Coinfection of Mycobacterium malmoense and Mycobacterium chimaera in a kidney transplant recipient: A case report and review of the literature.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in soil and water. Solid organ recipients are at increased risk of NTM infections due to impaired immunity. Although the NTM infections rate is low, it increases morbidity and the risk of mortality. Diagnosis is often delayed because of the lack of specific clinical symptoms and requires a high index of suspicion. Management may be challenging: long-term treatment with risks of side effects and interactions with immunosuppressive regimen; reduction of immunosuppression; and risk of allograft rejection. Prognosis is widely variable. We report the first case of Mycobacterium malmoense chest infection with concomitant Mycobacterium chimaera urinary tract infection in a kidney transplant recipient. The evolution was marked by poor tolerance of the treatment with severe adverse events and disabled functional status.

Isolated mediastinal lymphadenitis caused by Mycobacterium malmoense in an immunocompromised child.

Mycobacterium malmoense is a nontuberculous mycobacteria (NTM), that is uncommon in areas other than Northern Europe. We describe the case of mediastinal lymphadenitis caused by M. malmoense in a 4-year-old boy who has a past medical history of disseminated Bacille de Calmette et Guérin (BCG) infection. He presented with persistent high fever and computed tomography revealed mediastinal lymphadenopathy. We identified M. malmoense by hsp65 gene analysis from a lymph node biopsy sample. We treated him with rifampicin, ethambutol and clarithromycin with reference to the guidelines of the British Thoracic Society. M. malmoense can cause severe infections including mediastinal lymphadenitis in children with susceptibility to acid-fast bacteria (AFB).

Tenosynovitis caused by Mycobacterium malmoense in two kidney transplant recipients and review of the literature.

We report two unrelated cases of tenosynovitis caused by Mycobacterium malmoense in kidney transplant recipients. Both patients received immunosuppression and were referred to our tertiary hospital because of persisting complaints lasting >6 months not responding to corticosteroids or surgery. The mycobacterial cultures were positive for the slow-growing M. malmoense after several weeks of incubation. The patient in Case 1 was treated with a combination of surgical debridement and antibiotics, whereas the patient in Case 2 was only treated surgically. Both cases illustrate the doctor's delay in diagnosing mycobacterial infections, and remind us that nontuberculous mycobacterial infections should be part of the differential diagnosis of tenosynovitis, especially in immunocompromised patients.

Pulmonary Infection Caused by Mycobacterium malmoense and the Difficulties in Distinguishing It From the Pulmonary Mycobacterium tuberculosis Infection.

Mycobacterium malmoense is a rare species of non-tuberculosis mycobacteria detected in Japan that causes pulmonary infection and cervical lymphadenitis. Here, we report a case of pulmonary infection caused by M. malmoense, which was difficult to distinguish from Mycobacterium tuberculosis (Mtb) infection. A 64-year-old Japanese woman with a history of pulmonary tuberculosis had bloody phlegm, a cough, and discomfort in her chest. Chest computed tomography revealed a cavity, infiltration, and a nodule. A smear test for acid-fast bacilli was positive, a Mycobacterium avium complex transcription reverse-transcription concerted (TRC) test was negative, and an Mtb TRC test was withheld because the internal control was negative. After diluting the specimens, the internal control tested positive, and the sample tested negative. We diagnosed pulmonary M. malmoense infection based on a culture test. In conclusion, attention should be paid to the concentration of bacteria in Mtb TRC test samples, ensuring that the internal control provides expected results.

Clinical spectrum and relevance of Mycobacterium malmoense: Systematic review and meta-analysis of 859 patients.

INTRODUCTION: The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium. METHODS: A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed. RESULTS: One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively). CONCLUSION: In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.

Treatment of the Less Common Nontuberculous Mycobacterial Pulmonary Disease.

Nontuberculous mycobacterial pulmonary disease caused by the less common nontuberculous mycobacteria have distinct features depending on the species. Diagnostic evaluation follows the established criteria for all nontuberculous mycobacteria, but with certain qualifications given species-specific and regional differences in pathogenicity. Clinicians should first institute nonpharmacologic management and evaluate clinical, radiologic, and microbiologic factors in the decision regarding antimycobacterial therapy. Treatment is challenging, and evidence-based recommendations are limited for most species. Drug susceptibility testing is used to help with regimen selection; however, this approach is imperfect given the uncertain correlation between in vitro activity and clinical response for most drugs.

Novel and rare species of nontuberculous mycobacteria by Hsp-65 gene sequencing.

