LINCOSAMIDES

Lincomycin (from Streptomyces lincolnensis) +Clindamycin (semisynthetic derivative of Lincomycin) Clindamycin It is similar in mechanism of action (inhibits protein synthesis by binding to 50 S ribosome) and spectrum of activity to erythromycin.

Antibacterial activity: str., staph., pn., C. Diphtherine, Nocardia, Actinomycetes, Toxoplasma+ high activity against anaerobes, specially Bacteroides fragilis. Aerobic gram negative bacilli are not affected.

Pharmacokinetics: It is administered orally (Oral absorbtion is good ) but most often is administered parenterally (i.v.) because pseudomembranous colitis is less likely to follow parenteral administration. It penetrates to most skeletal and soft tissues, but not brain and cerebrospinal fluid; accumulates in neutrophils and macrophages.It is largely metabolized and metabolites are excreted in urine and bile.

Clinical uses: -skin and soft tissue infections caused by str. and staph. -anaerobic infections, specially by Bacteroides fragilis (abdominal, pelvic, lung abscesses); it is generally combined with an aminoglycoside or cephalosporin; -topical preparations of clindamycin are used to treat infected acne vulgaris. -clindamycin, sometimes in combination with an aminoglycoside or cephalosporin is used to treat penetrating wounds of the abdomen and the gut; - infections originating in the female genital tract; -it may be used instead of erythromycin for prophylaxis of endocarditis in patients with valvular heart diseases who are undergoing certain dental procedures. -in AIDS patients (in combination with other drugs) for toxoplasmosis and Pneumocystis carinii pneumonia.

Side effects: -rashes, urticaria;-abdominal pain; -the major problem is diarrhoea and pseudomembranous enterocolitis due to Clostridium difficile superinfection which is potentially fatal.The drug should be promptly stopped and metronidazole (alternatively vancomycin) given to treat it.

Dosages: Orally, 150-300 mg, every 6 hours: 10-20 mg / kg / day for children ; Intravenously, 600 mg, every 8 hours.

Lincomycin It is the forerunner of clindamycin. It has similar antibacterial and toxic properties but is less potent and produces a higher incidence of diarrhoea and colitis deaths have occurred. Thus, it has been largely replaced by clindamycin.

POLYPEPTIDE ANTIBIOTICS
POLYMYXIN B and POLYMYXIN E(COLISTIN )

They are natural compounds obtained from Bacillus polymyxa (polymyxin B) and Bacillus colistinus (Colistin ). Antibacterial activity: gram negative bacteria only; all except proteus, serattia, neisseria are inhibited.Both have very similar range of activity, but colistin is more potent on pseudomonas, salmonella and shigella.

 Mechanism of action: They are rapidly acting bactericidal agents. They act as cationic detergents.They atach to and disrupt bacterial cell membrane.

 Pharmacokinetics: They are not absorbed from gastrointestinal tract after oral administration and they act locally.They are rarely considered for systemic administration because of their poor tissue distribution and their serious adverse effects. They are now restricted for topical uses.Applied topically they are safe, no systemic effect or sensitization occurs.A rashe is rare.

 Clinical uses: -orally:

gram negative bacillary (E.coli, Salmonella, Shigella) diarrhoeas, specially in infants and children; -Pseudomonas enteritis; gut sterilization, to supress the aerobic gram negative members of the intestinal flora in immunosuppressed patients.

 -topically:-usually in combination with other antimicrobials (neomycin or bacitracin or glucocorticosteroids) for skin infections, burns, otitis externa, conjunctivitis, corneal ulcercaused by gram negative bacteria, including Pseudomonas. These preparations are available as ointments, solutions. -solutions with polymyxin B can be injected into joint spaces, pleural cavity(for local action).

 Adverse effects: -given orally, side effects are limited to the gastrointestinal tract: occasional nausea, vomiting, diarrhoea; -given parenterally they have high toxicity: marked kidney damage, neurological disturbances, neuromuscular blockade, flushing and paresthesias due to liberation of histamine from mast cells.

