{"paper_id":"4cf3cc0f-db4d-4ab8-a57f-d80eafe4609d","body_text":"Mycobacterium florentinum pulmonary disease: A case report and review of the literature | 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 Mycobacterium florentinum pulmonary disease: A case report and review of the literature Fabian Leo, Silke Polsfuss, Anne-Sophie Przewosnik, Christian Grohé, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7727745/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Dec, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 24 You are reading this latest preprint version Abstract Background: Following the initial description of Mycobacterium florentinum in 2005, very few clinical cases have been reported and the optimal antimicrobial treatment and clinical outcomes are uncertain. Amikacin liposomal inhalation suspension (ALIS) has received approval for the treatment of Mycobacterium avium/intracellulare complex (MAC) pulmonary disease. However, there is little experience with its use for infections caused by less common nontuberculous mycobacteria (NTM). Moreover, the awareness of uncommon adverse effects is still limited. Case presentation: A 69-year-old female patient suffering from nodular bronchiectatic Mycobacterium florentinum pulmonary disease was treated with azithromycin, ethambutol, and rifampicin, administered three times per week. After 13 months, owing to treatment failure, the therapy was changed to ALIS, moxifloxacin, and clofazimine. This resulted in rapid and sustained culture conversion. Concurrently, the patient exhibited increased cough and sputum, which was consistent with a clinical diagnosis of aspergillosis, as confirmed by evidence of Aspergillus fumigatus in respiratory specimens and a significant increase in serum anti-Aspergillus IgG antibody levels. Following a six-month course of antifungal therapy, a marked improvement in the patient's symptoms was observed. Conclusions: As with MAC pulmonary disease, combination antimicrobial therapy including ALIS was successful in a patient affected by a difficult-to-treat pulmonary infection caused by Mycobacterium florentinum , a rare NTM pathogen. Combination antibiotic treatment including ALIS may also be considered for difficult-to-treat non-MAC NTM- pulmonary diseases, when based on the results of in-vitro drug-susceptibility testing. Nontuberculous mycobacteria Mycobacterium florentinum Pulmonary aspergillosis Aspergillus fumigatus Amikacin Inhalation Drug Administration Figures Figure 1 Figure 2 Figure 3 Background Mycobacterium florentinum was first characterized by Tortoli et al. in 2005 in a case series comprising eight isolates from human samples. It is closely related to M. triplex , M. lentiflavum and M. montefiorense , but is clearly distinguishable by unique 16S rRNA and internal transcribed spacer (ITS) sequences as well as a unique PCR restriction analysis (PRA) pattern of the 65 kDa heat-shock protein-encoding gene (hsp65) ( 1 ). More than half of the isolates were considered clinically relevant infections (four out of six from respiratory samples, and one from cervical lymph node tissue). However, treatment and clinical outcome data were not reported. The authors also identified a previously documented case of NTM lung disease from 2001 as being attributable to a Mycobacterium florentinum infection ( 1 , 2 ). The patient was a 67-year-old female from Finland who was diagnosed with nontuberculous mycobacterial pulmonary disease (NTM-PD) with a nodular bronchiectatic radiologic phenotype. Data from antimicrobial susceptibility testing (AST) were not reported. However, the patient was considered clinically cured after 18 months of treatment with clarithromycin, ethambutol, rifampicin and ciprofloxacin. In the following years, only two additional case reports of M. florentinum infection have been published in the English-language literature: one in 2010, which detailed a second case of cervical lymphadenitis in a child, and one in 2014, documenting a single case of synovitis in an immunocompromised individual ( 3 , 4 ). In the case of cervical lymphadenitis, therapy consisted of complete surgical lymph node excision and no relapse occurred within 12 months of follow-up observation ( 3 ). The authors of this report also conducted a data query at a national reference laboratory in the United States (Associated Regional and University Pathologists Laboratories), covering the period between 2006 and 2010. This revealed four additional documented M. florentinum isolates: a 76-year-old man (source: bronchial aspirate), a 47-year-old man (sputum), a 5-year-old girl (neck lymph node), and a 46-year-old man (unspecified source). The cases were submitted from different regions in the United States. No information was provided on the clinical relevance of these findings ( 3 ). Nukui et al. described a case of synovitis in a 65-year-old, immunocompromised patient with a history of systemic lupus erythematosus (SLE), chronic kidney disease and long-term prednisolone therapy. M. florentinum was found to be the causative pathogen, and treatment consisted of surgical debridement and antimycobacterial drugs (clarithromycin, rifampicin, and levofloxacin). The patient died unexpectedly after three months from acute aortic dissection ( 4 ). A synopsis of all cases published to date, with at least basic clinical data and available AST results, is shown in Table 1 . Due to the limited number of cases reported thus far, the most effective treatment regimen remains unclear. Table 1 Overview of clinical Mycobacterium florentinum cases in the English-language literature. Reference/ year Gender and age (years) Source Clinical presentation CS MIC AMK mg/l MIC CIP mg/l MIC CLR mg/l MIC CFZ mg/l MIC EMB mg/l MIC MOX mg/l MIC LFX mg/l MIC RFB mg/l MIC RMP mg/l ( 1 ) / 2005 F, 6 Lymph node Lymphadenitis yes 2 4 2 0.12 8 n/a n/a 0.25 16 F, 82 Sputum Emphysema no 0.5 128 2 0.12 4 n/a n/a 0.06 8 M, 33 Stools Weight loss no 4 128 2 0.5 8 n/a n/a 0.25 4 F, 70 Sputum Pulmonary fibrosis, bronchiectasis yes n/a F, 93 Sputum, gastric aspirate Hemoptysis, fever n/a F, 84 Sputum Hemoptysis, pleurisy no M, 65 Sputum Pneumonia yes F, 64 Sputum Pneumonia yes ( 2 ) / 2001 F, 67 Sputum, BAL Hemoptysis yes ( 3 ) / 2010 F, 3 Lymph Node Lymphadenitis yes 0.5 8 0.5 n/a 4 1 n/a n/a 0.12 ( 4 ) / 2014 F, 65 Synovia (wrist) Arthritis yes 16 2 n/a 8 n/a 16 n/a 4 Leo et al. 2025 †; †† F, 69 Sputum Pneumonia, hemoptysis yes 16 > 16 1 n/a n/a > 8 n/a 0.25 > 8 Basic demographic data, isolation source, clinical presentation, clinical significance and antimicrobial susceptibility testing results of M. florentinum cases reported in the literature, including this case report. F = female; M = male; CS = clinical significance; MIC = minimal inhibitory concentration; AMK = Amikacin, CIP = Ciprofloxacin; CLR = Clarithromycin; CFZ = Clofazimine; EMB = Ethambutol; MOX = Moxifloxacin; LFX = Levofloxacin; RFB = Rifabutin; RMP = Rifampicin; n/a: not applicable (not done). † Antimicrobial susceptibility testing (AST) was performed and assessed by broth microdilution method (SensititreTM Myco susceptibility plates SLOMYCOI, Thermo Fisher Diagnostics GmbH, Germany) according to Clinical and Laboratory Standards Institute (CLSI M24Ed2 and M62Ed1 (November 2018 and CLSI M24S Ed2 (February 2023) guideline. †† More comprehensive data including repeat AST of isolates during antimycobacterial treatment can be found in Additional file 1 (Supplemental information). Amikacin liposome inhalation suspension (ALIS) is currently approved for the treatment of pulmonary infection caused by nontuberculous mycobacteria belonging to the Mycobacterium avium / intracellulare complex (MAC). There is little experience with the use of ALIS in less frequent NTM species. The use of systemic or inhaled antibiotics has been related to an increase in airway colonization with Aspergillus spp . in patients with cystic fibrosis (CF), non-CF bronchiectasis and NTM-PD ( 5 – 8 ). In patients with NTM-PD, the development of chronic pulmonary aspergillosis (CPA) is a prognostic factor for mortality ( 9 ). Owing to the many common symptoms and radiological features of NTM-PD and CPA, distinguishing between colonization and clinically relevant aspergillosis may be difficult. The specific impact of ALIS on Aspergillus spp. colonization and development of CPA has not been studied( 10 ). The objective of this report is to describe a very rare case of M. florentinum pulmonary disease with a view to its management utilizing an ALIS-based