Clinical outcomes in Mycobacterium xenopi versus Mycobacterium avium complex pulmonary disease: A retrospective matched cohort study

Zaheen, Ahmad; Hirama, Takashi; Mehrabi, Mahtab; Brode, Sarah K.; Marras, Theodore K.

doi:10.1016/j.rmed.2020.105967

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…Among LTX recipients who grew NTM species (Table 1), concomitant infection with Aspergillus was found in 9.8% (6/61) and Pseudomonas in 8.2% (5/61). Co-isolation with Aspergillus or Pseudomonas was found in 10%-15% of non-transplant populations with NTM-PD in Ontario 16,22 and more seen in alloHCT populations. 23 Given that co-isolation of NTM species with Pseudomonas is associated with worsened lung function and disease severity in noncystic fibrosis bronchiectasis, 24 pulmonary infection from multiple opportunistic organisms could be related to further decline in lung function among LTX recipients, resulting in poorer outcomes.…”

Section: Discussionmentioning

confidence: 96%

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients

Hirama

Singer

Brode

et al. 2021

Transplant Infectious Dis

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Background: Lung transplant (LTX) recipients are at risk miscellaneous infections, among whom the clinical significance of nontuberculous mycobacteria (NTM) is increasingly recognized. Despite anti-mycobacterial therapy becoming standardized worldwide, there is a lack of data on treatment outcomes in LTX recipients who develop NTM-pulmonary disease (PD). We aimed to review the treatment outcomes of NTM-PD among LTX recipients in our center. Methods: Patients who underwent LTX from January 2013 to December 2014 were consecutively enrolled in the retrospective cohort, with follow-up of data retrieved to December 2017. Clinical and radiological improvement and culture conversion after anti-mycobacterial therapy were reviewed in those who developed post-transplant NTM-PD. Results: Sixteen of 230 LTX recipients developed post-transplant NTM-PD. Ten of 16 patients with post-transplant NTM-PD were treated with macrolide-containing anti-mycobacterial therapy, leading to clinical improvement in 5/10 (50%), radiological improvement in 5/10 (50%) and culture conversion in 6/10 (60%) patients. Conclusion:Anti-mycobacterial therapy may relieve pulmonary symptoms and reduce microbial load among individuals with post-transplant NTM-PD. K E Y W O R D Slung transplant (LTX), Mycobacterium avium (MAC), nontuberculous mycobacteria (NTM), respiratory infection, treatment outcome future study. Third, we were also unable to address, in patients with a history of NTM-PD pre-or peri-operatively who were diagnosed with the same species of NTM-PD post-operatively, whether the disease was relapsing with the same strain or a re-infection with a new environmental strain. This issue is further complicated by the large proportion of patients with polyclonal infections in cohorts of patients with NTM-PD. 27 Because of a lack of genotypic analyses in large numbers of specimens from each patient we are unable to address this complex issue.To sum up, treatment outcomes of post-transplant NTM-PD after anti-mycobacterial therapy were reviewed in a large LTX center. A small fraction of LTX recipients developed post-transplant NTM-PD, of whom two third required macrolide-containing antimycobacterial therapy, resulting in clinical and radiological improvement and culture conversion in half patients. It appears that initiating anti-mycobacterial therapy leads to microbiologically favorable outcomes in patients with NTM-PD post-lung transplantation, but larger investigations are required to improve our understanding of this challenging clinical problem and its management. | E THIC AL CONS IDER ATIONThe study protocol (Research Ethics Board # 18-5209) was reviewed by Institutional Review Board of University Health Network. The requirement of informed consent was waived in consideration of the retrospective design.

