Linc Osami Des

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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 isgood ) but most often is administeredparenterally (i.v.) because pseudomembranouscolitis is less likely to follow parenteraladministration.

It penetrates to most skeletal and soft tissues,but not brain and cerebrospinal fluid;

accumulates in neutrophils and macrophages.It islargely metabolized and metabolites are excretedin 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 generallycombined with an aminoglycoside or cephalosporin;

-topical preparations of clindamycin are used to treat infectedacne vulgaris.

-clindamycin, sometimes in combination with anaminoglycoside or cephalosporin is used to treatpenetrating 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 whoare undergoing certain dental procedures.

-in AIDS patients (in combination with other drugs) fortoxoplasmosis and Pneumocystis carinii pneumonia.



Side effects:

-rashes, urticaria;-abdominal pain;

-the major problem is diarrhoea andpseudomembranous 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.



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 onpseudomonas, 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 topicallythey 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 gramnegative 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 ulcer-caused 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 thegastrointestinal 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 fromvarious Streptomyces species.



Common characteristics:

*they are all structurallyrelated : hexose ring to

which variousaminosugars(two or more)

are attached by glycosidiclinkages.



*they are all

structurally

related :

hexose ring towhich 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 excretedunchanged in urine by glomerular filtration.

*all are active primarily against aerobic gramnegative 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 bybinding to 30S ribosomal subunit, or toadditional sites on 50 S subunit as well asto 30S-50 S interface.

Recent experimental studies showthat the initial site of action is the outerbacterial membrane .The cationic

antibiotic molecules create fissures inthe outer cell membrane resulting inleakage of intracelullar contents andenhanced antibiotic uptake.



*The aminoglycosides produce toxic effects whichare common to all members, but the relativepropensity differs.All exhibit:

*ototoxicity: cochlear and vestibulardamages of VIIIth cranial nerve, with hearing loss,respectivelly with headache, nausea, vomiting,dizziness, nystagmus, vertigo, ataxia.

* nephrotoxicity: it manifests as tubulardamage.

* neuromuscular blockade.

* Resistance occurs rapidly ( inactivation bytransferase enzymes, impaired entry of aminoglycosides into the cell, alteration of protein receptor on the ribosome)



The most important aminoglycosides:

• AMIKACIN *APRAMYCIN

• ARBEKACIN *RHODOSTREPTOMYCIN

• GENTAMICIN

•

KANAMYCIN SPECTINOMYCIN-chemically related to AMG

• NEOMYCIN

• PAROMOMYCIN

• STREPTOMYCIN

• TOBRAMYCIN



STREPTOMYCIN -obtained from streptomyces

griseus.

-Antimicrobial activity:relatively narrow: only few strainsof E.coli, H. Infl., Klebsiella, Shigella, V. Cholerae,enterococci and some gram positive cocci are nowinhibited that too at higher concentrations.

Sensitive germs are: Brucella, Yersinia pestis,

Mycobacterium tuberculosis, Nocardia, Francisellatularensis.

Resistance: many organisms develop rapid resistance tostreptomycin.Eg: in the intestinal and urinary tractsresistant organisms may emerge within 2 days of therapy. E.coli, H. Infl., Str. Pneumoniae, staph. Aureushave become largely resistant. If it is used alone,Mycobacterium tuberculosis also become resistant.



Clinical uses:

-tuberculosis (in combination with other drugs becauseresistance emerges rapidly);

-subacute bacterial endocarditis (caused by streptococciviridans 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:



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 calculatedaccording to body weight and level of renal function.

The daily dose of gentamicin (and otheraminoglycosides) should be reduced in patients withimpaired renal function according to measuredcreatinine clearance.

For an average adult with normal renal function 3-5 mg/ kg/ day, i.m., either as single dose or divided inthree 8 hourly doses is recommended. Parenteralgentamicin is available as vials: 20, 60, 80, 240 mg per

vial.For topical use: 0,3 % eye / ear drops, 0,1 %skin

cream.