antibiotic regimen and close attention to possible adverse effects, including the emergence of fungal coinfection. Case presentation NTM-PD diagnosis and clinical course before ALIS treatment In December 2018, a 69-year-old female patient (163 cm, 53 kg) was first referred to our clinic for refractory pneumonia. She reported chronic cough and weight loss (6 kg in 12 months). Chest computed tomography (CT) revealed bronchiectasis and peribronchial consolidation focused in the middle lobe, lingula, and left lower lobe ( Fig. 1a ). C-reactive peptide, blood leucocytes, eosinophils, alpha1-antitrypsin and immunoglobulins IgA, IgE, IgG and IgM were within the respective reference ranges, whereas anti-Aspergillus-IgG was marginally elevated (ELISA 63 U/ml, reference < 50 U/ml, Serion Diagnostics GmbH, Wuerzburg, Germany). Bronchoalveolar lavage (BAL) revealed 95% neutrophils and evidence of Staphylococcus aureus (MSSA [10 2 /ml]), which was treated with ampicillin/sulbactam for 14 days. Acid fast bacilli (AFB) remained undetectable by microscopy of auramine-stained BAL fluid and in three sputum samples, whereas cultures from BAL fluid and two sputum samples each grew M. florentinum . In 02/2019, symptoms and radiologic findings improved, and the patient was managed with sodium saline inhalation and physical therapy using via a Flutter™ device. During a 24- month period of “watchful waiting”, specific antimycobacterial treatment was withheld according to the patient’s informed preference. Sputum cultures grew M. florentinum again in 12/2019, and M. avium grew in 12/2020. Both isolates showed in- vitro susceptibility to clarithromycin. In 12/2020, the patient reported frequent hemoptysis, and CT imaging showed increasing nodules and consolidations in the right upper lobe, middle lobe and left lower lobe ( Fig. 1b ) In 02/2021, antimycobacterial treatment was started, using a regimen of azithromycin (AZM), ethambutol (EMB) and rifampicin (RMP) three times weekly. In 04/2021, sputum culture for mycobacteria was negative, but became positive again in 06/2021 and 08/2021, with molecular species differentiation revealing M. florentinum once more, but not M. avium . Treatment was continued because the patient was considered to benefit from therapy from a clinical perspective. However, sputum microscopy detected AFB for the first time in 10/2021, and cultures grew M. florentinum again. Repeat in- vitro drug susceptibility testing excluded the development of macrolide resistance. The minimal inhibitory concentration (MIC) for Amikacin (AMK) was 16 mg/l, which corresponds to susceptibility according to the Clinical and Laboratory Standards Institute (CLSI) definition (see Additional file 1 ). ALIS treatment initiation, clinical course and outcome In 01/2022, CT imaging revealed progressive consolidation in the right upper lobe (segment 2) and progressive bronchiolitis in the inferior lower lobes and middle lobe (Fig. 1c). In 03/2022 (= month 0), the treatment was switched to ALIS 590 mg/d by inhalation, clofazimine 100 mg/d orally and moxifloxacin 400 mg/d orally. With this regimen, culture conversion was documented in 04/2022 (month + 1), and follow-up CT showed improvement in 06/2022 (month + 3). In 09/2022 (month + 6), the patient described increasing cough and sputum, while CT showed a mixed response, and mycobacterial cultures remained negative. Proof of Aspergillus fumigatus in sputum samples and a > 3-fold rise in Aspergillus-IgG serum antibody (207 U/ml) prompted antifungal treatment with oral voriconazole (VCZ) in 11/2022 (month + 8). Therapeutic drug monitoring was performed during treatment, and all VCZ trough levels were within the therapeutic range (1–5 mg/l). The patient´s clinical status improved gradually, as indicated by changes in body weight, cough, fatigue, and other factors ( Fig. 2) . Antimycobacterial treatment was terminated in 04/2023 (month + 13, 12 months after sputum conversion), and VCZ was continued until 05/2023 (treatment duration of 6 months). Chest CT at the end of treatment showed radiological improvement ( Fig. 3a ). During follow-up, sustained sputum conversion was documented until the last contact with the patient in 03/2025 (month + 36, 23 months after the end of treatment). The level of anti-Aspergillus-Ig G antibody decreased to 138 U/ml at the conclusion of VCZ treatment and to 98 U/ml at six months thereafter. Twenty-two months after completing VCZ treatment, the level Anti-Aspergillus-IgG was < 50 U/ml. Follow-up sputum samples exploring respiratory pathogens other than mycobacteria revealed S. aureus , Enterobacteriaceae and Scedosporium spp . and two episodes of antibiotic treatment for bronchiectasis exacerbation were necessary during nearly two years of follow-up. Adverse events during ALIS treatment From the beginning of ALIS therapy, the patient reported variable dry cough and dysphonia related to inhalation. These symptoms were tolerable throughout the entire treatment course, without the need for discontinuation of the inhalations. Chest CT imaging at month + 3 revealed ground glass opacities (GGO) in the upper lobes bilaterally and in segments 6 and 9 of the right lung. At month + 6, the GGO decreased slightly, but at month + 12, new GGO emerged in the right upper lobe and left upper and lower lobes ( Fig. 3b ). At month + 20, seven months after the end of ALIS treatment, the extent of GGO was markedly decreased ( Fig. 3c ). Data query A data query at the German National Reference Centre for Mycobacteria (Research Center Borstel) was conducted. No other strains of M. florentinum were identified during the period from January 2018 to April 2025. Discussion and conclusions This case of M. florentinum pulmonary disease ( M. florentinum -PD) is only the second documented case that provides detailed data on treatment and clinical outcomes. The other, by Suomalainen et. al in 2001, predates the classification of M. florentinum as an independent species. Initially, it was considered a subspecies of the closely related M. triplex taxon. A substantial case series pertaining to M. triplex pulmonary disease from Australia was published in 2019( 11 ). The collection was composed of 39 cases, with a significant portion (approximately 45%) meeting the criteria for NTM-PD( 12 ). The AST results obtained for 14 isolates revealed that 93% were susceptible to macrolides. However, only six patients with pulmonary infection received antimicrobial therapy (including azithromycin or clarithromycin), with five patients demonstrating treatment success ( 11 ). In conjunction with the existing data on AST for M. florentinum (Table 1 ), these findings support the selection of a macrolide-based combination as an initial therapy for the treatment of M. florentinum pulmonary disease. Amikacin liposomal inhalation suspension (ALIS) has the potential to serve as an ancillary option for patients who are difficult to treat, e.g. due to poor tolerability of oral drugs, or in cases where first-line therapy has failed. In addition to its in-label use for MAC-PD, ALIS was reported to be effective in CF bronchiectasis and non-CF bronchiectasis patients with M. abscessus infection ( 13 ). In the case of the M. florentinum -PD presented here, an ALIS-based treatment resulted in rapid culture conversion and microbiological and clinical cure as defined by the NTMnet group consensus ( 14 ). Remarkably, the MIC for amikacin was higher in this case than in the other M. florentinum strains reported in the literature. However, compared with conventional parenteral or inhaled amikacin, the use of ALIS results in higher concentrations of amikacin in macrophages, lung tissue and biofilms, potentially enhancing its efficacy against mycobacteria ( 15 ) Furthermore, in- vitro data across different NTM species suggest antimycobacterial synergy between amikacin and clofazimine, which was also part of the treatment regimen( 16 ). Inhaled antibiotics may promote airway colonization by Aspergillus fumigatus and other fungi. Insights are available from studies of CF -bronchiectasis: Microbiological data from two randomized, controlled trials studying inhaled tobramycin vs. placebo showed that isolation of Aspergillus and Candida was increased in the tobramycin group but did not affect the outcome( 5 ). In a more recent cohort of CF patients from Sweden, the use of inhaled antibiotics was also associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6–5.9, p < 0.05) but not with adverse effects on lung function( 6 ) In