RESUMEN
BACKGROUND: The prevalence of nontuberculous mycobacteria (NTM) infections is rising in people with cystic fibrosis (pwCF). NTM infection, especially infection with Mycobacterium abscessus complex (MABC), is commonly associated with severe lung deterioration. The current treatment modalities, including multiple intravenous antibiotics, frequently fail to achieve airway eradication. Although treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to modulate the lung microbiome, data regarding its role in eradicating NTM in pwCF is lacking. Our aim was to evaluate the impact of ETI on the rate of NTM eradication in pwCF. METHODS: This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment. RESULTS: Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05). CONCLUSIONS: For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.
Asunto(s)
Aminofenoles , Benzodioxoles , Fibrosis Quística , Indoles , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Pirazoles , Piridinas , Pirrolidinas , Quinolonas , Femenino , Humanos , Anciano , Adulto Joven , Adulto , Masculino , Micobacterias no Tuberculosas , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/epidemiología , Estudios de Cohortes , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Regulador de Conductancia de Transmembrana de Fibrosis QuísticaRESUMEN
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.
Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Mycobacterium abscessus/efectos de los fármacos , Anciano , Antibacterianos/análisis , Azitromicina/análisis , Azitromicina/uso terapéutico , Claritromicina/análisis , Claritromicina/uso terapéutico , Femenino , Humanos , Enfermedades Pulmonares/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/genética , Mycobacterium abscessus/aislamiento & purificación , Mycobacterium abscessus/fisiología , Estudios RetrospectivosRESUMEN
This study aimed to assess the clinical presentation, antibiotic therapy, surgery, and outcomes in patients with otitis media caused by Mycobacterium abscessus subsp. abscessus and discuss the efficacy of surgery. This is a retrospective case review of three patients diagnosed with otomastoiditis caused by M. abscessus subsp. abscessus. All patients had refractory otorrhea. One patient had granulation tissue in the tympanic membrane. They received medical treatment and underwent surgery. Otorrhea was resolved several months after the initiation of long-term multiantibiotic therapy in all cases. The timing of surgery varied among patients. Before initiating antibiotic therapy, mastoidectomy was performed to achieve definitive diagnosis in two patients, and wound dehiscence developed in these patients. Two patients underwent debridement after the initiation of multiantibiotic therapy. After antibiotic administration, tympanoplasty was performed to improve hearing in one patient. All patients achieved culture negativity after treatment, and no recurrences have been noted. From three cases, it is suggested that the mainstay of treatment for M. abscessus subsp. abscessus is long-term multiantibiotic therapy, and surgery itself may have little effect on achieving ear dryness. Thus, in most patients, drug therapy should be prioritized. Considering postoperative complications, surgery before achieving ear dryness should be avoided, except in emergency cases. In addition, if the diagnosis is not confirmed by repeated bacteriological tests, mastoidectomy should be performed to collect specimens. Tympanoplasty for hearing loss or eardrum perforation is recommended after discontinuation of medications.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Otitis Media , Antibacterianos/uso terapéutico , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Otitis Media/tratamiento farmacológico , Otitis Media/cirugía , Estudios RetrospectivosRESUMEN
The rapidly growing mycobacterium Mycobacterium abscessus is a clinically important organism causing pulmonary and skin diseases. The M. abscessus complex is comprised of three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Here, we aimed to develop a Cas12a/sgRNA-based nucleic acid detection platform to identify M. abscessus species and subspecies. By designing specific sgRNA probes targeting rpoB and erm(41), we demonstrated that M. abscessus could be differentiated from other major mycobacterial species and identified at the subspecies level. Using this platform, a total of 38 clinical M. abscessus isolates were identified, 18 as M. abscessus subsp. abscessus and 20 as M. abscessus subsp. massiliense. We concluded that the Cas12a/sgRNA-based nucleic acid detection platform provides an easy-to-use, quick, and cost-effective approach for identification of M. abscessus species and subspecies.
