Antibiotics in Dentistry

33
KMCT DENTAL COLLEGE Manassery, Mukkam ANTIBIOTICS IN DENTISTRY

description

Antibiotics are essential weapon against infection; hence wise use of antibiotics requires the clinician to take the stance that positive indication must be present before antibiotic drugs are prescribed. As a class, antibiotics are one of the most frequently used as well as misused drugs.

Transcript of Antibiotics in Dentistry

Page 1: Antibiotics in Dentistry

KMCT DENTAL COLLEGEManassery, Mukkam

ANTIBIOTICS

IN

DENTISTRY

Presented By:

Niyas Ummer1st Year PG

Department of Oral Medicine and Radiology

Page 2: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Overview

Introduction Terminology History Classification General Considerations

o Routes of administrationo Choice of agento Combined useo Problems with useo Prophylactic useo Failure

Commonly used antibiotics in dentistryo Mechanism of actiono Useso Adverse Effectso Interactionso Contra-indicationso Dosage and availability

Recent Advances Misuse Conclusion References

Page 3: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Introduction to Antibiotics

The magic word ‘Antibiotic’ inevitably springs to mind whenever an infection has to be dealt with. Antimicrobial drugs are the greatest contribution to 20th century of therapeutics - ‘Antibiotic era’. Their advent changed the outlook of the physician about the power drugs can have on diseases.

Antibiotics are essential weapon against infection; hence wise use of antibiotics requires the clinician to take the stance that positive indication must be present before antibiotic drugs are prescribed. As a class, antibiotics are one of the most frequently used as well as misused drugs.

Terminologies Used

Antibiotics: Substances produced by microorganisms, which selectively suppress the growth of or kill other microorganisms at very low concentrations. The term "antibacterial" is derived from Greek anti - "against” and baktēria, "staff, cane". The term "antibiotic" derived from anti and bios, "life".

Chemotherapy: Treatment of systemic infections with specific drugs that selectively suppress the infecting microorganism without significantly affecting the host

Antimicrobial Agent: Synthetic as well as naturally obtained drugs that attenuate microorganisms

History of Antibiotics

Milestones in History

Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics“

Term 'antibiosis‘ coined by the French bacteriologist Jean Paul Vuillemin Antibiosis first described in 1877 in bacteria when Louis Pasteur and Robert

Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis

Renamed ‘antibiotics’ by Selman Waksman, an American microbiologist, in 1942

Synthetic antibiotic chemotherapy began in Germany with Paul Ehrlich in the late 1880s

In 1928, Alexander Fleming observed antibiosis against bacteria by a fungus of the genus Penicillium. He postulated the effect was mediated by an antibacterial compound named penicillin, and that its antibacterial properties could be exploited. He attempted to use a crude preparation to treat some infections, but unable to pursue its further development.

Page 4: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Period of Empirical Use (16th - 17th Century)

Mouldy curd by Chinese on boils Chaulmoogra oil by Hindus in leprosy Chenopodium by Aztecs for intestinal worms Mercury by Paracelsus for syphilis Cinchona bark for fevers

Phase of Dyes and Organometallic Compounds

Paul Ehrlich (1890-1935) coined the term ‘chemotherapy’. He developed two antibiotics, atoxyl for sleeping sickness and arsphenamine for syphilis.

Modern Era of Antibiotics

Domagk (1935) developed Prontosil for use in pyogenic infections. It came to be known as the first commercially available antibiotic.

