Clinical features and therapeutic strategies for Talaromyces Marneffei pneumonia in kidney transplant recipients

Clinical features and therapeutic strategies for Talaromyces Marneffei pneumonia in kidney transplant recipients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical features and therapeutic strategies for Talaromyces Marneffei pneumonia in kidney transplant recipients Mingda Zhong, Hedong Zhang, HAN Yan, Yanjin Li, Daiwen Zhu, Shanbiao Hu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8965623/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Objective To analyze the clinical characteristics, diagnosis, treatment, and prognosis of Talaromyces marneffei pneumonia (TMP) in kidney transplant recipients, providing clinical evidence. Methods A retrospective analysis was conducted among 8 HIV-negative patients who underwent deceased donor kidney transplantation and were subsequently diagnosed with TMP at the Second Xiangya Hospital of Central South University from January 2015 to January 2025. Clinical data pertinent to the study, including demographic features, diagnostic modalities, therapeutic regimens, and prognosis, were systematically collected and analyzed. Results Of the 8 patients (7 males, 1 female; mean age 45.12 ± 9.03 years), the median time from transplantation to TMP onset was 356.5 days(IQR,302.75-771.75). All presented with fever (2 accompanied by cough), and chest CT showed diverse opacities. Metagenomic next-generation sequencing (mNGS) was the primary diagnostic tool, detecting Talaromyces marneffei in 7 cases (87.5% detection rate) with an average diagnosis time of 5 ± 2.56 days, while traditional culture only confirmed 3 cases. Amphotericin B was administered as the core induction therapy, followed by maintenance therapy after approximately 2 weeks, combined with individualized oral azole drugs tailored to each patient’s condition. All patients achieved clinical cure with no severe adverse reactions. The dosage of immunosuppressants was adjusted during anti-TMP treatment. Conclusion Kidney transplant recipients on long-term immunosuppressants are at significant risk of TMP. Combining mNGS with traditional culture enables early diagnosis, while amphotericin B and itraconazole are core treatments. Monitoring and adjusting immunosuppressant concentrations during azole therapy is critical for efficacy and long-term graft survival. Figures Figure 1 Figure 2 Figure 3 Introduction Talaromyces marneffei (TM) is a thermally dimorphic fungus. First isolated from bamboo rats in Vietnam in 1956, it was initially named Penicillium marneffei. Subsequent studies demonstrated that it does not belong to the genus Penicillium but to Talaromyces, leading to its renaming as Talaromyces marneffei (TM)[ 1 ].Initially, T. marneffei infections predominantly occurred in human immunodeficiency virus (HIV)-positive patients, accounting for 89.9% of cases. With the advancement of organ transplantation technology, such infections have also been reported in HIV-negative populations, accounting for approximately 10.1% of cases[ 2 ].As a pathogen capable of causing human systemic mycosis, TM primarily invades the human body via the respiratory tract. It mainly targets the host’s mononuclear phagocyte reticuloendothelial system. Given that the respiratory system is among the earliest and most frequently affected systems, this often results in the development of Talaromyces marneffei pneumonia (TMP). If the infection progresses further, it can spread through the lymphatic or hematogenous route, leading to systemic disseminated infection and life-threatening consequences[ 3 , 4 ]. Currently, kidney transplantation remains the first-line treatment modality for end-stage renal disease (ESRD). Studies have demonstrated that kidney transplant recipients exhibit significantly higher long-term survival rates compared to dialysis patients awaiting transplantation[ 5 ]. It is important to note that to prevent graft rejection, kidney transplant recipients must take immunosuppressive agents long-term; this places the body in a state of persistent immunosuppression, which in turn markedly increases the risk of various infections. Infection is not only one of the common causes of post-transplant mortality in kidney transplant recipients but may also trigger graft rejection, leading to a progressive decline in graft function and, in severe cases, graft failure[ 6 ]. Given the limited number of reports on TMP in kidney transplant recipients, the diagnosis and treatment strategies for this infection in this specific population remain to be improved. In this study, all kidney transplant recipients with TMP treated at our center between 2015 and 2025 were enrolled. Their clinical characteristics, diagnosis and treatment regimens, as well as the prognosis of both the recipients and grafts, were analyzed. This study aims to provide insights for the subsequent diagnosis and management of TMP in the transplant population. Materials and methods Study population From January 1, 2015 to January 1, 2025, a total of 2433 deceased donor kidney transplantations were performed in the Kidney Transplantation Department of the Second Xiangya Hospital of Central South University. A retrospective review of data was conducted on kidney transplant recipients who developed infections post-transplantation, and 8 patients diagnosed with Talaromyces marneffei pneumonia were enrolled in this study. All cases received kidneys from deceased donors (DD). Prior to transplantation, patients were tested for AIDS, and all test results were found to be negative. Date collection Collect the preoperative baseline data, post-infection clinical symptoms, laboratory test results, treatment regimens, treatment duration, prognosis and other clinical data of these infected patients. All data were obtained from China Hunan Organ Allocation and Sharing computer system (COTRS) and the electronic medical record system of the Second Xiangya Hospital of Central South University. Inclusion criteria Kidney transplant recipients(Age ≥ 18 years) who received deceased donor renal transplantation at the Second Xiangya Hospital of Central South University from January 1, 2015 to January 1, 2025. Recipients diagnosed with TMP after transplantation and receiving regular therapy. Patients with complete clinical data during treatment and follow-up duration ≥ 3 months. Diagnostic Criteria for TMP Fungal microscopic examination and culture are conducted on clinical specimens such as blood, sputum, and bronchoalveolar lavage fluid (BALF), and the isolation and culture of dimorphic TM from these specimens constitutes the gold standard for the diagnosis of talaromycosis marneffei. Clinical Diagnosis: TM identified by PCR/mNGS/tNGS in peripheral blood or BALF, with either respiratory symptoms or chest CT findings compatible with fungal pneumonia. Induction and maintenance of immunosuppression Mycophenolate Mofetil (MMF) 1 g was administered orally 30 min pre-transplantation. All recipients received methylprednisolone pulse therapy (500 mg/ day, total cumulative dose 1500 mg).​ Induction therapy with anti-thymocyte globulin (ATG) was administered preoperatively to recipients of deceased donor kidneys, whereas basiliximab was given as preoperative induction therapy to recipients of living donor kidneys. Maintenance therapy: A triple immunosuppressive regimen was adopted, consisting of tacrolimus, mycophenolate mofetil, and oral methylprednisolone. Postoperatively, tacrolimus dosage was dynamically adjusted according to blood concentration monitoring results. Treatment of TMP Induction therapy was administered with Amphotericin B Colloidal Dispersion(ABCD) at a dose of 3–4 mg per kilogram of body weight daily (3–4 mg/(kg·d)) for a total of 2 weeks, followed by consolidation therapy with oral itraconazole or voriconazole at 200 mg every 12 hours (q12h) for an additional 10 weeks. For patients intolerant to ABCD, voriconazole was used as an alternative agent for induction therapy. Statistical methods Statistical analyses were performed using R software (version 4.5.0). Data was analyzed using GraphPad Prism 10.0 software. The measurement data conforming to normal distribution is expressed by mean ± standard deviation, and the measurement data of non-normal distribution is expressed by median (interquartile distance). Based on the results of the normality test and variance homogeneity test, we compared quantitative data using the Student’s t-test.Statistical significance was set at P < 0.05. Results Demographic data and clinical characteristics The demographic characteristics and basic clinical data of the study are shown in Table 1. Following kidney transplantation, these patients were administered an immunosuppressive regimen consisting of tacrolimus, mycophenolate, and methylprednisolone. Among the patients, seven were male and one was female, with an average age of 45.12 ± 9.03 (SD) years. The onset date was 356.5 days (interquartile range [IQR], 302.75–771.75) after transplantation. All patients were admitted to the hospital with fever as the initial symptom, and 2 patients were also accompanied by cough. On admission, chest CT findings showed patchy opacities in 3 cases, nodular opacities in 2 cases, patchy opacities combined with nodular opacities in 1 case, and nodular opacities with