Antibiotics used in dentistry

Antibiotics used in dentistry
Terminologies
History
Classification of antibiotics
Principles of antibiotics use
Commonly used antibiotics
Drug interaction
Drug combination
Antibiotic resistance
Summary

1. A ntibiotics used in Dentistry Resource Faculties Dr. Jyotsna Rimal Dr. Iccha Kumar Maharjan Dr. Susma Pandey Dr. Pragya Regmee Presented by : Sushant Pandey 653 Department of Oral Medicine and Radiology

2. Contents : Terminologies History Classification of antibiotics Principles of antibiotics use Commonly used antibiotics Drug interaction Drug combination Antibiotic resistance Summary

3. Antibiotics : Substances produced by microorganisms which selectively suppress the growth of or kill other microorganisms. Antimicrobial agent : Includes synthetic as well as naturally obtained drugs that attenuate microorganism.

4. H istory E h r li ch ’ s M ag i c B u l l e t s G e r ha r d D omagk - P r on t o s il

5. v Flem i n g Selman W ak s man

6. Classification On the basis of chemical structure: B-lactams– Penicillins , cephalosporins, monobactams, carbapenam Tetracycline-- Doxycycline, Oxytetracycline Aminoglycosides -- Gentamicin , Neomycin, streptomycin Macrolides -- Clarithromycin, Erythromycin, Azithromycin Quinolones -- Ciprofloxacin , Norfloxacin Sulfonamides – Sulfadiazine Lincosamides – Clindamycin, Lincomycin Glycopoetides – Vancomycin Nitroimidazoles -- Metronidazole

7. On the basis of spectrum of activity: - Narrow spectrum : Penicillin G, Streptomycin, Erythromycin - Broad spectrum : Tetracycline, Chloramphenicol On the basis of type of action: - Bacteriostatic: Macrolides, Tetracycline, Sulfonamides, Chloramphenicol, Clindamycin - Bactericidal: Penicillin, Cephalosporin, Fluo r oquin o lones, Metronidazole, Aminoglycoside

8. Acting on cell membrane polypeptides bacitracin Daptomycin

9. P rinciples of antibiotics use Bacteriostatic versus bactericidal drugs Minimum inhibitory concentration Minimum bactericidal concentration Age Immune system Renal dysfunction Hepatic dysfunction Pregnancy and lactation

10. Indicated clinical conditions for antimicrobial therapy Pyrexia within last 24 hours – indicates a systemic response to the infection Systemic symptoms like malaise, fatigue, weakness, dizziness, rapid respiration and local tender lymphadenopathy – indicate an impending sepsis Trismus – indicates spread to perimandibular spaces and can extend to secondary spaces that can be potentially dangerous.

11. As a prophylaxis in patients with systemic conditions like rheumatic heart disease, endocarditis, heart / orthopaedic prosthesis. In patients with any kind of immunocompromise – AIDS, cancer, autoimmune diseases, corticosteroid therapy, patients with immune compromised diseases like cyclic neutropenia, pancytopenia, uncontrolled diabetes to name a few common ones.

12. Special Circumstances

13. Beta-Lactam Antibiotics Includes Penicillin , Cephalosporin , Monobactam, Carbapenem MOA : Inhibits cell wall formation by inhibiting transpeptidase

14. P enicillin Types: Natural penicillin : Penicillin G and Penicillin V --- grampositive and gram-negative cocci, gram-positive bacilli Anti-staphylococcal penicillins : Methicillin, nafcillin , oxacillin, dicloxacillin (penicillinase resistant penicillin) Extended-spectrum penicillins : Ampicillin, Amoxycillin --- additional action against gram negative bacilli Antipseudomonal penicillins : Piperacillin, Ticarcillin

15. Natural Penicillins They are obtained from the fungus Penicillium chrysogenum . Penicillin G (Benzyl Penicillin) Active against a number of gram positive and gram negative cocci and gram positive bacilli. Poor oral absorption as it is readily destroyed by gastric acids. Penicillin V ( Phenoxymethyl penicillin) Similar to Penicillin G in action but it is resistant to gastric acids and can be taken orally. They are ineffective against Penicillinase producing bacteria.

16. Penicillinase resistant penicillin (Anti-staphylococcal penicillins ) Methicillin, nafcillin, oxacillin, dicloxacillin Extended-spectrum penicillins : Ampicillin, Amoxycillin Antibacterial spectrum is similar to penicillin G but they have an additional action against gram negative bacilli.

17. Beta-lactamase inhibitors: Clavulanic acid + amoxicillin [ Clavum , Mega-CV] Clavulanic acid + ticarcillin Sulbactam + ampicillin Tazobactam + piperacillin Adverse reactions : Elimination = by kidney Jarisch Herxheimer reaction ?

