Antibiotics in dentistry.pptx

Antibiotics in dentistry

1. Antibiotic s Presented by : Dr. Stutee Beriwal Pg 1 st year Department of Oral Medicine and Radiology

2. I N T R O D UC T I ON Antimicrobial drugs are the greatest contribution of the 20 th century to therapeutics. The purpose of antimicrobial chemotherapy is to aid the host defences in controlling and eliminating microbes that temporarily have overwhelmed the protective host mechanisms.

3. HISTORY OF ANTIBIOTICS 1877 - Louis Pasteur & R obert K och Inhi b ition of so m e m i c r ob e s by others; anthrax ( Bacillus anthracis) named as antibiosis. In 1942 - W aks m a n rena m ed it a s antibiotic. 1908 - Gelmo Synthesized sulfanilamide (1st sulfonamide)

4. 1928 - Alexander Fleming Penicillin notatum inhibits growth of bacteria. ‘PENICILLINS’ 1941 - Chain n Florey Discovered properties of penicillin

5. DEFINITIONS

6. ▪ Waksman defined antibiotic as “a chemical substance p r oduced by m ic r o-organis m s h av i ng the prope r ty of inhibiti n g the g r o w t h of or d est r o y ing other m icro organisms . ▪ A nti b i otics are a natural l y o c cu r ring, s e m is y nthet i c or s y n t hetic t y pe of a n t i bacterial age n t t h at destro y s or inhibits the growth of selective microorganisms, generally at low concentrations.

7. CLASSIFICATION

8. Based on chemical structure Based on mechanism of action Based on type of organism against which primarily active Based on spectrum of activity Based on type of action Based on organism susceptible

9. Type of organism against which is primarily active . Antibacterial : Penicillins, Aminoglycosides, Erythromycin Antifungal : Griseofulvin, Amphotericin B, Ketoconazole Antiviral : Acyclovir, Amantadine, Zidovudine Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole ▪ ▪ ▪ ▪ ▪ Antihelminthic: Mebendazole, P raziquantel , diethyl carbamazine.

10. Classification Based on Spectrum of activity Narrow spectrum : Penicillin G, Streptomycin, Erythromycin Broad spectrum : Tetracyclines, Chloramphenicol

11. Classification based on Type of Action Primarily bacteriostatic : Sulfonamides, Tetracyclines. Chloramphenicol, Erythromycin, Ethambutol, clindamycin Primarily bactericidal : Penicillins, Cephalosporins, Aminoglycosides , Cotrimoxazole, Vancomycin, Nalidixic acid, isoniazid, ciprofloxacin, Metronidazole

12. Classification based on Antibiotics obtained from: Fungi : Penicillin, Cephalosporin, Griseofulvin Bacteria : Polymyxin B, Colistin, Bacitracin Actinomycetes : Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides .

13. Classification According To The Organisms Susceptible: Antibiotics mainly effective against Gm+ve bacteria : for systemic infections: e.g., Penicillins, Macrolides Antibiotics mainly effective against Gm-ve bacteria : e.g., Streptomyci n etc

14. Antibiotics effective against both Gm+ve and Gm-ve bacteria : For systemic infections: Ampicillin, Amoxicillin, Cephalosporins . For topical use: Neomycin, Framycetin Antibiotics effective against both Gm+ve and Gm-ve bacteria, Rickettsiae and Chlamydia: Tetracyclines, Chloramphenicol

15. Antibiotics effective against acid fast bacilli : Streptomycin, Rifampin, Kanamycin Antibiotic effective against protozoa : Tetracycline Antibiotic effective against fungi : Nystatin, Amphotericin B, Griseofulvin , Fluconazole, Micafungin. Antimalignancy antibiotics : Actinomycin D, Mitomycin

16. Problems that arise with the u s e o f AMA Super infection: Ap pearance of a new infection as a result of antimicrobial therapy due to destruction of commensal organisms . Commonly associated with the use of broad spectrum antibiotics e.g. tetracyclines, chloramphenicol, ampicillin etc. Toxicity: Local irritancy : Gastric irritation, thrombophlebitis. S ystemic toxicity : Based on therapeutic index.

17. Hypersensitivity reactions: The whole range of reactions from rash to anaphylactic shock can occur. M ore commonly involved are pencillins, cephalosporins, sulfonamides and fluoroquinolones. Drug resistance: Production of enzymes that inactivate the drug e.g B lactamase ( B lactam antibiotics), acetyl transferase (chloramphenicol) kinases and other enzymes (aminoglycosides) Alteration of drug binding site Reduction of drug uptake by the bacterium: Tetracyclines Nutritional deficiencies- Prolonged use of AMA may alter the flora may result in vitamin deficiency.

18. Antibiotic Strategies Cardinal Rules: Use the right drug. Use the right dose. Use the correct dosing schedule. Correct duration. Use a loading dose to rapidly achieve therapeutic blood levels. Avoid combination of bacteriostatic and bactericidal drugs.

19. Choice of an Antimicrobial ? Patient factors Infecting organism Drug related

20. Patient factors Age Chloramphenicol in new born-grey baby syndrome Tetracycline are C/I in children below 6 years Half life of aminoglycosides is prolonged in the elderly Impaired host defence Bactericidal drugs are must in immunocompromised patients. Pregnancy All antibiotics pose risk to the fetus when used in pregnancy. Penicillin's, most cephalosporins and macrolides appear safe.

21. The United States Food and Drug Administration (FDA) has established four levels of drug risk during Pregnancy : (A) Without demonstrated risk to fetus :- No antibiotic corresponds to group A. (B) Animal reproduction studies have failed to demonstrate risk to fetus but no adequate studies in pregnant women cephalosporins, azithromycin, erythromycin, metronidazole and penicillins with or without beta-lactamase inhibitors. (C ) Animal reproduction studies have shown an adverse effect on the fetus, no adequate study on pregnant women, Clarithromycin, the fluorquinolones and the sulfa drugs (including dapsone). (D) Teratogenic effects upon the fetus – use of the drug being conditioned to the obtainment of benefit that outweighs the risks:- Tetracyclines and Aminoglycosides.