general, the association between Aspergillus infection and NTM-PD has long been known, but it is not clear whether NTM-PD predisposes individuals to Aspergillus infection or vice-versa ( 17 ). Raats et al. studied the occurrence of Aspergillus isolation in a cohort of patients diagnosed with NTM-PD. During a median follow-up of 46 months after NTM-PD diagnosis, Aspergillus was isolated from at least one respiratory sample in 130/497 patients (26.2%). Inhaled corticosteroid use, a nodular bronchiectatic CT pattern and NTM-PD treatment initiation were more common in patients with isolated Aspergillus than in those without (p-values of 0.01, 0.03 and < 0.001, respectively). In patients who were treated for NTM-LD, most of the isolates were first detected during or after antibiotic therapy (65/92; 70.7%). However, treatment outcomes were not different between the Aspergillus group and the non-Aspergillus group ( 8 ). Although mere colonization does not appear to be critical, the development of CPA is a prognostic factor for mortality in patients with NTM-LD ( 18 , 19 ). Jhun et al. reported a hazard ratio (HR) of 3.49 (CI 2.07–5.88, p < 0.001) in a univariate regression model and an HR of 1.77 (1.01–3.11, p = 0.047) in a multivariate Cox proportional- hazards regression model( 19 ). The evolution from Aspergillus colonization to infection is poorly understood. Risk factors for developing CPA in NTM patients have been studied, but the influence of antimycobacterial treatment itself has not been investigated ( 9 , 18 ) In the case presented here, the patient did not meet the full diagnostic criteria for CPA, invasive aspergillosis (IA), or allergic bronchopulmonary aspergillosis (ABPA). However, the increase in anti-Aspergillus IgG levels was used as a surrogate marker of disease activity. The presence of an Aspergillus bronchitis phenotype of infection was considered, as described in the extant literature, primarily in patients with bronchiectasis( 20 ). Upon subsequent consideration, the clinical response to antifungal therapy ( Fig. 2 ) supported this hypothesis. Moreover, a greater than 50% reduction in Aspergillus-specific IgG titer was attained with antifungal treatment, a criterion for serologic improvement that was endorsed by the majority of experts in a consensus statement on definitions of treatment outcomes in CPA ( 21 ) Hypersensitivity pneumonitis, or allergic alveolitis, has been described as adverse drug reaction in ALIS treatment in 1,8% of patients in the CONVERT open-label extension trial and in single case reports, prompting treatment discontinuation and/or glucocorticoid therapy ( 22 – 25 ). In the case presented here, ground-glass opacities (GGO) – the radiological hallmark of hypersensitivity pneumonitis – may have been attributable to ALIS. However, GGO were transient and remained clinically inapparent. Therefore, no further investigations or treatment modifications were deemed necessary. In summary, Mycobacterium florentinum is an exceedingly rare pathogen causing pulmonary disease in elderly patients and lymphadenitis in children, similar to other NTM species. In the case of M. florentinum- PD presented here, a treatment regimen with ALIS, clofazimine and moxifloxacin was more effective than the combination of azithromycin, ethambutol and rifampicin three times weekly. The specific influence of ALIS treatment on Aspergillus colonization and infection remains to be clarified in future studies. Serial Aspergillus IgG antibodies should be determined prior to and during treatment. Abbreviations AFB acid-fast bacilli ALIS amikacin liposomal inhalation suspension AMK amikacin AST antimicrobial susceptibility testing AZM azithromycin CF cystic fibrosis CFZ clofazimine CLSI Clinical and Laboratory Standards Institute CPA chronic pulmonary aspergillosis CT computed tomography EMB ethambutol GGO ground-glass opacities MAC Mycobacterium avium/intracellulare complex NTM nontuberculous mycobacteria PCR polymerase chain reaction VCZ voriconazole Declarations Consent to participate Written informed consent was obtained from the patient before writing this report. Consent for publication The patient consented to the publication of her personal and clinical details, including medical images. Competing Interests C.L. is supported by the German Center of Infection Research. F.L. and C.L provided consultation service to Insmed, a biopharmaceutical company that produces liposomal amikacin as an inhalative suspension for the treatment of NTM-PD. F.L., S.P. and C.L. received speakers honoraria from this company, outside the scope of this work. Funding This research did not receive any specific funding. Clinical Trial number Not applicable Author Contribution F.L. was responsible for the acquisition of data, the design, composition and writing of the initial manuscript draft, the preparation of Figures 1 and 3, and the preparation of Table 1. S.P. contributed to manuscript writing, conducted and interpreted diagnostic procedures and prepared Additional file 1. A.S.P. analyzed patient-reported clinical outcome data and prepared Figure 2. C.G. made substantial revisions to the manuscript text. C.L. supervised the work and made substantial revisions to its design and manuscript text. All authors provided a critical review of the final manuscript and approved the submitted version. Acknowledgement The authors would like to thank the patient for consenting to the publication of this case report, as well as Dr. Martin Kuhns from the Research Centre Borstel (German Reference Centre for Mycobacteria), who conducted a data query on Mycobacterium florentinum strains. Data Availability The datasets supporting the conclusions of this article are included within the article and its additional file. References Tortoli E, Rindi L, Goh KS, Katila ML, Mariottini A, Mattei R, et al. Mycobacterium florentinum sp. nov., isolated from humans. Int J Syst Evol Microbiol. 2005;55(3):1101–6. 10.1099/ijs.0.63485-0 . Suomalainen S, Koukila-Kähkölä P, Brander E, Katila ML, Piilonen A, Paulin L, et al. Pulmonary infection caused by an unusual, slowly growing nontuberculous mycobacterium. J Clin Microbiol. 2001;39(7). 10.1128/JCM.39.7.2668-2671.2001 . Syed SS, Aderinboye O, Hanson KE, Spitzer ED. Acute Cervical Lymphadenitis Caused by Mycobacterium florentinum . 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A case of drug-induced organizing pneumonia caused by amikacin liposome inhalation suspension. J Infect Chemother. 2023;29(8):806–8. 10.1016/j.jiac.2023.04.013 . Kaneko T, Otoshi R, Sekine A, Baba T, Yamada C, Haga S, et al. Drug-related pneumonitis caused by amikacin liposome inhalation suspension: One pathologically proven case and single-center experience. Respir Investig. 2024;62(4):513–6. 10.1016/j.resinv.2024.04.003 . Loukeri AA, Papathanassiou E, Kavvada A, Kampolis CF, Pantazopoulos I, Moschos C, et al. Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study. Med (B Aires). 2024;60(10):1620. 10.3390/medicina60101620 . Additional Declarations Competing interest reported. C.L. is supported by the German Center of Infection Research. F.L. and C.L provided consultation service to Insmed, a biopharmaceutical company that produces liposomal amikacin as an inhalative suspension for the treatment of NTM-PD. F.L., S.P. and C.L. received speakers honoraria from this company, outside the scope of this work. Supplementary Files M.florentinumM.aviumAST.xlsx Cite Share Download PDF Status: Published Journal Publication published 17 Dec, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 29 Oct, 2025 Reviews received at journal 28 Oct, 2025 Reviews received at journal 28 Oct, 2025 Reviews received at journal 28 Oct, 2025 Reviewers agreed at journal 24 Oct, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviews received at journal 22 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers agreed at journal 21 Oct, 2025 Reviews received at journal 21 Oct, 2025 Reviewers agreed at journal 21 Oct, 2025 Reviewers agreed at journal 21 Oct, 2025 Reviewers agreed at journal 21 Oct, 2025 Reviewers agreed at journal 20 Oct, 2025 Reviewers agreed at journal 20 Oct, 2025 Reviewers agreed at journal 19 Oct, 2025 Reviewers agreed at journal 19 Oct, 2025 Reviewers agreed at journal 09 Oct, 2025 Reviewers invited by journal 09 Oct, 2025 Editor invited by journal 03 Oct, 2025 Editor assigned by journal 01 Oct, 2025 Submission checks completed at journal 01 Oct, 2025 First submitted to journal 27 Sep, 2025 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-7727745\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Case Report\",\"associatedPublications\":[],\"authors\":[{\"id\":533017225,\"identity\":\"c12010df-acc9-413e-8535-4996ea43a77a\",\"order_by\":0,\"name\":\"Fabian Leo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Evangelische Lungenklinik\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Fabian\",\"middleName\":\"\",\"lastName\":\"Leo\",\"suffix\":\"\"},{\"id\":533017226,\"identity\":\"1df9a56c-0a15-48c6-9d35-07f0e113209b\",\"order_by\":1,\"name\":\"Silke 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19:23:36\",\"extension\":\"html\",\"order_by\":14,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":100911,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"earlyproof.html\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/a4c99366de8f313228a1223a.html\"},{\"id\":94137840,\"identity\":\"9294fbbf-5d68-4bc1-95b0-fefb77bcd432\",\"added_by\":\"auto\",\"created_at\":\"2025-10-22 19:23:34\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":845891,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003ea\\u003c/strong\\u003e: CT Thorax scan 12/2018 revealing bronchiectasis predominantly in the left lung (lingula).