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1.
Diagn Microbiol Infect Dis ; 110(2): 116435, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39032320

RESUMEN

PURPOSE: Mycobacterium abscessus complex (MABC) infections are increasing worldwide. Furthermore, these infections have a low treatment success rate due to their resistance to many current antibiotics. This study aimed to determine the overall in vitro activity of the tetracyclines doxycycline (DOX), minocycline (MIN), and tigecycline (TGC) against MABC clinical isolates. PATIENTS AND METHODS: A systematic review of PubMed/MEDLINE, Web of Science, and Embase was conducted up to August 28, 2023. Studies applying the drug susceptibility testing standards of the Clinical and Laboratory Standards Institute were considered. A random effects model was used to assess the total in vitro resistance rates of the MABC clinical isolates to DOX, MIN, and TGC. The I2 and Cochran's Q statistics were employed to evaluate the origins of heterogeneity. All analyses were conducted using CMA V.3 software. RESULTS: Twenty-six publications (22, 12, and 11 studies on DOX, MIN, and TGC, respectively) were included. The pooled in vitro resistance rates of the MABC clinical isolates to DOX and MIN at the breakpoint of 8 µg/mL were 93.0 % (95 % CI, 89.2 %-95.5 %) and 87.2 % (95 % CI, 76.5 %-93.4 %), respectively. In the case of TGC, the breakpoints of 2, 4, and 8 µg/mL were associated with pooled resistance rates of 2.5 % (95 % CI, 0.5 %-11.6 %), 7.2 % (95 % CI, 4.0 %-12.5 %), and 16.8 % (95 % CI, 4.7 %-45.0 %), respectively. CONCLUSION: Among the three examined tetracyclines, MABC exhibited extremely high resistance rates to DOX and MIN, thereby limiting their use in treating MABC infections. Conversely, MABC showed an increased susceptibility rate to TGC, highlighting TGC administration as a viable treatment option for patients with MABC infections.


Asunto(s)
Antibacterianos , Doxiciclina , Pruebas de Sensibilidad Microbiana , Minociclina , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Tigeciclina , Minociclina/farmacología , Minociclina/análogos & derivados , Tigeciclina/farmacología , Humanos , Doxiciclina/farmacología , Doxiciclina/uso terapéutico , Mycobacterium abscessus/efectos de los fármacos , Antibacterianos/farmacología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Farmacorresistencia Bacteriana
2.
Jpn J Radiol ; 42(8): 852-861, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38705936

RESUMEN

PURPOSE: Mycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment. METHODS: We retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses. RESULTS: The CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure. CONCLUSIONS: A high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Tomografía Computarizada por Rayos X , Insuficiencia del Tratamiento , Humanos , Estudios Retrospectivos , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Antibacterianos/uso terapéutico , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/tratamiento farmacológico , Valor Predictivo de las Pruebas , Estudios de Cohortes , Adulto , Pulmón/diagnóstico por imagen , Pronóstico
3.
J Glob Antimicrob Resist ; 37: 135-140, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561143

RESUMEN

OBJECTIVE: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections. METHODS: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. RESULTS: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively. CONCLUSION: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.


Asunto(s)
Antituberculosos , Diarilquinolinas , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Complejo Mycobacterium avium , Diarilquinolinas/farmacología , Humanos , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/aislamiento & purificación , Complejo Mycobacterium avium/efectos de los fármacos , Complejo Mycobacterium avium/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Infección por Mycobacterium avium-intracellulare/microbiología
4.
Infect Drug Resist ; 17: 1243-1249, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38560704

