Antibiotics and the Dental Practice PDF

ANTIBIOTICS AND THE DENTAL PRACTICE Sanjay Chand MD Professor Integrated Biomedical Sciences Detroit Mercy Dental University of Detroit Mercy 1 Vignette # 1 12-year-old Joey presents...

ANTIBIOTICS AND THE DENTAL PRACTICE Sanjay Chand MD Professor Integrated Biomedical Sciences Detroit Mercy Dental University of Detroit Mercy 1 Vignette # 1 12-year-old Joey presents with a painful fractured tooth, a runny nose and body aches and pains. We should prescribe antibiotics to Joey as coverage for his dental procedure due to his symptoms. 1. True 2. False 2  Vignette # 2 ▪ Your patient presents with a cold sore which resembles the picture. You have a tightly scheduled day and want to complete the procedure ASAP. ▪ Should you give this patient a single high dose of antibiotics to cover the infection? ▪ Should you continue your procedure? 3 Vignette # 3 ▪ Your patient presents with an itchy throat and says they can scrape off the white, cheesy deposit at the back of their throat and tongue. ▪ Which of the following is drug of choice? 1. Penicillin 2. Acyclovir 3. Nystatin 4. Prednisone 4  Vignette # 4 ▪ A 54-year old previously healthy male presents with a painful, marble sized swelling in the submandibular region. He has high fever and vomiting for 2 days with skin rash involving the entire neck and shoulders. ▪ No history of trauma or injury. ▪ He has dysphagia, odynophagia and trismus ▪ He had a 3rd molar dental extraction 2 weeks ago. ▪ Examination reveals tachycardia with HR of 140 bpm, fever of 104oF and hypotension (BP of 80/58) ▪ He has multiple body piercings. 5  Vignette # 4 ▪ Examination reveals intensely red, blanchable erythema involving the entire skin of his neck and oropharyngeal mucous membranes. ▪ Swelling spread to jaw and regions of the neck ▪ 2 × 2 cm tender, fluctuant swelling, mobile over underlying tissue located at submandibular region ▪ I/D: drainage of 5 ml of purulent fluid ▪ Culture reveals alpha hemolytic Streptococci and Staphylococci 6 7  Ludwig’s Angina ▪ A serious, life-threatening cellulitis and infection of the floor of the mouth ▪ Occurs in adults with concomitant dental infections ▪ Airway obstruction necessitating tracheotomy ▪ Mixed infections: Aerobes and anaerobes ▪ Alpha-hemolytic streptococci, staphylococci,bacteroides ▪ Fascial space infection with involvement of submandibular, sublingual and submental spaces. ▪ Bilateral lower facial edema around upper neck. ▪ Dysphagia, odynophagia, difficulty breathing, and pain. 8 Case # 1 11-year-old patient presents: Localized pain and swelling on right side of face 101.2 Fever Thermal sensitivity Gingival bleeding Swelling and warmth Erythema Fluctuant mass that extends beyond the right buccal region Case # 1 On examination: Regional lymph node involvement right side Trismus Dysphagia Respiratory difficulty Necrotizing fasciitis Differential diagnosis Buccal bifurcation cyst Langerhans Cell Histiocytosis Periapical granuloma or cyst Peritonsillar Abscess Management: Dental abscess: assess the airway, oropharyngeal tissue swelling, or inability to handle secretions Collect specimen for Gram stain and aerobic and anaerobic cultures. Administer analgesia Hydrate the patient Empiric antibiotic therapy? Recommendation A Pulpectomy or incision and drainage is the recommended management of a localized acute apical abscess in the permanent dentition Incision and drainage or spontaneous rupture of the abscess quickly accelerates resolution of the infection The addition of antibiotics is not recommended for a localized dental abscess Which of the following is the most important clinical sign of a fulminant odontogenic infection requiring antibiotic treatment? 