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Open Forum Infectious Diseases May 2024Lung transplant recipients are at increased risk of complex (MABC) acquisition and invasive infection. We analyzed risk factors and outcomes of early post-lung...
BACKGROUND
Lung transplant recipients are at increased risk of complex (MABC) acquisition and invasive infection. We analyzed risk factors and outcomes of early post-lung transplant MABC acquisition.
METHODS
We conducted a retrospective matched case-control study of patients who underwent lung transplant from 1/1/2012 to 12/31/2021 at a single large tertiary care facility. Cases had de novo MABC isolation within 90 days post-transplant. Controls had no positive MABC cultures and were matched 3:1 with cases based on age and transplant date. Recipient demographics and pre-/peri-operative characteristics were analyzed, and a regression model was used to determine independent risk factors for MABC acquisition. We also assessed 1-year post-transplant outcomes, including mortality.
RESULTS
Among 1145 lung transplants, we identified 79 cases and 237 matched controls. Post-transplant mechanical ventilation for >48 hours was independently associated with MABC acquisition (adjusted odds ratio, 2.46; 95% CI, 1.29-4.72; = .007). Compared with controls, cases required more days of hospitalization after the MABC index date (28 vs 12 days; = .01) and had decreased 1-year post-transplant survival (78% vs 89%; log-rank = .02). One-year mortality appeared highest for cases who acquired subsp. (31% mortality) or had extrapulmonary infections (43% mortality).
CONCLUSIONS
In this large case-control study, prolonged post-transplant ventilator duration was associated with early post-lung transplant MABC acquisition, which in turn was associated with increased hospital-days and mortality. Further studies are needed to determine the best strategies for MABC prevention, surveillance, and management.
PubMed: 38746951
DOI: 10.1093/ofid/ofae209 -
Frontiers in Neurology 2024Nontuberculous mycobacteria (NTM) mediated infections are important to consider in cases with neuroinflammatory presentations. We aimed to characterize cases of NTM with...
INTRODUCTION
Nontuberculous mycobacteria (NTM) mediated infections are important to consider in cases with neuroinflammatory presentations. We aimed to characterize cases of NTM with neurological manifestations at the National Institutes of Health (NIH) Clinical Center and review the relevant literature.
MATERIALS AND METHODS
Between January 1995 and December 2020, six cases were identified. Records were reviewed for demographic, clinical, and radiological characteristics. A MEDLINE search found previously reported cases. Data were extracted, followed by statistical analysis to compare two groups [cases with slow-growing mycobacteria (SGM) vs. those with rapidly growing mycobacteria (RGM)] and evaluate for predictors of survival. NIH cases were evaluated for clinical and radiological characteristics. Cases from the literature were reviewed to determine the differences between SGM and RGM cases and to identify predictors of survival.
RESULTS
Six cases from NIH were identified (age 41 ± 13, 83% male). Five cases were caused by SGM [ complex (MAC) = 4; = 1] and one due to RGM (). Underlying immune disorders were identified only in the SGM cases [genetic ( = 2), HIV ( = 1), sarcoidosis ( = 1), and anti-interferon-gamma antibodies ( = 1)]. All cases were diagnosed using tissue analysis. A literature review found 81 reports on 125 cases (SGM = 85, RGM = 38, non-identified = 2). No immune disorder was reported in 26 cases (21%). Within SGM cases, the most common underlying disease was HIV infection ( = 55, 65%), and seizures and focal lesions were more common. In RGM cases, the most common underlying condition was neurosurgical intervention or implants (55%), and headaches and meningeal signs were common. Tissue-based diagnosis was used more for SGM than RGM (39% vs. 13%, = 0.04). Survival rates were similar in both groups (48% SGM and 55% in RGM). Factors associated with better survival were a solitary CNS lesion (OR 5.9, = 0.01) and a diagnosis made by CSF sampling only (OR 9.9, = 0.04).
DISCUSSION
NTM infections cause diverse neurological manifestations, with some distinctions between SGM and RGM infections. Tissue sampling may be necessary to establish the diagnosis, and an effort should be made to identify an underlying immune disorder.
PubMed: 38742044
DOI: 10.3389/fneur.2024.1360128 -
Frontiers in Immunology 2024complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised...
