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1.
Front Public Health ; 12: 1461854, 2024.
Article in English | MEDLINE | ID: mdl-39314789

ABSTRACT

Objective: To understand and analyze the factors relating to patient and diagnostic delays among groups with tuberculous pleurisy (TP), and its spatiotemporal distribution in Zhejiang Province. Methods: Data of all tuberculous pleurisy patients were collected from the existing Tuberculosis Information Management System. A time interval of > 2 weeks between first symptom onset and visit to the designated hospital was considered a patient delay, and a time interval of > 2 weeks between the first visit and a confirmed TP diagnosis was considered a diagnostic delay. Univariate and multivariate logistic regression analyses were used to explore factors influencing patient and diagnostic delays in patients with TP. Spatial autocorrelation and spatiotemporal scan analyses were used to identify hot spots and risk clusters, respectively. Results: In total, 10,044 patients with TP were included. The median time and interquartile range for patients seeking medical care and diagnosis were 15 (7-30) and 1 (0-8) days, respectively. The results showed that people aged > 65 years, retirees, and residents of Jinhua, Lishui, and Quzhou were positively correlated with patient delay, whereas retreatment patients, houseworkers, unemployed people, and residents of Zhoushan or Ningbo were positively correlated with diagnostic delay. Additionally, high-risk clusters of patient delays were observed in the midwestern Zhejiang Province. The most likely clusters of TP diagnostic delays were found in southeast Zhejiang Province. Conclusion: In summary, patient delay of TP in Zhejiang province was shorter than for pulmonary tuberculosis in China, while the diagnostic delay had no difference. Age, city, occupation, and treatment history were related to both patient and diagnostic delays in TP. Interventions in central and western regions of Zhejiang Province should be initiated to improve the early detection of TP. Additionally, the allocation of health resources and accessibility of health services should be improved in the central and eastern regions of Zhejiang Province.


Subject(s)
Delayed Diagnosis , Spatio-Temporal Analysis , Tuberculosis, Pleural , Humans , China/epidemiology , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/epidemiology , Female , Delayed Diagnosis/statistics & numerical data , Male , Middle Aged , Risk Factors , Aged , Adult , Adolescent , Young Adult
2.
Infect Med (Beijing) ; 3(3): 100125, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39314805

ABSTRACT

Background: People with cystic fibrosis (CF) may develop clinically significant chronic respiratory infections with Pseudomonas aeruginosa (PA) and non-tuberculous mycobacteria (NTM). Open water has been suggested to be an important source for continuous or intermittent exposure to these pathogens. To date, there has been a paucity of studies examining the relationship between chronic PA and NTM infection in CF patients and surfaces waters, including blue spaces. The aim of this study was therefore to examine the relationship between chronic pulmonary infection with PA and NTMs in children and adults with CF in European countries and area of surface waters, including blue spaces. Methods: European CF registry data detailing incidence of chronic PA and NTM infection in adults and children with CF in Europe (n=41,486 in 24 European countries) was correlated with surface water area data from the same countries (approx. 678,278 km2) employing Spearman coefficients. Results: Correlation of chronic PA infection in children and adults and surface water area were not significant (p=0.0680 and p=0.8448, respectively), as was NTM infection (p=0.7371 and p=0.0712, respectively). Conclusions: Acquistion of PA and its avoidance in people with CF is a complicated dynamic, not solely driven by close association with surface water, but through the integration of several other factors, including mitigations by people with CF to avoid high risk scenarios with surface water. This study was unable to demonstrate a correlation between PA and NTM infection in people with cystic fibrosis and surface water area at a national level. CF patients should continue to be vigilant about potential infection risks posed by water and take evidence-based decisions regarding their behaviour around water to protect them for acquiring these organisms from these sources.

