-
Ear, Nose, & Throat Journal Apr 2024
PubMed: 38686859
DOI: 10.1177/01455613241251559 -
Microorganisms Mar 2024Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or... (Review)
Review
Nontuberculous mycobacteria (NTM) are environmental and ubiquitous, but only a few species are associated with disease, often presented as nodular/bronchiectatic or cavitary pulmonary forms. Bronchiectasis, airways dilatations characterized by chronic productive cough, is the main presentation of NTM pulmonary disease. The current Cole's vicious circle model for bronchiectasis proposes that it progresses from a damaging insult, such as pneumonia, that affects the respiratory epithelium and compromises mucociliary clearance mechanisms, allowing microorganisms to colonize the airways. An important bronchiectasis risk factor is primary ciliary dyskinesia, but other ciliopathies, such as those associated with connective tissue diseases, also seem to facilitate bronchiectasis, as may occur in Lady Windermere syndrome, caused by infection. Inhaled NTM may become part of the lung microbiome. If the dose is too large, they may grow excessively as a biofilm and lead to disease. The incidence of NTM pulmonary disease has increased in the last two decades, which may have influenced the parallel increase in bronchiectasis incidence. We propose that ciliary dyskinesia is the main promoter of bronchiectasis, and that the bacteria most frequently involved are NTM. Restoration of ciliary function and impairment of mycobacterial biofilm formation may provide effective therapeutic alternatives to antibiotics.
PubMed: 38674609
DOI: 10.3390/microorganisms12040665 -
Pathogens (Basel, Switzerland) Apr 2024Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM...
BACKGROUND
Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes.
METHODS
A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021.
RESULTS
Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was complex (MAC), followed by and . In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response.
CONCLUSION
A favourable response to treatment was seen in 74% of patients with a high relapse rate.
PubMed: 38668299
DOI: 10.3390/pathogens13040344 -
Microbiology Spectrum Jun 2024Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method,...
Tuberculosis (TB) and infectious diseases caused by non-tuberculous mycobacteria (NTM) are global concerns. The development of a rapid and accurate diagnostic method, capable of detecting and identifying different mycobacteria species, is crucial. We propose a molecular approach, the BiDz-TB/NTM, based on the use of binary deoxyribozyme (BiDz) sensors for the detection of (Mtb) and NTM of clinical interest. A panel of DNA samples was used to evaluate Mtb-BiDz, /-BiDz, -BiDz, /-BiDz, and -BiDz sensors in terms of specificity, sensitivity, accuracy, and limit of detection. The BiDz sensors were designed to hybridize specifically with the genetic signatures of the target species. To obtain the BiDz sensor targets, amplification of a fragment containing the hypervariable region 2 of the 16S rRNA was performed, under asymmetric PCR conditions using the reverse primer designed based on linear-after-the-exponential principles. The BiDz-TB/NTM was able to correctly identify 99.6% of the samples, with 100% sensitivity and 0.99 accuracy. The individual values of specificity, sensitivity, and accuracy, obtained for each BiDz sensor, satisfied the recommendations for new diagnostic methods, with sensitivity of 100%, specificity and accuracy ranging from 98% to 100% and from 0.98 to 1.0, respectively. The limit of detection of BiDz sensors ranged from 12 genome copies (Mtb-BiDz) to 2,110 genome copies (Mkan-BiDz). The BiDz-TB/NTM platform would be able to generate results rapidly, allowing the implementation of the appropriate therapeutic regimen and, consequently, the reduction of morbidity and mortality of patients.IMPORTANCEThis article describes the development and evaluation of a new molecular platform for accurate, sensitive, and specific detection and identification of and other mycobacteria of clinical importance. Based on BiDz sensor technology, this assay prototype is amenable to implementation at the point of care. Our data demonstrate the feasibility of combining the species specificity of BiDz sensors with the sensitivity afforded by asymmetric PCR amplification of target sequences. Preclinical validation of this assay on a large panel of clinical samples supports the further development of this diagnostic tool for the molecular detection of pathogenic mycobacteria.