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Section: Discussionmentioning

confidence: 96%

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients

Hirama

Singer

Brode

et al. 2021

Transplant Infectious Dis

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“…In human medicine, M. xenopi is associated with the highest mortality among pulmonary nontuberculous mycobacterial (NTM) infections and is the second most commonly isolated NTM species responsible for pulmonary infection, behind M. avium complex [ 22 ]. A predisposing factor is immunosuppression, either local (lung disease) or systemic (lymphoproliferative malignancy, immunosuppressive therapy, or HIV infection) [ 3 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Mycobacteriosis in a Pet Ferret (Mustela putorius furo) Caused by Mycobacterium xenopi: A Case Report on Neglected Risk of Zoonotic Transmission

Mihaljević,

Reil,

Habuš

et al. 2024

Pathogens

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Ferrets are highly susceptible to a wide range of mycobacteria, mainly M. bovis, M. avium, and M. triplex. Therefore, ferrets pose a risk of transmission of mycobacteriosis, especially zoonotically relevant tuberculosis. The aim of this study was to describe the findings of M. xenopi mycobacteriosis in a pet ferret and emphasize its zoonotic potential. A pet ferret had a history of weight loss, apathy, hyporexia, and hair loss. Abdominal ultrasound revealed splenomegaly with two solid masses and cystic lesions of the liver. Fine-needle aspiration cytology revealed numerous acid-fast bacilli in epithelioid cells, thus leading to the suspicion of mycobacterial infection. Because of its poor general condition, the ferret was euthanized. Necropsy examination revealed generalized granulomatous lymphadenitis, pneumonia, myocarditis, splenitis, and hepatitis. Histologically, in all organs, there were multifocal to coalescing areas of inflammatory infiltration composed of epithelioid macrophages, a low number of lymphocytes, and plasma cells, without necrosis nor multinucleated giant cells. Ziehl–Neelsen staining detected the presence of numerous (multibacillary) acid-fast bacteria, which were PCR-typed as M. xenopi. This is the first study showing the antimicrobial susceptibility testing of M. xenopi in veterinary medicine, describing the resistance to doxycycline. Overall, our results could facilitate further diagnosis and provide guidelines for the treatment protocols for such infections.

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“…In the US, Mycobacterium avium complex (MAC) infections are quite prevalent among older women [ 45 ] and are typically a challenge to treat with antibiotics [ 46 , 47 ]. Other NTM pathogens are less common, including Mycobacterium xenopi , Mycobacterium chimera , Mycobacterium chelonae , and Mycobacterium kansasii , but can be difficult to treat as well [ 48 , 49 ]. Phages have been used to treat a small number of patients with some of these but, like M. abscessus , these strains typically show strong variations in phage susceptibility and require personalization.…”

Section: Prospects For Phage Therapy Of Mycobacterium ...mentioning

confidence: 99%

Phage Therapy for Nontuberculous Mycobacteria: Challenges and Opportunities

Hatfull

2022

Pulm Ther

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Non-tuberculous mycobacterium (NTM) infections are often clinically challenging, with lengthy antibiotic regimens that fail to resolve the infections with few good outcomes remaining. Mycobacteriophages-viruses that infect Mycobacterium hosts-show promise as therapeutic agents for NTM infections and have been used in 20 compassionate use cases. Favorable outcomes were observed in many but not all cases, although the phages show exceptional safety profiles and no evidence of phage resistance was observed, even when only a single phage was administered. Phage-specific antibodies are commonly present following intravenous administration and are often neutralizing for the phage in vitro. However, phage neutralization does not consistently correlate with poor treatment outcomes and may not be a therapeutic limitation in all patients, even when immunocompetent. Currently, the therapeutic potential of phages is substantially limited by the great variation in phage susceptibility and a relatively small repertoire of therapeutically useful phages. As many as 45% of clinical isolates can have a smooth colony morphotype, and phages that both efficiently infect and kill these strains have yet to be described. In contrast, * 75% of rough strains are susceptible to and killed by one or more phages and therapeutic options can be considered on a compassionate use basis. Although therapies must currently be personalized, elucidating the determinants of phage host specificity, expanding the useful phage repertoire, and identifying the key determinants of clinical outcomes will reveal their full therapeutic potential.

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Clinical outcomes in Mycobacterium xenopi versus Mycobacterium avium complex pulmonary disease: A retrospective matched cohort study

Cited by 13 publications

References 15 publications

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients

Mycobacteriosis in a Pet Ferret (Mustela putorius furo) Caused by Mycobacterium xenopi: A Case Report on Neglected Risk of Zoonotic Transmission

Phage Therapy for Nontuberculous Mycobacteria: Challenges and Opportunities

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