![Macrolide antibiotics
Erythromycin
Clarithromycin
Azithromycin
Azithromycin:
• Azithromycin is a newer macrolide developed to overcome some of the
shortcomings of erythromycin such as GI intolerance, low bioavailability,
and somewhat limited spectrum of activity.
Dosage
1. Azithromycin is available as a 250 mg tablet (or capsule) commonly
distributed in a “Z-pack” containing six tablets for a standard 5-day regimen
in adults (two tablets [500 mg] day 1 and then one 250 mg tablet qd days 2
to 5). Tablets can be taken with or without food.
2. The flavored oral suspension comes in 100-mg/5 ml and 200-mg/5 ml. The
suspension should be given 1 hour before or 1 hour after meal.
5. For IV azithromycin 500 mg IV once daily is infused over at least 60 minutes
in patients 16 years of age and older](https://image.slidesharecdn.com/ankitamam5-211223070120/85/ANTIBIOTICS-IN-ORAL-MAXILLOFACIAL-SURGERY-35-320.jpg)
ANTIBIOTICS IN ORAL & MAXILLOFACIAL SURGERY
- 1. ANTIBIOTICS IN ORAL & MAXILLOFACIAL SURGERY PRESENTED BY – Dr.ANKITA RAJ (MDS Reader) Oral & Maxillofacial Surgery Department Rama Dental College, Kanpur
- 2. cCONTENTS INTRODUCTION HISTORY CLASSIFICATION PRINCIPLES OF CHOOSING ANTIBIOTICS PRINCIPLES OF ADMINISTRATION ADVERSE REACTION CONCLUSION REFERENCES
- 3. ANTIBIOTICS • These are substances produced by microorganisms which suppress the growth or kill other microorganisms at very low concentrations • The term antibiotic means "against life".
- 4. History of chemotherapy DOMAGK the modern era of chemotherapy: started by the use of PRONTOSIL a sulfonamide dye . PASTEUR demonstrated the phenomenon of ANTIBIOSIS – growth of anthrax bacilli in urine was inhibited by airborne bacteria. Term antibiosis given by Jean Paul Vuillemin 1877 Renamed as Antibiotics by Selman waksman 1942
- 5. • FLEMMING found a substance formed from the pencillium mould could destroy staphylococcus on the culture plate. • In the past 50 years emphasis has shifted from searching newer antibiotic organism to developing semi synthetic derivatives of older antibiotics
- 6. • Classification 1.Based on chemical structure • Quinolones • Beta lactam antibiotics • Aminoglycosides • Macrolides • Nitro- imidazoles • Sulfonamides • Glycopeptides • Others 2.Based on mechanism of action • Inhibit cell wall synthesis • Inhibit protien synthesis • Interfere with DNA function • Cause misreading of m-RNA code & affect permeability • Inhibit DNA Gyrase enzyme • Interfere with intermediary metabolism
- 7. 3. Spectrum of activity • NARROW SPECTRUM: PENCILLIN G ERYTHROMYCIN • BROAD SPECTRUM: TETRACYCLINE CHLORAMPHENICOL • EXTENDED SPECTRUM: SEMISYNTHETIC PENCILLIN, CEPHALOSPORINS,AMINOGLYCOSIDES.
- 8. 4.Based on type of organism against which the drug is primarily active against: • Anti bacterial • Anti viral • Anti fungal • Anti protozoal • Anti helmenthic
- 9. 5. Type of action • Bacteriostatic: sulfonamides tetracyclines , erythromycin . • Bactericidal: penicillin , ciprofloxacin cephalosporin. 6. Source • Fungi: penicillin, cephalosporin. • Bacteria: polymyxin, bacitracin. • Actinomycetes: aminoglycosides, macrolides, tetracyclines, chloramphenicol.