Paul Ehrlich

DomagkProntosil

ChenopodiumChaulmoogra

Page 5: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Classification of Antibiotics

Based on Chemical Structure:

Sulfonamides Sulfadiazine, Sulfones (Dapsone)

Diaminopyridines Trimethoprim, Pyrimethamine

Quinolones Nalidixic Acid, Norfloxacin, Ciprofloxacin

β-lactam Penicillins, Cephalosporins, Monobactams, Carbapenems

Tetracyclines Oxytetracycline, Doxycycline

Nitrobenzene derivative Chloramphenicol

Aminoglycosides Streptomycin, Gentamycin, Amikacin, Neomycin

Macrolide Erythromycin, Clanthromycin, Azithromycin

Lincosamide Lincomycin, Clindamycin

Glycopeptide Vancomycin, Teicoplanin

Oxazolidinone Linezolid

Polypeptide Polymyxin-B, Colistin, Bacitracin, Tyrothricin

Nitrofuran derivatives Nitrofurantoin, Furazolidone

Nitroimidazoles Metronidazole, Tinidazole

Nicotinic acid derivatives Isoniazid, Pyrazinamide, Ethionamide

Polyene Nystatin, Amphotericin-B, Hamycin

Azote derivatives Miconazole, Clotrimazole, Ketoconazole, Fluconazole

Others Rifampin, Spectinomycin, Sodium fusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone, Clofazimine, Griseofulvin

Based on type of organisms against which primarily active:

Antibacterial Penicillins, Aminoglycosides, Erythromycin, etc.

Antifungal Griseofulvin, Amphotericin B, Ketoconazole, etc.

Antiviral Acyclovir, Amantadine, Zidovudine, etc.

Antiprotozoal

Chloroquine, Pyrimethamine, Metronidazole, Diloxanide, etc.

Page 6: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Anthelmintic Mebendazole, Pyrantel, Niclosamide, Diethyl carbamazine, etc.

Based on spectrum of activity:

Narrow-spectrum

Penicillin G, Streptomycin, Erythromycin

Broad-spectrum Tetracyclines, Chloramphenicol

Based on type of action:

Primarily bacteriostatic

Sulfonamides, Erythromycin, Tetracyclines, Ethambutol, Chloramphenicol, Clindamycin, Linezolid

Primarily bactericidal

Penicillins, Cephalosporins, Aminoglycosides, Vancomycin, Polypeptides, Nalidixic acid, Rifampin, Ciprofloxacin, Isoniazid, Metronidazole, Pyrazinamide, Cotrimoxazole

Based on source obtained from:

Fungi Penicillin, Cephalosporin, Griseofulvin

Bacteria Polymyxin B, Colistin, Bacitracin, Tyrothricin, Aztreonam

Actinomycetes

Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides, Polyenes

Choice of an Antibiotic Agent

Choosing the right antibiotic depends on qualities of patient, the infecting organism and the drug, as given below.

Patient Factors

a) Age:

o The age of the patient affects kinetics of drugs, including its absorption, metabolism and excretion.

b) Genetic Factors:

o Primaquine, nitrofurantoin, sulfonamides, chloramphenicol and fluoroquinolones produce haemolysis in Glucose-6-Phosphate Dehydrogenase deficient patient

Page 7: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

c) Renal and Hepatic Function:

o Cautious use and dose modification advised when the organ for disposal of the drug is defective/diseased

Renal Failure

Dose reduction in mild failure

Aminoglycosides, Amphotericin B, Cephalosporins, Ethambutol, Vancomycin, Flucytosine

Dose reduction in moderate-severe failure

Metronidazole, Carbenicillin, Cotrimoxazole, Aztreonam, Meropenem, Fluoroquinolones, Clarithromycin, Imipenem

Drugs to be avoidedCephalothin, Talampicillin,Nalidixic acid, Tetracyclines, Nitrofurantoin (except doxycycline)

Liver Disease

Dose reductionChloramphenicol, Isoniazid, Metronidazole, Rifampin, Clindamycin

Drugs to be avoided

Erythromycin estolate, Tetracyclines, Pyrazinamide, Nalidixic acid, Talampicillin, Pefloxacin

d) Local Factors:

o Pus and secretions decrease the efficacy of sulfonamides and aminoglycosides

o Necrotic material or foreign body makes eradication impossibleo Haematomas foster bacterial growtho Lowering of pH at the site of infection reduces activity of macrolides

and aminoglycosideso Anaerobic environment in the centre of an abscess impairs bacterial

transport processes which concentrate aminoglycosides in the cello Penetration barriers hamper the access to the site of infectiono Some drugs like trimethoprim and fluoroquinolones attain high

concentration due to ion trapping

e) Drug Allergy:

o If a drug has caused allergic reaction, it has to be avoided in that patient.

