effect size (LEfSe), with 6 bacterial genera, Actinomyces, Rothia, Abiotrophia, Neisseria, Prevotella, and Leptotrichia enriched in LTRs with rejection. Random forest analyses indicated that the combination of the 6 genera and procalcitonin (PCT) and T-lymphocyte levels showed area under the curve (AUC) values of 0.898, 0.919 and 0.895 to differentiate between event-free and infection recipients, event-free and rejection recipients, and infection and rejection recipients, respectively. In conclusion, our study compared the airway microbiota between LTRs with infection and acute rejection. The airway microbiota, especially combined with PCT and T-lymphocyte levels, showed satisfactory predictive efficiency in discriminating among clinically stable recipients and those with infection and acute rejection, suggesting that the airway microbiota can be a potential indicator to differentiate between infection and acute rejection after LT. IMPORTANCE Survival after LT is limited compared with other solid organ transplantations mainly due to infection- and rejection-related complications. Differentiating infection from rejection is one of the most important challenges to face after LT. Recently, the airway microbiota has been reported to be associated with either infection or rejection of LTRs. However, fewer studies have investigated the relationship between airway microbiota together with infection and rejection of LTRs. Here, we conducted an airway microbial study of LTRs and analyzed the airway microbiota together with infection, acute rejection, and clinically stable recipients. We found different airway microbiota between infection and acute rejection and identify several genera associated with each outcome and constructed a model that incorporates airway microbiota and clinical parameters to predict outcome. This study highlighted that the airway microbiota was a potential indicator to differentiate between infection and acute rejection after LT.

Metagenomic Next-Generation Sequencing for Diagnosing Infections in Lung Transplant Recipients: A Retrospective Study.

Background: Accurate identification of pathogens is essential for the diagnosis and control of infections. We aimed to compare the diagnostic performance of metagenomic next-generation sequencing (mNGS) and conventional detection methods (CDM) in lung transplant recipients (LTRs). Methods: We retrospectively analyzed 107 LTRs with suspected infection of pulmonary, blood, central nervous system or chest wall between March 2018 and November 2020. Bronchoalveolar lavage fluid and other body fluids were subject to pathogen detection by both mNGS and CDM. Results: Of the 163 specimens, 84 (51.5%) tested positive for both mNGS and culture, 19 (11.7%) of which were completely consistent, 44 (27.0%) were partially congruent, and 21 (12.9%) were discordant (kappa = .215; p = .001). Compared with CDM, mNGS detected a higher diversity of pathogens. Moreover, the turn-around time was significantly shorter for mNGS compared with culture (2.7 ± .4 vs. 5.5 ± 1.6 days, p < .001). As an auxiliary method, treatment strategies were adjusted according to mNGS findings in 31 cases (29.0%), including eight patients with non-infectious diseases, who were finally cured. Conclusion: mNGS can identify pathogens with a shorter turn-around time and therefore provide a more accurate and timely diagnostic information to ascertaining pulmonary infections. mNGS might have a role in differentiating infectious from non-infectious lung diseases in LTRs.

High-throughput next-generation sequencing for identifying pathogens during early-stage post-lung transplantation.

BACKGROUND: High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. METHODS: In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. RESULTS: HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P < 0.001). For three LTx recipients, treatment regimens were adjusted according to the results of HT-NGS, leading to a complete recovery. CONCLUSION: HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.

Recommended prophylactic and management strategies for severe acute respiratory syndrome coronavirus 2 infection in transplant recipients.

Since December 2019, increasing attention has been paid to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Wuhan, China. SARS-CoV-2 primarily invades the respiratory tract and lungs, leading to pneumonia and other systemic disorders. The effect of SARS-CoV-2 in transplant recipients has raised significant concerns, especially because there is a large population of transplant recipients in China. Based on the current epidemic situation, this study reviewed publications on this virus and coronavirus disease 2019 (COVID-19), analyzed common features of respiratory viral pneumonias, and presented the currently reported clinical characteristics of COVID-19 in transplant recipients to improve strategies regarding the diagnosis and treatment of COVID-19 in this special population.