Project description:We report a fatal case of native valve endocarditis due to Mycobacterium abscessus in a hemodialysis patient. The diagnosis was based on culture isolation of acid-fast bacilli from peripheral blood and a permanent catheter tip, and their identification as M abscessus by a reverse hybridization-based assay and direct DNA sequencing of the 16S-23S internal transcribed spacer region. Rapid diagnosis and combination therapy are essential to minimize mortality due to this pathogen. Although combination therapy was started with clarithromycin and tigecycline, the patient refused to take clarithromycin due to severe abdominal pain. The patient became afebrile after therapy with tigecycline alone although bacteremia persisted. He was discharged against medical advice and readmitted three months later for persistent fever. His blood cultures again yielded M abscessus and a transesophageal echocardiogram showed two mobile vegetations. The patient was noncompliant with therapy and died due to cardiac arrest and multiorgan failure. This report shows that M abscessus should also be considered in the differential diagnosis of infective endocarditis in hemodialysis patients.
Project description:Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the two most important human pathogen groups causing nontuberculous mycobacterial lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by mixed NTM infections. This study aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-LD caused by mixed infection with these two major NTM pathogen groups. Seventy-one consecutive patients who had been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M. intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010 and December 2015 were identified. Nearly all patients (96%) had the nodular bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n = 47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24, 34%), and among the 43 (61%) patients who were treated for NTM-LD for more than 12 months, sputum culture conversion rates were significantly lower in patients infected with MAC and M. abscessus (25% [3/12]) than in patients infected with MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and M. abscessus showed marked differences in clarithromycin susceptibility (90% versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment, 11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results indicating that the majority of cases were due to reinfection. Precise identification of etiologic NTM organisms could help predict treatment outcomes in patients with NTM-LD due to mixed infections.
Project description:Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical significance of the MAA isolates.We identified 53 of 180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those without (group 1) and those with (group 2) MAA lung disease.There were no significant demographic differences between patients with and without MAA isolation or between groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (P = .7; 95% CI, -13.4 to 8.6) and length of follow-up (P = .8; 95% CI, -21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA (mean±SD, 15.0 ± 11.1 vs 1.2 ± 0.4; P < .0001; 95% CI, -17.7 to -9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (P > .0001), and were significantly more likely to meet all three American Thoracic Society diagnostic criteria for nontuberculous mycobacterial disease (21 of 21 [100%] vs 0 of 32 [0%]; P < .0001) compared with group 1 patients. Group 1 patients were significantly more likely to have single, positive MAA cultures than group 2 patients (25 of 31 vs 0 of 21; P < .0001).Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant.
Project description:The rapidly growing mycobacterium M. abscessus sensu lato is the causative agent of emerging pulmonary and skin diseases and of infections following cosmetic surgery and postsurgical procedures. M. abscessus sensu lato can be divided into at least three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Clinical isolates of rapidly growing mycobacteria were previously identified as M. abscessus by DNA-DNA hybridization. More than 30% of these 117 clinical isolates were differentiated as M. abscessus subsp. massiliense using combinations of multilocus genotyping analyses. A much more cost-effective technique to distinguish M. abscessus subsp. massiliense from M. abscessus subsp. abscessus, a multiplex PCR assay, was developed using the whole-genome sequence of M. abscessus subsp. massiliense JCM15300 as a reference. Several primer sets were designed for single PCR to discriminate between the strains based on amplicons of different sizes. Two of these single-PCR target sites were chosen for development of the multiplex PCR assay. Multiplex PCR was successful in distinguishing clinical isolates of M. abscessus subsp. massiliense from samples previously identified as M. abscessus. This approach, which spans whole-genome sequencing and clinical diagnosis, will facilitate the acquisition of more-precise information about bacterial genomes, aid in the choice of more relevant therapies, and promote the advancement of novel discrimination and differential diagnostic assays.
