Mixed infections with Multiple Opportunistic Pathogens Resulting in Osteolytic Destruction and Acute Respiratory Failure: A Case Report

Mixed infections with Multiple Opportunistic Pathogens Resulting in Osteolytic Destruction and Acute Respiratory Failure: 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 Mixed infections with Multiple Opportunistic Pathogens Resulting in Osteolytic Destruction and Acute Respiratory Failure: A Case Report Yanmei Huang, Fei Zheng, Wenjuan Cao, Ye Qiu, Mianluan Pan, Hairong Lin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5356149/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract This study reports a case of disseminated infection caused by Cryptococcus, Pseudomonas aeruginosa, Aspergillus, and Mycobacterium abscessus in a diabetic patient. Male, 67 years old, presented with cough, sputum production, and bone pain. Chest computed tomography revealed a cavitary lesion in the dorsal segment of the left lower lobe, and lung tissue biopsy pathology confirmed a diagnosis of pulmonary cryptococcosis. Following antifungal therapy, the respiratory symptoms improved; however, the bone pain remained unresolved. Upon discontinuation of the medication, symptoms recurred and worsened, accompanied by fever and respiratory failure. Sputum culture revealed Pseudomonas aeruginosa, and Next-generation sequencing analysis of bronchoalveolar lavage fluid identified concurrent infections with Mycobacterium abscessus and Aspergillus fumigatus. Ultimately, the patient recovered and was discharged after targeted therapy. mixed infection Multiple Opportunistic Pathogens osteolytic destruction acute Respiratory Failure Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background The emergence of mixed infections with multiple opportunistic pathogens has added complexity to these diseases, presenting considerable challenges for diagnosis and treatment. Cryptococcus, Aspergillus, and non-tuberculous mycobacteria (NTM) are recognized as opportunistic pathogens. Infections caused by these organisms, whether occurring singly or in combination, can result in similar clinical symptoms, pulmonary imaging findings, and pathological features. If timely and effective treatment is not administered, patients often have a poor prognosis. These pathogens exhibit distinct biological characteristics, and traditional diagnostic methods may not adequately identify all relevant pathogens. Therefore, integrating traditional diagnostic methods with modern techniques, such as next-generation sequencing (NGS), along with repeated assessments, can provide a comprehensive understanding of the pathogen composition in infections. A thorough investigation of these complex cases will raise clinicians' awareness of mixed opportunistic infections, ultimately leading to optimized treatment strategies and improved patient outcomes. Case presentation A 67-year-old male patient was admitted on April 16, 2019, due to a cough and sputum production for 3 months. The patient presented with a cough productive of yellowish-white sputum in January 2019, without identifiable precipitating factors. In March 2019, he reported the onset of dyspnea, which exacerbated with physical exertion. Additionally, he experienced intermittent episodes of chest tightness and chest pain, along with palpitations and discomfort in the right wrist and lumbar region. The chest computed tomography (CT) conducted at a local hospital revealed a cavitary lesion in the posterior segment of the left lower lobe. Laboratory results indicated a white blood cell count of 7.11×10^9/L, hemoglobin of 125.0 g/L, and a neutrophil percentage of 88.1%. The patient was discharged after improvement following antibiotic treatment (details unspecified). After discharge, he continued to experience cough, sputum production, dyspnea on exertion, and joint pain, and was referred to our institute. The patient had a 3-year history of hypertension. He denied having a history of diabetes, tuberculosis, or other infectious diseases. He also denied any history of allergies and reported no habits of smoking or alcohol consumption. Physical examination demonstrated a temperature of 36.5℃, respiratory rate of 20 breaths/min, heart rate of 97 beats/min, and blood pressure of 151/76 mmHg (1 mmHg = 0.133 kPa). The patient was in stable condition, alert and oriented. No thoracic deformities were noted; breath sounds were diminished in the left lung, with no wheezing or crackles auscultated. Upon admission to our hospital, routine blood examination revealed a white blood cell count of 5.37 × 10^9/L, with neutrophils comprising 79.1%. Hemoglobin level was recorded at 94.1 g/L. The C-reactive protein (CRP) level was elevated at 69.0 mg/L. The serum galactomannan antigen test (GM test) yielded a value of 0.763, and the cryptococcal latex agglutination test (LAT) was positive with a dilution of 1:20. Glycated hemoglobin (HbA1c) was 10.2%, fasting blood glucose was 8.8 mmol/L, and postprandial blood glucose at 2 hours was 12.19 mmol/L. The results of the human immunodeficiency virus (HIV) antibody test, autoimmune antibody tests, Galactomannan test (G test), and pulmonary-related tumor marker tests were all negative. Chest CT revealed an oval thin-walled cavitary lesion measuring approximately 4×3×4 cm in the left lower lobe, associated with exudative changes (Figure 1). Emission computed tomography (ECT) demonstrated focal areas of increased radiotracer uptake in the L2 and L3 vertebrae as well as the right wrist joint (Figure 2). Bronchoalveolar lavage fluid (BALF) revealed a significant quantity of fungal spores, and the cryptococcal latex agglutination test was positive. Pathological examination of the bronchoscopy lung biopsy showed granulomatous inflammation in the left lower lobe, associated with chronic suppuration, multinucleated giant cells, and caseous necrosis, with negative acid-fast staining (Figure 3A). Pathological analysis of the percutaneous lung biopsy demonstrated inflammatory exudates and fibroblasts filling the alveoli, along with fibrous thickening of the alveolar