Vertebral osteomyelitis caused by Mycobacteroides abscessus subsp. abscessus resulting in spinal cord injury due to vertebral body fractures

Nontuberculous mycobacteria (NTM) rarely cause vertebral osteomyelitis; however, the clinical characteristics of vertebral osteomyelitis caused by NTM are poorly understood due to its rarity. A 74-year-old man with lung cancer was treated with prednisolone for immune checkpoint inhibitor-associated immune-related adverse events. He had been experiencing mild back pain without febrile episodes for five months, and was admitted to the hospital for worsening back pain and progressive paraplegia. Magnetic resonance imaging showed spinal cord compression at T4-5 due to fractures of the T5 and T7 vertebral bodies. The culture of a sample of pus from the T7 vertebral body obtained at the time of spinal fusion surgery yielded the Mycobacteroides abscessus (M. abscessus) complex. The patient was diagnosed with vertebral osteomyelitis caused by M. abscessus complex and treated with clarithromycin, amikacin, and imipenem; clarithromycin was later replaced by sitafloxacin because of inducible macrolide resistance. However, his neurologic deficits were irreversible, and he died due to a deteriorating general condition. The strain was identified up to subspecies level as M. abscessus subsp. abscessus by hsp65 and rpoB sequencing and nucleic acid chromatography. Although vertebral osteomyelitis due to NTM is rare, delayed diagnosis can lead to serious complications or poor outcomes. A prolonged clinical course, less frequent fever, vertebral destruction or spinal deformity, neurological deficits, or immunosuppressed conditions might be suggestive of NTM vertebral osteomyelitis.     

Inactivation of nontuberculous mycobacteria by gaseous ozone treatment

Nontuberculous mycobacteria (NTM) are environmental bacteria resistant to many common disinfectants and ultraviolet radiation. Inhalation of aerosols generated from NTM-containing water and soil causes NTM lung disease, especially in people with underlying lung diseases and decreased immunity. To prevent healthcare-acquired NTM infections, it is important to eradicate NTM living in hospital environments. Therefore, we evaluated the efficacy of gaseous ozone for the inactivation of NTM, namely Mycobacterium (M.) avium, M. intracellulare, M. kansasii, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense. Gaseous ozone treatment at 1 ppm for 3 h reduced the bacterial number of all strains by more than 97%. Gaseous ozone treatment could be a practical, effective and convenient disinfection method for NTM living in hospital environments.     

Pulmonary infection caused by nontuberculous mycobacteria in a medical center in Taiwan, 2005-2008

The aim of this study was to investigate the epidemiology and clinical characteristics of pulmonary infections caused by nontuberculous mycobacteria (NTM) in a university hospital in Taiwan from 2005 to 2008. During the study period, a total of 312 patients with NTM pulmonary infection were identified. Most patients with NTM pulmonary infection had preexisting pulmonary diseases or malignancies. The incidence (per 100,000 inpatients and outpatients) of patients with NTM isolations (6.67 in 2005 and 9.28 in 2008, P < .0001) from respiratory specimens and the incidence of patients with NTM pulmonary infection (3.54 in 2005 and 4.45 in 2008, P < .0141) increased significantly annually. The most common pathogens in patients with NTM-associated pulmonary infections were Mycobacterium avium complex (n = 110, 35.3%), followed by M. abscessus (n = 66, 21.2%). Incidence (per 100,000 inpatients and outpatients) of patients with pulmonary infections caused by rapidly growing mycobacteria (RGM) also increased significantly (1.06 in 2005 and 2.00 in 2008, P = .008). In conclusion, RGM, especially M. abscessus, had an increasingly important role in NTM pulmonary infections.     