Background: Nontuberculosis mycobacterium (NTM) is the emerging group of organisms being recognized as etiological agents for diverse clinical conditions such as lymphadenitis, cutaneous, and pulmonary or disseminated lesions. Diverse background patients can acquire these infections such as immunocompetent, immunocompromised patients, or postoperative settings. Rapid addition of newer strains to this group necessitates heightened suspicion in the clinical settings. Specific requirements for cultures, biochemical testing, and molecular methods are needed to diagnose these organisms. Methods: The prospective study conducted at Nizam's Institute of Medical Sciences from January 2019 to December 2021 using various clinical samples using molecular techniques such as line probe assay and hsp-65 gene sequencing to discover new NTM species. The management is challenging since it requires prolonged treatment, multiple drugs, drug resistance, and individualization of treatment in the combination of surgery if needed. In this article, we describe three different NTM species which were not reported in India and highlight to consider these organisms in adequate clinical situation. Results: Mycobacterium iranicum is a rare strain with quick growth and scotochromogenic colonies that are orange-colored. Eight distinct strains were discovered in clinical samples from six different countries: Two each from Iran, Italy, Greece, the Netherlands, Sweden, and the United States. Two of the strains were recovered from cerebrospinal fluid, which is unusual. Mycobacterium species AW6 is an unidentified and unclassified Mycobacterium according to NCBI taxonomy. Mycobacteria malmoense has been linked to lymphadenitis, notably cervical adenitis in children, and pulmonary infection in the majority of cases. Using Line Probe Assay and hsp-65 gene sequencing, novel and uncommon species of NTM were detected from a clinical samples, including sputum and tissue. Conclusion: We report three unusual species of NTMs: M. iranicum, M. species-AW6, and M. malmoense for the first time in India. Novel and rare emerging species of NTMs need to be considered in diverse clinical situations for appropriate therapy and good clinical outcomes.

A refractory tenosynovitis of the wrist: a case report.

BACKGROUND: Mycobacterium malmoense is a species of slow-growing nontuberculous mycobacteria. It causes mostly pulmonary infections or lymphadenitis in children, but is increasingly encountered in isolated tenosynovitis in adults. Diagnosis is often delayed because of the rarity of the condition and the difficulty of culturing the bacteria. CASE PRESENTATION: We report on a rare association of seronegative polyarthritis with infectious nontuberculous mycobacteria tenosynovitis. A 65-year-old Caucasian female was referred to our clinic because of persisting tenosynovitis of the finger flexor tendons of her right hand, despite two previous synovectomies. She also reported bilateral shoulder and left wrist pain. Paraclinical investigations showed slightly elevated inflammatory parameters. Ultrasound showed synovitis of metacarpophalangeal joints of the right hand and right knee, and a bilateral subacromial bursitis. Hand magnetic resonance imaging also revealed an erosive carpal synovitis. Bacteriological analysis of the second tenosynovectomy specimen showed no growths in aerobic and anaerobic cultures. An additional synovial fluid analysis of the wrist joint was negative for mycobacteria and crystals. Seronegative polyarthritis was suspected, but the initiated immunosuppressive treatment with prednisolone and methotrexate resulted in no clinical improvement of the tenosynovitis. Yet the other joints responded well, and the inflammatory parameters normalized. The immunosuppression was later stopped because of side effects. Due to massive worsening of the tenosynovitis, a third synovectomy was performed. Mycobacterium malmoense was identified on biopsy, leading to the diagnosis of infectious tenosynovitis. At this point, we started an antituberculous therapy, with incomplete response. A combination of antimicrobial and immunosuppressive treatment finally led to the desired clinical improvement. CONCLUSION: The treatment of nontuberculous mycobacteria tenosynovitis is not well established, but combining antibiotics with surgical debridement is probably the most adequate approach. Our case highlights the importance of having a high clinical suspicion of an atypical infection in patients with inflammatory tenosynovitis not responding to usual care.

Pulmonary Infection Caused by Mycobacterium malmoense in a Chronic HIV-Infected Individual Participating in a Therapeutic Vaccine Trial.

We report a case of Mycobacterium malmoense pulmonary infection and HIV-1 chronic co-infection in a 60-year-old man while participating in an HIV-1 therapeutic vaccine clinical trial and during the analytical treatment interruption. We present clinical and therapeutic features of a complicated M. malmoense pulmonary infection along with discussion of the possible relation to the HIV-1 cure-related interventions.

Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by Bronchopleural Fistula.

We present a case of M. malmoense and HIV co-infection complicated by aspergilloma leading to bronchopleural fistula with intractable pneumothorax and pleural aspergillosis, ultimately requiring surgical intervention. Treatment guidelines for M. malmoense are reviewed, literature regarding M. malmoense and HIV co-infection is reviewed, and the epidemiology of M. malmoense in North America is discussed.

Dissemination of localized Mycobacterium malmoense infection in an immunocompromised patient.

A 75-year-old woman with a history of immunosuppressive treatment for rheumatoid arthritis and non-Hodgkin lymphoma, was referred to our reference centre for treatment of tenosynovitis caused by Mycobacterium malmoense, which had disseminated due to immunosuppressive therapy. This rare diagnosis was made after years of treatment for supposed rheumatoid arthritis. The patient presented with relapsing tenosynovitis with wounds on her right middle finger and wounds on her left lower leg, despite 3 months of adequate therapy (rifampicin+ethambutol+clarithromycin). Therapy was intensified with amikacin, clofazimine, moxifloxacin, and interferon-gamma due to the lack of response. Amputation of the right middle finger was necessary due to advanced disease. Treatment was further complicated by a paradoxical reaction, requiring prednisone treatment, which ultimately led to cure.