1. Swelling 2. Pain 3. Fever 4. Loss of function Concept of Selective Toxicity ▪ Goal of antimicrobial and anticancer therapy ▪ Inhibition of pathways/targets that are critical for pathogen/ cancer cell survival ▪ Dose needed should not ideally affect host cells Mechanisms: 1. Attacking a target unique to pathogen 2. Targets that are similar to host but not identical 3. Targets shared by host and pathogen but are vital for pathogen/ cancer cell survival Therapeutic Index: Ratio of TD (toxic dose) 50/ ED (effective dose)50 Therapeutic window: (Aminoglycosides- Gentamicin, Digoxin, Theophylline, Lithium) 15  1. Unique Drug Targets ▪ Metabolic pathways, Enzymes and Mutated genes lacking in the host ▪ Bacterial peptidoglycan cell wall ▪ Penicillins and other beta-lactam antibiotics inhibit transpeptidases which catalyze cross linking of peptidoglycan strand formation ▪ Weak cell wall and cell lysis ▪ Fungi: Beta 1,3-D-Glycan in fungal cell wall as well as Ergosterol ( Azoles and Polyenes) 16  2. Selective Inhibition ▪ Organisms have similar metabolic pathways ▪ Evolutionary divergence with distinct enzymes ▪ Dihydrofolate reductase (DHFR) is a crucial enzyme in synthesis of folic acid ▪ Sulfamethoxazole and Trimethoprim have selectivity for folic acid pathways in bacteria ▪ Methotrexate (anticancer/ immunosuppressant) is non-selective but acts on folic acid ▪ Bacterial protein synthesis involves binding of mRNA to ribosome, decoding, translocation of peptide chain (Macrolides and Aminoglycosides) 17  3. Common targets ▪ Tumor cells arise from normal cells and share common pathways for growth / mutation ▪ Mutated and over expressed proteins in cancer cells help in targeting them ▪ Cancer cell growth behaviour, apoptosis and senescence differ from normal cells ▪ Rapidly proliferating cells targeted easily ▪ 5-FU (Fluorouracil) inhibits thymidylate synthase which is essential for building pyrimidine in DNA ▪ This results in DNA damage and early apoptosis in Cancer cells as well as normal cells 18  Microbial Resistance 1. Enzymatic inactivation 2. Modification of target site 3. Altered cell membrane permeability 4. Active Drug efflux 5. Failure to activate the antibiotic 6. Insensitivity to apoptosis 7. Overproduction of target sites  Natural Resistance  Bacterial has always been resistant due to inherent properties of the bacteria.  Acquired Resistance  Resistance seen in bacteria which were previously sensitive to an antimicrobial agent. This develops over time with long term use. 19 20  Genetic Mechanisms ▪ Chromosomal mutations maybe be transferred to the daughter cells (vertical transmission) or to other bacteria by sharing genetic material (horizontal) ▪ Bacteriophages: Bacterial viruses that may be shared ▪ Integrons: Genetic elements that capture and disseminate genes through a ‘Gene cassette’ ▪ Transposon: Mobile genetic element which may be transferred from one organism to another ▪ Plasmid : DNA molecule that can survive independently and inject itself into a naive bacteria 21  Insensitivity to apoptosis ▪ Drug resistance in cancer cells occurs through chromosomal mutations that are passed to daughter cells ▪ Resistant tumor is insensitive to apoptosis ▪ Chemotherapeutic agents cause molecular