To our knowledge, this is the first report on the etiology, treatment, and prognosis of catheter-related infection and peritonitis caused by NTM. Regarding the pathogens involved, M. fortuitum and M. chelonae account for one-third of reported cases of PD-related peritonitis2. In our study, M. abscessus, which is the most common NTM7, accounted for 40.1% of cases.
Previous reports have indicated that 70%, 20%, and 10% of NTM infections are diagnosed within 14, 21, and 28 days, respectively8. If acid-fast bacilli culture is not submitted in the initial attempt, diagnosis may take additional time. This suggests that NTM infections pose a challenge in diagnosis. In our study, cases were categorized into three groups according to diagnostic approaches or methods. With respect to the classification of cultures for diagnosis, Group 2 primarily comprised two types of diagnoses. The first type comprised patients who initially presented with bacterial peritonitis, which later progressed to a secondary NTM infection. The second type involved cases in which NTM infection could have been diagnosed using acid-fast stain but was initially misdiagnosed or undiagnosed when only gram stain was performed. Cases initially diagnosed as infections caused by Corynebacterium species, which exhibit a gram-stain appearance similar to that of NTM, were ultimately diagnosed as NTM infection due to the presence of acid-fast bacilli in the stain or culture. These cases might have originally belonged to Group 2, suggesting the importance of considering acid-fast stain to accurately diagnose NTM infections and ensure appropriate treatment. A previous study described this misidentification of NTM as ghost mycobacteria9, with patients being initially treated for bacterial PD-related infection. However, they were found to have NTM-related infection following treatment failure. For patients who show a poor response to antibiotics targeting gram-positive rods, such as Corynebacterium sp. or C. diphtheriae, it is important to perform acid-fast bacilli stain, followed by mycobacterium culturing or a PCR test in order to promptly detect NTM3. In the present study, patients with peritonitis caused by NTM showed high rates of PD discontinuation and mortality. Since many cases of catheter-related infection progress to peritonitis, early diagnosis and therapeutic intervention upon the occurrence of catheter-related infection are crucial.
In our review, 88% of cases were treated with combination therapy with multiple antibiotics, including macrolides, fluoroquinolones, carbapenems, tetracyclines, and aminoglycosides (Table 1). Although the FDA currently warns against the use of fluoroquinolones, infections caused by gram-negative rods have long been treated with fluoroquinolones as the first-choice medications. Notably, fluoroquinolones are partially effective against NTM infection, sometimes resulting in the induction of highly resistant strains, even in patients with a history of PD catheter-related infection. In our study, 25.2% and 8.6% of patients with PD catheter-related infection and peritonitis, respectively, were conservatively managed using antimicrobial therapy only. There remain no established guidelines for catheter removal in cases of tunnel infections caused by NTM; further, treatment approaches significantly vary across facilities. Although our findings do not confirm the validity of catheter removal, extended use of multiple antibiotics in patients with PD-related infection results in an increased risk of side effects7. Moreover, patients with renal dysfunction have an increased risk of strong side effects from antibiotics10. For example, fluoroquinolones involve risks of enteritis, Achilles tendon rupture, and malignant arrhythmias10. Macrolides can cause gastrointestinal symptoms and cardiovascular-related death11. Tetracyclines may cause pigment deposition and gastrointestinal symptoms, whereas aminoglycosides carry the risk of renal and hearing impairment. The average duration of antibiotic therapy was 3.8 and 6.0 months in patients with PD catheter-related infection and peritonitis, respectively. However, given the lack of randomized controlled trials, further prospective studies investigating and validating the potential impact of treatment duration on prognosis are required.
Notably, 15 (8.7%) patients with PD-related peritonitis died (Fig. 2), whereas only one (0.8%) patient with PD catheter-related infection died (Fig. 1). Regarding the continuation of PD, 79 (62.2%) and 26 (16.0%) of patients with PD catheter-related infection and peritonitis, respectively, continued/resumed PD. In the former group, almost half of the patients tolerated conservative multiple-antibiotic therapy; however, one patient died. All patients who underwent surgical intervention (including relocation of the exit site or removal and reinsertion) survived with PD. This could be attributed to early intervention preventing the progression of catheter-related infection to peritonitis12,13. Consistent with current guidelines2,3, our findings indicate that patients with PD-related peritonitis should undergo immediate catheter removal.
This study has several limitations. First, given its retrospective design, certain items had missing values, which impeded correct evaluation. Regarding culture submission, it was unclear in some cases whether both general bacterial culture and acid-fast bacterial culture were submitted in the initial attempt. Moreover, the timing of PD catheter surgery varied across the patients. In some cases, relocation of the exit site was initially performed for the diagnosis of catheter infection; however, there were cases where PD-related peritonitis occurred during the course. Moreover, we cannot completely avoid several bias types, including published bias and selective bias. Second, we did not thoroughly consider risk factors for NTM infection, such as a history of PD-related infection, presence of positive gram-positive rods in the bacterial culture, and unresponsiveness to antibiotic therapy. Further studies are warranted to elucidate these risk factors. Finally, the safety of and optimal duration until PD catheter reinsertion could not be elucidated because of the limited number of included cases.