Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

BACKGROUND: The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. PATIENTS AND METHODS: Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. RESULTS AND CONCLUSIONS: The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.

The Diagnosis of Nontuberculous Mycobacterial Pulmonary Disease by Single Bacterial Isolation Plus Anti-GPL-Core IgA Antibody.

Although serum anti-glycopeptidolipid (GPL)-core IgA antibody is a highly specific test for infection with Mycobacterium avium complex (MAC), Mycobacterium abscessus, and its subspecies abscessus, subsp. massiliense, and subsp. bolletii (MAB), its use for the definitive diagnosis of MAC pulmonary disease (PD) and MAB-PD are unknown. To clarify the diagnostic accuracy of the anti-GPL-core IgA antibody test among patients with radiologically suspected MAC-PD or MAB-PD who already have a single positive sputum culture test. The first isolations of MAC and MAB from patients with radiologically suspected MAC-PD or MAB-PD at the Osaka Toneyama Medical Center between January 2006 and December 2020 were collected. Patients were enrolled when their serum anti-GPL-core IgA antibody was measured during the 3 months before and after the first isolation. We retrospectively compared the results of anti-GPL-core IgA antibody testing with the final diagnoses based on the current guidelines. We included 976 patients for analysis. The serum anti-GPL-core IgA antibody was positive in 699 patients (71.6%). The positive predictive value of anti-GPL-core IgA antibody for the diagnosis of MAC-PD or MAB-PD was 97.4%. The median time required for the second positive culture after the first isolation was 51 days (interquartile range 12 to 196 days). The positive serum anti-GPL-core IgA antibody test allowed an early and definitive diagnosis of MAC-PD or MAB-PD in those who already had a single positive sputum culture test. IMPORTANCE To satisfy the microbiologic criteria of the current diagnostic guideline for nontuberculous mycobacterial pulmonary disease (PD), at least two positive sputum cultures of the same species of mycobacteria from sputum are required to avoid the casual isolation of mycobacteria. This study showed that the positivity of a serum anti-glycopeptidolipid (GPL)-core IgA antibody test has an excellent diagnostic ability among patients with radiologically suspected Mycobacterium avium complex (MAC)-PD or Mycobacterium abscessus (MAB)-PD who already had a single positive sputum culture test. The usage of single culture isolation plus anti-GPL-core IgA antibody as another diagnostic criterion has a time, cost, and effort-saving effect. Furthermore, it will facilitate the diagnosis of MAC-PD or MAB-PD in the early stage of disease because serum anti-GPL-core IgA antibody becomes high in these patients. Therefore, we proposed adding single culture isolation plus anti-GPL-core IgA antibody as "combined microbiological and serological criteria" to the diagnostic guidelines for MAC-PD and MAB-PD.

Painful Purulent Nodules Caused by Mycobacterium at Site of Lipodissolve Injections.

ABSTRACT: "Lipodissolve" (LD) is a non-FDA-approved solution of phosphatidylcholine in deoxycholate that was developed around 2004. A study of its safety reported minor and uncommon side effects including pain, tender nodules, pigmentary alterations, and ulceration at the site of injection. We present a 53-year-old woman who received LD injections bilaterally to her proximal arms. One week later, she developed painful nodules at each injection site. She was treated with a 10-day course of trimethoprim/sulfamethoxazole without improvement. An incisional biopsy was performed and showed deep dermal suppurative inflammation with numerous neutrophils and granulomas. Stains for bacteria, fungus, and acid-fast organisms were negative. Cultures for acid-fast bacilli grew Mycobacterium abscessus, sensitive to amikacin and clarithromycin. The patient was subsequently treated with intravenous amikacin, azithromycin, and bedaquiline with symptom resolution. Investigation revealed 3 similar infections linked to LD injections originating from the same physician's office. The most common organism implicated in injection infections is Staphylococcus aureus. Infections at injection sites caused by atypical mycobacteria have been reported to occur after tattooing, other types of injections, and implants. Of atypical mycobacteria, M. abscessus accounts for the greatest number of postinjection or iatrogenic infections. Common antitubercular drugs are not effective for treating atypical mycobacteria, making species identification and sensitivity testing imperative for treatment. This case highlights an unusual infection caused by cosmetic injections of LD, previously reported to be associated with minimal side effects, and the importance of examination for acid-fast bacilli and follow-up with culture, even in the absence of organisms identified on stained sections.

