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1.
J Infect Dev Ctries ; 18(5): 751-760, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38865399

ABSTRACT

INTRODUCTION: Although nontuberculous mycobacterial (NTM) infection is a common cause of pulmonary disease worldwide, few studies have focused on epidemiological and therapeutic factors related to NTM cases in Anhui Province, China. This retrospective study aimed to identify aetiological and clinical factors, and treatment outcomes of patients with NTM pulmonary disease (NTMPD) in Anhui. METHODOLOGY: Retrospective clinical data obtained from medical records of NTMPD patients seeking care at Anhui Chest Hospital from July 2019 to June 2022 were analyzed. Treatment outcomes were compared between two patient groups: one receiving a standardised NTM treatment regimen and the other receiving precision treatment regimens. RESULTS: Genotypic analysis of 672 clinical NTMPD-associated isolates revealed that most were Mycobacterium intracellulare, while drug-susceptibility test results demonstrated diverse antibiotic resistance profiles for these isolates. Cough was the most common symptom for 101 NTMPD patients. After patients of both groups received treatment, symptoms improved, sputum culture conversion was observed for some patients, imaging findings stabilised; however, no statistically significant intergroup differences in treatment outcomes were found. CONCLUSIONS: In this study, M. intracellulare was the predominant NTM species identified in isolates obtained from NTMPD patients. Drug resistance profiles of our patient isolates were complex, highlighting the need for administration of timely, more effective, standardised treatments for patients with NTMPD in Anhui Province, China.


Subject(s)
Anti-Bacterial Agents , Mycobacterium Infections, Nontuberculous , Humans , China/epidemiology , Retrospective Studies , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Male , Female , Middle Aged , Aged , Anti-Bacterial Agents/therapeutic use , Treatment Outcome , Nontuberculous Mycobacteria/isolation & purification , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/genetics , Adult , Microbial Sensitivity Tests , Lung Diseases/microbiology , Lung Diseases/drug therapy , Lung Diseases/epidemiology , Sputum/microbiology
2.
Gut Microbes ; 16(1): 2361490, 2024.
Article in English | MEDLINE | ID: mdl-38860456

ABSTRACT

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Mycobacterium Infections, Nontuberculous , Toll-Like Receptor 2 , Dysbiosis/microbiology , Animals , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Humans , Mice , Male , Female , Mycobacterium Infections, Nontuberculous/microbiology , Middle Aged , Feces/microbiology , Aged , Prevotella , Lung Diseases/microbiology , Nontuberculous Mycobacteria , Disease Susceptibility , Mice, Inbred C57BL , Lung/microbiology
3.
BMC Microbiol ; 24(1): 172, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38760693

ABSTRACT

BACKGROUND: We evaluated whether the sputum bacterial microbiome differs between nontuberculous mycobacteria pulmonary disease (NTM-PD) patients with stable disease not requiring antibiotic treatment and those requiring antibiotics. METHODS: We collected sputum samples from 21 clinically stable NTM-PD patients (stable group) and 14 NTM-PD patients needing antibiotic treatment (treatment group). We also obtained 13 follow-up samples from the stable group. We analyzed the 48 samples using 16S rRNA gene sequencing (V3-V4 region) and compared the groups. RESULTS: In the linear discriminant analysis effect size (LEfSe) analysis, the species Porphyromonas pasteri, Haemophilus parahaemolyticus, Prevotella nanceiensis, and Gemella haemolysans were significantly more prevalent in the sputum of the stable group compared to the treatment group. No taxa showed significant differences in alpha-/beta-diversity or LEfSe between the 21 baseline and 13 follow-up sputum samples in the stable group. In the stable group, the genus Bergeyella and species Prevotella oris were less common in patients who achieved spontaneous culture conversion (n = 9) compared to those with persistent NTM positivity (n = 12) (effect size 3.04, p = 0.039 for Bergeyella; effect size 3.64, p = 0.033 for P. oris). In the treatment group, H. parainfluenzae was more common in patients with treatment success (n = 7) than in treatment-refractory patients (n = 7) (effect size 4.74, p = 0.013). CONCLUSIONS: Our study identified distinct bacterial taxa in the sputum of NTM-PD patients based on disease status. These results suggest the presence of a microbial environment that helps maintain disease stability.