- 11. PRINCIPLES OF PROPHYLACTIC ANTIBIOTIC USE 1. PROCEDURE SHOULD HAVE SIGNIFICANT RISK OF INFECTION 2. CHOOSE CORRECT ANTIBIOTIC 3. ANTIBIOTIC PLASMA LEVEL MUST BE HIGH 4. TIME ANTIBIOTIC ADMINISTRATION CORRECTLY 5. USE SHORTEST ANTIBIOTIC EXPOSURE THAT IS EFFECTIVE
- 13. Prescribe or administer sufficient amounts to achieve the desired therapeutic effect but not enough to cause injury to the host. - For therapeutic purposes the peak concentration of the antibiotic at the site of infection should be 3 – 4 times the MIC. - Administration of doses above that level increases the likelihood of toxicity . - Subtherapeutic levels may mask an infection. - Each antibiotic has an established plasma half life , during which ½ of the absorb drug is excreted. - Usual dosage interval for the therapeutic use of antibiotics is 4 times the t½. - At 5 times the t½, 95% of the drug has been excreted. 1. Proper dose: 2. Proper time interval: PRINCIPLES OF ANTIBIOTIC ADMINISTRATION
- 14. -In some infections, only parental administration produces the necessary serum level of antibiotics -Oral route results in the most variable absorption. -Most antibiotics should be taken at in fasting state ( 30mins before or 2 hrs after meal) for maximum absorption. -When treating a serious, established infection, parental antibiotic therapy is frequently MOC. -Recurrence of infection is more likely by switching from parenteral to oral route on the 2nd or 3rd day of antibiotic therapy. -After 5th day of parental administration , the blood levels achievable with oral administration are usually sufficient. 3. Proper route of administration: 4. Consistency in route of administration
- 16. Problems with use of AMA Felix Marti-Ibanez, 1955.
- 17. Drug resistance • Natural resistance: some microbes are naturally resistant to certain drugs their metabolic process or target site is unaffected by this drug. • Acquired resistance: development of resistance over a period of time 1. mutation 2. Gene transfer (horizontal evolution).
- 18. • Mutation It is stable & heritable genetic change that occurs spontaneously & randomly among m-osms 1. Single step 2. Multi step • Gene transfer from one organism to another 1. conjugation: gram -ve 2. transduction: bacteriophage 3. transformation:
- 20. • The resistant m-osms may be, • Drug tolerant: loss of affinity of the target biomolecule of m-osms • Drug destroying: elaborate an enzyme which inactivates the drug • Drug impermeable: transport mechanism may be lost
- 21. TOXICITY • A) Local irritancy: pain gastric irritation , • B) Systemic toxicity: dose related • Aminoglycosides : 8th nerve toxicity-kidney toxicity. • Tetracyclines: liver and kidney damage,anti- anabolic effect. • Chloramphenicol: bone marrow depression.
- 22. Hypersensitivity reactions • These are unpredictable and unrelated to dose whole range of reactions from rashes to anaphylactic reactions can be produced. Superinfection • The use of antibiotics cause alteration in the normal microbial flora. The normal microbial flora contributes to host defence by producing substances called BACTERIOCINS. • Common when host defence is compromised
- 23. Nutritional deficiencies • Vit B complex and Vit K synthesised by intestinal flora • Prolonged use of antimicrobials disrupt this flora
- 24. Choice of an antibiotic • Patient factors • Organism related consideration • Drug factors
- 25. Combined use of antimicrobials • To achieve synergism • To reduce severity or incidence of adverse affects • To prevent emergence of resistance • To broaden spectrum of anti microbial action Disadvantages • Toxicity of one agent may be enhanced by other • Increased chances of suprainfections • Inadequate doses of non-synergistic drugs causes emergence of resistant strains • Increased cost of therapy
- 26. Failure of chemotherapy • Improper selection of drug • Treatment begun too late • Failure to take necessary adjuvant measures ; drainage of abscess, empyema. • Poor host defence – as in leukemia neutropenia.
- 27. PHARMACOLOGY
- 28. Sulfonamides • Sulfonamides are the anti-bacterial agent active against pyogenic bacterial infections . • Bacteriostatic act by interfering with bacterial synthesis of folic acid • Active against many gram+ve and gram- ve organisms • Nausea, vomitting, crystalluria.
- 29. Sulfonamides Preparations available and dosage regimens Short-acting: • Sulfisoxazole is excreted rapidly, is soluble in urine, and still is occasionally used in UTIs. • Sulfadiazine is less soluble in urine and therefore less suitable for use in UTI
- 30. Sulfonamides Intermediate-acting sulfonamides: • Sulfamethoxazole has been combined with trimethoprim and is available as cotrimoxazole. • Oral. Single-strength (SS) tablets contain 80 mg TMP and 400 mg SMX. The double-strength (DS) tablets contain 160 mg of TMP and 800 mg SMX. • Parenteral. An intravenous form of TMP-SMX is supplied in 5- ml ampules that contain 80 mg TMP and 400 mg SMX. Long-acting sulfonamides are no longer recommended
- 31. Quinolones • Entirely synthetic antimicrobial • Mainly active against Gram-ve bacteria, though newer type like flouroquinalones are active against gram positive organisms • Inhibit the bacterial DNA gyrase & thus inhibit the supercoiling of DNA, hence bactericidal Classification First generation: nalidixic acid Second generation: Ciproflox Norflox Lomeflox Oflox Third generation: sparflox Gatiflox Grepaflox Fourth generation: trovafloxacin
- 32. PENICLILLINS • Mechanism of action: • Inhibit transpeptidases which prevents the peptidoglycan cross linking in bacterial cell wall in actively dividing cells, thus causing abnormal cell wall development. • The efficacy of penicillins is maximum when there is active cell wall synthesis, hence do not combine bacteriostatic agent with penicillins. • Less effective against gram –ve organisms as they lack cell wall. • As cell wall is uniquely a bacterial feature not found in humans, it is this reason why penicillins are virtually nontoxic to humans.