STREPTOGRAMINS and OXAZOLIDINONES

STREPTOGRAMINS
QUINUPRISTIN DALFOPRISTIN It is a combination of two streptogramins; Antibacterial activity: GRAM + COCCI: multidrug resistant strept., penicillin resistant strept., staph., ec .faecium ( not faecalis); It is administered i.v.;

Clinical uses: -infections caused by staph. / by Vancomycin resistant E. faecium; Side effects: -pain at the site of infections;arthralgias.

OXAZOLIDINONES
LINEZOLID-synthetic compound; Antibacterial activity:GRAM + organisms ( staph., strept., ec., gram + rods); It is bacteriostatic or bactericidal ( on str.); Mechanism of action : it inhibits bacterial protein synthesis;

Clinical uses: -vancomycin resistant E. faecium; Nosocomial pneumonia; Community acquired pneumonia; Skin infections ! It should be reserved for treatment of infections caused by multidrug resistant gram positive bacteria. Toxicity : reversible, generally mild thrombocytopenia.

AMINOGLYCOSIDE

ANTIBIOTICS

Natural and semisynthetic antibiotics originally obtained from various Streptomyces species.

Common characteristics:

*they are all structurally related : hexose ring to which various aminosugars(two or more) are attached by glycosidic linkages.

*they are all structurally related : hexose ring to which various aminosugars( two or more) are attached by glycosidic linkages.

*most of them are given parenterally (i.m. and i.v.); *they distribute only extracellularly ; do not penetrate brain or cerebrospinal fluid. *all are used as sulphate salts( highly water soluble); solutions are stable for months. *they are not metabolized and all are excreted unchanged in urine by glomerular filtration. *all are active primarily against aerobic gram negative bacilli (E.coli, proteus, Pseudomonas), staph., str., but spectrum differs. Anaerobes are resistant because aminoglycosides transport into cells is oxygen dependent.

*They have the same mechanism of

action: they are bactericidal agents; they inhibit bacterial protein synthesis by binding to 30S ribosomal subunit, or to additional sites on 50 S subunit as well as to 30S-50 S interface. Recent experimental studies show that the initial site of action is the outer bacterial membrane .The cationic antibiotic molecules create fissures in the outer cell membrane resulting in leakage of intracelullar contents and enhanced antibiotic uptake.

*The aminoglycosides produce toxic effects which are common to all members, but the relative propensity differs.All exhibit: *ototoxicity: cochlear and vestibular damages of VIIIth cranial nerve, with hearing loss, respectivelly with headache, nausea, vomiting, dizziness, nystagmus, vertigo, ataxia. * nephrotoxicity: it manifests as tubular damage. * neuromuscular blockade. * Resistance occurs rapidly ( inactivation by transferase enzymes, impaired entry of aminoglycosides into the cell, alteration of protein receptor on the ribosome)

The most important aminoglycosides:

AMIKACIN ARBEKACIN GENTAMICIN KANAMYCIN NEOMYCIN PAROMOMYCIN STREPTOMYCIN TOBRAMYCIN *APRAMYCIN *RHODOSTREPTOMYCIN SPECTINOMYCINchemically related to AMG

STREPTOMYCIN -obtained from streptomyces griseus.

-Antimicrobial activity:relatively narrow: only few strains of E.coli, H. Infl., Klebsiella, Shigella, V. Cholerae, enterococci and some gram positive cocci are now inhibited that too at higher concentrations. Sensitive germs are: Brucella, Yersinia pestis, Mycobacterium tuberculosis, Nocardia, Francisella tularensis. Resistance: many organisms develop rapid resistance to streptomycin.Eg: in the intestinal and urinary tracts resistant organisms may emerge within 2 days of therapy. E.coli, H. Infl., Str. Pneumoniae, staph. Aureus have become largely resistant. If it is used alone, Mycobacterium tuberculosis also become resistant.