cavities in 2 cases(Fig. 1 ). Two cases yielded positive results in the plasma 1,3-β-D-glucan test (G test), while one patient was positive for the galactomannan test (GM test). Admission examination results of the 8 patients revealed that 7 cases exhibited decreased counts of CD3 + T cells and CD8 + T cells, while all 8 patients showed reduced CD4 + T cell numbers. Bronchoscopic examinations in these TMP patients demonstrated varying degrees of bronchial stenosis. Some patients also presented with mucosal hyperemia, nodules, ulcers, and inflammatory exudates. (Fig. 2 ). The average number of days from admission to confirmation of Talaromyces marneffei (TM) infection was 5 ± 2.56 days. Except for Patient P8 who underwent blood sampling for metagenomic next-generation sequencing (mNGS) due to high fever after admission, the remaining 7 patients underwent flexible bronchoscopy with bronchoalveolar lavage fluid (BALF) culture, and 6 patients had BALF sent for mNGS testing. TM was isolated from BALF culture in 1 patient, blood culture was positive for TM in 1 patient, and sputum culture was positive for TM in 1 patient. The baseline levels of creatinine (Cr), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in these patients were 138.55 ± 29.51 µmol/L (SD), 10.80 U/L (IQR: 9.30–15.22), and 16.89 ± 8.47 U/L (SD), respectively(Table.2). Table 1. Characterisitcs of the eight patients with TMP Patients Age (years) Gender Transplantat-ion date Onset date Initial clinical symptom CT imaging Days to diagnos-is Diagnostic methods Induction therapy Maintenance treatment Maintenance duration (months) Outcom-e P1 59 Male 28/6/2015 19/5/2023 Fever Patchy opacities 4 BALF mNGS ABCD 0.15g Qd ICZ 0.2g Q12h 7 months Cure P2 35 Male 8/4/2022 24/3/2023 Fever, Cough Nodules and patchy opacities 5 BALF mNGS ICZ 0.2g Q12h ICZ 0.2g Q12h 12 months Cure P3 49 Female 30/7/2021 26/4/2022 Fever Patchy opacities 3 BALF mNGS ABCD 0.15g Qd ICZ 0.2g Q12h 6 months Cure P4 44 Male 2/11/2016 8/2/2022 Fever Nodular opacities 5 BALF mNGS, Blood culture ABCD 0.15g Qd VCZ 0.2g Q12h 6 months Cure P5 57 Male 10/7/2021 22/5/2022 Fever Patchy opacities 5 BALF mNGS ABCD 0.15g Qd ICZ 0.2g Q12h 10 months Cure P6 38 Male 15/12/2022 12/1/2024 Fever Nodular opacities and cavities 9 BALF mNGS, Sputum culture ABCD 0.15g Qd ICZ 0.2g Q12h 6 months Cure P7 38 Male 1/2/2023 2/2/2024 Fever, Cough Nodular opacities and cavities 8 Blood culture ABCD 0.15g Qd VCZ 0.2g Q12h 6 months Cure Patients Age (years) Gender Transplantat-ion date Onset date Initial clinical symptom CT imaging Days for diagnosis Diagnostic methods Therapeutic strategy Maintenance treatment Maintenance duration (months) Outcom-e P8 41 Male 12/1/2024 25/7/2024 Fever Patchy opacities. 1 Blood mNGS ABCD 0.15g Qd VCZ 0.2g Q12h 7 months Cure BALF: bronchoalveolar lavage fluid; Blood: blood culture; Sputum: sputum culture; ABCD: Amphotericin B Colloidal Dispersion; ICZ: itraconazole; VCZ: voriconazole Table 2 Laboratory test results of patients with TMP Patients Cr pre-(µmol/L) ALT pre-(U/L) AST pre-(U/L) G-test (pg/ml) GM-test (pg/ml) CD3 + T (cells/µl) CD4 + T (cells/µl) CD8 + T (cells/µl) Cr post-(µmol/L) ALT post-(U/L) AST post- (U/L) P1 254 8.7 16.1 < 37.5 0.06 369 175 186 100 11.4 20.1 P2 190 6 13.8 < 37.5 0.05 796 288 473 169 3.3 8.6 P3 153 12 13.5 < 37.5 0.12 524 267 227 127 16.3 14.3 P4 323 24.5 34 578.7 0.25 413 185 154 247 21.9 41.1 P5 153 9.6 13.8 267.4 0.03 446 329 99 166 12.1 12.4 P6 176 12.2 7.2 < 37.5 0.05 629 330 266 113 17.4 8.6 P7 167 9.5 12 < 37.5 0.33 537 201 265 145 59 35.3 P8 169 24.3 24.7 < 37.5 0.57 544 352 172 175 17.9 21.6 Cr: creatinine; pre-: pre-treatment; post-: post-treatment; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CD3 + T: CD3 + T cells; CD4 + T: CD4 + T cells; CD8 + T:CD8 + T cells Treatments and outcomes During the anti-Talaromyces marneffei treatment for these eight patients, the average duration of induction therapy was 10.5 days (IQR,7.75–14). Among the 8 patients, 3 patients were initially treated based on the CT imaging findings which suggested fungal infection. They were empirically treated with voriconazole for anti-infection purposes. After diagnosis of TMP, 7 patients received induction therapy with amphotericin B lipid complex (ABCD), and 1 patient was given itraconazole 200 mg q12h orally for induction due to amphotericin B intolerance. During maintenance treatment, all 8 patients were administered itraconazole 200 mg q12h orally. Treatment was discontinued after the resolution of fever and other respiratory symptoms, as well as the nearly complete absorption of lesions on radiological imaging. The treatment duration ranged from 6 to 12 months, and all patients achieved clinical cure. Post-treatment, the levels of alanine aminotransferase and aspartate aminotransferase were 16.85 U/L (IQR,11.93–18.90) and 20.25 ± 12.14 (SD) U/L, respectively. Following the treatment, the mean creatinine level of the patients was 155.25 ± 46.06 (SD) µmol/L. Throughout the entire course of targeted therapy, maintenance therapy, and follow-up, none of the eight patients exhibited any signs of liver function impairment (Fig. 3 A, 3 B). Post-treatment, there was no significant alteration in creatinine levels when compared to the pre-treatment values (Fig. 3 C), and no notable adverse drug reactions were observed. During the treatment course, the dosage of immunosuppressants was either reduced or discontinued for all patients. Discussion Talaromyces marneffei can cause opportunistic invasive fungal infections, characterized by high recurrence and mortality rates. Due to its insidious onset and rapid progression, the diagnosis of talaromycosis is often delayed, resulting in a high mortality rate. In addition, the mortality rate among HIV-negative patients is higher than that among HIV-positive patients[ 7 ]. Nowadays, it is increasingly being reported in kidney transplant recipients. For kidney transplant recipients, long-term administration of immunosuppressants is required to prolong graft survival. However, the impairment of immune defense caused by these agents renders the host more susceptible to pneumonia, among which Talaromyces marneffei pneumonia is a relatively rare but high-risk type[ 8 ]. Study have shown that inhalation of Talaromyces marneffei spores through the respiratory tract is the most common route of infection, and the lungs are among the earliest and most frequently involved sites[ 9 ]. Therefore, understanding the clinical characteristics, diagnosis and treatment experience of Talaromyces marneffei pneumonia after kidney transplantation is of great significance for the prevention of such infections in the future. In this study, all 8 patients presented mainly with fever and respiratory symptoms, with 2 cases accompanied by cough. This is consistent with the results of previous studies, but these clinical features are also shared with other infections after kidney transplantation, such as Mycobacterium tuberculosis infection and Pneumocystis pneumonia, which can easily lead to misdiagnosis and delayed diagnosis and treatment[ 10 ]. Computed tomography (CT) has significant auxiliary diagnostic value for TMP. As the first and most frequently involved system, the respiratory system can present a variety of abnormal chest imaging findings, including patchy infiltrates, focal pulmonary consolidation, nodules, diffuse miliary lesions, and may also be complicated by pleural effusion. All 8 patients in this study showed obvious lesions on chest CT(Fig. 2 ). Flexible bronchoscopy may reveal pathological findings such as tracheal inflammatory changes and bronchial stenosis. Among the 7 patients who underwent bronchoscopy in the study, all presented with inflammatory manifestations including congestion, nodules, and inflammatory secretions, while 2 cases were found to have bronchial stenosis (Fig. 3 ). Therefore, to prevent further spread of infection and poor prognosis in patients, it is advisable to perform flexible bronchoscopy promptly once talaromycosis pneumonia is suspected, followed by further examinations of the bronchoalveolar lavage fluid (BALF). Herein, 2 patients tested positive for the G test and 1 patient for the GM test. The positive rates of both tests were relatively low, failing to provide effective and robust support for the diagnosis of Talaromyces marneffei infection. Additionally, the GM antigen exhibits cross-reactivity with Aspergillus infections, resulting in low specificity[ 11 ]. Currently, the gold standard for diagnosing Talaromyces marneffei infection remains the isolation of the pathogen in cultures of body fluid specimens. However, Hien et al[ 12 ]. noted that such cultures may require up to 14 days to detect the pathogenic bacteria, which significantly delays diagnosis and treatment and could lead to irreversible harm or even life-threatening consequences for patients. In contrast, mNGS not only shortens the detection time to within 24 hours but also exhibits higher specificity than culture methods. This enables rapid diagnosis and treatment of the disease, significantly improving the prognosis[ 13 ]. Our data showed that Talaromyces marneffei was identified in 6 patients through mNGS of bronchoalveolar lavage fluid, 1 via blood mNGS, and 1 via blood culture. The median time from admission to diagnosis was 5 ± 2.56 days, while the patient