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Transplantation Reviews (Orlando, Fla.) Dec 2023There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We... (Review)
Review
BACKGROUND
There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.
METHODS
Literature was reviewed on PubMed, Embase and the Cochrane Library, for articles published from inception to January 2022. Individual patient data were sought.
RESULTS
Sixteen studies were included reporting 92 patients. Most frequent used agents were aminoglycosides and macrolides for Mycobacterium abscessus (M. abscessus) and macrolides and tuberculostatic agents for Mycobacterium avium complex (M. avium complex). The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Longer treatment duration pre-LTx was observed in children and in patients with M. abscessus. 46% of the patients with NTM-PD pre-LTx developed NTM disease post-LTx, related mortality rate was 10%. Longer treatment duration pre-LTx (p < 0.001) and sputum non-conversion pre-LTx (p = 0.003) were significantly associated with development of NTM-disease post-LTx. Longer treatment duration pre-LTx (p = 0.004), younger age (p < 0.001) and sputum non-conversion (p = 0.044) were risk factors for NTM related death.
CONCLUSIONS
The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Patients with longer treatment duration for NTM-PD pre-LTx and with sputum non-conversion are at risk for NTM disease post-LTx and for NTM-related death. Children were particularly at risk for NTM related death.
Topics: Child; Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung Diseases; Lung Transplantation; Anti-Bacterial Agents; Macrolides
PubMed: 37832509
DOI: 10.1016/j.trre.2023.100800 -
Tropical Medicine and Health Sep 2023CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often... (Review)
Review
BACKGROUND
CNS manifestations represent an emerging facet of NTM infection with significant mortality. Due to protean presentation and low index of suspicion, many cases are often treated erroneously as tubercular meningitis or fungal infections.
OBJECTIVES
Literature on NTM CNS disease is scarce, with most available data on pulmonary disease. This systematic review aimed to evaluate the epidemiology, clinical presentation, diagnostic modalities, and predictors of outcome in CNS NTM infection.
METHODS
The literature search was performed in major electronic databases (PubMed, Google Scholar, and Scopus) using keywords "CNS," "Central nervous system," "brain abscess," "meningitis," "spinal," "Nontuberculous mycobacteria," "NTM". All cases of CNS NTM infection reported between January 1980 and December 2022 were included.
RESULTS
A total of 77 studies (112 cases) were included in the final analysis. The mean age of all patients was 38 years, with most patients male (62.5%). Mycobacterium avium complex (MAC) was the most common aetiology, followed by M. fortuitum and M. abscessus (34.8%, 21.4% and 15.2%, respectively). The disseminated disease was found in 33% of cases. HIV (33.9%) and neurosurgical hardware (22.3%) were the common risk factors. Intracranial abscess (36.6%) and leptomeningeal enhancement (28%) were the most prevalent findings in neuroimaging. The overall case fatality rate was 37.5%. On multivariate analysis, male gender (adjusted OR 2.4, 95% CI 1.2-7.9) and HIV (adjusted OR 3.7, 95% CI 1.8-6.1) were the independent predictors of mortality). M. fortuitum infection was significantly associated with increased survival (adjusted OR 0.18, 95% CI (0.08-0.45), p value 0.012).
CONCLUSIONS
Current evidence shows the emerging role of rapid-grower NTM in CNS disease. Male gender and HIV positivity were associated with significant mortality, while M fortuitum carries favourable outcomes.
PubMed: 37749661
DOI: 10.1186/s41182-023-00546-4 -
International Journal of... 2023Difficult-to-treat mycobacterial infections are increasing globally. There is an urgent need of new treatment alternatives for multidrug-resistant Mycobacterium... (Review)
Review
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 β-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 β-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, MIC, 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 β-lactamase inhibitors were included in the review. For MTB, the oral carbapenem tebipenem combined with the β-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.