Nontuberculous mycobacterial infections in cancer patients in a medical center in Taiwan, 2005-2008

Data on the nontuberculous mycobacterial (NTM) species that cause infection and the characteristics of disease caused by these pathogens in cancer patients are limited, so we perform this study to investigate the species distribution of NTM isolates from various clinical specimens and to elucidate the epidemiologic trends in NTM isolates and diseases among cancer patients. From 2005 through 2008, cancer patients with NTM infections as defined by the American Thoracic Society/Infectious Diseases Society of America criteria were identified at the National Taiwan University Hospital. The medical records of all patients were reviewed. During the study period, a total of 219 cancer patients with NTM infections were identified. Among them, 133 (60.7%) patients were older than 65 years, most of whom were men. Lung cancer was the most common type of cancer, followed by hematologic cancer and gastrointestinal tract cancer. Pulmonary NTM infection was the most common type of infection in 205 (93.6%) patients, followed by skin and soft tissue infections (n = 7, 3.2%), disseminated infections (n = 4, 1.8%), and genitourinary tract infection (n = 3, 1.4%). Disseminated infections occurred exclusively in patients with hematologic cancer. Mycobacterium avium complex (MAC) caused the majority of pulmonary NTM infections in cancer patients; in contrast, M. abscessus was the most common causative pathogen of extrapulmonary NTM diseases, followed by MAC. In conclusion, physicians need to be aware of the possibility of co-existing pulmonary NTM infection in patients with lung cancer. In addition, disseminated NTM infection should be considered in patients with hematologic cancer.     

Clinical characteristics of extrapulmonary nontuberculous mycobacteria infections in comparison with pulmonary infections: A single-center,retrospective study in Japan

IntroductionThe prevalence of nontuberculous mycobacteria (NTM) infections is increasing worldwide. Although NTM can affect extrapulmonary organs, studies on the clinical characteristics of extrapulmonary NTM are rare.MethodsWe retrospectively analyzed patients who were newly diagnosed with NTM infections at Hiroshima University Hospital between 2001 and 2021 to investigate species distribution, infected sites, and risk factors of extrapulmonary NTM compared to pulmonary NTM.ResultsOf the 261 NTM infections, 9.6% and 90.4% had extrapulmonary and pulmonary NTM, respectively. The mean ages of patients with extrapulmonary and pulmonary NTM were 53.4 and 69.3 years, 64.0% and 42.8% were male, 36.0% and 9.3% received corticosteroids, 20.0% and 0% had acquired immune deficiency syndrome (AIDS), and 56.0% and 16.1% had any immunosuppressive conditions, respectively. Younger age, corticosteroid use, and AIDS were associated with extrapulmonary NTM. In pulmonary NTM, Mycobacterium avium complex (MAC) accounted for 86.4% of NTM species, followed by M. abscessus complex (4.2%), whereas in extrapulmonary NTM, M. abscessus complex, MAC, M. chelonae, and M. fortuitum accounted for 36.0%, 28.0%, 12.0%, and 8.0%, respectively. Compared to pulmonary NTM, extrapulmonary NTM were significantly more likely to be rapid-growing mycobacteria (RGM) (56.0% vs. 5.5%). The most common sites of infection were the skin and soft tissues (44.0%), followed by the blood (20.0%), tenosynovium, and lymph nodes (12.0%).ConclusionYounger age and immunosuppressive conditions are associated with extrapulmonary NTM, with a higher prevalence of RGM in extrapulmonary NTM than in pulmonary NTM. These results provide a better understanding of extrapulmonary NTM.     

Treatment outcomes of macrolide-susceptible Mycobacterium abscessus lung disease

Mycobacterium abscessus lung disease is difficult to treat due to inducible resistance to macrolides. However, 15%–20% of isolates are macrolide susceptible. In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved in 93% (13/14) following antibiotic therapy.     

