This document provides information on the classification, mechanisms of action, antimicrobial activity, mechanisms of resistance, pharmacokinetics, therapeutic uses and dosages, and adverse effects of various antimycobacterial agents used to treat diseases caused by mycobacteria such as tuberculosis. It discusses cell wall synthesis inhibitors including isoniazid, ethambutol, ethionamide, and cycloserine. It also discusses the cell membrane disruptor clofazimine and its mechanisms of action and antimicrobial activity.
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs,or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Antivirals also can be found in essential oils of some herbs, such as eucalyptus oil and its constituents.
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Antiviral drugs are a class of medication used specifically for treating viral infections.Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs,or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Antivirals also can be found in essential oils of some herbs, such as eucalyptus oil and its constituents.
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
Tuberculosis is completely curable disease now a days but one should follow the treatment regimens correctly .so for under graduate MBBS students it is clearly explained with animations.Hope you all this will be helpful.
Anti mycobacterial drugs (tuberculosis drugs)Ravish Yadav
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Leprosy
Tuberculosis
TYB pharmacy
Pharmacology semester VI notes
Pharmacology VI semester
Pharmacology notes
Third year B pharmacy pharmacology notes
Pharmacology unit 3 notes
Pharmacology VI semester notes
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
Telegram: bmksupplier
signal: +85264872720
threema: TUD4A6YC
You can contact me on Telegram or Threema
Communicate promptly and reply
Free of customs clearance, Double Clearance 100% pass delivery to USA, Canada, Spain, Germany, Netherland, Poland, Italy, Sweden, UK, Czech Republic, Australia, Mexico, Russia, Ukraine, Kazakhstan.Door to door service
Hot Selling Organic intermediates
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. Introduction
Mycobacteria have caused epic diseases: TB and leprosy have terrorized
humankind since antiquity.
“Mycos” means wax.
Although the burden of leprosy has decreased, TB is still the most important
infectious killer of humans.
Mycobacterium abscessus has now been called a new “antibiotic” nightmare
because of-
Its tenacity,
Lack of response to combination antibiotics, and
A nearly universal propensity to develop acquired drug resistance
Mycobacterium avium-intracellulare (or MAC) infection continues to be difficult to
treat.
4. Classification of Antimycobacterial agents
• Based on the primary mechanism of action:
1. Cell wall synthesis inhibitors
a) Isoniazid
b) Ethambutol
c) Ethionamide
d) Cycloserine
2. Cell membrane disruptors
a) Clofazimine
3. RNA synthesis inhibitors
a) Rifamycins: Rifampicin, Rifapentine & Rifabutin
4. DNA synthesis inhibitors
a) Fluoroquinolones: ofloxacin, moxifloxacin, gatifloxacin, levofloxacin and
ciprofloxacin
5. Classification of Antimycobacterial agents
5. Protein synthesis inhibitors
a) Oxazolidinones: Linezolid, Tedizolid, and Sutezolid
b) Aminoglycosides: Streptomycin, Amikacin, and Kanamycin
c) Capreomycin
d) Macrolides: Azithromycin and Clarithromycin
6. Folate synthesis inhibitors
a) Para-aminosalicylic acid
b) Dapsone
7. Cellular energetics inhibitors
a) Pyrazinamide
b) Bedaquiline
8. Free radical producers
a) Bicyclic Nitroimidazole: Delaminid and Pretomanid
6. Important gene & gene products of
mycobacteria
1. InhA: enoyl acyl carrier protein reductase
2. KasA: β-ketoacyl-acyl carrier protein synthase
3. KatG: catalase peroxidase
4. NAT2: N-acetyltransferase type 2
5. ahpC: Alkyl hydroperoxide reductase C peptide
6. embAB: Arabinosyl transferases
7. EthaA: NADPH-specific, FAD-containing monooxygenase.
7. Cell wall synthesis inhibitors- Isoniazid
• Isoniazid (isonicotinic acid hydrazide), also called INH.
• It is an important drug for the chemotherapy of drug-susceptible
TB.
• The use of combination therapy (isoniazid + pyrazinamide +
rifampin) provides the basis for short-course therapy and
improved cure rates.
8. Cell wall synthesis inhibitors- Isoniazid
• Mechanism of Action:
Enters in bacilli by passive diffusion
Activated by KatG to toxic form isonicotinoyl radical & other free radical
Formation of nicotinoyl-NAD isomer mycobactericidal effects
of INH
Inhibits the activities of enoyl acyl carrier protein reductase (InhA) and
KasA
Inhibits synthesis of mycolic acid
9. Cell wall synthesis inhibitors- Isoniazid
• Antibacterial Activity
• M. tuberculosis
• Mycobacterium bovis and
• Mycobacterium kansasii
• Mechanisms of Resistance
1. Mutation or deletion of KatG.
2. Overexpression of the genes for InhA and ahpC.
3. Mutations in the ahpC.
4. Efflux pump induction.
10. Cell wall synthesis inhibitors- Isoniazid
• Pharmacokinetics:
A= Very well absorbed orally (Bioavailability=100%).
