Antibiotic-Driven Pathogen Replacement Events in a Kidney Transplant Recipient with ADPKD: A Case Report

Antibiotic-Driven Pathogen Replacement Events in a Kidney Transplant Recipient with ADPKD: A Case Report | 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 Case Report Antibiotic-Driven Pathogen Replacement Events in a Kidney Transplant Recipient with ADPKD: A Case Report Ziyan Yan, Yuchen Wang, Wenli Zeng, Jialiang Hui, Bin Yang, Jian Xu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5028400/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Mar, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 13 You are reading this latest preprint version Abstract Background Retaining the native bilateral kidneys after transplantation is a common alternative treatment for patients with end-stage autosomal dominant polycystic kidney disease. However, this strategy poses the risks of potential complications from polycystic kidney infection. The efficiency of antibiotic therapy (ATBT) and the optimal time for native nephrectomy in managing these infections remain uncertain. Case presentation: We report a case of a kidney transplant recipient with retained bilateral polycystic kidneys who experienced recurrent cyst and bloodstream infections, accompanied by antibiotic-driven pathogen replacement. After multiple failed attempts at ATBT, the patient subsequently underwent unilateral polycystic kidney resection. Subsequently, a new infection episode occurred, leading to a preemptive native nephrectomy. Cystic tissue and fluid samples were collected from both shallow and deep layers of the polycystic kidneys, along with peripheral blood and urine samples. These samples were analyzed using microbial culture, metagenome sequencing, and digital polymerase chain reaction to identify infectious pathogens. Pathogen replacement occurred across different infection episodes, with the dominant bacterial species being Escherichia coli , Klebsiella aerogenes , and Enterococcus faecium , in succession. Conclusions This case highlights the replacement of dominant pathogens under antibiotic selection pressure in polycystic kidney infections, primarily involving gram-negative bacilli. When initial and subsequent ATBT fail, re-evaluation of the cyst infection definition is necessary, and preemptive native nephrectomy should be considered. Cyst infection pathogen replacement antibiotic therapy kidney transplantation autosomal dominant polycystic kidney disease Figures Figure 1 Introduction Autosomal dominant polycystic kidney disease (ADPKD) accounts for up to 10% of patients undergoing kidney transplantation (KT)[ 1 , 2 ]. Most transplant centers proceed with KT without native nephrectomy (NN) due to the typically asymptomatic nature of cysts and the potential complications associated with NN[ 3 ]. Although the volume of native kidneys is expected to decrease by 30%-40% within 1 year following KT, various renal and extrarenal complications have been reported in KT recipients with ADPKD[ 4 ]. The most common reasons for impaired survival of patients and grafts are sepsis complications directly related to polycystic kidneys[ 5 , 6 ]. Cyst infection (CyI) in ADPKD are often recurrent and refractory due to limited antibiotic (ATB) penetration into cysts and fluid[ 7 ]. Repeated ATB therapy (ATBT) may lead to ATB-driven pathogenl replacement and the emergence of ATB-resistant strains. The optimal timing for post-KT NN when ATBT fails remains a subject of debate[ 8 , 9 ]. Herein, we present a case that illustrates the time course of ATB-driven predominant pathogen replacement and emphasize the importance of post-KT NN evaluation in KT recipients with ADPKD, particularly in the context of recurrent CyI. Case Presentation A 48-year-old man with end-stage ADPKD received KT without NN in 2016. His immunosuppressive regimen was “tacrolimus + mycophenolate mofetil + prednisolone”. Ultrasound examination in 2018 showed the volumes of native polycystic kidneys were 11.6 cm × 4.3 cm × 4.8 cm (left kidney) and 11.9 cm × 4.9 cm × 5.1 cm (right kidney), respectively. His postoperative serum creatinine (Scr) level stabilized at 90–105 µmol/L. In April 2023, the patient began having frequent hospital admissions owing to recurrent bacteremia-related fever (peak temperature of 38.5 o C, duration of 48 h) and chest pain. Laboratory test results were as follows: Scr 106 µmol/L, C-reactive protein (CRP) 206.9 mg/L, procalcitonin (PoCT) 1.2 ng/L, 1 + protein in urine, and no hematuria. Chest radiography and computed tomography (CT) were performed to rule out respiratory infections, and no significant abnormalities were detected. Ultrasound examination showed that the left polycystic kidney had increased to 14.2 cm × 7.7 cm × 7.9 cm, while the right one could not be measured. No abdominal or lumbar pain was observed. The results from midstream urine and peripheral blood microbial cultures, as well as metagenomic next-generation sequencing (mNGS) indicated Escherichia coli ( E. coli ) infection, suggesting hematogenous dissemination caused by a urinary tract infection, while there was insufficient evidence for cyst infection (CyI). Initial ATBT was meropenem (1 g, VD, every 12 hours) for a duration of 10 days and then amoxicillin (0.375 g, oral, TID) for 4 days. Considering that recurrent infections may be driven by excessive immune suppression, mycophenolate mofetil was switched to mizoribine. The patient was discharged after relief from infection symptoms. In May 2023, the patient was readmitted with sepsis caused by E. coli , with a Sequential Organ Failure Assessment score of 4. Laboratory test results were as follows: Scr 158 µmol/L, CRP 313.8 mg/L, PoCT 31.8 ng/L, and red blood cell count in urine (U_RBC) 16.6/µL. Abdominal CT did not indicate any changes in the cyst compared to before. Meropenem as the empirical therapy for 4 days exhibited poor efficacy. ATBT was then modified: combined with moxifloxacin (0.4 g, VD, QD) for a duration of 9 days. The infection symptoms were relieved. In November 2023, the patient was once again admitted to the hospital due to recurrent fever (peak temperature of 38.5 o C, duration of 72 h), accompanied by right lower chest pain, nausea, painful urination, and shortness of breath, with no abdominal or lumbar pain. Laboratory test results were as follows: Scr 87 µmol/L, CRP 286.7 mg/L, PoCT 13.6 ng/L, 2 + protein in urine, white blood cell count in urine (U_WBC) 71.5/µL, and U_RBC 9728.6/µL, indicating suspected cyst hemorrhage. Chest radiography and CT scans did not indicate a respiratory infection. Peripheral blood microbial cultures indicated infection with gram-negative bacilli. Considering the patient's history of resistant E. coli infection, empirical ATBT with meropenem (1 g, IV, every 12 hours) and immunoglobulin therapy for immune enhancement were initiated; however, this proved to be ineffective. Furthermore, peripheral blood mNGS identified Klebsiella aerogenes ( K. aerogenes ) as the dominant pathogen with 11,319 