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CONTENTS Introduction Endodontic microbiology Systemic chemotherapeutics Indications of antibiotic therapy Principles of antibiotic therapy Individual antibiotics Problems

roblems associated with antibiotics Antibiotic prophyla is Antibiotics for local use !isinfection of pulp spaces Irrigants Intracanal disinfectant materials Antimicrobial activity of root canal filling materials Antimicrobial activity of sealers Conclusion "eferences INT"O!#CTION Endodontic treatment is essentially directed towards the prevention and control of pulpal and periradicular infections$ The central role of microorganisms in such infections is well established$ Total elimination of these bacteria is difficult to accomplish by mechanical debridement alone$ Thus the treatment triad of mechanical cleaning% chemical disinfection and antimicrobial dressing is aimed at producing canals that are clean and free from infection$

EN!O!ONTIC &IC"O'IO(O)* Endodontic infections are polymicrobial$ +ast ma,ority of bacteria isolated are ANAE"O'IC$ The anaerobic bacteria that constitute endodontic infections areObligate Anaerobes . /0 . /12% 3acultative Anaerobes 4 15 . 1/2$ Anaerobic 'acteria causing endodontic infections can be grouped into% )ram Positive "ods Actinomyces sp$% (actobacillus sp% Eubacterium sp$ )ram Positive Cocci Peptostreptococcus sp$% Streptococcus sp$% Staphylococcus sp$ )ram Negative "ods 'acteroides sp$% 3usobacterium sp$% Campylobacter% Prevotella sp$% Porphyromonas sp$

Obligate anaerobes are easily eradicated during root canal treatment$ 3acultative bacteria li6e nonmutans streptococci% enterococci and lactobaccili survive chemomechanical preparation$

&IC"OO")ANIS&S ISO(ATE! 3"O& "E3"ACTO"* APICA( PE"IO!ONTITIS E$faecalis Actinomyces sp.A$israelli Candida sp.C$albicans Propionibacterium sp Peptostreptococcus Streptococcus sp Staphylococcus sp +eillonella sp 3#N)I IN EN!O!ONTIC IN3ECTIONS Candida albicans4dentinophilic organism C$glabrata C$guillermondii C$inconspicua )eotrichium candidum Invasion of fungi into dentinal tubules protect it from intracanal procedures$ Availability of Ca ions help in growth and adhesion$ +I"#SES IN PE"IAPICA( PAT7OSIS 7erpes +irus . 7uman cytomegalo virus Epstein 'arr virus 3I+ 4 3eline immunodeficiency virus (OCA( ANTI &IC"O'IA( A)ENTS 8$ &echanical instrumentation of the root canal system !uring pulpectomy and instrumentation% there is a gross removal of

microbes$ Subse9uent studies have shown that some microbes may remain behind in dentinal tubules$ 7owever% if the root canal is well obturated% these microbes usually die or remain dormant$ :$ Irrigation In vital cases% sodium hypochlorite at high concentrations is not advocated% because it is a pulp tissue solvent and could irritate tissue in lateral canals$ In vitro findings have shown that ;$:;2 sodium hypochlorite <usual clinical concentration= is more destructive to vital tissues than to microbes whereas 0$;2 sodium hypochlorite dissolves necrotic tissue but not vital tissue$ 7ence% a 0$;2 to 8$02 concentration of sodium hypochlorite is recommended for vital cases$ In necrotic cases% where there is a probability of dead tissue in lateral and accessory canals% irrigation with higher concentrations of sodium hypochlorite% which is a good necrotic tissue solvent% is suggested% it is also recommended in those type of cases because of its antimicrobial effect$ One study reported that 0$;2 sodium hypochlorite was more effective than saline as an antimicrobial agent$ 7owever% it did show that instrumentation and irrigation with saline could temporarily render root canals sterile ;02 of the time$ They also found no significant antimicrobial difference between 0$;2 and ;$02 sodium hypochlorite$ These same investigators also reported that the combined use of E!TA and ;$02 sodium hypochlorite was the most effective antimicrobially$ It has also been shown that ultrasonics along with sodium hypochlorite irrigation increased the effectiveness of the irrigant in debris removal$ Cavitation% which occurs from ultrasonic therapy% can destroy bacteria$ Care must be ta6en that no sodium hypochlorite solution is forcibly e pressed beyond the apical foramen% because pain and swelling will result$ 7ydrogen pero ide <12= alone and in combination with sodium hypochlorite

<;2= has also been used effectively for irrigation$ 7owever% forceful e pression of hydrogen pero ide can result in pain and emphysema$ One study has shown that the combination techni9ue is no more effective than sodium hypochlorite used alone$ It was also found that a combination of )ly.O ide <802 urea pero ide in an anhydrous glycerol base= and ;$:;2 sodium hypochlorite was no more effective than the hypochlorite alone in destroying 'acteroides melaninogenicus$ Saline was totally ineffective against this species$ Investigators also found that ;$:;2 sodium hypochlorite was the most effective irrigant against 'acteroides melaninogenicus$ )rossman has stated that merely opening the tooth and introducing atmospheric o ygen is sufficient to destroy obligate anaerobes> however% 3oley et al$ found that atmospheric o ygen was totally ineffective against 'acteroides melaninogenius$ ?hen properly used% ;$:;2 sodium hypochlorite causes no more pain that does saline and is the most effective irrigant for chemical.mechanical removal of pulpal and dentinal debris$ In support of this% others found that sodium hypochlorite effectively deto ified bacterial endoto ins$ Chlorhe idine has been investigated as an antibacterial root canal irrigant$ Although it was must more effective than saline% it was less effective than :$;2 sodium hypochlorite$ Considering all the evidence% it appears that sodium hypochlorite is the irrigant of choice but the optimum concentration has not yet been definitely established$ 1$ Intracanal medication In pulpless cases the main use of a medicament is to help destroy microbes> it may also be used for anodyne effect and for fluid removal$ Although periapical healing may be faster after the use of polyantibiotic root canal paste% results of a controlled study showed no difference in healing between cases treated with polyantibiotics and those treated with nonspecific

intracanal medications$ 5$ Obturation Some cements <e$g$% paraformaldehyde.containing pastes= have antimicrobial effects% but tissue destruction usually results as well$ Silver cones and amalgam are supposed to have an oligodynamic effect <antimicrobial action from the heavy metal ions=$ In these also% tissue destruction may result$ The obturation process itself can cause entrapment of microbes$ A recent study showed that these microbes die following obturation$ ;$ Periodontal curettage There are cases of the endodontic.periodontal syndrome in which open lateral canals or dentinal tubules feed microbes and their products into the pulp$ Apparently periodontal therapy% including curettage and surgical procedures% can decrease the ingress of these microbes into the pulp$ ANTI'IOTICS<ANTI&IC"O'IA(S= 3O" EN!O!ONTIC IN3ECTIONSIdeally susceptibility testing would be done when antibiotics are indicated$ however% because it may ta6e from several days to wee6s to do testing on strict anaerobes% empiric prescription of antibiotics is done$ Empiric prescription of antibiotics is based on past 6nowledge of the organisms most li6ely associated with endodontic infections$ Clinicians should inform the patients of the benefits% ris6s% side effects% and problems if the proper dosing schedule is not followed$ The prudent use of antibiotics to treat endodontic infections is an integral part of appropriate treatment$ In general an antibiotic should be ta6en for : to 1 days after resolution of the ma,or clinical signs and symptoms$ Thus

the typical regimen to treat an endodontic infection is from / to 80 days on an around.the.cloc6 schedule$ Improvement should be seen in :5 to 5@ hours after initial treatment and initiation of the prescription$ A high.dose regimen for a Short time is preferred to a low dose for a longer time$ the latter is much more li6ely to select for resistant organisms$ A loading dose is generally recommended to provide an initial effective serum level that is then followed by the maintenance dose$ ANTI'IOTICS 3O" &E!ICA((* CO&P"O&ISE! PATIENTS The American 7eart Association <A7A= has updated their guidelines for prophylactic antibiotic coverage for medically compromised patients$ The incidence of bacteremia is low for nonsurgical root canal therapy% but microorganisms can be e truded past the root ape $ A recent populationbased study concluded that dental treatments% in general% did not seem to be a ris6 factor for infective endocarditis$ If more studies support these findings% future consideration should be given to down.grading antibiotic prophyla is for most dental procedures% e cept for tooth e tractions and gingival surgery$ The A7A recommends antibiotic endocarditis prophyla is for root canal instrumentation or surgery beyond the root ape and for intraligamentaty local anesthetic in,ections$ Endocarditis prophyla is in not recommended for nonintraligamentatylocal anesthetic in,ections% rubber dam placement% or the ta6ing of radiographs$