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Proteínas Bacterianas/genética , Proteínas Asociadas a CRISPR/genética , Endodesoxirribonucleasas/genética , Tipificación Molecular/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/clasificación , Mycobacterium abscessus/genética , ARN Guía de Kinetoplastida , Sistemas CRISPR-Cas , ADN Bacteriano , Genes Bacterianos , Humanos , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Flujo de TrabajoRESUMEN
There have been no case reports of thoracic subcutaneous abscess after surgery for Mycobacterium abscessus complex associated empyema. We herein report a case of Mycobacterium abscessus subsp. abscessus (M. abscessus subsp. abscessus) induced subcutaneous abscesses following surgical treatment for concurrent M. abscessus subsp. abscessus -associated empyema and pneumothorax. A 75-year-old woman had M. abscessus subsp. abscessus -associated empyema and pneumothorax. She underwent surgical treatment of decortication and fistulectomy and suffered from M. abscessus subsp. abscessus -associated subcutaneous abscesses after thoracentesis/drainage. A multidisciplinary approach combined with surgical care, thermal therapy, and multidrug chemotherapy contributed to a successful result. An early multidisciplinary approach is believed to be important in cases of M. abscessus subsp. abscessus -associated empyema and subcutaneous abscess.
Asunto(s)
Absceso/microbiología , Empiema Pleural/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium abscessus/aislamiento & purificación , Tejido Subcutáneo/patología , Absceso/diagnóstico , Absceso/terapia , Anciano , Antibacterianos/uso terapéutico , Empiema Pleural/complicaciones , Empiema Pleural/diagnóstico , Empiema Pleural/tratamiento farmacológico , Femenino , Humanos , Hipertermia Inducida/métodos , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Neumotórax/complicaciones , Neumotórax/diagnóstico , Neumotórax/microbiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/microbiología , Tejido Subcutáneo/microbiología , Tórax/diagnóstico por imagen , Tórax/patología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Background: Among Mycobacterium abscessus complex infections, patients with M. abscessus subsp. abscessus (MAA) lung disease are difficult to treat and no standard therapy has been established. Few reports have investigated the drug susceptibility of these strains. We retrospectively investigated how in vitro drug susceptibility testing (DST) of MAA affects the induction of sputum conversion using pharmacotherapy. Methods: Patients with MAA lung disease diagnosed and treated between 2010 and 2014 at our hospital were enrolled and divided into Group A (sputum conversion without relapse within 1 year) and Group B (persistent positive cultured or negative conversion with relapse). MAA was identified in M. abscessus using sequence with genotyping, and DST of MAA was performed. Results: We assessed 23 patients (9 males and 14 females). There were 8 patients in Group A and 15 in Group B. Higher prevalence of susceptible isolates for clarithromycin (CAM) susceptibility on day 14 was noted in Group A than in Group B (P = 0.03) and no significant difference observed in the two groups for other drugs. Conclusions: In vitro DST of MAA, especially CAM susceptibility on day 14, affected the results of negative conversion. No other drugs were found to affect sputum culture negative conversion.
Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Enfermedades Pulmonares/microbiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/aislamiento & purificación , Esputo/microbiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: Macrolide susceptibility differs between subspecies in the Mycobacterium abscessus complex, likely due to differences in erm(41) sequevars. Patients with M. abscessus complex infection generally show poor clinical outcomes in response to antibiotic treatment. Here, the association between genotype and treatment outcome was investigated. METHODOLOGY: We collected 69 isolates from 35 patients with non-cystic fibrosis bronchiectasis: 24 had M. abscessus complex lung disease and non-cystic fibrosis bronchiectasis, and 11 were colonized. Outcome analysis was performed in the 24 infected patients. Molecular analyses, including erm(41) and rrl sequencing, and variable-number tandem-repeat (VNTR) analysis of 69 isolates, from 24 infected and 11 colonized patients, were performed to elucidate the influence of genotype on antibiotic susceptibility. RESULTS: Among the 24 patients, 18 (14 infected with M. abscessus subsp. abscessus and 4 with M. abscessus subsp. massiliense) showed unfavourable outcomes; six (three infected with M. abscessus subsp. abscessus and three with M. abscessus subsp. massiliense) exhibited favourable outcomes. Patients with unfavourable outcomes showed acquired clarithromycin resistance (33.3 vs 0â%), mixed sequevars (38.9 vs 16.7â%) and differing VNTR patterns between initial and serial isolates (33.3 vs 16.7â%). In contrast, in the 11 colonized patients, M. abscessus subsp. abscessus C28 (sequevar 02) and M. abscessus subsp. massiliense were the most prevalent subspecies. CONCLUSION: Patients infected with multiple sequevars and genotypes were more likely to exhibit treatment failure and/or recurrence. The precise identification of subspecies and analyses of mycobacterial characteristics may help to predict treatment outcomes in patients with M. abscessus complex lung disease.