Multidrug resistant tuberculosis (MDR TB) is a growing problem and few people have access to adequate diagnosis and treatment. The current recommended treatment regimen for MDR TB has a minimum of 20 months duration with high toxicity. Scale up of MDR TB treatment is associated with high default rates, and experience in the Medecins Sans Frontieres (MSF) programme in Uzbekistan shows that the current standard treatment greatly limits the ability to scale up to meet the high rates of MDR TB in the region.
Evidence from Bangladesh in 2010 showed that a 9-month short-course regimen could achieve a relapse-free cure rate of 88%. Several countries in West Africa started implementing similar regimens with similar outcomes. Evidence of effectiveness of this shortened regimen among regions with high second line drug use and resistance is still limited.
The investigators propose an observational study under programmatic conditions to evaluate the effectiveness of a shortened course MDR TB regimen in the high MDR/extensively drug resistant (XDR) TB prevalence and high second-line drug resistance setting of Karakalpakstan, Uzbekistan.

Start Date01 Sep 2013

Sponsor / Collaborator

Medecins Sans Frontières (UK)

[+1]

NCT00042289 / CompletedNot ApplicableIIT

Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum

IMPAACT P1026s is a Phase IV prospective clinical study to evaluate the pharmacokinetics (PKs) of antiretroviral (ARV) and tuberculosis (TB) medications in pregnant women and their infants. (Pharmacokinetics are the various interactions between a drug and the body.) This study also evaluated the PKs of certain ARVs in postpartum women before and after starting hormonal contraceptives. The PKs of these drugs were evaluated by measuring the amount of medicine present in blood and/or vaginal secretions.

Start Date09 Jun 2003

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

[+1]

NCT00000796 / CompletedNot ApplicableIIT

A Prospective Study of Multidrug Resistance and a Pilot Study of the Safety of and Clinical and Microbiologic Response to Levofloxacin in Combination With Other Antimycobacterial Drugs for Treatment of Multidrug-Resistant Pulmonary Tuberculosis (MDRTB) in HIV-Infected Patients.

To determine the demographic, behavioral, clinical, and geographic risk factors associated with the occurrence of multidrug-resistant pulmonary tuberculosis (MDRTB). To evaluate the clinical and microbiological responses and overall survival of MDRTB patients who are treated with levofloxacin-containing multiple-drug regimens chosen from a hierarchical list. Per 9/28/94 amendment, to assess whether persistent or recurrent positive sputum cultures of patients who show failure or relapse are due to the same strain or reinfection with a new strain.
Among TB patients, there has been an increase in progressive disease due to the emergence of antimycobacterial drug-resistant strains of Mycobacterium tuberculosis. Failure to identify patients at high risk for MDRTB increases the hazard for both treatment failure and development of resistance to additional therapeutic agents. Efforts to improve survival in patients with MDRTB will depend on improved methods of assessing the risk of acquisition of MDRTB and identifying drug susceptibility patterns in a timely fashion.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with Capreomycin Sulfate

100 Translational Medicine associated with Capreomycin Sulfate

100 Patents (Medical) associated with Capreomycin Sulfate

730

Literatures (Medical) associated with Capreomycin Sulfate

26 Nov 2024·CHEMISTRY-A EUROPEAN JOURNAL

What is the Origin of the Regioselective C₃‐Hydroxylation of L‐Arg by the Nonheme Iron Enzyme Capreomycin C?

Article

Author: Wong, Henrik P. H. ; de Visser, Sam P. ; Warwicker, Jim ; Hay, Sam ; Cao, Yuanxin

Abstract:

The nonheme iron dioxygenase capreomycin C (CmnC) hydroxylates a free L‐arginine amino acid regio‐ and stereospecifically at the C3‐position as part of the capreomycin antibiotics biosynthesis. Little is known on its structure, catalytic cycle and substrate specificity and, therefore, a comprehensive computational study was performed. A large QM cluster model of CmnC was created of 297 atoms and the mechanisms for C3−H, C4−H and C5−H hydroxylation and C3−C4 desaturation were investigated. All low‐energy pathways correspond to radical reaction mechanisms with an initial hydrogen atom abstraction followed by OH rebound to form alcohol product complexes. The work is compared to alternative L‐Arg hydroxylating nonheme iron dioxygenases and the differences in active site polarity are compared. We show that a tight hydrogen bonding network in the substrate binding pocket positions the substrate in an ideal orientation for C3−H activation, whereby the polar groups in the substrate binding pocket induce an electric field effect that guides the selectivity.

01 Nov 2024·Immunity Inflammation and Disease

Analysis of the Results of Tuberculosis Drug Resistance Surveillance in Yuexiu District, Guangzhou City, 2013–2022

Article

Author: Li, Xueqiu ; Liu, Jianxiong

ABSTRACT:

Introduction:

The objectives of the study are to understand the drug‐resistant situation and trend of tuberculosis patients in Yuexiu District, Guangzhou City, from 2013 to 2022, and to provide a scientific basis for the development of rational drug‐resistant tuberculosis prevention and control strategies in Guangzhou City.