$ )"A& POSITI+E 'ACTE"IAOf all the bacteria present in oral cavity% streptococci constitute the single largest group% most of the species produce greenish haemolysis around the colonies on blood agar and are% hence% collectively designated as viridance

streptococci$ Streptococci mutans has been shown to be the most important organism to initiate dental caries$ This capability is because of its ability to ferment sucrose to lactic acid and survive in the low ph which is re9uired for demineralisation of the pellicle coated enamel surface$ These properties help s$mutans in attaching to% and accumulating on tooth surface in the pla9ues$ (actobacilli are widely present in the human body and fre9uently found in oral cavity% intestinal tracts$ On an average% in the saliva of an adult man the lactobacilli count is A0%OOOBml$ (actobacilli promote the progression of dental caries which was initiated by streptococcus mutans though lactobacilli constitute less than 82 of pla9ue flora they are important in pit and fissure caries primarily because of their aciduric nature$ NO"&A( )"A& POSITI+E 'ACTE"IA( O"A( 3(O"A COCCI Streptococc us s$faecalis s$sangius s$mitis s$mutans group s$milleri s$salivarius Peptostreptococcus &icrococcus Staphylococcus

'ACI((I (actobacillus I$acidophilus I$salivarius I$casei 8$plantarum I$fermentum I$cellobiosus 8$brevis Arachnia Propionobacterum Actinomyces Eubacterium Clostridium Corynebacterium )"A& NE)ATI+E 'ACTE"IA+eillonella are the most numerous of gram .ve bacteria and account for almost 802 of the cultivable flora of saliva and on the surface of tongue$ Anaerobic gram.ve bacilli constitute another important group$ These are bacteroides% fusobacterium% leptotrichia% wolinella and selenomonas$ &ore than 50 species of bacteroides have been identified of these the commonly seen are '$oralis% '$ gracilis% '$ Oris <pigmented species= and '$ gingivalis% '$ dentiocola% '$ intermedius <non.pigmented species= 3usobacterium nuc8eatum is isolated most commonly from the gingival crevices and subgingival pla9ues 7$

parainfluenCas and 7$ segnis and commonly found in oral cavity$ Spirochaetes and Treponemes are common inhabitants of gingival crevices and subgingival areas$ Normal )ram Negative 'acterial Oral 3lora Cocci +eillanella parvula Neisseria &ora ella 'acilli 7aemophilus Actinobacillus Capnocytophaga Selenomonas Centipeda Treponema 'acteroides 3usobacterium (eptotrichia ?olinella Pesudomonas &*COP(AS&ASThese are pleomorphic bacteria which do not posses rigid cell wall$ Species of &ycoplasma have been isolated from almost all the lesions of oral cavity such as dental pla9ue and calculus% inflamed pulp% diseased gingival cervices and periodontal poc6ets% &$ salivarium is apparently the predominant species$ &ycoplasmas isolated from human oral

cavity are &$pheumonie &$salivarium &$hominis &$lipophilum &$orale 3#N)I% P"OTODOA AN! +I"#SESApart from bacteria% the normal oral flora may also have fungi% protoCoa and viruses$ Candida albicans is the commonest fungus isolated from oral cavity$ This species has also been detected in high numbers in the subgingival flora or in the gingival tissues of acute periodontal abscesses% in periodontitis and in those lesions of peridontitis which are produced in immunologically compromised individuals or lesions resistant to conventional treatment$ 3#N)I% P"OTODOA AN! +I"#SES IN O"A( CA+IT* 3#N)I 4 Candida albicans% C$tropicalis% C$pseudotropicalis% Cryptococcus% Penicillium% )eotrichum% Aspergillus% 7emispora ProtoCoa. Entamoeba% gingicalis% Trichomonas tena +iruses.7erpes simple % Cytomegalovirus% 7epatitis ' virus%7I+%. +aricella Doster%Epsteinbarr virus%&umps virus%&easeles virus%InfluenCa virus

&icrobiology of EndodonticsThe basis of pulpal disease and the ultimate demise of the dental pulp is found in the science of microbiology$ Clinicians must recogniCe the cause and effect of bacterial

invasion of the pulp space> what occurs to bacteria when treatment ensures> and final conse9uences when treatment is completed$ "egardless of whether indigenous oral bacteria enter the pulp through dental caries% microlea6age% or a fracture of the root surfaces the pulp can be irreversibly 'eside hard tissue communication periodontal organisms are thought to enter pulp via lymphatics and haematogenous routes$ In a study using both aerobic and anaerobic techni9ues% &ac !onald and associates found a host of organisms in intact teeth with the necrotic pulp$ PAT7OP7*SIO(O)* O3 EN!O!ONTIC IN3ECTION!ental pulp is a uni9ue formative organ with limited capacity to withstand bacterial% mechanical and chemical factors$ The mechanism for regeneration of this tissue is inade9uate to meet the challenge posed by foreign elements$ Once bacteria gain access into the pulp% it is unusual for the host defence to completely $eliminate them$ As a result healing of infected pulp is uncommon$ Irreversible pulpitis leads to necrosis of tissue$ Necrosis can be brought about by any bacterium that is resident of oral cavity% nasopharyn or gastro intestinal tract$ P#(PA( !ISEASES AN! T7EI" 'ACTE"IO(O)* 8$ "eversible pulpitis'acteria from caries may be a cause under normalcircumstances the enamel and cementum act as arelatively impermeable barrier to bloc6 the patency of the dentinal tubules at !EE or !CE$ ?hen cariesinterrupt this natural barrier% the dentinal tubulesbecome bidirectionally patent$ !entinal fluid flows outward as a result of intrapulpal pressure <lOmm7g= and e ternal substances <bacteria and bacterialproducts= diffuse towards pulp <inward=$

:$ Irreversible pulpitis&icroorganism are present in the Cone of necrosis 1$ Necrosis of pulpCan be caused by any no ious insult in,urious tothe pulp such as bacteria$ 'acteriology- 7ere in a high percentage the rootcanal contains mi ed microbial flora both aerobicand anaerobic$ 5$ Acute periradicular diseaseImmediate cause is invasion of dead pulp tissue$'acteriology- In an abscess% concentration ofmicro organisms is usually large$Streptococci and staphylococci are generallyrecovered% but if purulent material is collected as itdrains out of the root canal it may be sterilebecause it consists of dead leu6ocytes and deadbacteria$ ;$ Acute apical periodontitisOne cause is infection through root canal$ 'acteriology- 'acteria or to ic bacteria presentapical foramen and irritate periodontal tissues$ /$ Phoeni abscess'ecause of bacteria and their to ins these can havean inflammatory response$ 'acteriology- An abscess usually forms as a resultof microbial infection% although some abscessescalled sterile abscess form in absence of bacteria$ A$ Chronic alveolar abscessIt is a longstanding low grade infection ofperiradicular alveolar bone source of infection Inroot canal$ 'acteriology- Commonly recovered forma pulplesstooth with a chronic abscess are a haemolyticstreptococci of low virulence$

@$ )ranulomaA dental granuloma is growth of granulomatoustissue continuous with periodontal ligamentresulting from death of the pulp and diffusion ofbacteria and bacterial to ins from the root canalinto the surrounding periradicular tissues through the apical and lateral foramina$ 'acteriology- The periapical tissue is sterile inmost cases% even though microorganisms may bepresent in the root canal$ F$ "adicular cystA radicular cyst presupposes physical% chemical orbacterial in,ury resulting in the death of the pulp%followed by stimulation of epithelial rests ofmalasseC$ 'acteriology- A cyst mayor may not be infectedActinomyces organisms have been isolated from aperiapical cyst$ !*NA&ICS O3 &IC"O O")ANIS&SSome bacterial strains isolated from the pulp space have features that may complicate the diseases process and its treatment$ Some are refractory to antibacterial agents$ Eg'acteriodes fragilis% pseudomonas aeruginosa% staphylococcus aureus and streptococcus faecalis$ Some may synthesiCe products that can change the e9uilibrium of the infection process in favour of the invading microorganism with such products as to ins% capsules% metabolic irritants and e tracellular enCymes that degrade tissue or in activate antibiotics$ Some may establish infections at sites distant to the tooth by e tensions into fascial planes and or the development of bacteremia$

A$ IN+ASI+ENESSAntiphagocytic surface substances <capsules= protect bacteria against phagocytic ingestion by changing the bacterial surface topography$ Capsules are produced by some species in the serum$ Encapsulated bacteria cannot be efficiently engulfed by phagocytes in tissues having smooth surfaces or large amount of fluids$ Capsules maybe found on some microbes isolated from the pulp% including streptococcus% bacteroids and fusiformis$ ?hen rate of phagocytosis e ceeds rate of multiplication of the bacteria% healing and repair are li6ely to ensue$ '$ &etabolic adaptation of bacteria to its environment needs the presence of enCymes that can utiliCe the environment for growth and reproduction$ Environmental factors- O ygen is lethal to some bacteria that are unable to cope with some of the metabolic products formed in its presence$ Two substances in particular supero ide radical and hydrogen pero ide are formed with the transfer of one or two electrons to o ygen$ These two substances react with water to form the hydro yl radical <.O"=$ All these substances are damaging to the cells through reactions with lipids% nucleic acids and proteins$ Three enCymes produced by o ygen tolerant bacteria are able to destroy the to ic substances$ They are catalase% supero ide dismutase and pero idases$ !ue to the presence or absence of any of the above enCymes bacteria can be classified as-