CLINICAL CHARACTERISTICS AND VISUAL OUTCOMES IN ENDOPHTHALMITIS AFTER KERATOPROSTHESIS IMPLANTATION.

PURPOSE: To describe the presentation, microbiology, management, and prognosis of eyes with endophthalmitis after Boston keratoprosthesis implantation. METHODS: Retrospective case series with history, diagnostics, management, and outcomes data in endophthalmitis after keratoprosthesis implantation presenting to a tertiary center between 2009 and 2020. RESULTS: Of 137 keratoprosthesis-implanted eyes, 7 eyes of 7 patients (5%) developed endophthalmitis. On presentation, 6 (86%) reported decreased visual acuity, and only 1 (14%) reported pain. Peripheral corneal ulcers were present in 2 eyes (29%). Seidel testing was negative in all cases. Six eyes (86%) had retroprosthetic membranes. One (14%) underwent initial pars plana vitrectomy with mechanical vitreous biopsy, whereas 6 (86%) received a needle vitreous tap-half of which were dry. Organisms were isolated after vitreous tap in two eyes: Streptococcus intermedius and Mycobacterium abscessus. The mean visual acuity preendophthalmitis, at presentation, and at 6 months were 20/267, 20/5,944, and 20/734, respectively. The visual acuity improved 9.08 ± 11.78 Early Treatment Diabetic Retinopathy Study lines from presentation to 6 months. Six-month visual acuity was correlated with preendophthalmitis visual acuity (r = 0.92, P = 0.003) but not presenting visual acuity (P = 0.838). CONCLUSION: Visual acuity at 6 months is correlated with preendophthalmitis visual acuity, not presenting visual acuity. Endophthalmitis should be considered in the differential diagnosis of painless intraocular inflammation any time after keratoprosthesis implantation, even if Seidel negative.

Minimum Inhibitory Concentrations before and after Antibacterial Treatment in Patients with Mycobacterium abscessus Pulmonary Disease.

The clinical importance of Mycobacterium abscessus (MABS) pulmonary disease has been increasing. However, there is still a lack of information about MIC distribution patterns and changes in clinical practice settings. The MIC results of rapidly growing mycobacteria isolated from 92 patients with nontuberculous mycobacterial pulmonary disease diagnosed from May 2019 to March 2021 were retrospectively analyzed. Most of the patients (86 patients; 93.5%) were infected with MABS; 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma). Significant differences in susceptibility to clarithromycin (15.2% versus 80.0%, P < 0.001) and azithromycin (8.7% versus 62.5%, P < 0.001) were observed between Mab and Mma. Most isolates were susceptible to amikacin (80; 93.0%), and over half were susceptible to linezolid (48; 55.8%). Only one-quarter of isolates (22, 25.6%) were susceptible to imipenem, while more than half (56; 65.1%) had intermediate susceptibility. Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, which were significantly higher than isolates for moxifloxacin (5; 5.8%), especially in Mab. Sixty-five (75.6%) isolates had MICs of less than 0.5 µg/mL to clofazimine. Two patients showed obvious MIC result changes: from susceptible to resistant to clarithromycin and from resistant to susceptible to amikacin and imipenem. In conclusion, MABS isolates were relatively susceptible to amikacin and linezolid, and clarithromycin and azithromycin were especially effective against Mma. In addition, sitafloxacin and clofazimine had low MICs and might be effective treatment agents. IMPORTANCE The MICs of isolates from 86 patients with Mycobacterium abscessus (MABS); 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma) were retrospectively analyzed. The main findings are as follows: (i) Mma were significantly more susceptible to clarithromycin and azithromycin than Mab, and both subspecies tended to be more susceptible to clarithromycin than azithromycin. (ii) Most isolates were susceptible to amikacin (93.0%), and over half to linezolid (55.8%). (iii) Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, and 65 (75.6%) had less than 0.5 µg/mL for clofazimine, which seems worth clinical investigating. (iv) Among nine cases analyzed chronological changes, only two patients showed obvious MIC result changes even after the long-term multidrug treatment. The present study revealed MICs of MABS clinical isolates before and after treatment in clinical settings, which could help develop future MABS treatments strategies.