walls and varying degrees of mononuclear and lymphocytic infiltration, suggesting organizing pneumonia (Figure 3B). The Gomori's methenamine silver stain yielded a positive result, with morphological findings consistent with cryptococcus (Figure 3C). The final diagnoses were 1) cryptococcal pneumonia and 2) diabetes mellitus. The patient was treated with hypoglycemic agents and intravenous voriconazole for 7 days, followed by oral isavuconazole upon discharge. After one month of antifungal therapy, the respiratory symptoms (including cough, sputum production, dyspnea, chest tightness, and chest pain) showed improvement. Chest CT revealed a reduction in the size of the cavitary lesion in the left lower lobe, with thinning of the cavity wall (Figure 4). However, the patient continued to experience joint pain and lower back pain. In June 2019, the patient independently discontinued isavuconazole for two weeks, leading to a recurrence of respiratory symptoms, exacerbation of joint and lower back pain, and the emergence of new symptoms including fever and weight loss. A complete blood count performed at a local hospital revealed a white blood cell count of 12.80×10^9/L, with neutrophils constituting 72.00%, and a hemoglobin level of 99.00 g/L. Sputum culture revealed the presence of Pseudomonas aeruginosa. The patient received treatment with piperacillin-tazobactam and ceftazidime for 7 days without clinical improvement, necessitating readmission to our hospital. Physical examination showed a temperature of 37.9°C, a respiratory rate of 24 breaths/min, a pulse rate of 132 beats/min, and a blood pressure of 130/82 mmHg (1 mmHg = 0.133 kPa). Laboratory results indicated a white blood cell count of 6.69×10^9/L, with neutrophils accounting for 95.30%; hemoglobin was 97.90 g/L. CRP was elevated at 147.72 mg/L. The GM yielded a value of 0.825, and the LAT was positive at a dilution of 1:20. Arterial blood gas analysis revealed respiratory failure (pH 7.49, PO2 42.7 mmHg, pCO2 21.2 mmHg, ABE -5.6 mmol/L). The chest CT conducted on June 28, 2019, revealed bilateral pulmonary infection, with a slightly enlarged thin-walled cavitary lesion measuring approximately 4.3 cm×2.6 cm×3.8 cm in the posterior segment of the left lower lobe, along with bilateral pleural effusion (Figure 5). The patient was diagnosed with severe pneumonia, respiratory failure, and diabetes mellitus. Treatment with non-invasive ventilation, meropenem, voriconazole, and teicoplanin was ineffective. On July 3, the patient remained febrile, and follow-up CT revealed diffuse consolidation and ground-glass opacities in both lungs, with increased pericavitary exudation and worsening bilateral pleural effusion (Figure 6). A bronchoscopy and bronchoalveolar lavage were repeated, and NGS detected the presence of Mycobacterium abscessus and Aspergillus fumigatus in the bronchoalveolar lavage fluid. The final diagnosis was a mixed pulmonary infection caused by cryptococcus, Mycobacterium abscessus, Aspergillus fumigatus, and Pseudomonas aeruginosa. In response to these findings, treatment was escalated to include ethambutol and moxifloxacin, which resulted in significant improvement in fever, respiratory symptoms, and bone pain. Chest CT on July 16 showed significant absorption of pulmonary lesions, with a reduction in the size of the cavitary lesion in the posterior segment of the left lower lobe and a slight decrease in bilateral pleural effusion. The patient was discharged on July 22. Following discharge, he continued a regimen of oral moxifloxacin, clarithromycin, ethambutol, and voriconazole daily. The patient received the aforementioned oral medications and underwent follow-up at a local hospital. One month post-discharge, his bone pain resolved, and follow-up chest CT showed significant absorption of the bilateral pulmonary lesions. After one year of continued treatment, the pulmonary lesions were completely absorbed. Three years of telephone follow-up indicated no recurrence of infection. Discussion and Conclusions This case involves an elderly male patient with no history of diabetes. He presented with cough, sputum production, and bone pain. Chest CT revealed a cavitary lesion in the posterior segment of the left lower lobe, and the patient showed a poor response to antibiotic therapy. The diagnosis of pulmonary cryptococcosis was confirmed through peripheral blood and bronchoalveolar lavage cryptococcal latex agglutination tests, as well as lung tissue biopsy pathology. However, after treatment with oral itraconazole, the symptoms improved. Following discontinuation of the medication, the symptoms recurred and worsened, leading to respiratory failure. In addition to the original lesions, diffuse exudative lesions and pleural effusion also developed in the lungs. Culture results identified Pseudomonas aeruginosa, while NGS detected NTM and Aspergillus. The patient was treated with a regimen that included voriconazole, meropenem, moxifloxacin, clarithromycin, and ethambutol for one year, ultimately achieving complete recovery. Whether the patient initially had a mixed infection or subsequently developed secondary infections is a critical question. This issue warrants consideration in this case report. While the diagnosis of cryptococcosis can be confirmed through cryptococcal latex agglutination tests and pathology, several clinical issues were overlooked: 1) The pathology of cryptococcosis is predominantly characterized by granulomatous tissue formation, with purulent changes and caseous necrosis being infrequent (1). In contrast, the latter two pathological features are more commonly observed in infections caused by Aspergillus, Mucorales, NTM, and Mycobacterium tuberculosis (2-4). 2) Especially, a positive GM test is rare in cases of cryptococcosis. 