A$ Obligate aerobesThey re9uire 0: for growth$ Organisms in this posses catalase and supero ide dismutase$ Eg- Tubercle bacillus% pseudomonas '$ 3acultative anaerobesThese organisms grow in the presence or absence of o ygen and produce both catalase and supero ide dismutase$ Eg- Enteric bacteria% staphylococcus C$ &icro aerophilicThey grow in 0: environment% but derive their energy only from fermentation pathways that occur in the absence of 0:$ They contain super o ide dismutase lac6s catalase$ Eg- (actic acid bacteria% streptococci$ !$ Obligate anaerobesThese bacteria grow only in the absence of O:% but vary in their sensitivity to it$ These organisms lac6 both catalase and supero ide dismutase$ Eg-bacteroides% fuso bacterium$ 'ACTE"IA( P"OPA)ATIONAs a carious or periodontal lesion ages the relative number of obligate anaerobes increases at the e pense of aerobic bacteria$ Obligate anaerobes are prevented form growing in an o ygen environment due to supero yl radicals and 7:0:$ 'oth these molecules are produced in the :; &E!IATO"S O3 PE"IAPICA( 'ONE !EST"#CTION-

PAT7O)ENICIT* O3 EN!O!ONTIC 3(O"A Interactions with other micro.organisms in the root canal% to develop synergistically beneficial partners> Ability to interfere with and evade host defenses> Action of virulence factors INTE"ACTIONS ?IT7 OT7E" &IC"O.O")ANIS&S &icrobial interactions that influence the ecology of the endodontic flora may be positive <synergistic= or negative associations% as a result of certain organisms influencing the respiratory and nutritional environments of the entire root canal flora Sund9vist et al$% 8FAF> &icrobial interference Certain microbes have the ability to shir6 and interfere with the host defenses

'acterial to ins can effectively interfere with the various mechanisms of host immune system A$ israelii aggregate to form large cohesive colonies that cannot be 6illed by host phagocytes +I"#(ENCE 3ACTO"S Capsules .Present e ternal to the outer layer of the cell wall .Composed of polysaccharide%rarely polypeptide .3unctions Protects the cell from desiccation and from to ic materials in the environment$ Promotes the concentration of nutrients at the bacterial cell surface$ Adherence of bacteria to host cells$ "esistance to bactericidal action of complement and serum antibodies$ 3imbriae<pili= They are small appendages found on the surface of many gram.ve bacteria 3unctions Participates in the aggregation of bacteria or attachment to tissues$ Pili may e tend from one bacterium to another during con,ugation and e change !NA for virulence factors% including resistance to antibiotics$ END*&ES AS SP"EA!IN) 3ACTO"S 7yaluronidase Collagenase Neuraminidase Strepto6inase and Staphylo6inase EN!OTOGINS AN! EGOTOGINS

E oto ins are proteins formed by )ram Hve bacteria and are highly potent in minute 9uantities$ Endoto ins are polysaccharide protein comple es which form an integral part of the cell wall of )ram 4ve bacteria$ They are less potent than the e oto ins$ It has been shown that the concentration of endoto in in the canals of symptomatic teeth is higher than that in the canals of asymptomatic teeth$ 'iofilms The aggregations of microorganisms into communities at surfaces e hibiting well defined structures and succession% are biofilms$ "oot canal infection is essentially a bacterial biofilm coating the dentin surface% including the tubules to variable depths and e tending to the apical foramina and sometimes beyond$ 'acteria in biofilms are more resistant to 6illing becauseA$ The polysaccharide in which the bacteria are embedded restrict diffusion of antimicrobial agents$ '$ !ifferent layers of cells act as barrier to diffusion$ C$ Some bacteria may be slow growing or dormant and may be resistant$ Actinomyces sp Species of Actinomyces have been associated with endodontic treatment that failed to heal A$ viscosus A$ israelii A$ naeslundii were detected in clinical samples from infected root canals% and abscesses% and few were associated with cellulitis$ The ability of these species to form cohesive aggregates enables them to escape destruction by host defense mechanisms li6e phagocytosis$

These aggregates maintain an environment that supports its growth and also prevents antibiotics from reaching all the organisms$ Actinomyces infection causes persistent progression of periapical lesion in spite of ade9uate endodontic treatment with several e acerbations and drainage$ Enterococcus faecalis Invades into dentinal tubules and remains viable within the tubule$ Adheres to collagen$ "egulates internal p7 with an efficient proton pump$ ?ithstands high p7 up to 88$;% resisting effects of Ca<O7=:$ E$ faecalis can survive prolonged starvation$ It can grow as a mono.infection in treated canals in the absence of synergistic support from other bacteria$ ANTI&IC"O'IA( A)ENTS Antimicrobial agents fall largely into two groups 8$ Chemotherapeutics 4 systemic and local$ :$ Conventional antiseptics$

S*STE&IC C7E&OT7E"APE#TICS Chemotherapy is defined as the use of synthetic% semi synthetic and naturally occurring chemicals that selectively inhibit specific organisms causing disease$ The term antibiotic means Iagainst lifeJ <anti. against biosis 4 life=$ It refers to substances produced by microorganisms which suppress the growth of or 6ill other microorganisms at very low concentrations$ Antimicrobial agents refer to synthetic as well as naturally obtained drugs that attenuate microorganisms$

ANTI'IOTIC T7E"AP* 3O" &ANA)IN) O!ONTO)ENIC IN3ECTIONS Antibiotics are the greatest contribution of the :0th century to therapeutics$ Eudicious use of antibiotics in con,unction with surgical therapy is the most appropriate method to treat odontogenic infections$ 'ecause of lac6 of collateral circulation within the dental pulp% the normal host defenses <inflammation and immunity= are compromised and the root canal system becomes a uni9ue environment to harbor bacteria$ IN!ICATIONS 3O" #SE O3 ANTI'IOTICS Antibiotics should be used only as an ad,unct to dental treatment and never used alone as the first line of care$ Indicated when systemic signs of involvement are evident$ 3ever greater than 800K3% malaise% lymphadenopathy or trismus are clinical signs re9uiring antibiotic therapy$ A rapidly spreading infection or persistent infections also re9uire antibiotics$ Patients with compromised host defense systems e$g$ organ transplant patients and patients with poorly controlled diabetes$ P"INCIP(ES O3 ANTI'IOTIC T7E"AP* <A= Identification of the Causative organism <'=!etermination of Antibiotic Sensitivity- (aboratory methods li6e 8$ !isc 4 diffusion :$ Tube dilution methods #se of Narrow Spectrum Antibiotics- ?hen bacteria are e posed to antibiotics the opportunity for development of resistant strains is present$ 7ence initially if a broad spectrum is used many bacteria develop resistance$ Therefore if a narrow spectrum is used as fewer organisms have the opportunity to become resistant$ <!= #se of bactericidal drug rather than bacteriostatic drug$ = Proper !ose

3or therapeutic purposes the Pea6 concentration of an antibiotic% at the site of infection should be three times to four times the &IC$ The usual recommended dose of an antibiotic is actually sufficient to provide three.fold concentration against the susceptible organism$ Proper Time IntervalThe usual dosage interval for therapeutic use of an antibiotic is four times the half life$ Since most of the antibiotics are eliminated via 6idney% the patient with pre.e isting renal disease may re9uire longer intervals between the doses so as to avoid over dosing and e cessive plasma level$ Combination TherapyTo increase bactericidal effect $ To broaden the spectrum of antibacterial activity$ &*T7S "E)A"!IN) #SE O3 ANTI'IOTICS &yth L8- antibiotics are always indicated for treating pain$ Pain in irreversible pulpitis is caused due to release of inflammatory mediators that lower pain thresholds and cause increased vascular permeability$ 'ecause pulp is encased in hard tissue and low compliance environment% pain occurs$ Chemomechanical removal of pulp is the treatment of choice in pain due to irreversible pulpitis$ Antibiotics only cause microbial destruction% hence appropriate analgesics are indicated for pain control and not antibiotics$ &yth L:- antibiotics are always indicated in cases of periapical lesion% sinus tract% fistula and abscess

Such conditions indicate a necrotic% non vital pulp having minimal vasculariCation in these sites$ Thus therapeutic concentration of antibiotic at the site cannot be obtained$ 7ence local treatment li6e "CT and incision and drainage is most important in resolving these conditions$ &yth L1- antibiotics must be given for several days before dental treatment The microbial environment of odontogenic infections persists until source of irritation is removed$ The 6ey to successful resolution of infection is initial drainage and thorough chemomechanical debridement$ The vast ma,ority of localiCed infections can be successfully treated by appropriate dental treatment alone without prior antibiotic administration$ Only In medically compromised patients% prophylactic antibiotic therapy is warranted$ &yth L5- overpresription of antibiotic therapy does not occur in dentistry Over #se or abuse of antibiotics results only in the destruction of susceptible bacteria and selective proliferation of resistant bacteria% thus aiding the propagation of bacterial drug resistance$ !espite warnings% humans have chosen to abuse the gift of antibiotics and have created a situation where all microorganisms are resistant to some antibiotics and some microorganisms are resistant to all antibiotics In dentistry also% e cessive antibiotics are prescribed in situations which can be resolved with appropriate dental treatment$ IN!I+I!#A( ANTI'IOTICS . (actam AntibioticsThese are antibiotics having a (actam ring$ The two ma,or groups are penicillins and cephalosporins that are most commonly used antibiotics$

