Abstract
The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in > 95% cure in uncomplicated tuberculosis infection. Drug resistance greatly complicates treatment of this disease. Treatment of tuberculosis caused by multiply drug-resistant strains with “second-line” drugs remains complex, and is generally tailored to the individual patient and strain. Several of the fluoroquinolones have shown promise as second line drugs for treatment of active disease and, in combination with clarithromycin or azithromycin, ethambutol, and other agents, for treatment of Mycobacterium avium complex infection. While large clinical trials are not possible with second line drugs, clinical treatment data are available and suggest that the quinolones have various degrees of promise in treatment of these infections. Bacterial type II DNA topoisomerases, DNA gyrase and topoisomerase IV, are the targets of quinolones, and provide the genetic basis for quinolone activity in mycobacteria. Mutations in these enzymes results in resistance, and characterization of resistant mutants allows correlation of genotype with susceptibility phenotype. Structure-activity relationship studies have provided further insight into optimal use of quinolones in mycobacterial infections. Care should be taken in treating pneumonia with fluoroquinolones if there is a degree of suspicion of tuberculosis, since quinolone monotherapy may rapidly select for quinolone resistance, thereby removing that class of antibiotic from the small range of treatment options.
Keywords: mycobacteria, quinolones, mycobacterium tuberculosis, mycobacterium avium complex, fluoroquinolones, topoisomerase
Current Pharmaceutical Design
Title: Fluoroquinolones as Chemotherapeutics Against Mycobacterial Infections
Volume: 10 Issue: 26
Author(s): Michael R. Jacobs
Affiliation:
Keywords: mycobacteria, quinolones, mycobacterium tuberculosis, mycobacterium avium complex, fluoroquinolones, topoisomerase
Abstract: The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in > 95% cure in uncomplicated tuberculosis infection. Drug resistance greatly complicates treatment of this disease. Treatment of tuberculosis caused by multiply drug-resistant strains with “second-line” drugs remains complex, and is generally tailored to the individual patient and strain. Several of the fluoroquinolones have shown promise as second line drugs for treatment of active disease and, in combination with clarithromycin or azithromycin, ethambutol, and other agents, for treatment of Mycobacterium avium complex infection. While large clinical trials are not possible with second line drugs, clinical treatment data are available and suggest that the quinolones have various degrees of promise in treatment of these infections. Bacterial type II DNA topoisomerases, DNA gyrase and topoisomerase IV, are the targets of quinolones, and provide the genetic basis for quinolone activity in mycobacteria. Mutations in these enzymes results in resistance, and characterization of resistant mutants allows correlation of genotype with susceptibility phenotype. Structure-activity relationship studies have provided further insight into optimal use of quinolones in mycobacterial infections. Care should be taken in treating pneumonia with fluoroquinolones if there is a degree of suspicion of tuberculosis, since quinolone monotherapy may rapidly select for quinolone resistance, thereby removing that class of antibiotic from the small range of treatment options.
Export Options
About this article
Cite this article as:
Jacobs R. Michael, Fluoroquinolones as Chemotherapeutics Against Mycobacterial Infections, Current Pharmaceutical Design 2004; 10 (26) . https://dx.doi.org/10.2174/1381612043383296
DOI https://dx.doi.org/10.2174/1381612043383296 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Pharmacologic Role of Vitamin D Natural Products
Current Vascular Pharmacology Modern Drug Discovery Technologies: Opportunities and Challenges in Lead Discovery
Combinatorial Chemistry & High Throughput Screening In-vitro Antioxidant activity of ‘Aswathy Chooranam’- a Siddha Drug
Current Traditional Medicine Biotechnological Potential of <i>Streptomyces</i> Siderophores as New Antibiotics
Current Medicinal Chemistry Inflammasome as a New Therapeutic Target for Diabetic Complications
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Green Formation of Novel Pyridinyltriazole-Salicylidene Schiff Bases
Current Organic Synthesis Chemical Constituents and Biological Activities of Simira Genus: A Contribution to the Chemotaxonomic of Rubiaceae Family
The Natural Products Journal Asthma and High Altitude: Is It Safe to Be and Work?
Current Respiratory Medicine Reviews N-heterocycles: Recent Advances in Biological Applications
Mini-Reviews in Organic Chemistry A Scientometrics Analysis and Visualization of Depressive Disorder
Current Neuropharmacology The Role of Essential Oils and the Biological Detoxification in the Prevention of Aflatoxin Borne Diseases
Current Topics in Medicinal Chemistry Proteasome Structure, Function, and Lessons Learned from Beta-Lactone Inhibitors
Current Topics in Medicinal Chemistry An Overview of Neolignans of the Genus Piper L.: Isolation Methods and Biological Activities
Mini-Reviews in Medicinal Chemistry Do HIV-Infected Immigrants Initiating HAART have Poorer Treatment-Related Outcomes than Autochthonous Patients in Spain? Results of the GESIDA 5808 Study
Current HIV Research TLC Bioautography on Screening of Bioactive Natural Products: An Update Review
Current Analytical Chemistry Novel, Unifying Phagomimetic Mechanism of Vancomycin Therapeutic Action and Toxicity: Polyphenol, Electron Transfer and Reactive Oxygen Species
Anti-Infective Agents in Medicinal Chemistry The Influence of Cigarette Smoking on Sperm Quality and Sperm Membrane Integrity
Current Women`s Health Reviews Synthesis and Pharmacological Activities of Oxadiazole and Pyrimidine Bearing Thiocoumarin Derivatives
Current Microwave Chemistry Advances in Research on Pharmacological Activities and Synthesis of Oleanolic Acid Derivatives at C-3 Position
The Natural Products Journal Regulation of Inflammation: A Review of Recent Advances in Anti- Inflammatory Strategies
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents