LINEZOLID - A ANTIBIOTICS OF OXAZOLIDINONE GROUP

LINEZOLID

 A ANTIBIOTICS OF OXAZOLIDINONE GROUP

Linezolid a antibacterial agent of  a new class of antibiotics, know as Oxazolidinone used for treatment of Gram-positive bacterial infection that are resistant to other antibiotics.

Linezolid is active against most Gram-positive bacteria that cause disease, including Streptococci, Vancomycin-resistant Enterococci(VRI), methicillin-resistant staphylococcus aureus (MRSA), Streptococcus pneumoniae (penicillin-susceptible strains only), Staphylococcus epidermidis(including methicillin-resistant strains), streptocovvus pyogenes, & Enterococcus faecalis. The main uses are infections of the skin and pneumonia.

Mechanism of Action:

Linezolid are a protein synthesis inhibitor that it stops the growth of bacteria by disrupting their production of proteins. Although many antibiotics work this way but linezolid appears to be unique in that it blocks the initiation of protein synthesis and not one of the later steps; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.

Pharmacokinetics:

Plasma concentrations of linezolid at steady-state after oral doses of  600 mg given every 12 hours(q12 h).

Absorption :

Linozolid is rapidly and extensively adsorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing and the absolute bioavailability is approximately 100%. Therefore, linezolid may be given orally or intravenously without dose adjustment. It may be administered without regard to the timing of meals. The time to reach the maximum concentration is delayed from 1.5 to 2.2 hours and Cmax is decreased by about 17% when high fat food is given with linezolid.

Distribution:

Linezolid readily distributes to well-perfuse tissue. The plasma protein binding of it is approximately 31% and is concentration-independent.

Metabolism :

Linezolid in not detectably metabolized by human cytochrome P450 and it does not inhibit the activities of clinically significant human CYP isoforms .

Excretion:

Nonrenal clearance accounts for approximately 65% of the total clearance of linezolid. Under steady-state conditions, approximately 30% of the dose appears in the urin as linezolid, 50% as metabolite. The renal clearance of linezolid is low (average 40 ml/min) and suggests net reabsorption. Virtually no linezolid appears in the feces.

Dosage:

Adult- 600 mg orally every 12 hours.

Geriatric:

The  pharmacokinetics of linezolid are not significantly altered in elderly patients (65 yrs or older). Therefore, dose adjustment for geriatric patients is not necessary.

Pediatric:

Information indicates that pediatric patients dosed with 10mg/kg IV have a similar Cmax but a higher average clearance when corrected by body weight and shorter apparent elimination half-life than adults receiving 625 mg of linezolide. Studies with dose higher than 10mg/kg or more frequent than every 12 hours have not been conducted in pediatric patients.

Gender:

Females have a slightly lower volume of distribution of linezolide than male. Plasma concentrations are higher in female than in males ,which is partly due to body weight difference. After a 600mg dose, mean oral clearance is approximately 38% lower in females than in males. However, there are no significant gender difference in means apparent elimination –rate constant or half-life. Therefore, dose adjustment by gender does not appear to be necessary.

Renal Insufficiency:

Linozolide pharmacokinetics is not altered in patients with any degree of renal insufficiency; no dose adjustment is recommended for patients with renal insufficiency.

Hepatic Insufficiency:

The pharmacokinetics of linezolide in not altered in patients with mild-to-moderate hepatic insufficiency. On the basis of the available information, no dosage adjustment is recommended for patients with mild-to-moderate hepatic insufficiency.

Pregnancy: Teratogenic Effects:

Linezolide was not teratogenic in mice or rate at exposure levels 4-fold (in mice) the expected human exposure level.However, embryo and fetal toxicities were seen there are no adequate and well-controlled studies in pregnant women. Linezolide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Nosocomial Infections

Nosocomial Infections

Infections which are acquired from hospitals are called nosocomial infection. These infection occurring with in 48 hours of hospital admission, 3 day of discharge or 30 days of an operation. If the organisms come from another patient it is called cross infections and if patient himself carries the infection to some other site then it is autoinfection. Infection may become apparent during the stay of the patient in the hospital or after his discharge from the hospital. There is actual increase in frequency and severity of infection especially due to antibiotic resistant enterobacteria, Staphylococcus aureus and Pseudomonas aeruginosa.Thus prolonged stay of the patient in the hospital is undesired and may be a serious matter for the patient and his family.