sequences, leading to a diagnosis of K. aerogenes sepsis. Urine mNGS detected BK polyomavirus (30 sequences) and human herpesvirus 6B (17 sequences). The patient also developed diarrhea developed, and fecal examination revealed the presence of fungal spores. Therefore, the ATBT was modified to ceftazidime/avibactam (2.5 g IV, every 8 hours), vancomycin (0.5 g, oral, TID), and oseltamivir added as antiviral therapy (Fig. 1 A). Additionally, mizoribine was discontinued, and tacrolimus was reduced to lower immunosuppressive intensity. Despite these adjustments, the patient continued to experience recurrent fever. The ATBT was further adjusted to meropenem combined with sulfamethoxazole/trimethoprim (0.48 g, oral, BID), resulting in partial resolution of infection symptoms, although the fever persisted intermittently. Following specialist consultation, the infection was determined to be caused by multidrug-resistant K. aerogenes . The treatment was escalated to a combination of aztreonam (2.5 g, IV, every 8 hours) and ceftazidime/avibactam (2.5 g IV, every 8 hours). After three days of combination therapy, the patient’s temperature normalized. ATBT was maintained for 14 days, during which the CRP decreased from 286.67 mg/L to 30.85 mg/L. Repeat mNGS revealed 42 K. aerogenes sequences. Taking into account the patient's significant polycystic kidney disease and the recurrent bloodstream infections that likely originated from intrarenal CyI and cyst hemorrhage, a planned nephrectomy was proposed. The surgery aimed to prevent further extrarenal complications, persistent infection, and potential pathogen evolution under antibiotic pressure, which could lead to the emergence of superbugs. In December 2023, the patient was readmitted to the hospital due to fever (peak temperature of 39.0 o C, duration of 48 h) accompanied by cough and mild right lower chest pain. Laboratory test results were as follows: Scr 121 µmol/L, CRP 230.48 mg/L, and PoCT 1.3 ng/L. The other laboratory results are shown in Fig. 1 B. The transplanted kidney was enlarged, and the increased creatinine level raised the suspicion of acute kidney rejection. Methylprednisolone (40 mg, IV, QD) was administered for anti-rejection therapy for three days, and Scr levels decreased to 92 µmol/L. Peripheral blood mNGS identified K. aerogenes with 4,825 sequences. The patient was treated with ceftazidime/avibactam (2.5 g, IV, every 8 hours) for the infection, but the response was poor, with persistent recurrent fever. The antimicrobial regimen was adjusted to meropenem plus moxifloxacin, leading to the resolution of fever and cough symptoms. Anti-infection therapy was continued for 14 days. To address the persistent impact of a potential polycystic kidney infection as the primary source, a da Vinci robot-assisted laparoscopic right nephrectomy of the polycystic kidney was performed in January 2024after the infection had stabilized (Fig. 1 C). Both shallow and deep cyst tissue of polycystic kidney, as well as cyst fluid, were sent for mNGS and digital PCR (dPCR). Sequencing results indicated that the K. aerogenes found in the cyst tissue and fluid were consistent with those detected in the peripheral blood, further confirming the association between cystic kidney and bloodstream infections (Table 1 ). Postoperatively, the patient recovered well, and laboratory tests showed a consistent decline in inflammation-related markers. Table 1 mNGS and dPCR results from clinical specimens in two episodes of native nephrectomy. Specimens mNGS dPCR Pathogen (sequences) Klebsiella aerogenes Aspergillus fumigatus Right nephrectomy Urine Aspergillus fumigatus (1) positive negative Peripheral blood negative negative negative Shallow cyst fluid Torque teno virus (1296) Human gammaherpesvirus 4 (36) positive positive Shallow cyst tissue Aspergillus fumigatus (1) positive positive Deep cyst fluid Torque teno virus (206) negative negative Deep cyst tissue Human betaherpesvirus 6B (6) negative negative Left nephrectomy Urine Enterococcus faecium (1910) Corynebacterium pseudogenitalium (15) Corynebacterium aurimucosum (14) Aspergillus fumigatus (1) Human polyomavirus 1 (3342) negative positive Peripheral blood Torque teno virus (9) negative negative Shallow cyst fluid negative positive positive Shallow cyst tissue Torque teno virus (23) positive positive Deep cyst fluid Human betaherpesvirus 5 (1395) Torque teno virus (6) negative negative Deep cyst tissue negative negative negative * mNGS, metagenomic next-generation sequencing; dPCR, digital polymerase chain reaction. In April 2024, three months after the right nephrectomy, the patient was readmitted with fever, cough, chest tightness, and shortness of breath for three days, with symptoms resembling those of the previous episodes. Laboratory test results were as follows: Scr 109 µmol/L, CRP 194.5 mg/L, PoCT 2.0 ng/L, 1 + protein in urine, and U_RBC 22.2/µL. The CT examination results are basically the same as before. Peripheral blood cultures indicated infection by Staphylococcus aureus ( S. aureus ) infection, and urine mNGS identified Enterococcus faecium as the dominant pathogen, with 1,910 sequences, signifying a shift in the patient’s infection profile. Meropenem (1 g, IV, every 12 hours) was administered to prevent the recurrence of persistent bloodstream infection. After nine days of treatment, preemptive left nephrectomy was performed for the remaining polycystic kidney (Fig. 1 D). Both shallow and deep cyst tissue of polycystic kidney, as well as cyst fluid, were sent for mNGS and dPCR (Table 1 ). Sequencing results indicated the same K. aerogenes in the shallow cyst tissueand fluid. The patient had an uneventful postoperative recovery, with laboratory tests showing a consistent decline in inflammatary markers and was subsequently discharged. Discussion and Conclusions Although CyI remains one of the most prevalent complications in ADPKD, its diagnosis and management continue to present significant challenges. In KT recipients, the incidence of CyI is 1.6 per 100 person-years and is associated with an elevated risk of graft loss[ 10 , 11 ]. For patients with retained bilateral polycystic kidneys, the management of postoperative immunosuppression and infection prevention is particularly complex, and no consensus exists on the standard interventions. The development of effective antibiotic strategies to mitigate pathogen replacement and evolution, as well as determining the optimal time for preemptive NN, necessitates further clinical research and evidence to establish comprehensive guidelines. It has long been proposed that diffusion of ATBs into renal cysts depends more on transepithelial transport than on glomerular filtration[ 12 ]. Nevertheless, the properties of cyst walls limit or delay the diffusion of most antibacterial drugs, resulting in a high rate of treatment failures and recurrences in CyI[ 8 ]. Therefore, ATBT for CyI often requires higher doses and longer durations than those used for routine infections[ 6 , 13 ]. Studies have shown that a 28-day course may be necessary to achieve satisfactory outcomes[ 8 ]. This prolonged, ineffective antibiotic treatment approach provided ample time for pathogens to evolve or replace each other, further increasing the difficulty, recurrence, and incidence of new episodes of CyI. Meanwhile, under sustained high-intensity antibiotic pressure, the host's microbiome undergoes alterations, resulting in pathogen replacement in the extrarenal system. In our case, the predominant pathogen in bloodstream infections shifted from E. coli to K. aerogenes , and subsequently to S. aureus, while in urinary tract infections, E. coli was replaced by K. aerogenes and later by Enterococcus faecium . The patient consequently experienced frequent antibiotic exposure, immunosuppressive regimen adjustments, and multiple hospitalizations, ultimately leading to bilateral nephrectomy. Moreover, when the immunosuppressive regimen was adjusted early to more effectively manage recurrent infections, an increase in the transplanted kidney size and Scr levels was observed in this case. These changes were promptly addressed with steroid pulse therapy, which successfully reversed the progression of potential rejection episodes. Therefore, caution is warranted when reducing the intensity of immunosuppression to control infection, as this may increase the risk of graft rejection. Another challenge of CyI studies lies in definite diagnosis without invasive procedure. CyIs are classified into three definitions based on different diagnostic criteria: definite (cyst puncture), probable (imaging variables), and possible (clinical variables)[ 8 , 14 ]. Currently, cyst puncture is rarely performed, and the diagnostic accuracy of conventional CT imaging is limited[ 15 ]. Clinical evidence requires ruling out extrarenal factors and cyst hemorrhage as causes of abdominal or lumbar pain[ 16 ]. In cases like the one described, where none of these criteria can be fully met, the diagnosis of CyI can be delayed. Recent studies have shown that PET imaging with intravenous 18F-fluorodeoxyglucose, combined with CT imagine, is superior to conventional radiological techniques for identifying and localizing renal CyI[ 17 ]. Therefore, when there is a high clinical suspicion of CyI, FDG-PET/CT should be preferred over CT for evaluating polycystic kidneys. The need, indications, timing, and approach for NN in patients with ADPKD remain controversial. Evidence suggests no significant difference in outcomes whether NN is performed before or after KT [ 2 , 18 , 19 ]. NN after transplantation is generally indicated for infectious complications, elevated intra-abdominal pressure, or suspected malignancy, with cyst infection being the primary indication[ 20 ]. CyI is typically attributed to hematogenous spread or retrograde urinary tract infection[ 6 ]; however, this relationship can be bidirectional. Hematogenous or retrograde infection can colonize cysts, leading to CyI, cyst rupture, and exacerbation of bloodstream infections. Thus, when hematuria occurs, it is crucial to differentiate cyst hemorrhage from other causes and monitor for bacterial presence to prevent sepsis. In conclusion, recurrent and refractory CyI imposes significant ATB selection pressure in patients with ADPKD. The inability of ATBT to fully eradicate infection in polycystic kidneys leads to ongoing pathogen replacement. Therefore, in KT recipients with ADPKD, especially those with complex infection histories, the risks of retaining native kidneys should be carefully evaluated. Close monitoring of pathogen dynamics post-transplant is essential, and early consideration of NN should be made when warranted. Advanced technologies such as mNGS and dPCR enhance precise identification and tracking of infection sources, providing valuable insights for clinical management. Abbreviations ADPKD autosomal dominant polycystic kidney disease KT kidney transplantation NN native nephrectomy ATB antibiotic ATBT antibiotic therapy Scr serum creatinine CRP C-reactive protein PoCT procalcitonin CT computed tomography mNGS metagenomic next-generation sequencing CyI cyst infection U_RBC red blood cell count in urine U_WBC white blood cell count in urine dPCR digital polymerase chain reaction. Declarations Ethics approval and consent to participate The study was approved by the ethical committee of Nanfang Hospital, Southern Medical University (NFEC-2019-190). Written informed consent to participate was provided by the patient involved in our study. Consent for publication Written informed consent for publication of the clinical details and clinical images was obtained from the patient involved in our study. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the National Natural Science Foundation of China (grant numbers 82270784 and 82070770), Guangdong Basic and Applied Basic Research Foundation (grant number 2023A1515012276 and 2024A1515012700), and Clinical High-tech and Major Technology Projects in Guangzhou Area (grant number 2024CL-GX03). Authors’ contributions RFX, YM and ZYY designed and directed the study. ZYY wrote the manuscript. JX and BY contributed new reagents and analytic tools. ZYY, WLZ and JLH collected the data. YCW and RFX revised the manuscript. All authorship read and approved the final version. Acknowledgements Not applicable. References Neeff HP, Pisarski P, Tittelbach-Helmrich D, Karajanev K, Neumann HP, Hopt UT, Drognitz O. One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transpl. 2013;28(2):466–71. 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Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: a systematic review. Nephrol Dial Transpl. 2017;32(1):144–50. Gibson P, Watson ML. Cyst infection in polycystic kidney disease: a clinical challenge. Nephrol Dial Transpl. 1998;13(10):2455–7. Dang J, Scemla A, Loheac C, Chaba A, Bienaimé F, Joly D, Legendre C, Knebelmann B, Charlier C. Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease. Mayo Clin Proc. 2022;97(7):1305–17. Casteleijn NF, Geertsema P, Koorevaar IW, Inkelaar FDJ, Jansen MR, Lohuis SJ, Meijer E, Pol RA, Sanders JS, van de Streek PE, et al. The Need for Routine Native Nephrectomy in the Workup for Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease Patients. Urol Int. 2023;107(2):148–56. Ronsin C, Chaba A, Suchanek O, Coindre JP, Kerleau C, Garandeau C, Houzet A, Cantarovich D, Dantal J, Blancho G et al. Incidence, Risk Factors and Outcomes of Kidney and Liver Cyst Infection in Kidney Transplant Recipient With ADPKD. Kidney Int Rep 2022, 7(4):867–875. Čellár M, Ová MK, Lacková E, Hrubá T, Galajda P, Dedinská I. Recurrent urinary tract infections in kidney transplant patients with polycystic kidneys. Vnitr Lek. 2022;68(E–4):4–9. Persu A, Devuyst O. Transepithelial chloride secretion and cystogenesis in autosomal dominant polycystic kidney disease. Nephrol Dial Transpl. 