Clinical uses: -tuberculosis (in combination with other drugs because resistance emerges rapidly); -subacute bacterial endocarditis (caused by streptococci viridans or enterococci) in conjunction with penicillin (today gentamicin is preferred); -tularemia: it is the drug of choice for this rare disease; Adverse effects: -vestibulotoxicity(vestibular disturbances); -it has the lowest nephrotoxicity among aminoglycosides; -pain at site of injection is common, Streptomycine is administered i.m.: in acute infections 1 g i.m., twice daily, for 7-10 days.

GENTAMICIN -It was obtained from

Micromonospora purpurea . It is more potent, it has a broader spectrum of action (comparing with streptomycin); it is effective against Ps. Aeruginosa, and most strains of proteus, E.coli, Klebsiella, Enterobacter, Serratia. It is also active against staph.

Clinical uses: - preventing and treating respiratory infections in critical ill patients/ in those with impaired host defence; It is often combined with a penicillin or a cephalosporin; -pseudomonas, proteus and klebsiella infections: burns, urinary tract infections, pneumonia, lung abscesses, osteomyelitis, septicaemia ;It may be combined with a penicillin (piperacillin) or a cephalosporin; -endocarditis due to viridans streptococci or enterococci ; -meningitis caused by gram negative bacilli; - middle ear infections, infected burns, wounds, conjunctivitis with sensitive germs-topically (creams, ointments, solutions); -gentamicin PMMA (polymethyl methacrylate) chains is a new drug delivery system for use in osteomyelitis. Implanted in the bone cavity after thorough removal of sequestra and left in place for 10 days, it has achieved high cure rates.

Adverse effects: -nephrotoxicity ;-vestibular toxicity. Dose:The dose of gentamicin must be precisely calculated according to body weight and level of renal function. The daily dose of gentamicin (and other aminoglycosides) should be reduced in patients with impaired renal function according to measured creatinine clearance. For an average adult with normal renal function 35 mg/ kg/ day, i.m., either as single dose or divided in three 8 hourly doses is recommended. Parenteral gentamicin is available as vials: 20, 60, 80, 240 mg per vial. For topical use: 0,3 % eye / ear drops, 0,1 %skin cream.

! Once daily aminoglycoside dosing may be preferred in certain clinical situations. * AMG have c% dependent killing effect that is increasing c % AMG kill an increased % of bacterias. *AG have postantibiotic effect i.e. antibacterial effect persists several hours . Because of these AMG may have better efficacy when administered as a single dose than when adm. as multiple smaller doses.

KANAMYCINE- It was obtained from

streptomyces kanamycetus.

It is more toxic, both to the cohlea and to kidney.Hearing loss is more common than vestibular disturbance. It is ocassionally used as a second line drug in resistant tuberculosis. It is administered i.m., usual dose 0,5 g i.m. Today parenteral use has been largely replaced. It may be used topically.

TOBRAMYCIN- It was obtained from

Streptomyces tenebrarius. It should be used only as a reserve alternative to gentamicin. Serious infections caused by pseudomonas and proteus are its only current indications. Ototoxicity and nephrotoxicity - lower than gentamicin. It is administered i.m., usual dose 3-5 mg/kg in 1-3 doses.

AMIKACIN
It has the widest spectrum of activity, including many organisms resistant to other aminoglycosides (because it is resistant to bacterial aminoglycoside inactivating enzymes). However, relatively higher doses are needed for pseudomonas, proteus and staph. infections. It is recommneded as a reserve drug for hospital acquired gram negative bacillary infections where gentamicin or tobramycin resistance is high. More hearing loss than vestibular disturbance occurs in toxicity. It is administered parenterally.