o β-lactams, sulfonamides, fluoroquinolones, nitrofurantoin frequently cause allergy.

f) Impaired Host Defense:

o Pyogenic infections are common in neutropenic patients.

Page 8: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

o Infections by low grade pathogens and intracellular organisms occur if cell-mediated immunity is impaired.

o In a patient with normal host defense, a bacteriostatic AMA may achieve cure.

o But in an impaired host defense, intensive therapy with cidal drugs is recommended.

g) Pregnancy:

a. All AMAs should be avoided in the pregnant because of risk to the foetus

b. Penicillins, many cephalosporins and erythromycin - safec. Tetracyclines - acute yellow atrophy of liver, pancreatitis and kidney

damage in the mother - teeth and bone deformities in the offspringd. Aminoglycosides - foetal ear damage

Risk Category of Drugs in Pregnancy

Category

Description

AAdequate studies in pregnant women have failed to demonstrate a risk to the foetus

B

Adequate human studies are lacking, but animal studies have failed to demonstrate a risk to the foetus amoxicillinor,Adequate studies in pregnant women have failed to demonstrate a risk to the foetus, but animal studies have shown an adverse effect on the foetus

C

No adequate studies in pregnant women and animal studies are lacking or have shown an adverse effect on foetus, but potential benefit may warrant use of the drug in pregnant women despite potential risk

DThere is evidence of human foetal risk, but the potential benefits from use of the drug may be acceptable despite the potential risk

XStudies in animals or humans have demonstrated foetal abnormalities, and potential risk clearly outweighs possible benefit

Organism-related Factors

a) Initial Empirical Therapy:

Identification of the microorganism and antimicrobial sensitivity testing are time consuming, expensive & impractical. Sometimes, it is not possible to obtain appropriate samples of infected material. Furthermore, well defined site and features of the infection enable organisms causing such infections to be reliably deduced. SO empirical therapy is usually carried out. In addition, most dental infections are acute in nature, hence treatment cannot be delayed.

Page 9: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

b) Identification of Causative Organism:

Type of bacteria (aerobic/anaerobic) and their specific identification is necessary for proper management of the condition. Most odontogenic infections (70%) are caused by a mixture of aerobic and anaerobic bacteria. Well-circumscribed chronic non-advancing abscesses contain mostly anaerobic bacteria. Cellulitis type of lesions show exclusively aerobic bacteria. When the infection is contained longer & controlled, only anaerobic flora is evident. Abscesses may contain anaerobic bacteria.

c) Antibiotic Sensitivity for Causative Organism:

Antibiotic therapy is initial / empirical or definitive, depending on whether the organism is identified precisely.

Drug Factors

a) Spectrum of Activity:

For definitive therapy, a narrow-spectrum drug which selectively affects the concerned organism is preferred. For empirical therapy, often a broad-spectrum drug has to be used to cover all likely pathogens.

b) Type of Activity:

Acute infections resolve faster with a cidal drug and reduces the number of bacteria at the site of infection. For patients with impaired host defence, life-threatening infections, infections at less accessible sites (SABE) or when carrier state is possible (typhoid), a bactericidal drug is preferred.

c) Sensitivity of the Organism:

On the basis of MIC values (if available) and consideration of postantibiotic effect

d) Relative Toxicity:

Less toxic antibiotic is preferred

e) Pharmacokinetic Profile:

Antibiotic has to be present at the site of infection in sufficient concentration for an adequate length of time. Aminoglycosides and fluoroquinolones produce ‘concentration-dependent inhibition’, where the inhibitory effect depends on the ratio of peak concentration to the MIC. β-lactams, glycopeptides and macrolides produce ‘time-dependent inhibition’ where the antimicrobial action depends on the length of time the concentration remains above MIC. Drug which penetrates better and attains higher concentration at the site of infection is more effective.

f) Route of Administration:

Less severe infections warrant the use of oral antibiotic. Serious infections require parenteral antibiotics.