2000;15(6):747–50. Onuchic L, Sato VAH, de Menezes Neves PDM, Balbo BEP, Portela-Neto AA, Ferreira FT, Watanabe EH, Watanabe A, de Almeida MCS, de Abreu Testagrossa L, et al. Two cases of fungal cyst infection in ADPKD: is this really a rare complication? BMC Infect Dis. 2019;19(1):911. Sallée M, Rafat C, Zahar JR, Paulmier B, Grünfeld JP, Knebelmann B, Fakhouri F. Cyst infections in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2009;4(7):1183–9. Lantinga MA, Drenth JP, Gevers TJ. Diagnostic criteria in renal and hepatic cyst infection. Nephrol Dial Transpl. 2015;30(5):744–51. Lubennikov AE, Shishimorov AA, Trushkin RN, Isaev TK, Kotenko ON, Krupinov GE. [Diagnosis of infected kidney cysts in patients with autosomal dominant polycystic kidney disease and end-stage renal disease]. Urologiia 2021(3):50–5. Piccoli GB, Arena V, Consiglio V, Deagostini MC, Pelosi E, Douroukas A, Penna D, Cortese G. Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and cystic kidneys. a case series. BMC Nephrol. 2011;12:48. Brazda E, Ofner D, Riedmann B, Spechtenhauser B, Margreiter R. The effect of nephrectomy on the outcome of renal transplantation in patients with polycystic kidney disease. Ann Transpl. 1996;1(2):15–8. Jankowska M, Kuźmiuk-Glembin I, Skonieczny P, Dębska-Ślizień A. Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease. Transpl Proc. 2018;50(6):1863–7. Kanaan N, Devuyst O, Pirson Y. Renal transplantation in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2014;10(8):455–65. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Mar, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 22 Jan, 2025 Reviews received at journal 29 Dec, 2024 Reviews received at journal 28 Dec, 2024 Reviews received at journal 23 Dec, 2024 Reviewers agreed at journal 21 Dec, 2024 Reviewers agreed at journal 20 Dec, 2024 Reviewers agreed at journal 19 Dec, 2024 Reviews received at journal 19 Dec, 2024 Reviewers agreed at journal 16 Dec, 2024 Reviewers invited by journal 16 Oct, 2024 Editor assigned by journal 05 Sep, 2024 Submission checks completed at journal 04 Sep, 2024 First submitted to journal 03 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-5028400","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":359829171,"identity":"c4d08cf6-7fb3-4f56-b18b-37ab36fcc185","order_by":0,"name":"Ziyan Yan","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Ziyan","middleName":"","lastName":"Yan","suffix":""},{"id":359829174,"identity":"89ba8a66-0061-4470-8e9c-a6bb4f21bed6","order_by":1,"name":"Yuchen Wang","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Wang","suffix":""},{"id":359829177,"identity":"33863661-e390-410e-90bf-e09063f5acb1","order_by":2,"name":"Wenli Zeng","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Wenli","middleName":"","lastName":"Zeng","suffix":""},{"id":359829181,"identity":"d63c74e4-281a-41af-980d-880f0e401222","order_by":3,"name":"Jialiang Hui","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Jialiang","middleName":"","lastName":"Hui","suffix":""},{"id":359829186,"identity":"f7311763-173a-4397-83da-2023ac4a92fa","order_by":4,"name":"Bin Yang","email":"","orcid":"","institution":"Center for Infectious Diseases Vision Medicals Co., Ltd. Guangzhou","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Yang","suffix":""},{"id":359829189,"identity":"43576a5a-8940-4fd5-8ba3-f8812dbd1977","order_by":5,"name":"Jian Xu","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Xu","suffix":""},{"id":359829191,"identity":"de4451d7-a839-4ace-89a6-c1f2e421c104","order_by":6,"name":"Yun Miao","email":"","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"","lastName":"Miao","suffix":""},{"id":359829193,"identity":"f51bd544-ae5b-4c30-af85-89eccd5f4c92","order_by":7,"name":"Renfei Xia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACxvbGhgMfeGx42NgbiNTC3HP44MEZMmly/DwHiNTCPiMt+TCPzWFjyRkJRGrhnZFjcIAnhzlxw83HG28w1NhEE9Qi2fPG4IDEGbbEDbfTii0YjqXlNhDSYtgOtMWwhweoJcdMgrHhMGEt9geAWhL/SQAddoZILYwdaQkHDvAYAL3PQ6yWnsMHDjbwJAADGeiXBGL8AozK5s9/eP4Do/LwxhsfamwIa0EGBhIJpCiHaCFVxygYBaNgFIwMAAAg3kcH2oHRMgAAAABJRU5ErkJggg==","orcid":"","institution":"Southern Medical Univerisity","correspondingAuthor":true,"prefix":"","firstName":"Renfei","middleName":"","lastName":"Xia","suffix":""}],"badges":[],"createdAt":"2024-09-04 03:53:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5028400/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5028400/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-10804-x","type":"published","date":"2025-03-27T15:57:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67120009,"identity":"b0ec5f43-5878-4f6a-9536-230114591e55","added_by":"auto","created_at":"2024-10-21 11:07:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2195827,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical information of the patient from recurrent infection to bilateral native nephrectomy.\u003c/strong\u003e (A) The antibiotic therapy, immunosuppressive regimen, and predominant pathogen replacement in peripheral blood during the five infection episodes. (B) The clinical course across the five episodes of infection-related hospitalizations. (C, D) Gross photograph and pathology of the right (C) and left (D) native nephrectomy specimen, indicating focal calcification and chronic inflammation in polycystic kidney.\u003cem\u003e \u003c/em\u003eMEPM, meropenem; AMPC, amoxicillin; Mox, moxifloxacin; CAZ/AVI, ceftazidime/avibactam; VA, vancomycin; SXT, sulfamethoxazole/trimethoprim; AZT, aztreonam; Tac, tacrolimus; MMF, mycophenolate mofetil; PRED, prednisolone; MZR, mizoribine; CRP, C-reactive protein; PoCT, procalcitonin; WBC, white blood cell; NEU, neutrophils; LYM, lymphocyte; HGB, hemoglobin; Scr, serum creatinine.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5028400/v1/749a1ff779ae67b184765a7e.jpg"},{"id":79605109,"identity":"ff6188b7-179e-458b-9fa7-ed2c6e0d4aa8","added_by":"auto","created_at":"2025-03-31 16:10:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2751385,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5028400/v1/6156e20e-52ad-46f3-985e-8daf4fb0608d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibiotic-Driven Pathogen Replacement Events in a Kidney Transplant Recipient with ADPKD: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAutosomal dominant polycystic kidney disease (ADPKD) accounts for up to 10% of patients undergoing kidney transplantation (KT)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most transplant centers proceed with KT without native nephrectomy (NN) due to the typically asymptomatic nature of cysts and the potential complications associated with NN[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although the volume of native kidneys is expected to decrease by 30%-40% within 1 year following KT, various renal and extrarenal complications have been reported in KT recipients with ADPKD[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The most common reasons for impaired survival of patients and grafts are sepsis complications directly related to polycystic kidneys[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cyst infection (CyI) in ADPKD are often recurrent and refractory due to limited antibiotic (ATB) penetration into cysts and fluid[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Repeated ATB therapy (ATBT) may lead to ATB-driven pathogenl replacement and the emergence of ATB-resistant strains. The optimal timing for post-KT NN when ATBT fails remains a subject of debate[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHerein, we present a case that illustrates the time course of ATB-driven predominant pathogen replacement and emphasize the importance of post-KT NN evaluation in KT recipients with ADPKD, particularly in the context of recurrent CyI.