diagnosed by blood culture required 8 days from admission to confirmation. While the sample collection period of this study spans from 2015 to 2025, incident cases are predominantly concentrated in 2022 and beyond. This observation may be attributed to the integration of mNGS into routine testing for patients with post-transplant infection at our hospital in late 2021. Thus, performing mNGS on BALF or body fluids as early as possible in these patients is more conducive to their diagnosis, treatment, and long-term survival. In the eight kidney transplant recipients studied, T-lymphocyte subset analysis revealed a profound state of cellular immune deficiency, with median absolute counts of 530.5 cells/µL for CD3+, 277.5 cells/µL for CD4+, and 206.5 cells/µL for CD8 + T cells. While a CD4 + count below 200 cells/µL is the classic threshold for TMP susceptibility in HIV patients[ 14 , 15 ]. Our findings underscore that transplant recipients remain highly vulnerable even at levels exceeding this marker. This suggests that long-term maintenance immunosuppression creates a 'vulnerability window' characterized by functional T-cell impairment. Consequently, monitoring lymphocyte profiles is vital, as any downward trend—regardless of the absolute count—necessitates heightened clinical vigilance for early TMP detection. There is no unified treatment standard for HIV-negative patients such as those who have undergone kidney transplantation. Accumulating evidence from prior research has indicated that induction therapy with amphotericin B followed by sequential itraconazole treatment serves as the first-line therapeutic strategy for HIV-positive individuals diagnosed with mucormycosis[ 16 ]. Currently, three main types of lipid formulations of amphotericin B are clinically available, namely Liposomal Amphotericin B (L-AmB), Amphotericin B Lipid Complex (ABLC), and Amphotericin B Colloidal Dispersion (ABCD). These three formulations exhibit distinct compositional differences. Specifically, L-AmB has the smallest molecular size, which allows it to evade recognition and phagocytosis by mononuclear phagocytes. Its concentrations in the liver and spleen are significantly higher than those in the kidneys and lung tissues, endowing it with the characteristic of the lowest nephrotoxicity[ 17 ]. The recommended dosage of L-AmB is 3–6 mg/kg/day. In contrast, ABLC is the largest lipid formulation, enabling it to be rapidly recognized and phagocytosed by macrophages. The clinically recommended initial dosage is 5 mg/kg/day, but both its infusion reactions and nephrotoxicity are higher than those of L-AmB[ 18 ]. After intravenous injection of ABCD, the ABCD complex remains largely intact. In addition, only a small fraction of the drug binds to circulating low-density lipoprotein (LDL), resulting in low drug concentration delivered to the kidneys[ 17 ]. Bowden et al. [ 19 ]conducted an investigation into the therapeutic efficacy of lipid-based amphotericin B preparations for invasive fungal infections. Their results revealed that while ABCD exhibited equivalent efficacy to conventional amphotericin B and offered a more favorable renal safety profile, it had a notable drawback: a significantly higher rate of infusion-related adverse events. For all TMP patients managed at our institution, ABCD was the exclusive amphotericin B formulation administered during treatment. Owing to the abbreviated inpatient treatment course, no notable infusion-associated adverse events were detected; additionally, the patients exhibited no significant deterioration in renal function post-treatment. The optimal dosage of ABCD is 3–4 mg/kg per day, whereas a dose of 8 mg/kg per day will induce severe adverse reactions involving cardiovascular impairment[ 20 ]. However, voriconazole may be considered as an alternative for patients intolerant to amphotericin B. Induction therapy with voriconazole: A loading dose of 6 mg/kg/day is administered intravenously every 12 hours (q12h) on the first day. Subsequently, the dose is reduced to 4 mg/kg/day, given intravenously q12h, for 3 consecutive days. Thereafter, the regimen may be switched to oral administration of 200 mg q12h based on the patient’s renal function status[ 21 ]. In general, for TMP patients after renal transplantation, the recommended treatment regimen is as follows: ABCD at a dose of 3–4 mg/kg/day is administered intravenously for induction therapy, lasting for 2 weeks. Subsequently, the treatment is switched to oral itraconazole or voriconazole, 200 mg q12h, for maintenance therapy with a total course of 10 weeks. When voriconazole or itraconazole is used in combination with tacrolimus, strict monitoring of tacrolimus blood concentrations is required. This is because these agents can inhibit the metabolism of tacrolimus by CYP enzymes, thereby causing a significant increase in tacrolimus blood concentrations, which may lead to severe nephrotoxicity and excessive immunosuppression[ 22 ]. Caspofungin is one of the commonly used antifungal agents in kidney transplant recipients. Studies have shown that compared with amphotericin B, voriconazole, and itraconazole, caspofungin has the weakest minimum inhibitory concentration (MIC) against Talaromyces marneffei and exhibits poorer therapeutic efficacy in the treatment of Talaromyces marneffei infections[ 23 ]. Conclusion For patients who have undergone kidney transplantation, due to the long-term use of immunosuppressive drugs, the harm caused by TMP cannot be ignored. Strengthening clinical awareness of TMP prevention and combining metagenomic next-generation sequencing (mNGS) technology with traditional body fluid culture technology are conducive to the early diagnosis of this pathogenic bacterium, which is crucial for the formulation of clinical treatment strategies. For patients diagnosed with TMP, the main antifungal drugs currently used are amphotericin B and itraconazole. During treatment with azole drugs, it is necessary to timely monitor the blood concentration of immunosuppressants and adjust the dosage accordingly based on the monitoring results. This measure is of great significance for ensuring the therapeutic effect of patients and improving the long-term survival of the transplanted kidney. Declarations Author contributions MZ drafted the manuscript. HZ collected and analyzed data. HY, YL,LT, SH, LP, and XX revised the manuscript. GL designed the outline of the manuscript and revised the manuscript. All authors have contributed to editing of manuscript. Mingda Zhong and Hedong Zhang contribute equally to this work and share first authorship. Funding This work is supported by Hunan Provincial Natural Science Foundation of China(2023JJ30755), Natural Science Foundation of Hunan Province (2024JJ2088), Natural Science Foundation of Hunan Province (2025JJ70074), National Natural Science Foundation of China (82370760). Data availability No datasets were generated or analysed during the current study. Ethics approval and consent to participate This study was approved by the Ethics Committee of Second Xiangya Hospital, Central South University, in accordance with the requirements of the Declaration of Helsinki.Written informed consent was obtained from all patients prior to enrollment in this study. Written informed consent was also obtained from all individuals for the publication of any potentially identifiable images or data included in this article. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Competing interests The authors declare no competing interests. References Zhou, X., et al., A 40-year antifungal susceptibility surveillance of Talaromyces marneffei (1984-2024) at a tertiary hospital in Guangxi, China. Med Mycol, 2025. 63 (6). Wang, F., R. Han, and S. 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Emerg Microbes Infect, 2016. 5 (3): p. e19. Quinton, L.J., A.J. Walkey, and J.P. Mizgerd, Integrative Physiology of Pneumonia. Physiol Rev, 2018. 98 (3): p. 1417-1464. Kawila, R., R. Chaiwarith, and K. Supparatpinyo, Clinical and laboratory characteristics of penicilliosis marneffei among patients with and without HIV infection in Northern Thailand: a retrospective study. BMC Infect Dis, 2013. 13 : p. 464. Xu, L., et al., Disseminated Talaromyces marneffei infection after renal transplantation: A case report and literature review. Front Cell Infect Microbiol, 2023. 13 : p. 1115268. Shi, J.X., et al., Clinical features of influenza-associated pulmonary aspergillosis: a retrospective multicenter cohort study. Front Cell Infect Microbiol, 2025. 15 : p. 1648547. Hien, H.T.A., et al., Development and evaluation of a real-time polymerase chain reaction assay for the rapid detection of Talaromyces marneffei MP1 gene in human plasma. Mycoses, 2016. 59 (12): p. 773-780. Li, Y., et al., Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients. Eur J Clin Microbiol Infect Dis, 2020. 39 (2): p. 369-374. Zhu, X.L., et al., CT findings of Talaromyces marneffei infection among HIV patients with lymphadenopathy. Front Med (Lausanne), 2022. 9 : p. 930678. Huang, J.L., et al., Neutrophil-to-lymphocyte ratio and lactate dehydrogenase for early diagnosis of AIDS patients with Talaromyces marneffei infection. Ann Palliat Med, 2022. 11 (2): p. 588-597. Le, T., et al., A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med, 2017. 