D= Widely distributed.
M= Undergoes acetylation in liver.
E= Metabolites are excreted in urine.
• Microbial Pharmacokinetics-Pharmacodynamics:
• Isoniazid’s microbial kill, as well as resistance emergence, is best explained by the
ratios of AUC0/MIC and CPmax/MIC.
• Therapeutic Uses & Dosage:
• Available as pill, as an elixir, and for parenteral administration.
• 5 mg/kg (max. 300 mg) daily or 10 mg/kg (range 10–15 mg/ kg; max. 900
mg) two or three times a week.
11. Cell wall synthesis inhibitors- Isoniazid
• Untoward Effects:
1. Hepatotoxicity- Elevated serum aspartate and alanine
transaminases
2. Peripheral neuritis
3. Other neurological toxicities- convulsions, optic neuritis and
atrophy, muscle twitching, dizziness, ataxia, paresthesias, stupor,
and toxic encephalopathy.
4. Mental abnormalities- euphoria, transient impairment of memory,
loss of self-control, and florid psychoses.
5. Hypersensitivity reactions
6. Immune reactions- Vasculitis associated with antinuclear
antibodies, Drug induced lupus.
7. Anemia
12. Cell wall synthesis inhibitors- Isoniazid
• Isoniazid Overdose
• Seizures refractory to treatment with phenytoin and barbiturates
• Metabolic acidosis with an anion gap that is resistant to treatment with
sodium bicarbonate
• Coma
• M/m of Isoniazid Overdose:
• Intravenous pyridoxine is administered over 5–15 min on a gram-to-
gram basis with the ingested isoniazid.
• Benzodiazepines for seizures.
13. Cell wall synthesis inhibitors- Ethambutol
• Mechanism of Action
Inhibition of arabinosyl transferase III
Disrupting the transfer of arabinose into arabinogalactan
biosynthesis
Disrupts the assembly of mycobacterial cell wall
14. Cell wall synthesis inhibitors- Ethambutol
• Antibacterial Activity:
• M. tuberculosis,
• M. marinum,
• M. kansasii,
• M. gordonae,
• M. scrofulaceum,
• M. szulgai, and
• M. avium
15. Cell wall synthesis inhibitors- Ethambutol
• Mechanisms of Resistance:
1. Mutations in the embB gene.
2. Enhanced efflux pump activity.
• Pharmacokinetics:
A= Oral bioavailability is about 80%.
D= Widely distributed, 10-40% plasma protein bound.
M= 20% by liver (aldehyde dehydrogenase)
E= 80% by kidney.
16. Cell wall synthesis inhibitors- Ethambutol
• Microbial Pharmacokinetics-Pharmacodynamics:
• Microbial kill of M. tuberculosis is optimized by AUC/MIC.
• Against disseminated MAC is optimized by Cmax/MIC.
• Therapeutic Uses & Dosage:
• TB,
• Disseminated MAC, and
• M. kansasii infection
• 20 mg/kg (15–25 mg/kg) per day for both adults and children.
17. Cell wall synthesis inhibitors- Ethambutol
• Untoward Effects:
1. Optic neuritis- diminished visual acuity and loss of red-green
discrimination
2. Hyperuricemia
18. Cell wall synthesis inhibitors- Ethionamide
• Mechanism of Action:
Ethionamide sulfoxide 2-ethyl-4-aminopyridine
Inhibiting the activity of the inhA gene product, the enoyl-ACP
reductase of fatty acid synthase II
inhibition of mycolic acid biosynthesis
impairment of cell wall synthesis.
FAD-containing
monooxygenase
19. Cell wall synthesis inhibitors- Ethionamide
• Antibacterial Activity:
• M. tuberculosis
• Photochromogens
• Mechanism of Resistance:
• Mutation in EthaA decreased activation.
• Mutations in the inhA gene decreased action.
20. Cell wall synthesis inhibitors- Ethionamide
• Pharmacokinetics:
A=oral bioavailability approaches 100%.
D= Widely distributed
M= Hepatic
E= Renal
• Therapeutic Uses & Dosage:
• Resistant tuberculosis
• Adult dose: 250 mg twice daily; it is increased by 125 mg/d every 5 days until a dose of 15–
20 mg/kg/d is achieved (max. 1g/d).
• Best taken with meals in divided dose to minimize gastric irritation.
• Children should receive 10–20 mg/kg/d in two divided doses, not to exceed 1 g/d.
21. Cell wall synthesis inhibitors- Ethionamide
• Untoward Effects:
1. GI upset: anorexia, nausea and vomiting, gastric irritation.
2. Neurologic symptoms: olfactory disturbances, blurred vision,
diplopia, dizziness, paresthesias, headache, restlessness, and
tremors.