22. Principles of antibiotics use Identification of the infecting organism Empiric therapy prior to identification of the organism Determining antimicrobial susceptibility of infective organisms Bacteriostatic versus bactericidal drugs M i nimum inh i bitory con c entr a tion M i nimum b a c t e r icid a l con c entr a tion Patient factors Age Immune system R e n a l dysfunc t ion H e p a tic dysfunc t i on P r e g n a ncy a nd l a c t a tion Cost of therapy

23. Renal failure

24. Liver function

25. Genetic Factors: Antimicrobials producing haemolysis in G6PD deficient patients are: • Primaquine, Chloroquine, Quinine • Dapsone, Sulphonamides • Chloramphenicol, Nitrofurantoin, Fluoroquinolones

26. Organism Related Considerations ➢ Clinical Diagnosis itself directs the choice of the AMA. ➢Choice based on bacteriological examination. ➢Empirical Therapy: Refers to initiation of antibiotics depending upon knowledge and experience of physician before result of culture and sensitivity test is available Broad spectrum antibiotics started In serious infections like meningitis & septicemia

27. Drug related factors: Combined Use of Antimicrobial Agents ➢To achieve synergism (supra additive effect) e.g Penicillin/ampicillin + Streptomycin /Gentamycin- SABE ➢To reduce severity of adverse effects ➢To prevent emergence of resistance ➢To broaden the spectrum of antimicrobial action

28. General Principles make an accurate diagnosis use appropriate antibiotics and dosing schedules consider using narrow-spectrum antibacterial drugs in simple infections to minimize disturbance of the normal microflora, and preserve the use of broad-spectrum drugs for more complex infections

29. avoid unnecessary use of antibacterial drugs in treating viral infections Revise treatment regimen based on patient progress or test results obtain thorough knowledge of the side effects and drug interactions of an antibacterial drug before prescribing it

30. (7) educate the patient regarding proper use of the drug and stress the importance of completing the full course of therapy (that is, taking all doses for the prescribed treatment time).

31. GUIDELINES Antibiotic therapy should be used as an adjunct to dental treatment and never used alone as the first line of care. Antibiotics are indicated i n v o lve m e n t a r e ev ide n t. w h e n s y s t e m i c s igns of Pain alone or lo c a li z e d S welling s does not require antibiotic coverage

32. Guidelines…. Fevers, malaise, lymphadenopathy or trismus are clinical signs that possible spread of the infection has occurred. A rapidly spreading infection or persistent infections require antibiotic coverage Prescriptions written in generic names are as efficacious as brand names, and produce cost savings.

33. Antibiotic prophylaxis in dentistry Warranted for 2 distinct purposes: Prevention of local wound infection Prevention of distant infection ( e.g., bacterial endocarditis) in predisposed patients following dental procedure.

34. P rophylaxis given in patients with systemic conditions lik e rheumatic heart disease, previous history of endocarditis, heart / orthopaedic prosthesis . In patients with any kind of immunocompromise – AIDS, cancer, autoimmune diseases, corticosteroid therapy, cyclic neutropenia, pancytopenia, uncontrolled diabetes etc.

35. ANTIBIOTIC CHOICES

36. Beta Lactam Antibiotics.

37. Beta-Lactam Antibiotics Includes Penicillin , Cephalosporin , Monobactam, Carbapenem All members of this family has a Beta lactam ring and a carboxyl group resulting in similarities in the pharmacokinetics and mechanism of action. MOA : Inhibits cell wall formation by inhibiting transpeptidase and cross linking at the cell wall. Peptidoglycan cell wall is unique to bacteria. No such substance is synthesized in higher forms- hence penicillin is practically non toxic to man.

38. P enicillin : First antibiotic to be used clinically in 1941. Types: Natural penicillin : Penicillin G and Penicillin V --- Narrow spectrum primarily to gram - positive and gram-negative cocci, gram-positive bacilli Anti-staphylococcal penicillins : Methicillin, nafcillin, oxacillin, dicloxacillin (penicillinase resistant penicillin) Extended-spectrum penicillin s : Ampicillin, Amoxycillin - additional action against gram negative bacilli Antipseudomonal penicillins: Piperacillin, Ticarcillin

39. Natural Penicillins : They are obtained from the fungus Penicillium chrysogenum Penicillin G (Benzyl Penicillin) Antibacterial spectrum Streptococci (pyogenes & viridians) Meningococci C. diptheriae Acute suppurative pulpitis, abscess, Provotella & Porphymonas pericornitis , cellulitis) Spirochetes and fusobacteria ( ANUG) Actinomyces H .influenza Pharmacokinetics : Poor oral absorption as it is readily destroyed by gastric acids. Absorption from i.m site is rapid and complete and has rapid renal excretion.

40. Dose: 0.5- 5 MU i.m / i.v 6-12 hourly. Available as dry powder, to be dissolved in sterile water at the time of injection. Adverse effects : Rarely can cause hypersensitivity : Rash , itching, urticaria, & fever. Anaphylaxis is rare but life threatening. Penicillin G- Not preferred in dental practice due to fear of causing anaphylaxis. Precaution: History of penicillin allergy to be elicited Scratch/ Intradermal test (2-10U) Bacterial resistance : By Penicillinase which is narrow spectrum Beta lactamases that opens the beta lactam ring make it ineffective. Most staphylococci produce penicillinase .

41. Penicillin V ( Phenoxymethyl penicillin) Narrow spectrum antibiotic 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 like staphylococci. T1/2- 90-110 mins. Dose: 250-500 mg 4 times a day.