NEOMYCIN -obtained from Streptomyces

fradiae.
Neomycin is highly toxic to the internal ear(mainly auditory) and to kidney. It is therefore not used systematically. It is poorly absorbed from the gastrointestinal tract.Oral and topical administration does not ordinarily cause systemic toxicity. Clinical uses: -topically (often in combination with polymyxin, bacitracin, glucocorticosteroids) for infected wounds, ulcers, burn, external ear infections, conjunctivitis ; -orally for: -preparation of bowel before surgery: may reduce postoperative infections; -hepatic coma: neomycin by suppressing intestinal flora diminishes NH3 production and lowers its blood level; however, because of toxic potential it is infrequently used for this purpose and lactulose is preferred. -intestinal infections with sensitive germs.

Adverse effects: -applied topically neomycin has low sensitizing potential, however rashes do occur; -oral neomycin has a damaging effect on intestinal villi prolonged treatment can induce malabsorbtion syndrome ; also, due to marked suppression of gut flora, superinfection by candida can occur. Preparations, doses: Neomycine sulphate, 350, 500 mg; 0,3 % skin ointment; 0,5 % skin cream; 0,5% eye ointment. Neosporin: neomycin 3400 IU+ polymyxin 5000IU +bacitracin 400 IU / g ointment Neosporin-H: neomycin 3400 IU+ polymyxin 10.000 IU+hydrocortisone 10 mg / ml ear drops.

NETILMICIN
It has a broader spectrum of activity than gentamycin. It is relatively resistant to aminoglycoside inactivating enzymes and thus effective against many gentamicin resistant strains. It is more active against Klebsiella, Enterobacter, Staphylococci, but less active against pseudomonas. It is preferred in critically ill and neutropenic patients, and retain activity in hospitals where gentamicin resistance has spread. It is ototoxic. It is administered parenterally.

SPECTINOMYCIN
-aminocyclitol antibiotic that is structurally related to AMG; -it is used almost solely as an alternative treatment for drug resistant gonorrhoea or gonorrheae in penicillin allergic patients.

ANTITUBERCULAR DRUGS

TBC: a chronic disease caused by Mycobacterium tuberculosis. Its chronicity is due to:

-the intracellular location of mycobacteria; -the slow rate of multiplication of the germ; -the resistance develops quickly ; -there are atypical forms of Koch bacillus, which have a low susceptibility to drugs.

Classification of antitubercular drugs:

I: MAJOR / FIRST LINE ANTI TBC DRUGS: -they are very active; -they have the greatest efficacy; -they are frequently used. Streptomycin (S), Isoniazid (H), Rifampin (R), Ethambutol (E), Pyrazinamide (Z). II. MINOR / SECOND LINE DRUGS: -they are less efficacious; -they are less used; -they are more toxic. -they are used only when first line antitubercular drugs are ineffective (BK is resistant) or are contraindicated. Ethionamide, Paraaminosalicyloc acid, cycloserine, capreomycine, ciprofloxacin, ofloxacin, kanamycin, amikacin, clarithromycin.

I. MAJOR / FIRST LINE ANTI TBC DRUGS:

a)Isoniazide(isonicotinic acid hydrazide, H) It is the hydrazide of isonicotinic acid. It is a synthetic compound, strucurally related to vitamine B6 (pyridoxine). Mechanism of action: inhibition of synthesis of mycolic acids which is the unique fatty acid component of mycobacterial cell wall.

Pharmacokinetics: It is completely absorbed orally and penetrates all body tissues, tubercular cavities, placenta and meninges. It enters intracellularly. It is extensively metabolized in the liver by acetylation and metabolites are excreted in the urine. The rate of acetylation shows genetic variation: there are either fast acetylators and slow acetylators. Importance: some adverse effects are more common in slow acetylators (e.g. peripheral neuritis).

Clinical uses: *it is an essential component of all antitubercular regimens, unless the patient is not able to tolerate it or bacilli are resistant. It is indicated in all types of TBC (pulmonary and extrapulmonary), only in combination with other antitubercular drugs. Exception: when used in prophylaxis of TBC, when it is used alone. Usual dose: 5 mg/kg/ day (300mg /day, for an adult), once daily or 10 mg/kg/day, 3 days from one week. It is available as tablets.