Topics: Humans; beta-Lactamase Inhibitors; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium tuberculosis; Carbapenems; Penicillins; Clavulanic Acid; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycobacterium Infections, Nontuberculous
PubMed: 37721224
DOI: 10.4103/ijmy.ijmy_131_23 -
Journal of Global Health Sep 2023China has a high burden of nontuberculous mycobacterial (NTM) infections. Immunocompromised populations, such as those with human immunodeficiency virus/acquired... (Meta-Analysis)
Meta-Analysis
BACKGROUND
China has a high burden of nontuberculous mycobacterial (NTM) infections. Immunocompromised populations, such as those with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), are at a higher risk of being infected with NTM than immunocompetent individuals. Yet, there is a paucity of information on the clinical features of positive NTM isolates from patients with HIV/AIDS in China. To address this gap, we conducted a systematic review and meta-analysis of existing studies, comparing them against current expert consensus to provide guidance for clinical practice.
METHODS
Two researchers independently searched eight databases (SinoMed, China National Knowledge Infrastructure, Wanfang, VIP, Cochrane Library, PubMed, Embase, and Web of Science) from inception to 26 December 2022 to retrieve published Chinese- and English-language studies reporting clinical features of NTM-positive isolates among patients with HIV/AIDS in China.
RESULTS
We included 28 studies with 1861 patients. The rate of positive NTM isolates detected from men among all patients was 87.3%. NTM species distribution was mainly Mycobacterium avium complex (64.3%), which was predominant in different regions. The five most common clinical symptoms were fever (68.5%), cough or expectoration (67.0%), appetite loss (49.4%), weight loss (45.5%), and superficial lymphadenectasis (41.1%). The prevalence of laboratory tests were as follows: albumin <35 g/L (55.6%), erythrocyte sedimentation rate >20 mm/h (91.4%), anaemia (59.0%), predominantly mild, CD4+ T cell count ≤50 pieces/μL (70.3%), and CD4+ T cell count 51-200 pieces/μL (22.1%). Lesion manifestations in thoracic imaging mainly included bilateral lung involvement (83.8%), showed stripe shadows (60.3%), patchy shadows (42.9%), nodules (40.6%), and bronchiectasis (38.6%). Accompanied signs included thoracic lymph node enlargement (49.5%). Seventy per cent of symptoms improved after treatment.
CONCLUSIONS
Focusing on clinical symptoms, laboratory tests, and thoracic imaging helps with initial screening for NTM infections. Physicians should raise awareness of the diagnosis and treatment of Mycobacterium avium complex, providing guidance for experimental treatment, screening of priority populations for NTM infections, and prophylactic treatment of NTM disease.
REGISTRATION
PROSPERO CRD42023388185.
Topics: Humans; Male; Acquired Immunodeficiency Syndrome; China; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; HIV Infections
PubMed: 37651639
DOI: 10.7189/jogh.13.04093 -
Chest Nov 2023Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is widely underdiagnosed, and certain patient groups, such as those with underlying respiratory diseases, are at increased risk of developing the disease. Understanding patients at risk is essential to allow for prompt testing and diagnosis and appropriate management to prevent disease progression.
RESEARCH QUESTION
What are the risk factors for NTM-PD that should prompt a physician to consider NTM testing and diagnosis?
STUDY DESIGN AND METHODS
Electronic searches of PubMed and EMBASE were conducted in July 2021 for the period 2011-2021. Inclusion criteria were studies of patients with NTM-PD with associated risk factors. Data were extracted and assessed using the Newcastle-Ottawa Scale. Data analysis was conducted using the R-based "meta" package. Only studies that reported association outcomes for cases with NTM-PD compared with control participants (healthy populations or participants without NTM-PD) were considered for the meta-analysis.