Genome reorganization during emergence of host-associated Mycobacterium abscessus.

Mycobacterium abscessus is a rapid growing, free-living species of bacterium that also causes lung infections in humans. Human infections are usually acquired from the environment; however, dominant circulating clones (DCCs) have emerged recently in both M. abscessus subsp. massiliense and subsp. abscessus that appear to be transmitted among humans and are now globally distributed. These recently emerged clones are potentially informative about the ecological and evolutionary mechanisms of pathogen emergence and host adaptation. The geographical distribution of DCCs has been reported, but the genomic processes underlying their transition from environmental bacterium to human pathogen are not well characterized. To address this knowledge gap, we delineated the structure of M. abscessus subspecies abscessus and massiliense using genomic data from 200 clinical isolates of M. abscessus from seven geographical regions. We identified differences in overall patterns of lateral gene transfer (LGT) and barriers to LGT between subspecies and between environmental and host-adapted bacteria. We further characterized genome reorganization that accompanied bacterial host adaptation, inferring selection pressures acting at both genic and intergenic loci. We found that both subspecies encode an expansive pangenome with many genes at rare frequencies. Recombination appears more frequent in M. abscessus subsp. massiliense than in subsp. abscessus, consistent with prior reports. We found evidence suggesting that phage are exchanged between subspecies, despite genetic barriers evident elsewhere throughout the genome. Patterns of LGT differed according to niche, with less LGT observed among host-adapted DCCs versus environmental bacteria. We also found evidence suggesting that DCCs are under distinct selection pressures at both genic and intergenic sites. Our results indicate that host adaptation of M. abscessus was accompanied by major changes in genome evolution, including shifts in the apparent frequency of LGT and impacts of selection. Differences were evident among the DCCs as well, which varied in the degree of gene content remodelling, suggesting they were placed differently along the evolutionary trajectory toward host adaptation. These results provide insight into the evolutionary forces that reshape bacterial genomes as they emerge into the pathogenic niche.

Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus.

Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200-400 µg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 µg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 µg/ml of four potential AMPs, S61, S62, S63 and KLK1 after 3-days-incubation. At the MICs level, S63 showed the lowest toxicity with 1.50% hemolysis and 100% PBMC viability whereas KLK1 showed the highest hemolysis (10.21%) and lowest PBMC viability (93.52%). S61, S62 and S63 were further tested with clarithromycin-AMP interaction assays and found that 5/10 (50%) of selected isolates exhibited a synergistic interaction with 0.02-0.41 FICI values. This present study demonstrated the potential application of novel AMPs as an adjunctive treatment with clarithromycin against drug resistant Mab infection.

A first case report of nasopharyngeal Mycobacterium abscessus subspecies massiliense infection.

BACKGROUND: Mycobacterium abscessus subspecies massiliense is a non-tuberculous mycobacteriosis and was subdivided from Mycobacterium abscessus in 2006. This article is the first report on nasopharyngitis caused by Mycobacterium abscessus subspecies massiliense. CASE PRESENTATION: A 45-year-old woman had an 18-month history of recurrent nasopharyngitis and presented with pain in the throat. Mycobacterial tissue culture and polymerase chain reaction testing revealed the presence of Mycobacterium abscessus subspecies massiliense in the nasopharyngeal tissue. This patient underwent surgery, followed by multiple rounds of chemotherapy with oral and intravenous antibiotic agents for 16 weeks. She has had no recurrence during the 56 weeks since treatment. CONCLUSION: It is difficult to detect the presence of Mycobacterium abscessus subspecies massiliense in a culture from the swabbing sample. The tissue culture from a biopsy specimen is mandatory for the identification of the species. Currently, no definite treatment policy is available and only empirical treatment is applied. This case is an important for the diagnosis and treatment of this bacterial infection on nasopharynx.