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 48-year-old man with end-stage ADPKD received KT without NN in 2016. His immunosuppressive regimen was \u0026ldquo;tacrolimus\u0026thinsp;+\u0026thinsp;mycophenolate mofetil\u0026thinsp;+\u0026thinsp;prednisolone\u0026rdquo;. Ultrasound examination in 2018 showed the volumes of native polycystic kidneys were 11.6 cm \u0026times; 4.3 cm \u0026times; 4.8 cm (left kidney) and 11.9 cm \u0026times; 4.9 cm \u0026times; 5.1 cm (right kidney), respectively. His postoperative serum creatinine (Scr) level stabilized at 90\u0026ndash;105 \u0026micro;mol/L.\u003c/p\u003e \u003cp\u003eIn April 2023, the patient began having frequent hospital admissions owing to recurrent bacteremia-related fever (peak temperature of 38.5\u003csup\u003eo\u003c/sup\u003eC, duration of 48 h) and chest pain. Laboratory test results were as follows: Scr 106 \u0026micro;mol/L, C-reactive protein (CRP) 206.9 mg/L, procalcitonin (PoCT) 1.2 ng/L, 1\u0026thinsp;+\u0026thinsp;protein in urine, and no hematuria. Chest radiography and computed tomography (CT) were performed to rule out respiratory infections, and no significant abnormalities were detected. Ultrasound examination showed that the left polycystic kidney had increased to 14.2 cm \u0026times; 7.7 cm \u0026times; 7.9 cm, while the right one could not be measured. No abdominal or lumbar pain was observed. The results from midstream urine and peripheral blood microbial cultures, as well as metagenomic next-generation sequencing (mNGS) indicated \u003cem\u003eEscherichia coli\u003c/em\u003e (\u003cem\u003eE. coli\u003c/em\u003e) infection, suggesting hematogenous dissemination caused by a urinary tract infection, while there was insufficient evidence for cyst infection (CyI). Initial ATBT was meropenem (1 g, VD, every 12 hours) for a duration of 10 days and then amoxicillin (0.375 g, oral, TID) for 4 days. Considering that recurrent infections may be driven by excessive immune suppression, mycophenolate mofetil was switched to mizoribine. The patient was discharged after relief from infection symptoms.\u003c/p\u003e \u003cp\u003eIn May 2023, the patient was readmitted with sepsis caused by \u003cem\u003eE. coli\u003c/em\u003e, with a Sequential Organ Failure Assessment score of 4. Laboratory test results were as follows: Scr 158 \u0026micro;mol/L, CRP 313.8 mg/L, PoCT 31.8 ng/L, and red blood cell count in urine (U_RBC) 16.6/\u0026micro;L. Abdominal CT did not indicate any changes in the cyst compared to before. Meropenem as the empirical therapy for 4 days exhibited poor efficacy. ATBT was then modified: combined with moxifloxacin (0.4 g, VD, QD) for a duration of 9 days. The infection symptoms were relieved.\u003c/p\u003e \u003cp\u003eIn November 2023, the patient was once again admitted to the hospital due to recurrent fever (peak temperature of 38.5\u003csup\u003eo\u003c/sup\u003eC, duration of 72 h), accompanied by right lower chest pain, nausea, painful urination, and shortness of breath, with no abdominal or lumbar pain. Laboratory test results were as follows: Scr 87 \u0026micro;mol/L, CRP 286.7 mg/L, PoCT 13.6 ng/L, 2\u0026thinsp;+\u0026thinsp;protein in urine, white blood cell count in urine (U_WBC) 71.5/\u0026micro;L, and U_RBC 9728.6/\u0026micro;L, indicating suspected cyst hemorrhage. Chest radiography and CT scans did not indicate a respiratory infection. Peripheral blood microbial cultures indicated infection with gram-negative bacilli. Considering the patient's history of resistant \u003cem\u003eE. coli\u003c/em\u003e infection, empirical ATBT with meropenem (1 g, IV, every 12 hours) and immunoglobulin therapy for immune enhancement were initiated; however, this proved to be ineffective. Furthermore, peripheral blood mNGS identified \u003cem\u003eKlebsiella aerogenes\u003c/em\u003e (\u003cem\u003eK. aerogenes\u003c/em\u003e) as the dominant pathogen with 11,319 sequences, leading to a diagnosis of \u003cem\u003eK. aerogenes\u003c/em\u003e sepsis. Urine mNGS detected BK polyomavirus (30 sequences) and human herpesvirus 6B (17 sequences). The patient also developed diarrhea developed, and fecal examination revealed the presence of fungal spores. Therefore, the ATBT was modified to ceftazidime/avibactam (2.5 g IV, every 8 hours), vancomycin (0.5 g, oral, TID), and oseltamivir added as antiviral therapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Additionally, mizoribine was discontinued, and tacrolimus was reduced to lower immunosuppressive intensity. Despite these adjustments, the patient continued to experience recurrent fever. The ATBT was further adjusted to meropenem combined with sulfamethoxazole/trimethoprim (0.48 g, oral, BID), resulting in partial resolution of infection symptoms, although the fever persisted intermittently. Following specialist consultation, the infection was determined to be caused by multidrug-resistant \u003cem\u003eK. aerogenes\u003c/em\u003e. The treatment was escalated to a combination of aztreonam (2.5 g, IV, every 8 hours) and ceftazidime/avibactam (2.5 g IV, every 8 hours). After three days of combination therapy, the patient\u0026rsquo;s temperature normalized. ATBT was maintained for 14 days, during which the CRP decreased from 286.67 mg/L to 30.85 mg/L. Repeat mNGS revealed 42 \u003cem\u003eK. aerogenes\u003c/em\u003e sequences. Taking into account the patient's significant polycystic kidney disease and the recurrent bloodstream infections that likely originated from intrarenal CyI and cyst hemorrhage, a planned nephrectomy was proposed. The surgery aimed to prevent further extrarenal complications, persistent infection, and potential pathogen evolution under antibiotic pressure, which could lead to the emergence of superbugs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn December 2023, the patient was readmitted to the hospital due to fever (peak temperature of 39.0\u003csup\u003eo\u003c/sup\u003eC, duration of 48 h) accompanied by cough and mild right lower chest pain. Laboratory test results were as follows: Scr 121 \u0026micro;mol/L, CRP 230.48 mg/L, and PoCT 1.3 ng/L. The other laboratory results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB. The transplanted kidney was enlarged, and the increased creatinine level raised the suspicion of acute kidney rejection. Methylprednisolone (40 mg, IV, QD) was administered for anti-rejection therapy for three days, and