Subject(s)
Microbiota , Mycobacterium Infections, Nontuberculous , RNA, Ribosomal, 16S , Sputum , Humans , Sputum/microbiology , Male , Female , Microbiota/genetics , Microbiota/drug effects , Aged , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/drug therapy , RNA, Ribosomal, 16S/genetics , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Nontuberculous Mycobacteria/isolation & purification , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/drug effects , DNA, Bacterial/genetics , Lung Diseases/microbiology , Lung Diseases/drug therapy
4.
mSystems ; 9(6): e0131223, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38712927

ABSTRACT

Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.


Subject(s)
Dysbiosis , Gastrointestinal Microbiome , Lung Transplantation , Humans , Lung Transplantation/adverse effects , Female , Male , Middle Aged , Adult , Dysbiosis/microbiology , Lung Diseases/microbiology , Lung Diseases/surgery , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Feces/microbiology , Aged
5.
J Korean Med Sci ; 39(20): e167, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38804011

ABSTRACT

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.


Subject(s)
Coinfection , Lung Diseases , Mycobacterium Infections, Nontuberculous , Nontuberculous Mycobacteria , Humans , Female , Male , Middle Aged , Retrospective Studies , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/complications , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Aged , Coinfection/microbiology , Nontuberculous Mycobacteria/isolation & purification , Treatment Outcome , Lung Diseases/microbiology , Lung Diseases/complications , Mycobacterium avium Complex/isolation & purification , Anti-Bacterial Agents/therapeutic use , Republic of Korea
6.
Front Cell Infect Microbiol ; 14: 1367885, 2024.
Article in English | MEDLINE | ID: mdl-38784566

ABSTRACT

Objective: This study aims to investigate the clinical application value of Metagenome Next-Generation Sequencing (mNGS) for pulmonary diffuse exudative lesions. Methods: From January 1, 2014, to November 31, 2021, 136 cases with chest radiologic presentations of pulmonary diffuse exudative lesions admitted to Fujian Provincial Hospital were included in the study; of those, 77 patients underwent mNGS pathogen detection. Based on the pathogen detection outcomes and clinical diagnoses, patients were categorized into an infection group (IG) and a non-infection group (NIG). A comparison was made between the diagnostic efficacy of the mNGS technique and traditional culture methods. Meanwhile, 59 patients clinically identified as having infectious pulmonary diffuse exudative lesions but who did not receive mNGS testing were designated as the non-NGS infection group (non-IG). A retrospective cohort study was conducted on patients in both the IG and non-IG, with a 30-day all-cause mortality endpoint used for follow-up. Outcomes: When compared to conventional culture methods, mNGS demonstrated an approximate 35% increase in sensitivity (80.0% vs 45.5%, P<0.001), without significant disparity in specificity (77.3% vs 95.5%, P=0.185). Under antibiotic exposure, the positivity rate detected by mNGS was notably higher than that by traditional culture methods, indicating that mNGS is less affected by exposure to antibiotics (P<0.05). Within 30 days, the all-cause mortality rate for patients in the IG versus the non-IG was 14.55% and 37.29%, respectively (P<0.05). Following a COX regression analysis to adjust for confounding factors, the analysis revealed that a CURB-65 score ≥3 points (HR=3.348, P=0.001) and existing cardiovascular disease (HR=2.473, P=0.026) were independent risk factors for these patients. Conversely, mNGS testing (HR=0.368, P=0.017) proved to be an independent protective factor. Conclusion: mNGS technology makes it easier to pinpoint the cause of pulmonary diffuse infectious exudative lesions without much interference from antibiotics, helping doctors spot and diagnose these issues early on, thereby playing a key role in helping them decide the best treatment approach for patients. Such conclusions may have a bias, as the performance of traditional methods might be underestimated due to the absence of complete results from other conventional diagnostic techniques like serological testing and PCR.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenome , Humans , Retrospective Studies , Male , Female , High-Throughput Nucleotide Sequencing/methods , Middle Aged , Aged , Sensitivity and Specificity , Adult , Lung Diseases/microbiology , Lung Diseases/diagnosis , Lung/microbiology , Lung/pathology , Aged, 80 and over , Metagenomics/methods
7.
J Ethnopharmacol ; 331: 118288, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38705426

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. PURPOSE: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. METHODS: The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein-protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1ß, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. RESULTS: Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS.In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group, Colidextribacter, Romboutsia, and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. CONCLUSION: Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application.