\\u003cstrong\\u003eb\\u003c/strong\\u003e: Nodules and consolidations consistent with progressive NTM pulmonary disease in 12/2020. \\u003cstrong\\u003ec\\u003c/strong\\u003e: Disease progression under macrolide-based antimicrobial regimen in 01/2022.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/41f4b2a7ec3b02e26504b318.png\"},{\"id\":94137863,\"identity\":\"75fb7bc1-fc9f-4dca-b60c-40b43092af16\",\"added_by\":\"auto\",\"created_at\":\"2025-10-22 19:23:35\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":59398,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eTime course of symptoms under treatment (antimycobacterial therapy from March 2022 until April 2023; antifungal therapy from November 2022 until May 2023). Symptoms were recorded by the patient on a daily basis, using the “NTM Clinical Diary”, developed at the German Center for Infection Research (DZIF).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/d4c7ce0f28e2e939fe98d72b.png\"},{\"id\":94137873,\"identity\":\"8844a1c2-7940-4bce-a990-988df1e71042\",\"added_by\":\"auto\",\"created_at\":\"2025-10-22 19:23:36\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":760192,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003ea.\\u003c/strong\\u003e CT scan after completion of antimicrobial treatment 05/2023. \\u003cstrong\\u003eb.\\u003c/strong\\u003e Ground glass opacities (GGO) in the left upper lobe at 3 months of ALIS-based antimycobacterial treatment. \\u003cstrong\\u003ec. \\u003c/strong\\u003eDecrease of GGO at 7 months after completion of ALIS treatment.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/7b2ad16c72d22a89d63e8234.png\"},{\"id\":98814057,\"identity\":\"60a4d05c-73aa-49eb-9876-2a25a019cbf0\",\"added_by\":\"auto\",\"created_at\":\"2025-12-22 16:10:19\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2828967,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/48c2b130-801d-4a8b-a9c5-f1073b8c26a9.pdf\"},{\"id\":94137823,\"identity\":\"45a86b1c-0616-4bf2-bfcd-7cf35fa09d53\",\"added_by\":\"auto\",\"created_at\":\"2025-10-22 19:23:33\",\"extension\":\"xlsx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":11387,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"M.florentinumM.aviumAST.xlsx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7727745/v1/3732c8d1d345c7d9844b1675.xlsx\"}],\"financialInterests\":\"Competing interest reported. C.L. is supported by the German Center of Infection Research. F.L. and C.L provided consultation service to Insmed, a biopharmaceutical company that produces liposomal amikacin as an inhalative suspension for the treatment of NTM-PD. F.L., S.P. and C.L. received speakers honoraria from this company, outside the scope of this work.\",\"formattedTitle\":\"\\u003cp\\u003e\\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e pulmonary disease: A case report and review of the literature\\u003c/p\\u003e\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003e\\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e was first characterized by Tortoli et al. in 2005 in a case series comprising eight isolates from human samples. It is closely related to \\u003cem\\u003eM. triplex\\u003c/em\\u003e, \\u003cem\\u003eM. lentiflavum\\u003c/em\\u003e and \\u003cem\\u003eM. montefiorense\\u003c/em\\u003e, but is clearly distinguishable by unique 16S rRNA and internal transcribed spacer (ITS) sequences as well as a unique PCR restriction analysis (PRA) pattern of the 65 kDa heat-shock protein-encoding gene (hsp65) (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e). More than half of the isolates were considered clinically relevant infections (four out of six from respiratory samples, and one from cervical lymph node tissue). However, treatment and clinical outcome data were not reported. The authors also identified a previously documented case of NTM lung disease from 2001 as being attributable to a \\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e infection (\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e). The patient was a 67-year-old female from Finland who was diagnosed with nontuberculous mycobacterial pulmonary disease (NTM-PD) with a nodular bronchiectatic radiologic phenotype. Data from antimicrobial susceptibility testing (AST) were not reported. However, the patient was considered clinically cured after 18 months of treatment with clarithromycin, ethambutol, rifampicin and ciprofloxacin. In the following years, only two additional case reports of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e infection have been published in the English-language literature: one in 2010, which detailed a second case of cervical lymphadenitis in a child, and one in 2014, documenting a single case of synovitis in an immunocompromised individual (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e). In the case of cervical lymphadenitis, therapy consisted of complete surgical lymph node excision and no relapse occurred within 12 months of follow-up observation (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). The authors of this report also conducted a data query at a national reference laboratory in the United States (Associated Regional and University Pathologists Laboratories), covering the period between 2006 and 2010. This revealed four additional documented \\u003cem\\u003eM. florentinum\\u003c/em\\u003e isolates: a 76-year-old man (source: bronchial aspirate), a 47-year-old man (sputum), a 5-year-old girl (neck lymph node), and a 46-year-old man (unspecified source). The cases were submitted from different regions in the United States. No information was provided on the clinical relevance of these findings (\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e). Nukui et al. described a case of synovitis in a 65-year-old, immunocompromised patient with a history of systemic lupus erythematosus (SLE), chronic kidney disease and long-term prednisolone therapy. \\u003cem\\u003eM. florentinum\\u003c/em\\u003e was found to be the causative pathogen, and treatment consisted of surgical debridement and antimycobacterial drugs (clarithromycin, rifampicin, and levofloxacin). The patient died unexpectedly after three months from acute aortic dissection (\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e). A synopsis of all cases published to date, with at least basic clinical data and available AST results, is shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. Due to the limited number of cases reported thus far, the most effective treatment regimen remains unclear.\\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\\u003eOverview of clinical Mycobacterium florentinum cases in the English-language literature.