3.
Int J Surg Case Rep ; 124: 110335, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39317018

ABSTRACT

INTRODUCTION: Bezold's abscess is a rare complication of chronic suppurative otitis media since the advent of antibiotics. Otitis media can also result from uncommon infections such as tuberculosis, with a diagnosis often delayed due to clinical symptoms that closely resemble other chronic middle ear conditions. CASE REPORT: We present a case of Bezold's abscess as a complication of primary tuberculous otitis media in a 21-year-old male who reported right-sided neck swelling for four days, accompanied by fever, difficulty opening his mouth, and a history of persistent purulent discharge in both ears for six months that did not respond to topical antibiotics. DISCUSSION: This case underscores the diagnostic challenges of tuberculous otitis media, an unusual form of extrapulmonary tuberculosis that can closely mimic other types of chronic otitis media. The atypical presentation and low incidence of TOM contribute to frequent delays in diagnosis, highlighting the need for increased clinical vigilance, particularly in cases of persistent otorrhea unresponsive to standard antimicrobial therapy. Prompt recognition and initiation of appropriate antituberculous treatment, along with surgical intervention when indicated, are essential to prevent severe complications. This case illustrates the importance of considering TOM in the differential diagnosis of chronic ear infections and the value of advanced diagnostic modalities in facilitating early and accurate identification. CONCLUSION: Tuberculous otitis media should be considered when optimal treatment regimens fail to achieve expected outcomes. Prompt diagnosis is essential in avoiding delays in treatment, which can lead to severe complications such as Bezold's abscess.

4.
Clin Case Rep ; 12(9): e9446, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39301094

ABSTRACT

Key Clinical Message: Adult-onset immunodeficiency (AOID) is an emerging acquired immunodeficiency, characterized by multiple opportunistic infections including non-tuberculous mycobacterium (NTM) due to the presence of anti-IFN-γ autoantibody (AIGA). This case highlights the challenges of accurate diagnosis of monoclonal gammaglobulinemia with NTM infection and favorable outcomes of anti-plasma cell therapy in AOID. Abstract: Adult-onset immunodeficiency (AOID) is an emerging acquired immunodeficiency due to anti-IFN-γ autoantibody (AIGA) with low morbidity, frequent disseminated infections, a prolonged course, difficult diagnosis and treatment, and a poor prognosis. Here, we report a patient with positive AIGA and monoclonal gammaglobulinemia who was mimicking symptomatic multiple myeloma and resulting in a non-tuberculous mycobacterial (NTM) infection. While he achieved an excellent therapeutic effect with anti-plasma cell therapy, it also serves as a warning that monoclonal gammaglobulinemia with NTM infection is easily misdiagnosed as symptomatic multiple myeloma, and the screening for AIGA should not be ignored in patients with NTM infection.

5.
Front Microbiol ; 15: 1468383, 2024.
Article in English | MEDLINE | ID: mdl-39301186

ABSTRACT

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a refractory chronic respiratory infectious disease and its prevalence is increasing globally. The standard treatment regimen for NTM-PD involves long-term multidrug therapy including macrolides. The incidence of adverse events is high given the advanced age of many NTM-PD patients. In addition, drug-drug interactions under coexisting conditions add additional complexity. Despite guidelines advocating multidrug therapy for NTM-PD, low adherence rates probably owing to the relatively frequent adverse events and drug interactions. An appropriate treatment regimen can improve the bacteriological response rates, reduce the development of macrolide resistance, and mitigate adverse events. Of particular concern are the interactions arising from new complications that develop with NTM-PD. Notably, chronic pulmonary aspergillosis occasionally co-infects NTM-PD, which can lead to poor prognosis. The primary therapeutic modality for chronic pulmonary aspergillosis is the azoles. However, the interaction with rifamycin is problematic, making it challenging to continue standard treatment for NTM-PD and requiring drug adjustments. The implications of rifamycin extend beyond chronic pulmonary aspergillosis, impacting various other diseases such as those requiring immunosuppressive agents and AIDS patients requiring antiretroviral therapy. Hence, a comprehensive consideration of drug interactions is imperative for the initiation of NTM-PD treatment. This mini-review focuses on drug-drug interactions in a multidrug regimen for NTM-PD and discusses the essential points to be considered in the treatment of NTM.

6.
Ther Adv Infect Dis ; 11: 20499361241274251, 2024.
Article in English | MEDLINE | ID: mdl-39290458

ABSTRACT

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features. Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma). Design: Retrospective descriptive study. Methods: Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis. Results: Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died. Conclusion: Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed.