3. Severe postural hypotension.
4. mental depression, drowsiness, and asthenia.
5. Hepatitis
6. Allergic reactions.
22. Cell wall synthesis inhibitors- Cycloserine
• It is a broad-spectrum antibiotic produced by Streptococcus
orchidaceous.
• Mechanism of Action
1. Inhibition alanine racemase Inhibition of l-alanine to d-
alanine.
2. Inhibition of D-alanine: d-alanine ligase inhibition of d-
alanine incorporation into bacterial cell wall.
Cell wall synthesis inhibition
23. Cell wall synthesis inhibitors- Cycloserine
• Antibacterial Activity:
• M. tuberculosis
• MAC,
• enterococci,
• E. coli,
• S. aureus,
• Nocardia species, and
• Chlamydia.
• Mechanisms of Resistance
• Loss-of-function mutations in ald gene.
• Nonsynonymous SNPs in alr gene.
24. Cell wall synthesis inhibitors- Cycloserine
• Pharmacokinetics:
A= Almost complete oral absorption.
D= well distributed throughout body
M= 30 % metabolized
E= 70% unchanged in urine.
• Therapeutic Uses & Dosage:
• Resistant Tuberculosis
• The usual dose for adults is 250–500 mg twice daily.
• Untoward Effects:
• Neuropsychiatric symptoms are common and occur in 50% of patients on 1 g/d
“psych-serine.”
• Symptoms range from headache and somnolence to severe psychosis, seizures, and
suicidal ideas.
25. Clofazimine
• Mechanism of Action:
• The biochemical basis for the antimicrobial actions of clofazimine remains to be
established.
• Possible mechanisms of action-
1. Membrane disruption,
2. Inhibition of mycobacterial phospholipase A2,
3. Inhibition of microbial K+ transport,
4. Generation of hydrogen peroxide,
5. Interference with the bacterial electron transport chain, or
6. Efflux pump inhibition
• Has both antibacterial activity and anti-inflammatory effects via inhibition of
macrophages, T cells, neutrophils, and complement.
26. Clofazimine
• Antibacterial Activity:
• M. tuberculosis,
• M. avium,
• Mycobacterium ulcerans,
• S. aureus,
• Coagulase-negative staphylococci,
• Streptococcus pyogenes, and
• Listeria monocytogenes
• Mechanism of Resistance:
• Mutation in the gene encoding a transcription repressor for efflux pump
MmpL;
• This is associated with cross resistance to bedaquiline
27. Clofazimine
• Pharmacokinetics:
• A= oral bioavailability is 45%–60%; it is increased 2-fold by high-fat meals and
decreased 30% by antacids
• Prolonged absorption phase (Tmax- 5 to 8 hr)
• D= good penetration into many tissues.
• M= Liver
• Elimination T1/2= 70 days.
• Therapeutic Uses & Dosage:
1. Leprosy
• Adults: 300 mg once a month and 50 mg daily
• Children (10–14 years): 150 mg once a month, 50 mg on alternate days
• Children <10 years or <40kg body wt: 100 mg once a month, 50 mg twice weekly
2. MDR-TB
• Adults: 100–200 mg daily
• Children: 1 mg/kg/day
28. Clofazimine
• Untoward Effects:
• Abdominal pain (MC)
• Reddish-black discoloration body secretion, eye and skin.
• Crystal deposition in intestinal mucosa, liver, spleen, and abdominal lymph
nodes.
29. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Mechanism of Action:
Binds to the β subunit of DNA-dependent RNA polymerase (rpoB) to
form a stable drug-enzyme complex.
Drug binding suppresses chain formation in RNA synthesis.
30. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Antibacterial Activity:
Gram-positive bacteria Gram-negative bacteria Mycobacteria
• Staphylococcus
aureus and
• coagulase-
negative
staphylococci.
• Escherichia coli,
• Pseudomonas,
• Indole-positive and indole-negative
Proteus,
• Klebsiella
• Neisseria meningitidis and
• Haemophilus influenzae.
• M. tuberculosis
• Mycobacterium leprae
• Mycobacterium kansasii
• Mycobacterium
scrofulaceum,
• Mycobacterium
intracellulare, and
• Mycobacterium avium
31. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Mechanism of Bacterial Resistance:
1. Alteration of the target of this drug, rpoB.
2. Efflux pump induction
• Pharmacokinetics:
• A= Variable absorption
• Food decreases the rifampin CPmax by one-third; a high-fat meal increases the AUC of
rifapentine by 50%. Food has no effect on rifabutin absorption.
• D= Widely distributed
• M= Hepatic CYP3A4.
• E= 2/3 biliary & 1/3 renal.
32. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Microbial Pharmacokinetics-Pharmacodynamics:
• Bactericidal and sterilizing effect activity are best optimized by high AUCs and
a high AUC/MIC ratio
• Resistance suppression and rifampin’s enduring postantibiotic effect are best
optimized by high CPmax/ MIC.
33. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Therapeutic Uses & Dosage (Rifampicin):
1. Tuberculosis:
• Adults: 600 mg, given once daily, either 1 h before or 2 h after a meal.
• Children: 15 mg/kg (range 10–20 mg/kg), with the maximum dose 600 mg/d, given in the same
way.
2. Prophylaxis of meningococcal disease and H. influenzae meningitis.
• Adult: 600 mg twice daily for 2 days or 600 mg once daily for 4 days.
• Children >1month: 10–15 mg/kg, to a maximum of 600 mg daily.
3. Staphylococcal endocarditis or osteomyelitis: Along with beta lactam or
Vancomycin.
4. Eradication of the staphylococcal nasal carrier state in patients with chronic
furunculosis.
5. Brucellosis: 900 mg/d in combination with doxycycline for 6 weeks.
34. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Untoward Effects:
• Rifampicin is generally well tolerated
1. Hepatitis
2. Hypersensitivity reactions.
3. Flu like symptoms: particularly at high dose and less frequent administration.
• fever, chills, and myalgias.
• eosinophilia, interstitial nephritis, acute tubular necrosis, thrombocytopenia, hemolytic anemia,
and shock.
4. Orange-tan discoloration of skin, urine, feces, saliva, tears, and contact lenses,
• Unique ADRs associated with Rifabutin:
1. polymyalgia,
2. pseudojaundice, and
3. anterior uveitis.
35. Rifamycins- Rifampin, Rifapentine, and
Rifabutin
• Drug Interactions:
• Because of microsomal enzyme induction, t 1/2 decreases for a number of
compounds that are metabolized by these CYPs.
• Enzyme inducing property of Rifampin>Rifapentine>Rifabutin.
36. DNA Synthesis inhibitors- Fluoroquinolones
• Ofloxacin, ciprofloxacin moxifloxacin, gatifloxacin, and levofloxacin
• Mechanism of action:
• DNA gyrase inhibition
• Microbial Pharmacokinetics-Pharmacodynamics Relevant to TB:
• Fluoroquinolone microbial kill is best explained by the AUC0–24/MIC ratio.
• Therapeutic Uses in Treatment of TB:
• Pulmonary MDR-TB and
• Treatment of TB meningitis.
37. Protein synthesis inhibitors
• Oxazolidinones: Linezolid, Tedizolid, and Sutezolid
• MDR-TB
• Aminoglycosides: Streptomycin, Amikacin, and Kanamycin
• Antimicrobial spectrum:
• M. tuberculosis
• M. kansasii
• M. avium
• Macrolides: Azithromycin and clarithromycin
• Used for the treatment of MAC.
38. Protein synthesis inhibitors
• Capreomycin:
• An antimycobacterial cyclic peptide.
• Antimycobacterial activity and adverse effects is similar to that of
aminoglycosides.
• Given for MDR-TB.
• Recommended daily dose is 1 g (no more than 20 mg/kg) per day for 60–120
days, followed by 1 g two or three times a week.
39. Folate synthesis inhibitors- Dapsone
• Broad-spectrum agent with antibacterial, antiprotozoal, and
antifungal effects.
• Mechanism of Action:
• Structural analogue of PABA and a competitive inhibitor of dihydropteroate
synthase (folP1/P2) in the folate pathway,
• The anti-inflammatory effects by inhibition of neutrophil myeloperoxidase
activity and respiratory burst, and it inhibits activity of neutrophil lysosomal
enzymes.
40. Folate synthesis inhibitors- Dapsone
• Antimicrobial Effects:
• Antibacterial-
• Bacteriostatic against M. leprae.
• MAC and M. kansasii
• Antiparasitic-
• Toxoplasma gondii tachyzoites.
• Plasmodium falciparum
• Antifungal-
• Pneumocystis jiroveci.
• Mechanism of Drug Resistance:
• Mutations in genes encoding dihydropteroate synthase
41. Folate synthesis inhibitors- Dapsone
• Pharmacokinetics:
A= Complete oral absorption
D= Widely distributed
M= Undergoes N-acetylation by NAT2
E= Metabolites are excreted in urine.
• Therapeutic Uses:
1. Leprosy
2. Falciparum malaria (along with chlorproguanil)
3. P. jiroveci prophylaxis
4. Prophylaxis for T.gondii
5. Pemphigoid, dermatitis herpetiformis, linear IgA bullous disease, relapsing
chondritis,
42. Folate synthesis inhibitors- Dapsone
• Untoward Effects:
• Hemolysis in G6PD deficiency. Doses of 100 mg or less in healthy persons and
50 mg or less in healthy individuals with a G6PD deficiency do not cause
hemolysis.
• Methemoglobinemia.
• Neurological reactions: headache, nervousness, insomnia, blurred vision,
paresthesias, reversible peripheral neuropathy.
