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Dental Drugs in the World of Medicine: Assessing and Managing

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Dental Drugs in the World of Medicine: Assessing and Managing Academy of General Dentistry Dr. Art Jeske July 12, 2017 The opinions expressed in this presentation are those of the speaker and not necessarily those of the University of Texas School of Dentistry or the Academy of General Dentistry The opinions expressed in this course should not be construed as advice for the care of specific patients. The drugs and techniques contained in this course must be based on the clinical judgment of the individual practitioner. Dr. Art Jeske U.T. School of Dentistry 7500 Cambridge Street Suite 6336 Houston, TX 77054 USA [email protected] 713-486-4506 Copyright Reserved Understand the pharmacologic characteristics of newer medications and their impact on dental treatment Provide current, evidence-based information on major classes of drugs used in dentistry Review appropriate emergency drugs for general dental practice and methods of administration Review professional guidelines for the use of drugs in dentistry Microbial antibiotic resistance Selection of traditional vs. newer antibiotics Minimizing adverse effects & adverse drug interactions Antibiotic prophylaxis Designed primarily for use against MRSA (non-beta-lactam PBP binders, oxadiazoles) Dalbavancin (DALVANCE) Tedezolid (SIVEXTRO) Oritavancin (ORBACTIV) Rifaximin (XIFAXAN, E. coli) ___________________________________Clinical Research Antibiotic Resistance in Primary and Persistent Endodontic Infections Jungermann GB et al. Department of Endodontics, Prosthodontics and Operative Dentistry, Dental School, University of Maryland J. Endod. 2011; 37(10) Methods and Findings: Jungermann et al. Methods Findings Sampled bacteria in 30 bla TEM-1 = primary > primary/15 persistent persistent infections Treatment reduced Characterized isolates most EXCEPT tetM for antibiotic resistance No van A, D or E genes and phenotypic detected expression of resistance Antibiotic Resistance Genes in Anaerobic Bacteria Isolated From Primary Dental Root Canal Infections Rocas I.N., Siqueira J.F. Department of Endodontics, Estacio de Sa University, Rio de Janeiro, Brazil Anaerobe – Volume 18, Number 6, December 2012, pp. 576-80 Methods & Findings, Rocas & Siqueira, 2012 Methods Findings 26 endodontic patients 32% positive for at All had necrosis + AP least one r gene radiographically Most prevalent = Bacteriologic samples blaTEM (17%), tetW taken within 1 mm of (10%), ermC (10%) apices DNA extraction + PCR amplification for resistance genes Detection of Antibiotic Resistance Genes in Samples From Acute and Chronic Endodontic Infections Infections and After Treatment Rocas I.N., Siequeira, J.F. Department of Endodontics, Estacio de Sa University, Rio de Janeiro, Brazil Archives of Oral Biology – Volume 58, Number 9, September 2013, pp. 1123-8 Methods & Findings, Rocas & Siqueira, 2013 Methods Findings 25 abscess aspirates, 26 36% abscess samples & 67% of asymptomatic cases root canal samples positive for at least one All had asymptomatic AP resistance gene Most prevalent in abscesses Also sampled root canals = blaTEM (24%) & ermC after chemomechanical (24%) preparation tetM (42%) & tetW (29% prevailed in asymptomatic DNA extraction + PCR cases amplification for Tx eliminated detectable resistance genes resistance genes ______________________________Clinical_Research Beta-lactamic Resistance Profiles in Porphyromonas, Prevotella and Parvimonas Species Isolated from Acute Endodontic Infections Montagner F, Jacinto RC et al. Journal of Endodontics 2014;3:339-344 Methods & Findings, Montagner et al., 2014 Methods Findings 20 patients with 2 of 29 isolates positive spontaneous pain & for cfxA/cfxA2 gene pulpal necrosis Gene + lactamase Sterile access, paper production in 1 point samples Prevotella strain Pure cultures for 3 Gene only in 1 organisms Parvimoinas strain Assessed penicillin & aminopenicillin 3 strains expressed resistance lactamase w/o gene “Rational” Dental Antibiotics For Orofacial Infections) Narrow spectrum Good activity vs. anaerobic organisms Bactericidal agents preferred Endodontics Colleagues for Excellence Use and Abuse of Antibiotics AMERICAN ASSOCIATION OF ENDODONTISTS AAE Indications for Antibiotic Therapy (2006) Fever > 100 degrees F Malaise Lymphadenopathy Trismus Increased swelling Cellulitis Osteomyelitis Persistent infection Conditions NOT requiring adjunctive antibiotics… Pain without signs and symptoms of infection (symptomatic reversible pulpitis, acute periradicular periodontitis) Chronic apical abscess AAE Antibiotic Recommendations (Adult) Penicillin VK, 