PenicillinIt was the first antibiotic to be used clinically in 8F58$ It was originally obtained from the fungus Pencillium notatum% but the present source is a high yielding mutant of P$Chrysogenum$ ANTI&IC"O'IA( ACTI+IT* Penicillin is a narrow spectrum antibiotic very effective against aerobic and anaerobic gram.positive organisms$ 7ighly sensitive Streptococci Pneumococci '$anthracis Actinomyces israelii &EC7ANIS& O3 ACTION Penicillin is a bactericidal drug$ It acts by inhibiting the synthesis of bacterial cell wall$ This action is produced by inhibiting the synthesis and cross lin6age of peptidoglycans$ SE&I.S*NT7ETIC PENICI((IN Classification I$ Acid "esistant . Pheno y &ethyl Penicillin <Pencillin += II$ Penicillinase "esistant Penicillin . Clo acillin%&ethicillin III$ E tended Spectrum Penicillin . Ampicillin% Amo ycillin The reason for producing semi synthetic penicillins is to overcome the shortcomings of naturally occurring Pn)8$ Poor oral efficacy

:$ Susceptibility to penicillinase 1$ Narrow spectrum of activity 5$ 7ypersensitivity ;$ Penicillin is still the gold standard in treating odontogenic infections$ /$ Penicillin + is preferred over Pn) in odontogenic infections because of better oral absorption$ A$ A combination of penicillin with clavulanic acid may be necessary in bacteria producing M lactamase enCymes$ @$ A loading dose of 8000 mg should be followed by ;00 mg every / hrs for / 4 80 days$ A!+E"SE "EACTION Intolerance includes Allergic and anaphylactic reactions$ Allergy which is the ma,or problem with penicillin may occur in the form of s6in rashes% renal disturbances$ EA"ISC7 7E"G7EI&E" "EACTION Penicillin in,ected in a syphilitic patient may produce shivering% fever% myalgia% e acerbation of lesions% even vascular collapse$ This is due to sudden release of spirochetal lytic products and lasts for 8: 4 A: hours$ (OCA( I""ITANC* AN! !I"ECT TOGICIT* Pain at intra muscular in,ection site% nausea on oral ingestion and thrombophelbitis of in,ected vein$ CEP7A(OSPO"INS These are group of semisynthetic antibiotics derived from fungus cephalosporium$ CEP7A(EGIN- most commonly used orally effective first generation cephalosporin mainly prescribed for orodental infection$ Cephale in has high activity against gram positive bacteria and they have good penetration in to alveolar bone$

!ose- 0$:;g.8g /.@ hourly Cephale in and cephadro il are 8st generation cephalosporins$ Cephalosporins beyond the 8st generation is not indicated in orodental infections$ NIT"OI&I!ADO(ES &etronidaCole Introduced in 8F;F% a broad spectrum antiprotoCoal drug against Entoamoeba histolytica and )iardia lambia$ It is active strictly against anaerobic bacteria and protoCoa$ After entering the micro organisms by diffusion% its nitro group is reduced to intermediate compounds which cause cytoto icity by damaging !NA$ Nnown to inhibit cell mediated immunity$ It should be avoided during first trimester of pregnancy% blood dyscrasias and chronic alcoholism !ose :00 4 500mg @ hours% 8;mgB6g body weight / hourly I+ Adverse "eactions Nausea% headache% metallic taste% glossitis% stomatitis and hairy tongue$ Should be avoided in alcoholics because it causes disulfiram li6e reactions$ !isulfiram is an anti abuse drug administered to chronic alcoholics which causes violent vomiting$ &etronidaCole shares this property with disulfiram$ &AC"O(I!E ANTI'IOTICS &acrolide antibiotics contain a large lactone ring in their structure$ E"*T7"O&*CIN Source- obtained from fungus streptomycin erythreus$ Active against gram positive including Streptococcal% Staphylococcal and Pneumococci$

'acteriostatic in low concentrations and 'acteriocidal in high concentrations Acts by inhibiting protein synthesis by bacterial ribosomes$ Nausea% vomiting and epigastric pain on oral administration$ +ery high doses of erythromycin have caused reversible hearing impairment$ !ose- :;0 4 ;00mg / hourly !ental Infections Since erythromycin is safe and active against both aerobic and anerobic gram positive bacteria commonly used for !ental infections$ It is the second choice drug to penicillin for periapical abscesses% nercotiCing ulcerative gingivitis% post e traction infections% and celluitis$ Particularly valuable for patients allergic to penicillin NE?E" &AC"O(I!ES "OGIT7"O&*CIN Semi synthetic long acting macrolide whose antibacterial spectrum resembles closely with that of erythromycin but more potent action$ Improved e ternal absorption and tissue penetration on average plasma half life of t O . 8: hours ma6ing it suitable for twice daily dosing% as well as better gastric tolerance$ Thus it is an alternative to erythromycin for "$T$I$ ENT% orodental% s6in and genital tract infection !ose- 8;0mg 4 '! Children 4 :$; 4 ; mgB6g '! TET"AC*C(INE These are broad spectrum antibiotics$ They are effective against gram positive P gram negative organisms$

Chlortetracycline is obtained from streptomyces aureofaciens$ Tetracycline is obtained from catalytic hydrogenation of chlortetracycline$ !o ycycline. Semi synthetic% having )ood intestinal absorption 7igher and sustained blood levels$ (onger duration of action (ow renal To icity No or less tooth discoloration &echanism of action$ 8$ Inhibition of enCymes systems and protein synthesis$ :$ Chelation of cations li6e calcium P magnesium$ 1$ Interference with phosphorylation of glucose$ A!+E"SE "EACTIONS 8$ Intolerance li6e s6in rashes% photosensitivity% )$I$T$ disturbances$ :$ (iver damage li6e ,aundice% fatty changes$ 1$ "enal disturbances li6e proteinuria P )lycosuria$ 5$ 'one changes li6e decrease in linear )rowth ;$ !ental effects. tetracycline Stains$ C(IN!A&*CIN Is often indicated in endodontic infections$ 7as a good spectrum of 6illing oral pathogens including many anaerobes$ &echanism of action is similar to erythromycin i$e inhibition of protein synthesis$ &ain adverse effect is occurrence of pseudomembraneous colitis$ !ose - 8;0. 100 mg QI!$ +ANCO&*CIN !iscovered in 8F;@ as a penicillin substitute 4 Active against gram positive bacteria$

'actericidal. acts by interfering with cell wall synthesis and prevents cross lin6ing of pepetidoglycans$ 7igh systemic to icity$ #sed in patients allergic to penicillin$ !ose - ;00 mg QI!$ CIP"O3(OGACIN Is the most potent fluoro9uinolone with broad spectrum of activity$ Aerobic gram 4ve pathogens are highly susceptible$ 'actericidal 4 inhibits bacterial !NA gyrase causing irreversible damage to !NA$ #se in endodontics is limited to cases in which culture and sensitivity results prove their indication$ A&INO)(*COSI!ES These are compounds which contain amino sugars in glycosidic lin6age$ 'actericidal drug and acts by inhibiting bacterial protein synthesis$ They have good activity against aerobic bacilli but also active against aneorobic bacteria$ Streptomycin and )entamycin belong to this class$ #sed in con,unction with penicillin for acute infections and prophyla is for endocarditis$ P"O'(E&S T7AT A"ISE ?IT7 #SE O3 ANTI'IOTICS 8$ To icity 4 (ocal Irritancy- This is e perienced at the site of administration li6e pain at site of in,ection$ 4 Systemic To icity - All antimicrobials produce dose related to icity 4 characteristic to icities e hibited by Tetracyclines are (iver and 6idney damage% antianobolic effect$

7ypersensitivity reaction All antimicrobials are capable of causing hypersensitivity reactions$ It ranges from rashes to anaphylactic shoc6$ !rug "esistance- Natural Eg - )ram .ve bacilli are normally unaffected by penicillin$ Ac9uired "esistance It is the development of resistance by an organism due to the use of an antibiotic over a period of time Cross "esistance Eg- "esistance to one sulfonamide means resistance to all others and resistance to one tetracycline means insensitivity to all others$ Superinfection <Suprainfection= This refers to the appearance of new infection as a result of antimicrobial therapy% use of antimicrobials causes some alteration in the normal microbial flora of the body$ Superinfections are more common in !iabetes AI!S$ ANTI'IO&A ?hen a misplaced attempt has been made to cure an abscess by antibiotics the resulting lump is called Antibioma$ It is absolutely essential that an antibiotic should not be given if pus is already present$ If antibiotic is given the pus in the abscess fre9uently becomes sterile and a large brawny oedematous swelling is found and ta6es many wee6s to resolve$ ANTI'IOTIC P"OP7*(AGIS )#I(E(INES !ental e tractions

Periodontal procedures including surgery% scaling and root planning% probing% and recall maintenance !ental implant placement and replantation of avulsed teeth Endodontic instrumentation or surgery only beyond the ape $ Intraligamentary local anesthetic in,ections Prophylactic cleaning of teeth or implants where bleeding is anticipated !OSA)ES "ECO&&EN!E! '* T7E A7A SIT#ATION Standard Prophyla is #nable to ta6e oral medication &E!ICATION Amo icillin !OSA)E Adults> :$0 g- children- ;0 mgB6g orally 8 h before procedure Adults- :$0 g I& or I+> children:0 mgB6g I& or I+ within 10 min before procedure Adults- /00 mg Clindamycin or Allergic to Penicillin Cephale in or Children- :0 mgB6g orally 8 h before procedure Adults- :$0 g> children> ;0