376 (24): p. 2329-2340. Hamill, R.J., Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs, 2013. 73 (9): p. 919-34. Wingard, J.R., et al., A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis, 2000. 31 (5): p. 1155-63. Bowden, R., et al., A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis, 2002. 35 (4): p. 359-66. Bowden, R.A., et al., Phase I study of amphotericin B colloidal dispersion for the treatment of invasive fungal infections after marrow transplant. J Infect Dis, 1996. 173 (5): p. 1208-15. Ouyang, Y., et al., Administration of Voriconazole in Disseminated Talaromyces (Penicillium) Marneffei Infection: A Retrospective Study. Mycopathologia, 2017. 182 (5-6): p. 569-575. Yang, S., et al., Disseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review. BMC Infect Dis, 2024. 24 (1): p. 473. Zhang, J., et al., Antifungal Susceptibility Profiles of Olorofim (Formerly F901318) and Currently Available Systemic Antifungals against Mold and Yeast Phases of Talaromyces marneffei. Antimicrob Agents Chemother, 2021. 65 (6). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8965623","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":600723866,"identity":"2e5e2568-5761-4c83-a31d-034e71ee9d7e","order_by":0,"name":"Mingda Zhong","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Mingda","middleName":"","lastName":"Zhong","suffix":""},{"id":600723867,"identity":"0a1b7c52-8397-49b1-a332-ebf82b7856c1","order_by":1,"name":"Hedong Zhang","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Hedong","middleName":"","lastName":"Zhang","suffix":""},{"id":600723868,"identity":"666f029b-3819-4910-98fc-e28adb06609a","order_by":2,"name":"HAN Yan","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"HAN","middleName":"","lastName":"Yan","suffix":""},{"id":600723872,"identity":"5995ca99-cfd2-4f48-9647-441e682da8fa","order_by":3,"name":"Yanjin Li","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Yanjin","middleName":"","lastName":"Li","suffix":""},{"id":600723873,"identity":"8a4569b4-d040-4c77-a1b6-7590bc3b3d31","order_by":4,"name":"Daiwen Zhu","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Daiwen","middleName":"","lastName":"Zhu","suffix":""},{"id":600723874,"identity":"f3e0b3be-2af0-4971-920b-a3d0935912fa","order_by":5,"name":"Shanbiao Hu","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Shanbiao","middleName":"","lastName":"Hu","suffix":""},{"id":600723876,"identity":"b4f60dc3-7127-480f-8526-5b5d996c762f","order_by":6,"name":"Liang Tan","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Tan","suffix":""},{"id":600723878,"identity":"69bded6a-055f-4656-9927-10fa37a7f9f5","order_by":7,"name":"Longkai Peng","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Longkai","middleName":"","lastName":"Peng","suffix":""},{"id":600723882,"identity":"a9ea2742-659e-4b82-a36f-7d2a1f1a6bd4","order_by":8,"name":"Xubiao Xie","email":"","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Xubiao","middleName":"","lastName":"Xie","suffix":""},{"id":600723883,"identity":"656dd43c-2575-401c-89a9-a263bf3486ce","order_by":9,"name":"Gongbin Lan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBACPiidwMbAfADCPEBACxtCC1sCiVoYGHgMiNTCfvbwi487avP4pHs+fvzZxiDHdyOB8XMBPi08eWmWM88cL2aTObtZmreNwVjyRgKz9Ay8DssxM+ZtO5bYJpG7jZmxjSFxw40ENmYefFr438C05DxjBDqsnrAWiRzjx7xtNSAtbAxAhyUYENbyxoxxZtuBYjaJNGNpnnMShjPPPGyWxqeFnz/H+MPHtro8+RnJDz/+KLOR5zuefPAzPi1gixgYDsM4QDYDYwN+DQwMzB8YGOoIKRoFo2AUjIKRDABqIUcpTTEAdgAAAABJRU5ErkJggg==","orcid":"","institution":"Second Xiangya Hospital of Central South University","correspondingAuthor":true,"prefix":"","firstName":"Gongbin","middleName":"","lastName":"Lan","suffix":""}],"badges":[],"createdAt":"2026-02-25 09:09:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8965623/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8965623/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104181803,"identity":"d2e8923a-8f44-49cc-bd0f-2e52dc60d149","added_by":"auto","created_at":"2026-03-08 17:30:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":405676,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT findings in patients with TMP\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8965623/v1/f8f609976dad44310f9f3de7.png"},{"id":104181804,"identity":"8e7aee64-f824-4abd-8fbc-bca026621d2d","added_by":"auto","created_at":"2026-03-08 17:30:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":577277,"visible":true,"origin":"","legend":"\u003cp\u003eFlexible bronchoscopy findings in patients with TMP\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8965623/v1/a2ac9783871c84c39c9a53dc.png"},{"id":104779485,"identity":"1b82f05e-d86a-45c2-a737-6569437dae0c","added_by":"auto","created_at":"2026-03-17 07:40:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":55342,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in serum biochemical indicators of the patient before and after treatment(A) Changes in alanine aminotransferase (ALT) levels;(B) Changes in aspartate aminotransferase (AST) levels;(C) Changes in serum creatinine (Scr) levels.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8965623/v1/3b2b8e78a8a5600669e02aa4.png"},{"id":104784116,"identity":"c3559a09-8ec5-46ef-ad38-8f4010046029","added_by":"auto","created_at":"2026-03-17 08:05:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2201593,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8965623/v1/7f4d1029-6efe-441d-b6d1-0af5a648c009.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical features and therapeutic strategies for Talaromyces Marneffei pneumonia in kidney transplant recipients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTalaromyces marneffei (TM) is a thermally dimorphic fungus. First isolated from bamboo rats in Vietnam in 1956, it was initially named Penicillium marneffei. Subsequent studies demonstrated that it does not belong to the genus Penicillium but to Talaromyces, leading to its renaming as Talaromyces marneffei (TM)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].Initially, T. marneffei infections predominantly occurred in human immunodeficiency virus (HIV)-positive patients, accounting for 89.9% of cases. With the advancement of organ transplantation technology, such infections have also been reported in HIV-negative populations, accounting for approximately 10.1% of cases[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].As a pathogen capable of causing human systemic mycosis, TM primarily invades the human body via the respiratory tract. It mainly targets the host\u0026rsquo;s mononuclear phagocyte reticuloendothelial system. Given that the respiratory system is among the earliest and most frequently affected systems, this often results in the development of Talaromyces marneffei pneumonia (TMP). If the infection progresses further, it can spread through the lymphatic or hematogenous route, leading to systemic disseminated infection and life-threatening consequences[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, kidney transplantation remains the first-line treatment modality for end-stage renal disease (ESRD). Studies have demonstrated that kidney transplant recipients exhibit significantly higher long-term survival rates compared to dialysis patients awaiting transplantation[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It is important to note that to prevent graft rejection, kidney transplant recipients must take immunosuppressive agents long-term; this places the body in a state of persistent immunosuppression, which in turn markedly increases the risk of various infections. Infection is not only one of the common causes of post-transplant mortality in kidney transplant recipients but may also trigger graft rejection, leading to a progressive decline in graft function and, in severe cases, graft failure[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the limited number of reports on TMP in kidney transplant recipients, the diagnosis and treatment strategies for this infection in this specific population remain to be improved. In this study, all kidney transplant recipients with TMP treated at our center between 2015 and 2025 were enrolled. Their clinical characteristics, diagnosis and treatment regimens, as well as the prognosis of both the recipients and grafts, were analyzed. This study aims to provide insights for the subsequent diagnosis and management of TMP in the transplant population.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eFrom January 1, 2015 to January 1, 2025, a total of 2433 deceased donor kidney transplantations were performed in the Kidney Transplantation Department of the Second Xiangya Hospital of Central South University. A retrospective review of data was conducted on kidney transplant recipients who developed infections post-transplantation, and 8 patients diagnosed with Talaromyces marneffei pneumonia were enrolled in this study. All cases received kidneys from deceased donors (DD). Prior to transplantation, patients were tested for AIDS, and all test results were found to be negative.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDate collection\u003c/h3\u003e\n\u003cp\u003eCollect the preoperative baseline data, post-infection clinical symptoms, laboratory test results, treatment regimens, treatment duration, prognosis and other clinical data of these infected patients. All data were obtained from China Hunan Organ Allocation and Sharing computer system (COTRS) and the electronic medical record system of the Second Xiangya Hospital of Central South University.