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/aislamiento & purificación , Claritromicina/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Genotipo , Humanos , Japón , Macrólidos/uso terapéutico , Pruebas de Sensibilidad Microbiana/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: To separate Mycobacterium abscessus subsp. bolletii from Mycobacterium abscessus subsp. abscessus using species identification, and to investigate the in vitro activity of amikacin, cefoxitin, imipenem, levofloxacin, moxifloxacin, clarithromycin, azithromycin, and linezolid against Mycobacterium abscessus. METHODS: Seventy M. abscessus isolates, previously identified by 16S rRNA sequencing, were further identified by comparative sequence analysis of rpoB and hsp65. Drug susceptibility testing was conducted using the microplate Alamar Blue assay in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines and interpreted using CLSI breakpoints. RESULTS: Of the 70 strains, 45 (64%) were M. abscessus subsp. abscessus and 25 (36%) were M. abscessus subsp. bolletii. The majority of M. abscessus isolates were susceptible to azithromycin, amikacin, linezolid, and imipenem (M. abscessus subsp. abscessus: 93%, 98%, 93%, and 73%, respectively; M. abscessus subsp. bolletii: 96%, 96%, 80%, and 68%, respectively). Approximately half of the M. abscessus isolates were moderately susceptible to cefoxitin and moxifloxacin (M. abscessus subsp. abscessus 53% and 49%; M. abscessus subsp. bolletii 72% and 68%). Nearly all the M. abscessus isolates were resistant to levofloxacin (M. abscessus subsp. abscessus 96%, M. abscessus subsp. bolletii 100%). Inducible clarithromycin resistance was found in M. abscessus. After 14 days of incubation, 83% M. abscessus subsp. abscessus and 36% M. abscessus subsp. bolletii were resistant to clarithromycin. CONCLUSIONS: Using rpoB and hsp65, M. abscessus subsp. bolletii could be distinguished from M. abscessus subsp. abscessus. Amikacin and azithromycin showed excellent activity against M. abscessus in vitro. Imipenem, linezolid, cefoxitin, and moxifloxacin also showed good activity. Levofloxacin was inactive against M. abscessus. Although clarithromycin showed excellent activity against M. abscessus on day 3, inducible resistance occurred, and after 14 days clarithromycin showed little activity against M. abscessus subsp. abscessus, but still had good activity against M. abscessus subsp. bolletii.
Asunto(s)
Antibióticos Antituberculosos/farmacología , Proteínas Bacterianas/genética , Chaperonina 60/genética , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/efectos de los fármacos , Micobacterias no Tuberculosas/genética , Técnicas de Genotipaje , Humanos , Micobacterias no Tuberculosas/clasificación , Micobacterias no Tuberculosas/crecimiento & desarrollo , Fenotipo , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Esputo/microbiologíaRESUMEN
Mycobacterium abscessus complex (M. abscessus subsp. abscessus and M. abscessus subsp. bolletii) is an emerging pathogen causing various human infections. However, few studies have focused on M. abscessus complex bacteraemia with detailed species differentiation. The clinical characteristics of patients with bacteraemia due to M. abscessus complex treated at National Taiwan University Hospital from 2005-2012 were evaluated. Species identification was performed by molecular methods, and minimum inhibitory concentrations (MICs) were determined using a Sensititre RAPMYCO Panel Test for preserved M. abscessus complex isolates. During the study period, 15 patients with M. abscessus complex bacteraemia were found but only 14 isolates from 13 patients were preserved for analysis. One patient had two episodes of bacteraemia (one caused by M. abscessus subsp. bolletii and one by M .abscessus subsp. abscessus with a 9-month interval). Of the remaining 12 patients, 9 patients had M. abscessus subsp. bolletii bacteraemia and 3 had M .abscessus subsp. abscessus bacteraemia. Patients were mainly middle-aged adults with various co-morbidities. Steroid usage and malignancy (5/15) were the most common immunocompromised statuses, followed by diabetes mellitus (4/15). Surgical wound infection was the most common infection foci in all patients (5/15), particularly in M. abscessus subsp. bolletii bacteraemia patients. Clarithromycin and tigecycline exhibited good in vitro activities. Overall, the 14-day mortality was 20% (3/15). M. abscessus complex bacteraemia should be considered an emerging opportunistic infection in immunocompromised hosts. Clarithromycin and tigecycline have potent in vitro activities and are promising agents for treating infections due to M. abscessus complex.