Clinical features, results of brain imaging and other tests in the cerebrospinal fluid among children diagnosed with tuberculous meningitis ­ descriptive study Why was the study done? What did the researchers do? Records of children aged between 6 months and 12 years who presented to the health care centre with signs and symptoms of central nervous system (CNS) disease and assessed for tuberculous meningitis (TBM) clinical trial eligibility were reviewed. The research team studied the signs and symptoms of the TBM, results of the CT/MRI brain scan and tests which were done in the cerebrospinal fluid (CSF) during hospitalization. What did the researchers find? Total number of children who presented to the health centre during the study period with CNS complaints and underwent lumbar puncture were 600. Among them 61 were diagnosed with CNS TB (47 had TBM and 14 had tuberculoma). Half of them were less than five years of age. Ten had neurological dysfunction. Fever, vomiting were the common complaints. Almost half of the children had vomiting, altered level of consciousness and seizures. Tests done in the CSF detected the bacteria causing TBM in half of the children. Abnormal cell counts or biochemical changes in the CSF specific to TBM were observed in half of the children. Abnormalities in CT/MRI imaging with features specific to the disease were observed in closer to three fourth of the children. What do the findings mean? Children with TBM often present late for care with severe forms and its complications. There would be diagnostic challenges as the symptoms were vague and might not present in a specific manner, specific tests in the CSF could be negative and if undiagnosed could lead to severe morbidity impacting the quality of life or death. Taking the overall picture of presenting complaints, results of CSF test and brain scan and with high degree of suspicion, TBM should be diagnosed early and managed appropriately.

7.
J Child Neurol ; : 8830738241276234, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39263700

ABSTRACT

BACKGROUND: We sought to estimate the prevalence and clinical characteristics of paroxysmal sympathetic hyperactivity (PSH) in childhood tuberculous meningitis. METHODS: Hospital records of children (6 months to 14 years) with tuberculous meningitis were retrospectively analyzed from September 2019 through January 2022. In September 2019, the first case of paroxysmal sympathetic hyperactivity in tuberculous meningitis was identified in our division. Since then, all admitted children with tuberculous meningitis have been screened for paroxysmal sympathetic hyperactivity using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM). Paroxysmal sympathetic hyperactivity is suspected when any of the following are present: recurrence of fever after initial defervescence, episodic posturing, dystonia, or unexplained tachycardia. Outcome at 3 months was prospectively scored according to the Pediatric Cerebral Performance Category score. RESULTS: Forty-one hospital records of children with tuberculous meningitis were analyzed, and 6 of them had paroxysmal sympathetic hyperactivity (probable paroxysmal sympathetic hyperactivity, 5/6; possible paroxysmal sympathetic hyperactivity, 1/6). Paroxysmal sympathetic hyperactivity appeared after a mean duration of 17 weeks (range: 12-25 weeks) from the diagnosis of tuberculous meningitis in 4 of 6 children and at 4 weeks in 2 of 6 children. Children with tuberculous meningitis who developed paroxysmal sympathetic hyperactivity were younger (median age: 5 years) compared with the nonparoxysmal sympathetic hyperactivity tuberculous meningitis cohort (median age: 10 years). A high proportion of children who developed paroxysmal sympathetic hyperactivity had hydrocephalus at presentation (5 of 6 [83.3%] vs 12 of 35 [34.3%], P = .035). Hospital stay was significantly prolonged in children with probable paroxysmal sympathetic hyperactivity (mean: 71.2 ± 26.8 days) compared with tuberculous meningitis without paroxysmal sympathetic hyperactivity (mean: 20.8 ± 11.6 days; P < .0001). CONCLUSION: Paroxysmal sympathetic hyperactivity is a late complication of tuberculous meningitis observed in 14.6% cases and should be anticipated in children with reappearance of fever or neurologic worsening without any apparent cause.

8.
J Clin Tuberc Other Mycobact Dis ; 37: 100478, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39253556

ABSTRACT

Non-tuberculous mycobacteria (NTM) are among the most important pathogens in wild, captive, marine, and freshwater fish species. So, it is important to consider fish as the primary source of infection for aquarium fish and humans. The present study analyzed the occurrence of NTM in aquarium fish in Ilam, west of Iran. In total, 50 samples of infected fish were collected from different aquariums. Following initial sample processing, sediment of each sample was inoculated into Lowenstein-Jensen and Herrold egg media. The positive colonies were investigated with, growth rate, pigmentation, colony morphology, niacin accumulation, nitrate reduction, catalase activity, urease activity, and arylsulfatase activity. Also, molecular identification was carried out by sequencing of heat shock protein 65 kD gene (hsp65) sequence analysis. According to our results, NTM were isolated from 13 samples (26%), comprising 6 (46.2%) rapid growing, and 7 (53.8%) slow growing mycobacteria. In addition, Mycobacterium marinum was the most common NTM isolated in ornamental fish, which is potentially dangerous for both fish and humans. In conclusion, the current study indicates that ornamental fish play a significant role as a source of NTM.