RESUMEN

Background: In recent decades, there has been a substantial surge in the incidence of non-tuberculous Mycobacteria (NTM) infections. However, the diagnosis and management of NTM globally present significant challenges, particularly in cases involving Mycobacterium abscessus complex (MABC) infection where effective therapeutic options are limited. Case Presentation: We reported a 38-year-old female patient who was infected with MABC of skin due to "beauty needle" at a beauty salon, with mass on both cheeks, accompanied by redness, and pain, and some of them was ulcered and effused. Puncture pumping pus from bilateral cheek mass for many times, rinsed with "metronidazole", and oral "cephalosporin" treatment did not work. Therefore, she came to our hospital. MABC was detected in abscess paracentesis pus by nucleic acid mass spectrometry, and was proved by the cultured result of the pus. Thus, the patient was diagnosed as skin MABC infection, and anti-NTM treatment was taken. However, adverse reactions such as tinnitus, hepatotoxicity and neurovirulence occurred during the initial treatment. After adjusting to the contezolid-containing regimen, these adverse reactions improved. After nearly 6 months of treatment, the cheek mass was gradually reduced and the skin ruptures were gradually healed. Follow-up for 10 months showed that the patient's facial symptoms were significantly improved, and no drug-related adverse reactions happened. Conclusion: This was the first successful case of multiple drug resistance MABC infection of skin treated with contezolid-containing antibiotic management strategies, which exhibited remarkable efficacy and good safety in this intractable disease.

5.
Int J Infect Dis ; 139: 118-123, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37977501

RESUMEN

OBJECTIVES: Persistent growth of Mycobacterium abscessus complex (MABC) in the respiratory system is not uncommon and may indicate continuous infection of MABC lung disease (MABC-LD), but its prevalence, risk factors, and clinical impact have not been investigated. METHODS: The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression. RESULTS: Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed. CONCLUSIONS: MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression.


Asunto(s)
Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Prevalencia , Enfermedades Pulmonares/microbiología , Factores de Riesgo , Antibacterianos/uso terapéutico
6.
J Cyst Fibros ; 23(1): 41-49, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37173154

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 Quística
7.
Pol J Microbiol ; 72(4): 491-506, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38103008

RESUMEN

One of the most relevant and pathogenic groups among the rapidly growing mycobacteria (RGM) is Mycobacterium abscessus complex (MABC) that includes three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. bolletii, and M. abscessus subsp. massiliense. The aim of this study was the analysis of prevalence of MABC among other non-tuberculous mycobacteria isolated from patients in the Malopolska Region of Poland, between 2018 and 2021, as well as determination of their subspecies and molecular mechanisms of resistance to macrolides and aminoglycosides. The incidence of MABC was 5,4% (12/223). Eight strains were classified as M. abscessus subsp. abscessus, three as M. abscessus subsp. massiliense and one M. abscessus subsp. bolletii. Molecular analysis showed resistance to macrolides for eight strains of M. abscessus subsp. abscessus associated with erm(41)T28 gene mutations. One strain of M. abscessus subsp. abscessus showed resistance to macrolides (two mutations simultaneously: in erm(41)T28 and rrl genes) and aminoglycosides (point mutation in rrs gene). One strain of M. abscessus subs. bolletii was resistant to macrolides (erm(41)T28 mutation), whereas presented no mutations for aminoglycosides. M. abscessus subsp. massiliense reveal no mutations. High clarithromycin resistance of M. abscessus, determines the urgent need for susceptibility-based treatment. Molecular determination of resistance mechanisms to aminoglycosides and macrolides enables fast and accurate targeted treatment implementation.


Asunto(s)
Macrólidos , Mycobacterium abscessus , Humanos , Macrólidos/farmacología , Mycobacterium abscessus/genética , Aminoglicósidos/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Claritromicina , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética
8.
Cureus ; 15(10): e46897, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37954748

RESUMEN

The incidence of infections caused by nontuberculous mycobacteria (NTM) is rising around the world, and they are becoming increasingly difficult to treat due to the bacteria being drug-resistant to several antibiotics commonly used in practice. Mycobacterium abscessus complex (MABC) is particularly difficult to treat as it is one of the most antibiotic-resistant species and, therefore, has limited treatment options that are effective at clearing the infection. We present the case of an 81-year-old female who was diagnosed with Mycobacterium abscessus after several hospital admissions in a short period of time for similar complaints, and we will discuss her diagnosis and possible treatment plan. This case explores the challenges that physicians face in diagnosing NTM infections due to them mimicking several other conditions and raises the importance of having a high clinical suspicion.