Project description:Peritoneal dialysis (PD)-associated peritonitis constitutes a major complication associated with the procedure. PD-associated peritonitis caused by nontuberculous mycobacteria, usually as a result of an infection related to the PD catheter, has been reported in adults and is associated with significant complications and poor outcome. The management of PD-associated peritonitis caused by Mycobacterium abscessus is particularly challenging because this species is resistant to many antimicrobials commonly used to treat mycobacterial species. We present here the second reported case of PD-associated peritonitis caused by M. abscessus in children. Our patient was a 9-year-old boy with end-stage renal disease (ESRD) who presented with suspected peritonitis, and his PD fluid cultures eventually grew M. abscessus. The patient received a 3-week course of triple therapy with clarithromycin, amikacin, and meropenem in addition to PD catheter removal. The infection completely resolved even though a susceptibility report at the end of treatment revealed that the isolate was resistant to clarithromycin and had decreased susceptibility to carbapenems. Our observations suggest that PD catheter removal is important in PD-associated peritonitis caused by M. abscessus in children and that more studies are needed to define the optimal length of treatment.
Project description:BackgroundMycobacterium abscessus group includes antibiotic-resistant, opportunistic mycobacteria that are responsible for sporadic cases and outbreaks of cutaneous, pulmonary and disseminated infections. However, because of their close genetic relationships, accurate discrimination between the various strains of these mycobacteria remains difficult. In this report, we describe the development of a multispacer sequence typing (MST) analysis for the simultaneous identification and typing of M. abscessus mycobacteria. We also compared MST with the reference multilocus sequence analysis (MLSA) typing method.ResultsBased on the M. abscessus CIP104536T genome, eight intergenic spacers were selected, PCR amplified and sequenced in 21 M. abscessus isolates and analysed in 48 available M. abscessus genomes. MST and MLSA grouped 37 M. abscessus organisms into 12 and nine types, respectively; four formerly "M. bolletii" organisms and M. abscessus M139 into three and four types, respectively; and 27 formerly "M. massiliense" organisms grouped into nine and five types, respectively. The Hunter-Gaston index was off 0.912 for MST and of 0.903 for MLSA. The MST-derived tree was similar to that based on MLSA and rpoB gene sequencing and yielded three main clusters comprising each the type strain of the respective M. abscessus sub-species. Two isolates exhibited discordant MLSA- and rpoB gene sequence-derived position, one isolate exhibited discordant MST- and rpoB gene sequence-derived position and one isolate exhibited discordant MST- and MLSA-derived position. MST spacer n°2 sequencing alone allowed for the accurate identification of the different isolates at the sub-species level.ConclusionsMST is a new sequencing-based approach for both identifying and genotyping M. abscessus mycobacteria that clearly differentiates formerly "M. massiliense" organisms from other M. abscessus subsp. bolletii organisms.
Project description:BackgroundMycobacterium abscessus is an emerging opportunistic pathogen which diversity was acknowledged by the recent description of two subspecies accommodating M. abscessus, Mycobacterium bolletii and Mycobacterium massiliense isolates.ResultsHere, genome analysis found 1-8 prophage regions in 47/48 M. abscessus genomes ranging from small prophage-like elements to complete prophages. A total of 20,304 viral and phage proteins clustered into 853 orthologous groups. Phylogenomic and phylogenetic analyses based on prophage region homology found three main clusters corresponding to M. abscessus, M. bolletii and M. massiliense. Analysing 135 annotated Tape Measure Proteins found thirteen clusters and four singletons, suggesting that at least 17 mycobacteriophages had infected M. abscessus during its evolution. The evolutionary history of phages differed from that of their mycobacterial hosts. In particular, 33 phage-related proteins have been horizontally transferred within M. abscessus genomes. They comprise of an integrase, specific mycobacteriophage proteins, hypothetical proteins and DNA replication and metabolism proteins. Gene exchanges, loss and gains which occurred in M. abscessus genomes have been driven by several mycobacteriophages.ConclusionsThis analysis of phage-mycobacterium co-evolution suggests that mycobacteriophages are playing a key-role in the on-going diversification of M. abscessus.ReviewersThis article was reviewed by Eric Bapteste, Patrick Forterre and Eugene Koonin.