9.
Cureus ; 16(8): e66914, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39280503

ABSTRACT

Empyema necessitans is a very rare and morbid complication of pleural empyema. It is defined as the extension of pleural infection to the chest wall and surrounding soft tissues. Our case highlights an unusual presentation of empyema necessitans in a 29-year-old man. The patient had no prior comorbidities and presented to the emergency department with a 15-day history of growing left unilateral chest pain and swelling. This was initially clinically misdiagnosed as a post-traumatic hematoma. Contrast-enhanced chest CT scan allowed a diagnosis and the ruling out of the main differentials, such as skeletal lesions extending to adjacent structures but also benign and malignant soft tissue masses. The treatment involved surgical drainage of the abscess. Microbiological analysis of the abscess content identified Mycobacterium tuberculosis as the causative pathogen. The patient was subsequently treated with antituberculous drugs, leading to a favorable clinical outcome. This case outlines the importance of an enhanced chest CT scan in making an early diagnosis, defining the extent of the disease, and discussing differentials, all of which are paramount to better results with fewer complications. Moreover, it highlights the fact that blunt trauma may facilitate the formation of a fistula when an underlying infection is present.

10.
IJID Reg ; 12: 100425, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39281191

ABSTRACT

Objectives: Exudative pleural effusions have a broad etiology and usually necessitate further investigative workup, including invasive procedures. This study aimed to evaluate and compare the demographic, clinical, and biochemical characteristics of tuberculous, malignant, and chronic inflammatory pleural effusions. Methods: This is a 2-year prospective cohort study of patients referred for medical thoracoscopy with an exudative pleural effusion. Results: A total of 159 patients were enrolled in the study, with a mean age of 42.49 ± 13.8 years and the majority being males 121 (76.1%). As expected, patients with tuberculous effusions were significantly younger than those with non-tuberculous effusions (37.7 ± 10.9 vs 49.1 ± 14.9, P <0.001). Serum analysis showed significantly lower white blood cell count (7.5 × 109/L ± 2.7 vs 9.0 × 109/L ± 3.3, P = 0.004), higher total protein (76.2 g/dL ± 10.1 vs 70.2 g/dL ± 8.9, P <0.001), and higher median C-reactive protein (median 77.5, interquartile range 51-116 vs median 40.5, interquartile range 8-127, P <0.001) among tuberculous compared with non-tuberculosis effusions. Conclusions: Our study validates previous findings showing similar results in patients with tuberculous pleural effusions. A predictive model incorporating different demographic and clinical/laboratory characteristics may be useful in the early etiologic characterization of exudative pleural effusion.

11.
Open Forum Infect Dis ; 11(9): ofae496, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39286031

ABSTRACT

Background: Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB). Methods: In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment. Results: In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%-89.4%] vs 25% [8.9%-53.3%]; P = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%-93.4%] vs 86.9% [83.4%-89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)-infected versus uninfected participants (85.8% vs 66.7%). Conclusions: As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted.

14.
Article in English | MEDLINE | ID: mdl-39225226

ABSTRACT

BACKGROUND: Tuberculosis is an infectious disease caused by Mycobacterium tuber-culosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tubercu-lous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system. METHODS: In this work, ligands having improved BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules. RESULTS: In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase ß of Mycobacterium tuberculosis. CONCLUSION: The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