Dissemination of Mycobacterium abscessus via global transmission networks.

Mycobacterium abscessus, a multidrug-resistant nontuberculous mycobacterium, has emerged as a major pathogen affecting people with cystic fibrosis (CF). Although originally thought to be acquired independently from the environment, most individuals are infected with one of several dominant circulating clones (DCCs), indicating the presence of global transmission networks of M. abscessus. How and when these clones emerged and spread globally is unclear. Here, we use evolutionary analyses of isolates from individuals both with and without CF to reconstruct the population history, spatiotemporal spread and recent transmission networks of the DCCs. We demonstrate synchronous expansion of six unrelated DCCs in the 1960s, a period associated with major changes in CF care and survival. Each of these clones has spread globally as a result of rare intercontinental transmission events. We show that the DCCs, but not environmentally acquired isolates, exhibit a specific smoking-associated mutational signature and that current transmission networks include individuals both with and without CF. We therefore propose that the DCCs initially emerged in non-CF populations but were then amplified and spread through the CF community. While individuals with CF are probably the most permissive host, non-CF individuals continue to play a key role in transmission networks and may facilitate long-distance transmission.

Global phylogenomic analyses of Mycobacterium abscessus provide context for non cystic fibrosis infections and the evolution of antibiotic resistance.

Mycobacterium abscessus (MAB) is an emerging pathogen that leads to chronic lung infections. To date, the global population structure of non-cystic fibrosis (CF) MAB and evolutionary patterns of drug resistance emergence have not been investigated. Here we construct a global dataset of 1,279 MAB whole genomes from CF or non-CF patients. We utilize whole genome analysis to assess relatedness, phylogeography, and drug resistance evolution. MAB isolates from CF and non-CF hosts are interspersed throughout the phylogeny, such that the majority of dominant circulating clones include isolates from both populations, indicating that global spread of MAB clones is not sequestered to CF contexts. We identify a large clade of M. abscessus harboring the erm(41) T28C mutation, predicted to confer macrolide susceptibility in this otherwise macrolide-resistant species. Identification of multiple evolutionary events within this clade, consistent with regain of wild type, intrinsic macrolide resistance, underscores the critical importance of macrolides in MAB.

Clinical Whole Genome Sequencing for Clarithromycin and Amikacin Resistance Prediction and Subspecies Identification of Mycobacterium abscessus.

Mycobacterium abscessus infections are an emerging health care concern in patients with chronic pulmonary diseases, leading to high morbidity and mortality. One major challenge is resistance to clarithromycin, a cornerstone antibiotic with high efficacy. Therefore, treatment is primarily guided by phenotypic susceptibility results of clarithromycin, which requires extended incubation to assess for inducible resistance. Resistance mechanisms for clarithromycin include induction of erm(41) and mutations in the 23S rRNA gene (rrl). In addition, mutations in the 16S rRNA encoding gene (rrs) can confer high-level amikacin resistance, another essential drug in the treatment of M. abscessus infections. Herein, we developed a clinical whole genome sequencing (WGS) assay for clarithromycin resistance based on rrl and erm(41) gene sequences and amikacin resistance based on the rrs sequence in M. abscessus, as well as subspecies identification. Genotypic-based predictions were determined for 104 isolates from 68 patients. The overall accuracy of genotypic prediction for clarithromycin compared with phenotypic susceptibility results was 100% (95% CI, 96.45%-100%). For amikacin, we also obtained 100% accuracy (95% CI, 96.52%-100%). The high concordance between the genotypic and phenotypic results demonstrates that a WGS-based assay can be used in a clinical laboratory for determining resistance to clarithromycin and amikacin in M. abscessus isolates. WGS can also provide subspecies identification and high-definition phylogenetic information for more accurate M. abscessus strain typing.

Genomic characterization of sporadic isolates of the dominant clone of Mycobacterium abscessus subspecies massiliense.

