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Retinal Cases & Brief Reports Nov 2023To report the successful management of a rare case of Mycobacterium abscessus scleral buckle infection.
PURPOSE
To report the successful management of a rare case of Mycobacterium abscessus scleral buckle infection.
METHODS
Case report.
RESULTS
A 63-year-old woman with a history of sarcoid anterior uveitis and macula-off retinal detachment repaired by scleral buckle and pars plana vitrectomy presented with eye pain, redness, and purulent drainage in the left eye. Slit-lamp examination showed superonasal scleral buckle exposure, purulent conjunctival discharge, corneal edema, nongranulomatous keratic precipitates, and anterior chamber cell and flare. The patient underwent urgent scleral buckle removal. Intraoperatively, an area of scleral thinning without perforation underneath the exposed buckle was discovered and covered with a scleral patch graft, and an amniotic membrane graft was used to cover an area of bare sclera with significant conjunctival scarring and retraction. Cultures grew M. abscessus panresistant except to amikacin. After 6 weeks of fortified amikacin drops and a long taper of topical steroid therapy for persistent postoperative anterior uveitis, the patient's symptoms resolved.
CONCLUSION
Mycobacterium is an emerging causative agent of scleral buckle infections. Our report provides insights about the management of such cases.
Topics: Female; Humans; Middle Aged; Mycobacterium abscessus; Amikacin; Scleral Buckling; Retinal Detachment; Sclera; Postoperative Complications; Vitrectomy; Uveitis, Anterior
PubMed: 35344534
DOI: 10.1097/ICB.0000000000001277 -
Journal of Global Antimicrobial... Sep 2023Mycobacterium avium (M. avium) complex bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and consists of a macrolide, a rifamycin,...
OBJECTIVES
Mycobacterium avium (M. avium) complex bacteria cause opportunistic infections in humans. Treatment yields cure rates of 60% and consists of a macrolide, a rifamycin, and ethambutol, and in severe cases, amikacin. Mechanisms of antibiotic tolerance remain mostly unknown. Therefore, we studied the contribution of efflux and amikacin modification to antibiotic susceptibility.
METHODS
We characterised M. avium ABC transporters and studied their expression together with other transporters following exposure to clarithromycin, amikacin, ethambutol, and rifampicin. We determined the effect of combining the efflux pump inhibitors berberine, verapamil and CCCP (carbonyl cyanide m-chlorophenyl hydrazone), to study the role of efflux on susceptibility. Finally, we studied the modification of amikacin by M. avium using metabolomic analysis.
RESULTS
Clustering shows conservation between M. avium and M. tuberculosis and transporters from most bacterial subfamilies (2-6, 7a/b, 10-12) were found. The largest number of transporter encoding genes was up-regulated after clarithromycin exposure, and the least following amikacin exposure. Only berberine increased the susceptibility to clarithromycin. Finally, because of the limited effect of amikacin on transporter expression, we studied amikacin modification and showed that M. avium, in contrast to M. abscessus, is not able to modify amikacin.
CONCLUSION
We show that M. avium carries ABC transporters from all major families important for antibiotic efflux, including homologues shown to have affinity for drugs included in treatment. Efflux inhibition in M. avium can increase susceptibility, but this effect is efflux pump inhibitor- and antibiotic-specific. Finally, the lack of amikacin modifying activity in M. avium is important for its activity.
Topics: Humans; Amikacin; Mycobacterium avium; Clarithromycin; Ethambutol; Berberine; Anti-Bacterial Agents; Mycobacterium avium Complex; Membrane Transport Proteins; Mycobacterium tuberculosis; ATP-Binding Cassette Transporters
PubMed: 37453496
DOI: 10.1016/j.jgar.2023.07.007 -
Respiratory Medicine Oct 2023Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by...
BACKGROUND
Macrolide-resistant Mycobacterium avium complex (MAC) disease is very difficult to cure. Macrolide-resistance emerges in patients and is largely preventable by appropriate screening and treatment practices.
METHODS
Patients with macrolide-resistant MAC isolates between March 2019 and March 2022 were retrieved from the mycobacteriology reference laboratory database at Radboudumc, Nijmegen, the Netherlands. Clinical consultation reports were extracted from the database to assess the cause of macrolide resistance.
RESULTS
Sixteen patients with macrolide-resistant MAC disease were included, from a total of 815 patients with MAC isolates (2%); Macrolide monotherapy in bronchiectasis or CF was the most frequent cause of development of macrolide-resistance MAC disease (n = 8; 50%). Short (n = 3; mean duration 9 months, range 6-12) or guideline non-compliant (n = 2) treatment regimens and patient non-adherence (n = 2) were other key causes of macrolide-resistance.
CONCLUSIONS
Macrolide monotherapy after inappropriate screening is the most frequent cause of macrolide-resistant Mycobacterium avium complex disease in the Netherlands. Educational efforts are needed to prevent this.
Topics: Humans; Mycobacterium avium Complex; Anti-Bacterial Agents; Macrolides; Mycobacterium avium-intracellulare Infection; Drug Resistance, Bacterial; Lung Diseases
PubMed: 37481170
DOI: 10.1016/j.rmed.2023.107366 -
Biochemical and Biophysical Research... Sep 2023The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis...
The cases of lung disease caused by non-tuberculous mycobacterium Mycobacterium abscessus (Mab) are increasing and not reliably curable. Repurposing of anti-tuberculosis inhibitors brought the oxidative phosphorylation pathway with its final product ATP, formed by the essential FF-ATP synthase (subunits α:β:γ:δ:ε:a:b:b':c), into focus as an attractive inhibitor target against Mab. Because of the pharmacological attractiveness of this enzyme, we generated and purified a recombinant and enzymatically active Mab F-ATPase complex, including subunits α:β:γ:δ:ε (MabF-αβγδε) to achieve mechanistic, regulatory, and structural insights. The high purity of the complex enabled the first cryo-electron microscopy structure determination of the Mab F-ATPase complex to 7.3 Å resolution. The enzyme showed low ATP hydrolysis activity, which was stimulated by trypsin treatment. No effect was observed in the presence of the detergent lauryldimethylamine oxide.