Project description:Mycobacterium abscessus is an emerging human pathogen responsible for lung infections, skin and soft-tissue infections and disseminated infections in immunocompromised patients. It may exist either as a smooth (S) or rough (R) morphotype, the latter being associated with increased pathogenicity in various models. Genetic tools for homologous recombination and conditional gene expression are desperately needed to allow the study of M. abscessus virulence. However, descriptions of knock-out (KO) mutants in M. abscessus are rare, with only one KO mutant from an S strain described so far. Moreover, of the three major tools developed for homologous recombination in mycobacteria, only the one based on expression of phage recombinases is working. Several conditional gene expression tools have recently been engineered for Mycobacterium tuberculosis and Mycobacterium smegmatis, but none have been tested yet in M. abscessus. Based on previous experience with genetic tools allowing homologous recombination and their failure in M. abscessus, we evaluated the potential interest of a conditional gene expression approach using a system derived from the two repressors system, TetR/PipOFF. After several steps necessary to adapt TetR/PipOFF for M. abscessus, we have shown the efficiency of this system for conditional expression of an essential mycobacterial gene, fadD32. Inhibition of fadD32 was demonstrated for both the S and R isotypes, with marginally better efficiency for the R isotype. Conditional gene expression using the dedicated TetR/PipOFF system vectors developed here is effective in S and R M. abscessus, and may constitute an interesting approach for future genetic studies in this pathogen.
Project description:BackgroundMycobacterium abscessus complex (MABC) is the most drug resistant of the mycobacterial pathogens. M. abscessus subsp. abscessus encodes a functional erythromycin ribosomal methylase gene, erm(41), causing inducible macrolide resistance. However, some clinical isolates of M. abscessus subsp. abscessus harboring nonfunctional erm(41) were susceptible to macrolide, even after extended incubation of 14 days. Loss of function of the erm(41) genes was associated with a T-to-C substitution at position 28 of the gene (T28C), leading to an amino acid change from Trp to Arg at codon 10. Pulmonary disease caused by M. abscessus subsp. abscessus strains with an nonfunctional erm(41) (C28 sequevar) may be responsive to macrolide-containing antibiotic regimens. Therefore, all M. abscessus subsp. abscessus strains with a functional erm(41) (T28 sequevar) were thought to be resistant to macrolide with extended incubation. Here, we report the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus which was susceptible to macrolide due to T19 sequevar of erm(41) gene.Case presentationA 62-year-old Korean female was referred to our hospital due to chronic cough, sputum, and hemoptysis lasting more than 5 months. The patient's sputum was positive for acid-fast bacilli staining and nontuberculous mycobacteria (NTM) were isolated twice from sputum specimens. The isolate was identified as M. abscessus subsp. abscessus. The isolate had a point mutation of C → T at position 19 (C19 → T) in the erm(41) gene, instead of expected C28 sequevar of erm(41), and had no rrl mutation. The isolate displayed a clarithromycin susceptible phenotype with an Arg → Stop codon change in erm(41). The patient was successfully treated with a macrolide-containing regimen.ConclusionThis is the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus showing clarithromycin susceptible phenotype due to T19 sequevar of the erm(41) gene. The erm(41) gene is clinically important, and non-functional erm alleles may be an important issue for the management of MABC lung disease. The presence of a non-functional erm(41) allele in M. abscessus subsp. abscessus isolates may be associated with better outcomes.
Project description:M. abscessus complex prosthetic joint infections (PJI) of the knee are rare. We present a patient with an M. abscessus subsp. massiliense, a nontuberculous mycobacterium (NTM), peri-prosthetic knee infection who presented with wound drainage followed by sepsis. The published peer-reviewed literature on knee PJIs due to this organism is reviewed to highlight its clinical presentation,symptomatology, microbiology, surgical interventions, antimicrobial regimens, and outcomes.