Scr levels decreased to 92 \u0026micro;mol/L. Peripheral blood mNGS identified \u003cem\u003eK. aerogenes\u003c/em\u003e with 4,825 sequences. The patient was treated with ceftazidime/avibactam (2.5 g, IV, every 8 hours) for the infection, but the response was poor, with persistent recurrent fever. The antimicrobial regimen was adjusted to meropenem plus moxifloxacin, leading to the resolution of fever and cough symptoms. Anti-infection therapy was continued for 14 days. To address the persistent impact of a potential polycystic kidney infection as the primary source, a da Vinci robot-assisted laparoscopic right nephrectomy of the polycystic kidney was performed in January 2024after the infection had stabilized (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC). Both shallow and deep cyst tissue of polycystic kidney, as well as cyst fluid, were sent for mNGS and digital PCR (dPCR). Sequencing results indicated that the \u003cem\u003eK. aerogenes\u003c/em\u003e found in the cyst tissue and fluid were consistent with those detected in the peripheral blood, further confirming the association between cystic kidney and bloodstream infections (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Postoperatively, the patient recovered well, and laboratory tests showed a consistent decline in inflammation-related markers.\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 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003emNGS and dPCR results from clinical specimens in two episodes of native nephrectomy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSpecimens\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003emNGS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003edPCR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePathogen (sequences)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella aerogenes\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eAspergillus fumigatus\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eRight nephrectomy\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAspergillus fumigatus\u003c/em\u003e (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShallow cyst fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTorque teno virus\u003c/em\u003e (1296)\u003c/p\u003e \u003cp\u003e\u003cem\u003eHuman gammaherpesvirus 4\u003c/em\u003e (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShallow cyst tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAspergillus fumigatus\u003c/em\u003e (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep cyst fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTorque teno virus\u003c/em\u003e (206)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep cyst tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eHuman betaherpesvirus 6B\u003c/em\u003e (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeft nephrectomy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus faecium\u003c/em\u003e (1910)\u003c/p\u003e \u003cp\u003e\u003cem\u003eCorynebacterium pseudogenitalium\u003c/em\u003e (15)\u003c/p\u003e \u003cp\u003e\u003cem\u003eCorynebacterium aurimucosum\u003c/em\u003e (14)\u003c/p\u003e \u003cp\u003e\u003cem\u003eAspergillus fumigatus\u003c/em\u003e (1)\u003c/p\u003e \u003cp\u003e\u003cem\u003eHuman polyomavirus 1\u003c/em\u003e (3342)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral blood\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTorque teno virus\u003c/em\u003e (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShallow cyst fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShallow cyst tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTorque teno virus\u003c/em\u003e (23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003epositive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep cyst fluid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eHuman betaherpesvirus 5\u003c/em\u003e (1395)\u003c/p\u003e \u003cp\u003e\u003cem\u003eTorque teno virus\u003c/em\u003e (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep cyst tissue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e* mNGS, metagenomic next-generation sequencing; dPCR, digital polymerase chain reaction.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn April 2024, three months after the right nephrectomy, the patient was readmitted with fever, cough, chest tightness, and shortness of breath for three days, with symptoms resembling those of the previous episodes. Laboratory test results were as follows: Scr 109 \u0026micro;mol/L, CRP 194.5 mg/L, PoCT 2.0 ng/L, 1\u0026thinsp;+\u0026thinsp;protein in urine, and U_RBC 22.2/\u0026micro;L. The CT examination results are basically the same as before. Peripheral blood cultures indicated infection by \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (\u003cem\u003eS. aureus\u003c/em\u003e) infection, and urine mNGS identified \u003cem\u003eEnterococcus faecium\u003c/em\u003e as the dominant pathogen, with 1,910 sequences, signifying a shift in the patient\u0026rsquo;s infection profile. Meropenem (1 g, IV, every 12 hours) was administered to prevent the recurrence of persistent bloodstream infection. After nine days of treatment, preemptive left nephrectomy was performed for the remaining polycystic kidney (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). Both shallow and deep cyst tissue of polycystic kidney, as well as cyst fluid, were sent for mNGS and dPCR (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Sequencing results indicated the same \u003cem\u003eK. aerogenes\u003c/em\u003e in the shallow cyst tissueand fluid. The patient had an uneventful postoperative recovery, with laboratory tests showing a consistent decline in inflammatary markers and was subsequently discharged.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eAlthough CyI remains one of the most prevalent complications in ADPKD, its diagnosis and management continue to present significant challenges. In KT recipients, the incidence of CyI is 1.6 per 100 person-years and is associated with an elevated risk of graft loss[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. For patients with retained bilateral polycystic kidneys, the management of postoperative immunosuppression and infection prevention is particularly complex, and no consensus exists on the standard interventions. The development of effective antibiotic strategies to mitigate pathogen replacement and evolution, as well as determining the optimal time for preemptive NN, necessitates further clinical research and evidence to establish comprehensive guidelines.