- 33. Parenteral preparations of penicillin G : • AQUEOUS PENICILLIN G : 3 to 4million units q4hr. (children 25,000 to3, 00,000 units/kg/day) • PROCAIN PENICILLIN G : 3,00,000 to 6,00,000 units IM 12hr • BENZATHINE PENICILLIN G :0.6-2.4MU i.m every 2wks as aqueous suspension Semi synthetic penicillin • Acid resistant: – phenoxy methyl penicillin (penicillin V). • Penicillinase resistant penicillin: – methicilllin , cloxacillin. • Extended spectrum: 1. Aminopenicillin: Amoxycillin, Ampicilllin. 2. Carboxy Penicillins: Carbencillin 3. Ureidopenicillins: Piperacillin • Beta lactamase inhibitor : – clavulanic acid , sulbactam. Newer beta-lactam drugs Aztreonam , Imipenem
- 34. Cephalosporins Parenteral Oral 1st generation Cephalothin Cefazolin Cephapirin Cephradine Cephalexin Cephradine Cephadroxil 2nd generation Cefamandole Cefoxitin Cefotetan cefuroxime Cefuroxime axetil Cefprozil Cefaclor Loracarbef 3rd generation Cefotaxime Cefoperazone Cefuroxime Ceftizoxime Ceftriaxone Ceftazidime Cefixime Cefpodoxime proxetil Ceftibuten Cefdinir 4th generation Cefepime Cefpirome
- 35. Macrolide antibiotics Erythromycin Clarithromycin Azithromycin Azithromycin: • Azithromycin is a newer macrolide developed to overcome some of the shortcomings of erythromycin such as GI intolerance, low bioavailability, and somewhat limited spectrum of activity. Dosage 1. Azithromycin is available as a 250 mg tablet (or capsule) commonly distributed in a “Z-pack” containing six tablets for a standard 5-day regimen in adults (two tablets [500 mg] day 1 and then one 250 mg tablet qd days 2 to 5). Tablets can be taken with or without food. 2. The flavored oral suspension comes in 100-mg/5 ml and 200-mg/5 ml. The suspension should be given 1 hour before or 1 hour after meal. 5. For IV azithromycin 500 mg IV once daily is infused over at least 60 minutes in patients 16 years of age and older
- 36. Tetracycline
- 37. AMINOGLYCOSIDES • Streptomycin • Amikacin • Gentamicin is used in combination with another agent to achieve synergy against certain pathogens: I. With penicillin, ampicillin, or vancomycin against gentamicin- susceptible enterococci or viridans streptococci; II. With ampicillin against listeria monocytogenes; III. In conjunction with ampicillin (or vancomycin) for endocarditis prophylaxis in high-risk patients before genitourinary (GU) or gastrointestinal (GI) procedures; IV. Combined with an antistaphylococcal penicillin for right-sided endocarditis caused by S. Aureus. Gentamicin is the preferred aminoglycoside in combination therapy aimed at enterococci. Amikacin has been used in some atypical mycobacterial infections. Streptomycin remains a useful agent for M. tuberculosis therapy and for M. kansasii infections.
- 38. Vancomycin Active against resistant organisms Not well absorbed orally . Inhibits bacterial cell wall synthesis Clindamycin Oral absorption is good. It penetrates to most skeletal and soft tissues. Pseudomemberaneus enterocollitis superinfection due to clostridium difficle.