\u003c/p\u003e \u003cp\u003e \u003cb\u003eInclusion criteria\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eKidney transplant recipients(Age\u0026thinsp;\u0026ge;\u0026thinsp;18 years) who received deceased donor renal transplantation at the Second Xiangya Hospital of Central South University from January 1, 2015 to January 1, 2025.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eRecipients diagnosed with TMP after transplantation and receiving regular therapy.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePatients with complete clinical data during treatment and follow-up duration\u0026thinsp;\u0026ge;\u0026thinsp;3 months.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e\n\u003ch3\u003eDiagnostic Criteria for TMP\u003c/h3\u003e\n\u003cp\u003eFungal microscopic examination and culture are conducted on clinical specimens such as blood, sputum, and bronchoalveolar lavage fluid (BALF), and the isolation and culture of dimorphic TM from these specimens constitutes the gold standard for the diagnosis of talaromycosis marneffei.\u003c/p\u003e \u003cp\u003eClinical Diagnosis: TM identified by PCR/mNGS/tNGS in peripheral blood or BALF, with either respiratory symptoms or chest CT findings compatible with fungal pneumonia.\u003c/p\u003e\n\u003ch3\u003eInduction and maintenance of immunosuppression\u003c/h3\u003e\n\u003cp\u003eMycophenolate Mofetil (MMF) 1 g was administered orally 30 min pre-transplantation. All recipients received methylprednisolone pulse therapy (500 mg/ day, total cumulative dose 1500 mg).​ Induction therapy with anti-thymocyte globulin (ATG) was administered preoperatively to recipients of deceased donor kidneys, whereas basiliximab was given as preoperative induction therapy to recipients of living donor kidneys. Maintenance therapy: A triple immunosuppressive regimen was adopted, consisting of tacrolimus, mycophenolate mofetil, and oral methylprednisolone. Postoperatively, tacrolimus dosage was dynamically adjusted according to blood concentration monitoring results.\u003c/p\u003e\n\u003ch3\u003eTreatment of TMP\u003c/h3\u003e\n\u003cp\u003eInduction therapy was administered with Amphotericin B Colloidal Dispersion(ABCD) at a dose of 3\u0026ndash;4 mg per kilogram of body weight daily (3\u0026ndash;4 mg/(kg\u0026middot;d)) for a total of 2 weeks, followed by consolidation therapy with oral itraconazole or voriconazole at 200 mg every 12 hours (q12h) for an additional 10 weeks. For patients intolerant to ABCD, voriconazole was used as an alternative agent for induction therapy.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical methods\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using R software (version 4.5.0). Data was analyzed using GraphPad Prism 10.0 software. The measurement data conforming to normal distribution is expressed by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and the measurement data of non-normal distribution is expressed by median (interquartile distance). Based on the results of the normality test and variance homogeneity test, we compared quantitative data using the Student\u0026rsquo;s t-test.Statistical significance was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDemographic data and clinical characteristics\u003c/h2\u003e \u003cp\u003eThe demographic characteristics and basic clinical data of the study are shown in Table\u0026nbsp;1. Following kidney transplantation, these patients were administered an immunosuppressive regimen consisting of tacrolimus, mycophenolate, and methylprednisolone. Among the patients, seven were male and one was female, with an average age of 45.12\u0026thinsp;\u0026plusmn;\u0026thinsp;9.03 (SD) years. The onset date was 356.5 days (interquartile range [IQR], 302.75\u0026ndash;771.75) after transplantation. All patients were admitted to the hospital with fever as the initial symptom, and 2 patients were also accompanied by cough. On admission, chest CT findings showed patchy opacities in 3 cases, nodular opacities in 2 cases, patchy opacities combined with nodular opacities in 1 case, and nodular opacities with cavities in 2 cases(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTwo cases yielded positive results in the plasma 1,3-β-D-glucan test (G test), while one patient was positive for the galactomannan test (GM test). Admission examination results of the 8 patients revealed that 7 cases exhibited decreased counts of CD3\u003csup\u003e+\u003c/sup\u003e T cells and CD8\u003csup\u003e+\u003c/sup\u003e T cells, while all 8 patients showed reduced CD4\u003csup\u003e+\u003c/sup\u003e T cell numbers. Bronchoscopic examinations in these TMP patients demonstrated varying degrees of bronchial stenosis. Some patients also presented with mucosal hyperemia, nodules, ulcers, and inflammatory exudates. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe average number of days from admission to confirmation of Talaromyces marneffei (TM) infection was 5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56 days. Except for Patient P8 who underwent blood sampling for metagenomic next-generation sequencing (mNGS) due to high fever after admission, the remaining 7 patients underwent flexible bronchoscopy with bronchoalveolar lavage fluid (BALF) culture, and 6 patients had BALF sent for mNGS testing. TM was isolated from BALF culture in 1 patient, blood culture was positive for TM in 1 patient, and sputum culture was positive for TM in 1 patient.\u003c/p\u003e \u003cp\u003eThe baseline levels of creatinine (Cr), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in these patients were 138.55\u0026thinsp;\u0026plusmn;\u0026thinsp;29.51 \u0026micro;mol/L (SD), 10.80 U/L (IQR: 9.30\u0026ndash;15.22), and 16.89\u0026thinsp;\u0026plusmn;\u0026thinsp;8.47 U/L (SD), respectively(Table.2).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"12\" nameend=\"c14\" namest=\"c3\"\u003e \u003cp\u003eTable\u0026nbsp;1. Characterisitcs of the eight patients with TMP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatients\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(years)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eTransplantat-ion date\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eOnset\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003edate\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eInitial clinical symptom\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eCT imaging\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eDays to\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ediagnos-is\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eDiagnostic\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003emethods\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eInduction therapy\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eMaintenance treatment\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eMaintenance duration\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(months)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eOutcom-e\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28/6/2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19/5/2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePatchy opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8/4/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24/3/2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever,\u003c/p\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNodules and patchy opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eICZ\u003c/p\u003e \u003cp\u003e0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e12 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30/7/2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26/4/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePatchy opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2/11/2016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8/2/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNodular opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS,\u003c/p\u003e \u003cp\u003eBlood culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVCZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10/7/2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22/5/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePatchy opacities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e10 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15/12/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12/1/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNodular opacities and cavities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBALF mNGS,\u003c/p\u003e \u003cp\u003eSputum culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eICZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1/2/2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2/2/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever,\u003c/p\u003e \u003cp\u003eCough\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNodular opacities and cavities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBlood\u003c/p\u003e \u003cp\u003eculture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD\u003c/p\u003e \u003cp\u003e0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVCZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePatients\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eTransplantat-ion date\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003eOnset\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003edate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eInitial clinical symptom\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003eCT imaging\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eDays for\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ediagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eDiagnostic\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003emethods\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eTherapeutic strategy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cb\u003eMaintenance treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003eMaintenance duration\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cb\u003eOutcom-e\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12/1/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25/7/2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePatchy opacities.