Page 10: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

g) Evidence of Clinical Efficacy:

Relative value of different AMAs in treating an infection is decided on the basis of comparative clinical trials. Optimum dosage regimens and duration of treatment are also determined on the basis of such trials. Reliable clinical trial data, if available, is the final guide for choice of the antibiotic.

h) Cost:

Less expensive drugs are to be preferred

Principles of Antibiotic Dosing for Orofacial Infections

Employ high doses for a short duration Achieve blood levels of antibiotic at 2-8 times the MIC Use frequent dosing intervals Determine the duration of therapy by remission of disease Proper time intervals (four times the T½) Proper route of administration Penetration of drug

Routes of Administration

Antibiotic Combinations

More than one AMAs are frequently used concurrently to treat infections.

Objectives:

i. To achieve synergism and enhance antimicrobial actionii. To reduce severity or incidence of adverse effects

iii. To prevent emergence of resistanceiv. To broaden the spectrum of antimicrobial action for polymicrobial infectionsv. For empirical therapy of an infection in which the cause is unknown

Page 11: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Prophylactic Use

Antibiotic prophylaxis with dental procedures is reasonable only for patients with cardiac conditions associated with the highest risk of adverse outcomes from endocarditis.High Risk Patients:

Prosthetic cardiac valve or prosthetic material used in valve repair Previous endocarditis Congenital heart disease only in the following categories: Unrepaired cyanotic congenital heart disease, including those with palliative

shunts and conduits Completely repaired congenital heart disease with prosthetic material or

device, whether placed by surgery or catheter intervention, during the first six months after the procedure

Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

Cardiac transplantation recipients with cardiac valvular disease

Dental procedures for which prophylaxis is reasonable:

All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth, or perforation of the oral mucosa.

Antibiotic prophylaxis is NOT recommended for:

Routine anesthetic injections through noninfected tissue Taking dental radiographs Placement of removable prosthodontic or orthodontic appliances Adjustment of orthodontic appliances Placement of orthodontic brackets Shedding of deciduous teeth Bleeding from trauma to the lips or oral mucosa

Page 12: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Problems associated with Antibiotic use

1. Toxicity

a) Local Irritancy:

Toxicity that is exerted at the site of administration. Gastric irritation, pain and abscess formation are evident. Complication of IV administration that commonly arises is thrombophlebitis of the injected vein. E.g. erythromycin, tetracycline, chloramphenicol

b) Systemic Toxicity:

Dose related and predictable organ toxicities can also occur.

High Therapeutic Index Penicillins, some Cephalosporins, Erythromycin

Low Therapeutic Index Aminoglycosides, Tetracyclines, Chloramphenicol

Very Low Therapeutic Index

Polymyxin B, Vancomycin, Amphotericin B

2. Hypersensitivity

Reactions that range from rashes to anaphylactic shock, that are unpredictable and unrelated to dose. Practically all AMAs are capable of causing hypersensitivity. More common culprits include penicillins, cephalosporins, sulfonamides, fluoroquinolones.

3. Drug Resistance

Page 13: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

It is the unresponsiveness of a microorganism to an AMA. It can be of the following types:

Natural Resistance:Microorganisms inherently lack the metabolic process or the target site which

is affected by the particular drug. It is generally a group or species characteristic.

Acquired Resistance:Development of resistance by an organism (which was sensitive before) due

to the use of an AMA over a period of time. It occurs by mutation or gene transfer.