lesions which cause cell cycle arrest, inactivation of repair process and apoptosis ▪ Mutations in key proteins such as p53 and Bcl-2 lead to failure of apoptosis ▪ Pancreatic, lung and colon cancers have high incidence of such p53 mutations 22  Superinfections ▪ A new infection while patient is being treated for a primary infection  More likely with broad spectrum antibiotics  May also be opportunistic infections with fungi such as Candida albicans  May occur due to inhibition of normal flora such as Clostridioides difficile and pseudomembranous colitis  Difficult to treat  Drug resistant microbes usually involved 23 Chemoprophylaxis is recommended for invasive dental procedures in patients who have had hip replacement 6 months ago. 1. True 2. False  Antibiotic Therapy ▪ Empiric therapy  Initiation of treatment with a broad-spectrum drug  Begin treatment immediately in severe infection  Consider taking a sample for culture ▪ Treatment with combination drugs usually prevents resistance and superinfection development ▪ Standard of care in HIV/ TB/ Cancer ▪ Chemoprophylaxis: Before a potential exposure. Used in high-risk patients. Dental procedures to prevent endocarditis. Immunocompromised pts to prevent reactivation of latent infections 25  Antibiotic Stewardship The U.S. Centers for Disease Control and Prevention’s (CDC) Division of Oral Health defines antibiotic stewardship as: An effort to measure antibiotic prescribing To improve antibiotic prescribing by clinicians and use by patients so antibiotics are only prescribed and used when needed To minimize misdiagnoses or delayed diagnoses leading to underuse of antibiotics To ensure that the right drug, dose, and duration are selected when an antibiotic is needed. Antibiotic Resistance Researchers from Temple University School of Dentistry in November 2024 20-year study shows a marked increase in resistance in Porphyromonas gingivalis Main pathogen of gingivitis and periodontitis Resistance to Clindamycin affected 9.3% P. gingivalis resistance to Amoxicillin increased from 0.1% of patients in 2000 to 2.8% in 2020 28-fold increase Antibiotic Resistance Dentists are top prescribers of Clindamycin, the most common antibiotic leading to Clostridioides difficile (C. difficile) AHA: Clindamycin is no longer recommended for antibiotic premedication for Dental procedures. The study also determined that the P. gingivalis resistance rates to several other antibiotics showed no significant changes over the 20-year period studied Metronidazole, Metronidazole plus Amoxicillin, Clavulanic Acid plus Amoxicillin and Doxycycline In the United States, 70% of antibiotics sold are for use by________________: A. Dentists B. Gynecologists C. Pediatricians D. Farmers Spectrum of Activity  Narrow spectrum: Agents that are active against a single species or a limited group of pathogens. Penicillin G; Cloxacillin, Nafcillin, Methicillin PenicillinV; Erythromycin; Clindamycin  Extended: Agents have activity greater than a limited group but narrower than broad spectrum  Piperacillin, Ticarcillin  Broad spectrum: agents that are active against a wide range of pathogens Amoxycillin, Ampicillin, Tetracyclines; Chloramphenicol, Sulfamethoxazole 31  Bactericidal Bacteriostatic ▪ Penicillin V (Pen-Vee K) ▪ Erythromycin (Eryc) ▪ Amoxicillin (Amoxil) ▪ Clarithromycin (Biaxin) ▪ Cephalexin (Keflex) ▪ Azithromycin (Zithromax) ▪ Cefadroxil (Duricef) ▪ Clindamycin (Ceocin) ▪ Metronidazole (Flagyl) ▪ Tetracycline (Achromycin) ▪ Ciprofloxacin (Cipro) ▪ Doxycycline (Vibramycin) ▪ Aminoglycosides 32  Antibiotic Failure ▪ Blood concentration too low ▪ Patient compliance ▪ Impaired host immune system ▪ Inappropriate choice of drug ▪ Limited vascularity or blood flow to tissue ▪ Emergence of bacterial Resistance ▪ Delay in diagnosis ▪ Incorrect diagnosis ▪ Antibiotic antagonism or interactions 33 Which of the following is a diagnostic sign of Stevens Johnson syndrome? 