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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 -
Respiration; International Review of... 2021Although international bronchiectasis guidelines recommended screening of nontuberculous mycobacteria (NTM) both at initial evaluation and prior to administration of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although international bronchiectasis guidelines recommended screening of nontuberculous mycobacteria (NTM) both at initial evaluation and prior to administration of macrolide treatment, data regarding NTM in bronchiectasis remain elusive.
OBJECTIVE
To establish the prevalence, species, and clinical features of NTM in adults with bronchiectasis.
METHODS
We searched PubMed, Embase, and Web of Science for studies published before April 2020 reporting the prevalence of NTM in adults with bronchiectasis. We only included studies with bronchiectasis confirmed by computed tomography and NTM identified by mycobacteria culture or molecular methods. Random-effects meta-analysis was employed.
RESULTS
Of the 2,229 citations identified, 21 studies, including 12,454 bronchiectasis patients were included in the final meta-analysis. The overall pooled prevalence of NTM isolation and pulmonary NTM disease were 7.7% (5.0%-11.7%) (n/N = 2,677/12,454) and 4.1% (1.4%-11.4%) (n/N = 30/559), respectively, with significant heterogeneity (I2 = 97.7%, p < 0.001 and I2 = 79.9%, p = 0.007; respectively). The prevalence of NTM isolation varied significantly among different geographical regions with the highest isolation at 50.0% (47.3%-52.7%) reported in the United States. Mycobacterium avium complex and Mycobacterium abscessus complex accounted for 66 and 16.6% of all species, respectively. Some clinical and radiological differences were noted between patients with and without the presence of NTM isolation although the results are inconsistent.
CONCLUSIONS
Heterogeneity in prevalence estimates of NTM isolation indicated that both local surveys to inform development of clinical services tailored to patients with bronchiectasis and population-based studies are needed. The clinical features associated with NTM in bronchiectasis and their incremental utility in studying the association is unknown and merits further investigation.
Topics: Adult; Bronchiectasis; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Nontuberculous Mycobacteria; Prevalence
PubMed: 34515207
DOI: 10.1159/000518328 -
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 -
Paediatric Respiratory Reviews Feb 2020To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP).
OBJECTIVES
To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP).
DESIGN
Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases.
RESULTS
Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently.
CONCLUSION
Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Biopsy; Bronchoalveolar Lavage; Chest Pain; Child; Constipation; Cough; Culture; Dietary Supplements; Humans; Hypoxia; Laxatives; Mouthwashes; Mycobacterium Infections, Nontuberculous; Nasal Lavage; Oils; Osteoarthropathy, Primary Hypertrophic; Oxygen Inhalation Therapy; Palliative Care; Pneumonia, Bacterial; Pneumonia, Lipid; Pneumonia, Viral; Respiration, Artificial; Risk Factors; Tachypnea; Tuberculosis, Pulmonary
PubMed: 30962152
DOI: 10.1016/j.prrv.2019.01.001 -
Frontiers in Public Health 2020China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the... (Meta-Analysis)
Meta-Analysis
China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the prevention, control, and management of tuberculosis (TB) and posing a significant threat to human health. However, there is a lack of an organized monitoring system for NTM such as that used for tuberculosis. Comprehensive data on patient susceptibility, dominant species, and drug resistance profiles are needed to improve the treatment protocols and the management of NTM. Primary research reports of NTM clinical specimens from mainland China published between January 1, 2000 and May 31, 2019 were retrieved from four online resources (BIOSIS, Embase, PubMed, and Web of Science) and three Chinese medical literature databases (CNKI, Wanfang, and Vip) as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In total, 339 publications were included in the systematic review, 129 were used in the drug susceptibility analysis, and 95 were used in the meta-analysis. Traditional culture using Lowenstein-Jensen slants combined with P-nitrobenzene acid and thiophene-2-carboxylic acid hydrazine differential medium and proportional method was most commonly used for the isolation, identification, and drug susceptibility testing of NTM in China. The crude isolation rate for NTM among TB suspected cases was 4.66-5.78%, while the proportion of NTM among isolates was 11.57%. and complex were the most common clinical NTM species. NTM only showed general sensitivity to ethambutol, linezolid, clofazimine, amikacin, tobramycin, and clarithromycin. The prevalence of NTM in China has shown a decreasing trend. was replaced as the dominant species by over the course of the study. The geographic diversity of different species showed the effects of environmental and economic factors on the distribution of NTM and indicated that there were important factors still not identified. While there were only a limited number of antibiotics to which NTM showed any sensitivity, the drug resistance profiles of the isolates were highly variable and thus more caution should be taken when empirically treating NTM infection.