\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"14\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c6\\\" colnum=\\\"6\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c7\\\" colnum=\\\"7\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c8\\\" colnum=\\\"8\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c9\\\" colnum=\\\"9\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c10\\\" colnum=\\\"10\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c11\\\" colnum=\\\"11\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c12\\\" colnum=\\\"12\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c13\\\" colnum=\\\"13\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c14\\\" colnum=\\\"14\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eReference/\\u003c/p\\u003e\\u003cp\\u003eyear\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eGender and age (years)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSource\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eClinical presentation\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eCS\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eAMK\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eCIP\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eCLR\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eCFZ\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eEMB\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eMOX\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eLFX\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eRFB\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003eMIC\\u003c/p\\u003e\\u003cp\\u003eRMP\\u003c/p\\u003e\\u003cp\\u003emg/l\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"7\\\" rowspan=\\\"8\\\"\\u003e\\u003cp\\u003e(\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e) / 2005\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 6\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eLymph node\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eLymphadenitis\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e4\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.12\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003e0.25\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e16\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 82\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eEmphysema\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eno\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e0.5\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e128\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.12\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e4\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003e0.06\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e8\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eM, 33\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eStools\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eWeight loss\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eno\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e4\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e128\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003e0.5\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003e0.25\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e4\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 70\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003ePulmonary fibrosis, bronchiectasis\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colspan=\\\"9\\\" morerows=\\\"5\\\" nameend=\\\"c14\\\" namest=\\\"c6\\\" rowspan=\\\"6\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 93\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum, gastric aspirate\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eHemoptysis, fever\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 84\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eHemoptysis, pleurisy\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eno\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eM, 65\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003ePneumonia\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 64\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003ePneumonia\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e(\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) / 2001\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 67\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum, BAL\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eHemoptysis\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) / 2010\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 3\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eLymph 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align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e0.12\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e(\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e) / 2014\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 65\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSynovia (wrist)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eArthritis\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e16\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003e8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003e16\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e4\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eLeo et al.\\u003c/p\\u003e\\u003cp\\u003e2025\\u003c/p\\u003e\\u003cp\\u003e\\u0026dagger;; \\u0026dagger;\\u0026dagger;\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eF, 69\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eSputum\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003ePneumonia, hemoptysis\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003eyes\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c6\\\"\\u003e\\u003cp\\u003e16\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c7\\\"\\u003e\\u003cp\\u003e\\u0026gt;\\u0026thinsp;16\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c8\\\"\\u003e\\u003cp\\u003e1\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c9\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c10\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c11\\\"\\u003e\\u003cp\\u003e\\u0026gt;\\u0026thinsp;8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c12\\\"\\u003e\\u003cp\\u003en/a\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c13\\\"\\u003e\\u003cp\\u003e0.25\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c14\\\"\\u003e\\u003cp\\u003e\\u0026gt;\\u0026thinsp;8\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003ctfoot\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"14\\\"\\u003e\\u003cem\\u003eBasic demographic data, isolation source, clinical presentation, clinical significance and antimicrobial susceptibility testing results of M. florentinum cases reported in the literature, including this case report. F\\u0026thinsp;=\\u0026thinsp;female; M\\u0026thinsp;=\\u0026thinsp;male; CS\\u0026thinsp;=\\u0026thinsp;clinical significance; MIC\\u0026thinsp;=\\u0026thinsp;minimal inhibitory concentration; AMK\\u0026thinsp;=\\u0026thinsp;Amikacin, CIP\\u0026thinsp;=\\u0026thinsp;Ciprofloxacin; CLR\\u0026thinsp;=\\u0026thinsp;Clarithromycin; CFZ\\u0026thinsp;=\\u0026thinsp;Clofazimine; EMB\\u0026thinsp;=\\u0026thinsp;Ethambutol; MOX\\u0026thinsp;=\\u0026thinsp;Moxifloxacin; LFX\\u0026thinsp;=\\u0026thinsp;Levofloxacin; RFB\\u0026thinsp;=\\u0026thinsp;Rifabutin; RMP\\u0026thinsp;=\\u0026thinsp;Rifampicin; n/a: not applicable (not done).\\u003c/em\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"14\\\"\\u003e\\u0026dagger; \\u003cem\\u003eAntimicrobial susceptibility testing (AST) was performed and assessed by broth microdilution method (SensititreTM Myco susceptibility plates SLOMYCOI, Thermo Fisher Diagnostics GmbH, Germany) according to Clinical and Laboratory Standards Institute (CLSI M24Ed2 and M62Ed1 (November 2018 and CLSI M24S Ed2 (February 2023) guideline.\\u003c/em\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd colspan=\\\"14\\\"\\u003e\\u0026dagger;\\u0026dagger; More comprehensive data including repeat AST of isolates during antimycobacterial treatment can be found in Additional file 1 (Supplemental information).\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tfoot\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eAmikacin liposome inhalation suspension (ALIS) is currently approved for the treatment of pulmonary infection caused by nontuberculous mycobacteria belonging to the \\u003cem\\u003eMycobacterium avium\\u003c/em\\u003e/\\u003cem\\u003eintracellulare\\u003c/em\\u003e complex (MAC). There is little experience with the use of ALIS in less frequent NTM species. The use of systemic or inhaled antibiotics has been related to an increase in airway colonization with \\u003cem\\u003eAspergillus spp\\u003c/em\\u003e. in patients with cystic fibrosis (CF), non-CF bronchiectasis and NTM-PD (\\u003cspan additionalcitationids=\\\"CR6 CR7\\\" citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). In patients with NTM-PD, the development of chronic pulmonary aspergillosis (CPA) is a prognostic factor for mortality (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e). Owing to the many common symptoms and radiological features of NTM-PD and CPA, distinguishing between colonization and clinically relevant aspergillosis may be difficult. The specific impact of ALIS on \\u003cem\\u003eAspergillus spp.