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Antibacterianos/farmacología , Bacteriemia/microbiología , Bacteriemia/patología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/patología , Micobacterias no Tuberculosas/efectos de los fármacos , Adolescente , Anciano , Anciano de 80 o más Años , Femenino , Hospitales Universitarios , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Micobacterias no Tuberculosas/clasificación , Micobacterias no Tuberculosas/aislamiento & purificación , TaiwánRESUMEN
Rapidly growing, non-tuberculous mycobacteria (NTM) in the Mycobacterium abscessus (MAB) species are emerging pathogens that cause various diseases including skin and respiratory infections. The species has undergone recent taxonomic nomenclature refinement, and is currently recognized as two subspecies, M. abscessus subsp. abscessus (MAB-A) and M. abscessus subsp. bolletii (MAB-B). The recently reported outbreaks of MAB-B in surgical patients in Brazil from 2004 to 2009 and in cystic fibrosis patients in the United Kingdom (UK) in 2006 to 2012 underscore the need to investigate the genetic diversity of clinical MAB strains. To this end, we sequenced the genomes of two Brazilian MAB-B epidemic isolates (CRM-0019 and CRM-0020) derived from an outbreak of skin infections in Rio de Janeiro, two unrelated MAB strains from patients with pulmonary infections in the United States (US) (NJH8 and NJH11) and one type MAB-B strain (CCUG 48898) and compared them to 25 publically available genomes of globally diverse MAB strains. Genome-wide analyses of 27,598 core genome single nucleotide polymorphisms (SNPs) revealed that the two Brazilian derived CRM strains are nearly indistinguishable from one another and are more closely related to UK outbreak isolates infecting CF patients than to strains from the US, Malaysia or France. Comparative genomic analyses of six closely related outbreak strains revealed geographic-specific large-scale insertion/deletion variation that corresponds to bacteriophage insertions and recombination hotspots. Our study integrates new genome sequence data with existing genomic information to explore the global diversity of infectious M. abscessus isolates and to compare clinically relevant outbreak strains from different continents.
Asunto(s)
Pulmón/microbiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/clasificación , Enfermedades Cutáneas Bacterianas/microbiología , Proteínas Bacterianas/genética , Técnicas de Tipificación Bacteriana , Bacteriófagos/genética , Secuencia de Bases , Brasil/epidemiología , ADN Bacteriano/genética , Epidemias , Variación Genética , Genotipo , Humanos , Micobacterias no Tuberculosas/genética , Micobacterias no Tuberculosas/aislamiento & purificación , Filogenia , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
The aim of this study was to genetically analyse Mycobacterium abscessus subsp. abscessus (hereafter M. abscessus) and M. abscessus subsp. bolletii (hereafter M. bolletii) isolates from six different regions of Japan and to determine the antimicrobial susceptibility of these isolates. Subspeciation of 143 clinical isolates of M. abscessus group was done by comparative sequence analysis of the rpoB and hsp65 genes and the internal transcribed spacer (ITS) region. Genetic analysis led to the identification of 90 M. abscessus (62.9%) and 53 M. bolletii (37.1%; comprising 50 'M. massiliense' and 3 'M. bolletii' in the old nomenclature). No significant differences were found between the M. abscessus and M. bolletii isolates in any characteristics. Susceptibility to clarithromycin and linezolid for M. bolletii isolates was significantly higher than that for M. abscessus (P<0.05). Moreover, the results demonstrated that 82 M. abscessus isolates with T28 sequevar were resistant to clarithromycin owing to the expression of erm(41), which was induced by clarithromycin, whilst 8 isolates with C28 sequevar were susceptible. Acquired clarithromycin resistance in 'M. bolletii' isolates was significantly associated with previous Mycobacterium avium complex (MAC) treatment compared with that of M. abscessus isolates; however, intrinsic inducible susceptibility of M. abscessus isolates was not associated with MAC treatment. However, acquired resistance to clarithromycin by mutation in the rrl gene encoding 23S rRNA did not occur in 14 of 18 resistant isolates. Strains with acquired resistance to clarithromycin and mutation in rrl consisted of two M. bolletii (one 'M. massiliense' and one 'M. bolletii') and two M. abscessus T28 sequevar.