1. Kopliks spots 2. Bulls eye rash 3. Butterfly rash 4. Grape like lesions 34 35  Mechanisms of Antibacterial Action ▪ Inhibition of Cell wall synthesis ▪ Alteration of cell membrane permeability ▪ Inhibition of Ribosomal Protein synthesis ▪ Suppression of DNA synthesis ▪ Inhibition of Folic Acid synthesis 36 37  Vignette # 5 : Mrs. Smith ▪ Mrs. Smith 36 yr old housewife comes with complaint of nausea, severe abdominal cramps, watery diarrhea with mucus, fatigue and low-grade fever. She has no significant past medical history. ▪ She indicates that she lives a ‘healthy’ lifestyle with a regular daily swim, eats fresh salads, drinks fresh apple cider. ▪ She suffers from repeated bouts of dental infections for which she takes antibiotics off and on. ▪ She has recently received Clindamycin, Metronidazole and Ampicillin ▪ She received similar antibiotics in January and March ▪ What is Mrs. Smith’s diagnosis? 38 PENICILLINS 1. Parenteral Penicillin G / Oral Penicillin V : Used for mixed aerobic-anerobic infections of the head and neck and dental infections 2. Anti-staphylococcal Penicillins: Structurally resistant to beta lactamase. Skin and soft tissue infections ▪ Oxacillin, Cloxacillin, Methicillin, Nafcillin 3. Aminopenicillins: (Mouth, Ear, nose and throat) ▪ Ampicillin, Amoxicillin and clavulanic acid 39 PENICILLINS: Mechanism of action ▪ Bind to penicillin binding proteins (PBP).  Inhibit Transpeptidases  Inhibit the cross-linkages between the peptidoglycan polymer strands  Promote autolysins  Autolysin is an enzyme that breaks section of cell wall to permit bacteria cell growth and cell lysis  Most effect against growing and dividing cells. 40 Penicillin G (Benzylpenicillin) ▪ Parenteral use only (IV) ▪ Narrow spectrum [gram +ve & some gram -ve] ▪ Bactericidal ▪ Susceptible to Beta lactamase ▪ Administration: IM; IV (BUT NOT oral)  Not used routinely for outpatients  Emergency Rx: IV for Ludwig Angina 41  Aminopenicillins Ampicillin, Amoxicillin, Bacampicillin ▪ Effective against: Gram +ve cocci, gram –ve cocci such as Neisseria g and m (?) and gram –ve rods such as Hemophilus and E. coli ▪ Not resistant to beta lactams ▪ Extended Spectrum ▪ Used for uncomplicated ENT infections and component of triple therapy for H pylori ▪ Amoxicillin: Better oral absorption; can be taken with food, less adverse effects than Ampicillin. 42 Beta lactamase: Penicillinase ▪ An enzyme produced by some bacteria.  Penicillin V and Amoxicillin are ineffective against these bacteria.  Beta lactamase degrades or inactivates these antibiotics  Strategy to overcome these resistant bacteria  Amoxicillin and Clavulanic acid  Augmentin :Amoxicillin + Clavulanate  Clavulanic acid inhibits ß-lactamase  Molecular structure is similar to Beta lactam 43 If a patient suffers from severe Penicillin anaphylaxis, the following antibiotic should NOT be used: 1. Clindamycin 2. Doxycycline 3. Cephalexin 4. Sulfamethoxazole 44 Penicillin Allergy ▪ All penicillins are cross-sensitizing and cross-reacting although mainly nontoxic