3) The patient presented with a prominent complaint of bone pain, and bone ECT revealed osteolytic destruction. However, this was clinically overlooked, as we attributed the damage to cryptococcosis. Literature reports (5,6) suggest that osteolytic destruction attributed to cryptococcosis is uncommon, with only sporadic cases documented in immunocompromised patients. In clinical practice, osteolytic destruction is more commonly associated with infections caused by Mycobacterium tuberculosis, NTM, Aspergillus species, Mucorales, Nocardia, and Actinomyces. Initially, no investigation for other pathogens was performed. Although respiratory symptoms showed improvement following antifungal treatment, the bone pain remained unrelieved. 4) CT manifestations of pulmonary cryptococcosis typically present as solitary or multiple pulmonary nodules or masses, often situated near the pleura. Cavitary lesions in the lungs may also be observed, with an incidence ranging from 11.0% to 34.6% (7). CT manifestations of pulmonary aspergillosis may include dense, well-defined lesions, with or without the halo sign; the air crescent sign; single or multiple cavities containing irregular contents; as well as wedge-shaped, segmental, or lobar consolidations (8). Upon meticulous review of the patient's lung CT, in addition to the thin-walled cavitary lesion in the left lower lung, irregular lesions were observed that align more closely with the imaging characteristics of aspergillosis. Surrounding these irregularities were small nodular lesions, while the mediastinal window revealed a granulomatous dense opacity, which is more consistent with changes associated with cryptococcosis. After the discontinuation of antifungal therapy, the respiratory symptoms recurred, accompanied by fever. A follow-up CT scan demonstrated marked thickening of the walls of the cavitary pulmonary lesions, along with an increased number of surrounding exudative lesions. Both the clinical progression and imaging findings were consistent with the advancement of pulmonary aspergillosis. Upon readmission, the patient exhibited respiratory failure, with Pseudomonas aeruginosa infection identified as a significant contributing factor to the exacerbation of the clinical condition. Subsequent bronchoscopy and bronchoalveolar lavage with NGS ultimately confirmed the diagnosis by identifying Aspergillus. However, Mycobacterium abscessus was also detected, leaving it uncertain whether this pathogen is a causative agent. Upon reviewing the patient's clinical course, we noted that while pulmonary status improved following antifungal therapy, the bone pain persisted. Initially, osteolytic lesions and increased metabolic activity in the joints were observed, along with chronic suppurative inflammation in the lung pathology—findings that are consistent with the clinical features associated with NTM infections. An increasing number of studies have reported osteolytic destruction associated with NTM (9,10), including infections caused by Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium intracellulare, Mycobacterium chelonae, and Mycobacterium intermedium, all of which have been documented in bone and joint infections. Particularly following the initiation of combination therapy with meropenem, moxifloxacin, clarithromycin, and ethambutol, the patient exhibited a rapid improvement in bone pain. Clinically, it can be concluded that the observed osteolytic destruction was likely attributable to NTM infection. At the onset of the disease, the patient presented with hyperglycemia, as indicated by a glycated hemoglobin level exceeding 10%. This finding effectively excludes infection-related hyperglycemia and suggests an underlying diabetic condition. It is well established that diabetes is a risk factor for tuberculosis and Aspergillus infections, but not for NTM or cryptococcal infections. Coinfections involving fungi (including cryptococci and Aspergillus) and NTM are commonly observed in patients with congenital or acquired immunodeficiency (such as those with positive γ-interferon antibodies, HIV-positive individuals, organ transplant recipients, those on immunosuppressive therapy, or with malignancies) or underlying pulmonary diseases (for instance, post-tuberculosis, cystic fibrosis, and chronic obstructive pulmonary disease) (11). Diabetes is not the sole host susceptibility factor for these opportunistic coinfections. There may also be unknown cellular or extracellular immune abnormalities, warranting further immunological investigation. In summary, this diabetic patient had a simultaneous polymicrobial opportunistic infection from the outset, involving Cryptococcus, Aspergillus, and Mycobacterium abscessus. In the initial phase of this case, a diagnosis of cryptococcal infection was made; however, investigations for other pathogens were overlooked. Irregular treatment and missed diagnoses, coupled with a concurrent infection with Pseudomonas aeruginosa, contributed to the worsening of the patient's condition. The comprehensive diagnosis was ultimately established through the combined use of culture and NGS. This underscores the importance of conducting comprehensive microbiological investigations using multiple sites, methods, and repeated assessments throughout the diagnostic process. In patients with underlying conditions, refractory pulmonary infections are frequently caused by either single or polymicrobial infections involving intracellular pathogens, and NGS demonstrates considerable utility in early diagnosis. Furthermore, other underlying immune deficiency mechanisms in the host should be noted by clinicians. Abbreviations non-tuberculous mycobacteria NTM next-generation sequencing NGS computed tomography CT C-reactive protein CRP latex agglutination test LAT Glycated hemoglobin HbA1c human immunodeficiency virus HIV Galactomannan test G test Emission computed tomography ECT galactomannan antigen test GM Bronchoalveolar lavage fluid BALF Declarations Ethics approval and consent to participate Signed consent was obtained for the publication of the case details from the participant. This study was approved by the First Affiliated Hospital of Guangxi Medical University’s Ethical Review Committee (2023-E067-01). Consent for publication Signed consent was obtained for the publication of the case details from the participant Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests The authors declare that they have no competing interests. Funding The article was supported by the Shenzhen Science Technology Program (Project Number: JCYJ20210324115000002) and Futian Healthcare Research Project (Project Number: FTWS2021004). Authors' contributions YH, FZ and WC made substantial contributions to the conception and design of the study; acquisition, analysis, and interpretation of the data; and drafting of the manuscript. YQ, MP and HL participated in the analysis and interpretation of the data. JZ and HY made substantial contributions to the conception and design of the study; acquisition, analysis, and interpretation of the data; and critical revision of the manuscript for important intellectual content and was accountable for all aspects of the work to ensure that questions related to the accuracy and integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript Acknowledgements None. References Ristow LC, Davis JM. The granuloma in cryptococcal disease. PLoS Pathog. 2021;17:e1009342. Dong S, Wang F, Jin H, et al. Five cases of pulmonary Aspergillus nodules diagnosed at surgery and by pathology in immunocompetent patients, with a literature review. Therapeutic Adv Rare Disease. 2024;5. 10.1177/https://doi.org/10./26330040241252446 . Jain D, Ghosh S, Teixeira L, et al. Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts, misconceptions, and practical tips for pathologists. Semin Diagn Pathol. 2017;34:518–29. 邱晔 吴昕. 陈丽坤 et al 播散性马尔尼菲篮状菌病合并肺隐球菌病1例并文献复习 国际呼吸杂志. 2023;43:714–8. Tao Z, Pu Q, Shen Y et al. Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis. BMC Infect Dis 2024;24. Yeung CM, Fabbri N. Disseminated Cryptococcus infection presenting as lytic skeletal lesions suggesting bony metastatic disease. Skeletal Radiol. 2023;53:2297–305. Huang J, Li H, Lan C et al. Disseminated cryptococcal infection with pulmonary involvement presenting as diffuse cavitary nodules in an immunocompromised patient: a case report. BMC Pulm Med 2023;23. Alexander BD, Lamoth F, Heussel CP, et al. Guidance on Imaging for Invasive Pulmonary Aspergillosis and Mucormycosis: From the Imaging Working Group for the Revision and Update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC. Clin Infect Dis. 2021;72:S79–88. Tang M, Huang J, Zeng W, et al. Retrospective Analysis of 10 Cases of Disseminated Nontuberculous Mycobacterial Disease with Osteolytic Lesions. Infect Drug Resist. 2021;14:4667–79. Kim S, Kim AR, Bae M et al. Clinical Characteristics and Outcomes of Extrapulmonary Nontuberculous Mycobacterial Infections in a Tertiary-Care Hospital: A Retrospective Study. J Clin Med 2024;13. Joao I, Bujdakova H, Jordao L. Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients. Antibiotics. 2020;9:771. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Nov, 2024 Editor assigned by journal 31 Oct, 2024 Submission checks completed at journal 31 Oct, 2024 First submitted to journal 29 Oct, 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5356149","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":374254989,"identity":"71340cf4-f1e6-4a70-bb91-674e12fad75b","order_by":0,"name":"Yanmei Huang","email":"","orcid":"","institution":"The Eighth Affiliated Hospital of Sun Yat-Sen University","correspondingAuthor":false,"prefix":"","firstName":"Yanmei","middleName":"","lastName":"Huang","suffix":""},{"id":374254990,"identity":"cf49c704-af39-472f-af5a-71946989b436","order_by":1,"name":"Fei Zheng","email":"","orcid":"","institution":"Minzu Hospital of Guangxi Zhuang Autonomous 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17:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5356149/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5356149/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69448842,"identity":"08ed9866-d085-4f32-adf1-651161e4d776","added_by":"auto","created_at":"2024-11-20 12:24:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":22316,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT prior to treatment on April 18, 2019, demonstrating a thin-walled cavity in the left lower lobe with accompanying exudate and irregular tissue, along with subpleural small nodules.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/86389bc049ab0b4534ab919e.jpg"},{"id":69448841,"identity":"a293970c-ece2-41e1-a4ea-3c947a6bc175","added_by":"auto","created_at":"2024-11-20 12:24:11","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":12173,"visible":true,"origin":"","legend":"\u003cp\u003eBone ECT on April 18, 2019, showing metabolic uptake in the right wrist joint of the second and third lumbar vertebrae.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/f291f10c5434b0250ff946bb.jpg"},{"id":69448825,"identity":"76238197-8c29-4be0-a2d4-a6aabef523ab","added_by":"auto","created_at":"2024-11-20 12:24:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2751600,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3A. Bronchoscopic lung biopsy pathology: Granulomatous inflammation with chronic suppuration, showing multinucleated cells, caseous necrosis, and acid-fast staining negative. Figure 3B. Percutaneous lung biopsy pathology: Alveoli filled with inflammatory exudate and fibroblasts, with fibrous thickening of the alveolar walls and varying degrees of infiltration by mononuclear cells and lymphocytes. Figure 3C. Positive Gomori's methenamine silver staining: Morphology consistent with cryptococcosis.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/6b9416c47be4c62e55cd4bce.png"},{"id":69448840,"identity":"17f90a0e-7a5c-43f5-81a1-98ef05ef6f15","added_by":"auto","created_at":"2024-11-20 12:24:10","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":20879,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT after 1 month of antifungal therapy on May 20, 2019: Reduction of the lesion in the left lower lobe with thinning of the cavity wall.