9.
Expert Rev Respir Med ; 17(11): 973-988, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37962332

RESUMEN

INTRODUCTION: Nontuberculous mycobacteria (NTM) are a diverse group of mycobacterial species that are ubiquitous in the environment. They are opportunistic pathogens that can cause a range of diseases, especially in individuals with underlying structural lung disease or compromised immune systems. AREAS COVERED: This paper provides an in-depth analysis of NTM infections, including microbiology, environmental sources and transmission pathways, risk factors for disease, epidemiology, clinical manifestations and diagnostic approaches, guideline-based treatment recommendations, drugs under development, and management challenges. EXPERT OPINION: Future approaches to the management of NTM pulmonary disease will require therapies that are well tolerated, can be taken for a shorter time period and perhaps less frequently, have few drug-drug interactions, and are active against the various strains of pathogens. As the numbers of infections increase, such therapies will be welcomed by clinicians and patients.


Asunto(s)
Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Micobacterias no Tuberculosas , Pulmón/microbiología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/terapia , Factores de Riesgo
10.
Clin Chest Med ; 44(4): 847-860, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37890921

RESUMEN

Non-tuberculous mycobacteria (NTM) infection is a major cause of morbidity in people with cystic fibrosis (pwCF) with rates of infection increasing worldwide. Accurate diagnosis and decisions surrounding best management remain challenging. Treatment guidelines have been developed to assist physicians in managing NTM in pwCF, but involve prolonged and complex mycobacterial regimens, often associated with significant toxicity. Fortunately, current management and outcomes of NTM in CF are likely to evolve due to improved understanding of disease acquisition, better diagnostics, emerging antimycobacterial therapies, and the widespread uptake of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies.


Asunto(s)
Fibrosis Quística , Infecciones por Mycobacterium no Tuberculosas , Humanos , Fibrosis Quística/complicaciones , Fibrosis Quística/terapia , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Micobacterias no Tuberculosas , Antibacterianos/uso terapéutico
11.
Int J Mycobacteriol ; 12(3): 211-225, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37721224

RESUMEN

Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium tuberculosis (MTB), as well as nontuberculous mycobacteria such as the Mycobacterium abscessus complex (MABC) and Mycobacterium avium complex (MAC). Recently, new carbapenems and combinations of carbapenems with ß-lactamase inhibitors have become available, but activity data in vitro against mycobacteria are so far scarce. Therefore, we performed a systematic review collating the minimum inhibitory concentrations (MICs) of carbapenems, with or without a ß-lactamase inhibitors for MTB, MABC, and MAC. The databases PubMed and Web of Science were searched for the relevant articles in English up until September 21, 2022. Screening of studies was performed by two independent reviewers. MIC data by recommended methods with at least five individual MICs were included. Data were reported as MIC range, MIC50, modal MIC, and/or histograms when individual MICs were available. The study protocol was registered at PROSPERO (CRD42021258537). After screening, a total of 75 studies with MIC data for carbapenems with or without ß-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the ß-lactamase inhibitor clavulanic acid resulted in the most significant reduction of MICs. For MABC, the addition of avibactam to tebipenem resulted in a 64-fold reduction of modal MIC. Data were insufficient for the analysis of MAC. Carbapenems, and in particular the novel oral compound tebipenem, in combination with clavulanic acid for MTB and avibactam for MABC may be an untapped potential for difficult-to-treat mycobacterial infections.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Inhibidores de beta-Lactamasas/farmacología , Complejo Mycobacterium avium , Carbapenémicos/farmacología , Penicilinas , Ácido Clavulánico , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Mycobacterium no Tuberculosas/microbiología
12.
Ann Clin Microbiol Antimicrob ; 22(1): 87, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735687

