We demonstrated the impact of co-infection with other pathogenic microorganisms after initiation of treatment for pulmonary MAC disease. Although co-infection with other pathogenic microorganisms does not affect therapeutic efficacy in MAC, these organisms may interfere with improvement of chest CT findings. Few studies have investigated the impact of co-infection with other pathogenic microorganisms in pulmonary MAC disease [5, 9]. Fujita et al. reported chronic co-infection with other pathogenic microorganisms including MSSA, P. aeruginosa, and Aspergillus spp. in 45.1% of patients with pulmonary MAC disease . According to Kamata et al., chronic co-infection with P. aeruginosa was seen in 7.8% of patients with pulmonary MAC disease . It is important to note that these were cross-sectional studies, and so did not clarify the impact of co-infection on the efficacy of MAC treatment. To our knowledge, this is the first report to investigate the impact of co-infection with other pathogenic microorganisms on clinical course after initiation of treatment for pulmonary MAC disease.
This study showed that sputum culture conversion or treatment success rate was 81%, improvement in chest CT score was 63%, and the rate of CAM resistance was 8.3%. These results were consistent with those from previous studies. Earlier reports of macrolide-inclusive daily regimens have shown that the rate of sputum culture conversion was 42-92% [10–14], chest imaging improvement was 68-82% [12, 13], and macrolide resistance was 9-15% [10, 11, 14]. In addition, the rates of MAC culture conversion and CAM resistance did not differ significantly between the co-infection and MAC alone groups. These results suggest that co-infection after the initiation of treatment for MAC did not affect the treatment efficacy.
Nevertheless, the proportion of patients with improved chest CT scores was significantly lower in the co-infection group than in the MAC alone group at 24 months after initiation of treatment. Furthermore, serial changes in chest CT score in the co-infection group showed no significant improvement, even after excluding patients with MAC treatment failure. Thus, co-infection with other pathogenic microorganisms does not affect the outcome of MAC treatment but worsens chest CT findings. The worse chest CT findings may have been as a result of other pathogenic microorganisms that gained dominance due to weakening of the competing MAC.
Among 6 of the 12 patients who had base co-infection in the co-infection group, only 3 had the same bacterial species detected until post MAC treatment. Clarithromycin-susceptible bacteria such as MSSA and H. influenzae decreased after MAC treatment while clarithromycin-resistant bacteria such as P. aeruginosa and Nocardia spp. increased after MAC treatment. We speculated that MAC treatment suppressed the proliferation of MAC and other clarithromycin (CAM)-susceptible bacteria, and this might foster a conversion of the bacteria to clarithromycin-resistant. This result is consistent with previous reports showing that P. aeruginosa was less frequently isolated from positive MAC sputum cultures and more often isolated after MAC sputum conversion .
Previous studies showed that patients with NTM bronchiectasis, including those with cystic fibrosis, had a lower rate of chronic P. aeruginosa infection compared with non-NTM infection [15, 16]. MAC and other pathogenic microorganisms, especially P. aeruginosa, interact with each other and culture results may reflect the dominant pathogenic species at that time. Therefore, we speculate that the negative MAC culture in the co-infection group may not only be due to the effect of MAC treatment but also due to the suppression of MAC culture by other potentially infectious pathogenic microorganisms that became dominant.
In this study, subjective symptoms were more severe in the co-infection group at baseline. Specifically, high sputum score at baseline was an independent risk factor for co-infection. According to Kamata et al., co-infection with P. aeruginosa worsened subjective symptoms in patients with pulmonary MAC . Previous reports showed that P. aeruginosa colonization was an independent predictor of hospital admission in bronchiectasis . But in our study, the rate of baseline co-infection showed no significant difference between the co-infection and MAC alone groups. We surmised that the presence of trace amounts of other bacteria undetectable by conventional culture in the co-infection group at baseline was the cause of the severe subjective symptoms, and that the bacteria may have become apparently detectable with MAC treatment.
Several risk factors for developing co-infection in patients with MAC have been reported. This study showed that bronchiectasis score was significantly higher in the co-infection group than the MAC alone group. However, cavitary lesion score and the frequency of concomitant emphysema did not differ between the two groups. In addition, 7 out of 12 patients had P. aeruginosa co-infection and none had Aspergillus co-infection. In the Fujita study, of the 124 patients with co-infection, 18 and 35 patients had aspergillus and P. aeruginosa infection, respectively. Risk factors for co-infection were reported to be COPD and M. intracellulare infection . Patients with M. intracellulare infection were more likely to have fibro-cavitary disease than those with M. avium infection  and cavitary lesions have been reported to be a risk factor for complications of chronic pulmonary aspergillus infection in pulmonary MAC . In contrast, the Kamata study included 19 patients with MAC and P. aeruginosa exclusively. The severity of bronchiectasis, but not cavitary lesions, was associated with P. aeruginosa co-infection. The disparity in risk factors for co-infection in these studies may be due to the presence or absence of Aspergillus. A previous study showed that severity of bronchiectasis was significantly associated with the presence of chronic P. aeruginosa infection in patients with non-cystic fibrosis bronchiectasis . We speculate that patients with cavitary lesions are more likely to have co-infection with Aspergillus, whereas those with severe bronchiectasis were more likely to be infected with certain types of bacteria including P. aeruginosa.
These findings notwithstanding, this study had several limitations that should be mentioned. Firstly, it was a single-center study in a small number of patients. Thus, the findings may not be generalizable to a larger, more diverse population. Secondly, some patients were excluded from this study due to missing sputum examination and chest CT evaluations. These excluded patients might have had infections from a different type of pathogen. Thirdly, the potential presence of indigenous oral bacterial populations cannot be ruled out, and so this may not accurately reflect the status of the lower airway flora because not all patients underwent bronchoscopy.