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBlood\u003c/p\u003e \u003cp\u003emNGS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eABCD 0.15g Qd\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eVCZ 0.2g Q12h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"14\"\u003eBALF: bronchoalveolar lavage fluid; Blood: blood culture; Sputum: sputum culture; ABCD: Amphotericin B Colloidal Dispersion; ICZ: itraconazole; VCZ: voriconazole\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory test results of patients with TMP\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCr pre-(\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALT pre-(U/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAST pre-(U/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eG-test\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGM-test\u003c/p\u003e \u003cp\u003e(pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCD3\u003csup\u003e+\u003c/sup\u003eT\u003c/p\u003e \u003cp\u003e(cells/\u0026micro;l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003eT\u003c/p\u003e \u003cp\u003e(cells/\u0026micro;l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD8\u003csup\u003e+\u003c/sup\u003eT\u003c/p\u003e \u003cp\u003e(cells/\u0026micro;l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCr post-(\u0026micro;mol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eALT post-(U/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eAST post- (U/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e20.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e473\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e16.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e14.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e578.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e21.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e41.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e267.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e166\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e537\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e201\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e544\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eCr: creatinine; pre-: pre-treatment; post-: post-treatment; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CD3\u003csup\u003e+\u003c/sup\u003eT: CD3\u003csup\u003e+\u003c/sup\u003eT cells; CD4\u003csup\u003e+\u003c/sup\u003eT: CD4\u003csup\u003e+\u003c/sup\u003eT cells; CD8\u003csup\u003e+\u003c/sup\u003eT:CD8\u003csup\u003e+\u003c/sup\u003eT cells\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTreatments and outcomes\u003c/h2\u003e \u003cp\u003eDuring the anti-Talaromyces marneffei treatment for these eight patients, the average duration of induction therapy was 10.5 days (IQR,7.75\u0026ndash;14). Among the 8 patients, 3 patients were initially treated based on the CT imaging findings which suggested fungal infection. They were empirically treated with voriconazole for anti-infection purposes. After diagnosis of TMP, 7 patients received induction therapy with amphotericin B lipid complex (ABCD), and 1 patient was given itraconazole 200 mg q12h orally for induction due to amphotericin B intolerance. During maintenance treatment, all 8 patients were administered itraconazole 200 mg q12h orally. Treatment was discontinued after the resolution of fever and other respiratory symptoms, as well as the nearly complete absorption of lesions on radiological imaging. The treatment duration ranged from 6 to 12 months, and all patients achieved clinical cure.\u003c/p\u003e \u003cp\u003ePost-treatment, the levels of alanine aminotransferase and aspartate aminotransferase were 16.85 U/L (IQR,11.93\u0026ndash;18.90) and 20.25\u0026thinsp;\u0026plusmn;\u0026thinsp;12.14 (SD) U/L, respectively. Following the treatment, the mean creatinine level of the patients was 155.25\u0026thinsp;\u0026plusmn;\u0026thinsp;46.06 (SD) \u0026micro;mol/L. Throughout the entire course of targeted therapy, maintenance therapy, and follow-up, none of the eight patients exhibited any signs of liver function impairment (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA,\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). Post-treatment, there was no significant alteration in creatinine levels when compared to the pre-treatment values (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC), and no notable adverse drug reactions were observed. During the treatment course, the dosage of immunosuppressants was either reduced or discontinued for all patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eTalaromyces marneffei can cause opportunistic invasive fungal infections, characterized by high recurrence and mortality rates. Due to its insidious onset and rapid progression, the diagnosis of talaromycosis is often delayed, resulting in a high mortality rate. In addition, the mortality rate among HIV-negative patients is higher than that among HIV-positive patients[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nowadays, it is increasingly being reported in kidney transplant recipients.\u003c/p\u003e \u003cp\u003eFor kidney transplant recipients, long-term administration of immunosuppressants is required to prolong graft survival. However, the impairment of immune defense caused by these agents renders the host more susceptible to pneumonia, among which Talaromyces marneffei pneumonia is a relatively rare but high-risk type[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Study have shown that inhalation of Talaromyces marneffei spores through the respiratory tract is the most common route of infection, and the lungs are among the earliest and most frequently involved sites[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, understanding the clinical characteristics, diagnosis and treatment experience of Talaromyces marneffei pneumonia after kidney transplantation is of great significance for the prevention of such infections in the future.\u003c/p\u003e \u003cp\u003eIn this study, all 8 patients presented mainly with fever and respiratory symptoms, with 2 cases accompanied by cough. This is consistent with the results of previous studies, but these clinical features are also shared with other infections after kidney transplantation, such as Mycobacterium tuberculosis infection and Pneumocystis pneumonia, which can easily lead to misdiagnosis and delayed diagnosis and treatment[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Computed tomography (CT) has significant auxiliary diagnostic value for TMP. As the first and most frequently involved system, the respiratory system can present a variety of abnormal chest imaging findings, including patchy infiltrates, focal pulmonary consolidation, nodules, diffuse miliary lesions, and may also be complicated by pleural effusion. All 8 patients in this study showed obvious lesions on chest CT(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Flexible bronchoscopy may reveal pathological findings such as tracheal inflammatory changes and bronchial stenosis. Among the 7 patients who underwent bronchoscopy in the study, all presented with inflammatory manifestations including congestion, nodules, and inflammatory secretions, while 2 cases were found to have bronchial stenosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Therefore, to prevent further spread of infection and poor prognosis in patients, it is advisable to perform flexible bronchoscopy promptly once talaromycosis pneumonia is suspected, followed by further examinations of the bronchoalveolar lavage fluid (BALF).