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/2c7f33db9b690e4045bfc2ff.jpg"},{"id":69448826,"identity":"90e64aad-73f9-4bf4-b6ce-bd6cfee921b0","added_by":"auto","created_at":"2024-11-20 12:24:09","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":21300,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT on June 28, 2019: Bilateral diffuse exudative lesions, bilateral pleural effusion, and slight enlargement of the cavitary lesion in the dorsal segment of the left lower lobe.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/e89414ac20fba09ab60a36c5.jpg"},{"id":69448839,"identity":"a6539e35-354c-4b78-84e6-6a1e709119ce","added_by":"auto","created_at":"2024-11-20 12:24:09","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":20870,"visible":true,"origin":"","legend":"\u003cp\u003eChest CT on July 3, 2019: Bilateral diffuse consolidation and ground-glass opacities, with increased exudate around the cavity.\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/06ee1b7726c07eb5f7eacb33.jpg"},{"id":69448847,"identity":"42ec6e52-90a8-4d7e-98bc-43208b5ae681","added_by":"auto","created_at":"2024-11-20 12:24:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2978207,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5356149/v1/a8d18384-0edf-43f7-b5ab-405be7a057be.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mixed infections with Multiple Opportunistic Pathogens Resulting in Osteolytic Destruction and Acute Respiratory Failure: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eThe emergence of mixed infections with multiple opportunistic pathogens has added complexity to these diseases, presenting considerable challenges for diagnosis and treatment. Cryptococcus, Aspergillus, and non-tuberculous mycobacteria (NTM) are recognized as opportunistic pathogens. Infections caused by these organisms, whether occurring singly or in combination, can result in similar clinical symptoms, pulmonary imaging findings, and pathological features. If timely and effective treatment is not administered, patients often have a poor prognosis. These pathogens exhibit distinct biological characteristics, and traditional diagnostic methods may not adequately identify all relevant pathogens. Therefore, integrating traditional diagnostic methods with modern techniques, such as next-generation sequencing (NGS), along with repeated assessments, can provide a comprehensive understanding of the pathogen composition in infections. A thorough investigation of these complex cases will raise clinicians' awareness of mixed opportunistic infections, ultimately leading to optimized treatment strategies and improved patient outcomes.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 67-year-old male patient was admitted on April 16, 2019, due to a cough and sputum production for 3 months. The patient presented with a cough productive of yellowish-white sputum in January 2019, without identifiable precipitating factors. In March 2019, he reported the onset of dyspnea, which exacerbated with physical exertion. Additionally, he experienced intermittent episodes of chest tightness and chest pain, along with palpitations and discomfort in the right wrist and lumbar region. The chest computed tomography (CT) conducted at a local hospital revealed a cavitary lesion in the posterior segment of the left lower lobe. Laboratory results indicated a white blood cell count of 7.11\u0026times;10^9/L, hemoglobin of 125.0 g/L, and a neutrophil percentage of 88.1%. The patient was discharged after improvement following antibiotic treatment (details unspecified). After discharge, he continued to experience cough, sputum production, dyspnea on exertion, and joint pain, and was referred to our institute. The patient had a 3-year history of hypertension. He denied having a history of diabetes, tuberculosis, or other infectious diseases. He also denied any history of allergies and reported no habits of smoking or alcohol consumption.\u003c/p\u003e\n\u003cp\u003ePhysical examination demonstrated a temperature of 36.5℃, respiratory rate of 20 breaths/min, heart rate of 97 beats/min, and blood pressure of 151/76 mmHg (1 mmHg = 0.133 kPa). The patient was in stable condition, alert and oriented. No thoracic deformities were noted; breath sounds were diminished in the left lung, with no wheezing or crackles auscultated. Upon admission to our hospital, routine blood examination revealed a white blood cell count of 5.37 \u0026times; 10^9/L, with neutrophils comprising 79.1%. Hemoglobin level was recorded at 94.1 g/L. The C-reactive protein (CRP) level was elevated at 69.0 mg/L. The serum galactomannan antigen test (GM test) yielded a value of 0.763, and the cryptococcal latex agglutination test (LAT) was positive with a dilution of 1:20. Glycated hemoglobin (HbA1c) was 10.2%, fasting blood glucose was 8.8 mmol/L, and postprandial blood glucose at 2 hours was 12.19 mmol/L. The results of the human immunodeficiency virus (HIV) antibody test, autoimmune antibody tests, Galactomannan test (G test), and pulmonary-related tumor marker tests were all negative. Chest CT revealed an oval thin-walled cavitary lesion measuring approximately 4\u0026times;3\u0026times;4 cm in the left lower lobe, associated with exudative changes (Figure 1). Emission computed tomography (ECT) demonstrated focal areas of increased radiotracer uptake in the L2 and L3 vertebrae as well as the right wrist joint (Figure 2). Bronchoalveolar lavage fluid (BALF) revealed a significant quantity of fungal spores, and the cryptococcal latex agglutination test was positive. Pathological examination of the bronchoscopy lung biopsy showed granulomatous inflammation in the left lower lobe, associated with chronic suppuration, multinucleated giant cells, and caseous necrosis, with negative acid-fast staining (Figure 3A). Pathological analysis of the percutaneous lung biopsy demonstrated inflammatory exudates and fibroblasts filling the alveoli, along with fibrous thickening of the alveolar walls and varying degrees of mononuclear and lymphocytic infiltration, suggesting organizing pneumonia (Figure 3B). The Gomori\u0026apos;s methenamine silver stain yielded a positive result, with morphological findings consistent with cryptococcus (Figure 3C). The final diagnoses were 1) cryptococcal pneumonia and 2) diabetes mellitus. The patient was treated with hypoglycemic agents and intravenous voriconazole for 7 days, followed by oral isavuconazole upon discharge. After one month of antifungal therapy, the respiratory symptoms (including cough, sputum production, dyspnea, chest tightness, and chest pain) showed improvement. Chest CT revealed a reduction in the size of the cavitary lesion in the left lower lobe, with thinning of the cavity wall (Figure 4). However, the patient continued to experience joint pain and lower back pain.