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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 -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
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 -
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 Antimicrobial... Jun 2024This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections.
METHODS
We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I statistic. All analyses were performed using CMA V3.0.
RESULTS
A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively.
CONCLUSION
This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.
Topics: Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium Infections, Nontuberculous; Antitubercular Agents; Drug Resistance, Bacterial; Mycobacterium avium-intracellulare Infection
PubMed: 38561143
DOI: 10.1016/j.jgar.2024.03.009 -
The Journal of Infection Jun 2024The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this... (Review)
Review
INTRODUCTION
The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium.
METHODS
A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed.
RESULTS
188 patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n=106/188, 56.4%). One third (n=61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p=0.002, and 0.23, 95% CI 0.04-0.86, p=0.03, for lethal events, respectively).
CONCLUSION
In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.
PubMed: 38906266
DOI: 10.1016/j.jinf.2024.106203 -
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 -
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 -
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 -
Journal of Orthopaedic Surgery (Hong... 2023(MAC) prosthetic joint infection (PJI) has been rarely reported.
BACKGROUND
(MAC) prosthetic joint infection (PJI) has been rarely reported.
METHODS
This study aimed to investigate the epidemiology and outcomes of MAC PJI. A systematic review of the literature regarding the MAC infection following total joint arthroplasty including hip and knee joint was performed. Multiple databases were searched for published English-written articles up to May 2023. Studies that reported cases of PJI by MAC were reviewed.
RESULTS
A total of 17 patients were identified and analyzed from 11 published studies. All patients presented with joint symptom of pain or swelling prior to the diagnosis and MAC was confirmed by culture. The most of the patients (16/17 patients, 94.1%) were noted to have underlying medical condition(s) that might have affected immunity. Treatment consisted of anti-MAC medication therapy only in two patients and anti-MAC medication therapy plus surgery in 15 patients. Among the patients who underwent surgery, 14 patients (82.3%) had removal of the prosthesis including seven patients who had two-stage surgery to have reimplantation of the prosthesis. No relapse of MAC infection was reported despite of one case of relapse of infection caused by different pyogenic bacteria. The rate of overall mortality was 29.4%, however, identified attributable mortality due to MAC infection was low (5.9%).
CONCLUSION
PJI by MAC is a rare disease. However, MAC needs to be considered in the differential diagnosis in immunocompromised patients presenting with symptoms of PJI. Two-stage exchange arthroplasty may result in successful treatment outcomes without higher risks of relapse of infection if undertaken in association with appropriate active anti-MAC antibiotic therapy.
Topics: Humans; Mycobacterium avium Complex; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip; Mycobacterium avium-intracellulare Infection; Prostheses and Implants; Anti-Bacterial Agents; Arthritis, Infectious; Recurrence; Prosthesis-Related Infections; Retrospective Studies
PubMed: 37878458
DOI: 10.1177/10225536231199392