RESUMEN

OBJECTIVES: This study investigated the differences in epidemiological and clinical data, and antimicrobial susceptibilities among different subspecies of Mycobacterium abscessus complex (MABSC) clinical isolates at a medical school in Thailand. METHODS: A total of 143 MABSC clinical isolates recovered from 74 patients were genotypically analyzed for erm(41), rrl, and rrs mutations, and antimicrobial susceptibilities were determined using a broth microdilution method. Patient characteristics and clinical outcomes were reviewed from the medical records. RESULTS: Seventy-four patients were infected with 28/74 (37.8%) M. abscessus subspecies abscessus (MAB), 43/74 (58.1%) M. abscessus subsp. massiliense (MMA), and 3/74 (4.1%) M. abscessus subsp. bolletii (MBO). The clinical findings and outcomes were generally indistinguishable between the three subspecies. All three subspecies of MABSC clinical isolates exhibited high resistance rates to ciprofloxacin, doxycycline, moxifloxacin, TMP/SMX, and tobramycin. MAB had the highest resistance rates to clarithromycin (27.8%, 20/72) and amikacin (6.9%, 5/72) compared to MBO and MMA, with p < 0.001 and p = 0.004, respectively. In addition, the rough morphotype was significantly associated with resistance to amikacin (8.9%, 5/56), clarithromycin (26.8%, 15/56), and imipenem (76.8%, 43/56) (p < 0.001), whereas the smooth morphotype was resistant to linezolid (57.1%, 48/84) (p = 0.002). In addition, T28 of erm(41), rrl (A2058C/G and A2059C/G), and rrs (A1408G) mutations were detected in 87.4% (125/143), 16.1% (23/143), and 9.1% (13/143) of MABSC isolates, respectively. CONCLUSIONS: Three MABSC subspecies caused a variety of infections in patients with different underlying comorbidities. The drug susceptibility patterns of the recent circulating MABSC strains in Thailand were different among the three MABSC subspecies and two morphotypes.


Asunto(s)
Antiinfecciosos , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Claritromicina , Facultades de Medicina , Tailandia/epidemiología , Mycobacterium abscessus/genética , Amicacina/farmacología , Infecciones por Mycobacterium no Tuberculosas/epidemiología
13.
J Microbiol Methods ; 212: 106792, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37517511

RESUMEN

Mycobacterium abscessus complex (MABSC) subspecies differentiation improves patients' therapy and outcome. Fourier-Transform-Infrared Spectroscopy (FT-IRS) was applied for subspecies discrimination of 15 strains on different media: Löwenstein-Jensen showed the best resolution power; Linear Discriminant Analysis model differentiated M. abscessus susbsp. abscessus from M. abscessus subsp. massiliense. FT-IRS has a potential role in rapidly MABSC subspecies identification.


Asunto(s)
Mycobacterium abscessus , Humanos , Espectroscopía Infrarroja por Transformada de Fourier
14.
Clin Microbiol Infect ; 29(10): 1335.e9-1335.e16, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37364635

RESUMEN

OBJECTIVES: Mycobacterium abscessus complex is responsible for 2.6-13.0% of all non-tuberculous mycobacterial pulmonary infections and these are notoriously difficult to treat due to the complex regimens required, drug resistance and adverse effects. Hence, bacteriophages have been considered in clinical practice as an additional treatment option. Here, we evaluated antibiotic and phage susceptibility profiles of M. abscessus clinical isolates. Whole-genome sequencing (WGS) revealed the phylogenetic relationships, dominant circulating clones (DCCs), the likelihood of patient-to-patient transmission and the presence of prophages. METHODS: Antibiotic susceptibility testing was performed using CLSI breakpoints (n = 95), and plaque assays were used for phage susceptibility testing (subset of n = 88, 35 rough and 53 smooth morphology). WGS was completed using the Illumina platform and analysed using Snippy/snp-dists and Discovery and Extraction of Phages Tool (DEPhT). RESULTS: Amikacin and Tigecycline were the most active drugs (with 2 strains resistant to amikacin, and one strain with Tigecycline MIC of 4 µg/mL). Most strains were resistant to all other drugs tested, with Linezolid and Imipenem showing the least resistance, at 38% (36/95) and 55% (52/95), respectively. Rough colony morphotype strains were more phage-susceptible than smooth strains (77%-27/35 versus 48%-25/53 in the plaque assays, but smooth strains are not killed efficiently by those phages in liquid infection assay). We have also identified 100 resident prophages, some of which were propagated lytically. DCC1 (20%-18/90) and DCC4 (22%-20/90) were observed to be the major clones and WGS identified 6 events of possible patient-to-patient transmission. DISCUSSION: Many strains of M. abscessus complex are intrinsically resistant to available antibiotics and bacteriophages represent an alternative therapeutic option, but only for strains with rough morphology. Further studies are needed to elucidate the role of hospital-borne M. abscessus transmission.