• Infectious mononucleosis-like syndrome
43. Folate synthesis inhibitors- PAS
• Para-aminosalicylic acid, discovered by Lehman in 1943, was the first
effective treatment of TB.
• Mechanism of Action:
• PAS is thought to be a competitive inhibitor folP1, but in vitro the inhibitory
activity against folP1 is very poor
• Antibacterial Activity:
• Bacteriostatic against M. tuberculosis.
• Mechanism of Bacterial Resistance
• Mutations in thyA, folC, dfrA and ribD.
44. Folate synthesis inhibitors- PAS
• Pharmacokinetics:
A= oral bioavailability is more than 90%.
The Cmax increases 1.5-fold and AUC 1.7-fold with food compared to fasting
D= Widely distributed, Protein binding is 50%–60%.
M= N-acetylated in the liver.
E= Both metabolites and active drug excreted in urine.
• Therapeutic Uses:
• MDR-TB
• Adults: daily dose of 12 g divided in 3 doses.
• Children: 150–300 mg/kg/d in three or four divided doses.
• Untoward Effects:
• GI problem
• Hypersensitivity reactions
45. Cellular energetics inhibitors- Pyrazinamide
• Mechanism of Action:
pyrazinamide passively diffuses into mycobacterial cells
Pyrazinoic acid (POA−, in its dissociated form)
Passive diffusion of the POA− to the extracellular milieu
In an acidic extracellular milieu, a fraction of POA– is protonated to the uncharged form, POAH
Reenters the bacillus and accumulates due to a deficient efflux pump
The acidification of the intracellular milieu is believed to inhibit enzyme function and collapse the
transmembrane proton motive force, thereby killing the bacteria.
Pyrazinamidase
46. Cellular energetics inhibitors- Pyrazinamide
• Mechanisms of Resistance:
1. Production of pyrazinamidase with reduced affinity for pyrazinamide.
2. Mutations in the genes encoding proposed pyrazinamide targets.
3. Increased efflux rate of POA.
• Pharmacokinetics:
A= oral bioavailability >90%.
D= concentrated 20-fold in lung epithelial lining fluid.
M= By microsomal deamidase & hydroxylases.
E= Metabolites are excreted in urine.
47. Cellular energetics inhibitors- Pyrazinamide
• Microbial Pharmacokinetics-Pharmacodynamics
• Pyrazinamide’s sterilizing effect is closely linked to AUC0–24/MIC
• Therapeutic Uses:
• Tuberculosis
• 35 mg/kg (30–40) mg/kg/d.
• The coadministration of pyrazinamide with isoniazid or rifampin has led to-
• one-third reduction in the duration of anti-TB therapy and a
• two-thirds reduction in TB relapse.
• Untoward Effects:
• Hepatotoxicity
• Hyperuricemia
48. Cellular energetics inhibitors- Bedaquiline
• Mechanism of Action:
Binds to subunit c of the ATP synthase of M. tuberculosis,
Inhibition of the proton pump activity of the ATP synthase
Inhibition of energy metabolism.
49. Cellular energetics inhibitors- Bedaquiline
• Antibacterial Activity:
• M. tuberculosis.
• MAC,
• M. leprae,
• M. bovis,
• M. marinum,
• M. kansasii,
• M. ulcerans,
• M. fortuitum,
• M. szulgai, and
• M. abscessus
50. Cellular energetics inhibitors- Bedaquiline
• Mechanism of Bacterial Resistance:
• Mutation in gene encoding ATP synthase c subunit.
• Increased expression of efflux pump.
• Pharmacokinetics:
A= Slow absorption (Tmax- 5hr)
D= Large aVd but poor CNS penetration
M= Hepatic CYPs
The terminal t 1/2 is about 5.5 months, mainly driven by redistribution from the
tissues
51. Cellular energetics inhibitors- Bedaquiline
• Microbial Pharmacokinetics-Pharmacodynamics:
• Microbial kill of bedaquiline is believed to be linked to AUC/MIC ratios.
• Efficacy and Therapeutic Use:
• MDR-TB:
• 400 mg daily for 2 weeks followed by 200 mg three times a day thereafter added to a background second-line
regimen of either kanamycin or amikacin, ofloxacin with or without ethambutol.
• Untoward Effects:
• Nausea and diarrhoea (MC)
• Arthralgia, pain in extremities, and hyperuricemia.
• major concern with this drug is cardiovascular toxicity and death.
52. Bicyclic Nitroimidazoles: Delaminid and
Pretomanid
• Mechanisms of Action:
• Pretomanid & delaminid are a prodrug that requires activation by the bacteria
via a nitroreduction step.
• Has two mechanisms of action:
• First, under aerobic conditions it inhibits M. tuberculosis mycolic acid and protein
synthesis at the step between hydroxymycolate and ketomycolate
• Second, generates reactive nitrogen species such as NO via its des-nitro metabolite,
• Antibacterial Activity:
• M. tuberculosis
• Mechanism of Resistance:
• Changes in structure of FGD, due to point mutations in the fgd gene
decreased activation.