Adverse effects: -hepatotoxicity ; -peripheral neuritis (paresthesias) and a variety of neurological manifestations (euphoria, mental disturbances, rarely convulsions) dose-dependent toxic effects. These are due to interference with utilization of pyridoxine and its increased excretion in urine. Pyridoxine given prophylactically (10 mg/ day) prevents neurotoxicity.Izoniazide neurotoxicity is treated by pyridoxine 100 mg/day.

b)Rifampin (Rifampicin, R)

It is a semisynthetic derivative of rifamycin B obtained from Streptomyces mediterranei. It is bactericidal to mycobacterium tuberculosis and many other gram + and bacteria like staph. aureus, N. Meningitidis, H. Infl., E.coli, Klebsiella, Pseudomonas, Proteus, legionella, Mycobacterium leprae.

Mechanism of action: Rifampin inhibits DNA dependent RNA synthesis. It enters intracellularly. Clinical uses: - treatment of tuberculosis only in association with other drugs; usual dose: 10 mg/kg/day, or 600 mg/day, daily; it is available as capsules, tablets. -other clinical uses: leprosy, prophylaxis of meningococcal and H. Infl. Meningitis and carrier state; treatment of serious staphylococcal infections (osteomyelitis etc.); brucellosis etc.

Adverse effects: -hepatotoxicity(hepatitis) ; -urine and secretions (tears, sweat, contact lenses) may become orange-red; - flu-like syndrome with chills, fever, headache, malaise and bone pain; -it is an enzymatic inducer enhances its own metabolism, as well as that of many drugs including warfarin, oral contraceptives, corticosteroids etc. - cutaneous syndrome flushing, pruritus, rash (specially on face and scalp), redness and watering of eyes. -"abdominal syndrome nausea, vomiting, abdominal cramps with or without diarrhoea.

c) Ethambutol (E)
It is a synthetic compound. It is selectively tuberculostatic. It is distributed widely but penetrates meninges incompletely and is temporarily stored in red blood cells. Clinical uses: TBC in association with other antitubercular drugs ; usual dose: 15-20 mg/kg/day, daily, or 1000 mg / day, daily.It is available as tablets. Adverse effects: -optic neuritis with loss of visual acuity / colour vision (it is reversible); ophthalmologic control is obligatory before, during and after treatment with ethambutol; -nausea, rashes, fever, are infrequent.

d) Streptomycin(S) It is an aminoglycoside. It is tuberculocidal but less effective than isoniazid or rifampin. It acts only on extracellular bacilli. It penetrates tubercular cavities, but does not cross to the CSF and has poor action in acidic medium. Resistance developed rapidly when S was used alone in tuberculosis. It is used only in combination with other drugs. Adverse effects: vestibulotoxic; pain at the site of i.m. injection. Usual dose: 15 mg/kg/day, daily(1000 mg/day), i.m.

e) Pyrazinamide(Z)
It is chemically similar to isoniazid. It is weakly tuberculocidal but more active in acidic medium. Clinical uses: TBC in association. It is highly effective during the first 2 months of therapy when inflammatory changes are present. It is highly lethal to intracellularly located bacilli as well as to those at sites showing an inflammatory response (pH is acidic at both of these locations). Usual dose: 25-30 mg/kg/day, daily (1000 mg/day).It is available as tablets. Adverse effects: -hepatotoxicity; -hyperuricemia is due to inhibition of uric acid secretion in kidney; gout can occur. -rashes, fever, arthralgias etc.