antigens are degradation products ▪ 1-8% of population are sensitive ▪ 400 - 800 deaths/year in U.S. ▪ Mild anaphylaxis: 1/200 courses ▪ Severe anaphylaxis: ≈1/2,000 courses ▪ Fatality rate: 1/60,000 ▪ >95% of fatal reactions occur within 60mins 45 Penicillin Anaphylaxis ▪ Serum Sickness type 1 ▪ Fever, urticaria, joint pain and swelling, pruritis, skin rash ▪ Oral lesions, interstitial nephritis, eosinophilia, hemolytic anemia and vasculitis ▪ Anaphylactic shock and death 46  Penicillins - Drug Interactions ▪ Aminoglycosides (Gentamicin) – inactivation ▪ Oral contraceptives: Hepatic enzyme induction CYP 450, thus failure of contraception ▪ Probenecid - Decreases renal tubular secretion of Penicillin ▪ Used therapeutically for increasing serum concentrations in patients with renal toxicity 47  Cephalosporins ▪ Similar structure to Penicillins except a 6 membered ring instead of 5 in Penicillin ▪ Stable against Beta lactamases ▪ Possess 7- aminocephalosporanic acid ring instead of 6- aminopenicillanic acid ▪ 4 Generations 48 Cephalosporins ▪ 1st generation destroyed by Beta lactamases.  Cephalexin (Keflex), Cefazolin: Streptococci, pneumococci and Staph  Used for soft tissue abscess in oral cavity  Drug of choice for surgical prophylaxis ▪ 2nd generation more resistance to lactamases: Cefuroxime and Cefoxitin ▪ Effective against all bacteria of First generation plus Gram –ve ( Klebsiella, H influenza) ▪ Cefuroxime: Used to treat Sinusitis, otitis and lower Respiratory infections 49 Third and Fourth Generation ▪ Third Generation: Cefotaxime, Ceftriaxone ▪ Expanded Gram-ve coverage with resistance to beta lactamases ▪ Able to cross Blood brain barrier ▪ Used in Meningitis caused by Pneumococi, Meningococci and H influenza ▪ Sepsis in immunocompromised patients ▪ Fourth Generation: Cefepime: Highly active against Neisseria, H influenza, P aeruginosa ▪ Not approved for the treatment of meningitis 50 Fifth Generation ▪ Ceftaroline is distinct in being active against MDR staph aureus, methicillin resistant (MRSA), Vancomycin resistant staph aureus ▪ Approved by the FDA for community acquired skin infections and pneumonia ▪ Teflaro ▪ Approval from the U.S. Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin infections 51 Cephalosporins: Adverse effects  Similar to penicillins  Allergic reactions; GI  Allergic Reactions have Penicillin cross –sensitivity  Toxicity: Local irritation after IM inj. And thrombophlebitis after IV inj.  Renal toxicity: Nephritis and tubular necrosis  Have been known to cause Hypothrombinemia and bleeding disorders in some 52 If an antimicrobial agent acts through the mechanism of inhibition of cell wall synthesis it is considered to be: 1. Bacteriostatic 2. Bactericidal 3. Virucidal 4. Fungicidal 53  Protein Synthesis Inhibitors Erythromycin Azithromycin Clarithromycin Clindamycin Tetracyclines Chloramphenicol Aminoglycosides ▪ Referred to as ‘Broad Spectrum antibiotics’ ▪ Greater affinity for microbial Ribosomal subunits 30S, 50S and 70 S ▪ Protein synthesis occurs at a much faster rate in microbial cells and therefore antibacterial activity is strong 54 Protein Synthesis Inhibitors ▪ Bacteriostatic  Tetracyclines  Tetracycline, Doxycycline, Minocycline  Macrolides  Erythromycin, Azithromycin; Clarithromycin  Lincosamines: Clindamycin  Broad spectrum: Chloramphenicol  Aminoglycosides: Streptomycin, Amikacin 55 TETRACYLINES ▪ Broad Spectrum, gram +ve and gram -ve ▪ Also Anerobes, Rickettsia, Chlamydia and some