Frederick A. Sirgel
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View article: Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment
Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment Open
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View article: Ancient and recent differences in the intrinsic susceptibility of <i>Mycobacterium tuberculosis</i> complex to pretomanid
Ancient and recent differences in the intrinsic susceptibility of <i>Mycobacterium tuberculosis</i> complex to pretomanid Open
Objectives To develop a robust phenotypic antimicrobial susceptibility testing (AST) method with a correctly set breakpoint for pretomanid (Pa), the most recently approved anti-tuberculosis drug. Methods The Becton Dickinson Mycobacterial …
View article: Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa
Rifampicin-Monoresistant Tuberculosis Is Not the Same as Multidrug-Resistant Tuberculosis: a Descriptive Study from Khayelitsha, South Africa Open
Rifampin monoresistance (RMR; rifampin resistance and isoniazid susceptibility) accounts for 38% of all rifampin-resistant tuberculosis (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-…
View article: 1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in <i>Mycobacterium tuberculosis</i>
1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in <i>Mycobacterium tuberculosis</i> Open
Phenotypic whole cell high-throughput screening of a ∼150,000 diverse set of compounds against Mycobacterium tuberculosis (Mtb) in cholesterol-containing media identified 1,3-diarylpyrazolyl-acylsulfonamide 1 as a moderately …
View article: 1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis
1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis Open
This is the accepted manuscript version of the work published in its final form as Khonde, Lutete Peguy; Müller, Rudolf; Boyle, Grant A.; Reddy, Virsinha; Nchinda, Aloysius T.; Eyermann, Charles J.; Fienberg, Stephen; Singh, Vinayak; Myric…
View article: Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa
Rifampicin mono-resistant tuberculosis is not the same as multidrug-resistant tuberculosis: a descriptive study from Khayelitsha, South Africa Open
Rifampicin mono-resistant TB (RMR-TB) constitutes 38% of all rifampicin-resistant TB (RR-TB) in South Africa and is increasing. We aimed to compare RMR-TB with multidrug-resistant TB (MDR-TB) within a high TB, RR-TB and HIV burden setting.…
View article: Antitubercular 2-Pyrazolylpyrimidinones: Structure–Activity Relationship and Mode-of-Action Studies
Antitubercular 2-Pyrazolylpyrimidinones: Structure–Activity Relationship and Mode-of-Action Studies Open
[Image: see text] Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using vari…
View article: Discordances between molecular assays for rifampicin resistance in <i>Mycobacterium tuberculosis</i>: frequency, mechanisms and clinical impact
Discordances between molecular assays for rifampicin resistance in <i>Mycobacterium tuberculosis</i>: frequency, mechanisms and clinical impact Open
Background Molecular assays are endorsed for detection and confirmation of rifampicin-resistant TB. The frequency, causal mechanisms and impact of discordant results between molecular tests are not well understood. Methods The prevalence o…
View article: Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection
Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection Open
The World Health Organization (WHO) recently recommended that linezolid be prioritized in treatment regimens for drug-resistant tuberculosis (TB), but there are limited data on its pharmacokinetics (PK) in patients with this disease. We co…
View article: Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis
Drug-Penetration Gradients Associated with Acquired Drug Resistance in Patients with Tuberculosis Open
These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assess…
View article: Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies
Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies Open
A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds…
View article: Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence
Low Frequency of Acquired Isoniazid and Rifampicin Resistance in Rifampicin-Susceptible Pulmonary Tuberculosis in a Setting of High HIV-1 Infection and Tuberculosis Coprevalence Open
Treatment with standardized antituberculosis regimens dosed daily throughout, high uptake of antiretroviral therapy, and low prevalence of isoniazid monoresistance were associated with a low frequency of ADR.
View article: Concentration-Dependent Antagonism and Culture Conversion in Pulmonary Tuberculosis
Concentration-Dependent Antagonism and Culture Conversion in Pulmonary Tuberculosis Open
PK/PD analyses using MARS identified isoniazid Cmax and rifampicin Cmax/MIC thresholds below which there is concentration-dependent antagonism that reduces 2-month sputum culture conversion.
View article: Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study
Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study Open
View article: Correction: The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks
Correction: The Rationale for Using Rifabutin in the Treatment of MDR and XDR Tuberculosis Outbreaks Open
There is an error in Table 1. An AspTyr mutation is wrongly abbreviated as D516T (1). It should be listed as D516Y (1). Please see the corrected Table 1 here.
Table 1
MICs and relative resistance of rifampicin and rifabutin in M.…
View article: Novel<i>katG</i>mutations causing isoniazid resistance in clinical<i>M. tuberculosis</i>isolates
Novel<i>katG</i>mutations causing isoniazid resistance in clinical<i>M. tuberculosis</i>isolates Open
We report the discovery and confirmation of 23 novel mutations with previously undocumented role in isoniazid (INH) drug resistance, in catalase-peroxidase (katG) gene of Mycobacterium tuberculosis (Mtb) isolates. With these mutations, a s…