In Vitro Synergy between Clofazimine and Amikacin in Treatment of Nontuberculous Mycobacterial Disease

Disease caused by nontuberculous mycobacteria (NTM) is increasing in frequency. The outcome of treatment for NTM lung disease is poor, particularly lung disease caused by Mycobacterium simiae and M. abscessus. Exploring synergy between active available drugs is a sensible way forward given the lack of new active drugs. We tested for synergy between amikacin and clofazimine, using standardized methods, in 564 consecutive clinical isolates identified as 21 species of rapidly growing mycobacteria, 16 clinical M. avium complex isolates, and 10 M. simiae isolates. Clofazimine and amikacin are each active in vitro against NTM; 97% (n = 548) of the rapid growers revealed MICs of clofazimine of ≤1 μg/ml, and 93% (n = 524) proved susceptible to amikacin. The combination showed significant synergistic activity in 56 of 68 (82%) eligible M. abscessus isolates, 4 of 5 M. chelonae isolates, and 1 M. fortuitum and 1 M. cosmeticum isolate, with 4- to 8-fold decreases in MICs to both drugs. Significant synergy could also be demonstrated against all M. avium complex and M. simiae isolates, with fractional inhibitory concentrations of <0.5. Clofazimine and amikacin show significant synergistic activity against both rapidly and slowly growing nontuberculous mycobacteria. The safety and tolerability of adding clofazimine to amikacin-containing regimens should be tested in clinical trials, and the results of susceptibility tests for these two compounds and their combination merit clinical validation. Synergy between clofazimine and other antibiotics with intracellular targets should be explored.     

Antimicrobial susceptibility testing of Mycobacteroides (Mycobacterium) abscessus complex,Mycolicibacterium (Mycobacterium) fortuitum,and Mycobacteroides (Mycobacterium) chelonae

The drug susceptibility of rapidly growing mycobacteria (RGM) varies among isolates. Treatment strategies similarly differ depending on the isolate, and for some, no clear strategy has been identified. This complicates clinical management of RGM. Following Clinical and Laboratory Standards Institute standard M24-A2, we assessed the susceptibility of 140 RGM isolates to 14 different antimicrobial drugs by measuring their minimal inhibitory concentrations (MICs). We also investigated the correlation of clarithromycin (CAM) MICs with the erm(41) and rrl gene mutations in the Mycobacteroides (Mycobacterium) abscessus complex, the rrl mutation in Mycobacteroides (Mycobacterium) chelonae, and the erm(39) mutation in Mycolicibacterium (Mycobacterium) fortuitum to determine the contribution of these mutations to CAM susceptibility. The five species and subspecies examined included 48 M. abscessus subsp. abscessus isolates (34.3%), 35 (25.0%) being M. abscessus subsp. massiliense, and two (1.4%) being M. abscessus subsp. bolletii. The M. abscessus complex accounted for 85 isolates (60.7%) in total, whereas 43 isolates (30.7%) were M. fortuitum, and 12 (8.6%) were M. chelonae. Our results demonstrated species-specific susceptibility to antimicrobials. In most cases, susceptibility to CAM could be predicted based on genetic pattern, but since one isolate did not fit that pattern, MIC values needed to be measured. Some isolates also exhibited rates of resistance to other drugs that differed from those previously reported in other locations, indicating that accurate identification of the bacterial isolate and use of the correct method for determining MIC are both important for the diagnosis of RGM.     

Pulmonary Mycobacterium abscessus disease in a patient receiving low-dose methotrexate for treatment of early rheumatoid arthritis

A 70-year-old woman with methotrexate (MTX)-refractory rheumatoid arthritis (RA) was referred to our hospital for introduction of biological therapy. On high-resolution computed tomography scans, the patient exhibited abnormal findings such as bronchiectasis and centrilobular small nodules, which were highly suggestive of pulmonary nontuberculous mycobacterial (NTM) disease. Although mycobacterial cultures of sputum specimens yielded negative results, cultures of bronchoalveolar lavage fluids grew Mycobacterium abscessus. Frequent follow-up chest radiographs indicated that the patient’s pulmonary disease became rapidly worse in 1 month following dose escalation of MTX and administration of low-dose prednisolone. Oral clarithromycin and levofloxacin, chosen on the basis of in vitro susceptibility testing, led to a dramatic recovery from this potentially life-threatening complication. Through our experience with this case, we have learned that (1) pulmonary M. abscessus disease can progress rapidly, even during nonbiological anti-RA therapy; (2) regular follow-up chest radiographs are useful to ensure timely implementation of anti-NTM treatment; (3) bronchoscopic testing should be considered when patients are suspected of pulmonary NTM disease but do not meet the diagnostic criteria; and (4) early isolation, identification, and susceptibility testing of causative NTM species are critical for favorable outcomes.     

Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

Multidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment. Mycobacterium abscessus and Mycobacterium avium type strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25× to 2× MIC. Pharmacodynamic interactions were assessed by response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA), calculating the percentage of statistically significant Bliss interactions and interaction indices (I), respectively. Monte Carlo simulations with predicted human lung concentrations were used to calculate target attainment rates for combination and monotherapy regimens. Clofazimine alone was bacteriostatic for both NTM. Clofazimine-amikacin was synergistic against M. abscessus (I = 0.41; 95% confidence interval [CI], 0.29 to 0.55) and M. avium (I = 0.027; 95% CI, 0.007 to 0.048). Based on RSBI analysis, synergistic interactions of 28.4 to 29.0% and 23.2 to 56.7% were observed at 1× to 2× MIC and 0.25× to 2× MIC for M. abscessus and M. avium, respectively. Clofazimine-clarithromycin was also synergistic against M. abscessus (I = 0.53; 95% CI, 0.35 to 0.72) and M. avium (I = 0.16; 95% CI, 0.04 to 0.35), RSBI analysis showed 23.5% and 23.3 to 53.3% at 2× MIC and 0.25× to 0.5× MIC for M. abscessus and M. avium, respectively. Clofazimine prevented the regrowth observed with amikacin or clarithromycin alone. Target attainment rates of combination regimens were >60% higher than those of monotherapy regimens for M. abscessus and M. avium. The combination of clofazimine with amikacin or clarithromycin was synergistic in vitro. This suggests a potential role for clofazimine in treatment regimens that warrants further evaluation.     

Clinicopathologic characteristics of nontuberculous mycobacterial lung disease in Taiwan

Taiwan is an endemic area for tuberculosis (TB), and the incidence of pulmonary infection caused by nontuberculous mycobacteria (NTMs) is also increasing. This study aims to investigate the clinicopathologic characteristics of patients with NTM lung disease during 1998 to 2007 at a medical center in Taiwan. The medical records of patients with confirmed NTM pulmonary infections who underwent open lung surgery in a medical center were reviewed. Twenty-four patients with confirmed NTM pulmonary infections were identified. These patients were histologically classified into 4 types: fibrocavitary/tuberculoid (n = 10), nodular bronchiectatic (n = 4), sarcoidal (n = 6), and other (n = 4). The fibrocavitary/tuberculoid type usually (90%) develops in the upper lobes of old patients with preexisting lung disease. Pulmonary TB (n = 7, 70%) was the major underlying disease before 2003. Nodular bronchiectatic type occurred mainly in the middle lobe of middle-aged women without preexisting lung disease. Sarcoidal type was usually associated with Mycobacterium avium complex infection and develops in middle-aged women. Immunoreactive bacilli were detected in 21 patients (87 %) by immunohistochemical staining using a polyclonal antibody against Mycobacterium tuberculosis and other mycobacterial species (M. avium-intracellulare, Mycobacterium phlei, and Mycobacterium parafortuitum), whereas conventional acid-fast staining was positive in only 21% of patients. In conclusion, TB was the major underlying disease in patients with NTM lung disease in Taiwan. The different histologic types of pulmonary NTM infection suggest each had a distinct pathogenesis.     

Mycobacterium abscessus infection after facial injection of argireline: A case report

BACKGROUNDThe incidence of infection with Mycobacterium abscessus (M. abscessus) has increased in recent years. This increase is partly associated with invasive cosmetic procedures. CASE SUMMARYThe purpose of this case summary is to increase clinicians'' awareness of M. abscessus infection and reduce mycobacterial infection caused by cosmetic procedures. We report the case of a 45-year-old woman who received acetyl hexapeptide-8 (argireline) injections in the forehead and temples, and erythema, nodules, and abscesses appeared at the injection sites after one week. The pus specimens were examined by microbiological culture and confirmed to be positive for M. abscessus. Clarithromycin 500 mg twice daily and moxifloxacin 400 mg once daily were administered for 5 mo and the lesions gradually subsided. CONCLUSIONWe report here for the first time a case of infection with M. abscessus after argireline injection. This condition is easily misdiagnosed as a common bacterial infection. Microbiological examinations are helpful for diagnosis and standardized cosmetic procedures can prevent infection with M. abscessus.     

Successful treatment with chemotherapy and corticosteroids of pulmonary Mycobacterium abscessus infection accompanied by pleural effusion

We describe a 50-year-old woman with rapidly progressive pulmonary Mycobacterium abscessus (M. abscessus) infection accompanied by pleural effusion and organizing pneumonia (OP). CT scan showed consolidation, centrilobular shadows, ground-glass opacity (GGO), and cavities. A transbronchial lung biopsy showed nonnecrotizing granuloma surrounded by infiltrative lymphocyte-dominant inflammatory cells, and lymphocytes in bronchoalveolar lavage fluid (BALF) were increased. We considered OP occurred secondary to M. abscessus infection because clarithromycin, amikacin, and imipenem/cilastatin administration resulted in partial improvement. We added corticosteroids to the regimen, which resulted in a remarkable improvement. We report a case of pulmonary M. abscessus infection involving pleural effusion that responded favorably to medical therapy including corticosteroids.     

Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex

IntroductionCo-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines.MethodsBALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines.ResultsEleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR⁺, CD40^?, and CD163^?) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome.ConclusionThe proportion of alveolar macrophages (HLA-DR⁺, CD40^?, and CD163^?) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.     

Macrolide-resistant Mycoplasma pneumoniae in children in Taiwan

The aim of this study was to estimate the prevalence of macrolide-resistant Mycoplasma pneumoniae in Taiwan and to compare the clinical courses of pediatric patients with macrolide-resistant (MR) M. pneumoniae and macrolide-susceptible (MS) M. pneumoniae infection. Patients were among the children admitted to Chang Gung Children’s Hospital with mycoplasmal pneumonia between February and December 2011. Detection for macrolide resistance was performed after informed consent was obtained. We retrospectively reviewed medical records and compared the clinical courses of two groups of patients of 73 children enrolled into our study. The rate of macrolide resistance in M. pneumoniae was 12.3 %. Longer hospital stay was observed in the MR patients than MS patients [median, 7 days vs. 5 days (P = 0.019)]. Clinical features or radiographic or laboratory findings are not helpful to differentiate MR from MS mycoplasmal pneumonia. Early diagnosis of MR mycoplasmal pneumonia is crucial for the best management of these patients and obviates the need for extensive etiological searches of these nonresponding cases.     

Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection

Background

We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy.

Nontuberculous mycobacteria pulmonary infection in medical intensive care unit: the incidence,patient characteristics,and clinical significance

Background  The clinical significance of nontuberculous mycobacteria (NTM) pulmonary infection in medical intensive care unit (ICU) is still unclear. Materials and methods  We conducted a retrospective study in the medical ICUs of a medical center in Taiwan from January 1999 to June 2007. Patients with NTM isolated from respiratory specimens within 1 month before or during the ICU course were identified. Those who fulfilled the diagnostic criteria of NTM pulmonary infection were identified and compared with patients with NTM colonization and control subjects who were culture-negative for mycobacteria. Results  Among the 5,378 patients admitted to medical ICUs, 2,866 (53.3%) had received mycobacterial culture for respiratory specimens. NTM were isolated from 169 (5.8%) patients. Of them, 47 (27.8%) were considered NTM pulmonary infection. M. avium complex and M. abscessus were the most common pathogens. Within 100 days after ICU admission, significantly more patients with NTM infection died than those with NTM colonization and control subjects (47 vs. 8 vs. 14%, P < 0.001). Twenty-one (49%) patients with NTM pulmonary infection received anti-NTM treatment, with four experiencing adverse effects. Although statistically insignificant, anti-NTM treatment was associated with prolonged survival for those who died in the ICU and shorter ICU stay for those who survived the ICU course. Conclusion  Our findings suggest that NTM pulmonary infection seems to associate with higher mortality in medical ICUs. Anti-NTM treatment is probably associated with a better outcome. Therefore, keeping a high suspicion when NTM is isolated and using careful consideration when starting anti-NTM treatment should be emphasized. Taiwan Anti-Mycobacteria Investigation (TAMI) group: J.-Y. Wang, L.-N. Lee, C.-J. Yu, P.-C. Yang, W.-J. Su, C.-C. Shu, H.-C. Lai, C.-H. Lee and M.-C. Yu.     