42. Penicillinase resistant penicillin (Anti-staphylococcal penicillins ) Methicillin, oxacillin, dicloxacillin Their only indication is infections caused by penicillinase producing Staphylococci for which they are the drugs of choice However their use is limited as except methicillin resistant staph. Aureus (MRSA) have become predominant.

43. Methicillin It is highly penicillinase resistant but not acid resistant must be injected. MRSA is susceptible to Vancomycin/linezolid. Adverse reaction- hematuria, albuminuria, reversible intestitial nephritis

44. Cloxacillin/ Dicloxacillin Highly Penicillinase and Acid resistant More active than methicillin, 5 to 10 times more active than methicillin against resistant staphylococci. Less active against PnG sensitive organisms: should not be used as its substitute Incompletely but dependably absorbed (oral route) >90% protein bound, eliminated primarily by kidney, also partly by liver Plasma half life is about 1hr Given in staphylococcus infection resistant to benzyl penicillin Active against a variety of gram-negative bacilli as well. Amoxicillin + Cloxacillin : NOVACLOX 250 + 250 mg cap

45. 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 -1 g 12 hourly i.v Linezolid - 600 mg BD Oral

46. Extended-spectrum penicillins : Ampicillin, Amoxycillin Antibacterial spectrum : Broad spectrum covering both gram- positive and gram- negative aerobic and anaerobic bacteria commonly causing dental infections. Most preferred antibiotic for dental infections. Majority of dental cases resolve with 250-500 mg TDS for 5 days.

47. Ampicillins Active against all organisms sensitive to PnG ; in addition, many gram-negative bacilli Pharmacokinetics: • Acid resistant • Oral absorption is incomplete but adequate • Primary excretion is kidney, partly enterohepatic circulation occurs • Plasma half life is 1hr

48. Medical Uses: • UTI, RTI, Meningitis, Gonorrhoea , typhoid fever, bacillary dysentery, Subacute bacterial endocarditis and Septicemias Adverse effects: • Diarrhoea (it is incompletely absorbed –the unabsorbed drug irritates the lower intestine as well as causes marked alteration of bacterial flora) • Rashes • Hypersensitivity Interactions: • Hydrocortisone –inactivates ampicillin if mixed in the I.V solution. • Oral contraceptive –failure of oral contraception • Probenecid–retards renal excretion

49. DOSE • Adult- 0.5-2g oral/ i.m / i.v depending on severity of infection , every 6 hr • Child-50-100 mg/kg given in equally divided doses every 6 hr • Maximum-2-4 g/ day AMPILIN, ROSCILLIN, BIOCILIN 250, 500mg CAP; 250mg/5ml dry syrup: 100mg/ml pediatric drops 250,500mg and 1g per vial inj.

50. Amoxicillin Close congener of ampicillin Similar in all respects except – Oral absorption is better Food doesn’t interfere with absorption Higher and more sustained blood levels produced Incidence of diarrheoa is lower due to complete absorption in the GI tract Uses: Most frequently used in dental infections 250-500mg for 5 days TDS Prophylaxis for local and distant infection AMOXILIN, NOVAMOX, SYNAMOX 250,500mg cap, 125mg/5ml dry syr.

51. Antipseudomonal penicillins : Carbenicillin, Piperacillin, Ticarcillin Carbenicillin : Antibacterial spectrum- Active against Pseudomonas aeruginosa and Indole positive Proteus which are not inhibited by PnG or aminopenicillins. e.g Burns, urinary tract infection, septicaemia etc Dose- Carbelin 1g, 5g, i.m / i.v per vial inj. Adverse reactions : High dose can cause bleeding by interfering with platelet function. It has been replaced by Ticarcillin/ Piperacillin due to fewer side effects.

52. Ticarcillin Antibacterial spectrum- Active against Pseudomonas and Proteus infections like carbenicillin but has fewer side effects and is more active. Gentamycin is often combined with it for treating serious pseudomonas infections. Dose - 3 g i.m / i.v 6 hourly. Piperacillin Antibacterial spectrum- Active against Pseudomonas , Proteus, Klebsiella (Pneumonia in pts with alcohol & DM) and some Bacteroides. Used in serious gram negative infections in immunocompromised patients and in burn cases. Dose- 100-150 mg/kg/day in 3 divided doses

53. Beta-lactamase inhibitors Clavulanic acid Sulbactam Tazobactam Beta lactamases are a family of enzymes produce by many gram positive and gram negative bacteria that inactivate beta lactam antibiotics by opening the beta lactam ring. Therefore. 3 inhibitors of this enzyme are used in combination with specific penicillin's or cephalosporins.

54. Clavulanic acid: Obtained from Streptomyces clavuligerus , it has beta lactam ring but no antibacterial activity of its own. MOA: Permeates the outer layers of the cell wall of gram- negative bacteria and inhibits the periplasmically located beta lactamases. Adverse effects : Poor G.I tolerance, Candida stomatitis, Rashes. Uses: Augmentin (amoxicillin +clavulanic acid) useful in the management of refractory periodontitis, periapical abscess, cellulites, pericoronitis, Osteomyelitis. Amoxicillin 250mg +clavulanic acid 125 mg TDS Amoxicillin 500mg + clavulanic acid 125 mg TDS

55. Beta-lactamase inhibitors: Sulbactam: Semisynthetic, less potent than clavulanic acid. Oral absorption is inconsistent, hence given parenterally with ampicillin. Indications: Skin/soft tissue infections, especially acquired in hospital Adverse effects: Pain at injection site, Thrombophlebitis etc A mpicillin 1g + Sulbactam 500 mg i.v every 6 hours.