II. MINOR / SECOND LINE DRUGS

a) Ethioamide(Etm)
- moderate efficay;it is seldom used (only in case of resistance to better tolerated drugs); resistance develops rapidly. -it acts on both intra- and extracellular bacteria. -atypical mycobacteria are sensitive; Adverse effects: -anorexia, nausea, abdominal upset, vomiting; -aches, pains, rashes; -hepatitis;-peripherasl or optic neuritis, mental disturbances.

b) Para-amino salicylic acid(PAS) -PAS is tuberculostatic and one of the least active drugs; -patient acceptability of PAS is poor because of frequent anorexia, nausea and epigastric pain.

c) Cycloserine(Cys)
-it is an antibiotic obtained from Streptomyces orchidaceus; it inhibits bacterial cell wall synthesis; -it is tuberculostatic and inhibits some other gr+ bacteria, E. Coli, Chlamydia also; Adverse effects: -CNS toxicity:sleepiness, headache, tremor and psychosis; convulsions may be prevented by pyridoxine 100 mg/day; It is rarely used only in resistant cases.

d) Amikacin, Kanamycin, Capreomycin -reserve drugs in rare cases not responding to the usual therapy, or infection by atypical mycobacteria.They are toxic antibiotics (otoand nephrotoxicity).

*Newer drugs e) *Ciprofloxacin, Ofloxacin, Moxifloxacin, Spartfloxacin= fluorchinolones They are used in multidrog resistant tuberculosis and mycobacterium avium complex infection in HIV patients. f)*Clarithromycin, azithromycin macrolides active against mycobacterium avium complex and other atypical mycobacteria.

TREATMENT OF TUBERCULOSIS
The treatment is followed under the Revised national tuberculosis controll programme.It is a long term therapy. General principles: -drug combinations are used (a combination of two or more drugs must be used) to reduce the incidence of resistance; -conventional regimens are used: duration of the treatment is 68 months with: -an initial intensive phase lasting 2-3 months, with daily administration of drug combinations (4-5 antitubercular drugs), - it is followed by a continuation phase lasting 4-6 months, when 2 antitubercular drugs are given, thrice weekly ; -sputum examintion.

Chemoprophylaxis:
It is indicated in: -contact with active TBC; -neonate of tubercular mother; -patients with old inactive disease who are assessed to have received inadequate therapy; -children with a TB patient in the family; -patients of leukemia, diabetes, silicosis, or those who are HIV positive, or are on corticosteroid therapy. The drug generally used has been isoniazid 300 mg, daily for 6-12 months. Now because of high incidence of resistance, a combination of isoniazid (5 mg/kg)+rifampin (10 mg/ kg) given for 6 months is preferred.

TREATMENT OF LEPROSY

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae ; primarily affecting skin , mucous membranes and nerves.It is more prevalent among the lowest socio-economic strata.

CLASSIFICATION OF DRUGS USED IN LEPROSY:

1)Sulfone: DAPSONE 2)Phenazine derivatives: CLOFAZIMINE 3)Antitubercular drugs: RIFAMPIN, ETHIONAMIDE 4)Other antibiotics: OFLOXACINE, CLARITHROMYCIN, MINOCYCLINE.

DAPSONE
It is diamino diphenylsulfone , the simplest ,oldest, cheapest, most active and most commonly used member of its class. All other sulfones are converted in the body to dapsone. Mechanism of action : -dapsone is chemically related to sulfonamides and has the same mechanism of action , i.e. inhibition of PABA incorporation into folic acid; its antibacterial action is antagonized by PABA. - It is leprostatic at low concentrations and arrests the growth of many other bacteria sensitive to sulfonamides. Doses of dapsone needed for the treatment of acute infections are too toxic , so not used.

Resistance to dapsone: *it may be primary in untreated patients , i.e. they have acquired infection from a patient harbouring resistant bacilli or * secondary which develops during therapy in an individual patient with a single drug.