Asunto(s)
Bacteriófagos , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Amicacina/farmacología , Tigeciclina/uso terapéutico , Bacteriófagos/genética , Filogenia , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Resistencia a Múltiples Medicamentos , Atención a la Salud , Pruebas de Sensibilidad Microbiana
15.
J Infect Dis ; 228(3): 321-331, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37254795

RESUMEN

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective. METHODS: We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays. RESULTS: We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds. CONCLUSIONS: We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Mycobacterium abscessus/genética , Claritromicina , Adaptación al Huésped , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Genómica
16.
Infect Drug Resist ; 16: 279-287, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36683910

RESUMEN

Purpose: Unsatisfactory efficacies of currently recommended anti-Mycobacterium abscessus complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates. Methods: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. A checkerboard method was used to investigate efficacies of various antimicrobial drug combinations. Results: BDQ MICs for MABC isolates ranged from <0.031 to 1 µg/mL, while MIC50 and MIC90 values were 0.125 µg/mL and 0.25 µg/mL, respectively. TZD MIC50 and MIC90 values for MABC isolates were 1 µg/mL and 4 µg/mL, respectively, which were fourfold lower than corresponding LZD values (P < 0.001). DZD MIC90 values for MABC isolates was 8 µg/mL, which were 0.5-fold lower than corresponding LZD values (P < 0.01). MICs of BDQ, SZD, and LZD for M. abscessus subspecies massiliense isolates were significantly lower than corresponding MICs for M. abscessus subspecies abscessus isolates (P < 0.05). Notably, use of oxazolidinones (DZD, SZD, LZD, or TZD) with BDQ against MABC isolates led to reduction of the oxazolidinone median MIC range from 4 to 0.125 µg/mL to 1-0.031 µg/mL. Conclusion: These results demonstrated excellent BDQ inhibitory activity against MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections.

17.
J Infect Dis ; 227(6): 820-827, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36637124

RESUMEN

BACKGROUND: The Mycobacterium abscessus complex (MABC) is a difficult to treat mycobacterium with two distinct morphologies: smooth and rough. As the clinical implications are unclear, we explored the morphology of MABC in relation to disease and outcome. METHODS: We performed a retrospective multicenter cohort study including patients with confirmed MABC in Sweden, 2009-2020, with treatment outcome as the primary outcome. MABC colony morphology was determined by light microscopy on Middlebrook 7H10 agar plates. RESULTS: Of the 71 MABC isolates, a defined morphology could be determined for 63 isolates, of which 40 were smooth (56%) and 23 were rough (32%). Immunosuppression, pulmonary disease, and cavitary lesion on chest radiographs were significantly associated with a rough isolate morphology. Participants with smooth isolates had more favorable treatment outcomes (12/14, 86%) compared to those with rough isolates (3/10, 30%). In an age-adjusted logistic regression, rough morphology of MABC was associated to lower odds of clinical cure compared to smooth morphology (adjusted odds ratio, 0.12; P = .049). CONCLUSIONS: Study participants with rough MABC colony morphology of isolates had a worse clinical outcome compared to those with smooth isolates. The biological mechanisms should be further characterized and colony morphology of MABC taken into account during clinical management.