Topics: Humans; Mycobacterium tuberculosis; Polymerase Chain Reaction; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Sensitivity and Specificity; RNA, Ribosomal, 16S; Tuberculosis; DNA, Bacterial; Biosensing Techniques
PubMed: 38651877
DOI: 10.1128/spectrum.03506-23 -
Open Forum Infectious Diseases Apr 2024The objective of our study is to describe the clinical presentation, management, and outcome of a large cohort with nontuberculous mycobacteria (NTM) hand infection.
BACKGROUND
The objective of our study is to describe the clinical presentation, management, and outcome of a large cohort with nontuberculous mycobacteria (NTM) hand infection.
METHODS
We reviewed the medical records of all adults (≥18 years) managed at the Mayo Clinic (Rochester, MN) for NTM hand infection between 1998 and 2018.
RESULTS
Our cohort included 81 patients. The median age was 61.3 (interquartile range 51.7, 69.6) years; 39.5% were immunocompromised, and 67.9% reported a triggering exposure preceding infection. Infection was deep in 64.2% and disseminated in 3.7%. Up to 16.0% received intralesional steroids because of misdiagnosis with an inflammatory process. Immunocompromised patients had deeper infection, and fewer reports of a triggering exposure. , complex, and complex were the most common species. The median antibiotic duration was 6.1 (interquartile range 4.6, 9.9) months. Deep infection and infection with species other than were associated with using a greater number of antibiotics for combination therapy and an extended duration of treatment. Immunosuppression was also associated with longer courses of antibiotic therapy. Surgery was performed in 86.5% and 32.4% required multiple procedures. Ten patients, mostly with superficial infections, were treated with antibiotics alone. The 5-year cumulative rate of treatment failure was 30.3% (95% confidence interval, 20.9-44.0). Immunosuppression and intralesional steroid use were risk factors for failure.
CONCLUSIONS
Treatment of NTM hand infection usually requires surgery and antibiotics, but antibiotics alone may occasionally be attempted in select cases. Immunosuppression and intralesional steroids are risk factors for treatment failure.
PubMed: 38651140
DOI: 10.1093/ofid/ofae152 -
Microbiology Spectrum May 2024an emerging pathogen responsible for severe pulmonary infections in cystic fibrosis patients, displays either a smooth (S) or a rough (R) morphotype. Infections with R...
UNLABELLED
an emerging pathogen responsible for severe pulmonary infections in cystic fibrosis patients, displays either a smooth (S) or a rough (R) morphotype. Infections with R are associated with increased pathogenicity in animal models and humans. While the S-to-R transition correlating with reduced glycopeptidolipid (GPL) production is well-documented, the recent screening of a transposon library revealed additional gene candidates located outside of the locus involved in this transition. These genes include , encoding the putative lipoprotein peptidase LpqM. However, experimental confirmation of the implication of this gene in the morphotype switch is lacking. Herein, we re-examined the role of , and its homolog , in colonial morphotype changes by generating unmarked deletion mutants in S. Our results indicate that the morphotype of these mutants stayed smooth in different media. Unexpectedly, the intracellular growth of Δ and Δ in THP-1 macrophages was significantly reduced as compared to the parental S strain, and these defects were rescued upon complementation with their corresponding genes. Strikingly, the intracellular survival defect was further exacerbated in a mutant lacking both and genes. This implies that, despite their primary sequence relatedness, the two proteins are not functionally redundant. Collectively, this suggests that these two LpqM-related lipoproteins are unlikely to be involved in the S-to-R transition but are key players for intramacrophage survival of .
IMPORTANCE
causes persistent infections in patients with underlying pulmonary diseases, resulting in progressive lung function deterioration. The rough (R) morphotype is well-established as associated with chronic and more aggressive infections in patients. In this study, we individually and simultaneously deleted the and genes in S, without observing changes in colony morphotypes. However, these mutants exhibited a severe impairment in their ability to survive within human macrophages, highlighting the critical role of these two lipoproteins in virulence.