Mycobacterium abscessus Complex – a Particular Challenge in the Setting of Lung Transplantation

Mycobacterium abscessus complex is an emerging pathogen in lung transplant candidates and recipients. M. abscessus complex is widespread in the environment and can cause pulmonary, skin and soft tissue, and disseminated infection, particularly in lung transplant recipients. It is innately resistant to many antibiotics making it difficult to treat. Herein we describe the epidemiology, clinical manifestations, diagnosis and treatment of M. abscessus with an emphasis on lung transplant candidates and recipients. We also outline the areas where data are lacking and the areas where further research is urgently needed.     

Standardization of multilocus sequence typing scheme for Mycobacterium abscessus and Mycobacterium massiliense

This study aims to develop a multilocus sequence typing (MLST) scheme for Mycobacterium abscessus complex for the typing of stains within each species. A total of 89 clinical isolates of M. abscessus complex from 71 patients of 2 tertiary care hospitals in South Korea were included. Forty-two isolates were identified as M. abscessus, and 29, as Mycobacterium massiliense through sequencing of 8 housekeeping genes and rpoB. The MLST scheme identified 26 different sequence types(STs) and 13 different clonal complexes (CCs) in M. abscessus and 12 different STs and 6 different CCs in M. massiliense. The MLST data showed high concordance with the XbaI-macrorestriction patterns of pulsed-field gel electrophoresis in the duplicated isolates. Our MLST schemes could identify different strains of M. abscessus and M. massiliense, and the schemes also showed a reliable reproducibility. Therefore, our MLST schemes may be useful in studying the epidemiology of M. abscessus and M. massiliense infections.     

In vitro activity between linezolid and other antimicrobial agents against Mycobacterium abscessus complex

Linezolid (LZD) serves as an effective option in the treatment of Mycobacterium abscessus complex (MABC) infection. Unfortunately, the combined activities of LZD with other antimicrobial agents against MABC have not been evaluated systemically. In this study, we randomly selected 32 Mycobacterium abscessus and 32 Mycobacterium massiliense isolates for the determination of in vitro synergistic effect between LZD and other antimicrobial agents, including amikacin (AMK), moxifloxacin (MOX), cefoxitin (CFX) and tigecycline (TGC). Out of 64 MABC isolates tested, only one (1.6%, 1/64) and two (3.2%, 2/64) exhibited resistance to AMK and LZD, respectively. Statistical analysis revealed that the percentage of TGC-resistant isolates was significantly lower among M. massiliense (9.4%, 3/32) than that among M. abscessus (25.0%, 8/32, P < 0.001). In addition, LZD and AMK showed synergy for 29 MABC isolates (45.3%), whereas no antagonism was noted for this combination. The second mostly frequent synergistic effect was found in LZD plus TGC combination, and 26.6% (17/64) of the strains tested exhibited synergy. In contrast, LZD-CFX and LZD-MOX combinations appeared antagonistic for half of the isolates (48.4%, 31/64 for CFX and 51.6%, 33/64), and almost no synergistic effect was reported in any of the strains for these two combinations. In conclusion, our data reveal that LZD and AMK show the most potent activity against MABC. The frequent synergism is observed in LZD-AMK and LZD-TGC combinations, while LZD rarely exhibits in vitro synergy with MOX and CFX when tested against MABC.