Subject(s)
Drugs, Chinese Herbal , Lung , Network Pharmacology , Rats, Sprague-Dawley , Streptococcus pneumoniae , Animals , Drugs, Chinese Herbal/pharmacology , Lung/drug effects , Lung/microbiology , Lung/pathology , Lung/metabolism , Male , Streptococcus pneumoniae/drug effects , Rats , Cytokines/metabolism , Disease Models, Animal , Protein Interaction Maps , Intestines/drug effects , Intestines/microbiology , Fever/drug therapy , Gastrointestinal Microbiome/drug effects , Lung Diseases/drug therapy , Lung Diseases/microbiology
9.
Comp Med ; 74(2): 121-129, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561234

ABSTRACT

Chlamydia muridarum (Cm), an intracellular bacterium of historical importance, was recently rediscovered as moderately prevalent in research mouse colonies. Cm was first reported as a causative agent of severe pneumonia in mice about 80 y ago, and while it has been used experimentally to model Chlamydia trachomatis infection of humans, there have been no further reports of clinical disease associated with natural infection. We observed clinical disease and pathology in 2 genetically engi- neered mouse (GEM) strains, Il12rb2 KO and STAT1 KO, with impaired interferon-γ signaling and Th1 CD4+ T cell responses in a colony of various GEM strains known to be colonized with and shedding Cm. Clinical signs included poor condition, hunched posture, and poor fecundity. Histopathology revealed disseminated Cm with lesions in pulmonary, gastrointestinal, and urogenital tissues. The presence of Cm was confirmed using both immunohistochemistry for Cm major outer membrane protein-1 antigen and in situ hybridization using a target probe directed against select regions of Cm strain Nigg. Cm was also found in association with a urothelial papilloma in one mouse. These cases provide additional support for excluding Cm from research mouse colonies.


Subject(s)
Chlamydia Infections , Chlamydia muridarum , Mice, Knockout , STAT1 Transcription Factor , Animals , Chlamydia Infections/pathology , Chlamydia Infections/veterinary , Chlamydia Infections/microbiology , Mice , STAT1 Transcription Factor/genetics , STAT1 Transcription Factor/metabolism , Female , Receptors, Interleukin-12/deficiency , Receptors, Interleukin-12/genetics , Male , Lung Diseases/microbiology , Lung Diseases/pathology , Lung Diseases/veterinary
10.
Ugeskr Laeger ; 186(14)2024 Apr 01.
Article in Danish | MEDLINE | ID: mdl-38606709

ABSTRACT

This review focuses on the treatment of nontuberculous pulmonary disease caused by Mycobacterium avium complex and M. abscessus. It covers treatment indications, antibiotic choice, resistance and side effects. Treatment of nontuberculous pulmonary disease is complex, lengthy, and fraught with side effects. Increased attention on this disease is needed in order to alleviate the severe consequences of this growing disease. Cooperation between pulmonologists and infectious disease specialists is needed to ensure uniform treatment, and to account for the heterogeneity seen in patients and mycobacteria alike.


Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Pneumonia , Humans , Nontuberculous Mycobacteria , Mycobacterium Infections, Nontuberculous/drug therapy , Lung Diseases/drug therapy , Lung Diseases/microbiology , Anti-Bacterial Agents/therapeutic use
11.
Ann Clin Microbiol Antimicrob ; 23(1): 25, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500139

ABSTRACT

BACKGROUND: Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high. RESULTS: In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility. CONCLUSIONS: In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.


Subject(s)
Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Mycobacterium avium Complex/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/microbiology , Lung Diseases/drug therapy , Lung Diseases/microbiology , Ethambutol/pharmacology , Ethambutol/therapeutic use
12.
Vet Microbiol ; 292: 110039, 2024 May.
Article in English | MEDLINE | ID: mdl-38502977