Cross Resistance:Acquisition of resistance to one AMA conferring resistance to another AMA,

to which the organism has not been exposed. It may be complete, or partial; two-way, or one-way.

Prevention:

No indiscriminate and inadequate or unduly prolonged use – prefer symptom determined shorter courses

Prefer rapidly acting and selective (narrow spectrum) AMAs Broad-spectrum drugs - only when a specific one cannot be determined or is

not suitable Use combination of AMAs for prolonged therapy Infection by organisms notorious for developing resistance treated intensively

4. Superinfection

Appearance of a new infection as a result of antimicrobial therapy. It is commonly associated with the use of broad/extended-spectrum antibiotics. It is more common when the host defense is compromised. Sites involved are those that normally harbor commensals. They are generally more difficult to treat.

To minimize superinfections:

Use specific (narrow-spectrum) AMA Do not use antimicrobials to treat trivial, selflimiting or untreatable (viral)

infections Do not unnecessarily prolong antimicrobial therapy

5. Nutritional Deficiencies

Some of the B complex group of vitamins and Vitamin K are synthesized by the intestinal flora. Prolonged use of antimicrobials which alter this flora result in vitamin deficiencies.

6. Masking of an infection

Short course of an AMA may be sufficient to treat one infection but only briefly suppress another one contacted concurrently. Other infection will be masked initially, but will manifest later in a severe form.

Page 14: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Failure of Antibiotic Therapy

Success of therapy measured either clinically in terms of improvement in symptoms/signs or microbiologically as eradication of the infecting organism. Antimicrobials may fail to cure an infection/fever, or there may be relapses. When a real or apparent failure of the antimicrobial regimen occurs, the diagnosis and therapy should be reviewed.

Causes of failure:i. Improper selection of drug, dose, route or duration

ii. Treatment begun too lateiii. Failure to take necessary adjuvant measuresiv. Poor host defensev. Infecting organism present behind barriers

vi. Trying to treat untreatable infections or other causes of fevervii. Presence of dormant or altered organisms which later give rise to a relapse

Common Antibiotics in Dentistry

1. PENICILLINS

Classification:

Natural penicillin Penicillin G

Acid resistant penicillin Penicillin V

Penicillinase resistant penicillin Methicillin

β lactamase inhibitors Clavulanic acid

Penicillin active against pseudomonas

Carboxy and ureidopenicillins

Extended spectrum penicillinsAminopenicillins: AmpicillinCarboxypenicillin: CarbenicillinUreidopenicillin: Piperacillin

a) Penicillin G

Antibacterial Spectrum: Streptococci, pneumococci, N. gonorrhoea, clostridia, M. TB, spirochaetes, actinomyces israeli, B. anthracis

Mechanism of Action:Interfere with the synthesis of bacterial cell wall

Adverse Effects:

Page 15: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Local irritancy and direct toxicity Hypersensitivity reactions Super infections Jarisch-Herxhemier reactions

Uses:i. Dental infections: periodontal abscess, periapical abscess, pulpitis

ii. Medicinal uses: Gonorrhoea, syphilis, tetanus

Preparations and Dose:Sodium penicillin G inj.: Benzyl pen 0.5,1 MU inj.Procaine penicillin G inj.: 0.5,1 MU dry powders in vialFortified procaine penicillin G inj.: 3+1 lac U vialBenzathine penicillin G: Penidure LA 0.6, 1.2, 2.4 MU as dry

powder in vial

Contraindications: Allergies Poor renal function

Drug Interactions:Oral contraceptives

Pregnancy category: B

Trade Names: PENCIP, PENTIDS, SODICILLIN

b) Ampicillin

Antibacterial Spectrum: E. coli, proteus, salmonella, shigella and many Gram positive organisms like cocci, bacilli etc.