56. Cephalosporins

57. Cephalosporins Mechanism of action : All cephalosporins have the same mechanism of action as penicillin, i.e. inhibition of bacterial cell wall synthesis Spectrum of Activity: Bactericidal

58. Parenteral Oral First generation Cephalothin Cephalexin Cefazolin Cefadroxil Second Generation Cefamandole Cefachlor Cefuroxime Cefuroxime axetil Third generation Cefotaxime Cefixime Ceftrioxone cefdinir Cefoperazone ceftibuten Fourth generation Cefepime cef p i r o m e Fifth generation Ceftaroline

59. 1st generation 2nd generation Predominantly act against Gram +ve organisms Wide coverage against Gram -ve organism Staphylococci, streptococci, pneumococci H. influenzae Efficacy against Beta lactamase producing organisms is POOR . Efficacy against Beta lactamase producing organisms is GOOD Used for Prophylaxis of surgical procedures. Given IM/IV Less activity against Gram + compared to 1st generation.
Active against Anaerobes. Cefalexin - In dentistry alternative to amoxicillin Cefodroxil -Good tissue penetration including alveolar bone (socket) Cefaclor Cefuroxime axetil - Effective against anaerobes hence used in dental infections

60. 3rd generation 4th generation In serious Gram negative infections , a third generation cephalosporin is combined with gentamicin or amikacin. useful for serious gram - ve infections Anti pseudomonal activity Active against streptococci and methicillin sensitive staphylococci More active against Gram - ve bacilli than 1&2nd generations The indications for these drugs include aminoglycoside resistant or multi-resistant Gram negative bacillary systemic infections. They have almost replaced the second generation cephalosporins for this purpose. CNS penetration is better than 1st & 2nd generation CNS penetration is excellent Ceftaroline is new addition to this group. Its active against MRSA

61. Plasma Half life Dose Preparations 1st Generation Oral Cephalexin 0.9h 0.25-1.0g 6-8h SPORIDEX, CEPHAXIN, 250,500mg cap Cefadroxil 1.6h 0.5-1g 12h DROXYL 0.5,1g tab Parenteral Cephazolin 1.8h 0.5-1g I.m / I.v 6-8h ALCIZON,ORIZOLIN 0.25g,0.5g ,1g per vial inj 2nd Generation Oral Cefaclor 0.6h 0.25-0.5 6h KEFLOR,VERCEF 250, 150 mg cap Cefuroxime axetil 1.3h 0.25-0.5 12h CEFOGEN,SUPACEF,FUROXIL 250mg and 750mg Parenteral Cefuroxime 1.4h 0.75-1.5g IM/IV CEFOGEN,SUPACEF 250mg and 750mg/vial inj

62. Plasma Half life Dose Preparations 3rd Generation Oral Cefixime 3.5h 200-400mg BD TOPCEF, ORFIX 100,200 mg tab/cap , Cefpodoxime Proxetil 2.2h 200mg BD(max 800mg/day) CEPODEM ,100,200 mg tab, 50mg/5ml susp Parenteral Cefotaxime 0.9h 0.5-1g I.m/I.v
q6-8h OMNATAX 0.25,0.5,1.0g per vial inj Cefaperazone 1.7h 1-3g i.m/i.v 12hourly MAGNAMYCIN 0.25g, 1,2 g inj ; 4th Generation Oral Cefepime 2.0h 1-2g i.v, 8-12hourly CEPIME- 0.5,1g inj. 5th Genration Parenteral Ceftaroline 600mg i.v over 60mins , 12h TEFLARO,ZINFORO 600mg/vial inj.

63. Diarrhoea - due to altered gut ecology common with oral cephradine and parenteral cefoperazone which is significantly excreted in bile Hypersensitivity- similar to penicillin. rashes, anaphylaxis, angioedema, asthma and urticaria Cross resistance between penicillin & cephalosporin reported Nephrotoxicity – low grade. May be attenuated by existing renal disease. Dose reduction required even in cases of mild renal failure Bleeding – cefoperazone , ceftriaxone due to Neutropenia and thrombocytopenia are rare adverse effects reported with ceftazidime and some others A disulfiram like reaction with alcohol in cefoperazone Adverse effects

64. Acquired Resistance to Cephalosporins Mechanism same as in penicillin. Alteration in target proteins reducing affinity for antibiotic Impermeability so that it does not teach its site of action Elaboration of beta lactamases .

65. Alternative to penicillin/amoxicillin (if pt develop resistance/allergy), orally active 1 st and 2 nd gen drugs are used in orodental infections 1 st gen cephalexin., cephadroxil used due to high activity against gram + ve bacteria and good penetration in alveolar bone(socket) 2 nd gen cefuroxime axetil and cefaclor are the only ones which have good activity against oral anaerobes and preferred in dentistry, eg : klebsiella which may occurs in neutropenic patients Cephalexin and cephadroxil are alternatives to amoxicillin for prophylaxis of local wound infection as well as bacterial endocarditis following dental surgery in predisposed patients. Dental Uses

66. Disulfiram like reaction: Inhibition of aldehyde dehydrogenase results in inhibition of metabolism of acetaldehyde to acetate. The increase in serum acetaldehyde results in unplea sant clinical manifestations . Symptoms: P alpitations, facial flushing, nausea, vertigo, hypotension, and tachycardia. This aggregation of symptoms is known as the disulfiram-alcohol reaction Eg : M etronidazole (Flagyl and other brands), trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS) Tinidazole ,

67. First AMA to be effective against pyogenic bacterial infection SULFONAMIDES MOA : It inhibits bacterial folate synthesis. As a result, a number of essential metabolic reactions suffer . Not active in pus and tissue extracts as it contains purines and thymidine that decreases the bacterial requirement of FA, thus antagonising the action.