\u003c/p\u003e\n\u003cp\u003eIn June 2019, the patient independently discontinued isavuconazole for two weeks, leading to a recurrence of respiratory symptoms, exacerbation of joint and lower back pain, and the emergence of new symptoms including fever and weight loss. A complete blood count performed at a local hospital revealed a white blood cell count of 12.80\u0026times;10^9/L, with neutrophils constituting 72.00%, and a hemoglobin level of 99.00 g/L. Sputum culture revealed the presence of Pseudomonas aeruginosa. The patient received treatment with piperacillin-tazobactam and ceftazidime for 7 days without clinical improvement, necessitating readmission to our hospital. Physical examination showed a temperature of 37.9\u0026deg;C, a respiratory rate of 24 breaths/min, a pulse rate of 132 beats/min, and a blood pressure of 130/82 mmHg (1 mmHg = 0.133 kPa). Laboratory results indicated a white blood cell count of 6.69\u0026times;10^9/L, with neutrophils accounting for 95.30%; hemoglobin was 97.90 g/L. CRP was elevated at 147.72 mg/L. The GM yielded a value of 0.825, and the LAT was positive at a dilution of 1:20. Arterial blood gas analysis revealed respiratory failure (pH 7.49, PO2 42.7 mmHg, pCO2 21.2 mmHg, ABE -5.6 mmol/L). The chest CT conducted on June 28, 2019, revealed bilateral pulmonary infection, with a slightly enlarged thin-walled cavitary lesion measuring approximately 4.3 cm\u0026times;2.6 cm\u0026times;3.8 cm in the posterior segment of the left lower lobe, along with bilateral pleural effusion (Figure 5). The patient was diagnosed with severe pneumonia, respiratory failure, and diabetes mellitus. Treatment with non-invasive ventilation, meropenem, voriconazole, and teicoplanin was ineffective. On July 3, the patient remained febrile, and follow-up CT revealed diffuse consolidation and ground-glass opacities in both lungs, with increased pericavitary exudation and worsening bilateral pleural effusion (Figure 6). A bronchoscopy and bronchoalveolar lavage were repeated, and NGS detected the presence of Mycobacterium abscessus and Aspergillus fumigatus in the bronchoalveolar lavage fluid. The final diagnosis was a mixed pulmonary infection caused by cryptococcus, Mycobacterium abscessus, Aspergillus fumigatus, and Pseudomonas aeruginosa. In response to these findings, treatment was escalated to include ethambutol and moxifloxacin, which resulted in significant improvement in fever, respiratory symptoms, and bone pain. Chest CT on July 16 showed significant absorption of pulmonary lesions, with a reduction in the size of the cavitary lesion in the posterior segment of the left lower lobe and a slight decrease in bilateral pleural effusion. The patient was discharged on July 22. Following discharge, he continued a regimen of oral moxifloxacin, clarithromycin, ethambutol, and voriconazole daily. The patient received the aforementioned oral medications and underwent follow-up at a local hospital. One month post-discharge, his bone pain resolved, and follow-up chest CT showed significant absorption of the bilateral pulmonary lesions. After one year of continued treatment, the pulmonary lesions were completely absorbed. Three years of telephone follow-up indicated no recurrence of infection.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":"\u003cp\u003eThis case involves an elderly male patient with no history of diabetes. He presented with cough, sputum production, and bone pain. Chest CT revealed a cavitary lesion in the posterior segment of the left lower lobe, and the patient showed a poor response to antibiotic therapy. The diagnosis of pulmonary cryptococcosis was confirmed through peripheral blood and bronchoalveolar lavage cryptococcal latex agglutination tests, as well as lung tissue biopsy pathology. However, after treatment with oral itraconazole, the symptoms improved. Following discontinuation of the medication, the symptoms recurred and worsened, leading to respiratory failure. In addition to the original lesions, diffuse exudative lesions and pleural effusion also developed in the lungs. Culture results identified Pseudomonas aeruginosa, while NGS detected NTM and Aspergillus. The patient was treated with a regimen that included voriconazole, meropenem, moxifloxacin, clarithromycin, and ethambutol for one year, ultimately achieving complete recovery.\u003c/p\u003e\n\u003cp\u003eWhether the patient initially had a mixed infection or subsequently developed secondary infections is a critical question. This issue warrants consideration in this case report.\u003c/p\u003e\n\u003cp\u003eWhile the diagnosis of cryptococcosis can be confirmed through cryptococcal latex agglutination tests and pathology, several clinical issues were overlooked: 1) The pathology of cryptococcosis is predominantly characterized by granulomatous tissue formation, with purulent changes and caseous necrosis being infrequent (1). In contrast, the latter two pathological features are more commonly observed in infections caused by Aspergillus, Mucorales, NTM, and Mycobacterium tuberculosis (2-4). 2) Especially, a positive GM test is rare in cases of cryptococcosis. 3) The patient presented with a prominent complaint of bone pain, and bone ECT revealed osteolytic destruction. However, this was clinically overlooked, as we attributed the damage to cryptococcosis. Literature reports (5,6) suggest that osteolytic destruction attributed to cryptococcosis is uncommon, with only sporadic cases documented in immunocompromised patients. In clinical practice, osteolytic destruction is more commonly associated with infections caused by Mycobacterium tuberculosis, NTM, Aspergillus species, Mucorales, Nocardia, and Actinomyces. Initially, no investigation for other pathogens was performed. Although respiratory symptoms showed improvement following antifungal treatment, the bone pain remained unrelieved. 