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Abstract Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.

ABSTRACT Mycobacterium abscessus (MABS) is the most pathogenic and drug-resistant rapidly growing mycobacteria. However, studies on MABS epidemiology, especially those focusing on subspecies level, are scarce. We aimed to determine MABS subspecies distribution and its correlation with phenotypic and genotypic antibiotic profiles. A retrospective multicenter study of 96 clinical MABS isolates in Madrid between 2016 to 2021 was conducted. Identification at the subspecies level and resistance to macrolides and aminoglycosides were performed by the GenoType NTM-DR assay. The MICs of 11 antimicrobials tested against MABS isolates were determined using the broth microdilution method (RAPMYCOI Sensititer titration plates). Clinical isolates included 50 (52.1%) MABS subsp. abscessus; 33 (34.4%) MABS subsp. massiliense; and 13 (13.5%) MABS subsp. bolletii. The lowest resistance rates corresponded to amikacin (2.1%), linezolid (6.3%), cefoxitin (7.3%), and imipenem (14.6%), and the highest to doxycycline (100.0%), ciprofloxacin (89.6%), moxifloxacin (82.3%), cotrimoxazole (82.3%), tobramycin (81.3%), and clarithromycin (50.0% at day 14 of incubation). Regarding tigecycline, although there are no susceptibility breakpoints, all strains but one showed MICs ≤ 1 μg/mL. Four isolates harbored mutations at positions 2058/9 of the rrl gene, one strain harbored a mutation at position 1408 of the rrl gene, and 18/50 harbored the T28C substitution at erm(41) gene. Agreement of the GenoType results with clarithromycin and amikacin susceptibility testing was 99.0% (95/96). The rate of MABS isolates showed an upward trend during the study period, being M. abscessus subsp. abscessus the most frequently isolated subspecies. Amikacin, cefoxitin, linezolid, and imipenem showed great in vitro activity. The GenoType NTM-DR assay provides a reliable and complementary tool to broth microdilution for drug resistance detection. IMPORTANCE Infections caused by Mycobacterium abscessus (MABS) are increasingly being reported worldwide. Identifying MABS subspecies and assessing their phenotypic resistance profiles are crucial for optimal management and better patient outcomes. M. abscessus subspecies differ in erm(41) gene functionality, which is a critical determinant of macrolide resistance. Additionally, resistance profiles of MABS and the subspecies distribution can vary geographically, highlighting the importance of understanding local epidemiology and resistance patterns. This study provides valuable insights into the epidemiology and resistance patterns of MABS and its subspecies in Madrid. Elevated resistance rates were observed for several recommended antimicrobials, emphasizing the need for cautious drug use. Furthermore, we assessed the GenoType NTM-DR assay, which examines principal mutations in macrolides and aminoglycosides resistance-related genes. We observed a high level of agreement between the GenoType NTM-DR assay and the microdilution method, indicating its usefulness as an initial tool for early initiation of appropriate therapy.

Phage therapy is an alternative therapy that is being used as the last resource against infections caused by multidrug-resistant bacteria after the failure of standard treatments. Pseudomonas aeruginosa can cause pneumonia, septicemia, urinary tract, and surgery site infections mainly in immunocompromised people, although it can cause infections in many different patient profiles. Cystic fibrosis patients are particularly vulnerable. In vitro and in vivo studies of phage therapy against P. aeruginosa include both bacteriophages alone and combined with antibiotics. However, the former is the most promising strategy utilized in clinical infections. This review summarizes the recent studies of phage-antibiotic combinations, highlighting the synergistic effects of in vitro and in vivo experiments and successful treatments in patients.

Mycobacterium abscessus complex is extremely difficult to treat. Intrinsic and acquired bacterial resistance makes this species one of the most challenging pathogens and treatments last from months to years, associated with potential risky antibiotic toxicity and a high number of failures. Nonantibiotic antimicrobial agents against this microorganism have recently been studied so as to offer an alternative to current drugs. This review summarizes recent research on different strategies such as host modulation using stem cells, photodynamic therapy, antibiofilm therapy, phage therapy, nanoparticles, vaccines and antimicrobial peptides against M. abscessus both in vitro and in vivo.