15.
Acta Trop ; 260: 107398, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260760

ABSTRACT

Non-tuberculous mycobacteria (NTM) are one of major public health concern. The current study aimed to find the prevalence trends of NTM in Guangzhou, China from January 2018 to December 2023. A total of 26,716 positive mycobacterial cultures were collected. Thirty-six specimens with incomplete personal information were excluded. The remaining 26,680 specimens were identified using a gene chip method. 16,709 isolates were Mycobacterium tuberculosis (MTB) (62.63 %), and 9,971 were NTM (37.37 %). 43.43 % (4,330/9,971) of NTM isolates were male, and 56.57 % (5,641/9,971) were female (χ2 = 24.36, P < 0.05), a male to female ratio of approximately 1:1.30. Infections in individuals with aged 40 years and above was higher (77.63 %) than below 40 years (22.37 %) (χ2 = 4.94, P = 0.026). The annual NTM isolation rates from 2018 to 2023 were 32.03 %, 34.00 %, 36.27 %, 38.58 %, 38.99 %, and 43.24 %, respectively, showing an increasing trend (χ2 for trend = 0.097, P < 0.05) (R = 0.097, P < 0.05). Out of 9,971 NTM isolates, 8,881 cases include only five common NTM species (MAC, M. abscessus/M. chelonae, M. kansasii, M. fortuitum, and M. gordonae). The overall NTM isolation rate was 37.37 %. The NTM isolation rate was significantly higher than the national average, showing an increasing trend over the last six years.

16.
Respir Med ; 234: 107805, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39265839

ABSTRACT

BACKGROUND: Tuberculosis frequently poses diagnostic challenge when it presents as a peripheral pulmonary lesion (TB-PPL). The growing use of radial endobronchial ultrasound (rEBUS) for PPL biopsy highlights the need to identify predictive factors for TB-PPL, which is crucial for procedure safety. METHODS: A six-year retrospective review at our institution on adult patients with TB and malignant-PPL diagnosed from rEBUS procedure from October 1, 2016, to December 31, 2022. Clinical, radiological, procedural, histological and microbiological data were extracted and analysed. RESULTS: 387 PPLs were included in our cohort, 32 % were TB-PPL and 68 % were malignant-PPL. The median age was 63 (IQR 55-70) years, with the TB-PPL group significantly younger. The median size of the target lesion was 2.90 (IQR 2.26-4.00) cm. The overall rEBUS diagnostic yield was 85.3 %, with a 1.3 % pneumothorax risk. Multivariate analysis identified independent predictors for TB-PPL, including age <60 years (adj OR 2.635), target lesion size <2 cm (adj OR 2.385), upper lobe location (adj OR 2.020), presence of a cavity on pre-procedural CT (adj OR 4.186), and presence of rEBUS bronchogram (adj OR 2.722). These variables achieved an area under the curve of 0.729 (95 % CI 0.673-0.795) with a diagnostic accuracy of 75.49 % (95 % CI 70.68-79.88). CONCLUSIONS: Despite non-specific radiological findings in TB-PPL, our study identifies younger age, target lesion size less than 2 cm, upper lobe location, the presence of cavitation, and rEBUS bronchogram were independent clinical predictors for TB-PPL. This prediction model potentially helps mitigate the risk of accidental TB exposure during bronchoscopic procedures. A future prospective cohort study to validate these findings is essential to allow proper triaging of patient planning for rEBUS procedure.

17.
Chem Biol Drug Des ; 104(3): e14612, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39237482

ABSTRACT

The Mycobacterium cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti-TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating Mtb infection.


Subject(s)
Antitubercular Agents , Bacterial Proteins , Cell Wall , Mycobacterium tuberculosis , Cell Wall/metabolism , Cell Wall/drug effects , Antitubercular Agents/pharmacology , Antitubercular Agents/chemistry , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/metabolism , Humans , Bacterial Proteins/metabolism , Bacterial Proteins/antagonists & inhibitors , Tuberculosis/drug therapy , Oxidoreductases/metabolism , Oxidoreductases/antagonists & inhibitors , Mycolic Acids/metabolism , Alcohol Oxidoreductases , Membrane Transport Proteins
18.
Front Med (Lausanne) ; 11: 1399381, 2024.
Article in English | MEDLINE | ID: mdl-39234035

ABSTRACT

Mycobacterium riyadhense is an emerging slowly growing species that belongs to the group of nontuberculous mycobacteria (NTM) with approximately 20 cases reported worldwide. We highlight the first case of pulmonary infection by Mycobacterium riyadhense in United Arab Emirates (UAE). A 44-year-old female presented with chronic productive cough; a bronchial breathing pattern was appreciated on auscultation of her right upper lung. She was treated multiple times with allergic medications and antibiotics. Thorough investigations revealed Mycobacterium riyadhense and antitubercular drugs were started, eventually she was cured, however she had multiple relapses later. This case report holds a significant potential to make considerable contribution to the diagnosis of NTM, primarily because it presents the first documented case in UAE, as well as insights on how to address possible similar cases in the future.