4) CT manifestations of pulmonary cryptococcosis typically present as solitary or multiple pulmonary nodules or masses, often situated near the pleura. Cavitary lesions in the lungs may also be observed, with an incidence ranging from 11.0% to 34.6% (7). CT manifestations of pulmonary aspergillosis may include dense, well-defined lesions, with or without the halo sign; the air crescent sign; single or multiple cavities containing irregular contents; as well as wedge-shaped, segmental, or lobar consolidations (8). Upon meticulous review of the patient\u0026apos;s lung CT, in addition to the thin-walled cavitary lesion in the left lower lung, irregular lesions were observed that align more closely with the imaging characteristics of aspergillosis. Surrounding these irregularities were small nodular lesions, while the mediastinal window revealed a granulomatous dense opacity, which is more consistent with changes associated with cryptococcosis. After the discontinuation of antifungal therapy, the respiratory symptoms recurred, accompanied by fever. A follow-up CT scan demonstrated marked thickening of the walls of the cavitary pulmonary lesions, along with an increased number of surrounding exudative lesions. Both the clinical progression and imaging findings were consistent with the advancement of pulmonary aspergillosis.\u003c/p\u003e\n\u003cp\u003eUpon readmission, the patient exhibited respiratory failure, with Pseudomonas aeruginosa infection identified as a significant contributing factor to the exacerbation of the clinical condition. Subsequent bronchoscopy and bronchoalveolar lavage with NGS ultimately confirmed the diagnosis by identifying Aspergillus. However, Mycobacterium abscessus was also detected, leaving it uncertain whether this pathogen is a causative agent.\u003c/p\u003e\n\u003cp\u003eUpon reviewing the patient\u0026apos;s clinical course, we noted that while pulmonary status improved following antifungal therapy, the bone pain persisted. Initially, osteolytic lesions and increased metabolic activity in the joints were observed, along with chronic suppurative inflammation in the lung pathology\u0026mdash;findings that are consistent with the clinical features associated with NTM infections. An increasing number of studies have reported osteolytic destruction associated with NTM (9,10), including infections caused by Mycobacterium abscessus, Mycobacterium avium complex, Mycobacterium kansasii, Mycobacterium fortuitum, Mycobacterium intracellulare, Mycobacterium chelonae, and Mycobacterium intermedium, all of which have been documented in bone and joint infections. Particularly following the initiation of combination therapy with meropenem, moxifloxacin, clarithromycin, and ethambutol, the patient exhibited a rapid improvement in bone pain. Clinically, it can be concluded that the observed osteolytic destruction was likely attributable to NTM infection.\u003c/p\u003e\n\u003cp\u003eAt the onset of the disease, the patient presented with hyperglycemia, as indicated by a glycated hemoglobin level exceeding 10%. This finding effectively excludes infection-related hyperglycemia and suggests an underlying diabetic condition. It is well established that diabetes is a risk factor for tuberculosis and Aspergillus infections, but not for NTM or cryptococcal infections. Coinfections involving fungi (including cryptococci and Aspergillus) and NTM are commonly observed in patients with congenital or acquired immunodeficiency (such as those with positive \u0026gamma;-interferon antibodies, HIV-positive individuals, organ transplant recipients, those on immunosuppressive therapy, or with malignancies) or underlying pulmonary diseases (for instance, post-tuberculosis, cystic fibrosis, and chronic obstructive pulmonary disease) (11). Diabetes is not the sole host susceptibility factor for these opportunistic coinfections. There may also be unknown cellular or extracellular immune abnormalities, warranting further immunological investigation.\u003c/p\u003e\n\u003cp\u003eIn summary, this diabetic patient had a simultaneous polymicrobial opportunistic infection from the outset, involving Cryptococcus, Aspergillus, and Mycobacterium abscessus. In the initial phase of this case, a diagnosis of cryptococcal infection was made; however, investigations for other pathogens were overlooked. Irregular treatment and missed diagnoses, coupled with a concurrent infection with Pseudomonas aeruginosa, contributed to the worsening of the patient\u0026apos;s condition. The comprehensive diagnosis was ultimately established through the combined use of culture and NGS. This underscores the importance of conducting comprehensive microbiological investigations using multiple sites, methods, and repeated assessments throughout the diagnostic process. In patients with underlying conditions, refractory pulmonary infections are frequently caused by either single or polymicrobial infections involving intracellular pathogens, and NGS demonstrates considerable utility in early diagnosis. Furthermore, other underlying immune deficiency mechanisms in the host should be noted by clinicians.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003col\u003e\n \u003cli\u003enon-tuberculous mycobacteria NTM\u003c/li\u003e\n \u003cli\u003enext-generation sequencing NGS\u003c/li\u003e\n \u003cli\u003ecomputed tomography CT\u003c/li\u003e\n \u003cli\u003eC-reactive protein CRP\u003c/li\u003e\n \u003cli\u003elatex agglutination test LAT\u003c/li\u003e\n \u003cli\u003eGlycated hemoglobin HbA1c\u003c/li\u003e\n \u003cli\u003ehuman immunodeficiency virus HIV\u003c/li\u003e\n \u003cli\u003eGalactomannan test G test\u003c/li\u003e\n \u003cli\u003eEmission computed tomography ECT\u003c/li\u003e\n \u003cli\u003egalactomannan antigen test GM\u003c/li\u003e\n \u003cli\u003eBronchoalveolar lavage fluid BALF\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSigned consent was obtained for the publication of the case details from the participant. This study was approved by the First Affiliated Hospital of Guangxi Medical University\u0026rsquo;s Ethical Review Committee (2023-E067-01).