ABSTRACT

The intensification of pig farming has posed significant challenges in managing and preventing sanitary problems, particularly diseases of the respiratory complex. Monitoring at slaughter is an important control tool and cannot be overstated. Hence, this study aimed at characterizing both macroscopical and microscopical lesions and identifying the Actinobacillus pleuropneumoniae (APP), Mycoplasma hyopneumoniae (Mhyo), and Pasteurella multocida (PM) associated with pleurisy in swine. For this, a selected slaughterhouse in São Paulo State underwent a thorough examination of carcasses on the slaughter line, followed by lung sampling. The carcasses and lungs underwent macroscopical examination and were classified according to the score of pleurisy and lung samples were allocated into five groups, being: G0: score 0 - no lesions; G1: score 1; G2: score 2; G3: score 3; and G4: score 4. In total, 217 lung fragments were collected, for the histopathological evaluation and detection of the following respiratory pathogens: APP, Mhyo, and PM by qPCR. The results demonstrated that Mhyo and APP were the most prevalent etiological agents (single and co-identification) in lung samples, in different scores of pleurisies, while bronchopneumonia and bronchus-associated lymphoid tissue (BALT) hyperplasia lesions were the most frequent histopathological findings. Positive correlations were found between the quantification of APP DNA with 1) the score of pleurisy (R=0.254); 2) with the score of lung consolidation in all lung lobes (R=0.181 to R=0.329); and 3) with the score of lung consolidation in the entire lung (R=0.389). The study brings relevant information regarding the main bacterial pathogens associated with pleurisy in pigs and helps with understanding the relationship between the abovementioned pathogens and their impact on the respiratory health of pigs.


Subject(s)
Lung Diseases , Pasteurella multocida , Pleurisy , Swine Diseases , Swine , Animals , Swine Diseases/microbiology , Brazil , Lung/pathology , Pleurisy/veterinary , Pleurisy/microbiology , Pleurisy/pathology , Lung Diseases/microbiology , Lung Diseases/veterinary
13.
Diagn Microbiol Infect Dis ; 109(2): 116254, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38492490

ABSTRACT

The prevalence of Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) is increasing worldwide. The advancement in molecular diagnostic technology has greatly promoted the rapid diagnosis of NTM-PD clinically, and the pathogenic strains can be identified to the species level through molecular typing, which provides a reliable basis for treatment. In addition to the well-known PCR and mNGS methods, there are numerous alternative methods to identify NTM to the species level. The treatment of NTM-PD remains a challenging problem. Although clinical guidelines outline several treatment options for common NTM species infections, in most cases, the therapeutic outcomes of these drugs for NTM-PD often fall short of expectations. At present, the focus of research is to find more effective and more tolerable NTM-PD therapeutic drugs and regimens. In this paper, the latest diagnostic techniques, therapeutic drugs and methods, and prevention of NTM-PD are reviewed.


Subject(s)
Mycobacterium Infections, Nontuberculous , Nontuberculous Mycobacteria , Humans , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/isolation & purification , Nontuberculous Mycobacteria/classification , Anti-Bacterial Agents/therapeutic use , Lung Diseases/diagnosis , Lung Diseases/microbiology , Lung Diseases/drug therapy , Molecular Diagnostic Techniques/methods
14.
Sci Rep ; 14(1): 4438, 2024 02 23.
Article in English | MEDLINE | ID: mdl-38396118

ABSTRACT

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.


Subject(s)
Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Male , Middle Aged , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/microbiology , Retrospective Studies , Drug Therapy, Combination , Leprostatic Agents/pharmacology , Lung Diseases/microbiology , Prognosis
15.
Int J Tuberc Lung Dis ; 28(2): 73-80, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38303039

ABSTRACT

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD.RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association.CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.


Subject(s)
Lung Diseases , Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , Humans , Anti-Bacterial Agents/therapeutic use , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/microbiology , Lung Diseases/drug therapy , Lung Diseases/microbiology , Prospective Studies , Retrospective Studies
16.
Nat Rev Drug Discov ; 23(5): 381-403, 2024 May.
Article in English | MEDLINE | ID: mdl-38418662

ABSTRACT

Tuberculosis (TB) drug discovery and development has undergone nothing short of a revolution over the past 20 years. Successful public-private partnerships and sustained funding have delivered a much-improved understanding of mycobacterial disease biology and pharmacology and a healthy pipeline that can tolerate inevitable attrition. Preclinical and clinical development has evolved from decade-old concepts to adaptive designs that permit rapid evaluation of regimens that might greatly shorten treatment duration over the next decade. But the past 20 years also saw the rise of a fatal and difficult-to-cure lung disease caused by nontuberculous mycobacteria (NTM), for which the drug development pipeline is nearly empty. Here, we discuss the similarities and differences between TB and NTM lung diseases, compare the preclinical and clinical advances, and identify major knowledge gaps and areas of cross-fertilization. We argue that applying paradigms and networks that have proved successful for TB, from basic research to clinical trials, will help to populate the pipeline and accelerate curative regimen development for NTM disease.