Patients Requiring Isolation:

Some patients really need isolation. Patients of tuberculosis, typhoid, diphtheria, lassa fever or smallpox should not be treated or nursed in open ward as these disease are serious and easily transmissible. Similarly infants with measles or whooping cough should not be nursed in general ward but may be treated at home. Staphylococcus aureus infection cases especially resistant to many antibiotics belonging to phase types (80/81 or 75/77) capable of causing serious epidemic of hospital sepsis, certainly require isolation. Isolation cubicles are suggested for these purposes which should be so designed, equipped and managed that no microorganism can pass from them to a ward. Attendant should use gown on entering the cubicle and remove on leaving. Washing facilities for the patient and attendant of the patient must be provided in the cubicle. Dressing should be discarded into paper bags which may be removed to incinerator. Bedding and clothing should be kept in disinfectant solution before sending to laundry. When the patient finally leaves the cubicle,it must be thoroughly washed with disinfectant and all equipment must be sterilized as far as possible.

Hospital Infection and Prevention:

We should be aware of some important hospital infections and their prevention:

1. Wounds and burns: It is important to remove all tissue debris from accidental wounds and burns as bacteria can establish more easily in damaged tissue. A careful and aseptic technique for dressing of wound preferable in dressing room reduces chances of cross infection.
2. Urinary tract infection: Catheter or other instruments into the bladder may cause urinary tract infection. Used catheters are difficult to sterilize and may be the cause of cross infection also, hence disposable sterilized catheter should be used aseptically.
3. Alimentary tract infections: Outbreak of E.coli gastroenteritis in children and Shigella sonnei, dysentery do occur quite oftenly  in hospital. Isolation, general hygiene and exclusion of carriers are important preventive measures.

Epidemiological Markers Useful in investigating Hospital Infection:

• Antibiogram and resistogram.
• Biotyping.
• Phage typing.
• Bacteriocin typing.
• Serotyping.
• Serum opacity factor.
• RNA electropharesis as in done in rotavirus.
• Cytotoxicity assay, e.g. Proteus mirabilis.
• Plasmid profile.

Prevention of Nosocomial Infections:

• Proper washing
• Isolation of patients, e.g. plague, influenza, measles, etc.
• Careful and appropriate use of instruments.
• Use of antibiotics only if required. It may be given to carrier staff or patient.
• Use of blood transfusion only if must. Disinfectants of excreta and infected material.
• Surveillance of infection properly and regularly.
• Use of vaccine, e.g. tetany gas sangrene, hepatitis – B, etc.

Factors Responsible for Hospital Infections:

• Neonates and aged patients have risk of getting hospital infection because of long stay and decreased immunity.
• Impaired defense mechanisms of patients due to disease or treatment.
• Hospital environment contains relatively heavy load of microorganisms.
• Major invasive diagnostic or therapy procedures.
• Advance treatment of cancer, organ transplantation, etc.
• Presence of multidrug resistant bacteria, etc.

Source of Hospital Infection :

• Infecting microorganisms from fellow patients which may be multidrug resistant.
• Infected organisms from hospital staff
• Infecting organisms from instruments, blood products, intravenous fluid, etc.
• From patient’s normal flora, etc.
• Insects are also source multidrug infection.
• Organism may be present in air, dust, water, antiseptic solution, food, etc.
• Surface contaminated by patient’s secretions, blood fluid, etc.

Mode of Infection :

• Airborne.
• Contact, e.g. hand, clothing, etc.
• Food and water.
• Hospital equipments and instruments.
• By parenteral routs.

Roll of Mycobacterium Tubercolosis Bacteria (TB) in HIV positive Person

Roll of Mycobacterium Tubercolosis Bacteria (TB) in HIV positive Person

When person has both HIV & TB , each disease speeds up the progress of other.

HIV positive person have weak immune system & therefore they are more prone to TB infection because TB bacteria get a conducive environment for their activation (its replication & growth). Generally TB does not affect normal person due to strong immune system of body.

Viruses do not have own enzymes which is necessary for protein & nucleic acid synthesis. For this reason virus depend upon synthetic machinery of host cells where they use host cell’s enzymes for their replication. When HIV positive person received TB cause bacteria, HIV found a new host cell in body for their replication.

