k11. Antiinfective Agents

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M.Djanaluddin MGDepartement of Pharmacology

Achmad Yani School of Medicine


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Antiinfective agents play an important rolein dentistry because:

Infection and after pain,is the dentalproblem for which drugs are most aftenprescribed.


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As the knowledge about the etiology ofdental diseases is countinually increasing

and the involvement of microorganismsbecoming understood, dental health care workers continue to better a understood

the proper place of antibiotics and theireffect on microorganisms


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Types of Dental Infection

1.CariesCaries produced by Streptococcus mutantFirst important dental infection of the

newly erupting teeth of of the youngpatientThe traditional antiinfective agents have

not useful for this problem in thegeneral population.


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The treatment of choice involve use offloured water, local physical removal of

bacterial plaque, on regular basis (goodoral hygiene,dental prophylaxis), andapproprietly placed scalant


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2. Periodontal disease:It is the biggest dental problemCaused by Actinobacillus actinomycesetemcomitansTreatment that used localized method of thedrug delivery (e.g Tetracycline fibres) holdpromise for the future management ofperiodontal disease


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3.Localized Dental InfectionExtensios from either periodontic or endodontic

related source

For most localized dental infections,if adequatedrainage can beobtained antiinfective agent arenot indicated unless the patient isimmunocompromised.in occusional situation in which antibiotic are indicated the antibioticchoice is determine by the organism likely to bepresent.


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4.Systemic IsnfectionSystemic infection can be identified becausethey produced systemic symptons as

fever,malaise and tachycardia.Lesionassociated with infections producing thesetype of symptoms shoul be drained but if

this possible,antibiotic should be given.


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DENTAL INFECTION EVOLUlTION Dental infection often follow similar pathwayevolution from their begining to their end.

In the beginning the dental infection are primarycaused by gram positive cocci such as Streptococcus viridans or -hemolytic streptococi.


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After a short time to include variety of grampositive and gram negative anaerobic

organism,such as Peptostreptococcus(Peptococcus) and Bacteriodes. At this point is termed mixed infection.Over time the proportion of organismsthatbareanaerobic increases.Wit additional time and notreatment the infection progresses until itconsist of predominantly anaerobic flora


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cocci penicillin gram positive


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DEFINITION Antiinfective agents Antiimicrobial agents

Antibiotic agents Antibacterial agents Antiviral agents Anti fungal agentsBactericidalBacteriostatic


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Blood/serum levelconcentration (MIC)Spectrum

InfectionMinimal Inhibitory (MIC)Super/suprainfectionSynergism AntonismPotentiation


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INFECTIONThe factors that determine the likehood of mocausing anfection are:

Vurulence of microorganismeNumber of microorganismResistence of host (Immunologic response)


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CULTURE AND SENSITIVITYIdealy,all infectons requiring antimicrobial therapy would be cultured,and sensitivity tests would beperformed. Culture an d sensivity is the only way to be sure that adrug will kill or inhibit the growth of infectingmicroorganism in a patient specific infection

In cases of a serious infection that is not respondingto treatment,it is imperative that a culture be taken


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RESISTENCE When a culture is taken,proper collection materials(tubes or vials with correct media) and methods mustbe used to obtain reliable result.Dental professionals need to communicate to thelaboratory personnel the nature of approviate cultureto be taken

The laboratory personnel should performed a Gramstain so thay they may report all of the bacteria thatare present an high number


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SENSITIVITYObserving wether the organism are sensitive orresistent to certain test antibiotic assists indetermining which antibiotic to use in difficultinfections.Antiinfective, 1 or 2 days are required beforethe results of this test are available And may be changed,after the media results areavailable.If clinical respone has been adequate,often originalantibiotic is continued despite sensivity results


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RESISTANCEResistance related to antibiotic is natural or acquired

ability of an organism to be immune to r to resist theeffects of an antiinfective agent.

Natural resistance because of the bacterias normalproperties such as lipid structur in the cell wall.

Acquired resistance occurs when an organism that was

previously sensitive to an antimirobial agent developsresistance.


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A decrease in the use of an antibiotic drcreases theproportion of organism resistant to that antibiotic inthat given population.The first organism,which is resistant to one or moreantibiotics.


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The second organism which was not previouslyresistant,thus becomes resistant to the same antibioticas the first organism without ever having been exposedto that antibioticThe three most common mechanisms of acquiredresistance are decrease in bacterialpermeability,theproduction of bacterial enzymes andan alteration in the target site


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INDICATION FOR ANTIMICROBE1.Therapeutic indication2.Prophylactic indication


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H.M.DJAMALUDIN,DR.,Sp.FK.,M.KES

2014


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INDICATION OF ANTIMICROBIALAGENTSTwo categories :1. Prophylactic2. Therapeutic

Therapeutic indication : No simple rule to determine

Patient withouth immune deficiencies need no antibiotic tomanage their infection


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SEVERAL FACTOR THAT MUST BE CONSIDERED

PatientBest defence against patogen is host response, when these

defense lacking the need for antimicrobial is pressing.