Recent studies have characterized a dominant clone (Clone 1) of Mycobacterium abscessus subspecies massiliense (M. massiliense) associated with high prevalence in cystic fibrosis (CF) patients, pulmonary outbreaks in the United States (US) and United Kingdom (UK), and a Brazilian epidemic of skin infections. The prevalence of Clone 1 in non-CF patients in the US and the relationship of sporadic US isolates to outbreak clones are not known. We surveyed a reference US Mycobacteria Laboratory and a US biorepository of CF-associated Mycobacteria isolates for Clone 1. We then compared genomic variation and antimicrobial resistance (AMR) mutations between sporadic non-CF, CF, and outbreak Clone 1 isolates. Among reference lab samples, 57/147 (39%) of patients with M. massiliense had Clone 1, including pulmonary and extrapulmonary infections, compared to 11/64 (17%) in the CF isolate biorepository. Core and pan genome analyses revealed that outbreak isolates had similar numbers of single nucleotide polymorphisms (SNPs) and accessory genes as sporadic US Clone 1 isolates. However, pulmonary outbreak isolates were more likely to have AMR mutations compared to sporadic isolates. Clone 1 isolates are present among non-CF and CF patients across the US, but additional studies will be needed to resolve potential routes of transmission and spread.

Isolation of non-tuberculous mycobacteria among tuberculosis patients, a study from a tertiary care hospital in Lahore, Pakistan.

BACKGROUND: There is scarce knowledge on the prevalence of diseases caused by non-tuberculous mycobacteria (NTM) in Pakistan. In the absence of culture and identification, acid-fast bacilli (AFB) causing NTM disease are liable to be misinterpreted as tuberculosis (TB). Introduction of nucleic acid amplification testing for Mycobacterium tuberculosis complex (MTBC) offers improved diagnostic accuracy, compared with smear microscopy, and also assists in differentiating MTBC from other mycobacteria. This study aimed to investigate the prevalence of NTM among patients investigated for TB and describe NTM disease and treatment outcomes at a tertiary care hospital in Pakistan. METHODS: This is a retrospective study, data on NTM isolates among culture-positive clinical samples over 4 years (2016-19) was retrieved from laboratory records. Information on clinical specimens processed, AFB smear results, and for the AFB positive isolates, results of species identification for MTBC, and for NTM isolates, results of species characterization and drug susceptibility testing was collected. Additional clinical data including patient characteristics, treatment regimens, and outcomes were collected for patients with NTM disease treated at Gulab Devi Hospital, Lahore. RESULTS: During the study period, 12,561 clinical specimens were processed for mycobacterial culture and 3673 (29%) were reported positive for AFB. Among these 3482 (95%) were identified as MTBC and 191 (5%) as NTM. Among NTM, 169 (88%) were isolated from pulmonary and 22 (12%) from extrapulmonary specimens. Results of NTM speciation were available for 60 isolates and included 55% (n = 33) M. avium complex and 25% (n = 15) M. abscesses. Among these patients, complete clinical records were retrieved for 12 patients with pulmonary disease including nine infected with M. avium complex and three with M. abscessus. All 12 patients had a history of poor response to standard first-line anti-TB treatment. Ten patients were cured after 18 months of treatment, whereas, one with M. abscessus infection died and another was lost to follow up. CONCLUSION: In TB endemic areas, NTM can be misdiagnosed as pulmonary TB leading to repeated failed anti-TB treatment and increased morbidity, emphasizing the need for improved diagnosis.

Simultaneous catheter removal and reinsertion, is it acceptable in M. abscessus exit site infection?