Viruses that infect animal cells generally use cell-surface receptor that is found on those cell types in which the virus can replicate. Usually many viruses use a single type of receptor & some viruses can use several different receptor. Moreover, different viruses that infect the same cell type may each use a different receptor.  

However HIV requires both a primary receptor as a CD4 & a secondary co-receptor as a CCR5 OR CXCR4(a receptor for α-chemokines) depending on the particular variant of the virus for attachment & entry in to host cells. CD4 are protein involved in immune recognition which is found on the surface of many T-cells & macrophages. Macrophages are susceptible only to HIV variants that use CCR5 for entry, whereas T cells are most efficiently infected by variants that use CXCR4. The viruses that are found within the first few months after HIV infection almost invariably require CCR5, which presumably explains why individuals who carry a defective ccr5 gene are not susceptible to HIV infection. In the later stages of infection, viruses may either switch to use the CXCR4 co-receptor or adapt to use both co-receptors; in this way, the virus can change the cell types it infects as the disease progresses. 

After recognition and attachment to the host cell surface, the virus must next enter the host cell and release its nucleic acid genome from its protective protein coat or lipid envelope within so that the host's genetic coding can be altered to produce other HIV virions.

Roll of CD4 cells on HIV/ AIDS

CD4 T-cells & HIV

CD4 is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes and macrophages cells. CD4 cells (sometimes called T-cells, T-lymphocytes, or helper cells) are white blood cells that play an important role in the immune system. Your CD4 cell count gives you an indication of the health of your immune system – your body’s natural defence system against pathogens, infections and illnesses.

CD4 T-cells are considered "helper" cells because they do not neutralize infections but rather triggers the body's response to infections. In response, CD8 T-cells—classified as such because of the type of glycoprotein on their surface—play a part as so-called "killer" cells by producing antiviral substances (antibodies) that help fight off foreign invaders.

Structure of CD 4 cells:

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin super family

It has four immunoglobulin domains (D1 to D4) that are exposed on the extra cellular surface of the cell:

• D₁ and D₃ resemble  immunoglobulin variable (IgV) domains.
• D₂ and D₄ resemble immunoglobulin constant (IgC) domains.

CD4 uses its D₁ domain to interact with the β₂-domain of MHC class II  molecules. T cells expressing CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class II (they are MHC class II-restricted). MHC class I contains Beta-2 macroglobulin.

How HIV Affects CD4 Cells:

As a retrovirus, HIV do not have own enzymes necessary for protein & nuclic acid synthesis and so depend upon synthetic machinery oh host cells. Therefore, HIV needs to infect certain "host" cells in order to make copies of itself. CD4 cells are the prime targets for this in the course of an infection.

During infection, HIV attaches to surface of CD4 cells, emptying its genetic material within so that the host's genetic coding can be altered to produce other HIV virions.

How Do We Measure CD4 T-Cells

By determining how many functioning CD4 cells are circulating in the blood, a doctor can determine the status of a person's immune system. A simple blood tested called the CD4 COUNT estimates the number of functioning CD4 cells in a cubic millimetre of blood. The higher the CD4 count, the stronger the immune function.

Your CD4 cell count is the measurement of the number of blood cells in a cubic millimeter of blood (a very small blood sample). It is not a count of all the CD4 cells in your body.

• The CD4 cell count of a person who does not have HIV can be anything between 500 and 1500.
• People living with HIV who have a CD4 count over 500 are usually in pretty good health.
• People living with HIV who have a CD4 cell count below 200 are at significant risk of developing serious illnesses. While HIV treatment is recommended for all people living with HIV, it is especially important for people with low CD4 counts.

If you have HIV and do not take HIV treatment, your CD4 count will fall over time. The lower the CD4 cell count, the greater the damage to the immune system and the greater the risk of illness.

When you take HIV treatment, your CD4 count should gradually increase

HIV POSITIVE Vs AIDS

HIV POSITIVE Vs AIDS

AIDS (Acquired immune deficiency syndrome or acquired immunodeficiency syndrome) is a syndrome caused by a virus called HIV (Human Immunodeficiency Virus). This virus attack on cells of the immune system & destroying or impairing their function which lead to progressive deterioration of the immune system, leading to "immune deficiency.” As the immune system weakens, the person is at risk of getting life-threatening infections and cancers and finally person have symptoms of AIDS.