Protozoans (Amoeba) ▪ Tetracycline; Doxycycline; Minocycline ▪ Block protein synthesis by penetrating through the bacterial cell wall by passive diffusion and binding to 30S subunit ▪ Prevent binding of tRNA to mRNA-ribosome complex ▪ Prevent addition of Amino Acids to chain 56  TETRACYLINES ▪ Erratic absorption and remains in GIT and kills flora ▪ Absorption impaired by food, Ca++ Milk, Antacids (Al+++ Mg++ Fe++) ▪ Reaches fetus thus damaging developing bones and teeth  Hypertrophy of papilla  Darkened or discolored tongue  Fanconi’s Syndrome (ARF) ▪ Clinical uses: Acne, peptic ulcer disease, periodontal diseases, Cholera, Chlamydia and other STDs, Plague, Lyme Ds, Skin infections 57 Macrolides: Erythromycin ▪ Azithromycin, Erythromycin, Clarithromycin ▪ Narrow spectrum (newer classified as broad spectrum) ▪ Gram +ve (Pneumococci, Strep, Staph, Chlamydia, Legionella) ▪ Gram – ve (Treponema pallidum) ▪ Alternative for patients allergic to Penicillins ▪ Binds to 50S subunit of ribosomes  Blocks addition of new amino acids to the growing peptide (Blocks protein synthesis) ▪ Bacteriostatic at normal or bactericidal at larger concentrations 58  Newer macrolides ▪ Telithromycin ▪ FDA approved 2004 semi-synthetic derivative ▪ Formerly known as Ketolide ▪ High affinity for 50S ribosomal binding ▪ Bind to an additional site on 23S ribosome ▪ May be used where resistance to Macrolides has developed in bacterial strains ▪ Large number of drug interactions ▪ Rare cases of fulminant hepatic necrosis 59 All the following are mechanisms of genetic mechanisms for drug resistance in bacteria EXCEPT: 1. Bacteriophages 2. Transposons 3. Plasmids 4. Efflux pump 60 Chloramphenicol ▪ Bacteriostatic: Aerobic/ anerobic/ Gram +ve/ -ve ▪ H influenza, N meningitidis, Bacteroides ▪ Salmonella: Typhoid fever, bacterial meninigitis ▪ Rickettsia ▪ Binds to 50S ribosomal subunit ▪ Resistance: Plasmid encoded acetyltransferases that inactivate the drug ▪ Toxicity: Inhibition of mitochondrial protein synthesis. Gray baby syndrome ▪ Lack of conjugation: vomiting, flaccidity, hypothermia, respiratory distress, gray color. 61  Clindamycin (Cleocin) ▪ Derivative of Lincomycin ▪ Lincosamide ▪ Binds to 50S subunit of bacteria ribosome ▪ Bacteriostatic for Strep, Staph and Pneumo ▪ Spectrum  Anaerobic (gram +ve & -ve)  Aerobes (gram +ve)  Used for skin and soft tissue infections  Alternate for odontogenic infections  Penetrating wound of skin and muscle  Prophylaxis of infective endocarditis 62  Clindamycin ADRx ▪ Incidence More Frequent ▪ Incidence Less Frequent  GI disturbances  Allergy  Pseudomembranous  Neutropenia colitis  Thrombocytopenia  abdominal pain & cramps  nausea & vomiting  Diarrhea  Fungal overgrowth 63  Pseudomembranous Colitis ▪ Risk factors:  Antibiotics  Clindamycin  Cephalosporins  Ampicillin  Amoxicillin  Erythromycin  Elderly  Females with genitourinary diseases 64  Pseudomembranous Colitis: Clostridiodes difficile ▪ Clinical features: ▪ Treatment  Crampy abdominal  Stop all antibiotics pain  Hydration  Lower quadrant  Vancomycin (Oral; abdominal tenderness 500 mg QID for 10-14  Watery diarrhea days)  Fever  Fidaxomicin (Dificid)  Leukocytosis  Metronidazole (500 mg TID, 7 -14 days). 65  Vignette # 6 ▪ 48 year old woman presents to the dental clinic with a 4 day history of painful lesions around the perioral area with burning. ▪ She had fever with chills and pain in her flanks during micturition a week ago for which she was prescribed Bactrim DS (Sulfamethoxazole and Trimethoprim) by her PCP. ▪ What is your diagnosis for this lesion? ▪ What would best practice guidelines for management of this patient ? 