\u003c/p\u003e \u003cp\u003eIt has long been proposed that diffusion of ATBs into renal cysts depends more on transepithelial transport than on glomerular filtration[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Nevertheless, the properties of cyst walls limit or delay the diffusion of most antibacterial drugs, resulting in a high rate of treatment failures and recurrences in CyI[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, ATBT for CyI often requires higher doses and longer durations than those used for routine infections[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Studies have shown that a 28-day course may be necessary to achieve satisfactory outcomes[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This prolonged, ineffective antibiotic treatment approach provided ample time for pathogens to evolve or replace each other, further increasing the difficulty, recurrence, and incidence of new episodes of CyI. Meanwhile, under sustained high-intensity antibiotic pressure, the host's microbiome undergoes alterations, resulting in pathogen replacement in the extrarenal system. In our case, the predominant pathogen in bloodstream infections shifted from \u003cem\u003eE. coli\u003c/em\u003e to \u003cem\u003eK. aerogenes\u003c/em\u003e, and subsequently to S. aureus, while in urinary tract infections, \u003cem\u003eE. coli\u003c/em\u003e was replaced by \u003cem\u003eK. aerogenes\u003c/em\u003e and later by \u003cem\u003eEnterococcus faecium\u003c/em\u003e. The patient consequently experienced frequent antibiotic exposure, immunosuppressive regimen adjustments, and multiple hospitalizations, ultimately leading to bilateral nephrectomy.\u003c/p\u003e \u003cp\u003eMoreover, when the immunosuppressive regimen was adjusted early to more effectively manage recurrent infections, an increase in the transplanted kidney size and Scr levels was observed in this case. These changes were promptly addressed with steroid pulse therapy, which successfully reversed the progression of potential rejection episodes. Therefore, caution is warranted when reducing the intensity of immunosuppression to control infection, as this may increase the risk of graft rejection.\u003c/p\u003e \u003cp\u003eAnother challenge of CyI studies lies in definite diagnosis without invasive procedure. CyIs are classified into three definitions based on different diagnostic criteria: definite (cyst puncture), probable (imaging variables), and possible (clinical variables)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Currently, cyst puncture is rarely performed, and the diagnostic accuracy of conventional CT imaging is limited[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Clinical evidence requires ruling out extrarenal factors and cyst hemorrhage as causes of abdominal or lumbar pain[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In cases like the one described, where none of these criteria can be fully met, the diagnosis of CyI can be delayed. Recent studies have shown that PET imaging with intravenous 18F-fluorodeoxyglucose, combined with CT imagine, is superior to conventional radiological techniques for identifying and localizing renal CyI[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Therefore, when there is a high clinical suspicion of CyI, FDG-PET/CT should be preferred over CT for evaluating polycystic kidneys.\u003c/p\u003e \u003cp\u003eThe need, indications, timing, and approach for NN in patients with ADPKD remain controversial. Evidence suggests no significant difference in outcomes whether NN is performed before or after KT [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. NN after transplantation is generally indicated for infectious complications, elevated intra-abdominal pressure, or suspected malignancy, with cyst infection being the primary indication[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. CyI is typically attributed to hematogenous spread or retrograde urinary tract infection[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; however, this relationship can be bidirectional. Hematogenous or retrograde infection can colonize cysts, leading to CyI, cyst rupture, and exacerbation of bloodstream infections. Thus, when hematuria occurs, it is crucial to differentiate cyst hemorrhage from other causes and monitor for bacterial presence to prevent sepsis.\u003c/p\u003e \u003cp\u003eIn conclusion, recurrent and refractory CyI imposes significant ATB selection pressure in patients with ADPKD. The inability of ATBT to fully eradicate infection in polycystic kidneys leads to ongoing pathogen replacement. Therefore, in KT recipients with ADPKD, especially those with complex infection histories, the risks of retaining native kidneys should be carefully evaluated. Close monitoring of pathogen dynamics post-transplant is essential, and early consideration of NN should be made when warranted. Advanced technologies such as mNGS and dPCR enhance precise identification and tracking of infection sources, providing valuable insights for clinical management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADPKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eautosomal dominant polycystic kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ekidney transplantation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enative nephrectomy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eATB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eantibiotic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eATBT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eantibiotic therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eScr\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eserum creatinine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePoCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprocalcitonin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emNGS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emetagenomic next-generation sequencing\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCyI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecyst infection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eU_RBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ered blood cell count in urine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eU_WBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewhite blood cell count in urine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003edPCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edigital polymerase chain reaction.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the ethical committee of Nanfang Hospital, Southern Medical University (NFEC-2019-190). Written informed consent to participate was provided by the patient involved in our study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of the clinical details and clinical images was obtained from the patient involved in our study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (grant numbers 82270784 and 82070770), Guangdong Basic and Applied Basic Research Foundation (grant number 2023A1515012276 and 2024A1515012700), and Clinical High-tech and Major Technology Projects in Guangzhou Area (grant number 2024CL-GX03).