Topics: China; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Prevalence
PubMed: 32850570
DOI: 10.3389/fpubh.2020.00295 -
The Cochrane Database of Systematic... Aug 2018Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Buruli ulcer is a necrotizing cutaneous infection caused by infection with Mycobacterium ulcerans bacteria that occurs mainly in tropical and subtropical regions. The infection progresses from nodules under the skin to deep ulcers, often on the upper and lower limbs or on the face. If left undiagnosed and untreated, it can lead to lifelong disfigurement and disabilities. It is often treated with drugs and surgery.
OBJECTIVES
To summarize the evidence of drug treatments for treating Buruli ulcer.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (Ovid); and LILACS (Latin American and Caribbean Health Sciences Literature; BIREME). We also searched the US National Institutes of Health Ongoing Trials Register (clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en/). All searches were run up to 19 December 2017. We also checked the reference lists of articles identified by the literature search, and contacted leading researchers in this topic area to identify any unpublished data.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that compared antibiotic therapy to placebo or alternative therapy such as surgery, or that compared different antibiotic regimens. We also included prospective observational studies that evaluated different antibiotic regimens with or without surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria, extracted the data, and assessed methodological quality. We calculated the risk ratio (RR) for dichotomous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included a total of 18 studies: five RCTs involving a total of 319 participants, ranging from 12 participants to 151 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. Only one RCT reported adequate methods to minimize bias. Regarding monotherapy, one RCT and one observational study evaluated clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. The remaining studies examined combination therapy.Rifampicin combined with streptomycinWe found one RCT and six observational studies which evaluated rifampicin combined with streptomycin for different lengths of treatment (2, 4, 8, or 12 weeks) (941 participants). The RCT did not demonstrate a difference between the drugs added to surgery compared with surgery alone for recurrence at 12 months, but was underpowered (RR 0.12, 95% CI 0.01 to 2.51; 21 participants; very low-certainty evidence).An additional five single-arm observational studies with 828 participants using this regimen for eight weeks with surgery (given to either all participants or to a select group) reported healing rates ranging from 84.5% to 100%, assessed between six weeks and one year. Four observational studies reported healing rates for participants who received the regimen alone without surgery, reporting healing rates ranging from 48% to 95% assessed between eight weeks and one year.Rifampicin combined with clarithromycinTwo observational studies administered combined rifampicin and clarithromycin. One study evaluated the regimen alone (no surgery) for eight weeks and reported a healing rate of 50% at 12 months (30 participants). Another study evaluated the regimen administered for various durations (as determined by the clinicians, durations unspecified) with surgery and reported a healing rate of 100% at 12 months (21 participants).Rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phaseOne RCT evaluated this regimen (four weeks in each phase) against continuing with rifampicin and streptomycin in the consolidation phase (total eight weeks). All included participants had small lesions, and healing rates were above 90% in both groups without surgery (healing rate at 12 months RR 0.94, 95% CI 0.87 to 1.03; 151 participants; low-certainty evidence). One single-arm observational study evaluating the substitution of streptomycin with clarithromycin in the consolidation phase (6 weeks, total 8 weeks) without surgery given to a select group showed a healing rate of 98% at 12 months (41 participants).Novel combination therapyTwo large prospective studies in Australia evaluated some novel regimens. One study evaluating rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery reported a healing rate of 76.5% at 12 months (132 participants). Another study evaluating combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin with surgery reported a healing rate of 100% (90 participants).Adverse effects were reported in only three RCTs (158 participants) and eight prospective observational studies (878 participants), and were consistent with what is already known about the adverse effect profile of these drugs. Paradoxical reactions (clinical deterioration after treatment caused by enhanced immune response to M ulcerans) were evaluated in six prospective observational studies (822 participants), and the incidence of paradoxical reactions ranged from 1.9% to 26%.