\\u003c/em\\u003e colonization and development of CPA has not been studied(\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eThe objective of this report is to describe a very rare case of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e pulmonary disease with a view to its management utilizing an ALIS-based antibiotic regimen and close attention to possible adverse effects, including the emergence of fungal coinfection.\\u003c/p\\u003e\"},{\"header\":\"Case presentation\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e\\n\\u003ch2\\u003eNTM-PD diagnosis and clinical course before ALIS treatment\\u003c/h2\\u003e\\n\\u003cp\\u003eIn December 2018, a 69-year-old female patient (163 cm, 53 kg) was first referred to our clinic for refractory pneumonia. She reported chronic cough and weight loss (6 kg in 12 months). Chest computed tomography (CT) revealed bronchiectasis and peribronchial consolidation focused in the middle lobe, lingula, and left lower lobe (\\u003cstrong\\u003eFig.\\u0026nbsp;1a\\u003c/strong\\u003e). C-reactive peptide, blood leucocytes, eosinophils, alpha1-antitrypsin and immunoglobulins IgA, IgE, IgG and IgM were within the respective reference ranges, whereas anti-Aspergillus-IgG was marginally elevated (ELISA 63 U/ml, reference\\u0026thinsp;\\u0026lt;\\u0026thinsp;50 U/ml, Serion Diagnostics GmbH, Wuerzburg, Germany). Bronchoalveolar lavage (BAL) revealed 95% neutrophils and evidence of \\u003cem\\u003eStaphylococcus aureus\\u003c/em\\u003e (MSSA [10\\u003csup\\u003e2\\u003c/sup\\u003e/ml]), which was treated with ampicillin/sulbactam for 14 days. Acid fast bacilli (AFB) remained undetectable by microscopy of auramine-stained BAL fluid and in three sputum samples, whereas cultures from BAL fluid and two sputum samples each grew \\u003cem\\u003eM. florentinum\\u003c/em\\u003e. In 02/2019, symptoms and radiologic findings improved, and the patient was managed with sodium saline inhalation and physical therapy using via a Flutter\\u0026trade; device. During a 24- month period of \\u0026ldquo;watchful waiting\\u0026rdquo;, specific antimycobacterial treatment was withheld according to the patient\\u0026rsquo;s informed preference. Sputum cultures grew \\u003cem\\u003eM. florentinum\\u003c/em\\u003e again in 12/2019, and \\u003cem\\u003eM. avium\\u003c/em\\u003e grew in 12/2020. Both isolates showed in- vitro susceptibility to clarithromycin. In 12/2020, the patient reported frequent hemoptysis, and CT imaging showed increasing nodules and consolidations in the right upper lobe, middle lobe and left lower lobe (\\u003cstrong\\u003eFig.\\u0026nbsp;1b\\u003c/strong\\u003e) In 02/2021, antimycobacterial treatment was started, using a regimen of azithromycin (AZM), ethambutol (EMB) and rifampicin (RMP) three times weekly. In 04/2021, sputum culture for mycobacteria was negative, but became positive again in 06/2021 and 08/2021, with molecular species differentiation revealing \\u003cem\\u003eM. florentinum\\u003c/em\\u003e once more, but not \\u003cem\\u003eM. avium\\u003c/em\\u003e. Treatment was continued because the patient was considered to benefit from therapy from a clinical perspective. However, sputum microscopy detected AFB for the first time in 10/2021, and cultures grew \\u003cem\\u003eM. florentinum\\u003c/em\\u003e again. Repeat in- vitro drug susceptibility testing excluded the development of macrolide resistance. The minimal inhibitory concentration (MIC) for Amikacin (AMK) was 16 mg/l, which corresponds to susceptibility according to the Clinical and Laboratory Standards Institute (CLSI) definition (see \\u003cstrong\\u003eAdditional file 1\\u003c/strong\\u003e).\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003ch3\\u003eALIS treatment initiation, clinical course and outcome\\u003c/h3\\u003e\\n\\u003cp\\u003eIn 01/2022, CT imaging revealed progressive consolidation in the right upper lobe (segment 2) and progressive bronchiolitis in the inferior lower lobes and middle lobe (Fig.\\u0026nbsp;1c). In 03/2022 (=\\u0026thinsp;month 0), the treatment was switched to ALIS 590 mg/d by inhalation, clofazimine 100 mg/d orally and moxifloxacin 400 mg/d orally. With this regimen, culture conversion was documented in 04/2022 (month\\u0026thinsp;+\\u0026thinsp;1), and follow-up CT showed improvement in 06/2022 (month\\u0026thinsp;+\\u0026thinsp;3). In 09/2022 (month\\u0026thinsp;+\\u0026thinsp;6), the patient described increasing cough and sputum, while CT showed a mixed response, and mycobacterial cultures remained negative. Proof of \\u003cem\\u003eAspergillus fumigatus\\u003c/em\\u003e in sputum samples and a\\u0026thinsp;\\u0026gt;\\u0026thinsp;3-fold rise in Aspergillus-IgG serum antibody (207 U/ml) prompted antifungal treatment with oral voriconazole (VCZ) in 11/2022 (month\\u0026thinsp;+\\u0026thinsp;8). Therapeutic drug monitoring was performed during treatment, and all VCZ trough levels were within the therapeutic range (1\\u0026ndash;5 mg/l). The patient\\u0026acute;s clinical status improved gradually, as indicated by changes in body weight, cough, fatigue, and other factors (\\u003cstrong\\u003eFig.\\u0026nbsp;2)\\u003c/strong\\u003e. Antimycobacterial treatment was terminated in 04/2023 (month\\u0026thinsp;+\\u0026thinsp;13, 12 months after sputum conversion), and VCZ was continued until 05/2023 (treatment duration of 6 months). Chest CT at the end of treatment showed radiological improvement (\\u003cstrong\\u003eFig.\\u0026nbsp;3a\\u003c/strong\\u003e). During follow-up, sustained sputum conversion was documented until the last contact with the patient in 03/2025 (month\\u0026thinsp;+\\u0026thinsp;36, 23 months after the end of treatment). The level of anti-Aspergillus-Ig G antibody decreased to 138 U/ml at the conclusion of VCZ treatment and to 98 U/ml at six months thereafter. Twenty-two months after completing VCZ treatment, the level Anti-Aspergillus-IgG was \\u0026lt;\\u0026thinsp;50 U/ml. Follow-up sputum samples exploring respiratory pathogens other than mycobacteria revealed \\u003cem\\u003eS. aureus\\u003c/em\\u003e, \\u003cem\\u003eEnterobacteriaceae\\u003c/em\\u003e and \\u003cem\\u003eScedosporium spp\\u003c/em\\u003e. and two episodes of antibiotic treatment for bronchiectasis exacerbation were necessary during nearly two years of follow-up.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003ch3\\u003eAdverse events during ALIS treatment\\u003c/h3\\u003e\\n\\u003cp\\u003eFrom the beginning of ALIS therapy, the patient reported variable dry cough and dysphonia related to inhalation. These symptoms were tolerable throughout the entire treatment course, without the need for discontinuation of the inhalations. Chest CT imaging at month\\u0026thinsp;+\\u0026thinsp;3 revealed ground glass opacities (GGO) in the upper lobes bilaterally and in segments 6 and 9 of the right lung. At month\\u0026thinsp;+\\u0026thinsp;6, the GGO decreased slightly, but at month\\u0026thinsp;+\\u0026thinsp;12, new GGO emerged in the right upper lobe and left upper and lower lobes (\\u003cstrong\\u003eFig.\\u0026nbsp;3b\\u003c/strong\\u003e). At month\\u0026thinsp;+\\u0026thinsp;20, seven months after the end of ALIS treatment, the extent of GGO was markedly decreased (\\u003cstrong\\u003eFig.\\u0026nbsp;3c\\u003c/strong\\u003e).\\u003c/p\\u003e\\n\\u003ch3\\u003eData query\\u003c/h3\\u003e\\n\\u003cp\\u003eA data query at the German National Reference Centre for Mycobacteria (Research Center Borstel) was conducted. No other strains of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e were identified during the period from January 2018 to April 2025.