53. Bicyclic Nitroimidazoles: Delaminid and
Pretomanid
• Microbial Pharmacokinetics-Pharmacodynamics:
• T>MIC
• Therapeutic Uses:
• MDR TB
• Delaminid is currently dispensed in 50-mg tablets at 100 mg twice daily, with food.
• Pretomanid is administered at 200 mg a day and is undergoing phase III trials in
combination with other drugs.
• Untoward Effects:
• Delamanid is associated with QT segment prolongation
55. Principles of Antituberculosis Chemotherapy
• Introduction
• Mycobacterium tuberculosis is not a single species, but a complex of species
with 99.9% similarity at the nucleotide level.
• The complex includes M. tuberculosis (typus humanus), M. canettii, M.
africanum, M. bovis, and M. microti.
• They all cause TB, with M. microti responsible for only a handful of human
cases.
56. Principles of Antituberculosis Chemotherapy
• Antituberculosis Therapy: General Points
1. Traditionally, isoniazid (H), pyrazinamide (Z), rifampin (R), and ethambutol (E)
have been considered first-line anti-TB agents.
2. Second-line drugs included ethionamide, PAS, cycloserine, amikacin,
kanamycin, and capreomycin.
3. However, the concept of specific drugs as first line is being replaced with
focus on regimens to be ranked by faster sterilizing effect.
4. Traditionally, first-line agents were more efficacious and better tolerated
relative to second-line agents.
57. Principles of Antituberculosis Chemotherapy
• Antituberculosis Therapy: General Points
5. The mutation rates to anti-TB drugs are between 10-6 and 10-10 so that the
likelihood of resistance is high to any single anti-TB drug in patients with
cavitary TB who have about 109 CFU of bacilli in a 3-cm pulmonary lesion.
6. However, the likelihood that bacilli would develop mutations to two or more
different drugs is the product of two mutation rates (between 1 in 1014 and
1 in 1020), which makes the probability of resistance emergence to more
than two drugs acceptably small.
7. Thus, only combination anti-TB therapy is currently recommended.
8. Multidrug therapy has led to a reduction in length of therapy.
58. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Prophylaxis
• After infection with M. tuberculosis, about 10% of people will develop active disease over a
lifetime.
• The highest risk of reactivation TB is in patients with Mantoux tuberculin skin test reaction
5mm or greater but ≤ 10 mm, who also fall into one of the following categories:
a) Recently exposed to TB,
b) HIV coinfection,
c) Fibrotic changes on chest radiograms, Or
d) Immunosuppressed due to HIV infection or posttransplantation or are taking immunosuppressive medications
for any reason.
• Any person with a skin test greater than 10 mm is also at high risk of disease.
• In these patients at high risk of active TB, prophylaxis is recommended to prevent active
disease.
59. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Prophylaxis
• Prophylaxis consists of either of following regimens:
1. Shortest-duration regimen that is effective consists of isoniazid 15 mg/kg (maximum 900
mg) and weight band–based rifapentine doses administered orally once a week for 12
weeks.
• The weight bands for rifapentine are 300 mg for 10–14 kg, 450 mg for 14.4–25 kg, 600 mg for
25.1–32 kg, 750 mg for 32.1–49.9 kg, and 900 mg for above 50 kg.
2. The traditional regimens consist of oral isoniazid, 300 mg daily or twice weekly, for 6
months in adults.
• In children, isoniazid 10–15 mg/kg daily (maximum 300 mg) is administered, or 20–30 mg/kg
two times a week directly observed, for 9 months.
3. Those who cannot take isoniazid should be given rifampin, 10 mg/kg daily, for 4 months.
• In children who cannot tolerate isoniazid, rifampin 10–20 mg/kg daily for 6 months is
recommended.
60. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Susceptible TB
• All active TB cases should be confirmed by culture or rapid diagnostic methods such as
nucleic acid amplification tests (e.g., Xpert MTB/RIF) and have antimicrobial susceptibilities
determined.
Population Initial/ Intensive Phase Continuation Phase
Adult Isoniazid (5 mg/kg, Max. 300 mg/d),
Rifampin (10 mg/kg, max. 600 mg/d), and
Pyrazinamide (15–30 mg/kg, max. of 2 g/d)
for 2 months
Isoniazid (15mg/kg) and Rifampicin (10-mg/kg) two
or three times a week
for 4 months
Rifapentine (10 mg/kg once a week) may be
substituted for rifampin in patients with no evidence
of HIV infection or cavitary TB.
If there is resistance to isoniazid, initial therapy also may
include ethambutol (15–20 mg/kg/d) or streptomycin (1
g/d) until isoniazid susceptibility is documented
Paediatric Isoniazid 10–15 mg/kg at a max. 300 mg/d.