 

Human Immunodeficiency Virus (HIV):

It belongs to the Lentivirus sub-group of Retroviridac family. HIV is an RNA retrovirus. The unique morphologic feature oh HIV is its cylindrical nucleotide in mature virion.The virus contain the 3 genes required for a replicating retrovirus – gap,pol and env. The virus has outermost envelope rich in glycoproteins (gp41,gp120,gp160) & inner core with two component protein (p18 ,p24).while the enzyme reverse transcriptase capable of the retrograde transcription of viral RNA to viral DNA mark its special feature. The incubation period seem to be long, ranging from 6 months to more than 2 years.

Inactivation of HIV:

10 minutes, treatment at 37 C can inactivate this virus, with 10% household bleach, 50% ethanol, 35% isopropanol, 0.5% Lysol & 0.3% hydrogen per oxide.

How is HIV transmitted?

The virus is transmitted person-to-person in any of the following ways:

• Unprotected sexual intercourse (vaginal or anal), and oral sex with an infected person.
• Transfusion of contaminated blood.
• Sharing of contaminated needles, syringes or other sharp instruments.
• Mother and her infant during pregnancy, childbirth and breastfeeding.

Listed below are health problems common in people with AIDS:

AIDS is characterized by pronounced suppression of immune system, the development of unusual neoplasm especially Kaposi’s sarcoma or wide variety of sever opportunistic infections. Other symptom include:-

• Loss of vision
• Coughing and shortness of breath
• Problems swallowing
• Severe and constant diarrhea
• Nausea, stomach cramps, and vomiting
• Fever
• Weight loss
• Feeling very tired all the time
• Seizures
• Pneumonia
• Coma
• Cancers of the skin or immune system

Treatment

There is no cure for HIV but some drugs are used in the treatment and prevention of HIV infection which is called antiretroviral therapy (ART), they fight HIV by stopping or interfering with the reproduction of the virus in the body, reducing the amount of virus in the body.

In the past, people with HIV infection would start antiretroviral treatment after their CD4 count dropped or they developed HIV complications. Today, HIV treatment is recommended for all people with HIV infection, even if their CD4 count is still normal.

If the CD4 count already dropped before treatment was started, it will usually slowly go up. HIV complications often disappear as the immune system recovers.

How is AIDS different from HIV positive?

HIV positive can be defined as when You have HIV but not have any symptoms that’s  mean HIV alive  in your body but they do not attack on your immune system i.e CD-4 cells  and some HIV tests will not show a positive result for as long as 3 months after infection. This is referred to as the  HIV test window period, and has to do with how HIV tests detect the virus.

Some people recently infected with HIV will experience some "flu-like" symptoms. These might include: Fever, Severe Fatigue, A non-itchy rash, swollen glands/lymph nodes, Muscle aches, Sore throat. Night sweats. These symptoms are called Acute Retroviral Syndrome and last from a few days to a few weeks.

After the acute phase, the virus typically becomes less active in the body for as long as 10 years, during which you might have no symptoms at all. An HIV test will still detect the virus during this period. This is one of the reasons that it's important for sexually active people to routinely get tested regularly - the signs of HIV infection are easy to miss or misinterpret.

AIDS can be defined as disease that later develops in people with HIV when HIV attack on CD 4 cells (immune cell) & continuing to replicate, leading to a gradual decline of CD4 cells and result in person are not able to protect himself from other infectious disease. Today, drugs make it possible for people with HIV infection to live a very long time before ever getting AIDS. How long you have the HIV infection before developing AIDS depends on a few things. Some of these things you can control, like taking your medicine on time every day.

Effect of Tuberculosis in pregnancy

 Pregnant woman infected with Tuberculosis

In 2005.WHO was declared a public health emergency for Tuberculosis. TB become more complicated in case of maternal mortality & is among the three leading causes of death among  of women aged 13-45 years.

If you infected by TB during pregnancy & you don’s treated it early, there is an increased risk of:

·        A chance of Miscarriage.

·        Premature Baby.

·        Baby burn with low birth weight.

·        Baby born with TB.

So proper treatment is vary necessary for TB infected pregnant woman.

Diagnosis:

If pregnant women are coughing up sputum( Phlegm) for more than three weeks, it must be go for sputum test which pick up most form of TB. This may be followed by a chest X-ray. Skin test or a blood test.If you have no specific symptom of TB,you will be given the tuberculosis test, also called Mantoux Test.