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRFX, YM and ZYY designed and directed the study. ZYY wrote the manuscript. JX and BY contributed new reagents and analytic tools. ZYY, WLZ and JLH collected the data. YCW and RFX revised the manuscript. All authorship read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNeeff HP, Pisarski P, Tittelbach-Helmrich D, Karajanev K, Neumann HP, Hopt UT, Drognitz O. One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transpl. 2013;28(2):466\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaxeiner A, Bichmann A, Oberl\u0026auml;nder N, El-Bandar N, Sug\u0026uuml;nes N, Ralla B, Biernath N, Liefeldt L, Budde K, Giessing M et al. 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J Am Soc Nephrol. 1995;5(12):2048\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLantinga MA, Casteleijn NF, Geudens A, de S\u0026eacute;vaux RG, van Assen S, Leliveld AM, Gansevoort RT, Drenth JP. Management of renal cyst infection in patients with autosomal dominant polycystic kidney disease: a systematic review. Nephrol Dial Transpl. 2017;32(1):144\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibson P, Watson ML. Cyst infection in polycystic kidney disease: a clinical challenge. Nephrol Dial Transpl. 1998;13(10):2455\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDang J, Scemla A, Loheac C, Chaba A, Bienaim\u0026eacute; F, Joly D, Legendre C, Knebelmann B, Charlier C. Efficacy of Prolonged Antibiotic Therapy for Renal Cyst Infections in Polycystic Kidney Disease. 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Clin J Am Soc Nephrol. 2009;4(7):1183\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLantinga MA, Drenth JP, Gevers TJ. Diagnostic criteria in renal and hepatic cyst infection. Nephrol Dial Transpl. 2015;30(5):744\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLubennikov AE, Shishimorov AA, Trushkin RN, Isaev TK, Kotenko ON, Krupinov GE. [Diagnosis of infected kidney cysts in patients with autosomal dominant polycystic kidney disease and end-stage renal disease]. Urologiia 2021(3):50\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiccoli GB, Arena V, Consiglio V, Deagostini MC, Pelosi E, Douroukas A, Penna D, Cortese G. Positron emission tomography in the diagnostic pathway for intracystic infection in adpkd and cystic kidneys. a case series. BMC Nephrol. 2011;12:48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrazda E, Ofner D, Riedmann B, Spechtenhauser B, Margreiter R. The effect of nephrectomy on the outcome of renal transplantation in patients with polycystic kidney disease. Ann Transpl. 1996;1(2):15\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJankowska M, Kuźmiuk-Glembin I, Skonieczny P, Dębska-Ślizień A. Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease. Transpl Proc. 2018;50(6):1863\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanaan N, Devuyst O, Pirson Y. Renal transplantation in autosomal dominant polycystic kidney disease. Nat Rev Nephrol. 2014;10(8):455\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\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":"Cyst infection, pathogen replacement, antibiotic therapy, kidney transplantation, autosomal dominant polycystic kidney disease","lastPublishedDoi":"10.21203/rs.3.rs-5028400/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5028400/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRetaining the native bilateral kidneys after transplantation is a common alternative treatment for patients with end-stage autosomal dominant polycystic kidney disease. However, this strategy poses the risks of potential complications from polycystic kidney infection. The efficiency of antibiotic therapy (ATBT) and the optimal time for native nephrectomy in managing these infections remain uncertain.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe report a case of a kidney transplant recipient with retained bilateral polycystic kidneys who experienced recurrent cyst and bloodstream infections, accompanied by antibiotic-driven pathogen replacement. After multiple failed attempts at ATBT, the patient subsequently underwent unilateral polycystic kidney resection. Subsequently, a new infection episode occurred, leading to a preemptive native nephrectomy. Cystic tissue and fluid samples were collected from both shallow and deep layers of the polycystic kidneys, along with peripheral blood and urine samples. These samples were analyzed using microbial culture, metagenome sequencing, and digital polymerase chain reaction to identify infectious pathogens. Pathogen replacement occurred across different infection episodes, with the dominant bacterial species being \u003cem\u003eEscherichia coli\u003c/em\u003e, \u003cem\u003eKlebsiella aerogenes\u003c/em\u003e, and \u003cem\u003eEnterococcus faecium\u003c/em\u003e, in succession.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case highlights the replacement of dominant pathogens under antibiotic selection pressure in polycystic kidney infections, primarily involving gram-negative bacilli. When initial and subsequent ATBT fail, re-evaluation of the cyst infection definition is necessary, and preemptive native nephrectomy should be considered.\u003c/p\u003e","manuscriptTitle":"Antibiotic-Driven Pathogen Replacement Events in a Kidney Transplant Recipient with ADPKD: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-21 11:07:35","doi":"10.21203/rs.3.rs-5028400/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-22T14:39:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-29T14:43:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-28T05:37:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-23T14:16:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"88197992340007421281951240466966499404","date":"2024-12-21T12:24:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267975258907017961681479355805891681149","date":"2024-12-21T00:05:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99518421632176326209513347410705665097","date":"2024-12-19T12:30:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-19T12:15:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217186052911726415601977382256831305611","date":"2024-12-16T12:34:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-16T21:49:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-05T06:15:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-04T15:44:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-09-04T03:52:22+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":"592d1f45-ded5-4684-a082-f1f4c0a37a5d","owner":[],"postedDate":"October 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-31T16:06:21+00:00","versionOfRecord":{"articleIdentity":"rs-5028400","link":"https://doi.org/10.1186/s12879-025-10804-x","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-03-27 15:57:08","publishedOnDateReadable":"March 27th, 2025"},"versionCreatedAt":"2024-10-21 11:07:35","video":"","vorDoi":"10.1186/s12879-025-10804-x","vorDoiUrl":"https://doi.org/10.1186/s12879-025-10804-x","workflowStages":[]},"version":"v1","identity":"rs-5028400","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5028400","identity":"rs-5028400","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}