Pharmacokinetics: Dapsone is completely absorbed after oral administration and is widely distributed in the body though penetration is CSF is poor. It is 70% plasma protein bound , but more importantly concentrated in skin ( specialy lepromatous skin) , muscle, liver and kidney.It is metabolized in the liver ; metabolites are excreted in bile and reabsorbed from intestine and finally they are excretd in urine.The drug is cumulative due to retention in tissues and enterohepatic circulation. Elimination takes 1-2 weeks or longer.

Adverse effects: -well tolerated at doses of 100 mg/day or less; -gastric intolerance in the beginning ; it decreases later; -mild haemolytic anemia is comon( dose related toxicity);patients with glucoso-6-PD deficiency are more susceptible; -cutaneous reactions: allergic rashes, drug eruption, phototoxicity etc. -lepra reaction ( it is a Jarish Herxheimer type of reaction due to release of antigens from the killed bacilli; it may be mild, severe or life threatening erythema nodosum leprosum).

CLOFAZIMINE

-it is a substance with leprostatic and antiinflammatory properties; -it acts by interfering with function of DNA; -when used alone resistance develops in 1-3 years; -it is administered orally ; it is well distributed in many tissues but entry in CSF is poor.

Adverse effects: in usual doses it is well tolerated; *skin: reddish black discolouration of skin, especially on exposed parts;discolouration of hair and body secretions may also occur; *gastrointestinal symptoms: enteritis with nausea, abdominal pain, anorexia , weight loss particularly when higher doses are used to control lepra reaction; *clofazimine should be avoided during early pregnancy and in patients with liver or kidney damage.

RIFAMPIN
-bactericidal to M. Leprae; -upto 99.99% M. Leprae are killed in 3-7 days; -however, it is not satisfactory if used alone resistance develops. -it has been included in the multidrug therapy of leprosy and shortens duration of treatment. -600 mg once a month.

ETHIONAMIDE
-it has significant antileprotic activity but causes hepatotoxicity; -it should be used ( 250 mg / day) only when absolutely necessary.

OTHER ANTIBIOTICS:
OFLOXACIN: -over 99.99% bacilli were found to be killed by 22 daily doses of ofloxacin monotherapy; -however, it is not included in the standard treatment protocols but can be used in alternative regimens in case rifampin cannot be used or to shorten the duration of treatment. -dose: 400 mg/day.
OFLOXACIN, PEFLOXACIN, SPARTFLOXACIN - are highly active against M. Leprae

MINOCYCLIN:
-its antibacterial activity is much less than that of rifampin but greater than that of clarithromycin; -in doses of 100 mg/day it may be used in alternative multidrug therapy of leprosy.

CLARITHROMYCIN:
-it is the only macrolide antibiotic with significant activity against M. Leprae; -however, it is less bactericidal than rifampin; -monotherapy with clarithromycin 500 mg daily causes 99.9% bacterial killing in 8 weeks; -it is being included in alternative multidrug therapy of leprosy.

TREATMENT OF LEPROSY
-conventionally , all forms of leprosy had been treated with dapsone alone ( monotherapy), 100-200 mg daily , 5 days a week, duration of treatment depending on the type ( 5-12 years or life long) ; monotherapy is no longer used because of emergence of resistance; -to deal with dapsone resistant strains of M.leprae and the problem of microbial persisters ( dormant forms) ,multidrug therapy with dapsone, rifampin and clofazimine was introduced in 1981.Multidrug therapy is the regimen of choice for all cases of leprosy.

-alternative regimens incorporating newer antileprotic drugs are now investigated ; these should be used only in cases of rifampin resistance or when it is impossible to employ the standard multidrug therapy.Some altrenative regimens are : * clofazimine 50 mg+ ofloxacine 400 mg/ minocycline 100 mg/ clarithromycin 500 mg , daily for 6 months followed by clofazimine 50 mg+ ofloxacine 400 mg/ minocycline 100 mg daily for additional 18 months. *in some cases having few bacteria in the body and only one skin lesion : a single dose of rifampin 600 mg +ofloxacin 400 mg+ minocycline 100 mg. Many other shorter regimens are under evaluation.