Treatment for TB during pregnancy

TB can  be fully cured  by using full  course of medication  (antibiotics) without interruption of medication. The course can go for between six and  nine months. Occasionally  the treatment  might go on for longer, depending on the severity of the case. Your doctor will tell you when it is safe to stop your medication.

You may feel better within a few weeks of treatment, but the bacteria will still be alive. So it is very important to complete the full course of medication. If you don't take the drugs as exactly prescribed, there is a very strong chance of a relapse. And you could pass the infection on to your family members. You may also end up with drug-resistant forms of the disease which are more difficult to treat.

Using of Directly Observed Therapy, Short Course (DOTS) is better option for treatment of TB with Pregnancy. This therapy entails the use of combination therapy for at least 6 months, depending on the combination of antituberculous agents that are available. This combination includes isoniazide and rifampicin compulsorily, supported by ethambutol and pyrazinamide .For patients with drug-susceptible TB and, these regimens will cure around 90% of TB cases. The use of these first-line antituberculosis drugs in pregnancy is considered safe for the mother and the baby by The British Thoracic Society, International Union against Tuberculosis and Lung Disease, and the World Health Organization.

 

Isoniazide

INH is safe during pregnancy even in the first trimester, though it can cross the placenta and may be cause of INH-induced hepatotoxicity. Pyridoxine supplementation is recommended for all pregnant women taking INH at a dose of 50 mg daily.

Rifampicin

This is also believed to be safe in pregnancy, though there may be an increased risk of haemorrhagic disorders in the newborn (some authorities prescribe supplemental vitamin K (10 mg/day) for the last four to eight weeks of pregnancy.)

Ethambutol

It may cause retro bulbar neuritis (optic neuritis) in adults because it may interfere with ophthalmological development when used in pregnancy but this has not been demonstrated when the standard dose is used. This was also confirmed in experimental studies on some abort uses.

 Pyrazinamide

The use of pyrazinamide in pregnancy was avoided by many physicians for a long time due to unavailability of adequate data on its teratogenicity. Presently, many international organizations now recommend its use. There are no reports of significant adverse events from the use of this drug in the treatment of TB in pregnant women despite its use as part of the standard regimen in many countries.

Its use is particularly indicated in women with tuberculosis meningitis in pregnancy, HIV infection, and suspected INH resistance.

Streptomycin

The drug has been proven to be potentially teratogenic throughout pregnancy. It causes fetal malformations and eighth-nerve paralysis, with deficits ranging from mild hearing loss to bilateral deafness. Many centres are against the use of this drug in pregnancy.

Multidrug-Resistant Tuberculosis  in Pregnancy

Pregnant women with MDR-TB have much difficult to treatment. They may sometimes require treatment with second-line drugs, including cycloserine, ofloxacin, amikacin, kanamycin, capreomycin, and ethionamide. The safety of these drugs is unfortunately not well-established in pregnancy.

Ethionamide is associated with growth retardation, central nervous system and skeletal abnormalities in early pregnancy. Its use is, therefore, not recommended in pregnancy.

Therapeutic abortion has been proposed as an option of management for these women, as MDR-TB poses more risk to the woman and the society at large. Another option is to delay initiating treatment to the second trimester where possible. Individualized Treatment Regimen (ITR) using various combinations of the 2nd line antituberculosis  agents based on their susceptibility profile had, however, been tried in some pregnant women with no adverse obstetric outcome

The outlook for those patients is expected to improve as experience and knowledge in the management of the condition increases.

In addition to your antibiotics, it is important to take good care of yourself so that you strengthen your immune system:

• Eat a well balanced diet.
• Get plenty of fresh air.
• Don't miss antenatal visits of doctor.
• Report any side effects, such as vision changes, headaches or increased nausea to your doctor immediately.
  

As long as you are infectious, maintain good  personal hygiene. Ensure that you wash your hands regularly and cover your mouth and nose with a tissue when you cough or sneeze so that you do not spread the germs around. Make sure you dispose of your soiled tissues in a covered bin or sealed plastic bag. 

Biggest Global Health Threats of "Drug-Resistant Tuberculosis"

Drug Resistant Tuberculosis

DRTB is defined as a form of TB infection caused by bacterial stain resistant to Anti Tuberculosis Agent which used in its treatment.