\u003c/p\u003e \u003cp\u003eHerein, 2 patients tested positive for the G test and 1 patient for the GM test. The positive rates of both tests were relatively low, failing to provide effective and robust support for the diagnosis of Talaromyces marneffei infection. Additionally, the GM antigen exhibits cross-reactivity with Aspergillus infections, resulting in low specificity[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the gold standard for diagnosing Talaromyces marneffei infection remains the isolation of the pathogen in cultures of body fluid specimens. However, Hien et al[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. noted that such cultures may require up to 14 days to detect the pathogenic bacteria, which significantly delays diagnosis and treatment and could lead to irreversible harm or even life-threatening consequences for patients. In contrast, mNGS not only shortens the detection time to within 24 hours but also exhibits higher specificity than culture methods. This enables rapid diagnosis and treatment of the disease, significantly improving the prognosis[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Our data showed that Talaromyces marneffei was identified in 6 patients through mNGS of bronchoalveolar lavage fluid, 1 via blood mNGS, and 1 via blood culture. The median time from admission to diagnosis was 5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56 days, while the patient diagnosed by blood culture required 8 days from admission to confirmation. While the sample collection period of this study spans from 2015 to 2025, incident cases are predominantly concentrated in 2022 and beyond. This observation may be attributed to the integration of mNGS into routine testing for patients with post-transplant infection at our hospital in late 2021. Thus, performing mNGS on BALF or body fluids as early as possible in these patients is more conducive to their diagnosis, treatment, and long-term survival.\u003c/p\u003e \u003cp\u003eIn the eight kidney transplant recipients studied, T-lymphocyte subset analysis revealed a profound state of cellular immune deficiency, with median absolute counts of 530.5 cells/\u0026micro;L for CD3+, 277.5 cells/\u0026micro;L for CD4+, and 206.5 cells/\u0026micro;L for CD8\u0026thinsp;+\u0026thinsp;T cells. While a CD4\u0026thinsp;+\u0026thinsp;count below 200 cells/\u0026micro;L is the classic threshold for TMP susceptibility in HIV patients[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our findings underscore that transplant recipients remain highly vulnerable even at levels exceeding this marker. This suggests that long-term maintenance immunosuppression creates a 'vulnerability window' characterized by functional T-cell impairment. Consequently, monitoring lymphocyte profiles is vital, as any downward trend\u0026mdash;regardless of the absolute count\u0026mdash;necessitates heightened clinical vigilance for early TMP detection.\u003c/p\u003e \u003cp\u003eThere is no unified treatment standard for HIV-negative patients such as those who have undergone kidney transplantation. Accumulating evidence from prior research has indicated that induction therapy with amphotericin B followed by sequential itraconazole treatment serves as the first-line therapeutic strategy for HIV-positive individuals diagnosed with mucormycosis[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Currently, three main types of lipid formulations of amphotericin B are clinically available, namely Liposomal Amphotericin B (L-AmB), Amphotericin B Lipid Complex (ABLC), and Amphotericin B Colloidal Dispersion (ABCD). These three formulations exhibit distinct compositional differences. Specifically, L-AmB has the smallest molecular size, which allows it to evade recognition and phagocytosis by mononuclear phagocytes. Its concentrations in the liver and spleen are significantly higher than those in the kidneys and lung tissues, endowing it with the characteristic of the lowest nephrotoxicity[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The recommended dosage of L-AmB is 3\u0026ndash;6 mg/kg/day. In contrast, ABLC is the largest lipid formulation, enabling it to be rapidly recognized and phagocytosed by macrophages. The clinically recommended initial dosage is 5 mg/kg/day, but both its infusion reactions and nephrotoxicity are higher than those of L-AmB[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. After intravenous injection of ABCD, the ABCD complex remains largely intact. In addition, only a small fraction of the drug binds to circulating low-density lipoprotein (LDL), resulting in low drug concentration delivered to the kidneys[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Bowden \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]conducted an investigation into the therapeutic efficacy of lipid-based amphotericin B preparations for invasive fungal infections. Their results revealed that while ABCD exhibited equivalent efficacy to conventional amphotericin B and offered a more favorable renal safety profile, it had a notable drawback: a significantly higher rate of infusion-related adverse events. For all TMP patients managed at our institution, ABCD was the exclusive amphotericin B formulation administered during treatment. Owing to the abbreviated inpatient treatment course, no notable infusion-associated adverse events were detected; additionally, the patients exhibited no significant deterioration in renal function post-treatment. The optimal dosage of ABCD is 3\u0026ndash;4 mg/kg per day, whereas a dose of 8 mg/kg per day will induce severe adverse reactions involving cardiovascular impairment[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, voriconazole may be considered as an alternative for patients intolerant to amphotericin B. Induction therapy with voriconazole: A loading dose of 6 mg/kg/day is administered intravenously every 12 hours (q12h) on the first day. Subsequently, the dose is reduced to 4 mg/kg/day, given intravenously q12h, for 3 consecutive days. Thereafter, the regimen may be switched to oral administration of 200 mg q12h based on the patient\u0026rsquo;s renal function status[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In general, for TMP patients after renal transplantation, the recommended treatment regimen is as follows: ABCD at a dose of 3\u0026ndash;4 mg/kg/day is administered intravenously for induction therapy, lasting for 2 weeks. Subsequently, the treatment is switched to oral itraconazole or voriconazole, 200 mg q12h, for maintenance therapy with a total course of 10 weeks. When voriconazole or itraconazole is used in combination with tacrolimus, strict monitoring of tacrolimus blood concentrations is required. This is because these agents can inhibit the metabolism of tacrolimus by CYP enzymes, thereby causing a significant increase in tacrolimus blood concentrations, which may lead to severe nephrotoxicity and excessive immunosuppression[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Caspofungin is one of the commonly used antifungal agents in kidney transplant recipients. Studies have shown that compared with amphotericin B, voriconazole, and itraconazole, caspofungin has the weakest minimum inhibitory concentration (MIC) against Talaromyces marneffei and exhibits poorer therapeutic efficacy in the treatment of Talaromyces marneffei infections[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFor patients who have undergone kidney transplantation, due to the long-term use of immunosuppressive drugs, the harm caused by TMP cannot be ignored. Strengthening clinical awareness of TMP prevention and combining metagenomic next-generation sequencing (mNGS) technology with traditional body fluid culture technology are conducive to the early diagnosis of this pathogenic bacterium, which is crucial for the formulation of clinical treatment strategies. For patients diagnosed with TMP, the main antifungal drugs currently used are amphotericin B and itraconazole. During treatment with azole drugs, it is necessary to timely monitor the blood concentration of immunosuppressants and adjust the dosage accordingly based on the monitoring results. This measure is of great significance for ensuring the therapeutic effect of patients and improving the long-term survival of the transplanted kidney.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMZ drafted the manuscript. HZ collected and analyzed data. HY, YL,LT, SH, LP, and\u003cbr\u003e\u0026nbsp;XX revised the manuscript. GL designed the outline of the manuscript and revised the manuscript. All authors have contributed to editing of manuscript. Mingda Zhong and Hedong Zhang contribute equally to this work and share first authorship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work is supported by Hunan Provincial Natural Science Foundation of China(2023JJ30755), Natural Science Foundation of Hunan Province (2024JJ2088), Natural Science Foundation of Hunan Province (2025JJ70074), National Natural Science Foundation of China (82370760).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Second Xiangya Hospital, Central South University, in accordance with the requirements of the Declaration of Helsinki.Written informed consent was obtained from all patients prior to enrollment in this study. Written informed consent was also obtained from all individuals for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZhou, X., et al., \u003cem\u003eA 40-year antifungal susceptibility surveillance of Talaromyces marneffei (1984-2024) at a tertiary hospital in Guangxi, China.\u003c/em\u003e Med Mycol, 2025. \u003cstrong\u003e63\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003eWang, F., R. Han, and S. Chen, \u003cem\u003eAn Overlooked and Underrated Endemic Mycosis-Talaromycosis and the Pathogenic Fungus Talaromyces marneffei.\u003c/em\u003e Clin Microbiol Rev, 2023. \u003cstrong\u003e36\u003c/strong\u003e(1): p. e0005122.