\\u003c/p\\u003e\"},{\"header\":\"Discussion and conclusions\",\"content\":\"\\u003cp\\u003eThis case of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e pulmonary disease (\\u003cem\\u003eM. florentinum\\u003c/em\\u003e-PD) is only the second documented case that provides detailed data on treatment and clinical outcomes. The other, by Suomalainen et. al in 2001, predates the classification of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e as an independent species. Initially, it was considered a subspecies of the closely related \\u003cem\\u003eM. triplex\\u003c/em\\u003e taxon. A substantial case series pertaining to \\u003cem\\u003eM. triplex\\u003c/em\\u003e pulmonary disease from Australia was published in 2019(\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). The collection was composed of 39 cases, with a significant portion (approximately 45%) meeting the criteria for NTM-PD(\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e). The AST results obtained for 14 isolates revealed that 93% were susceptible to macrolides. However, only six patients with pulmonary infection received antimicrobial therapy (including azithromycin or clarithromycin), with five patients demonstrating treatment success (\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e). In conjunction with the existing data on AST for \\u003cem\\u003eM. florentinum\\u003c/em\\u003e (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e), these findings support the selection of a macrolide-based combination as an initial therapy for the treatment of \\u003cem\\u003eM. florentinum\\u003c/em\\u003e pulmonary disease.\\u003c/p\\u003e\\u003cp\\u003eAmikacin liposomal inhalation suspension (ALIS) has the potential to serve as an ancillary option for patients who are difficult to treat, e.g. due to poor tolerability of oral drugs, or in cases where first-line therapy has failed. In addition to its in-label use for MAC-PD, ALIS was reported to be effective in CF bronchiectasis and non-CF bronchiectasis patients with \\u003cem\\u003eM. abscessus\\u003c/em\\u003e infection (\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e). In the case of the \\u003cem\\u003eM. florentinum\\u003c/em\\u003e-PD presented here, an ALIS-based treatment resulted in rapid culture conversion and microbiological and clinical cure as defined by the NTMnet group consensus (\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eRemarkably, the MIC for amikacin was higher in this case than in the other \\u003cem\\u003eM. florentinum\\u003c/em\\u003e strains reported in the literature. However, compared with conventional parenteral or inhaled amikacin, the use of ALIS results in higher concentrations of amikacin in macrophages, lung tissue and biofilms, potentially enhancing its efficacy against mycobacteria (\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e) Furthermore, in- vitro data across different NTM species suggest antimycobacterial synergy between amikacin and clofazimine, which was also part of the treatment regimen(\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e).\\u003c/p\\u003e\\u003cp\\u003eInhaled antibiotics may promote airway colonization by \\u003cem\\u003eAspergillus fumigatus\\u003c/em\\u003e and other fungi. Insights are available from studies of CF -bronchiectasis: Microbiological data from two randomized, controlled trials studying inhaled tobramycin vs. placebo showed that isolation of \\u003cem\\u003eAspergillus\\u003c/em\\u003e and \\u003cem\\u003eCandida\\u003c/em\\u003e was increased in the tobramycin group but did not affect the outcome(\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e). In a more recent cohort of CF patients from Sweden, the use of inhaled antibiotics was also associated with \\u003cem\\u003eA. fumigatus\\u003c/em\\u003e colonization (adjusted OR 3.1, 95% CI 1.6\\u0026ndash;5.9, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05) but not with adverse effects on lung function(\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e)\\u003c/p\\u003e\\u003cp\\u003eIn general, the association between Aspergillus infection and NTM-PD has long been known, but it is not clear whether NTM-PD predisposes individuals to Aspergillus infection or vice-versa (\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e). Raats et al. studied the occurrence of Aspergillus isolation in a cohort of patients diagnosed with NTM-PD. During a median follow-up of 46 months after NTM-PD diagnosis, Aspergillus was isolated from at least one respiratory sample in 130/497 patients (26.2%). Inhaled corticosteroid use, a nodular bronchiectatic CT pattern and NTM-PD treatment initiation were more common in patients with isolated Aspergillus than in those without (p-values of 0.01, 0.03 and \\u0026lt;\\u0026thinsp;0.001, respectively). In patients who were treated for NTM-LD, most of the isolates were first detected during or after antibiotic therapy (65/92; 70.7%). However, treatment outcomes were not different between the Aspergillus group and the non-Aspergillus group (\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e). Although mere colonization does not appear to be critical, the development of CPA is a prognostic factor for mortality in patients with NTM-LD (\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e). Jhun et al. reported a hazard ratio (HR) of 3.49 (CI 2.07\\u0026ndash;5.88, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001) in a univariate regression model and an HR of 1.77 (1.01\\u0026ndash;3.11, p\\u0026thinsp;=\\u0026thinsp;0.047) in a multivariate Cox proportional- hazards regression model(\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e). The evolution from Aspergillus colonization to infection is poorly understood. Risk factors for developing CPA in NTM patients have been studied, but the influence of antimycobacterial treatment itself has not been investigated (\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e)\\u003c/p\\u003e\\u003cp\\u003eIn the case presented here, the patient did not meet the full diagnostic criteria for CPA, invasive aspergillosis (IA), or allergic bronchopulmonary aspergillosis (ABPA). However, the increase in anti-Aspergillus IgG levels was used as a surrogate marker of disease activity. The presence of an Aspergillus bronchitis phenotype of infection was considered, as described in the extant literature, primarily in patients with bronchiectasis(\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e). Upon subsequent consideration, the clinical response to antifungal therapy (\\u003cb\\u003eFig.\\u0026nbsp;2\\u003c/b\\u003e) supported this hypothesis. Moreover, a greater than 50% reduction in Aspergillus-specific IgG titer was attained with antifungal treatment, a criterion for serologic improvement that was endorsed by the majority of experts in a consensus statement on definitions of treatment outcomes in CPA (\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e)\\u003c/p\\u003e\\u003cp\\u003eHypersensitivity pneumonitis, or allergic alveolitis, has been described as adverse drug reaction in ALIS treatment in 1,8% of patients in the CONVERT open-label extension trial and in single case reports, prompting treatment discontinuation and/or glucocorticoid therapy (\\u003cspan additionalcitationids=\\\"CR23 CR24\\\" citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e). In the case presented here, ground-glass opacities (GGO) \\u0026ndash; the radiological hallmark of hypersensitivity pneumonitis \\u0026ndash; may have been attributable to ALIS. However, GGO were transient and remained clinically inapparent. Therefore, no further investigations or treatment modifications were deemed necessary.\\u003c/p\\u003e\\u003cp\\u003eIn summary, \\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e is an exceedingly rare pathogen causing pulmonary disease in elderly patients and lymphadenitis in children, similar to other NTM species. In the case of \\u003cem\\u003eM. florentinum-\\u003c/em\\u003ePD presented here, a treatment regimen with ALIS, clofazimine and moxifloxacin was more effective than the combination of azithromycin, ethambutol and rifampicin three times weekly. The specific influence of ALIS treatment on Aspergillus colonization and infection remains to be clarified in future studies. Serial Aspergillus IgG antibodies should be determined prior to and during treatment.