68. Pharmacokinetics Nearly completely absorbed from GIT Plasma protein binding varies (10-95%) Highly protein bound-long acting Cross placenta freely Less soluble in acidic urine – can precipitate and cause crystalluria Sulphonamides – mainly excreted by kidney

69. Sulfadiazine- Short acting. Rapidly absorbed orally and rapidly excreted in urine Good permeability – brain, CSF – preferred compound for meningitis Dose: 0.5 g QID to 2 g TDS Sulfamethoxazole- Intermediate acting Slow oral and urine absorption and urinary excretion Intermediate duration of action T1/2 10 hrs Combination with trimethoprim as the t1/2 of both is the same Dose: 1g BD for 2 days ,then 0.5g BD

70. Sulfadoxine , Sulfamethopyrazine Ultralong acting High plasma protein binding Hence Action >1week Slow renal secretion ( t1/2 : 5-9 days ) Not suitable for pyogenic infections Used in combination with pyrimethamine in malaria, pneumonia in AIDS patient.

71. Sulfasalazine Anti inflammatory activity Used in ulcerative colitis and rheumatoid arthritis Not a typical sulphonamide It is only used topically Active in pus and against pseudomonas and clostridia Mainly employed for burn dressing to prevent infection Topical – 1% cream Active against large no. of bacteria and fungi. eg - Psedomonas Slowly releases silver ions which have antimicrobial action One of the most effective drug for burnt surfaces and chronic ulcers and is well tolerated Mefenide Sliver sulfadiazine

72. Adverse effects Nausea, vomiting, epigastric pain Crystalluria- Hypersensitivity reactions:- Hepatitis, Stevens-Johnson syndrome and other severe cutaneous reactions especially with long acting sulfonamides Stevens-Johnson syndrome (SJS) is a rare, serious, self limiting disorder of the skin and mucous membranes. It's usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters. .

73. Interactions Sulfonamides inibit the metabolism of phenytoin and warfarin- enhance their action They displace methotrexate from binding and decrease its renal excretion- toxicity can occur Uses: Because of rapid emergence of bacterial resistance, currently used only in combination with trimethoprim ( Sulfadoxine + trimethoprime ) or pyrimethamine (for malaria). Ocular sulfacetamide sod. (10-30%) is used for conjunctivitis. Topical silver sulfadiazine (1%) or Mafenide used for preventing infection on burn surfaces.

74. Use of Dapsone in Oral lesions It’s a sulfone antibiotic. Its mechanism of action includes both antibacterial and anti-inflammatory effects. It inhibits neutrophil activation and chemotaxis. It reduces the number and size of oral and genital ulcers seen in Bechet's disease. Dapsone is used for treating erosive lichen planus -100mg/day for 3 months

75. COTRIMOXAZOLE

76. Cotrimoxazole Fixed dose combination of trimethoprim + sulfamethoxazole is called cotrimoxazole Both have the same t1/2 :- 10 hrs Trimethoprim:- selectively inhibits bacterial dihydrofolate reductase (DHFR) Causes sequential block of folate metabolism Individually both are bacteriostatic but when both are combined they become bactericidal against many organism

77. Uses 1. Occasional use in orodental infections only if allergic to beta lactams 2. Used in tonsillitis, pharyngitis, sinusitis, otitis media, chronic bronchitis 3. In high doses first line of drug for pneumonia in AIDS patients SEPTRAN, SEPMAX, BACTRIM, CIPLIN etc. Trimethoprim + Sulfamethoxazole BD 80 mg + 400 mg tab 160 mg + 800 mg tab 20 mg + 100 mg pediatric tab.

78. Adverse effects All adverse effects seen with sulphonamides may be produced by cotrimaxazoles . Folate deficiency (megaloblastic anemia) infrequent, seen only in patients with marginal folate levels Should not be given during pregnancy , Can cause teratogenic risk as trimethoprim is anti folate. Neonatal hemolysis and methemoglobinemia can occur if given close to term Dose to be reduced in moderately severe renal impairment Diuretics given with cotrimoxazoles have produced higher incidence of thrombocytopenia.

79. Quinolones

80. Quinolones Bactericidal Active primarily against gram – ve First member of quinolones is Nalidixic acid Newer members inhibit gram + ve as well Fluorination of quinolone structure resulted in the derivative called fluoroquinolones, this as; High potency Expanded spectrum Slow development of resistance Better tissue penetration & Good tolerabili ty

81. Nalidixic acid Resistance developing is rapid Absorbed orally ,highly plasma protein bound and partly metabolized in liver Plasma t1/2- 8 hrs Excreted in urine. High concentration is lethal to normal urinary pathogens

82. Nalidixic acid Active against Gram – ve Inhibits bacterial DNA gyrase & is bactericidal Uses: Primarily used as urinary antiseptic, has practically no utility in dentistry. Given in diarrhea caused due to proteus ,E coli, shigella or salmonella. Adverse effects GI upset and rashes Most important toxicity is neurological – headache, drowsiness, vertigo , visual disturbances , occasionally seizures (especially in children Dose :0.5-1g TDS/ QID

83. Fluoroquinolones

84. Fluoroquinolones Extended antimicrobial activity to gram positive cocci and anaerobes . (2 nd generation) Longer t1/2 MOA: Inhibits bacterial DNA gyrase which results in relaxation of supercoiled DNA, promoting DNA strand breakage.

85. Fluoroquinolones First generation fluoroquinolones Norfloxacin Ciprofloxacin Ofloxacin Pefloxacin Second generation fluoroquinolones Lomefloxacin Sparfloxacin Levofloxacin Gatifloxacin moxifloxacin * 3rd generation Gemifloxacin Prulifloxacin

86. Mechanism of action Inhibits enzyme bacterial DNA gyrase which nicks double stranded DNA. Antibacterial spectrum: Aerobic Gram – ve bacilli are the most susceptible ones, especially the Enterobacteriaceae and Neisseria

87. Ciprofloxacin (prototype) Most potent 1 st gen FQ. Remarkable microbiological features of ciprofloxacin are: Rapid bactericidal High potency Long post antibiotic effect on ,Enterobacteriaceae, pseudomonas and staph. Post-antibiotic effect (PAE) is the continued suppression of bacterial growth following a limited exposure to an antimicrobial agent Low frequency of mutational resistance Protective intestinal streptococci and anaerobes are spared