Topics: Mycobacterium abscessus; Humans; Macrophages; Bacterial Proteins; Mycobacterium Infections, Nontuberculous; THP-1 Cells; Virulence
PubMed: 38619262
DOI: 10.1128/spectrum.03837-23 -
Evaluation and activity of new porphyrin-peptide cage-type conjugates for the photoinactivation of .Microbiology Spectrum May 2024is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases and cutaneous infections. However, treatment of infections remains...
is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases and cutaneous infections. However, treatment of infections remains particularly challenging, largely due to intrinsic resistance to a wide panel of antimicrobial agents. New therapeutic alternatives are urgently needed. Herein, we show that, upon limited irradiation with a blue-light source, newly developed porphyrin-peptide cage-type photosensitizers exert a strong bactericidal activity against smooth and rough variants of in planktonic cultures and in biofilms, at low concentrations. Atomic force microscopy unraveled important morphological alterations that include a wrinkled and irregular bacterial surface. The potential of these compounds for a photo-therapeutic use to treat skin infections requires further evaluations.IMPORTANCE causes persistent infections and is extremely difficult to eradicate. Despite intensive chemotherapy, treatment success rates remain very low. Thus, given the unsatisfactory performances of the current regimens, more effective therapeutic alternatives are needed. In this study, we evaluated the activity of newly described porphyrin-peptide cage-type conjugates in the context of photodynamic therapy. We show that upon light irradiation, these compounds were highly bactericidal against , thus qualifying these compounds for future studies dedicated to photo-therapeutic applications against skin infections.
Topics: Mycobacterium abscessus; Porphyrins; Photosensitizing Agents; Anti-Bacterial Agents; Biofilms; Humans; Mycobacterium Infections, Nontuberculous; Microbial Sensitivity Tests; Peptides; Photochemotherapy; Light
PubMed: 38619253
DOI: 10.1128/spectrum.00006-24 -
Ugeskrift For Laeger Apr 2024This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications,... (Review)
Review
This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications, antibiotic choice, resistance and side effects. Treatment of nontuberculous pulmonary disease is complex, lengthy, and fraught with side effects. Increased attention on this disease is needed in order to alleviate the severe consequences of this growing disease. Cooperation between pulmonologists and infectious disease specialists is needed to ensure uniform treatment, and to account for the heterogeneity seen in patients and mycobacteria alike.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung Diseases; Pneumonia; Anti-Bacterial Agents
PubMed: 38606709
DOI: 10.61409/V06230603 -
Revista Espanola de Quimioterapia :... Jun 2024Mycobacterium avium complex (MAC) and Mycobacterium abscessus are a group of nontuberculous mycobacteria (NTM) that have been described as human pathogens. Their ability...
OBJECTIVE
Mycobacterium avium complex (MAC) and Mycobacterium abscessus are a group of nontuberculous mycobacteria (NTM) that have been described as human pathogens. Their ability to develop biofilms in tissues and medical devices is one of the most important pathogenicity factors, with important implications in diagnosis and treatment. Macrolides are usually considered one of the bases of this treatment.
METHODS
Here we have studied the biofilm prevention concentration (BPC) of 16 strains (n=16) with clarithromycin to avoid the biofilm development by these NTM.
RESULTS
In this study, all M. abscessus strains have similar BPC, while MAC strains showed different values. For MAC the concentrations ranged between 1-16 mg/L, while for M. abscessus the concentration was 32 mg/L for all strains except one that was 64 mg/L.
CONCLUSIONS
These results open the possibility of using macrolides for the prevention of biofilm development in patients with a risk of developing NTM disease.
Topics: Clarithromycin; Biofilms; Anti-Bacterial Agents; Nontuberculous Mycobacteria; Humans; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium abscessus
PubMed: 38602224
DOI: 10.37201/req/014.2024 -
Journal of Bone and Joint Infection 2024: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are...
: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. : A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. : A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (). The isolated RGM species included (three cases), (three cases), and one case each of and . Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. : PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.
PubMed: 38601002
DOI: 10.5194/jbji-9-99-2024