Asunto(s)
Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Estudios de Cohortes , Enfermedades Pulmonares/tratamiento farmacológico , Suecia/epidemiología , Antibacterianos/uso terapéutico
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-993733

RESUMEN

Mycobacterium abscessus complex (MABC), a rapidly growing nontuberculous mycobacterium, has received increasing attention worldwide due to its rising isolation rate. The similarity of symptoms between MABC pulmonary disease and tuberculosis, different treatment methods required by different subtypes, as well as high levels of innate, adaptive and acquired antibiotic resistance, make MABC treatment more difficult and lead to unfavorable clinical outcomes of patients. This article reviews the basic characteristics, common antibiotic resistance mechanisms, as well as diagnosis and treatment of MABC, to provide reference for future research and clinical treatment of MABC lung disease.

19.
Cureus ; 15(12): e49881, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38174196

RESUMEN

Cosmetic surgeries are very popular and glamorized by the mainstream media and celebrities. Many individuals perceive certain bodily features as appealing for physical attraction and will attempt to obtain these features by surgery. However, these surgeries are not without risk, and significant consequences can occur if not performed by qualified medical professionals under sterile procedures. The authors present novel cases of two healthy young female patients who underwent a Brazilian butt lift (BBL) procedure a week apart by the same plastic surgeon in Mexico and developed dark painful lesions secondary to Mycobacterium abscessus (M. abscessus), a multidrug-resistant non-tuberculous mycobacterium (NTM). The literature review shows a paucity of data concerning NTM infections via surgical procedures of this type. The first case was of a 31-year-old woman who underwent a BBL and presented with bilateral dark painful buttock lesions weeks later. The patient returned to the plastic surgeon, who drained some lesions and prescribed oral antibiotics. The patient's clinical status continued to deteriorate and presented to the hospital for further assessment. The patient was initially started on broad-spectrum antibiotic therapy. The patient was found to have an HIV infection with a relatively preserved CD4 lymphocyte count and was started on antiretroviral therapy (ART). Intraoperative excisional tissue sample cultures grew M. abscessus. The patient was started on empiric tigecycline, cefoxitin, and linezolid. Preliminary culture susceptibilities showed resistance to linezolid. Linezolid was discontinued, amikacin was started, and cefoxitin and tigecycline were continued. Tigecycline, cefoxitin, and amikacin were continued and final susceptibilities showed sensitivity to the current treatment. The patient received a total of four months of treatment with tigecycline, cefoxitin, and amikacin. The second case was of a 28-year-old woman who underwent a BBL a week after the first patient by the same surgeon and developed multiple gluteal and body abscesses. The patient underwent bilateral thigh and gluteal, right chest wall, and breast surgical debridements with intraoperative cultures at a different hospital facility, which grew M. abscessus. Susceptibilities were not performed there. The patient was transferred to our facility for further care. Intraoperative cultures remained negative, and the patient was treated with a six-month course of tigecycline, cefoxitin, and amikacin.

20.
Pathogens ; 11(12)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36558733

RESUMEN

BACKGROUND: Members of Micobacterium. abscessus complex comprises three subspecies (M. abscessus subsp. Abscessus, M. abscessus subsp. Bolletii, and M. abscessus subsp. Massiliense) and are a rapid-growing nontuberculous mycobacteria present in different aquatic habitats and soil. It often causes a wide spectrum of infections involving pulmonary infections, surgical wound infections, and infections related to mesotherapy, catheters, hemodialysis devices, endocarditis, and disseminated infections in immunocompromised individuals. METHODS: In this article we comment on the most relevant aspects of nine patients with skin lesions caused by M. abscessus subsp. massiliense infection. Clinical characteristics, histopathology, and molecular identification were performed. RESULTS: The patients in the clinical cases presented a history of trauma, tattoos, and physical therapy techniques. The most common treatments were minocycline and clindamycin, doxycycline, ceftriaxone, cephalexin, moxifloxacin, rifampicin, and trimethoprim-sulfamethoxazole. The evolution of the treated patients was acceptable, except for one patient, who showed a partial improvement. M. massiliense were identified in all clinical cases using a species-specific PCR. CONCLUSION: Our series consisted of nine cases of skin biopsies recorded in different years; for this reason, we do not have all the data necessary for a complete description, in particular in four cases, causing limitations in the manuscript, especially in the therapy used and the evolution of patients due to lack of follow-up.

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