66 Sulfonamides: Sulfamethoxazole ▪ Bacteria manufacture their own Folic acid ▪ Sulfonamides inhibit Folic acid synthesis ▪ Sulfonamides resemble PABA (Para-amino Benzoic Acid) as structural analogues ▪ Resistance may occur  Increase synthesis of PABA  Alter enzyme structure  Reduce sulfonamide uptake ▪ Clinical uses  Systemic: Urinary tract infection  Topical : Conjunctivitis; Corneal ulcer 67  Sulfonamides- Adverse effects ▪ Blood Dyscrasias ▪ Photosensitivity ▪ Stevens-Johnson Syndrome ▪ Allergy - metabolite (PABA) ▪ Renal damage from Crystalluria 68  Trimethoprim ▪ 40,000 times greater affinity for bacterial DHFR ▪ Minimal effects on mammalian cells ▪ Trimethoprim and Sulfamethoxazole (1:5 ratio) act in concert with each other ▪ Brand names: Bactrim, Septra, Cotrim, Co- trimoxazole ▪ Resistance  Increase synthesis of enzyme (DHFR)  Reduce permeability to trimethoprim 69 The following groups of antimicrobials both contain the Beta lactam ring: 1. Tetracyclines and Cephalosporins 2. Penicillins and Cephalosporins 3. Macrolides and Penicillins 4. All antimicrobials contain the beta lactam ring 70  Nucleic Acid Synthesis Inhibitors ▪ Fluoroquinolones (Quinolones)  Ciprofloxacin  Norfloxacin  Levofloxacin  Ofloxacin ▪ Results in loss of helical structure, strand breakage and resultant inhibition of nucleic acid synthesis and cell death. ▪ Bactericidal 71 Fluoroquinolones ▪ Ciprofloxacin, Norfoxacin, Levofloxacin  Mechanism of Action  Inhibits bacterial DNA gyrase  DNA gyrase converts closed circular DNA into supercoiled configuration  Prevents supercoiling, stops DNA replication  Resistance :  Alteration of DNA gyrase  Decrease permeability 72  Fluoroquinolones ▪ Ciprofloxacin  Broad spectrum  Most aerobic gram -ve and some gram +ve  Bactericidal  Adverse effects, mild (relative)  GI upset: Nausea Vomiting Diarrhea  CNS - Dizziness, headaches, confusion  Children - cartilage damage.  Not used in children under 18-year-old  Not used in Elderly patients/ Tendonitis. 73  Metronidazole (Flagyl) ▪ Metronidazole: antibiotic and antiprotozoal ▪ Used for Gram –ve anerobic odontogenic infections ▪ Pelvic inflammatory disease, endocarditis, and bacterial vaginosis ▪ Clostridium difficile colitis if vancomycin or fidaxomicin is unavailable ▪ Chemically reduced to a toxic metabolite  This reaction is unique to anaerobic bacteria ▪ Toxic metabolite interacts with DNA 74  Metronidazole ▪ Adverse effects  CNS disturbances: dizziness, lightheadedness  GI disturbances: abdominal pain & cramps; nausea & vomiting; diarrhea  Taste: changes in sensation; sharp metallic taste  Dry mouth, Dark urine  Seizures (high doses)  Disulfiram like reaction 75 Metronidazole Drug Interactions ▪ Alcohol - Disulfiram-like reaction: Nausea, giddiness, flushing, abdominal cramps; accumulation of acetaldehyde. ▪ This results due to the non conversion of Acetaldehyde which accumulates ▪ Disulfiram (Antabuse)- confusion, psychotic reactions, convulsions; 2-week washout period recommended. ▪ Anticoagulants - inhibit metabolism; increase plasma levels; monitor prothrombin time. ▪ Phenytoin - Phenytoin toxicity. 