Many cases of  Tuberculosis Disease can be cured with antibiotics treatment as First-line drugs which are :-

• Isoniazid
• Rifampicin
• Pyrazinamide
• Ethambutal
• Streptomycin

But TB bacterium resist to antibiotics are vary common which arise due to improper management or improper use of antibiotics in chemotherapy of Drug-Susceptible TB patient.This improper management means administration of improper treatment regimens &/or incomplete the course of treatment.This is called Drug-resistant Tuberculosis Disease (DRTB) which is very lethal to human being because it vary difficult to Doctor to cure this due to limited drugs are available. 

The medical aid organization Medecins Sans Frontieres/Doctors Without Borders  has published a briefing paper about the alarming spread of deadly strains of drug-resistant tuberculosis (DR-TB) is one of the biggest global health threats we face today. It calls on governments, pharmaceutical companies and researchers to mobilise urgently to save more lives and find new treatments to stem the virulent disease.

Every year, around eight million people worldwide fall ill with tuberculosis (TB) and 1.3 million people die from the infectious airborne disease.   In Ireland in 2013, 384 cases of TB were reported, representing on average one person being diagnosed with the disease every day.   TB is curable, but an inadequate global response has allowed drug-resistant TB to take a hold.

Around half a million new cases of Drug-resistant TB  occur every year and are reported in virtually all countries worldwide, with even harder to treat forms reported in nearly 100 countries. Now these deadlier DR-TB strains are spreading from person to person. Yet today, no matter where you live, there is no means to treat it effectively.

Now Tuberculosis bacterium become a more powerful bacteria due to its resistance power against antibiotics.If we are not to be alert about DRTB,the tuberculosis will gets untreatable. Therefore DRTB become a global health problem & we should proper guide to people that how protect to us against TB  & also guide to  Drug-Susceptible TB patient to complete the  exact course of treatment  to increase the chance of successful eradication of infection and to reduce the risk of antibiotic resistance developing.If normal person come in contact to DRTB patient then normal person directly receive to drug resistant bacterium. Therefore it is vary necessary to isolate the drug resistant TB patients from community because these patient do't affected to other person.

Types of Drug-Resistant Tuberculosis:

There are two main types of drug resistant TB:

1. Multi-Drug Resistant Tuberculosis (MDR TB)
2. Extensively-Drug Resistant Tuberculosis (XDR TB)

Another type of drug resistant TB is:-

• Total-Drug Resistant Tuberculosis (TDR TB)

Multi-Drug Resistant Tuberculosis (MDR TB):

MDR TB is the name given to TB when the bacteria (that are causing it) are resistant to at least two of the most powerful First-Line anti TB drugs,Isoniazid & Rifampicin.


Extensively-Drug Resistant Tuberculosis (XDR TB):

XDR TB is defined as strain resistant to at least Rifampicin & Isoniazid in addition to being resistant to one of the Fluoroquinolones  as well as resistant to at least one of the second line injection TB drugs Amikacin,Kanamycin or capreomycin.

TB drugs for the treatment of drug resistant TB:

For the treatment of drug resistant TB, the current TB drugs are grouped according their effectiveness, experience of use, and drug class, as shown below.

All the drugs in Groups 2 to 5, apart from streptomycin, are referred to as “second line” or reserve TB drugs.

The first four groups of TB drugs listed below, are those that are mainly used for the treatment of drug resistant TB. The fifth group of TB drugs are some drugs that are unknown in how effective they are in the treatment of TB, but they can be tried when there is no other option. An example is using them in the treatment of totally drug resistant TB. 

TB drugs used to treat drug resistant TB according to group (class)

Group 1 TB drugs : First Line Oral Agents-

                                        
                                       pyrazinamide

                                        ethambutol

                                        rifabutin

Group 2 TB drugs : Injectable Agents-

                                       
                                        kanamycin

                                        amikacin

                                        capreomycin

                                        streptomycin

Group 3 TB drugs : Fluoroquinolones-

                                        
                                        levofloxacin

                                        moxifloxacin

                                        ofloxacin

Group 4 TB drugs : Oral Bacteriostatic Second Line Agents-

                                        
                                        para–aminosalicylic acid

                                        cycloserine

                                        terizidone

                                        thionamide

                                        protionamide

Group 5 TB drugs: Agents with an unclear role in the treatment of drug                                                        

resistant TB -
                                       
                                       clofazimine

                                       linezolid

                                       amoxicillin/clavulanate

                                       thioacetazone

                                       imipenem/cilastatin

                                       high dose isoniazid

                                       clarithromycin