Subject(s)
Antitubercular Agents , Mycobacterium Infections, Nontuberculous , Humans , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/microbiology , Antitubercular Agents/therapeutic use , Antitubercular Agents/pharmacology , Animals , Drug Development/methods , Tuberculosis/drug therapy , Tuberculosis/microbiology , Nontuberculous Mycobacteria/drug effects , Drug Discovery , Lung Diseases/drug therapy , Lung Diseases/microbiology
17.
J Infect Chemother ; 30(8): 780-784, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38182008

ABSTRACT

Patients with Mycobacterium avium complex pulmonary disease (MAC-PD) often suffer from chronic symptoms such as sputum production, which reduces quality of life. Oscillatory positive expiratory pressure (OPEP) devices are used in physiotherapy to promote the clearance of respiratory secretions. We report two cases of improved lung function and improved scores on the Leicester Cough Questionnaire (LCQ) and the Breathlessness, Cough and Sputum Scale (BCSS) after the use of OPEP in patients with MAC-PD where treatment with guideline-based therapy, including amikacin liposome inhalation suspension, had proved ineffective for symptoms. Use of OPEP might maximize the efficacy of therapy and thereby improves outcomes in patients with MAC-PD. It is important to use both guideline-based therapy and OPEP, especially in patients whose health-related quality of life is affected by sputum symptoms. Further prospective studies are warranted to assess the benefit of adding OPEP to guidelines concerning therapy for patients with MAC-PD and sputum symptoms.


Subject(s)
Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection , Quality of Life , Humans , Mycobacterium avium-intracellulare Infection/therapy , Mycobacterium avium-intracellulare Infection/microbiology , Male , Aged , Sputum/microbiology , Female , Positive-Pressure Respiration/instrumentation , Positive-Pressure Respiration/methods , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Treatment Outcome , Lung Diseases/microbiology , Lung Diseases/therapy , Lung Diseases/physiopathology
18.
Antimicrob Agents Chemother ; 68(3): e0115723, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38259101

ABSTRACT

Mycobacterium avium complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model. THP-1 cells, which are monocytes isolated from peripheral blood from an acute monocytic leukemia patient, were infected with M. avium ATCC 700898 and exposed to a regimen of azithromycin and ethambutol with either rifampicin or clofazimine. Intrapulmonary pharmacokinetic profiles of azithromycin, ethambutol, and rifampicin were simulated. For clofazimine, a steady-state average concentration was targeted. Drug concentrations and bacterial densities were monitored over 21 days. Exposures to azithromycin and ethambutol were 20%-40% lower than targeted but within clinically observed ranges. Clofazimine exposures were 1.7 times higher than targeted. Until day 7, both regimens were able to maintain stasis. Thereafter, regrowth was observed for the rifampicin-containing regimen, while the clofazimine-containing regimen yielded a 2 Log10 colony forming unit (CFU) per mL decrease in bacterial load. The clofazimine regimen also successfully suppressed the emergence of macrolide tolerance. In summary, substitution of rifampicin with clofazimine in the hollow-fiber model improved the antimycobacterial activity of the regimen. Clofazimine-containing regimens merit investigation in clinical trials.


Subject(s)
Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Rifampin/pharmacology , Rifampin/therapeutic use , Clofazimine/pharmacology , Clofazimine/therapeutic use , Ethambutol/pharmacology , Ethambutol/therapeutic use , Azithromycin/pharmacology , Mycobacterium avium , Mycobacterium avium-intracellulare Infection/drug therapy , Drug Therapy, Combination , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mycobacterium avium Complex , Lung Diseases/microbiology
20.
J Infect Chemother ; 30(2): 159-163, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37717608

ABSTRACT

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.


Subject(s)
Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Amikacin/pharmacology , Amikacin/therapeutic use , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Lung Diseases/microbiology , Culture Media , Microbial Sensitivity Tests
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