88. Pharmacokinetics Rapidly absorbed orally T1/2 : 3-5hrs Food delays absorption High tissue penetrability CSF levels are low Excreted in urine

89. Uses Wide spectrum bactericidal activity ,oral efficacy, good tolerability- it is extensively used as blind therapy for many infections. Caution: Should not be used for minor cases or where gram positive organisms are primarily causative Primarily used for serious infections like septicemia and meningitis. Ciprofloxacin + Metronidazole – often used for mixed refractory periodontitis. Ofloxacin, gatifloxacin , moxifloxacin are more active against gram + ve bacteria and anaerobics and have potential use in dentistry Combination chemotherapy for multidrug resistant tuberculosis

90. Adverse effects Gastrointestinal: nausea, vomiting, bad taste , anorexia. (gut anaerobes not affected so diarrhea is less common) CNS- dizziness, headache , restlessness , anxiety , insomnia , impairment of concentration , tremor. Seizures are rare occur only at high doses Skin/hypersensitivity: rash , pruritus, photosensitivity, urticaria , swelling of lips etc Contraindicated in pregnancy In children require caution due to damage to weight bearing joints

91. Interactions Plasma concentration of theophyline and warfarin increased by ciprofloxacin due to inhibition of metabolism :toxicity of these drugs can occur NSAIDS may enhance the CNS toxicity of FQs ; seizures have been reported Antacids, sucralfate and iron salts given concurrently reduce absorption of FQs CIFRAN, CIPLOX, 250,500,750 mg tab 200 mg/100ml i.v. infusion , 3mg/ml eye drops

92. Norfloxacin Less potent than ciprofloxacin Psuedomonas and many gram + ve are not inhibited at clinical concentrations Metabolized as well as excreted in urine Used in urinary and genital tract infections NORBACTIN, NORFLOX 200,400,800MG tab, 3mg/ml eye drops; UROFLOX, NORILET 200,400mg tab .

93. Ofloxacin Intermediate between ciprofloxacin and norfloxacin in activity against gram – ve bacteria More potent than ciprofloxacin for gram + ve organisms. Better suited for orodental infections Excreted largely in urine Dose to be reduced in renal failure ZANOCIN,TARIVID, 100,200,400mg tab;

94. Levofloxacin- 2 nd gen FQ Improved activity against Gram + ve and gram – ve bacteria Anearobes moderately susceptible Oral bioavilability -100% Excreted unchanged and single dose daily is enough Used in community acquired pneumonias and exacerbations of chronic bronchitis High cure rates for Sinusitis, skin and soft tissue infections TAVANIC ,GLEVO 500mg tab OD

95. Gatifloxacin 2 nd gen FQ Improved activity against Gram + ve bacteria Used in upper and lower respiratory tract infections , community acquired pneumonia, chronic bronchitis. Significant activity against gram + ve cocci and anerobes prompted its use in dental infections Dose :400mg on 1 st day ,followed by 200-400mg OD, oral or i ,.v.

96. Moxifloxacin Long acting 2 nd gen FQ Used in pneumonia, bronchitis, sinusitis, otitis media etc Not to be given in pts predisposed to seizures Phototoxicity is rare Dose: 400 mg OD

97. NITROIMIDAZOLES `

98. M etronidaz o le MOA: Nitro group reacts with bacterial DNA, causing inhibition of DNA replication, fragmentation of existing DNA Antimicrobial spectrum: Narrow spectrum . Effective against Gram-negative anaerobes such as P . intermedia, Porphyomonas gingivalis , Bacteroides , Fusobacterium etc Does not affect aerobic bacteria Used in : -Necrotizing ulcerative gingivitis -Aggressive periodontitis -Abscesses -Orofacial infection along with Penicillins

99. Phramacokinetics T ½:- 8 hrs Almost completely absorbed by small intestines Little unabsorbed drug reaches colon Widely distributed in body Attaining therapeutic concentration in saliva, CSF, vaginal secretion, semen Metabolised in liver by primarily oxidation and glucuronide conjugation Then excreted in urine

100. 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 Dose: [Metron, Flagyl] 200-400 mg 8 hourly Adverse effects : Anorexia, nausea, bitter, metallic taste and abdominal cramps. Diarrhoea less common Prolonged administration may cause peripheral neuropathy and CNS effects - seizures are seen in very high doses

101. Contraindication Neurological disease Blood dyscrasias Chronic alcoholism Interaction Disulfiram intolerance to alcohol occurs among some patients Enzyme inducers (rifampin )may reduce its therapeutic effect Cimetidine (Antihistaminic- peptic ulcers) can reduce metronidazole metabolism :its dose may need to be decreased Enhances warfarin action by inhibiting its metabolism Prothrombin time of patients taking warfarin should be monitored

102. Tinidazole Similar to metronidazole except that, t ½ is 12 hours slow metabolism Longer duration of action Thus single dose or once daily therapy Lower side effects metallic taste (2%) Nausea (1%) Rash (0.2%) TINIBA 300,500,1000 mg tabs 800mg/400ml i.v. infusion; In orodental infection it is used in a dose of 500 mg BD for 5 days

103. Ornidazole Similar activity to metronidazole Slow metabolism t1/2 12-14hr Side effect similar to tinidazole Used in amoebiasis, giardiasis,etc DAZOLIC 500mg tb,500mg/100ml vial for i.v. infusion.

104. TETRACYCLINES These are class of antibiotics having a nucleus of four cyclic rings. All are obtained from soil actinomycetes. The first to be introduced was chlortetracycline in 1948 . Clinically relevant tetracyclines and glycycline are: Tetracycline Demeclocycline Oxytetracycline Doxycycline Minocycline Glycycline : Tigecycline. Mechanism of action : The tetracyclines are primarily bacteriostatic; inhibit protein synthesis by binding to 30S ribosomes in susceptible organism. Antibacterial spectrum: B road-spectrum antibiotic. Inactive against Enterobacteriaceae i.e E.coli, Klebsiella, Pseudomonas.