Ampicillin

cefadro il mgB6g orally 8 h before procedure ACithromycin or Adults- ;00 mg> children- 8; clarithromycin mgB6g orally 8 h before procedure Adults- /00 mg> children- :0 mgB6g I+ within 10 min before procedure Adults- 8$0 g> children- :; mgB6g I& or I+ within 10 min before procedure !OSA)E &E!ICATION

Allergic to penicillin and medications SIT#ATION Clindamycin or unable to ta6e oral CefaColin

Adults.ampicillin :$0g I& or I+ <not to e ceed :$0g= plus gentamicin 8$;mgB6g <not to e ceed 8:0mg= within 10 min before procedure > / h later% ampicillin 8g I&BI+ or 7igh "is6 Patients Ampicillin Plus )entamicin amo icillin 8g orally$ Children.ampicillin ;0mgB6g I& or I+ <not to e ceed :$0g= plus gentamicin 8$;mgB6g within 10 min before procedure> /h later% ampicillin% :; mgB6g I&BI+ or amo icillin :; mgB6g orally$ Adults.vancomycin 8$0g I+ over 8.: h plus gentamicin 8$; mgB6g I+BI& <not to e ceed 8:0 7igh.ris6 patients allergic to ampicillin B amo icillin )entamicin mg=> complete in,ectionBinfusion +ancomycin Plus within 10 min before procedure$ Children.+ancomycin :0mgB6g I+ or 8.: h plus gentamicin 8$; mgB6g I+BI&> complete in,ectionBinfusion within 10 min before procedure$ !OSA)E SIT#ATION &oderate."is6 Patients &E!ICATION Amo icillin or ampicillin Adults.amo icillin :$0g orally 8h before procedure% or ampicillin :$0g I+BI& within 10 min before procedure$ Children.amo icillin ;0 mgB6g

orally 8 h before procedure or ampicillin ;0mgB6g I&BI+ within 10 min before procedure$ Adults.vancomycin 8$0g IC over 8.: &oderate.ris6 patients allergic to ampicillin B amo icillin !ISIN3ECTION O3 P#(P SPACE SO!I#& 7*POC7(O"ITE Sodium hypochlorite was recommended by (abarra9ue <8AAA.8@;0= to prevent infectious diseases$ In ?orld ?ar I% 7enry !rysdale !a6in used buffered 0$;2 sodium hypochlorite for irrigation of infected wounds$ #se of sodium hypochlorite in endodontics as the main irrigant was as early as 8F:0$ 7as wide spectrum of activity% non specific 6illing efficacy on all microbes% also sporicidal% virucidal and shows tissue dissolving effects$ Cheap% easily available and demonstrates good shelf life$ Other chlorine releasing compounds li6e chloramine 4T and sodium dichloroisocyanurate have been used but are less effective than hypochlorite <Naenni et al=$ Sodium hypochlorite is both an o idiCing and hydrolyCing agent$ It is bactericidal and proteolytic$ Is e tremely corrosive to metals> strongly al6aline% has low viscosity% hypertonic and has an unpleasant taste$ Commercial NaOCl is buffered to a p7 of appro imately 8: to 81$ +ancomycin h> complete infusion within 10 min before procedure$ Children.vancomycin :0 mgB6g I+ or 8.: h> complete infusion within 10 min before procedure$

P"O!#CTION O3 SO!I#& 7*POC7(O"ITE Sodium hypochlorite has traditionally been produced by bubbling chlorine gas through a solution of sodium hydro ide <NaO7=% to produce sodium hypochlorite <NaOCl=% salt <NaCl= and water <7:0=$ Cl: H :NaO7 .R NaOCl H NaCl H 7:0 An alternative method uses electrolysis of a saturated brine solution to produce sodium hypochlorite$ Commercial sodium hypochlorite solutions typically have concentrations of 80 to 852 available chlorine$ They deteriorate with time% temperature% e posure to light% and contamination with metallic ions$ E cess chlorine in sodium hypochlorite solutions leads to an acid solution which is unstable$ These chemical changes are summariCed in the two e9uations below$ :NaOCl .R :NaCl H0: 1NaOCl.R :NaCl H NaCl01 CONCENT"ATION O3 NaOCl The antimicrobial effectiveness and tissue dissolving capacity is a function of its concentration% but so is its to icity$ ;$:;2 is the commonly used strength but severe irritations have been reported <7ulsman et al= and significant decrease in the elastic modulus and fle ural strength of dentin is seen than with 0$;2 concentration$ <Sim et al=$ The reduction of the microbiota % however% is not any greater when ;2 is used compared to 0$;2 <'ystrom et al=$ !uring irrigation% fresh hypochlorite reaches the canals and the concentration does not play a decisive role$ 7ence% based on several studies% the currently recommended concentration of sodium hyochlorite is 82 wtBvol$

TE&PE"AT#"E O3 SO!I#& 7*POC7(O"ITE There is increased amount of tissue dissolution by increasing the concentration% contact time and volume of sodium hypo chlorite and by maintaining the temperature of the solution at 1/KC$ 7eated hypochlorite solutions remove organic debris from dentin shavings more effectively than unheated counterparts$ A temperature raise of :;KC increased NaOCl efficacy by a factor 800$ Preheating NaOCl solutions appears to improve their necrotic pulp dissolution capacity and efficacy against E$3aecalis cells$ ANTI &IC"O'IA( ACTI+IT* The antimicrobial activity of NaOCl is due to the availability of free chlorine and its high p7$ Causes biosynthetic alterations in cellular metabolism and phospholipid destruction$ !issolution of organic tissue occurs when sodium hypochlorite degrades fatty acids and lipids resulting in soap and glycerol$ The high p7 alters the integrity of the cytoplasmic membrane by means of chemical in,uries to organic components and transport of nutrient% or by means of the degradation of phospholipids and unsaturated fatty acids% observed in the pero idation process$ O idation promotes irreversible bacterial enCymatic inhibition replacing hydrogen with chlorine$ 'y combining ;$02 NaOCl with E!TA however% the bactericidal effect was considerably enhanced$ This could be related to the removal of contaminated smear layer by E!TA$

Possibly the bactericidal effect gained by combining sodium hypochlorite with other chemicals comes from the release of chlorine gas$ This was especially true for citric acid and to some e tent with E!TA$ C7(O"7EGI!INE !eveloped in late 8F50s in the research laboratories of Imperial Chemical Industries (td$ Symmetrical cationic molecule consisting of two 5.chlorophenyl and two biguanide groups connected to a central he amethylene chain$ Strong base% common preparation with digluconate salt because of its water solubility$ Active against a wide range of gram positive% gram negative organisms% yeast% fungi% facultative anaerobes and aerobes$ Action is due to its adsorption onto the cell wall of the microorganism% resulting in lea6age of intracellular components$ (ow concentrations 4 small molecular weight substances li6e potassium P phosphorous leach out% e erting a bacteriostatic effect$ 7igh concentrations 4 bacteriocidal because of precipitation or coagulation of the cytoplasm caused by protein cross lin6ing$ 'acteriocidal effect is less important than bacteriostatic effect due to slow release of chlorhe idine$ 'ecause of its cationic properties% chlorhe idine binds to the hydro yapatite of enamel% pellicle% bacteria and e tracellular polysaccharides of bacterial origin$ A9ueous solutions of 0$8 to 0$:2 are recommended for pla9ue control and :2 for endodontic irrigating solution$ !elany et al found that :2 solution to be an effective antimicrobial agent when used as an endodontic irigating solution and as an intracanal% inter appointment dressing$

?ennberg reported good tissue recovery and no more tissue to icity than with any other endodontic agents tested in vivo and in vitro$ C7G has the property of substantivity <residual effect=$'oth :2 and 0$8:2 C7G cause residual antimicrobial activity for A: hours when used as an endodontic irrigant% and even as long as 8/@ hours$ <Parson et al=$ C7G has been reported to cause staining% especially when combined with NaOCl% which means it needs to be used ,udiciously$ A saline rinse between the NaOCl and the C7G will eliminate the brown pigmentation that develops when these two solution are mi ed in the canal$ 'aumgartner et al found that Chlorhe idine with Ca<O7=: shows additive antimicrobial activity against common bacterial pathogens$ !espite its usefulness as a final irrigant% it cannot be advocated as the main irrigant in standard endodontic cases because8$ Chlorhe idine is unable to dissolve necrotic tissue remnants :$ Is less effective on gram negative than on gram positive bacteria$ <Dehnder et al=$ In primary endodontic infections% gram negative anaerobes predominate$ 7owever% C7G may still be useful as an alternative endodontic irrigant if the patient is found to be allergic to NaOCl$ 7*!"O)EN PE"OGI!E 7ydrogen pero ide <7:O:= is also widely used in endodontics$ 7as two modes of action8$ 'ubbling of solution when in contact with tissue and certain chemicals physically foams debris from the canal$ :$ (iberation of o ygen destroys strictly anaerobic organisms$