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 3-5mg/kg in 1-3 doses.



AMIKACIN

It has the widest spectrum of activity, includingmany organisms resistant to other aminoglycosides(because it is resistant to bacterial aminoglycosideinactivating enzymes). However, relatively higherdoses are needed for pseudomonas, proteus andstaph. infections.

It is recommneded as a reserve drug for hospitalacquired gram negative bacillary infections wheregentamicin or tobramycin resistance is high.

More hearing loss than vestibular disturbanceoccurs in toxicity.

It is administered parenterally.

NEOMYCIN



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 poorlyabsorbed from the gastrointestinal tract.Oral and topicaladministration does not ordinarily cause systemic toxicity.

Clinical uses:

-topically (often in combination with polymyxin, bacitracin,glucocorticosteroids) for infected wounds, ulcers, burn, external earinfections, conjunctivitis ;

-orally for:

-preparation of bowel before surgery: may reducepostoperative 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 purposeand 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 gutflora, 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 10.000IU+hydrocortisone 10 mg / ml ear drops.



NETILMICIN

It has a broader spectrum of activity thangentamycin. It is relatively resistant toaminoglycoside inactivating enzymes and thuseffective 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 neutropenicpatients, 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 byMycobacterium tuberculosis.

It’s chronicity is due to:

-the intracellular location of mycobacteria;

-the slow rate of multiplication of thegerm;

-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 areineffective (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 andmeninges. It enters intracellularly. It is

extensively metabolized in the liver by

acetylation and metabolites are excreted inthe 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 totolerate it or bacilli are resistant.

• It is indicated in all types of TBC (pulmonary andextrapulmonary), 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 anadult), once daily or 10 mg/kg/day, 3 days fromone week. It is available as tablets.



Adverse effects:

-hepatotoxicity ;

-peripheral neuritis (paresthesias) and a varietyof neurological manifestations (euphoria,mental disturbances, rarely convulsions) – dose-dependent toxic effects.

These are due to interference with utilizationof pyridoxine and its increased excretion inurine. Pyridoxine given prophylactically (10

mg/ day) prevents neurotoxicity.Izoniazideneurotoxicity is treated by pyridoxine 100mg/day.



b)Rifampin (Rifampicin, R)

It is a semisynthetic derivative of

rifamycin B obtained from Streptomycesmediterranei.

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) maybecome 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 includingwarfarin, oral contraceptives, corticosteroids etc.

-„ cutaneous syndrome” –flushing, pruritus, rash(specially on face and scalp), redness and watering of eyes.

-"abdominal syndrome” –

nausea, vomiting, abdominalcramps with or without diarrhoea.



c) Ethambutol (E) It is a synthetic compound. It is selectively

tuberculostatic.

It is distributed widely but penetrates meningesincompletely and is temporarily stored in red bloodcells.

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 (itis reversible); ophthalmologic control is obligatorybefore, during and after treatment with ethambutol;

-nausea, rashes, fever, are infrequent.



d) Streptomycin(S)

It is an aminoglycoside.

It is tuberculocidal but less effective thanisoniazid or rifampin.

It acts only on extracellular bacilli.

It penetrates tubercular cavities, but does

not cross to the CSF and has poor action in acidicmedium. Resistance developed rapidly when Swas used alone in tuberculosis. It is used only incombination with other drugs.

Adverse effects: vestibulotoxic; pain at thesite of i.m. injection. Usual dose: 15 mg/kg/day,daily(1000 mg/day), i.m.

) P i id (Z)



e) Pyrazinamide(Z) It is chemically similar to isoniazid. It is weaklytuberculocidal but more active in acidic medium.

Clinical uses: TBC in association. It is highly effective duringthe first 2 months of therapy when inflammatory changesare present. It is highly lethal to intracellularly locatedbacilli as well as to those at sites showing an inflammatoryresponse (pH is acidic at both of these locations).

