NTM is classified into two types: rapid-growing and slow-growing. Slow-growing mycobacteria include the Mycobacterium avium complex (MAC), Mycobacterium kansasii, Mycobacterium ulcerans and Mycobacterium marinum and so on. Among them, MAC is the NTM with the newest species or subspecies discovered. Mycobacterium maeseillense is a slow-growing mycobacterium and a member of the MAC complex. In recent years, there has been an increasing number of reported cases of NTM infections, with the main sites of infection being the lungs, skin, and soft tissues.
To the best of our knowledge, there is currently no literature reporting Mycobacterium massiliense causing bloodstream infections. Due to its slow growth and poor gram staining, this bacterium can be easily missed in microbiology laboratories. Subsequently, molecular diagnostic techniques can be used to identify M. massiliense. Identifying the species of NTM is crucial for patients because different species of NTM require different types of antibiotics and treatment durations. [2,25] In addition, due to long-term use of immunosuppressive drugs after kidney transplantation, patients have a weakened immune system and are classified as immunocompromised individuals. Early mNGS of skin tissue indicated an infection with Trichophyton rubrum and Staphylococcus capitis. Clinically, the primary consideration was a fungal infection combined with a Staphylococcus infection on the patient’s skin, without considering the less common pathogen NTM that can cause bloodstream infection. Additionally, clinical cases of bloodstream infection caused by this particular bacterium are very rare, and the clinical features may not be apparent, leading to challenges in making a diagnosis. Although so, we have successfully diagnosed the case and initiated a combination therapy of anti-NTM and antifungal medications for the patient. The question is why the acid-fast stain of the patient’s skin tissue was positive but NTM was not detected by mNGS. It is possible that the patient’s skin tissue had a low bacterial load of mNTM, making it difficult to lyse the NTM cells during the nucleic acid extraction process, which could lead to a false-negative result. Additionally, for mycobacteria in tissue samples, the sensitivity of mNGS may not be very high, and in some cases, even lower than traditional culture methods [5]. Unfortunately, both the patient’s skin tissue and wound pus did not yield any NTM in culture. The inability to detect NTM in the skin tissue may be due to a low bacterial load and slow growth. Additionally, the presence of other microorganisms such as Trichophyton rubrum may have overshadowed the growth of NTM. Therefore, it is possible that there were not enough NTM colonies present in the culture to be detected. The possible reason for the failure to detect NTM in the pus culture could be the short duration of the laboratory cultivation, leading to a missed detection. Additionally, the clinical suspicion of NTM infection was not communicated to the laboratory in advance, resulting in the use of standard culture duration, which might not have been sufficient to cultivate NTM. In general, the detection of NTM in blood cultures is often considered as a sign of pathogenic bacteria [6]. In patients undergoing solid organ transplantation, kidney transplant recipients have the highest rate of NTM infection. This could be attributed to the higher frequency of kidney transplantation compared to other solid organ transplants [7]. The risk factors for NTM infection generally include immunodeficiency, genetic defects, monoclonal antibody therapy, and various other factors. Patients with chronic rejection after solid organ transplantation are at an increased risk of developing NTM infections [8]. Immunodeficiency can facilitate the progression of NTM infection, and enhancing immunosuppression (such as post-transplant anti-rejection therapy) further increases the risk of infection [9].
Various molecular diagnostic techniques are available for identifying NTM strains, such as mNGS, PCR technology, direct or indirect homologous gene or sequence comparison methods. In clinical settings, the implementation of mass spectrometry technology and mNGS has greatly improved the accuracy of NTM species identification, while also significantly reducing the identification time. Among these techniques, mNGS stands out as the most advanced and precise method for identifying and distinguishing NTM species [2].
According to relevant studies, combination therapy has been reported as superior to monotherapy for NTM bacteremia, and it is associated with a lower rate of recurrence [10]. Currently, the breakpoint criteria for drug susceptibility reference CLSI M24-A2 only exist for clarithromycin, moxifloxacin, and linezolid. However, the breakpoints for ethambutol, rifampin, rifambutin, streptomycin, and amikacin, which are clinically useful, have not been established yet. In this case, the patient has selected azithromycin, moxifloxacin, ethambutol, clofazimine, and contizolamide for combating the NTM infection. The results of drug susceptibility testing indicate sensitivity to clarithromycin and intermediate susceptibility to moxifloxacin and linezolid. However, the clinical evaluation confirms the effectiveness of the chosen treatment. It is recognized that there may be variations in NTM susceptibility between in vivo and in vitro conditions; therefore, there is no recommendation to switch antibiotics for the patient. As per the recommended guidelines [2], the treatment course for disseminated MAC patients requires prolonged medication for one year or even lifelong. In our survey of 18 cases, it is evident that 83% of the patients have a favorable prognosis, highlighting the higher cure rate of disseminated NTM infections. Nonetheless, it is crucial to tailor the duration of treatment based on individual patient circumstances.