- 39. Metronidazole 1. Metronidazole is very active and bactericidal against anaerobes, especially gram-negative anaerobes, including Bacteroides fragilis, other Bacteroides spp., and Fusobacterium spp. Clostridium spp., including C.perfringens and C.difficile are susceptible to metronidazole 2. The activity of metronidazole against anaerobic gram-positive cocci is much more variable with resistance in up to half of tested isolates 3. Strains of Actinomyces and Propionibacterium (e.g., P.acnes) are resistant Parasites. Metronidazole is very active against Entamoeba histolytica, Giardia lamblia, and Tricahomonas vaginalis
- 40. NEW ANTIBIOTICS OF INTEREST TO ORAL AND MAXILLOFACIAL SURGEONS Moxifloxacin And Gemifloxacin LINEZOLID Approved by FDA for infections caused by vancomycin resistant E. faecium, nosocomial pneumonia caused by MRSA Dose : 600mg BD for Enterococci Quinupristin / dalfopristin Daptomycin Otravacin Remoplanin Tigilcycline
- 42. PREGNANCY RISK CATEGORIES OF SELECTED ANTIBIOTICS ANTIBIOTIC PREGNANCY RISK CATEGORY PREGNANCY RISK PENICILLINS PENICILLIN G AND V AMPICILLIN AMOXICILLIN AMOX + CLAVUNATE TICARCILLIN + CLAVUNATE B CEPHALOSPORINS CEPHALEXIN CEFAZOLIN CEFACLOR CEFOTAXIME B ANTIANEROBIC CLINDAMYCIN METRONIDAZOLE B
- 43. FLUOROQUINOLONES CIPROFLOXACIN MOXIFLOXCIN C SPONTANEOUS ABORTIONS IN RABBITS FETAL TOXICITY IN RODENTS AND MONKEYS AMINOGLYCOSIDES GENTAMICIN TOBRMYCIN D OTOTOXICITY IN HUMAN FETUSES MACROLIDES ERYTHROMYCIN CLARITHROMYCIN AZITHROMYCIN B C B FETAL DEFECTS IN MICE AND MONKEYS OTHER VANCOMYCIN TETRACYCLINES DOXYCYCLINE LINEZOLID C D D C OTOTOXICITY IN FETUSES INTRINSIC DENTAL STAINING FETAL TOXICITY IN RODENTS
- 44. Antibiotic Second drug Adverse effects Mechanism Erythromycin E Clarithromycin C Theophylline Seizures , dysrhythmias Inhibits cytochrome P 450 metabolism of 2nd drug Carbamazepine Ataxia, vertigo, drowsiness Methylprednisolo ne immunosuppressi on Erythromycin Clindamycin antibiotic effect Mutual antagonism Erythromycin E Clarithromycin C Metronidazole warfarin anticoagulation Interferes with the metabolism Cephalosporin Aminoglycosides nephrotoxicity Additive effect Drug interactions
- 45. Tetracycline , Cefotetan, Cefoperazone , Aminoglycosides, sulfonamides Warfarin anticoagulation Antibiotic kills gut flora that synthesize vit k , which antagonizes the 2nd drug Penicillins , cephalosporins Metronidazole Erythromycin Tetracyclines Estrogen and progestin containing oral contraceptives Contraceptive failure Interference with enterohepatic circulation of estrogen caused by killing of gut flora Fluoroquinolones Sulfonamides Chloramphenicol Oral hypoglycemic agents Hypoglycemia Antibiotic displaces 2nd drug from plasma proteins Ciprofloxacin sulfonamides Chloramphenicol Phenytoin Increases serum level of phenytoin , confusion, delirum Interference with phenytoin metabolism
- 46. PRIMARY REASONS FOR REVISION OF THE INFECTIVE ENDOCARDITIS PROPHYLAXIS GUIDELINES Infective endocarditis (IE) is much more likely to result from frequent exposure to random bacteremias associated with daily activities than from bacteremia caused by a dental,GI tract or genitourinary (GU) tract Procedure Prophylaxis may prevent an exceedingly small number of cases of IE, if any, in people who undergo a dental, GI tract or GU tract procedure The risk of antibiotic-associated adverse events exceeds the benefit, if any, from prophylactic antibiotic therapy Maintenance of optimal oral health and hygiene may reduce the incidence of bacteremia from daily activities and is more important than prophylactic antibiotics for a dental procedure to reduce the risk of IE
- 47. Previously/No longer recommended Currently recommended Mitral valve prolapse. Rheumatic heart disease. Bicuspid valve disease. Congenital heart conditions (eg atrial septal defect, ventricular septal defect, hypertrophic cardiomyopathy). Calcified aortic stenosis Patients with history of previous IE Patients with a prosthetic cardiac valve Recipients of cardiac transplantation who develop cardiac valvulopathy Patients suffering from the following forms of congenital heart disease (CHD). Completely repaired CHD with prosthetic device or material during the first six months following the procedure where placement is either by surgery or catheter. Unrepaired cyanotic CHD, which includes palliative shunts and conduits. Repaired CHD with residual defects at or adjacent to the site of a prosthetic device or patch (inhibiting endothelialization). Antibiotic therapy is no longer recommended for any other form of CHD other than those named above.