105. Tetracylines except Doxycycline and minocycline are incompletely absorbed from g.i.t : absorption is better if taken in an empty stomach Tetracyclines have chelating property – form insoluble and unabsorbable complexes with calcium and other metals – Teeth discoloration. Milk , iron preparations , non systemic antacids and sucralfate reduce their absorption Excreted in urine by glomerular filtration- dose to be reduced in renal failure. Exception is doxycycline as it is primarily eliminated via the bile into the feces. Pharmacokinetics

106. Adverse effects Teeth and bones : due to chelating property of tetracyclines, calcium-tetracycline chelate get deposited in bones and teeth Irritative effects: nausea, epigastric pain, vomiting and diarrhea Dose related toxicity Liver damage. Oxytetracycline & tetracyclines are safer in this regards. Tetracyclines are risky in pregnant women , can precipitate acute hepatic necrosis Kidney damage Phototoxicity Increased intracranial pressure is noted in infants Vestibular toxicity-Minocycline. \

107. Superinfection Most common drug which is responsible for superinfection, because they cause marked suspension of normal residential flora Precautions : Not used in pregnancy, lactation and in children under 8 yrs. Patients on diuretics as blood urea may rise in such patients. Used cautiously in renal or hepatic patient Do not mix injectable tetracyclines with penicillin's –inactivation occurs

108. Uses in Oro dental conditions They benefit certain periodontal condition due to their broad spectrum antimicrobial action as well as by suppressing the activity of collagenases that contribute to gingival inflammation. It can be used in chronic periodontitis, juvenile periodontitis Dose: 2-weeks tetracycline(1g/day) or doxycycline (0.1-0.2g/day ) therapy controls 2-4 week tetracycline therapy & surgery halts the progression of juvenile periodontitis

109. Tigecycline New class of synthetic tetracycline analogue which is active against bacteria that has developed resistance to tetracyclines e.g Enterobacteriaceae. Approved only for treatment of serious infections in hospitalized patients like pneumonia, complicated skin/ intra abdominal infections etc. Dose: 100 mg loading dose followed by 50 mg 12 hourly iv

110. Chloramphenicol It was initially obtained from the Streptomyces venezuelae . Antibacterial spectrum Broad spectrum like tetracycline. Mechanism of action —Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis by attaching at 50S ribosome subunit .

111. Adverse effects — Major adverse effect - Bone marrow depression — Gray baby syndrome: It occurred when high doses (~100 mg/kg) were given prophylactically to neonates, especially premature. The baby stopped feeding, with irregular respiration ; an ashen gray cyanosis developed, followed by cardiovascular collapse and death. It occurs because of inability of the newborn to adequately metabolize and excrete chloramphenicol .

112. Uses - Due to risk of bone marrow aplasia Never use it for minor infections or infections that can be treated by safer antimicrobials. Daily dose should not exceed 2-3 g, duration less than 2-3 weeks, total dose less than 28 g There is no indication in dentistry that warrants use of chloramphenicol despite its broad-spectrum antimicrobial action

113. Aminoglycosides

114. Streptomycin was the first member discovered in 1944 by Waksman. They are extensively used in medical, surgical, gynecological and other systemic infections but seldom employed in dentistry. All aminoglycosides are obtained from soil actinomycetes and have many common properties. They ionize in solution are not absorbed orally, distribute only extracellularly, Excreted unchanged in urine. (Dose to be reduced even in mild renal failure) Bactericidal All exhibit ototoxicity and nephrotoxicity

115. Classification Systemic aminoglycosides Streptomycin Gentamicin Kanamycin Tobramycin Amikacin Sisomycin netimicin Topical aminoglycosides Neomycin
framycetin

116. Antibacterial spectrum: All are active primarily against aerobic gram negative bacilli; do not inhibit anaerobes. e.g. E.coli, klebsiella pneumonia, Enterobacter, H. influenza, Proteus, Pseudomonas. MOA: They act by interfering with bacterial protein synthesis by binding to several sites on 30S and 50S subunits that freezes initiation of protein formation and caused misreading of the code.

117. SHARED TOXICITY:- Ototoxicity- Drug gets concentrated in the labyrinthine fluid and slowly gets removed once plasma concentration falls- concentration dependent destructive changes. Cochlear damage- Permanent deafness , tinnitus often disappears on stopping the drug. Vestibular Damage- Headache, vomiting, nystagmus, vertigo, ataxia. Recovery occurs in 1-2 years. Nephrotoxicity- More in elderly patients with pre-existing renal disease. Totally reversible. Neuromuscular Blockade- Rare. However, effects happens due to reduce Ach release from motor nerve endings.

118. PRECAUTIONS & INTERACTIONS: Avoid during pregnancy: risk of fetal ototoxicity( crosses placenta) Avoid concurrent use of other Nephrotoxic drugs eg : NSAIDs, amphotericin B, vancomycin, cyclosporine. Cautious use in elderly patients and those with Kidney damage. Do not mix amino glycoside with any drug in the same syringe/infusion bottle.

119. Dosing regime Because of low safety margin, the daily dose must be precisely calculated according to body weight and level of renal function. Normal renal function: CLcr > 70 ml/min. Gentamycin/tobramycin: 3-5 mg/kg/day ( i.m ) Streptomycin/kanamycin/amikacin: 7.5-15 mg/kg/day

120. STREPTOMYCIN: Practically restricted to treatment of Tuberculosis. Streptomycin is not used in dentistry. Lowest nephrotoxicity. GENTAMICIN : The only application in dentistry is to give gentamicin 2 mg/kg i.m. / i.v. (single dose) to supplement amoxicillin or vancomycin for prophylaxis of bacterial endocarditis following dental surgery in patients with prosthetic heart valves or past history of BE. TOBRAMYCIN : Identical to gentamicin, but it is 2–4 times more active. It should be used only as a reserve alternative to gentamicin. Ototoxicity and nephrotoxicity is probably lower than gentamicin.