Mechanism of Action:Interfere with the synthesis of bacterial cell wall

Adverse Effects: Diarrhoea Rashes

Drug Interactions:Oral contraceptives

Uses:i. Urinary tract infection

ii. Respiratory tract infectioniii. Meningitis, gonorrhoeaiv. SABE, typhoid fever

Page 16: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

v. Bacillary dysentery, septicemias

Contraindications: Allergies Poor renal function

Dosage:0.5-2g oral/I.M/I.V every 6 hrs for adults25-50 mg/kg/day for children

Trade Names: AMPISYN, AMPILIN, AMPI-500, ALFACILLIN, AMPICILLIN

c) Amoxicillin

Similar to ampicillin in all aspects except: Oral absorption is better Incidence of diarrhea It is less active against Shigella and H. influenzae

Dosage:250-500mg TDS given for 5 daysUses:Choice of drug for prophylaxis of local wound infection as well as distant infection following dental surgery

Trade Names: MOX, AMOX, AMOXIL, AMOXIPEN, AUGMENTIN (Amoxicillin and clavulanic acid)

d) Methicillin

MRSA (methicillin resistant staph. aureus) are organisms resistant to methicillin.

Drug of choice: vancomycin/linezolid. Ciprofloxacin can also be used

2. CEPHALOSPORINS

Mechanism of Action:Interfere with the synthesis of bacterial cell wall

Classification:

a) First Generation:

Effective against gram positive cocci, including penicillinase producing staph, most anaerobes and community acquired infections caused by E.coli, Proteus and klebsiella

Examples are: Cefalexin, Cefadroxil

b) Second Generation:

Page 17: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Show increased antibacterial activity Cefmandole has markedly increased activity. But it has less activity

against strep. Cefactor, increased activity against H.influenzae

c) Third Generation:

Ceftriaxone shows high efficacy in bacterial meningitis, multi resistant typhoid fever, complicated urinary tract infections, abdominal sepsis and septicemias

Examples are: Cefpodoxime proxetil, cefoperazone

d) Fourth Generation:

Examples are: Cefepime, cefpirome

Dosage: 250-1000 mg q 6 h x 7-10 days

Uses:i. Dental infections

ii. General medical uses like meningitis, typhoid etc

Adverse Effects: Pain after I.M injection Diarrhoea Hypersensitivity reactions Nephrotoxicity Bleeding Neutropenia and thrombocytopenia

Contraindications: Allergies Poor renal function

Drug Interactions: Probenecid

Pregnancy Category: B

3. TETRACYCLINES

Antibacterial Spectrum: Cocci: N. gonorrhoea and N. menigitidisBacilli: Clostridia and anaerobic bacilli, H. ducreyiSome spirochetes, mycoplasma, actinomyces

Mechanism of Action:Inhibit protein synthesis by binding to 30S ribosomes - prevent aminoacyl transfer RNA from entering the acceptor sites on the ribosome

Page 18: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Uses:

i. Orodental infectionsii. Gingivitis

iii. Periodontal ligament related diseases

Adverse Effects:

Irritative effects Liver damage Kidney damage Phototoxicity Teeth and bones: Enamel hyperplasty, inhibition of fibula growth, dental

caries, brown discolouration, formation of calcium tetracycline crystals Antianaboilic effects Increased intracranial pressure Diabetes insipidus Vestibular toxicity Hypersensitivity Superinfection

Dosage: 100 mg qd-bid x 7-14 days

Contraindications:

Food Pregnancy

Drug Interactions:Anti-epileptics

Pregnancy category: D

4. CHLORAMPHENICOL

Antibacterial Spectrum: H. influenzae, salmonella, klebsiella along with those sensitive to tetracycline

Mechanism of Action:Inhibit protein synthesis binding to 50S subunit

Uses:

i. Enteric feverii. H. influenzae meningitis

iii. Anaerobic reactions iv. Intraocular infections

Adverse Effects:

Bone marrow depression Hypersensitivity reactions Irritative effects

Page 19: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Superinfections Gray baby syndrome