complex (MAC) is a non-tuberculous mycobacterium widely distributed in the environment. Even though MAC infection is increasing in older women and immunocompromised patients, to our knowledge there has been no comprehensive analysis of the MAC-infected host-cell transcriptome-and particularly of long non-coding RNAs (lncRNAs). By using cultured primary mouse bone-marrow-derived macrophages (BMDMs) and Cap analysis of gene expression, we analyzed the transcriptional and kinetic landscape of macrophage genes, with a focus on lncRNAs, during MAC infection. MAC infection of macrophages induced the expression of immune/inflammatory response genes and other genes similar to those involved in M1 macrophage activation, consistent with previous reports, although (M1 activation) and (M2 activation) had distinct expression profiles. We identified 31 upregulated and 30 downregulated lncRNA promoters corresponding respectively to 18 and 26 lncRNAs. Upregulated lncRNAs were clustered into two groups-early and late upregulated-predicted to be associated with immune activation and the immune response to infection, respectively. Furthermore, an Ingenuity Pathway Analysis revealed canonical pathways and upstream transcription regulators associated with differentially expressed lncRNAs. Several differentially expressed lncRNAs reported elsewhere underwent expressional changes upon M1 or M2 preactivation and subsequent MAC infection. Finally, we showed that expressional change of lncRNAs in MAC-infected BMDMs was mediated by toll-like receptor 2, although there may be other mechanisms that sense MAC infection. We identified differentially expressed lncRNAs in MAC-infected BMDMs, revealing diverse features that imply the distinct roles of these lncRNAs in MAC infection and macrophage polarization.
Topics: RNA, Long Noncoding; Animals; Macrophages; Mycobacterium avium Complex; Mice; Gene Expression Profiling; Mycobacterium avium-intracellulare Infection; Transcriptome; Macrophage Activation; Mice, Inbred C57BL; Cells, Cultured; Gene Expression Regulation
PubMed: 38711507
DOI: 10.3389/fimmu.2024.1374437 -
Scientific Reports May 2024Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility...
Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility to MAC infections in a canine breed. Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait. A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9. Whole genome sequencing of 2 MAC-infected dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide β-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1. While CARD9-deficient knockout mice are susceptible to experimental challenges by fungi and mycobacteria, Miniature Schnauzer dogs with systemic MAC susceptibility represent the first spontaneous animal model of CARD9 deficiency, which will help to further elucidate host defense mechanisms against mycobacteria and fungi and assess potential therapies for animals and humans.
Topics: Animals; CARD Signaling Adaptor Proteins; Dogs; Genetic Predisposition to Disease; Mycobacterium avium-intracellulare Infection; Mycobacterium avium Complex; Genome-Wide Association Study; Dog Diseases; Sequence Deletion; Pedigree; Female; Male; Whole Genome Sequencing; Homozygote; Lectins, C-Type
PubMed: 38710903
DOI: 10.1038/s41598-024-61054-x -
Heliyon May 2024The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable...
BACKGROUND
The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis.
PATIENTS AND METHODS
We retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system.
RESULTS
The median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and -glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis.
CONCLUSION
The diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.
PubMed: 38707468
DOI: 10.1016/j.heliyon.2024.e30060 -
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 -
Microbiology Spectrum Apr 2024The latest guidelines include azithromycin as a preferred regimen for treating complex (MAC) pulmonary disease. However, serially collected susceptibility data on...
The latest guidelines include azithromycin as a preferred regimen for treating complex (MAC) pulmonary disease. However, serially collected susceptibility data on clinical MAC isolates are limited, and no breakpoints have been determined. We investigated the minimum inhibitory concentrations (MICs) of azithromycin and clarithromycin for all MAC strains isolated in 2021 from a single center in Japan, excluding duplicates. The MICs were determined using a panel based on the microbroth dilution method, according to the latest Clinical and Laboratory Standards Institute recommendations. The MICs were determined for 318 MAC strains. Although there was a significant positive correlation between the MICs of azithromycin and clarithromycin, the MICs of azithromycin tended to be higher than those of clarithromycin. Among the cases in which the strains were isolated, 18 patients initiated treatment, including azithromycin treatment, after sample collection. Some patients infected with stains with relatively high azithromycin MICs achieved a microbiological cure with azithromycin-containing regimens. This study revealed a higher MIC distribution for azithromycin than clarithromycin, raising questions about the current practice of estimating azithromycin susceptibility based on the clarithromycin susceptibility test result. However, this was a single-center study that included only a limited number of cases treated with azithromycin. Therefore, further multicenter studies that include a greater number of cases treated with azithromycin are warranted to verify the distribution of azithromycin MICs and examine the correlation between azithromycin MICs and treatment effectiveness.IMPORTANCEThe macrolides serve as key drugs in the treatment of pulmonary complex infection, and the administration of macrolide should be guided by susceptibility test results. Azithromycin is recommended as a preferred choice among macrolides, surpassing clarithromycin; however, drug susceptibility testing is often not conducted, and clarithromycin susceptibility is used as a surrogate. This study represents the first investigation into the minimum inhibitory concentration of azithromycin on a scale of several hundred clinical isolates, revealing an overall tendency for higher minimum inhibitory concentrations compared with clarithromycin. The results raise questions about the appropriateness of using clarithromycin susceptibility test outcomes for determining the administration of azithromycin. This study highlights the need for future discussions on the clinical breakpoints of azithromycin, based on large-scale clinical research correlating azithromycin susceptibility with treatment outcomes.
PubMed: 38687080
DOI: 10.1128/spectrum.00218-24 -
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 -
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 -
Cureus Mar 2024The increasing prevalence of complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity...
The increasing prevalence of complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.
PubMed: 38646349
DOI: 10.7759/cureus.56622