1$ The solvent action is much less than that of NaOCl and is also less damaging to periapical tissues and therefore is preferred in perforation cases$ 5$ It is usually used alternatively with NaOCl$ ;$ Preferred irrigant for canals that have been left open since effervescence is effective in removing lodged food particles$ /$ Should not be used as the last irrigant since nascent o ygen may remain and build up pressure$ ET7*(ENE!IA&INETET"A ACETIC ACI! <E!TA= In 8F;8% the first reports on the demineraliCing activity of E!TA on dental hard tissues was published$ <7ahn et al=$ Chelators were first introduced in endodontics by Nygaard.Ostby in 8F;A$ E!TA is the chemical compound ethylenediaminetetraacetic acid% otherwise 6nown as edetate% versene% or diaminoethanetetraacetic acid disodium salt$ E!TA or its disodium salt is a chelating agent%with most divalent <or trivalent= metal ions% such as calcium <Ca:H= and magnesium<&g:H= or copper <Cu:H=$ The most common chelating solutions used for irrigation include Tublicid% E!TAC% 3ile.ECe% and "C.Prep all of which E!TA is the active ingredient$ Nygaard.0stby introduced E!TAC% E!TA with Cetrimide% 9uaternary ammonium bromide% used to reduce surface tension and increase penetration$ E)TA contains Ethylene glycol.bis<'eta aminoethyl ether= tetraacetic Acid$ It binds ca:H more specifically and the combination with NaOCl is more effective in removal of smear layer$

!emineraliCation of hard tissue is due to the principle of constant solubility product$ In dentin% calcium P phosphates are soluble in water$ ?hen E!TA is added% Ca ions are removed from the solution$ This leads to the further dissolution of ions so that the solubility constant remains the same leading to decalcification of dentin$ The optimal p7 for the demineraliCing efficacy of E!TA on dentin was shown by +aldrighi to be between ;$0 and /$0$ "E&O+A( O3 S&EA" (A*E" &c Comb and Smith <8FA;= were the first to describe the smear layer on instrumented canal walls$ Contains of ground dentin and predentin% pulpal remnants% odontoblastic processes and in case of infected teeth% bacteria$ Partial if not complete smear layer removal is achieved only with acids and chelators$ <*amada et al=$ Numerous studies show that the irrigation with 8A2 E!TA solution has a good cleaning effect on the root canal walls by removing the smear layer$ Some studies have detected tubule orifice enlargement and erosion of the tubules$ To reduce the erosive effects of E!TA solutions lower concentrations of E!TA at neutral p7 should be used$ ANTI'ACTE"IA( E33ECTS O3 E!TA E!TA has a certain but limited antibacterial effect$ This is thought to be due to the chelation of cations from the outer membrane of the bacteria$ Also results in the formation of a Cone of inhibition of bacterial growth$

Antibacterial properties depend upon concentration and p7 $ Antibacterial effect is maintained only as along as the chelators have not formed bonds with metal ions$ #rea pero ide<802= content also is thought to have antimicrobial effect in some preparations$ *oshida et al found that E!TA in combination with ultrasonics was very effective against endopathogens$ The minimum concentration to yield an inhibitory effect was 0$8:;2 for E!TA and minimum bactericidal concentration was 0$:;2$ <Steinberg et al=$ Combined use of E!TA and ;2 NaOCl has greater antimicrobial activity than when used alone$ <Sund9vist et al=$ Increasing the time period from 80 to 5; min also increases the antimicrobial effect$ E(ECT"O C7E&ICA((* ACTI+ATE! ?ATE" T$&arais et al reported antimicrobial effect of electrochemically activated water$ Electro.chemically activated water <ECA= is the sub,ect of more than 100 "ussian patents$ ECA is produced from tap water and saline solution by a special unit that houses a uni9ue flow.through electrolytic module <3E&=$ The 3E& contains the anode made from titanium and coated with ruthenium.o ide% iridium and platinum$ The cathode made from titanium coated with pyrocarbon% and glasscarbon$ The solution supposedly e ists in a metastable state after production and contains many free radicals and a variety of molecules and ions$

Two types of ECA solution are produced Anolyte has a high o idation potential <H 500 to H8:00 millivolts= and is antimicrobial$ Catholyte is an al6aline solution <p7 A8:= with a high reduction potential <. @0 to . F00 millivolts=$ Catholyte is reputed to have a strong cleaning or detergent effect$ The use of ECA caused a reduction in number of anaerobic bacteria within the root canal system% but this was not statistically significant when compared to sodium hypochlorite$ &TA! &TA! is a mi ture of tetracycline isomer <do ycycline=% an acid <citric acid=% and a detergent <Tween @0=$ The protocol for clinical use of &TA! is :0 minutes with 8$12 NaOCl followed by ; minutes of &TA!$ The solubiliCing effects of &TA! on pulp and dentin are somewhat similar to those of E!TA$ !o ycycline also has antibacterial activity% chelating ability and substantivity$ The effectiveness of &TA! is due to the removal of the smear layer by citric acid thus allowing the antibacterial agent <tetracycline= to enter the entire root canal system$ Another advantage is that there is no dentinal erosion when compared with E!TA for :0 min <Torabine,ad et al=$ &TA! is significantly more effective in 6illing E$ faecalis than NaOCl when the solutions are diluted$

&TA! is still effective in 6illing E$ faecalis at :00 dilution% but NaOCl ceases to be effective at 1: dilution$ <Shabahang et al=$ 802 CIT"IC ACI! Citric acid has been used for smear layer removal and elimination of occluding dentinal debris during root canal preparation$ Citric acid has limited action on endodontic biofilm$ <Cehnder et al=$ 7as no tissue dissolution activity and has negligible endoto in inactivation$ 7owever% The #S Air 3orce army institute of dental science tested both citric acid and NaOCl against anaerobic bacteria and reported e9ual effect as a bactericide in ; to 8; mins$ Other irrigantsS The efficacy of F.amino acridine has been reviewed by SchmitC$ An antiseptic of low to icity and antimicrobial action$It is not a tissue solvent or chelator% its use is not widespread$ Chloramine.T is still sometimes used in endodontic treatment% but also has little ability to dissolve necrotic tissue Naufman has reported the success of several cases using bis.de9ualinium acetate <'!A= as a disinfectant and chemotherapeutic agent$ 7e cites its low to icity% lubrication action% disinfecting ability% and low surface tension% as well as its chelating properties and low incidence of post.treatment pain$ Another root canal chelating irrigant is SalviCol$ consisting of decamethylene.bis.5.amino9uinaldinium acetate$ SalviCol%with a neutral p7% has a broad spectrum of bactericidal activity as well as the ability to chelate calcium$ I""I)ATION TEC7NIQ#E

One of several plastic disposable syringes is ade9uate$ The irrigating solution is 6ept in a dappen dish and is filled by immersing the hub into the solution while withdrawing the plunger$ The needle is then attached$ The needle may be one of several types$ It should be bent to allow easier delivery of the irrigating solution$The needle most commonly used is :A gauge with a notched tip allowing for solution flowbac6 or the blunt end &a .I.Probe It is strongly recommended that the needle lie passively in the canal and not engage the walls$ Severe complications have been reported from forcing irrigating solutions beyond the ape by wedging the needle in the canal and not allowing an ade9uate bac6f8ow INT"A CANA( !ISIN3ECTANT &ATE"IA(S 'iomechanic instrumentation and irrigation with an antimicrobial solution may not be sufficient for complete elimination of microorganisms in a necrotic pulp space$ 7ence% further disinfection with an effective antimicrobial agent may be necessary$ The primary function of intracanal medicament is to prevent canal infection where none is present and Bor eliminate bacteria already infecting the root canal$ "ATIONA(E 3O" INT"ACANA( &E!ICATION &ain rationale using such medication is to help fulfill the aim of root canal system preparation that is to degrade residual microbial biofilm and organic tissue and to 6ill remaining bacteria$ The medication should% therefore % also prevent bacteria recoloniCation of the root canal system% from either those bacteria left behind after

preparation or new invaders through lateral communication or the coronal access$ There are two main types of intra canal medications8$ Chemical antiseptics :$ Topical antibiotics as intra canal medicaments$ P"I&A"* 3#NCTION O3 EN!O!ONTIC &E!ICA&ENTS IS ANTI &IC"O'IA( ACTI+IT* ANTI SEPSIS !ISIN3ECTION ANTI SEPSIS Is the endeavor to eliminate infecting or contaminating microbes$ In vital pulp e tirpation % anti septic measures are necessary to prevent infection if there is a breach in the chain of asepsis$ Irrigating solutions and inter appointment dressings need to be antibacterial in action to prevent any micro organisms which may contaminate the canal system from multiplying and establishing themselves$ !ISIN3ECTION Is the elimination of pathogenic micro organisms %usually by chemical or physical means$ !isinfection by antiseptic agents is what is attempted in the treatment of infected teeth$ It entails mechanical removal of tissue and debris containing microbes % irrigation and dressing with antiseptic agents$ SECON!A"* 3#NCTIONS O3 &E!ICA&ENTS 7A"! TISS#E 3O"&ATION PAIN CONT"O( EG#!ATION CONT"O( "ESO"PTION CONT"O(