18. D ose : Amoxicillin [Amoxil, Ranoxyl ] Adult : 250-500 mg every 8 hour Child 125-250 mg every 8 hour Ampicillin [ Ampilin , Zycilin ] Adult : 250-500 mg every 6 hour Child : 50-100 mg/kg daily Cloxacillin [ Klox ] Adult : 250-500 mg every 4 hour Child : 50-100 mg/kg daily Amoxicillin is the most commonly used to treat odontogenic infections followed by amoxicillin + clavulanic acid Amoxycillin is available as : capsules, tablets, chewable tablets, oral suspension

19. MRSA (Methicillin-resistant Staphylococcus aureus)  Staphylococcus aureus that have become resistant to antibiotics that once destroyed it like methicillin, amoxicillin, penicillin, oxacillin , and many other common antibiotics. They have acquired penicillin binding protein which has low affinity for β-lactam antibiotics. About 2% Staphylococcal infections are caused by MRSA Treated by : Vancomycin, Linezolid

20. C ephalosporins First generation – action similar to penicillin G Second generation – greater action against gram negative organism Third generation -- enhanced activity against gram-negative bacilli Fourth generation – wide antibacterial spectrum GENERATION: PARENTERAL ORAL FIRST GENERATION CEFAZOLIN CEPHALEXIN CEPHADROXIL SECOND GENERATION CEFUROXIME CEFOXITIN CEFACLOR CEFUROXIME AXETIL CEFPROZIL THIRD GENERATION CEFOTAXIME CEFTIZOXIME CEFTRIAXONE CEFTAZIDIME CEFOPERA ZONE CEFEXIME CEFPODOXIME PROXETIL CEFDINIR CEFTIBUTEN CEFTAMET PIVOXIL FOURTH GENERATION CEFEPIME CEFPIROME

21. A dverse reactions : Similar to Penicillin Patients who have had an anaphylactic response, Stevens-Johnson syndrome to penicillins should not receive cephalosporins The cross-reactivity between penicillin and cephalosporins is around 3% to 5% Elimination – by kidney but ceftriaxone is excreted through the bile into the feces and, should be employed in patients with renal insufficiency.

22. Tetracyclines Doxycycline, Minocycline, Demeclocycline Mechanism of action : Inhibits protein synthesis by binding to 30s ribosomes U ses Localized aggressive periodontitis (inhibits the growth of Actinobacillus actinomycetemcomitans ) Refractory periodontitis Actinomycosis Juvenile periodontitis Chronic periodontal disease

23. Adverse reactions They are effective in treating periodontal diseases because their concentration in the gingival crevice is 2-10 times that in serum They inhibit synthesis and release of collagenase from human polymorphonuclear leukocytes and inhibit tissue destruction and may aid bone regeneration.

24. E limination = by kidney In renally compromised patients, doxycycline is preferred, as it is primarily eliminated via the bile into the feces. The tetracyclines should not be used in pregnant or breast-feeding women or in children less than 8 years of age. May cause discoloration and hypoplasia of teeth. Do not take tetracyclines with antacids, iron, dairy products . Dose : [Doxy, Emdox ] 100-200 mg once daily

25. 20 mg of Doxycycline Hyclate is used in host modulation therapy. Used as an adjunct to SRP in treatment of chronic periodontitis. Taken twice daily for 3-9 months. Suppress the activity of Collagenase. No antibacterial activity. Doxycycline as Host modulating agent

26. Doxycycline gel (10%): Applied in periodontal pocket in cases of chronic periodontits

27. M acrolides Azithromycin Clarithromycin Erythromycin Telithromycin MOA : The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting translocation steps of protein synthesis. Alternative to penicillin in individuals with an allergy to β-lactam antibiotics in treatment of acute oro -facial infection. Erythromycin Dose : 250-500 mg orally every 6 hours

28. Adverse reactions Should be used cautiously in patients with hepatic dysfunction. Interference with the metabolism of drugs, such as theophylline, statins, antiepileptics , digoxin

29. LINCOSAMIDE CLINDAMYCIN MOA : similar to macrolides Better bone penetration due to relatively small molecular size. So used in treatment of Osteomyelitis. Most common adverse effect is diarrhea, due to pseudomembranous colitis caused by overgrowth of C. difficile . significant activity against many gram-positive and gram negative anaerobic and aerobic microorganisms, including Bacteroides , Prevotella , Porphyromonas , Veillonella , Dose : 600mg IV/PO

30. Fluoroquinolones Inhibits bacterial DNA gyrase which results in relaxation of supercoiled DNA, promoting DNA strand breakage. 1 st Generation : Nalidixic acid 2 nd Generation: Norfloxacin, Ciprofloxacin 3 rd Generation: Levofloxacin 4 th Generation: Moxifloxacin effective against gram-negative organisms

31. ADR : Phototoxicity, Diarrhea, Nausea, Headache, Tendon rupture They are not indicated for any acute orofacial infections unless dictated by culture and sensitivity tests. Drugs with better antimicrobial spectra are readily available. Prescribed in dentistry if a patient is allergic to penicillin and/or has substantial gastrointestinal upset with erythromycin and clindamycin.