- 48. Current recommended regimens for dental procedure Patient Antibiotic One dose 30–60 min before procedure Adults Children Able to take oral medication Amoxicillin 2 gm 50 mg/kg Not able to take oral medications Ampicillin Cefazolin Ceftriaxone 2 g IM or IV 1 g IM or IV 50 mg/kg IM or IV 50 mg/kg IM or IV Allergy to Penicillins or ampicillin oral Cephalexin* Clindamycin Azithromycin Clarithromycin 2 g 600 mg 500 mg 50 mg/kg 20 mg/kg 15 mg/kg Allergy to penicillins or ampicillin and not able to take oral medications Cefazolin Ceftriaxone Clindamycin 1 g IM or IV 600 mg IM or IV 50 mg/kg IM or IV 20 mg/kg IM or IV *Do not use cephalosporins in patients with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin
- 49. TOTAL JOINT REPLACEMENT Procedures – requiring prophylaxis Dental extractions Periodontal procedures, scaling n root planing Dental implant Periapical endodontic procedures Intraligamentary LA Placement of orthodontic bands ADA and AAOS most pts with a prosthetic joint are not at risk of joint infection after a dental surgical procedure.
- 50. EXODONTIA AND DENTOALVEOLAR SURGERY • Although intraoral surgical wounds are contaminated by the oral flora, the ability of patients normally to tolerate this bacterial population and the excellent blood supply to the oral tissues allow such wounds to be managed similarly to clean wounds. It is unnecessary to use prophylactic antibiotics to prevent infection when performing most types of exodontia and dentoalveolar surgery unless there are other contributing risk factors. • If the procedure involves the maxillary sinus or nasal cavity, however, this can result in cross-contamination with new organisms, and prophylactic antibiotics should be used except when there is already infection in these areas. In the latter instance, therapeutic antibiotics are indicated.
- 51. IMPACTED THIRD MOLAR SURGERY • Although many practitioners routinely prescribe antibiotics for patients who have impacted third molars removed, they are generally prescribed postoperatively. No convincing data show a significant reduction in postoperative infections after third molar removal when antibiotics are used in this manner. • Prophylactic antibiotics treatment should be reserved only for patients with significant medical risk factors for infection. In these cases it should be given immediately before surgery, having a high tissue concentration present at the time of surgery when the wound is exposed to bacterial contamination, and for 3 to 5 days after surgery to provide an adequate period of coverage.
- 54. Osteomyelitis Antibiotic impregnated beads Tobramycin and gentamicin in acrylic resin bone cement beads They are removed after 10-14 days.
- 56. ORTHOGNATHIC SURGERY • Orthognathic surgery performed via an extraoral approach is considered a clean procedure and prophylactic antibiotics should not be necessary unless communication with the mouth is anticipated. • Intraoral procedures and procedures that involve the maxillary sinus and nasal passages are clean-contaminated operations, and short-term prophylactic antibiotics have been shown to reduce the postoperative infection rate.
- 57. MANDIBULAR FRACTURES • Patients with condylar process fractures treated by either open or closed reduction require no prophylactic antibiotics. The same is true for fractures in other non– tooth-bearing areas that are not in communication with the mouth, because these are all clean wounds. • In patients with compound mandibular fractures, however, which are contaminated wounds, studies have shown that the use of antibiotics is effective in reducing postoperative infections. • Fractures for which there is delayed treatment should be considered dirty wounds, and such patients should receive therapeutic antibiotics postoperatively
- 58. In relation to trauma and Soft tissue injury • Not indicated when the patient is first seen in the ED, for laceration wounds which are not extensive visibly clean treated early • Indicated when the patient is first seen in the ED, for laceration wounds which are extensive • For extensive laceration wounds seen early, in which a delay in treatment is expected, prophylactic antibiotics should be started immediately and continued until definitive treatment • Laceration wounds seen late or wounds which are visibly contaminated should be assumed to be infected Open fractures of the facial bones • Antibiotic prophylaxis is indicated and should be administered when the patient is first seen in the Emergency Department • When a delay in treatment for open fractures is expected antibiotics should be started on admission and continued until temporary or definitive fixation of the fractures • Open fractures that are seen late should be assumed to be infected • Antibiotic prophylaxis is indicated in the surgical management of open fractures of the facial bones
- 59. Dental implants
- 61. References • ORAL AND MAXILLOFACIAL INFECTIONS – TOPAZIAN • Essentials of Medical Pharmacology- K D Tripathi • Basic & Clinical Pharmacology- Katzung • Articles from internet – sciendirect.com Infections are ultimately cured by the host and not the antibiotic ! - Topazian
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