1,000 mg, then 500 mg q. 4-6 h. for 5 - 7 days Amoxicillin, 1,000 mg, then 500 mg q. 8 h. for 5 – 7 days (also with clavulanate) Clindamycin, 600 mg, then 300 mg q. 6 h. for 5 - 7 days Metronidazole, 1,000 mg, then 500 mg q. 6 h. for 5 - 7 days (add to Pen VK or clindamycin) AAE Antibiotic Recommendations (2006) Clarithromycin, 500 mg, then 250 mg q. 12 h. for 5 – 7 days Azithromycin, 500 mg, then 250 mg once daily for 5 – 7 days Comparative Pharmacokinetics Absorption/Distribution Plasma Half-Life Penicillin V: 1 hr Penicillin V: moderate, inhibited by food, 80% protein-bound Amoxicillin: well absorbed, 20% Amoxicillin: 1.3 hr protein-bound Clindamcyin: well-absorbed, 92- 94% protein-bound Clindamycin: 2.4-3 hr Metronidazole: well-absorbed, <20% protein-bound Metronidazole: 8 hr Clarithromycin: well-absorbed, 65-75% protein bound Clarithromycin: 3-7 hr Azithromycin: well-absorbed, 7- 50% protein-bound Azithromycin: 68 hrs Beta lactamase inhibitor + antibiotic combinations Amoxicillin/clavulanate (AUGMENTIN) Ampicillin/sulbactam (UNASYN) Ticarcillin/clavulanate (TIMENTIN) Piperacillin/tazobactam (ZOSYN) Microbiological Analysis of a Prospective, Randomized, Double-Blind Trial Comparing Moxifloxacin and Clindamyin in the Treatment of Odontogenic Infiltrates and Abscesses SOBOTTKA I ET AL. ANTIMICROB. AGENTS CHEMOTHER. 2012;56(5):2565-9 Sobottka et al. Methods/Outcomes Outcomes (overall Methods susceptibility absecess/infilt.) Subjects randomized to MXF: 98%/98% moxifloxacin (MXF) or AMC: 97%/96% clindamycin (CLI) LVX: 83%/86% Isolates obtained from infiltrates & abscesses PEN: 66%/67% All bacteria identified CLI: 59%/60% Antibiotic susceptibilities DOX: 51%/49% determined to MXF, CLI, 8/71 subjects failed to LVX, PEN, AMC & DOX recover What are the Antibiotics of Choice for Odontogenic Infections, and How Long Should the Treatment Course Last? FLYNN TR ORAL AND MAXILLOFAC. SURG. N. AM. 2011;23:519-36 (SYSTEMATIC REVIEW) Outcomes from Flynn 2011 Studies Included Outcomes Clinical (8), laboratory Difference in patient cure (4) rate in only 1 study A penicillin used in all No one antibiotic studies superior Aerobes & anaerobes Antibiotics of choice lab-tested with a pen, a (outpatients) = amoxicillin clindamycin, pen + lactamase azithromycin, inhibitor, clindamycin, metronidazole, & a fluroquinolone moxifloxacin The Use of Systemic Antibiotics in the Treatment of Refractory Periodontitis Santos R. et al. JADA 2016;147(7):577-585 Methods Findings Systematic review No Meta analysis 6 included RCTs done Assessments based 1 study only had on reductions in parallel design probing depth or loss High risk of bias of attachment across all studies SRP alone vs. SRP + (lack of controls) antibiotics “Quality of evidence does not allow the conclusion that adjunct 5 antibiotics (incl. systemic antibiotics are of metronidazole & additional benefit to SRP alone.” tetracycline Santos et al., JADA 2016 Dentists, Antibiotics an Clostridium difficile- associated Disease BEACHER N, SWEENEY MP, BAGG J BRITISH DENTAL JOURNAL 2015;219(6):275-279 Spectrum of Clostridium difficile-associated Disease (CDAD) (modified from Beacher N et al. Brit. Dent. J. 2015;219(6):275-9 Severity Defined by Management Mild 3 loose stools/day Oral metronidazole (no change WCC) (500 mg tid/10-14 d) Moderate 5-7 loose stools/day + Oral metronidazole elevated WCC (500 mg tid/10-14 d) Severe Variable loose stools, Oral vancomycin 125 mg WCC>15x109/L or qid/10-14 d 50% ↑Serum [Creatinine] or temp > 101◦ or abdominal/radiologic signs Life-Threatening Above + hypotension, ileus/toxic megacolon or CT evidence Clostridium difficile-associated Disease Risk Factors Warnings Antibiotic exposure Risk factors NOT necessary to produce Severe systemic disease CDAD Older age Fluoroquinolones & Immune suppresion cephalosporins increasingly implicated Onset typically within 7 weeks of beginning of antibiotic therapy Antibiotic Prophylaxis ________________Retrospective Secular Trend Study___ Incidence of Infective Endocarditis in England, 2000-2013 Lodi G, Figini L, Sardella A et al. Dayer MJ, Jones S, Prendergast B, Baddour LM, Lockhart PB, Thornhill MH Volume 385, March 28, 2015 “Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly…” “This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk.” Areas of Controversy Routine removal of third molars (uninfected) Patients with breast, chin and other non- cardiovascular plastic surgical implants Routine periodontal surgery Diabetic patients Patients with HIV-AIDS Evidence Insufficient to Recommend Routine Antibiotics for Joint Replacement Patients Who Undergo Dental Procedures (AAOS/ADA, 2012, http://www.aaos.org/guidelines) • Practitioners
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