ABSTRACT
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Drug Resistance, Multiple, Bacterial/genetics , Genotype , High-Throughput Screening Assays/methods , Humans , Isoniazid/pharmacology , Microbial Sensitivity Tests/methods , Mutation , Mycobacterium tuberculosis/genetics , Phenotype , Rifampin/pharmacology , Sensitivity and Specificity , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
Molecular tests to detect the presence of Mycobacterium tuberculosis and genetic polymorphisms in the rpoB gene conferring resistance to rifampicin (RMP) have become integral parts of tuberculosis diagnostics worldwide. These assays are often performed sequentially or in parallel to phenotypic drug susceptibility testing. Discordances between molecular and phenotypic tests invariably occur. Root causes range from pre-, post- and analytic errors to co-existence of non-tuberculous mycobacteria, silent mutations, mutations outside the 81 base-pair RMP resistance-determining region, non-canonical mutations conferring increased minimal inhibitory concentrations below the critical concentration in some phenotypic drug susceptibility tests, and heteroresistance. Resolving discordant results is challenging. This guide aims to assist both clinicians and microbiologists in interpreting discordances by providing a structured approach to manage further investigations. Case scenarios are discussed, including the likelihood of occurrence.
Subject(s)
Molecular Diagnostic Techniques/methods , Mycobacterium tuberculosis/drug effects , Rifampin/pharmacology , Antibiotics, Antitubercular/pharmacology , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Drug Resistance, Bacterial , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Polymorphism, Genetic , Tuberculosis/diagnosis , Tuberculosis/microbiologyABSTRACT
QuantiFERON-TB Gold IT analyses interferon-γ release from CD4(+) T cells after stimulation with specific tuberculosis (TB) antigens. Its sensitivity is approximately 80% for active TB. A new test generation (QFTGplus) also analyses the response of CD8(+) T cells. We investigated both test generations in a direct head-to-head comparison in a German pulmonary hospital. Sensitivity rates for active TB were identical, no matter whether diagnosis was bacteriologically confirmed or not.
Subject(s)
Interferon-gamma Release Tests/methods , Mycobacterium tuberculosis , Tuberculosis/diagnosis , Humans , Interferon-gamma Release Tests/standards , Latent Tuberculosis/diagnosis , Reagent Kits, Diagnostic , Sensitivity and Specificity , Tuberculosis/immunology , Tuberculosis/metabolism , Tuberculosis/microbiologyABSTRACT
Because of global mobility and migration resulting in a growing diversity of the donor pool, the risk for donor-derived tuberculosis in solid organ transplant recipients becomes more and more relevant, even in countries with a low overall tuberculosis incidence. Here, we describe a case series of donor-derived tuberculosis in 2 of 3 solid organ transplant recipients and one medical staff member in Germany resulting in the death of one recipient. This case series highlights the relevance of this topic to clinicians. It advocates for a better communication between organ procurement organizations and transplant centers regarding donor information and transplant recipient outcome. Furthermore, it underpins the necessity for a standardized critical incident reporting system in the german transplant system to improve short- and long-term recipient's safety, health and survival.
Subject(s)
Organ Transplantation/adverse effects , Tissue Donors , Transplant Recipients , Transplants/microbiology , Tuberculosis , Aged , Antitubercular Agents/administration & dosage , Antitubercular Agents/therapeutic use , Female , Health Personnel , Humans , Male , Middle Aged , Tuberculosis/drug therapy , Tuberculosis/microbiology , Tuberculosis/transmissionABSTRACT
Heteroresistance of Mycobacterium tuberculosis (MTB) is defined as the coexistence of susceptible and resistant organisms to anti-tuberculosis (TB) drugs in the same patient. Heteroresistance of MTB is considered a preliminary stage to full resistance. To date, no mechanism causing heteroresistance of MTB has been proven. Clinical specimens and cultures from 35 TB patients from Tashkent, Uzbekistan, were analysed using the Genotype MTBDR assay (Hain Lifescience, Nehren, Germany), which is designed to detect genetic mutations associated with resistance to rifampin and isoniazid. Cases of heteroresistance were further subjected to genotyping using mycobacterial interspersed repetitive unit-variable-number tandem repeat typing, spoligotyping and IS6110 fingerprinting. Heteroresistance to rifampin and/or isoniazid was found in seven cases (20%). In five of them, heteroresistance was caused by two different strains and in two by a single strain of the Beijing genotype. The latter cases had a history of relapse of their TB. For the first time, two different mechanisms of heteroresistance in tuberculosis have been proven using a stepwise molecular-biological approach: 1) superinfection with two different strains, which is of interest for clinical infection control practitioners; and 2) splitting of a single strain into susceptible and resistant organisms. The latter mechanism is most likely to be related to poor treatment quality and could serve as a quality marker for tuberculosis therapy programmes in the future.