Infection Virulence & invasive of m.o are important in deciding the

acutness, if periodontal pocket (site) remains active despiterepeating root planing, use of antibiotic to alter flora maybe

considered. If antimicrobial agent are to be used, thanorganism likely to produce the infection to antimicrobial agentmust be considered.


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TABLE OF ANTIMICROBE AGENTINFECTION SITUATION DRUG OF CHOICE ALTERNATIVE DRUGS

Periodontal disease

Acute necrotizing ulcerative ginggivitist Abcess (perio)

LJP

Adult periodontitist

RAP

Penicillin VK AmoxicillinPenicillin VK

Doxycycline

Tetracycline

Not usually treated with drugs

Doxycycline

Tetracycline

Metronidazole

Metronidazole TetracyclineTetracycline

Amoxicillin + metronidazole Augmentine(Amoxicillin+Clavulanate)

Clindamycin

Amoxicillin + Metronidazole

Oral infectionSoft tissue infection(Abcess, cellulitis, post surgical perocoronitis)

Osteomyelitis

Penicillin VK

Amoxicillin

Penicillin VK

Amoxicillin

Doxycycline

Clindamycin

Cephalosporine

Tetracycline

Clindamycin

Cephalosporine


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TABLE OF ANTIMICROBE AGENTINFECTION SITUATION DRUG OF CHOICE ALTERNATIVE DRUGS

Mixed infection insensitive to

Penicillin

Aerobes

Anaerobs & chronic infection

Amoxicillin

Metronidazole

Clindamycin

Cephalosporine

SulfonamideTetracyclineCephalosporine

Augmentine

Tetracycline

penicillin + Metronidazole

Prophylaxis for infective endocarditis

Prosthetic hearth valve

Patient with LJP

No penicillin allergy : amoxicillin

Doxycycline for 3 weeks followed byusual regimen.

Penicillin allaergyClarithromycine

AzithromycinClindamycin


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Prophylactic IndicationFew situation arise for whhich a definite indication forindication for prophylactic (AHA and ADA):1.History of infective endocarditis2.Present of heart valve prosthesisCongental heart disease


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GENERAL ADVERSE REACTIONSuperinfectionOvergrowth of an organism that different from the originalinfecting organism and resistant to the agent being used.The wider the spectrum of the antiinfective and the longer thebagentis administered.

Allergic reaction All antiinfective agent have potential to produce a variety ofallergic.Penicillin and cephalos porin are most allergenic thanother agents.Erythromycin and clindamycin have a lowallergenic potential


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Drug interaction Antiinfective can interact with other drugs and food(minerals) e.c.:Oralcontraceptive,anticoagulant,calcium.Gatrointerstinal ComplaintsPregannacy Concideration


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ORAL CONTRACEPTIVESome antibiotic have been found to decrease oralcontraceptive efficacy by increasing clearancefrom the body.(Ampicillin and tetracyclines). Antituberculosis;ripamficine induce metabolismof oral contraceptives


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ORAL ANTICOAGULANTS Antiinfective agents can potetiate the effect oforal anticoagulant.Oral anticoagulant are vitaminK inhibitors,so interfering wih the production of vitamin K could increase the anticoagulant effect.


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Tetracyclines reduce the bacterial f lora thatproduce most of the vitamin K in human bodies.Erythromycin inhibits the enzymes thatmetabolize warfarin,leading to increase in warfarin level.


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The incidence depending on the particularagent,the dose of the agent and wether the patienttakes the drug with food.Erythromycin is thehighest incidence of git complain


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Clindamycin is probably also acceptableMetronidazole is not usually used duringpregnancy but exception existTetracyclines are contraindicated because of theirefffect on teeth and skleton


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DOSE FORM Adult dose of antibiotics are commonly tabletsand capsules.Childrens dose form,including liqui andchewable antibiotic dose forms,contain sugar astheir sweetening agent

After the use of these agents,the parent or childmush brush the teeth.


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COSTImportant factor in choosing antibiotic for apatient.Interfere the successful of medicationThe best inexpensive antibiotic that can be taken will be more effective than expensive one that

cannot be purchased.


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PENICILLINDivided into four major groups1.Penicillin G and V

2.Penicillinase resistant penicillin 3.Amoxicillin4.Extended-spectrum penicillin


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Source : The mold Penicillium notatumPharmacokinetic:

Penicillin can be administered either orally orparenterally but should be applied topically.Mechanism of Action:

Penicillin is a very potent bactericidal agent that

attaches in penicillin-binding proteins (PBPs) on thebacterial cell membrane.PBPs involved in the synthesisof the cell wall and the maintenance of the cellsstructural integraty


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SPECTRUMPenicillin is a narrow spectrum antibiotic

RESISTANCEIt can occur by several different mechanismStaphylococci produce penicillinase thatnactivate the penicillin moiety by cleaving the B-

lactam ring.


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ADVERSE REACTIONToxic,allergic or hypersensitivity

Penicillins toxicity is almost nonexist,large doseshave been tolerated without adverse becausepenicillin have margin of safety. With m ssive IV doses direct CNS irritation canresult onvulsion

Penicillin G renal damage fever,eosinophilia,albuminuria and BUN)


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USESPenicillin ios mportant antibiotic in medical anddental practice.Its use in dentistry results ffromits bactericidal potency,lack toxicity,andspectrum of action.Penicillin effectiveness in the treatment of dental

infection is explained by effectiveness againstmany aerobic and anaerobic bacteria.