Rifampin 10–20 mg/kg at a max. 600 mg/d,and
Pyrazinamide 30–40 mg/kg/d,.
Ethambutol doses are 20 mg/kg/d (maximum 1 g) or 50
mg/kg twice weekly (2.5 g).
Rifabutin 5 mg/kg/d can be used as preferred rifamycin for the entire 6 months of therapy in adult HIV-infected patients
61. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Susceptible TB
• Pyridoxine, vitamin B6, (10–50 mg/d) should be administered with isoniazid to
minimize the risks of neurological toxicity.
• To ensure compliance, therapy is administered as DOT.
• The duration of therapy of drug-susceptible pulmonary TB is 6 months.
• A 9-month duration should be used for patients with cavitary disease who are
still sputum culture positive at 2 months.
62. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Susceptible TB
• HIV-infected patients with CD4+ lymphocyte cell counts less than 100/mm3
are at increased risk of developing rifamycin resistance.
• Therefore, daily therapy is recommended during the continuation phase.
• Most cases of extrapulmonary TB are treated for 6 months, TB meningitis is an
exception that requires a 9- to 12-month duration.
• The optimal regimen for treatment of TB pericarditis remains to be identified.
63. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Susceptible TB
• RNTCP Guidelines (2018)
Type of TB Case Intensive Phase Continuation Phase**
New (2) HRZE (4) HRE
Previously Treated (2) HRZE (4) HRE
** May be extended for 3-6 months in extrapulmonary TB of CNS, skeleton or disseminated TB
Weight Band
(Adults)
No. of Tablets (FDC) Inj. Streptomycin
(in gm)Intensive Phase- HRZE
(75/150/400/275)
Continuation Phase-
HRE (75/150/275)
25-39 kg 2 2 0.5
40-54 kg 3 3 0.75
55-69 kg 4 4 1.0
>/= 70 kg 5 5 1.0
For pts. >50 years of age max. dose of streptomycin in 0.75 gm
64. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Resistant TB
• Multi Drug resistant TB (MDR-TB):
• Resistance to both Isoniazid (H) and Rifampin (R) with or without
resistance to other first line anti-tubercular drugs.
• Extensive Drug resistant TB (XDR-TB):
• MDR-TB also resistant to fluoroquinolones and at least one of three injectable
second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
65. Principles of Antituberculosis Chemotherapy
• Types of Antituberculosis Therapy: Definitive Therapy of
Drug-Resistant TB
• The exact regimens to use are still unknown.
• Thus, in documented drug resistance, therapy should be based on evidence of
susceptibility and should include:
a) At least three drugs to which the pathogen is susceptible, with at least one of the
injectable anti-TB agents.
b) In the case of MDR-TB, a prolonged course (24 months) of 5 to 7 agents, except a
shorter 9-12 month regimen if there is no resistance to fluoroquinolones and second-
line injectable agents.
c) The addition of a fluoroquinolone and surgical resection of the main lesions have been
associated with improved outcome.
66. Principles of Therapy Against Mycobacterium
avium Complex
• Introduction
• The MAC is made up of at least two species: M. intracellulare and M. avium.
• Mycobacterium intracellulare causes pulmonary disease often in
immunocompetent individuals.
• Mycobacterium avium is further divided into a number of subspecies:
• M. avium subsp. hominissuis causes disseminated disease in immunocompromised
patients,
• M. avium subsp. Paratuberculosis has been implicated in the etiology of Crohn disease,
and
• M. avium subsp. avium causes TB of birds.
67. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of MAC Pulmonary Infection:
• Criteria in favor of therapy includes:
1. Bacteriological evidence, which consists of positive cultures from at least two
sputums or one positive culture from bronchoalveolar lavage or pulmonary
biopsy with a positive culture or histopathological features, and
2. Clinical evidence of infection, and
3. Radiological evidence of infection such as pulmonary cavitation, nodular lesions,
or bronchiectasis.
• In newly diagnosed patients with MAC pneumonia, triple-drug therapy
is recommended.
• These drugs include a rifamycin, ethambutol, and a macrolide.
68. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of MAC Pulmonary Infection:
• For nodular and bronchiectatic disease:
• Clarithromycin, 1000 mg, or azithromycin, 500 mg, + ethambutol, 25 mg/kg, +
rifampin, 600 mg, and administered three times a week.
• For cavitary disease:
• Azithromycin, 250 mg, + ethambutol, 15 mg/kg, + rifampin, 600 mg, and
administered three times a week.
• Parenteral streptomycin or amikacin at 15 mg/kg is recommended as a fourth
drug.
• Advanced pulmonary disease or during re-treatment:
• Rifabutin 300 mg daily may replace rifampin.
• Therapy is continued for 12 months after the last negative
culture.
69. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of Disseminated M. avium Complex:
• Disseminated MAC disease is caused by M. avium in 95% of patients.
• This is a disease of the immunocompromised patient, especially with
reduced cell-mediated immunity.