RESULTS
Of the 9,530 searched publications, 99 met the criteria for the study. Of these, 24 formally reported an association between possible risk factors and the presence of NTM-PD against a control population and were included in the meta-analysis. Comorbid respiratory disease was associated with a significant increase in the OR for NTM-PD (bronchiectasis [OR, 21.43; 95% CI, 5.90-77.82], history of TB [OR, 12.69; 95% CI, 2.39-67.26], interstitial lung disease [OR, 6.39; 95% CI, 2.65-15.37], COPD [OR, 6.63; 95% CI, 4.57-9.63], and asthma [OR, 4.15; 95% CI, 2.81-6.14]). Other factors noted to be associated with an increased risk of NTM-PD were the use of inhaled corticosteroids (OR 4.46; 95% CI, 2.13-9.35), solid tumors (OR, 4.66; 95% CI, 1.04-20.94) and the presence of pneumonia (OR, 5.54; 95% CI, 2.72-11.26).
INTERPRETATION
The greatest risk for NTM-PD is conferred by comorbid respiratory diseases such as bronchiectasis. These findings could help with identification of patient populations at risk for NTM-PD to drive prompt testing and appropriate initiation of therapy.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Risk Factors; Bronchiectasis; Asthma; Respiratory Tract Diseases; Nontuberculous Mycobacteria; Lung Diseases; Retrospective Studies
PubMed: 37429481
DOI: 10.1016/j.chest.2023.06.014 -
The Journal of Infection Sep 2023Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
METHODS
We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961.
RESULTS
Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5).
CONCLUSION
Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
Topics: Humans; Adult; Pregnancy; Female; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Antitubercular Agents
PubMed: 37356629
DOI: 10.1016/j.jinf.2023.06.014 -
JB & JS Open Access 2023Although infection following anterior cruciate ligament (ACL) reconstruction is rare, these cases have potentially catastrophic ramifications. Nontuberculous...
UNLABELLED
Although infection following anterior cruciate ligament (ACL) reconstruction is rare, these cases have potentially catastrophic ramifications. Nontuberculous mycobacteria (NTM) are ubiquitous, located in the water supply and soil. Our objective was to review the literature to characterize NTM infection following ACL reconstruction.
METHODS
A database search was performed for arthroscopic ACL reconstructions that resulted in a postoperative diagnosis of NTM infection.
RESULTS
The literature search returned 6 case reports that met the inclusion criteria. The initial postoperative presentation occurred after 3 to 52 weeks, which is consistent with reports of postoperative NTM infection.
CONCLUSIONS
The common indolent course of NTM infection hinders prompt diagnosis and treatment. Organism susceptibility testing is crucial for effective treatment and limiting unnecessary antibiotic exposure.
CLINICAL RELEVANCE
The duration of medical treatment for NTM infection is 4 to 6 months, depending on the severity of disease and species. Based on the aggregate literature, we recommend removal of local implants if the infection is localized and without articular involvement. However, in cases of articular involvement, all fixation and graft material should be removed.
PubMed: 37123505
DOI: 10.2106/JBJS.OA.23.00030 -
One Health (Amsterdam, Netherlands) Jun 2023() disease is an important infection disease throughout the world. () is a common . Extrapulmonary infections due to , particularly spine infections, are a rare...
BACKGROUND AND PURPOSE
() disease is an important infection disease throughout the world. () is a common . Extrapulmonary infections due to , particularly spine infections, are a rare occurrence, but lack of research is cited as a constraint for implementing control in such patients. The purposes of this paper are to describe a case of spondylodiscitis, to review the published literature on cases of spine infections, and to summarize the predisposing factors, diagnosis, and treatment of infection.
METHODS
A case of spondylodiscitis was caused by in a patient with systemic lupus erythematosus (SLE). Research was conducted using the PubMed, ScienceDirect, Embase, Wiley Online Library, and Scopus databases using the following search terms: "", "vertebral", "spinal", "spondylodiscitis", "infection", and "osteomyelitis".
RESULTS
We retrieved 14 cases published before August 2022. The risk factors for infection were iatrogenic infections (3/14, 21.43%), SLE (4/14, 28.57%), AIDS (4/14, 28.57%), and immunocompetence without any comorbidities (3/14, 21.43%). The most common sites of infection were thoracic vertebrae (10/14, 71.43%) and lumbar vertebrae (4/14, 28.57%). A total of 14 cases were isolated and identified as from a toad by mycobacterial culture. The identification time was 55.00 ± 7.55 days (the present report identification time of metagenomic next generation sequencing (mNGS) was only 2 days). All patients were treated with antibiotic therapy, and the duration of treatment was 13.18 ± 2.13 months. Clarithromycin-based therapy showed a higher improvement rate (5/6, 83.33%). Surgical intervention was performed in 5 patients. Only 1 patient did not show any improvement after surgical treatment.