76 Sulfonamides act by inhibition of the following: 1. Gamma Amino Butyric Acid (GABA) 2. Para amino Benzoic Acid (PABA) 3. Transpeptidase enzyme 4. DNA gyrase 77 Vancomycin ▪ Mechanism of action  Acts by binding to Peptidoglycan strand of cell wall and preventing further growth ▪ Effective against MRSA ▪ Pharmacokinetics  Not absorbed from the GI  Excreted unchanged via the kidneys ▪ Clinical uses  Oral, for serious GI infection (?)  Slow infusion, serious systemic infection  Bolus IV injection: ‘Red man syndrome’ 78  Vignette # 7 ▪ A 17- year-old man with no significant medical history was admitted to the ICU after suffering third degree burns over 40% of his body. He has been relatively stable for the past 24 hrs but has fever and chills and his white blood cell count is rising. ▪ Blood cultures have been taken: result pending ▪ Hospitalist is concerned about Sepsis ▪ What treatment would this patient receive? 79  Aminoglycosides ▪ Streptomycin is prototype drug ▪ Gentamicin, Tobramycin, Amikacin ▪ Bind to 30 S subunit and inhibit protein synthesis ▪ Virtually the same spectrum as Fluoroquinolones plus Enterococci ▪ Used for Sepsis, Pneumonia, ▪ Given only IV, at low cost ($3/day). ▪ Drug monitoring required ▪ Hardest drugs to dose  Side effects ▪ Vestibular toxicity (Irreversible) loss of balance, hearing and dizziness (Ototoxic) ▪ Renal toxicity (Reversible) Monitor Creatinine (Nephrotoxic) ▪ Neuromuscular blockade can occur during surgery because Aminoglycosides can have an additive effect with paralyzing agents ▪ Adding Furosemide or other nephrotoxic drugs increases risk of renal damage ▪ Can also happen if patient is given an overdose. The following antibiotic is a drug of choice for gram –ve anerobic infections: 1. Tetracycline 2. Amoxicillin 3. Metronidazole 4. Cephalexin 82 Antibiotic Stewardship in Dentistry Facts About Antibiotics Serious public health threat 2.8 million illnesses and 35,000 deaths/ year Infections with antibiotic resistance are difficult to treat Few antibiotics available for treatment Clostridioides difficile Infection (CDI) Emergency room visits for adverse effects and interactions Antibiotic Prescribing in Dentistry 80 - 90% antibiotic prescribing: Out-patient settings 30% out-patient prescribing is inappropriate ✓Indication ✓Diagnosis ✓Dosage ✓Duration Dentists are 3rd largest prescribers by volume in US  Antibiotic Prescribing in Dentistry Oral bacterial infections: pain, swelling, redness, purulent exudate, fever, systemic spread, immunosuppression Focus on eliminating the pathology Use radiographic identification Clean periodontal infection Provide endodontic treatment I & D of abscess Prevent transition of cellulitis into abscess Differential: Fungal, Viral, Ulcers, Chemical, Trauma  Challenges Faced by the Dentist When should I prescribe an antibiotic? Antibiotic adverse effects Interactions with food, medications and recreational drugs Lack of awareness of published guidelines Cardiac conditions requiring antibiotic prophylaxis Prosthetic joints requiring antibiotic prophylaxis Providers overestimate patient demand for antibiotics Hospital ER visits: Antibiotics / Opioids Decreased preventative dental care ADA: Optimal Antibiotic Prescribing Diagnosis of bacterial infection ‘Rationale for treatment’ decision Use of Narrow-spectrum antibiotics Do NOT combine narrow and broad spectrum Use for the shortest duration possible Amoxicillin 500 mg TID/ Augmentin (Clavulanic acid) Azithromycin 1 gm stat then 500 mg OD Adequate Disposal of unused drugs Some Do Not’s Do not prescribe antibiotics based on: Patient demand Peer pressure Convenience Prophylaxis Social pressure Claimed allergy: 10% report allergy,