Keisuke Kamada

Genetic epidemiological analysis of mobile genetic elements, such as plasmids, has rarely been carried out in Mycobacterium abscessus, regardless of its usefulness in speculating the historical contact between bacteria. In this study, through whole genome sequencing analysis of M. abscessus isolated from the same patient, we identified three plasmids (pMAB625-1, pMAB625-2, and pMAB625-3) that were not found in the type strain ATCC 19977. We conducted an in silico analysis to investigate the distribution of previously identified plasmids, including the pMAB625 plasmids, in M. abscessus isolated from 462 clinical specimens worldwide. pMAB625-3 was the most prevalent plasmid, detected in 11.5% (53/462) of isolates. Furthermore, phylogenetic tree analysis revealed that these plasmids transferred beyond regions and subspecies and acquired unique mutations. These results indicate that the transmission of plasmids increases the genomic diversity in M. abscessus, and plasmid epidemiology is useful for estimating the historical contact between bacteria.

Nontuberculous mycobacteria are rare but serious pathogens in peritoneal dialysis (PD)-associated infections. Mycobacterium abscessus (M. abscessus) is usually resistant to standard anti-tuberculosis drugs. Macrolide antibiotics are key drugs for treating M. abscessus, but macrolide-resistant strains pose particular challenges, and an optimal antimicrobial treatment strategy or duration has not been established for M. abscessus PD-associated infections. We report a case of a 63-year-old man on PD who developed persistent purulent discharge from his PD catheter exit site. Skin swab culture identified macrolide-resistant M. abscessus, with imaging confirming inflammation along the catheter tunnel. These findings led to the diagnosis of M. abscessus PD catheter tunnel infection, with peritonitis excluded. Initial management included early catheter removal, extensive surgical debridement, and 6 weeks of combination antibiotic therapy, including imipenem-cilastatin, amikacin, and clarithromycin, achieving clinical cure. However, the infection recurred after 5 months, necessitating retreatment with debridement and an antibiotic regimen including imipenem-cilastatin, amikacin, azithromycin, and clofazimine for 4 weeks, followed by a continuation regimen with amikacin, clofazimine, and sitafloxacin for 4 months. This approach achieved sustained clinical cure without recurrence at 14 months of follow-up. Based on a literature review of 67 cases of M. abscessus PD-associated infections, all six cases treated with clofazimine achieved clinical cure, but there were no reports on cases of macrolide-resistant M. abscessus treated with clofazimine. Our case represents the first successful clofazimine treatment of macrolide-resistant M. abscessus PD-associated infection, demonstrating clofazimine as a potentially effective oral antibiotic option in combination therapy, particularly in macrolide-resistant cases with limited therapeutic options.

PURPOSE: Amikacin (AMK) is a widely used therapeutic drug monitoring (TDM)-recommended treatment for nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its optimal dosage and TDM target remain unclear. In this study, we aimed to clarify the relationship between AMK exposure, ototoxicity, and efficacy. METHODS: Patients with NTM-PD treated with AMK at Fukujuji Hospital were retrospectively included in this study. The correlation between AMK exposure, measured by peak and trough levels and the area under the concentration-time curve (AUC), ototoxicity, and culture conversion was analyzed using the Mann-Whitney U test and Cox regression analysis. A population pharmacokinetic/pharmacodynamic (PPK/PD) model was developed to predict ototoxicity using TDM measurements. RESULTS: A total of 185 patients were enrolled. The median AMK dose and observation period were 500 (interquartile range [IQR], 500-600) mg/day and 45.8 (IQR, 31.3-76.5) months, respectively. Ototoxicity and culture conversion were observed in 39% and 54% of the enrolled patients, respectively, after initiating AMK. The median time to the development of ototoxicity was 69 (IQR; 43-97) days. Neither ototoxicity nor culture conversion was associated with pharmacokinetic parameter of AMK exposure, including its minimum inhibitory concentration. However, the cumulative AUC was significantly higher in patients who developed ototoxicity (P < 0.001) than in those without ototoxicity. The developed PPK/PD model enabled calculation of cumulative AUC from TDM data and prediction of ototoxicity onset. CONCLUSION: Cumulative AMK exposure was associated with ototoxicity, and our findings allow prediction of ototoxicity onset using AMK TDM data.

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterium that causes extrapulmonary infections, including surgical site infections. Mycobacterium abscessus subsp. abscessus (MAA) frequently develops macrolide resistance, resulting in difficult-to-treat infections. Recently, surgical site infections caused by MAAs after cosmetic surgeries have become a notable concern, particularly as the number of cosmetic surgery clinics in Japan continues to increase. Therefore, vigilance for MAA infections following cosmetic procedures is necessary. However, reports on the treatment of macrolide-resistant MAA are limited. We report a case of surgical site infection following cosmetic surgery caused by macrolide-resistant MAA. A 47-year-old woman developed subcutaneous erythema, induration, and fistula formation several months after a thread lift procedure. Exudate culture revealed MAA harboring a full-length erm41 gene associated with inducible macrolide resistance, and susceptibility testing confirmed macrolide resistance. Treatment was initiated with combination antimicrobial therapy, including imipenem/cilastatin, amikacin, and tigecycline for 4 weeks, followed by clofazimine and sitafloxacin for 11 months as maintenance therapy. Local debridement was performed; however, complete removal of the threaded material was not feasible because thread had dissolved. After 12 months of treatment, the fistula closed, and no recurrence occurred during follow-up. This case highlights the importance of considering MAA in surgical site infections following cosmetic surgery and suggests that individualized combination antimicrobial therapy based on susceptibility testing may lead to successful outcomes in macrolide-resistant extrapulmonary MAA.

Mycobacterium mageritense is a species of rapidly growing mycobacteria (RGM) found in environmental sources, possibly causing skin, soft tissue, and intravascular device infections. We encountered a case of prostatic abscess caused by M. mageritense that developed three months after transurethral resection of a bladder tumor. The patient was treated with antibiotics and underwent radical cystectomy. Prostatic abscesses due to RGM are rare, but may sometimes be overlooked. Mycobacterial cultures may be helpful in the diagnosis of culture-negative prostatic abscesses following these procedures.