A(!E7*!ES 3ormaldehyde% Paraformaldehyde P )lutraldehyde$ They are water soluble% protein denaturing agents and are among the most potent disinfectants$ They are 9uite to ic% allergenic and some may be carcinogenic$ 3O"&A(!E7*!E E tensively used despite high to icity P mutagenicity$ 3ormocresol 4 8F2 . formaldehyde Tricresol formalin 4 802 tricresol% F02 formaldehyde$ 3ormladehyde is volatile and releases antimicrobial vapors for disinfection of pulp chamber$ Is more potent to in with low antimicrobial efficacy$ 7ence their use must be discontinued$ PA"A3O"&A(!E7*!E It is the polymer form of formaldehyde% best 6nown for its inclusion in the root canal filling materials N: and Endomethasone$ It slowly decomposes to give its monomer% formaldehyde> which is to ic% allergenic P genoto ic$ Considering its tissue destructive effects and carcinogenic potential% there is no rationale for its use$ P7ENO(IC CO&PO#N!S Phenol or carbolic acid is one of the oldest compound for controlling microorganisms and serves as the basis for a number of derivatives e tensively used in dentistry$ !espite its severe to icity% derivatives of phenol li6e paramonochlorophenol% thymol and cresol are in common use$

A nonspecific protoplasm poison% phenol is highly effective in as low a concentration as 8 to :2$ Studies have shown that antimicrobial effectiveness does not correspond favorably to their to icity$ CA&P7O"ATE! P7ENO( Phenol is li9uefied in camphor and used in endodontics as a solution of camphorated phenol <Phenol.1;2% Camphor./02% Ethyl alcohol.802=$ Camphorating process aims at developing a less caustic medicament as a result of the slow release of phenol$ In clinical use% the phenolic compounds are relatively ineffective as antiseptics$ &ONOC7(O"P7ENO(<C/75O7C(= Is a derivative of phenol that has three isomers % of which paramonochlorophenol is the most effective$ The antimicrobial effect of monochlorophenol is good %and appro imately 82 monochlorophenol is needed for elimination of the typical root canal flora in vitro $ Parachlorophenol commercially available concentrations < F@2 in water or 1;2 in camphor= is too to ic to be a rational alternative in endodontic therapy$ Thymol<C/71O7C71C17A= Is included in many endodontic preparations%such as Endomathasone % &ynol cement % and Tubli.seal$ ThymolTs to icity is e9ual to or higher than that of phenol% although its antimicrobial effect is better$ It is seldom recommended as an intracanal antiseptic in modern endodontics $

Cresol <C/75O7C71= 7as three isomers % of which metacresol is most effective as an antiseptic $ The most fre9uently used formula in endodontics is 3ormocresol <formaldehyde 8F2 % cresol 1;2 % water and glycerin 5/ 2 = $ 3ormocresol wor6s as a poison and causes widespread destruction of living tissue $ The bacterial effect of formocresol is good at a level as low as :2 of the concentration generally used$ Creosote Is a mi ture of phenol derivatives )uaiacol % the methyl ether of pyrocatechin % is the ma,or constituent </0 to F0 2 = of creosote $ 'eechwood creosote has long been used in endodontic therapy $ Coolidge recommended the use of cresatin <metacresylacetate = % the acetic acid of metecresol % in combination with benCene as an endodontic medicament$ 'iocompatibility studies show that the effect on tissues ranges from mild to severe $ 'ased on the adverse possibilities % the use of cresatin as an intracanal medicament should be discouraged $ 7alogens Chlorine and iodine are the basis of a number of o idising antiseptics commonly used in endodontic practice$ Chloramine 4T is a chlorine compound with e cellent antimicrobial 9ualities $ Chloramine <;2=% which has a low to icity % is a good alternative intracanal dressing when a history of allergy prevents the use of iodine compounds$ Chloramine is also used for disinfecting guttapercha points $It also remains stable for a long time if stored in cold and protected from light$

Iodine Iodine has been used for many years and is 6nown for its mild effect on living tissue$ The two most common preparations used in dentistry are iodine tincture <;2 iodine in alcohol= and iodine potassium iodide <iodine.:2 % potassium iodide . 52 % distilled water . F52= $ The former solution is advocated for surface disinfection of the endodontic field% and the latter is advocated for intracanal medication$ Iodine potassium iodide <INI :2= has an e cellent antimicrobial activity and has minimal to icity% thus it continues to provide an active antimicrobial effect at a concentration that is not cytoto ic$ The vapor forming effect ma6es it suitable for antimicrobial use in root canals$ Studies show that it penetrated more than 8000 Um of dentin in ; mins in vitro$ Effective disinfectant and is capable of 6illing bacteria in ; min$ Can be prepared by mi ing :g iodine in 5g of potassium iodide and is then dissolved in F5 ml of distilled water$ Iodophores They are organic solutions of iodine and because of their low 4surface tension% are e cellent aids% for cleaning root canals$ The most commonly used preparations are ?escodyne% providing 8$;2 iodine and Iodopa % providing ;2 iodine $ $ The iodine concentrations must be at least 0$0;2% which corresponds to a 12 solution of wescodyne and 82 of iodopa $ 7eavy &etal Salts-

Salts of silver% copper and mercury coagulate proteins % act as enCyme inhibitors % and are generally to ic $ ?ith the e ception of mercury salts % they have no clinical value $ The mercury salts group includes &ercurophen % metaphen % &ercurochrome % and &erthiolate$ Phenyl. mercuric borate is another to ic organic mercury antiseptic % well 6nown in endodontics because of its inclusion in the N: formula$ CA(CI#& 7*!"OGI!E Ca<O7=: Introduced by 7ermann in 8F:0$ Strong al6aline substance 4 p7 8:$;$ ?hite odorless powder$ &olecular weight 4 A5$0@ (ow solubility in water 4 8$: g (V8 at :;WC &ain actions come from the ionic dissociation of Ca:H and O74 ions$ 'iological properties include antimicrobial activity% tissue dissolving ability% inhibition of tooth resorption and induction of repair by hard tissue formation$ &EC7ANIS&S O3 ANTI&IC"O'IA( ACTI+IT* 8$ &ost endopathogens are unable to survive in the highly al6aline environment provided by calcium hydro ide$ <p7 8:$;= :$ 7ydro yl ions released are highly o idant free radicals that show e treme reactivity with several biomolecules$ <3reeman et al=$ !amage to bacterial cytoplasmic membrane-

7ydro yl ions induce lipid pero idation causing destruction of phospholipids . structural components of cellular membrane$ Also removes hydrogen atoms from unsaturated fatty acids generating a free lipidic radical$ This radical reacts with o ygen forming a pero ide radical which removes another hydrogen atom from a second fatty acid% generating another lipidic pero ide$ Thus initiating an autocatalytic chain reaction resulting in e tensive membrane damage$ <7alliwell Cotran et al= Protein denaturation 7igh p7 causes brea6down of ionic bonds that maintain the tertiary structure of proteins$ These changes result in the loss of biologic activity of enCyme and disruption of cellular metabolism <+oet et al=$ It also has the ability to hydrolyCe the lipid moiety of bacterial lipopolysaccharides% thus inactivating the endoto in$ This effect is very desirable because the dead cell wall material remains after 6illing of the bacteria !amage to !NA 7ydro yl ions react with the bacterial !NA and induce splitting of strands$ !NA replication is inhibited and cellular activity is disarranged$ 3ree radicals may also induce lethal mutations$ "oot canal disinfection 'acteria inside dentinal tubules constitute an important reservoir of infection$ 3or calcium hydro ide to act effectively% the hydro yl ions must be able to penetrate dentinal tubules and diffuse through pulpal remnants$

Also dentin has buffering ability because of proton donors li6e 7:PO54% 7:CO1 and 7CO14$ 'acterial cells located at the periphery of the colonies also protect those located more inside the tubules$ Therefore a short term dressing with calcium hydro ide appears to eliminate only the bacteria in direct contact located in the main root canal or the circumpulpal dentin$ The period needed for optimal disinfection is controversial$ "anges from 1 months <Cve6 et al= to 8 wee6 <Ostravi6 et al=$ "easons for bacterial survival after intracanal medication with Ca<O7=: Ca<O7=: has limited antibacterial spectrum$ 7as low solubility and diffusibility ma6es it difficult to reach a rapid and significant increase in p7 to eliminate bacteria in enclosed in dentinal tubules$ Influence of vehicle on antimicrobial activity !ifferent vehicles have been used with Ca<O7=:$ !istilled water% saline and glycerine 4 no antibacterial activity$ Camphoratred monochlrophenol<C&CP= and metacresylacetate 4 antibacterial activity$ Association of Ca<O7=: with C&CP has broader antibacterial spectrum and higher radius of antibacterial action than mi tures of Ca<O7=: with inert vehicles$ CA(CI#& 7*!"OGI!E AN! OT7E" S#'STANCES Quillin et al <8FF:= suggested adding metronidaCole and chlorhe idine to Ca<O7=: for increased antimicrobial efficacy$ Ta6euti et al <8FFA= proposed mi ing Ca<O7=: <0$81g=% metronidaCole <0$/g=% ciproflo acin <0$/g= and polyethyleneglycol 8000$