121. NEOMYCIN: Uses 1. Topically (often in combination with polymyxin, bacitracin, etc.) for infected wound, ulcers, burn, external ear infections, conjunctivitis. ADVERSE EFFECTS : Oral neomycin has a damaging effect on intestinal villi—prolonged treatment can induce malabsorption syndrome with diarrhea and steatorrhea. Superinfection by Candida can also occur.

122. Macrolides

123. Macrolides These are group of antibiotics that have in common macrocyclic lactone ring linked with amino sugars. Natural: Erythromycin Semisynthetic: Developed to overcome the limitations of erythromycin Narrow spectrum of activity Gastric irritation on oral ingestion Gastric acid liability Lower oral bioavailability Azithromycin, Clarithromycin, Telithromycin

124. Erythromycin Antibacterial spectrum : Overlaps with Penicillin G and hence widely used as an alterative to the beta lactam antibiotics. Provide good coverage against Gram positive organisms. e.g. Str. Pyogenes, Str. Pneumonia. N. gonorrhea, Clostridia etc. MOA Bacteriostatic & interfere with bacterial protein synthesis by binding to the 50s ribosomal subunits This interfere with the translocation step of protein synthesis Erythromycin is bacteriostatic at low but cidal at high concentrations Renal excretion is minor, hence dose need not to be altered in renal failure.

125. Adverse effects – Remarkably safe drug Mild GI symptoms Hepatotoxicity- Hepatitis can occur after 1-3 weeks. Incidence higher in pregnant women. Should be used cautiously in patients with hepatic dysfunction Drugs are excreted in human breast milk so should be cautious when prescribing the drug to nursing mother Very high doses have caused reversible hearing impairment. Interference with the metabolism of drugs, such as theophylline, statins, antiepileptics, digoxin

126. Dental uses : Because erythromycin is orally administered, safe and active against both aerobic and anaerobic gram-positive bacteria commonly infecting dental structures and mouth. It is the second choice drug to penicillin’s (pts allergic to penicillin ) for periodontal/ periapical abscesses, necrotizing ulcerative gingivitis, post extraction infections, gingival cellulitis, etc. Dosage : Erythromycin – orally 250-500 mg QID, in children 30-60 mg/kg/day It is acid labile. To protect it from gastric acid, it is given as enteric coated tablets Medical uses: Pharyngitis, Tonsilitis, First line of drug- Mycoplasma pneumonia, chancroid.

127. Newer macrolides Roxithromycin- Used as an Alternate to erythromycin. Better gastric tolerance, t half of 12 hrs. Dose: 150-300 mg BD 30 min before meals, children 2.5-5 mg/kg BD Clarithromycin – Additional antibacterial spectrum First line against Mycobacterium avium complex Second line drug against Mycobact . Leprae. Dose: 250 mg BD for 7 days (Mild cases) 500 mg BD for 14 days Azithromycin – Extended spectrum against H. influenza Dose: 500 mg once daily 1 hr before or 2 hr after food- 3 days

128. LINCO S AMIDE CLINDAMYCIN MOA : similar to macrolides significant activity against many gram-positive and gram negative anaerobic and aerobic microorganisms, including Bacteroides, Prevotella, Porphyromonas, Veillonella, Better bone penetration due to relatively small molecular size. So used in treatment of Osteomyelitis , Dentoalveolar abscess. Most common adverse effect is diarrhea, due to pseudomembranous entero colitis caused by overgrowth of C. difficile. ( Treatment- Stop the drug and start Metronidazole/Vancomycin) Dose : 150-300 mg QID 200-600 mg IV 8 hourly.

129. Glycopeptide Vancomycin: Vancomycin was discovered in 1956 as penicillin substitute. Antibacterial spectrum : Active particularly against MRSA. MOA : It inhibits cell wall synthesis. Pharmacokinetics: Vancomycin is poorly absorbed orally . 90% of the drug is excreted by glomerular filtration- Dose reduction in renal insufficiency.

130. Clinical uses: Parenteral: I ndicated for serious MRSA infections. Dose: 500 mg 6 hourly or 1 g 12 hourly i.v Oral: 2 nd choice of drug to metronidazole for antibiotic associated pseudomembranous enterocolitis. Dose: 125- 500 mg QID Adverse effects Concentration dependent nerve deafness & kidney damage. Rapid i.v injection can cause chills, fever, urticaria, and intense flushing- Red man syndrome .

131. Bacitracin Bacitracin is active against gram-positive microorganisms. It inhibits cell wall formation. It is markedly nephrotoxic if administered systemically, thus limited to topical use in burns from getting infected. Cycloserine Cycloserine is used almost exclusively to treat tuberculosis caused by strains of M tuberculosis resistant to first-line agents. Most of the drug is excreted in active form into the urine. Cycloserine causes serious dose-related central nervous system toxicity with headaches, tremors, acute psychosis, and convulsions.

132. Topical Antibiotics

133. Atridox :(doxycycline hyclate ) ® Available as a tray or pouch containing a doxycycline hyclate syringe (50 mg).Use in the treatment of chronic adult periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction in bleeding on probing . ARESTIN ARESTIN (minocycline HCl) Microspheres, 1 mg is a concentrated, locally applied antibiotic that remains active in the pocket for an extended period of time to reduce pocket depth.

134. PerioChip Its a Orange-brown, rectangular chip (rounded at one end) for insertion into periodontal pockets as a part of maintenance therapy Contains 2.5 mg of chlorhexidine gluconate Others: Actisite Elyzol

135. Handle antibiotics with care to prevent resistance!

136. Thank you!!