19.
Appl Microbiol Biotechnol ; 108(1): 456, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39222096

ABSTRACT

The diagnosis of mycobacterial infections, including both the Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), poses a significant global medical challenge. This study proposes a novel approach using immunochromatographic (IC) strip tests for the simultaneous detection of MTBC and NTM. Traditional methods for identifying mycobacteria, such as culture techniques, are hindered by delays in distinguishing between MTBC and NTM, which can affect patient care and disease control. Molecular methods, while sensitive, are resource-intensive and unable to differentiate between live and dead bacteria. In this research, we developed unique monoclonal antibodies (mAbs) against Ag85B, a mycobacterial secretory protein, and successfully implemented IC strip tests named 8B and 9B. These strips demonstrated high concordance rates with conventional methods for detecting MTBC, with positivity rates of 93.9% and 85.9%, respectively. For NTM detection, the IC strip tests achieved a 63.2% detection rate compared to culture methods, considering variations in growth rates among different NTM species. Furthermore, this study highlights a significant finding regarding the potential of MPT64 and Ag85B proteins as markers for MTBC detection. In conclusion, our breakthrough method enables rapid and accurate detection of both MTBC and NTM bacteria within the BACTEC MGIT system. This approach represents a valuable tool in clinical settings for distinguishing between MTBC and NTM infections, thereby enhancing the management and control of mycobacterial diseases. KEY POINTS: • Panel of mAbs for differentiating MTB versus NTM • IC strips for diagnosing MTBC and NTM after the BACTEC MGIT • Combined detection of MTP64 and Ag85B enhances diagnostic accuracy.


Subject(s)
Antibodies, Monoclonal , Antigens, Bacterial , Bacterial Proteins , Mycobacterium tuberculosis , Nontuberculous Mycobacteria , Tuberculosis , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/isolation & purification , Mycobacterium tuberculosis/genetics , Antibodies, Monoclonal/immunology , Humans , Nontuberculous Mycobacteria/isolation & purification , Nontuberculous Mycobacteria/classification , Nontuberculous Mycobacteria/growth & development , Antigens, Bacterial/analysis , Antigens, Bacterial/immunology , Tuberculosis/diagnosis , Tuberculosis/microbiology , Bacterial Proteins/genetics , Chromatography, Affinity/methods , Sensitivity and Specificity , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Acyltransferases , Antibodies, Bacterial/immunology
20.
Eur J Clin Pharmacol ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39240337

ABSTRACT

PURPOSE: Therapeutic drug monitoring (TDM) is a standard clinical procedure that uses the pharmacokinetic and pharmacodynamic parameters of the drug in the body to determine the optimal dose. The pharmacokinetic variability of the drug(s) is a significant contributor to poor treatment outcomes, including the development of acquired drug resistance. TDM aids in dose optimization and improves outcomes while lessening drug toxicity. TDM is used to manage patients with tuberculosis (TB) who exhibit a slow response to therapy, despite good compliance and drug-susceptible organisms. Additional indications include patients at risk of malabsorption or delayed absorption of TB drugs and patients with drug-drug interaction and drug toxicity, which confirm compliance with therapy. TDM usually requires two blood samples: the 2 h and the 6 h post-dose. This narrative review will discuss the pharmacokinetics and pharmacodynamics of TB drugs, determinants of poor response to therapy, indications of TDM, methods of performing TDM, and its interpretations. METHODS: This is a narrative review. We searched PubMed, Embase, and the CINAHL from inception to April 2024. We used the following search terms: tuberculosis, therapeutic drug monitoring, anti-TB drugs, pharmacokinetics, pharmacodynamics, limited sample strategies, diabetes and TB, HIV and TB, and multidrug-resistant TB. All types of articles were selected. RESULTS: TDM is beneficial in managing TB, especially in patients with slow responses, drug-resistance TB, recurrent TB, and comorbidities such as diabetes mellitus and human immunodeficiency virus infection. CONCLUSION: TDM is beneficial for improving outcomes, reducing the risk of acquired drug resistance, and avoiding side effects.

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