Usual dose: 25-30 mg/kg/day, daily (1000 mg/day).It isavailable 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



II. MINOR / SECOND LINE DRUGS

a) Ethioamide(Etm) - moderate efficay;it is seldom used (only in case of

resistance to better tolerated drugs); resistancedevelops 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 100mg/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 (oto-and nephrotoxicity).



*Newer drugs

e) *Ciprofloxacin, Ofloxacin, Moxifloxacin,Spartfloxacin= fluorchinolones

• They are used in multidrog resistanttuberculosis and mycobacterium aviumcomplex infection in HIV patients.

f)*Clarithromycin, azithromycin –

macrolidesactive against mycobacterium avium complexand other atypical mycobacteria.

TREATMENT OF TUBERCULOSIS



TREATMENT OF TUBERCULOSIS

The treatment is followed under the Revised nationaltuberculosis 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 6-

8 months with:

-an initial intensive phase lasting 2-3 months, with dailyadministration 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 HIVpositive, 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 thelowest socio-economic strata.

CLASSIFICATION OF DRUGS USED IN



CLASSIFICATION OF DRUGS USED IN

LEPROSY:

1)Sulfone: DAPSONE

2)Phenazine derivatives: CLOFAZIMINE

3)Antitubercular drugs: RIFAMPIN,

ETHIONAMIDE

4)Other antibiotics: OFLOXACINE,

CLARITHROMYCIN, MINOCYCLINE.



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 oraladministration and is widely distributed in the bodythough penetration is CSF is poor. It is 70% plasma

protein bound , but more importantly concentrated inskin ( specialy lepromatous skin) , muscle, liver andkidney.It is metabolized in the liver ; metabolites areexcreted in bile and reabsorbed from intestine and

finally they are excretd in urine.The drug is cumulativedue to retention in tissues and enterohepaticcirculation. Elimination takes 1-2 weeks or longer.

Adverse effects:



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 deficiencyare more susceptible;

-cutaneous reactions: allergic rashes, drugeruption, 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 lifethreatening –erythema nodosum leprosum).

CLOFAZIMINE



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 hairand body secretions may also occur;

*gastrointestinal symptoms: enteritis withnausea, abdominal pain, anorexia , weight lossparticularly when higher doses are used tocontrol lepra reaction;

*clofazimine should be avoided during earlypregnancy and in patients with liver or kidneydamage.

RIFAMPIN



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



ETHIONAMIDE

-it has significant antileprotic activity but causes

hepatotoxicity;

-it should be used ( 250 mg / day) only when

absolutely necessary.

OTHER ANTIBIOTICS:



OTHER ANTIBIOTICS:OFLOXACIN, PEFLOXACIN, SPARTFLOXACIN

- are highly active against M. Leprae

OFLOXACIN:

-over 99.99% bacilli were found to be killed by22 daily doses of ofloxacin monotherapy;

-however, it is not included in the standardtreatment protocols but can be used inalternative regimens in case rifampin cannotbe used or to shorten the duration of treatment.

-dose: 400 mg/day.

MINOCYCLIN:



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 inalternative multidrug therapy of leprosy.

CLARITHROMYCIN:



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.





-conventionally , all forms of leprosy had been treatedwith dapsone alone ( monotherapy), 100-200 mg daily, 5 days a week, duration of treatment depending onthe 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 therapyis the regimen of choice for all cases of leprosy.

-alternative regimens incorporating newer antileprotic



alternative regimens incorporating newer antileproticdrugs are now investigated ; these should be used onlyin cases of rifampin resistance or when it is impossible

to employ the standard multidrug therapy.Somealtrenative regimens are :

* clofazimine 50 mg+ ofloxacine 400 mg/minocycline 100 mg/ clarithromycin 500 mg , daily for

6 months followed by clofazimine 50 mg+ ofloxacine400 mg/ minocycline 100 mg daily for additional 18months.

*in some cases having few bacteria in the body

and only one skin lesion : a single dose of rifampin 600mg +ofloxacin 400 mg+ minocycline 100 mg.

Many other shorter regimens are under evaluation.

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