• MAC usually occurs in patients whose CD4 cell count is less than 50/mm3.
• The symptoms and laboratory findings of disseminated disease are
nonspecific and include fever, night sweats, weight loss, elevated serum
alkaline phosphates, and anemia at the time of diagnosis.
• However, when disease occurs in patients already on antiretroviral therapy, it
may manifest as a focal disease of the lymph nodes, osteomyelitis,
pneumonitis, pericarditis, skin or soft-tissue abscesses, genital ulcers, or
CNS infection
70. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of Disseminated M. avium Complex: Prophylactic
Therapy
• Monotherapy with either oral azithromycin 1200 mg once a week or
clarithromycin 500 mg twice a day is started when patients present with a CD4
count below 50/mm3.
• For patients intolerant to macrolides, rifabutin 300 mg a day is administered.
• Once the CD4 count is greater than 100 per mm3 for 3 months or longer, MAC
prophylaxis should be discontinued.
71. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of Disseminated M. avium Complex: Definitive &
Suppressive Therapy
• Goals of therapy include:
• Suppression of symptoms and
• Conversion to negative blood cultures.
• The infection itself is not completely eradicated
until immune reconstitution.
72. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of Disseminated M. avium Complex: Definitive &
Suppressive Therapy
• Therapy is divided into initial therapy and chronic suppressive therapy.
Clarithromycin 500 mg twice a day
+
ethambutol 15 mg/kg daily
±
rifabutin 300 mg/d
±
Amikacin, 10–15 mg/kg intravenously daily OR streptomycin, 1 g intravenously or
intramuscularly daily OR ciprofloxacin, 500–750 mg orally twice daily OR levofloxacin,
500 mg orally daily OR moxifloxacin, 400 mg orally daily.
73. Principles of Therapy Against Mycobacterium
avium Complex
• Therapy of Disseminated M. avium Complex: Definitive &
Suppressive Therapy
• Patients should be continued on suppressive therapy until
all three of the following criteria are met:
• Therapy duration of at least 12 months
• CD4 count greater than 100/mm3 for at least 6 months
• Asymptomatic for MAC infection
74. Principles of Antileprosy Therapy
• Introduction:
• Mycobacterium leprae was discovered by Armauer Hansen in 1873.
• M. leprae is difficult to culture on synthetic media, an impediment to basic
research on the disease.
• The global prevalence of leprosy has markedly declined, largely due to the
global initiative of the WHO to eliminate leprosy (Hansen disease) as a public
health problem by providing multidrug therapy (rifampin, clofazimine, and
dapsone) free of charge.
• Four major clinical types of leprosy:
1. Tuberculoid
2. borderline (dimorphous) tuberculoid.
3. Indeterminate.
4. Lepromatous.
75. Principles of Antileprosy Therapy
• Therapy of leprosy is based on multidrug regimens using rifampin, clofazimine, and
dapsone.
• The reasons for using combinations of agents include:
1. Reduction in the development of resistance,
2. The need for adequate therapy when primary resistance already exists, and
3. Reduction in the duration of therapy.
• The most bactericidal drug in current regimens is rifampin.
• Because of high kill rates and massive release of bacterial antigens, rifampin is not
often given during a “reversal” reaction or in patients with erythema nodosum
leprosum.
• Clofazimine is only bacteriostatic against M. leprae. However, it also has anti-
inflammatory effects and can treat reversal reactions and erythema nodosum
leprosum.
76. Principles of Antileprosy Therapy
• Types of Antileprosy Therapy: Definitive Therapy; Standard
Therapy
• Paucibacillary Leprosy (1-5 skin lesion± Nerve involvement):
• The WHO regimen consists of a single dose of oral rifampin, 600 mg + dapsone, 100 mg,
administered under direct supervision once every month for 6 months, and dapsone,
100 mg a day, in between for 6 months
• Multibacillary Leprosy (>5 skin lesion + > or =1 Nerve involvement) :
• The WHO recommends the same regimen as for paucibacillary leprosy, with two major
changes:
1. Clofazimine, 300 mg once a month f/b 50 mg daily, is added for the entirety of therapy.
2. Regimen lasts 1 year instead of 6 months.
77. Principles of Antileprosy Therapy
• Types of Antileprosy Therapy: Treatment of reactions in leprosy
• Reversal reactions:
• Seen in Patients with tuberculoid leprosy.
• Manifestations of delayed hypersensitivity to antigens of M. leprae.
• Cutaneous ulcerations and deficits of peripheral nerve function may occur.
• Early therapy with corticosteroids or clofazimine is effective.
• Erythema Nodosum Leprosum (ENL):
• Reactions in the lepromatous form of the disease.
• Characterized by the appearance of raised, tender, intracutaneous nodules, severe constitutional
symptoms, and high fever.
• It is thought to be an Arthus-type reaction.
• Treatment with clofazimine or thalidomide is effective.