Topics: Humans; Cryoelectron Microscopy; Mycobacterium abscessus; Amino Acid Sequence; Proton-Translocating ATPases; Tuberculosis; Adenosine Triphosphate
PubMed: 37302287
DOI: 10.1016/j.bbrc.2023.05.095 -
Frontiers in Microbiology 2024Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions,... (Review)
Review
Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions, numbers will continue to rise. Effective treatments for NTM infections remain suboptimal. Standard therapy for complex, the most commonly isolated NTM, requires a 3-drug regime taken for approximately 18 months, with rates of culture conversion reported between 45 and 70%, and high rates of relapse or reinfection at up to 60%. New therapeutic options for NTM treatment are urgently required. A survey of ongoing clinical trials for new NTM therapy listed on ClinicalTrials.Gov using the terms '', '', '', 'Non tuberculous Mycobacteria' and 'Nontuberculous Mycobacteria' and a selection criterion of interventional studies using antibiotics demonstrates that most trials involve dose and combination therapy of the guideline based therapy or including one or more of; Amikacin, Clofazimine, Azithromycin and the anti-TB drugs Bedaquiline and Linezolid. The propensity of NTMs to form biofilms, their unique cell wall and expression of both acquired and intrinsic resistance, are all hampering the development of new anti-NTM therapy. Increased investment in developing targeted treatments, specifically for NTM infections is urgently required.
PubMed: 38887711
DOI: 10.3389/fmicb.2024.1394220 -
Clinics in Chest Medicine Dec 2023Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured.... (Review)
Review
Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured. The identification of the cause of bronchiectasis and/or coexisting diseases is important because it may affect therapeutic strategies. Airway clearance is the mainstay of bronchiectasis management. It can include multiple breathing techniques, devices, and mucoactive agents. The exact airway clearance regimen should be customized to each individual patient. Chronic pathogenic airway bacteria, such as Pseudomonas aeruginosa, may warrant consideration of eradication therapy and/or chronic use of maintenance inhaled antibiotics.
Topics: Humans; Bronchiectasis; Lung; Mycobacterium Infections, Nontuberculous; Lung Diseases; Nontuberculous Mycobacteria; Anti-Bacterial Agents
PubMed: 37890912
DOI: 10.1016/j.ccm.2023.07.005 -
The European Respiratory Journal May 2024https://bit.ly/3PUGvbV
https://bit.ly/3PUGvbV
Topics: Humans; Mycobacterium avium-intracellulare Infection; Rifampin; Mycobacterium avium Complex; Anti-Bacterial Agents; Lung Diseases; Treatment Outcome
PubMed: 38697635
DOI: 10.1183/13993003.02210-2023 -
Nature Communications Mar 2024The growth and division of mycobacteria, which include clinically relevant pathogens, deviate from that of canonical bacterial models. Despite their Gram-positive...
The growth and division of mycobacteria, which include clinically relevant pathogens, deviate from that of canonical bacterial models. Despite their Gram-positive ancestry, mycobacteria synthesize and elongate a diderm envelope asymmetrically from the poles, with the old pole elongating more robustly than the new pole. The phosphatidylinositol-anchored lipoglycans lipomannan (LM) and lipoarabinomannan (LAM) are cell envelope components critical for host-pathogen interactions, but their physiological functions in mycobacteria remained elusive. In this work, using biosynthetic mutants of these lipoglycans, we examine their roles in maintaining cell envelope integrity in Mycobacterium smegmatis and Mycobacterium tuberculosis. We find that mutants defective in producing mature LAM fail to maintain rod cell shape specifically at the new pole and para-septal regions whereas a mutant that produces a larger LAM becomes multi-septated. Therefore, LAM plays critical and distinct roles at subcellular locations associated with division in mycobacteria, including maintenance of local cell wall integrity and septal placement.
Topics: Lipopolysaccharides; Mycobacterium smegmatis; Cell Wall; Mycobacterium tuberculosis
PubMed: 38467648
DOI: 10.1038/s41467-024-46565-5 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacteria (NTM) typically cause opportunistic pulmonary infections and reliable laboratory results can assist with diagnosis of disease. Microscopy can... (Review)
Review
Nontuberculous mycobacteria (NTM) typically cause opportunistic pulmonary infections and reliable laboratory results can assist with diagnosis of disease. Microscopy can detect acid-fast bacilli from specimens though it has poor sensitivity. Solid and liquid culture are used to grow NTM, which are identified by molecular or protein-based assays. Because culture has a long turnaround time, some assays are designed to identify NTM directly from sputum specimens. When indicated, phenotypic susceptibility testing should be performed by broth microdilution as per the guidelines from the Clinical Laboratory Standards Institute. Genotypic susceptibility methods may be used to decrease the turnaround time for some antimicrobials.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung; Anti-Bacterial Agents
PubMed: 37890913
DOI: 10.1016/j.ccm.2023.06.001 -
Respiratory Research Dec 2023Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani... (Review)
Review
INTRODUCTION
Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619-623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce.
MAIN BODY
This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies.
CONCLUSIONS
The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.
Topics: Humans; Cystic Fibrosis; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Comorbidity; Pneumonia, Bacterial
PubMed: 38104098
DOI: 10.1186/s12931-023-02612-1