CONCLUSION
spine infection in humans presents with atypical clinical symptoms. mNGS identification may be a good choice. may be considered in immunocompromised patients with spinal infection. We recommend a clarithromycin-containing regimen and prolonging the duration of treatment to ensure effectiveness.
PubMed: 36817979
DOI: 10.1016/j.onehlt.2023.100502 -
ERJ Open Research Jan 2023People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We... (Review)
Review
BACKGROUND
People living with cystic fibrosis have an increased risk of lung infection with nontuberculous mycobacteria (NTM), the prevalence of which is reportedly increasing. We conducted a systematic review of the literature to estimate the burden (prevalence and incidence) of NTM in the cystic fibrosis population.
METHODS
Electronic databases, registries and grey literature sources were searched for cohort and cross-sectional studies reporting epidemiological measures (incidence and prevalence) of NTM infection or NTM pulmonary disease in cystic fibrosis. The last search was conducted in September 2021; we included reports published since database creation and registry reports published since 2010. The methodological quality of studies was appraised with the Joanna Briggs Institute tool. A random effects meta-analysis was conducted to summarise the prevalence of NTM infection, and the remaining results are presented in a narrative synthesis.
RESULTS
This review included 95 studies. All 95 studies reported on NTM infection, and 14 of these also reported on NTM pulmonary disease. The pooled estimate for the point prevalence of NTM infection was 7.9% (95% CI 5.1-12.0%). In meta-regression, sample size and geographical location of the study modified the estimate. Longitudinal analysis of registry reports showed an increasing trend in NTM infection prevalence between 2010 and 2019.
CONCLUSIONS
The overall prevalence of NTM infection in cystic fibrosis is 7.9% and is increasing over time based on international registry reports. Future studies should report screening frequency, microbial identification methods and incidence rates of progression from NTM infection to pulmonary disease.
PubMed: 36605902
DOI: 10.1183/23120541.00336-2022 -
PloS One 2022The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for...
INTRODUCTION
The prevalence of Mycobacterium avium complex (MAC) is increasing globally. Macrolide-based multidrug regimens have been recommended as the first-line treatment for patients with MAC pulmonary disease. However, developing macrolide resistance was associated with poor treatment outcomes and increased mortality. In 2018, the U.S. Food and Drug Administration approved liposomal amikacin for inhalation (LAI) to treat refractory MAC pulmonary disease. The current systematic review aimed to evaluate LAI's outcomes and adverse events in MAC pulmonary disease.
METHODS
The systematic search was performed in PubMed/Medline, EMBASE, and the Cochrane Controlled Register of Trials (CENTRAL) up to March 8, 2022. The search terms included Mycobacterium avium complex, MAC, amikacin, and liposomal amikacin.
RESULTS
After reviewing 1284 records, four papers met the inclusion criteria, including three clinical trials and one prospective cohort study. These studies showed that adding LAI to guideline-based therapies can increase sputum culture conversion rate and achieve early sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for three months after treatment) negative sputum culture. In addition, extended LAI use was a potential benefit in patients considered refractory to initial treatment. The most prevalent treatment-emergent adverse events (TEAE) reported in the LAI group were the respiratory TEAE.
CONCLUSIONS
LAI could increase the sputum culture conversion rate and achieve early sustainable, durable negative sputum culture. However, additional large-scale research is required to confirm the results.
Topics: Humans; Amikacin; Mycobacterium avium Complex; Anti-Bacterial Agents; Liposomes; Mycobacterium avium-intracellulare Infection; Prospective Studies; Macrolides; Drug Resistance, Bacterial; Lung Diseases
PubMed: 36574432
DOI: 10.1371/journal.pone.0279714