\\u003c/p\\u003e\"},{\"header\":\"Abbreviations\",\"content\":\"\\u003cdiv class=\\\"DefinitionList\\\"\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAFB\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eacid-fast bacilli\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eALIS\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eamikacin liposomal inhalation suspension\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAMK\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eamikacin\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAST\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eantimicrobial susceptibility testing\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eAZM\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eazithromycin\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCF\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003ecystic fibrosis\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCFZ\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eclofazimine\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCLSI\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eClinical and Laboratory Standards Institute\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eCPA\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003echronic pulmonary aspergillosis\\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\\\"\\u003eEMB\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eethambutol\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eGGO\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eground-glass opacities\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eMAC\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003eMycobacterium avium/intracellulare complex\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eNTM\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003enontuberculous mycobacteria\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003ePCR\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003epolymerase chain reaction\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003cdiv class=\\\"DefinitionListEntry\\\"\\u003e\\u003cdiv class=\\\"Term\\\"\\u003eVCZ\\u003c/div\\u003e\\u003cdiv class=\\\"Description\\\"\\u003e\\u003cp\\u003evoriconazole\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\\u003c/div\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eConsent to participate\\u003c/strong\\u003e\\u003cp\\u003eWritten informed consent was obtained from the patient before writing this report.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003cp\\u003eThe patient consented to the publication of her personal and clinical details, including medical images.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eCompeting Interests\\u003c/strong\\u003e\\u003cp\\u003eC.L. is supported by the German Center of Infection Research. F.L. and C.L provided consultation service to Insmed, a biopharmaceutical company that produces liposomal amikacin as an inhalative suspension for the treatment of NTM-PD. F.L., S.P. and C.L. received speakers honoraria from this company, outside the scope of this work.\\u003c/p\\u003e\\u003c/p\\u003e\\u003ch2\\u003eFunding\\u003c/h2\\u003e\\u003cp\\u003eThis research did not receive any specific funding.\\u003c/p\\u003e\\u003cp\\u003eClinical Trial number\\u003c/p\\u003e\\u003cp\\u003eNot applicable\\u003c/p\\u003e\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eF.L. was responsible for the acquisition of data, the design, composition and writing of the initial manuscript draft, the preparation of Figures 1 and 3, and the preparation of Table 1. S.P. contributed to manuscript writing, conducted and interpreted diagnostic procedures and prepared Additional file 1. A.S.P. analyzed patient-reported clinical outcome data and prepared Figure 2. C.G. made substantial revisions to the manuscript text. C.L. supervised the work and made substantial revisions to its design and manuscript text. All authors provided a critical review of the final manuscript and approved the submitted version.\\u003c/p\\u003e\\u003ch2\\u003eAcknowledgement\\u003c/h2\\u003e\\u003cp\\u003eThe authors would like to thank the patient for consenting to the publication of this case report, as well as Dr. Martin Kuhns from the Research Centre Borstel (German Reference Centre for Mycobacteria), who conducted a data query on Mycobacterium florentinum strains.\\u003c/p\\u003e\\u003ch2\\u003eData Availability\\u003c/h2\\u003e\\u003cp\\u003eThe datasets supporting the conclusions of this article are included within the article and its additional file.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eTortoli E, Rindi L, Goh KS, Katila ML, Mariottini A, Mattei R, et al. 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Eur Respir J. 2022;59(6):2102950. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1183/13993003.02950-2021\\u003c/span\\u003e\\u003cspan address=\\\"10.1183/13993003.02950-2021\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eWinthrop KL, Flume PA, Thomson R, Mange KC, Yuen DW, Ciesielska M, et al. Amikacin Liposome Inhalation Suspension for \\u003cem\\u003eMycobacterium avium\\u003c/em\\u003e Complex Lung Disease: A 12-Month Open-Label Extension Clinical Trial. 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J Infect Chemother. 2023;29(8):806\\u0026ndash;8. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.jiac.2023.04.013\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.jiac.2023.04.013\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eKaneko T, Otoshi R, Sekine A, Baba T, Yamada C, Haga S, et al. Drug-related pneumonitis caused by amikacin liposome inhalation suspension: One pathologically proven case and single-center experience. Respir Investig. 2024;62(4):513\\u0026ndash;6. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.resinv.2024.04.003\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.resinv.2024.04.003\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003cli\\u003e\\u003cspan\\u003eLoukeri AA, Papathanassiou E, Kavvada A, Kampolis CF, Pantazopoulos I, Moschos C, et al. Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study. Med (B Aires). 2024;60(10):1620. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/medicina60101620\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/medicina60101620\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\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\":\"info@researchsquare.com\",\"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\":\"Nontuberculous mycobacteria, Mycobacterium florentinum, Pulmonary aspergillosis, Aspergillus fumigatus, Amikacin, Inhalation Drug Administration\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7727745/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7727745/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFollowing the initial description of \\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e in 2005, very few clinical cases have been reported and the optimal antimicrobial treatment and clinical outcomes are uncertain. Amikacin liposomal inhalation suspension (ALIS) has received approval for the treatment of \\u003cem\\u003eMycobacterium avium/intracellulare complex\\u003c/em\\u003e (MAC) pulmonary disease. However, there is little experience with its use for infections caused by less common nontuberculous mycobacteria (NTM). Moreover, the awareness of uncommon adverse effects is still limited.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCase presentation:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA 69-year-old female patient suffering from nodular bronchiectatic \\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e pulmonary disease was treated with azithromycin, ethambutol, and rifampicin, administered three times per week. After 13 months, owing to treatment failure, the therapy was changed to ALIS, moxifloxacin, and clofazimine. This resulted in rapid and sustained culture conversion. Concurrently, the patient exhibited increased cough and sputum, which was consistent with a clinical diagnosis of aspergillosis, as confirmed by evidence of \\u003cem\\u003eAspergillus fumigatus\\u003c/em\\u003e in respiratory specimens and a significant increase in serum anti-Aspergillus IgG antibody levels. Following a six-month course of antifungal therapy, a marked improvement in the patient's symptoms was observed.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAs with MAC pulmonary disease, combination antimicrobial therapy including ALIS was successful in a patient affected by a difficult-to-treat pulmonary infection caused by \\u003cem\\u003eMycobacterium florentinum\\u003c/em\\u003e, a rare NTM pathogen. Combination antibiotic treatment including ALIS may also be considered for difficult-to-treat non-MAC NTM- pulmonary diseases, when based on the results of \\u003cem\\u003ein-vitro\\u003c/em\\u003e drug-susceptibility testing.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Mycobacterium florentinum pulmonary disease: A case report and review of the literature\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-10-22 19:23:25\",\"doi\":\"10.21203/rs.3.rs-7727745/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision 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