AUTHORS' CONCLUSIONS
While the antibiotic combination treatments evaluated appear to be effective, we found insufficient evidence showing that any particular drug is more effective than another. How different sizes, lesions, and stages of the disease may contribute to healing and which kind of lesions are in need of surgery are unclear based on the included studies. Guideline development needs to consider these factors in designing practical treatment regimens. Forthcoming trials using clarithromycin with rifampicin and other trials of new regimens that also address these factors will help to identify the best regimens.
Topics: Anti-Bacterial Agents; Buruli Ulcer; Clarithromycin; Clofazimine; Drug Therapy, Combination; Humans; Mycobacterium ulcerans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Rifampin; Streptomycin; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 30136733
DOI: 10.1002/14651858.CD012118.pub2 -
New Microbes and New Infections Nov 2018is one of the most common nontuberculous mycobacteria (NTM) microorganisms causing lung disease in many countries in the world. A reliable estimate of the extent of...
is one of the most common nontuberculous mycobacteria (NTM) microorganisms causing lung disease in many countries in the world. A reliable estimate of the extent of pulmonary disease has not been well investigated in Iran. We systematically searched multiple databases to identify relative studies. Studies were excluded if they did not use the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) diagnostic criteria for NTM diseases. Data were extracted independently and in duplicate. We assessed pooled estimate by using a random model effect, and sources of heterogeneity were assessed by using Cochran's and the statistic. The potential for publication bias was explored by using Begg's and Egger's tests. All analyses were conducted with Stata 14.0 (StataCorp, College Station, TX, USA). Of 172 articles identified, seven met the inclusion criteria. Of 355 patients who were culture positive for NTM, 82 had M pulmonary disease according to the ATS/IDSA diagnostic criteria. The pooled frequency of pulmonary disease among patients with NTM was 25.0% (95% confidence interval, 16.8-33.2). No evidence of publication bias was observed among the included studies (p >0.05 for Begg's and Egger's tests). Clinical isolates of are increasingly being recognized as a cause of pulmonary disease in Iran and need further attention by health authorities.
PubMed: 30370055
DOI: 10.1016/j.nmni.2018.09.008 -
International Journal of Infectious... Mar 2022Otomastoiditis caused by Mycobacterium abscessus is rare, but its incidence has increased over the past decades and its optimal treatment remains unknown. This study... (Meta-Analysis)
Meta-Analysis Review
Clinical characteristics and an evaluation of predictors for a favourable outcome of Mycobacterium abscessus otomastoiditis: a systematic review and meta-analysis of individual participant data.
BACKGROUND
Otomastoiditis caused by Mycobacterium abscessus is rare, but its incidence has increased over the past decades and its optimal treatment remains unknown. This study aims to summarise the clinical and therapeutic features and find characteristics of patients with M. abscessus otomastoiditis associated with favourable treatment outcomes.
METHODS
We searched MEDLINE, Embase and Web of Science to identify studies including patients with M. abscessus otomastoiditis. A 1-stage individual patient data (IPD) meta-analysis was conducted. A 2-level mixed-effects linear regression model was provided for antimycobacterial treatment duration.
RESULTS
Twenty-three studies reported a total of 85 patients. Children possess a unique clinical profile including a history of ear infections, tympanostomy tube placement and antibiotic treatment. Antimycobacterial treatment was administered for 26 (interquartile range [IQR]: 15-35) weeks. Macrolides were prescribed in 98.8% of the cases. Surgery was performed in 80.5% of the cases, of which, 47.1% required revision surgery. Otalgia was a significant predictor (β = 9.3; P = .049) of antimycobacterial treatment duration.
CONCLUSIONS
Mastoid surgery (regularly requiring revision) and a multidrug regimen for a minimum of 6 months, including a minimum of 3 active agents, are most often needed to attain cure. The presence of otalgia significantly extends the treatment duration of M. abscessus otomastoiditis.
Topics: Anti-Bacterial Agents; Child; Humans; Macrolides; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 35038600
DOI: 10.1016/j.ijid.2022.01.017 -
The Journal of Antimicrobial... Feb 2024Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible.
METHOD
Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline's impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans.
RESULTS
Fifty studies met the inclusion criteria: 33 assessed bedaquiline's impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline's efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection.
CONCLUSIONS
Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Diarylquinolines; Anti-Bacterial Agents
PubMed: 38134888
DOI: 10.1093/jac/dkad372 -
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