Methods:

All patients who were diagnosed with active tuberculosis in Guangzhou Chest Hospital from January 1, 2013 to December 31, 2022 were collected as study subjects, and a total of 5191 patients were enrolled in the study. Comprehensive data on the basic characteristics, diagnostic, and therapeutic information of the study subjects were collected. Sputum specimens were subjected to smear, isolation, and culture. Culture‐positive strains of bacteria were identified by bacterial groups. A total of 1659 strains of Mycobacterium tuberculosis (MTB) isolates were obtained. The drug susceptibility test was carried out using the proportionality method on the MTB isolates for nine types of antituberculosis medicines: isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km), ofloxacin (Ofx), capreomycin (Cm), propylthioisonicotinamide (Pto), and p‐aminosalicylic acid (PAS). A comparative analysis of the resistance patterns among the strains was conducted.

Results:

A total of 1659 patients with MTB were cultured, revealing 438 drug‐resistant cases. Among these, 255 were monoresistant, 121 were polyresistant, and 62 were multidrug resistant. The overall resistance rate was 26.40% (438/1659), with mono‐resistance rate at 15.37% (255/1659), polyresistance rate at 7.29% (121/1659), and multidrug resistance rate at 3.74% (62/1659). In descending order, the resistance rates of MTB isolates to any of the nine antituberculosis drugs were Sm (12.24%, 203/1659), INH (9.22%, 153/1659), EMB (7.35%, 122/1659), RFP (6.99%, 116/1659), PAS (3.25%, 54/1659), Pto (3.13%, 52/1659), Ofx (2.71%, 45/1659), Cm (2.17%, 36/1659), and Km (2.17%, 36/1659). The differences in resistance rates were statistically significant (p < 0.01), with Sm exhibiting the highest resistance rate and Km the lowest.In the primary treatment group, 388 patients (25.55%) were drug resistant, while 50 patients (35.46%) in the retreatment group were drug resistant. Thirty‐nine patients (2.57%) in the primary treatment group were multidrug resistant, compared to 23 patients (16.31%) in the retreatment group. The resistance rate and multidrug resistance rate of isolates from retreatment patients were significantly higher than primary treatment patients (p < 0.05).

Conclusions:

The problem of drug‐resistant tuberculosis transmission in Guangzhou requires attention, and drug‐resistant screening should be further increased to effectively control the source of infection.

16 Oct 2024·JOURNAL OF CLINICAL MICROBIOLOGY

Nanopore-based targeted sequencing test for direct tuberculosis identification, genotyping, and detection of drug resistance mutations: a side-by-side comparison of targeted next-generation sequencing technologies

Article

Author: Moghaddasi, Kiarash ; Cabibbe, Andrea Maurizio ; Di Marco, Federico ; Morgan, Godstime Stephen Kojo ; Batignani, Virginia ; Cirillo, Daniela Maria

ABSTRACT:

We investigated the performance of the targeted next-generation sequencing (tNGS)-based Oxford Nanopore Diagnostics AmPORE TB assay, recently approved by the World Health Organization (WHO) as tuberculosis (TB) diagnostic test for the detection of drug resistance on respiratory specimens. A total of 104 DNA samples from Xpert MTB/RIF-positive TB sputum specimens were tested using the AmPORE TB kit, with the GenoScreen Deeplex Myc-TB as a comparative tNGS assay. For AmPORE TB, DNA samples were divided into five sequencing runs on the MinION device. Data analysis was performed using proprietary software. The WHO catalog of mutations was used for drug resistance interpretation. The assay achieved a high validity rate of 98% (102/104 DNA samples), homogeneous mean reads coverage across TB-positive specimens, and 100% positive and negative agreements for detecting mutations associated with resistance to rifampicin, pyrazinamide, fluoroquinolones, ethambutol, and capreomycin compared with Deeplex Myc-TB. The main discrepancies for the remaining drugs were attributable to the different assay panel designs. The AmPORE TB turnaround time was approximately 5–6 hours from extracted DNA to tNGS reporting for batches of 22 DNA samples. The AmPORE TB assay drastically reduced the time to tNGS reporting from days to hours and showed good performance for drug-resistant TB profiling compared with Deeplex Myc-TB.

IMPORTANCE:

Targeted next-generation sequencing (tNGS) of Mycobacterium tuberculosis provides comprehensive resistance predictions matched to new multidrug-resistant/rifampicin-resistant tuberculosis regimens and received World Health Organization approval for clinical use in respiratory samples in 2024. The advanced version of the Oxford Nanopore Diagnostics AmPORE TB tNGS kit was evaluated in this study for the first time and demonstrated good performance, flexibility, and faster turnaround time compared with the existing solutions.

100 Deals associated with Capreomycin Sulfate

External Link

KEGG	Wiki	ATC	Drug Bank
D00135	Capreomycin Sulfate	J04AB30	DB00314

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Pulmonary Tuberculosis	US	Epic Pharma LLC	02 Jun 1971

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2018	Not Applicable	Chronic Kidney Diseases	-	Capreomycin	puqxppzlse(cimtcwysnk) = This case demonstrates a rapid, severe alteration of the GFR in a diabetic, normotensive patient with no evident proteinuria. The biopsy did not reveal kidney impairment from the DM. The literature reports few cases on nephrotoxicity from CPM. This study emphasizes the importance of strict controlling the GFR in patients on CPM, especially the elderly and those with comorbidities. nyqjlvqkbp (mrcinwhaie )	-	23 Oct 2018
				Rifampicin, Isoniazid, Pyrazinamide, Etambutol, Levofloxacin, Terizidone

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