\u003c/li\u003e\n\u003cli\u003eWaters, M., A. Beliavsky, and K. Gough, \u003cem\u003eTalaromyces marneffei fungemia after travel to China in a Canadian patient with AIDS.\u003c/em\u003e CMAJ, 2020. \u003cstrong\u003e192\u003c/strong\u003e(4): p. E92-E95.\u003c/li\u003e\n\u003cli\u003eZhou, Y., Y. Liu, and Y. Wen, \u003cem\u003eGastrointestinal manifestations of Talaromyces marneffei infection in an HIV-infected patient rapidly verified by metagenomic next-generation sequencing: a case report.\u003c/em\u003e BMC Infect Dis, 2021. \u003cstrong\u003e21\u003c/strong\u003e(1): p. 376.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;Connell, P.J., et al., \u003cem\u003eThe role of kidney transplantation as a component of integrated care for chronic kidney disease.\u003c/em\u003e Kidney Int Suppl (2011), 2020. \u003cstrong\u003e10\u003c/strong\u003e(1): p. e78-e85.\u003c/li\u003e\n\u003cli\u003eBharati, J., et al., \u003cem\u003eDiagnosis, Prevention, and Treatment of Infections in Kidney Transplantation.\u003c/em\u003e Semin Nephrol, 2023. \u003cstrong\u003e43\u003c/strong\u003e(5): p. 151486.\u003c/li\u003e\n\u003cli\u003eChan, J.F., et al., \u003cem\u003eTalaromyces (Penicillium) marneffei infection in non-HIV-infected patients.\u003c/em\u003e Emerg Microbes Infect, 2016. \u003cstrong\u003e5\u003c/strong\u003e(3): p. e19.\u003c/li\u003e\n\u003cli\u003eQuinton, L.J., A.J. Walkey, and J.P. Mizgerd, \u003cem\u003eIntegrative Physiology of Pneumonia.\u003c/em\u003e Physiol Rev, 2018. \u003cstrong\u003e98\u003c/strong\u003e(3): p. 1417-1464.\u003c/li\u003e\n\u003cli\u003eKawila, R., R. Chaiwarith, and K. Supparatpinyo, \u003cem\u003eClinical and laboratory characteristics of penicilliosis marneffei among patients with and without HIV infection in Northern Thailand: a retrospective study.\u003c/em\u003e BMC Infect Dis, 2013. \u003cstrong\u003e13\u003c/strong\u003e: p. 464.\u003c/li\u003e\n\u003cli\u003eXu, L., et al., \u003cem\u003eDisseminated Talaromyces marneffei infection after renal transplantation: A case report and literature review.\u003c/em\u003e Front Cell Infect Microbiol, 2023. \u003cstrong\u003e13\u003c/strong\u003e: p. 1115268.\u003c/li\u003e\n\u003cli\u003eShi, J.X., et al., \u003cem\u003eClinical features of influenza-associated pulmonary aspergillosis: a retrospective multicenter cohort study.\u003c/em\u003e Front Cell Infect Microbiol, 2025. \u003cstrong\u003e15\u003c/strong\u003e: p. 1648547.\u003c/li\u003e\n\u003cli\u003eHien, H.T.A., et al., \u003cem\u003eDevelopment and evaluation of a real-time polymerase chain reaction assay for the rapid detection of Talaromyces marneffei MP1 gene in human plasma.\u003c/em\u003e Mycoses, 2016. \u003cstrong\u003e59\u003c/strong\u003e(12): p. 773-780.\u003c/li\u003e\n\u003cli\u003eLi, Y., et al., \u003cem\u003eApplication of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients.\u003c/em\u003e Eur J Clin Microbiol Infect Dis, 2020. \u003cstrong\u003e39\u003c/strong\u003e(2): p. 369-374.\u003c/li\u003e\n\u003cli\u003eZhu, X.L., et al., \u003cem\u003eCT findings of Talaromyces marneffei infection among HIV patients with lymphadenopathy.\u003c/em\u003e Front Med (Lausanne), 2022. \u003cstrong\u003e9\u003c/strong\u003e: p. 930678.\u003c/li\u003e\n\u003cli\u003eHuang, J.L., et al., \u003cem\u003eNeutrophil-to-lymphocyte ratio and lactate dehydrogenase for early diagnosis of AIDS patients with Talaromyces marneffei infection.\u003c/em\u003e Ann Palliat Med, 2022. \u003cstrong\u003e11\u003c/strong\u003e(2): p. 588-597.\u003c/li\u003e\n\u003cli\u003eLe, T., et al., \u003cem\u003eA Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.\u003c/em\u003e N Engl J Med, 2017. \u003cstrong\u003e376\u003c/strong\u003e(24): p. 2329-2340.\u003c/li\u003e\n\u003cli\u003eHamill, R.J., \u003cem\u003eAmphotericin B formulations: a comparative review of efficacy and toxicity.\u003c/em\u003e Drugs, 2013. \u003cstrong\u003e73\u003c/strong\u003e(9): p. 919-34.\u003c/li\u003e\n\u003cli\u003eWingard, J.R., et al., \u003cem\u003eA randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group.\u003c/em\u003e Clin Infect Dis, 2000. \u003cstrong\u003e31\u003c/strong\u003e(5): p. 1155-63.\u003c/li\u003e\n\u003cli\u003eBowden, R., et al., \u003cem\u003eA double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients.\u003c/em\u003e Clin Infect Dis, 2002. \u003cstrong\u003e35\u003c/strong\u003e(4): p. 359-66.\u003c/li\u003e\n\u003cli\u003eBowden, R.A., et al., \u003cem\u003ePhase I study of amphotericin B colloidal dispersion for the treatment of invasive fungal infections after marrow transplant.\u003c/em\u003e J Infect Dis, 1996. \u003cstrong\u003e173\u003c/strong\u003e(5): p. 1208-15.\u003c/li\u003e\n\u003cli\u003eOuyang, Y., et al., \u003cem\u003eAdministration of Voriconazole in Disseminated Talaromyces (Penicillium) Marneffei Infection: A Retrospective Study.\u003c/em\u003e Mycopathologia, 2017. \u003cstrong\u003e182\u003c/strong\u003e(5-6): p. 569-575.\u003c/li\u003e\n\u003cli\u003eYang, S., et al., \u003cem\u003eDisseminated Talaromyces marneffei infection initially presenting as cutaneous and subcutaneous lesion in an HIV-Negative renal transplant recipient: a case report and literature review.\u003c/em\u003e BMC Infect Dis, 2024. \u003cstrong\u003e24\u003c/strong\u003e(1): p. 473.\u003c/li\u003e\n\u003cli\u003eZhang, J., et al., \u003cem\u003eAntifungal Susceptibility Profiles of Olorofim (Formerly F901318) and Currently Available Systemic Antifungals against Mold and Yeast Phases of Talaromyces marneffei.\u003c/em\u003e Antimicrob Agents Chemother, 2021. \u003cstrong\u003e65\u003c/strong\u003e(6).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8965623/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8965623/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo analyze the clinical characteristics, diagnosis, treatment, and prognosis of Talaromyces marneffei pneumonia (TMP) in kidney transplant recipients, providing clinical evidence.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective analysis was conducted among 8 HIV-negative patients who underwent deceased donor kidney transplantation and were subsequently diagnosed with TMP at the Second Xiangya Hospital of Central South University from January 2015 to January 2025. Clinical data pertinent to the study, including demographic features, diagnostic modalities, therapeutic regimens, and prognosis, were systematically collected and analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 8 patients (7 males, 1 female; mean age 45.12\u0026thinsp;\u0026plusmn;\u0026thinsp;9.03 years), the median time from transplantation to TMP onset was 356.5 days(IQR,302.75-771.75). All presented with fever (2 accompanied by cough), and chest CT showed diverse opacities. Metagenomic next-generation sequencing (mNGS) was the primary diagnostic tool, detecting Talaromyces marneffei in 7 cases (87.5% detection rate) with an average diagnosis time of 5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.56 days, while traditional culture only confirmed 3 cases. Amphotericin B was administered as the core induction therapy, followed by maintenance therapy after approximately 2 weeks, combined with individualized oral azole drugs tailored to each patient\u0026rsquo;s condition. All patients achieved clinical cure with no severe adverse reactions. The dosage of immunosuppressants was adjusted during anti-TMP treatment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eKidney transplant recipients on long-term immunosuppressants are at significant risk of TMP. Combining mNGS with traditional culture enables early diagnosis, while amphotericin B and itraconazole are core treatments. Monitoring and adjusting immunosuppressant concentrations during azole therapy is critical for efficacy and long-term graft survival.\u003c/p\u003e","manuscriptTitle":"Clinical features and therapeutic strategies for Talaromyces Marneffei pneumonia in kidney transplant recipients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 17:30:07","doi":"10.21203/rs.3.rs-8965623/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-31T18:11:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-31T04:01:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196269177574989595147077442636011728185","date":"2026-03-25T19:07:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-15T12:51:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118068135016696232612276740519362583573","date":"2026-03-13T09:15:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110792967404954982537459701160108790689","date":"2026-03-12T16:14:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317221727289679139333023022024799559721","date":"2026-03-10T17:00:06+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-02T15:17:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-02T03:12:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-28T09:12:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2026-02-28T08:44:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"71ee8305-d202-45a0-9098-b407536b5453","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T07:55:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 17:30:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8965623","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8965623","identity":"rs-8965623","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}