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Assessment of the efficacy of clofazimine alone and in combination with primary agents against Mycobacterium tuberculosis in vitro.
Mashele, Sizeka A; Steel, Helen C; Matjokotja, Maborwa T; Rasehlo, Sam S M; Anderson, Ronald; Cholo, Moloko C.
Afiliação
  • Mashele SA; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  • Steel HC; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  • Matjokotja MT; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  • Rasehlo SSM; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  • Anderson R; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
  • Cholo MC; Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. Electronic address: moloko.cholo@up.ac.za.
J Glob Antimicrob Resist ; 29: 343-352, 2022 06.
Article em En | MEDLINE | ID: mdl-35339735
ABSTRACT

OBJECTIVES:

The chemotherapeutic regimens of patients with drug-susceptible (DS)- tuberculosis (TB) comprise four primary anti-TB drugs rifampicin (RMP), isoniazid (INH), ethambutol (EMB) and pyrazinamide (PZA), administered for six-to-nine months. These drug regimens target the various microbial populations that include actively replicating (AR), slow-replicating (SR) and non-replicating (NR) organisms. Clofazimine (CFZ) has showed benefit in shortening DS-TB treatment in vivo from six to four months when used in combination with this regimen in murine models of experimental infection. However, its antimicrobial efficacy when used in combination with the primary drugs against the various microbial populations of Mycobacterium tuberculosis has not been demonstrated.

METHODS:

In the current in vitro study, the inhibitory and bactericidal activities of CFZ in combination with the primary anti-TB drugs, RMP, INH and EMB against the AR and SR organisms in planktonic and biofilm-forming cultures, respectively, were evaluated by fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) determinations, using the Loewe Additivity Model.

RESULTS:

In planktonic cultures, CFZ demonstrated synergistic growth inhibitory activity in combination with RMP and INH individually and collectively. With respect to bactericidal activity, CFZ exhibited synergistic activity only in a two-drug combination with RMP. However, in biofilm-forming cultures, all CFZ-containing anti-TB drug combinations exhibited synergistic inhibitory and bactericidal effects, particularly in combination with RIF and INH.

CONCLUSION:

Clofazimine exhibited synergistic effects in combination with primary anti-TB drugs against both planktonic and biofilm-forming cultures, showing potential benefit in augmenting treatment outcome when used during standard TB chemotherapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tuberculose / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2022 Tipo de documento: Article