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSigned consent was obtained for the publication of the case details from the participant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe article was supported by the Shenzhen Science Technology Program (Project Number: JCYJ20210324115000002) and Futian Healthcare Research Project (Project Number: FTWS2021004).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYH, FZ and WC made substantial contributions to the conception and design of the study; acquisition, analysis, and interpretation of the data; and drafting of the manuscript. YQ, MP and HL participated in the analysis and interpretation of the data. JZ and HY made substantial contributions to the conception and design of the study; acquisition, analysis, and interpretation of the data; and critical revision of the manuscript for important intellectual content and was accountable for all aspects of the work to ensure that questions related to the accuracy and integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRistow LC, Davis JM. The granuloma in cryptococcal disease. PLoS Pathog. 2021;17:e1009342.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong S, Wang F, Jin H, et al. Five cases of pulmonary Aspergillus nodules diagnosed at surgery and by pathology in immunocompetent patients, with a literature review. Therapeutic Adv Rare Disease. 2024;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/https://doi.org/10./26330040241252446\u003c/span\u003e\u003cspan address=\"10.1177/10./26330040241252446\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain D, Ghosh S, Teixeira L, et al. Pathology of pulmonary tuberculosis and non-tuberculous mycobacterial lung disease: Facts, misconceptions, and practical tips for pathologists. Semin Diagn Pathol. 2017;34:518\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e邱晔 吴昕. 陈丽坤 et al 播散性马尔尼菲篮状菌病合并肺隐球菌病1例并文献复习 国际呼吸杂志. 2023;43:714\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTao Z, Pu Q, Shen Y et al. Clinical characteristics and prognostic factors of pulmonary and extrapulmonary cryptococcosis. BMC Infect Dis 2024;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeung CM, Fabbri N. Disseminated Cryptococcus infection presenting as lytic skeletal lesions suggesting bony metastatic disease. Skeletal Radiol. 2023;53:2297\u0026ndash;305.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang J, Li H, Lan C et al. Disseminated cryptococcal infection with pulmonary involvement presenting as diffuse cavitary nodules in an immunocompromised patient: a case report. BMC Pulm Med 2023;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlexander BD, Lamoth F, Heussel CP, et al. Guidance on Imaging for Invasive Pulmonary Aspergillosis and Mucormycosis: From the Imaging Working Group for the Revision and Update of the Consensus Definitions of Fungal Disease from the EORTC/MSGERC. Clin Infect Dis. 2021;72:S79\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang M, Huang J, Zeng W, et al. Retrospective Analysis of 10 Cases of Disseminated Nontuberculous Mycobacterial Disease with Osteolytic Lesions. Infect Drug Resist. 2021;14:4667\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim S, Kim AR, Bae M et al. Clinical Characteristics and Outcomes of Extrapulmonary Nontuberculous Mycobacterial Infections in a Tertiary-Care Hospital: A Retrospective Study. J Clin Med 2024;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoao I, Bujdakova H, Jordao L. Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients. Antibiotics. 2020;9:771.\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":"mixed infection, Multiple Opportunistic Pathogens, osteolytic destruction, acute Respiratory Failure","lastPublishedDoi":"10.21203/rs.3.rs-5356149/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5356149/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study reports a case of disseminated infection caused by Cryptococcus, Pseudomonas aeruginosa, Aspergillus, and Mycobacterium abscessus in a diabetic patient. Male, 67 years old, presented with cough, sputum production, and bone pain. Chest computed tomography revealed a cavitary lesion in the dorsal segment of the left lower lobe, and lung tissue biopsy pathology confirmed a diagnosis of pulmonary cryptococcosis. Following antifungal therapy, the respiratory symptoms improved; however, the bone pain remained unresolved. Upon discontinuation of the medication, symptoms recurred and worsened, accompanied by fever and respiratory failure. Sputum culture revealed Pseudomonas aeruginosa, and Next-generation sequencing analysis of bronchoalveolar lavage fluid identified concurrent infections with Mycobacterium abscessus and Aspergillus fumigatus. Ultimately, the patient recovered and was discharged after targeted therapy.\u003c/p\u003e","manuscriptTitle":"Mixed infections with Multiple Opportunistic Pathogens Resulting in Osteolytic Destruction and Acute Respiratory Failure: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-20 12:23:29","doi":"10.21203/rs.3.rs-5356149/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-05T08:48:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-01T03:11:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-01T03:11:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-10-29T17:01:53+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":"6e3429b3-33d8-4b30-948b-1ba15be73d0c","owner":[],"postedDate":"November 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-21T05:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-20 12:23:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5356149","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5356149","identity":"rs-5356149","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}