Mycobacterium malmoense pulmonary infection in France: a case report.

BACKGROUND: Mycobacterium malmoense infections have frequently been reported in northern Europe since the late 1970s. Factors accounting for this geographically localized epidemiology remain poorly understood. CASE PRESENTATION: We report the case of a 54-year old man concomitantly diagnosed with non-small cell lung carcinoma and M. malmoense pulmonary infection. We present detailed clinical, microbiological and radiological elements strongly arguing for M. malmoense true pathogenicity. Since M. malmoense infection has rarely been reported in France, we also provide elements of the epidemiological investigation and a literature review of potential acquisition and transmission pathways of M. malmoense. We detail therapeutic interventions and subsequent favorable evolution. CONCLUSION: Mycobacterium malmoense is a recognized respiratory pathogen for which routes of infection need to be better investigated.

[Pulmonary infection with Mycobacterium malmoense. Difficulties in diagnosis and treatment]. / Infection pulmonaire à Mycobacterium malmoense. Difficultés diagnostiques et de thérapeutiques.

INTRODUCTION: Pulmonary infection due to Mycobacterium malmoense can be difficult to diagnose. These difficulties can be responsible for a delay in the implementation of optimal treatment. Moreover, the treatment is not standardized. OBSERVATION: We report the case of a 56-year-old patient who developed a Mycobacterium malmoense pulmonary infection whose diagnosis was delayed due to initial suspicion of pulmonary Mycobacterium tuberculosis infection. Once the diagnosis was confirmed, the patient was treated empirically with rifampicin, ethambutol, and clarithromycin for 12 months after culture conversion, giving a total of 15 months. The clinical and radiological outcomes were favorable. DISCUSSION: This clinical case highlights the difficulties of diagnosing pulmonary atypical mycobacterial infection according to the American Thoracic Society criteria, particularly Mycobacterium malmoense, a non-tuberculous mycobacterium (NTM) quite uncommon in France. Currently, there are new diagnostic techniques such as GenoType Mycobacteria Direct®. The second issue is the poorly standardized treatment of this NTM and many others, that are based on the recommendations of the British Thoracic Society. A national register has been set up by the MycoMed network, based essentially on the work of microbiologists but this register is unfortunately not exhaustive. CONCLUSION: A more systematic reporting strategy could allow cohort studies and therefore provide us with data on the most efficient drugs in the treatment of the rarest NTM infections.

An atypical mycobacterial infection of the shoulder.

Mycobacterium malmoense is an acid-fast non-tuberculous organism that most commonly causes pulmonary infection. Extrapulmonary infection has also been reported. With an increased emphasis being placed on the clinical importance of this organism, especially within Europe, we report the first case of septic arthritis of the shoulder caused by this organism. We also highlight the importance of considering atypical mycobacterium infection in the differential diagnosis of shoulder infection and issues surrounding the management of this entity.

Importancia diagnóstica de las infecciones extrapulmonares causadas por el género Mycobacterium / Diagnostic importance of extrapulmonary infections caused by the genus Mycobacterium

Introducción: el género Mycobacterium provoca infecciones pulmonares y extrapulmonares, dentro de estas últimas las localizaciones más frecuentes son; sistema nervioso linfático, central, circulatorio, genitourinario, gastrointestinal, tejido osteoarticular, y la piel. Objetivo: realizar las caracterizaciones etiológica de infecciones extra pulmonares producidas por el género Mycobacterium, destacar su importancia diagnóstica tanto en pacientes VIH- como VIH/sida. Métodos: se realiza un estudio descriptivo-prospectivo de corte transversal realizado de enero 2012 a mayo 2014. Durante este período se recibió un total de 825 muestras, 232 de pacientes VIH- y 593 de pacientes con VIH/sida. Las muestras que lo requerían se le aplicaron descontaminación cultivo, se utilizó el método de ácido sulfúrico al 4 por ciento, para el cultivo se usó el medio de Löwenstein-Jensen. Resultados: de las 825 muestras extra pulmonares en 29 (3,5 por ciento) se obtuvo cultivo positivo,14 (48,3 por ciento) con aislamiento de Mycobacterium tuberculosis (11 VIH+ y 3 VIH-), y 15 (51,7 por ciento) con aislamiento de otras especies micobacterianas (12 VIH+ y 3 VIH-), Mycobacterium avium-intracellulare, y Mycobacterium malmoense fueron las especies más aisladas. Conclusión: por todo lo anterior expuesto se recomienda mantener la vigilancia diagnóstica en este tipo de infección extra pulmonar, en especial en pacientes con sida, pues en muchos casos pueden tener fatales consecuencias por su diagnóstico tardío(AU)