Dosage: Daily dose not to exceed 2–3 g; duration of therapy to be < 2 weeks, total dose in a course < 28 g

Contraindications:Pregnancy

Drug Interactions:

Inhibits metabolism of tolbutamide, chlorpropamide, warfarin, cyclophosphamide and phenytoin

Phenobarbitone, phenytoin, rifampin enhance metabolism Antagonize the cidal action of β-lactams/aminoglycosides on certain bacteria

Pregnancy category: D

5. AMINOGLYCOSIDES

Antibacterial Spectrum: Gram negative bacilli, H.ducreyi, yersinia pestis, gram positive cocci, enterococci

Mechanism of Action:Inhibit protein synthesis

Uses:

i. Tuberculosisii. Plaque

iii. Tularemiaiv. Brucellosisv. Enterococcal infections

vi. Subacute bacterial infections

Adverse Effects:

Ototoxicity Nephrotoxicity Neuromuscular blockade Allergy Superinfection

Dosage: 0.5-1 gm by I.M injection

Contraindications:

Pregnancy (risk of foetal ototoxicity)

Page 20: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Concurrent use of other ototoxic drugs, e.g. high ceiling diuretics, minocycline.

Concurrent use of other nephrotoxic drugs, e.g. amphotericin B, vancomycin

Precautions:

Patients past middle age Kidney damage

Drug Interactions:Cautious use of muscle relaxants

Trade Names: GENTACIL, GENTYCIN, GENTAMICIN

6. MACROLIDES

Antibacterial Spectrum: Streptococcus, staphylococcus, gonorrhea, clostridia

Mechanism of Action:Act by inhibiting protein synthesis by binding to the bind to the 23S rRNA of 50S ribosomal subunits

Uses:

i. Dental infections: Periodontal, periapical abscess, necrotizing ulcerative gingivitis, gingival cellulites

ii. General medical uses: Pharyngitis, tonsillitis, rheumatic fever

Adverse Effects:

Gastrointestinal problems Hypersensitivity Reversible hearing impairment

Dosage:Erythromycin: 250-500 mg 6 hourly (max.4g/day), children 30-60-mg/kg/dayAzithromycin: 500 mg once daily 1hr before or 2hrs after food for 3 days

Precautions:Poor hepatic function

Drug Interactions:Cytochrome P-450

Pregnancy category: B

Page 21: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

7. METRONIDAZOLE

Antibacterial Spectrum: Entamoeba histolytica, giardia lamblia, anaerobic bacteria, like clostridium, spirochetes, peptococcus

Mechanism of Action:Reduced intermediate interacts and breaks the bacterial or parasitic DNA

Adverse Effects:

Anorexia, nausea, metallic taste, abdominal cramps Headache, dryness of mouth, rashes, and Glossitis (rare) Thrombophlebitis of the injected vein

Uses:

i. Orodental infectionsii. Drug of choice in acute necrotizing ulcerative gingivitis

iii. Periodontitis, pericoronitis, acute apical infections, brain abscessiv. Drug of choice for all forms of anaerobic infections, acute dysentery, liver

abscessv. Drug of choice for intestinal giardiasis and trichomonas vaginitis

Dosage: 200-400 mg TDS (15-30mg/kg/day)

Trade Names: METROGYL, FLAGYL

Contraindications:

Pregnancy Chronic alcoholism

Precautions:Poor hepatic function

Drug Interactions:

EtOH Warfarin Li+

Pregnancy category: D

8. FLUOROQUINOLONES

Antibacterial Spectrum: All organisms are susceptible except some strep, anaerobic cocci, mycobacterium

Mechanism of Action:Bind to A subunit of DNA gyrase with high affinity and interfere with strand cutting and resealing functions

Page 22: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Adverse Effects:

GIT: Nausea, vomiting, bad taste, anorexia CNS: Dizziness, headache, restlessness, anxiety Skin/hypersensitivity