32. M etronidazole MOA: Nitro group reacts with bacterial DNA, causing inhibition of DNA replication, fragmentation of existing DNA Effective against Gram-negative anaerobes such as Prevotella intermedia, Porphyomonas gingivalis , Bacteroides , Fusobacterium Used in : -Necrotizing ulcerative gingivitis -Aggressive periodontitis -Abscesses -Orofacial infection along with Penicillins Developed as antiprotozoal drug

33. Ingestion of alcohol when taking metronidazole could cause Disulfiram like reaction i.e hallucinations and confusion, abdominal cramps, nausea, facial flushing and headache can occur. Also avoid alcohol containing mouth rinses. Decreases the metabolism of Warfarin resulting in bleeding ADR : Dose: [ Metron , Flagyl ] 200-400 mg 8 hourly

34. Drug interactions ß-lactams : Tetracyclines and other bacteriostatic antibiotics = effectiveness is decreased Allopurinol = increase incidence of ampicillin allergy Tetracyclines: Antacids and dairy products = decreases absorption Metronidazole: Ethanol = severe disulfiram like reaction Lithium = decreases its excretion Carbamazepine = increases blood level Cephalosporins and macrolides: Warfarin = increased anticoagulant effect

35. Combination of antimicrobial drugs

36. Commonly used combinations Ampicillin (250mg) + Cloxacillin (250mg) [ Megapen , Ampikem ] Amoxicillin (500mg) + Clavulanic Acid (125mg) [Clavam, mega-cv]

37. Quadrajel dental gel : Lidocaine hydrochloride 2 % w/w + Metronidazole benzoate 1 % w/w + Chlorhexidine gluconate 1 % w/w Delta gel: Metronidazole + Lidocaine + Chlorhexidine

38. Disadvantages of combination : Increased incidence and variety of adverse effects Vancomycin + gentamicin  exaggerated kidney failure Increases the chance of superinfections Inadequate dose of non-synergistic drugs  emergence of resistance Higher cost of therapy

39. Topical antibiotics : Chlorhexidine digluconate MOA : has antibacterial and antiplaque action. At low concentration increases the permeability of cell membrane causing leakage of intracellular components including potassium. At high concentration, chlorhexidine causes precipitation of bacterial cytoplasm and cell death. Effective against : Bacteria, Some fungi (candida), some viruses (HIV, HBV) Shows Substantivity i.e gets adsorbed to tooth surfaces and shows a persistent antibacterial action lasting in excess of 12 hours Available as : Mouthrinse (0.2%, 0.12% ) Gels [ Hexi gel chlorhexidine gluconate 1 %] Spray 0.1 %

40. Adverse effects : Enhanced supragingival calculus formation

41. Uses : As an adjunct to oral hygiene and professional prophylaxis Post oral surgery including periodontal surgery or root planning Medically compromised individuals predisposed to oral infections Recurrent oral ulceration Denture stomatitis Oral malodor

42. A ntibiotic resistance

43. Summary

44. Reference : A review of use of antibiotics in dentistry and recommendations for rational antibiotic usage by dentists, Dr. Akilesh Ramasamy, THE INTERNATIONAL ARABIC JOURNAL OF ANTIMICROBIAL AGENTS

45. MCQs: Which antibiotic acts by interfering with DNA function in the bacteria ? A. Doxycycline B. Ciprofloxacin C. Erythromycin D. Amoxycillin

46. Cloxacillin is indicated in infections caused by the following organism(s): A. Staphylococci B. Streptococci C. Gonococci D. All of the above

47. An 8-year-old child presented with brownish discoloured and deformed anterior teeth. History of having received an antibiotic about 4 years earlier was obtained. Which antibiotic could be responsible for the condition: A. Chloramphenicol B. Tetracycline C. Erythromycin D. Gentamicin

48. Antimicrobial drug combinations are aimed at achieving the following except: A. Faster and more complete elimination of the infecting organism B. Treat infection when nature and sensitivity of the infecting organism is not definite C. Prevent emergence of resistant strains D. Prevent superinfection

49. Prophylactic dose of Amoxycillin for adults is : 1 gm 1 hour before procedure 1 gm 2 hours before procedure 2 gm 1 hour before procedure 2 gm 2 hours before procedure

50. References : Lippincott Illustrated Reviews, Pharmacology Essentials of medical pharmacology, KD Tripathi Pharmacology and therapeutics for dentists, John A. Yeigla Carranza’s clinical periodontology

51. Thanks! Any questions?

52. Between 1962 and 20 0, no m ajor c lasses of antibiotics w ere introd u ced Fi s chba c h MA and W alsh CT S c ien c e 2009

53. In the USA, dentists prescribed 24.5 million courses of antibiotics in 2013, a prescribing rate of 77.5 prescriptions per 1,000 people. Penicillins were the most commonly prescribed antibiotic category.