In recent times, increasing reports of exit site infections (ESI) in peritoneal dialysis (PD) patients related to environmentally acquired atypical organisms, such as nontuberculous mycobacterium (NTM), have been reported in the literature. Among these NTM, Mycobacterium abscessus (M. abscessus) is unique and is associated with high morbidity and treatment failure rates. The international society of PD guidelines suggests individualizing therapeutic options for NTM-related ESI. Moreover, the guidelines encourage simultaneous catheter removal and reinsertion (SCRR) in isolated ESI, not responding to antimicrobial therapy to avoid PD interruptions. Physicians should be aware of the limitations of such approaches as delay in appropriate PD catheter intervention can be fraught with complications in patients with M. abscessus ESI. We report an M. abscessus ESI in a PD patient who underwent SCRR in conjunction with targeted antimicrobial therapy, and developed M. abscessus peritonitis requiring PD catheter removal and conversion to hemodialysis. The patient also developed ESI at the new exit site long after the PD catheter was removed, requiring prolonged antimicrobial therapy. Our case, taken together with available published case reports, highlights the futility of the SCRR approach towards the M. abscessus ESI and makes the cases for early PD catheter removal in these patients.

Geographical distribution and regional differences in 532 clinical isolates of rapidly growing mycobacterial species in Japan.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly becoming a major global problem. Additionally, Mycobacteroides abscessus subsp. abscessus (MAB) infections are refractory to macrolides. This study was conducted to investigate the epidemiology of rapidly growing mycobacteria (RGM) species isolated from clinical specimens in Japan and assess differences in the regional distribution of lower respiratory specimens (LRS)- and non-lower respiratory specimens (NLRS)-derived species. 532 strains (427 LRS, 92 NLRS and 15 unknown specimens) were isolated in nine areas of Japan. We collected 418 specimens from Bio Medical Laboratories (BML), Inc., and 114 specimens from 45 hospitals in Japan. Their epidemiological differences were examined according to the specimen type, region, and climate. Fifteen species were identified. The proportion of M. abscessus group (MAG) strains was significantly lower in NLRS than in LRS (35.9% vs. 68.4%). The proportion of MAG strains was higher in northern Japan than in other regions (83.7% vs. 60.5%). Variations in strain abundance among RGM species was evident in regions with a mean annual temperature below 15 °C. We conclude that the proportions of MAG strains differed between NLRS and LRS in Japan. In addition, the mean annual temperature likely influenced the distribution of RGM species.

Association between 16S rRNA gene mutations and susceptibility to amikacin in Mycobacterium avium Complex and Mycobacterium abscessus clinical isolates.

We evaluated the association between 16S rRNA gene (rrs) mutations and susceptibility in clinical isolates of amikacin-resistant nontuberculous mycobacteria (NTM) in NTM-pulmonary disease (PD) patients. Susceptibility was retested for 134 amikacin-resistant isolates (minimum inhibitory concentration [MIC] ≥ 64 µg/ml) from 86 patients. Amikacin resistance was reconfirmed in 102 NTM isolates from 62 patients with either Mycobacterium avium complex-PD (MAC-PD) (n = 54) or M. abscessus-PD (n = 8). MICs and rrs mutations were evaluated for 318 single colonies from these isolates. For the 54 MAC-PD patients, rrs mutations were present in 34 isolates (63%), comprising all 31 isolates with amikacin MICs ≥ 128 µg/ml, but only three of 23 isolates with an MIC = 64 µg/ml. For the eight M. abscessus-PD patients, all amikacin-resistant (MIC ≥ 64 µg/ml) isolates had rrs mutations. In amikacin-resistant isolates, the A1408G mutation (n = 29) was most common. Two novel mutations, C1496T and T1498A, were also identified. The culture conversion rate did not differ by amikacin MIC. Overall, all high-level and 13% (3/23) of low-level amikacin-resistant MAC isolates had rrs mutations whereas mutations were present in all amikacin-resistant M. abscessus isolates. These findings are valuable for managing MAC- and M. abscessus-PD and suggest the importance of phenotypic and genotypic susceptibility testing.

Outcomes of Inhaled Amikacin-Containing Multidrug Regimens for Mycobacterium abscessus Pulmonary Disease.

BACKGROUND: Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics. RESEARCH QUESTION: What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens? STUDY DESIGN AND METHODS: We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form. RESULTS: Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]). INTERPRETATION: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Comparison of drug-susceptibility patterns and gene sequences associated with clarithromycin and azithromycin resistance in Mycobacterium abscessus complex isolates and evaluation of the accumulation of intrinsic macrolide resistance.