Uses:

i. Urinary tract infectionsii. Gonorrhea

iii. Soft tissue, bone and joint infections especially gram negative organismsiv. Community acquired pneumonia

Dosage: Ciprofloxacin 250-500 mg QD x 7-10 days

Trade Names: BIOCIP, CIP, CIPLOX, CIPLO

Contraindications:

Children (damage of the cartilage in weight bearing joints) Pregnancy

Drug Interactions:

Probenacid Warfarin

Pregnancy category: C

9. CLOTRIMOXAZOLE

Combination of trimethoprim and sulfamethoxazole (1:20)

Antibacterial Spectrum: Same as sulfonamide but include salmonella typhi, klebsiella, enterobacter

Mechanism of Action:Inhibit bacterial dihydrofolate reductase

Uses:

i. Pneumocystis carnii pneumonia in AIDS patientsii. Tonsillitis, Pharyngitis, sinusitis

iii. Urinary tract infections, orodental infections

Adverse Effects:

Methamoglobinemia Blood dyscarasis Nausea, vomiting, stomatitis, headache and rashes Neonatal hemolysis

Contraindications:Pregnancy

Page 23: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Newer Antibiotics

i. Ceftolozane/tazobactam: Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor)

ii. Ceftazidime/avibactam: Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor)

iii. Ceftaroline/avibactam: Anti-MRSA cephalosporin/ β-lactamase inhibitor combination (cell wall synthesis inhibitor)

iv. Plazomicin: Aminoglycoside (protein synthesis inhibitor)v. Eravacycline: A synthetic tetracycline derivative / protein synthesis inhibitor

targeting the ribosomevi. Brilacidin: Peptide defense protein mimetic (cell membrane disruption)

Misuse in Dentistry

Treatment of Nonresponsive Infections:

Diseases caused by viruses are self-limited

Therapy of Fever of Unknown Origin:

Fever persisting for 2 or more weeks – only 1/4th are due to infections Require treatment with agents that are not used commonly for bacterial

infections, surgical drainage or prolonged courses of pathogen-specific therapy

May mask an underlying infection, delay the diagnosis, and prevent identification of the infectious pathogen

Noninfectious causes

Page 24: Antibiotics in Dentistry

KMCT DENTAL COLLEGE ORAL MEDICINE AND RADIOLOGY

Inappropriate Reliance on Chemotherapy Alone:

Drainage, debridement, and removal of foreign body Misuse in Dentistry Improper Dosage: Dosing errors (wrong frequency of administration or use of either an

excessive or a subtherapeutic dose) Excessive amounts can result in significant toxicities Too low a dose may result in treatment failure or resistance

Lack of Adequate Bacteriological Information:

Bacterial cultures and Gram stains of infected material Frequent use of drug combinations or drugs with the broadest spectra Agents are selected more likely by habit than for specific indications Dosages employed are routine rather than individualized

Conclusion

Antibiotic therapy is an art and a science. There are so many confounding variables (such as suspected pathogen, ability to establish drainage, pharmacokinetic properties of the drug, mechanism of action of the antibiotic, virulence of the infection, the current health status of the host, and host defense mechanisms), that it is not possible to make antibiotic therapy into a mechanistic technologic science.

The most important decision for the dental practitioner to make is not only which antibiotic to use but whether to use one at all.

References

i. Essentials of Medical Pharmacology, 6th Edition – K. D. Tripathiii. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th

Editioniii. Pharmacology and Pharmacotherapeutics - R. S. Satoskariv. Manoj Kumar Jain, Sheetal Oswal K. Antibiotics in Dentistry – An Art and

Science. Annals of Dental Specialty 2013; 1(1):20-25.v. Prevention of Infective Endocarditis: Guidelines From the American Heart

Association, by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease. Circulation, 2007; 116: 1736-1754.

Online sources:http://www.medclik.comhttp://en.wikipedia.org/wiki/Antibacterial