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Specific PenicillinsPenicillin GIs available as sodium,potassium,procaine orbenzafhine salts.These salts differ in their onset ofv action andduration of action.Caution:Sodium salts should not be avoided in

patients with a limited sodium intake such as CVpatients.Renal patients should not be given potassiumsalts.Patients may be allergic to the procaine inpenicillin procaine


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Penicillin VSpectrum is similar to Penicillin G

The potassium salts of penicillin is more solublethan the free acid and therefore is betterabsorbed when takken orally.PENICILLINAS PENICILLINS

Used only for penicillinase-producingstaphylococci.EXP:Cloxacillin and Dicloxacillin


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EXTENDED-SPECTRUM PENICILLINSCarbenicillin:

Wider spectrum of action than penicillin G


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PHARMACOKINETICSRoute of administration

Orally as tablets and capsules,IV and IM suspensionand topical preparations. ADVERSE REACTIONSGit effects (Stomatitis,abdominal

cramps,nausea,vomiting and diarrhea)Cholestatic jaundice


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USES: Aerobic and anaerobic bacteria infection.

Such as Bacteroide species implicated in dentalinfections


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AZITHROMYCIN and CLARITHROMYCINThe newer macrolide antibiotics like erythromycin Are indicated as alternative antibiotics in thetreatment of common orofacial infection caused byaerobic gram-positive cocci and susceptible anaerobsDoses: Azithromycin for 5 days of therapy:First day 250mg twice a day,and then 250 mg/day for 4 days.

Clarithromycin:500 mg twice a day for 7 days.


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DRUG INTERACTION: Azithromycin can increase the level of Astemizole,loratadine,carbamazepine,digoxjn,andtriazolamClarithromycin increase level of drugs metabolized inliver such as:Theophylline,carbamazepine,digoxin,omeprazole,andastemizole


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CLINDAMYCINClindamycin is bacteriostatic antibioticEffective primarilyvagainst gram-positive orgganismsand anaerobic Bacteriodes species.ROA:Orally,topically,iM,IV,and vaginally.Oral clindamycin is well absorbed.

Excreted as inactive metabolit in the urine and fece(via bile)


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Adverse ReactionGIT EffectsSuperinction

AllergyOther EffectsUSES


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PHARMACOKINETICS .Taken orally,metronidazole is well absorbed in 1 and 2hours after administration.Half life 8 hours.Distributed into LCS fluid,saliva,and breast milkConcentrated in the ginggival crevicular fluid

producing concentrations that are bactericidal topathogenic periodontal organism


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SpectrumThe spectrum of metronidazole includes protozoa andBacteriodes,Fusobacterium,Veillonella,Treponema,Clostridium,Peptococcus,Camptlobacter,andPeptostreptococcus.


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Adverse ReactionsGastrointestinal Effects : Stomach distress iscommon(Nausea,anorexia,diarrhea)CNS(Headache,dizziness,vertigo,ataxia,confusion,depression,weakness,insomnia and serious convulsive seizure

are rarely associated with metronidazole)


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ORAL EFFECTS Xerostomia,unpleasant metalic tasteRENAL TOXICITYCystitis,polyuria,dysuria,darkning urine (rarely)

DRUG INTERACTIONNo alcohol with metronidazole disulfiram effect


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CEPHALOSPORINS A group of antibiotics is structurely related to thepenicillin.Cephalosporins iare active against a wide variety ofboth gram-positive and negative organisms.The source of cephalosporins was Cephalosporiumacremonium near Sardinia in Italy


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GENERATION OF CEPHALOSPORINSFirst Generation:CephalexinCephradineCefadroxilSecond GenerationCefadorCefuroximeCefrozil


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Third-GenerationCefimeCefpodoximeCefdinir

Fourth GenerationCefepime


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SpectrumBactericidalEffective for Gram-positive and Gram-negativeorganismMOACephalosporins inhibit of cell wall synthesiss


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Adverse ReactionsGIT EffectsNephrotoxicitySuperinfectionLocal IrritationHemostasis and Disulfiram-Like Reaction Allergy


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RATIONAL USE OF ANTIINFECTIVE AGENTS IN

DENTISTRYStage 1 Acute abscess and cellulitis are primarily the result ofgram-positive organismDOC Penicillin 500 mg, 4 times for 5-7 days


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Stage 2During stage 2,the infecttion in micxedThis can be handled by attacking gram-positive andgram-negativeDOC Clindamycin


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TETRACYCLINESSpectrum Adverse Reaction GIT EffectsEffects on Teeth and BonesHepatotoxicity


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NephrotoxicityHematogenic EffectsSuperinfectionPphootosensitivity Allergy


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RefferenceElena Bablenis Haveles,BS Pharm,PharmDin Applied Pharmacology for the DenttalHygienist

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k11. Antiinfective Agents