Introduction. Mycobacterium abscessus complex (MABC) is an infectious agent associated with macrolide resistance and treatment failure.Hypothesis/Gap Statement. Despite drug-susceptibility testing for MABC isolates including clarithromycin (CAM), long-term treatment with azithromycin (AZM) for MABC disease is recommended.Aim. We compared phenotypic and genotypic resistance to AZM and CAM in clinical isolates and evaluated the accumulation of intrinsic macrolide resistance (AIM) and morphological changes by macrolides exposure.Methodology. Forty-nine isolates were characterized regarding erm(41) sequevars. Sequencing data were compared to the nucleotide sequence of rrl and whiB7. The AIM MIC was performed in three reference strains and 15 isolates were randomized [each set of five isolates with M. abscessus subsp. abscessus (MAA) T28, MAA C28 and subsp. massiliense (MAM)].Results. The 49 isolates were distributed as 24 MAA T28, 5 MAA C28 and 20 MAM. The MIC50 values to CAM at day 3 in MAA T28, C28 and MAM were 1, 0.12 and 0.12 µg ml-1, while those at day 14 were 32, 0.5 and 0.12 µg ml-1, respectively. The AZM-MIC50 values at day 3 of the above isolates were 4, 0.25 and 0.5 µg ml-1, while those at day 14 were >64, 0.5 and 0.5 µg ml-1, respectively. Neither mutations in rrl of MAA T28 with acquired resistance nor deletions in whiB7 of MAA T28 without inducible resistance were observed . For AIM MIC, MAA T28 showed that the time-to-detection of AZM resistance was significantly faster over that of CAM (P<0.05). Morphological changes were not determined in all isolates.Conclusion. Our findings did not support the suggestion for the preferential use of AZM for, at least, MAA T28 disease due to the high-level MIC value and the increased AIM. The long duration of AZM-based treatment eventually may favour the emergence of isolates with a high-level of intrinsic resistance.

Comparison of two-drug combinations, amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin against Mycobacteroides abscessus subsp. abscessus using the in vitro time-kill assay.

Nontuberculous mycobacteria include 198 mycobacterial species. Among these, Mycobacteroides abscessus is a rapidly growing mycobacteria that causes lung and skin infections. M. abscessus lung infections are difficult to treat due to the high levels of resistance to several classes of antibiotics. The current treatment is based on combining at least two or three antibiotics. However, treatment outcomes remain very poor. The objective was to compare the in vitro activity of amikacin, tigecycline, imipenem, and clarithromycin, alone and in two different three-drug combinations (amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin) against seven M. abscessus subsp. abscessus clinical isolates using the time-kill assay. The two combinations showed greater activity than the antibiotics tested individually. Even though both combinations showed similar activity as well as no antagonistic activity, the combination including imipenem could not be an alternative treatment against M. abscessus subsp. abscessus lung infections caused by clarithromycin susceptible isolates. However, this combination could be considered against clarithromycin resistant isolates. Future studies are necessary to confirm this hypothesis.

Mycobacterium abscessus exit-site infection in peritoneal dialysis patients: should we ever aim to salvage the catheter?

Improvements in the exit-site care for peritoneal dialysis (PD) patients have uncovered a trend for increasing incidence of rapidly growing nontuberculous mycobacterium exit-site infections (ESI). Among these, Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates. The international society of PD guidelines encourage PD catheter removal in patients with M. abscessus peritonitis but, do not have evidence-based recommendations for the management of ESIs related to this organism. We report an unusual case in which an asymptomatic end-stage renal disease patient with multiple favorable clinical characteristics, i.e., no apparent immunodeficiency, sensitivity pattern showing possibility of treatment with multiple antibiotics, no evidence of peritonitis, and early clinical response, was treated with a 9-month combination antimicrobial regimen administered orally and intraperitoneally. Despite excellent clinical response with a resolution of the ESI, our patient relapsed quickly, within 30 days of stopping antimicrobial therapy and required PD catheter removal. Our case, taken together with available published case reports, highlights the futility of the conservative approach towards the M. abscessus ESI and makes the cases for early PD catheter removal in these patients.