(edermi is a corticosteroid containing medicament available in slow and fast setting cements$ Powder- Triamcinolone acetonide % !emeclocycline hydrochloride% Ca<O7=: P DnO$ (i9uid- Eugenol% rectified turpentine oil and polyethylene glycol$ Other medicamentsS 'ioactive glass- Is composed of ;12 SiO:% :12 Na:O% 52 P:O;$ Is a slowly acting antimicrobial with a long lasting effect$ Antimicrobial action may be due to 8= its high p7% := Causes the precipitation of CaBP from dentin thus ImineraliCesJ the bacteria$ NISIN . is a naturally occurring antimicrobial agent which can be used as an intracanal medicament$ ?as discovered in 8F:@% is an antibiotic peptide and class I bacteriocin$ Produced by strains of lactobacillus lactis$ Antimicrobial action is due to interaction with phosopholipid membrane of target bacterial cell$ Is effective against a broad range of )ram negative flora$ ANTI'IOTICS 3O" (OCA( #SE There are three main concerns about the local use of antibiotics in the root canal8$ SensitiCation Topical application of an antibiotic increases the ris6 of the patient becoming allergic to it$

Induced allergy to an antibiotic may limit the options for treatment of more severe infections which would otherwise be curable with that particular drug $ :$ !evelopment of bacterial drug resistance The drug 6inetics of antibiotics applied in the root canal not well 6nown $ ?ide spread use of antibiotics causes a general increase in pathogenic and indigenous micro organisms that are resistant to a variety of antibiotics $ 1$ (imited spectrum No one antibiotic is efficacious against all endodontic micro organism $ Sulpha Preparations SulphathiaCole as part of a dressing was advocated in the ;0s and /0s They are effective against many gram 4ve and gram Hve micro organisms % sulpha drugs are ineffective against enterococci and pseudomonas organism $ Penicillin )rossmanTs polyantibiotic paste contained penicillin as an important ingredient $ M.lactamase produced by several species found in the root canal ma6es them resistant to penicillin $ <P$ aeruginosa and several gram negetive rods=$ &etronidaCole 7as good effect against several gram negative anaerobic organisms$ Suggested as an irrigating solution% as an intracanal dressing% for application in combination with other antibiotics% in particular penicillin TET"AC*C(INE It shows affinity for hard tissues and may be retained on tooth surfaces$ Its antimicrobial spectrum is 9uite narrow$ Its derivative do ycyline forms the antibiotic ingerdient in (edermi and in &TA!$

C(IN!A&*CIN One study has reported on the use of it as an interappointment dressing% but only limited antibacterial efficacy could be demonstrated P'SC PASTE The constituents areP 4 Pencillin 4 effective against )ram Positive &icro organisms$ ' 4 'acitracin 4 effective against Pencillin resistant &icro organisms$ S 4 Streptomycin 4 effective against gram negative &icro organisms$ C. Caprylate 4 as the sodium salt effective against fungi$ Nystatin replaces sodium caprylate as the antifungal agent in a similar medicament$ 3O"&#(AE O3 &E!ICA&ENTS CONTAININ) ANTI'IOTICS AN! B O" CO"TICOSTE"IO!S (edermi Paste Triamcinolone acetonide !emethylchlortetracycline <demeclocycline= Calcium in a water.soluble cream consisting of Triethanolamine N3 Calcium Chloride% Dinc O ide Sodium Sulphite <anhydrous= Polyethylene )lycol !istilled water 'oots Polyantibiotic "oot Canal Cream Crystalline pencillin ) Streptomycin <as in a silicone base containing barium sulphate 8;0 000 units 0$8; g 0$8; g sulphate= Chloramphenicol Sodium Caprylate 0$8; g 8$02 1$:82

Pulpomi ine !e amethosone acetate 3ramycetin Sulphate Polymy in ' Sulphate Soluble e cipient Par6e.!avis Polyantibiotic root canal cream Crystalline Pencillin ) Streptomycin <as sulphate= Chloramphenicol Sodium Caprylate In a silicone base containing barium sulphate Eastman !ental 7ospital Endodontic compound Neomycin Sulphate Polymy in ' Sulphate 'acitracin Nystatin Polyethylene )lycol Physical barrier-

8g 8$/A; million IC : million IC 800g

8;0 000 units 0$8; g 0$8; g 0$8; g

80$0g 1$0 mega units <&#= :$88) :$; mega units <&#= :;$/ g 88$0g

Intracanal medicaments can also act as a physicochemical barrier preventing the proliferation of residual microorganisms and preventing the reinfection of root canal$ 8$ Act as chemical barrier against lea6age by 6illing bacteria$ :$ Act as a physical barrier against bacterial penetration$ "econtamination will occur only by solubility or permeability of medicament to saliva$ 1$ ?hen all facts are considered% two medicaments can be chosen to treat infected root canals$ They are Ca<O7=: paste or a :2 concentration of iodine potassium iodide$

5$ The most effective safest intracanal medicament is the iodine potassium iodide solution$ ;$ The iodine solution is% however% very short acting% and if the time period e ceeds 1 days the ne t choice is Ca<O7=: as it allows longer inter visit periods while still being highly effective$ ANTI&IC"O'IA( E33ECT O3 &E!ICATE! )#TTA PE"C7A Ideally% all bacteria must be eradicated prior to obturation% however bacteria may persist in root canal system despite debridement and disinfection$ The material of choice for endodontic obturation is gutta percha$ 'y itself% gutta percha has shown to e hibit some antimicrobial activity due to its Cinc content$<//2=$ 'ut regular gutta percha is neither intentionally antiseptic nor bacteriostatic$ "ecently% iodoform has been included in gutta percha cones <mar6eted as &)P= suggesting that it has an antimicrobial activity$ The iodoform in the &)P cones remains inert until it comes in contact with tissue fluids that activate free iodine$ &artin has shown that X&)PT gutta percha has antimicrobial activity against S$viridans% S$aureus P '$fragilis$ I&)PJcontains 802 iodoform <C7I1= which interact with cell walls of microorganisms causing pore formation leading to loss of cytosol material and enCyme degradation$ 7owever % 'arthel et al stated that free iodine released is not substantial and must be used cautiously$ ANTI&IC"O'IA( E33ECTS O3 SEA(E"S The use of sealer during root canal obturation enhances the possible attainment of an impervious seal and serves as filler for canal irregularities and minor discrepancies between the root canal and core filling material$

A sealer with antimicrobial activity is desirable to eliminate the remaining microbes after chemomechanical preparation and to prevent reinfection$ Dinco ide eugenol based sealers have been tradionally the most commonly employed sealers$ Dinc o ide 4eugenol - Eg$ "ic6erts % Tubliseal% )rossmanTs sealer% wachTs paste$ Eugenol a phenolic compound acts on microorganisms by protein denaturation whereby the protein becomes non functional$ Eugenol is also found to be effective against mycotic cells and vegetative forms$ In order to improve the antimicrobial efficacy% 6nown bactericidal agents li6e iodoform has been incorporated resulting in modified Cinc o ide sealers such as Endoflas 3S and medicated root canal sealer <&CS=$ The antimicrobial effect of epo y resin based sealer A7 :/ is due to bisphenol diglycidyl ether$ In addition formaldehyde is released during polymeriCation which is also bactericidal$ 7owever formaldehyde is a 6nown mutagen and carcinogen$ 7ence% this is replaced by A7 Plus which is free of formaldehyde but the antimicrobial efficacy is also reduced$ Paraformaldehyde root filling materials li6e N: 6nown as "C:' contains lead and mercury which are ma,or systemic poisons$ Paraformaldehyde is included to obtain release of formaldehyde gas for antiseptic and fi ative action$ Irreversibly affects nerve endings in tissue area% thereby mas6ing inflammation process and is not currently in use$

SPA! is a resorcinol 4formaldehyde resin $ Essential reaction is to form resin between resorcinol and formaldehyde$ Antimicrobial activity is due to formaldehyde$ Endomethasone also contains paraformaldehyde with corticosteroids$ 'oth are highly to ic and not recommended for use$ Calcium hydro ide based sealers li6e ape it% C"CS%sealape % life% vitape have antimicrobial properties because of the dissociation into calcium and hydro yl ions causing a high p7$ 7igh p7 causes inhibition of enCymatic activities essential for microbial metabolism% growth and cell division$ 7owever they have been shown to have negligible effect against E$ faecalis$ )lass ionomer based sealer li6e 6etac endo has antimicrobial activity based on fluoride ion release$ Also shows disinfection of affected dentin because of its e cellent flow and the diffusion of its antibacterial components$ CONC(#SION Ideal ob,ective of root canal treatment is to eliminate bacteria and prevent reinfection$ The prudent use of antimicrobial agents to treat endodontic infections is an integral part of appropriate treatment$ Thus a thorough 6nowledge of the various antimicrobial agents is imperative for successful endodontic treatment$ "E3E"ENCES Pathways of the pulp 4 Cohen @th P Fth ed Endodontics 4 Ingle 4 ;th ed 7artyTs endodontics in clinical practice 4 5th ed

Endodontic therapy 4 ?eine 4 ;th ed Endodontic practice 4 )rossman 88th ed Endodontics 4 Stoc6% )ulabivala% ?al6er Essentials of medical pharmacology. N! Tripathi !CNA <:00:= 4 !ental chemotherapeutics$