NMT150 Spotlight on Antibiotics, Wk1 (1) PDF

ANTIBIOTIC PHARMACOLOGY Dr. Adam Gratton NMT150 MSc ND January 9, 2023 LECTURE COMPETENCIES 1. Describe the basic principles of antibiotic stewardship 2. Describe the mechanisms bacteria may have that lead to antibiotic resistance 3. Differentiate the main classes of antibiotic...

ANTIBIOTIC PHARMACOLOGY Dr. Adam Gratton NMT150 MSc ND January 9, 2023 LECTURE COMPETENCIES 1. Describe the basic principles of antibiotic stewardship 2. Describe the mechanisms bacteria may have that lead to antibiotic resistance 3. Differentiate the main classes of antibiotics discussed based on the mechanism of action 4. Describe the adverse effects of the drugs presented 5. Predict which drugs would be contraindicated in patients with penicillin allergy 6. Describe patient factors that would warrant an antibiotic prescription for Group A Strep pharyngitis INTRODUCTION Antibiotic resistance is responsible for an estimated 2 million infections and 23,000 deaths per year in the United States Approximately half of outpatient antibiotic prescribing in humans might be inappropriate At least 30% of outpatient antibiotic prescriptions in the United States are unnecessary 2019 AR THREATS REPORT https://www.cdc.gov/drugresistance/biggest-threats.html 2019 AR THREATS REPORT https://www.cdc.gov/drugresistance/biggest-threats.html 2019 AR THREATS REPORT https://www.cdc.gov/drugresistance/biggest-threats.html MECHANISMS OF ANTIBIOTIC RESISTANCE Modifications of the Antibiotic Molecule Decreased Antibiotic Penetration and Efflux Changes in Target Sites Resistance Due to Global Cell Adaptations ANTIBIOTIC STEWARDSHIP to measure antibiotic prescribing to improve antibiotic prescribing by clinicians and use by patients so that antibiotics are only prescribed and used when needed to minimize misdiagnoses or delayed diagnoses leading to the underuse of antibiotics to ensure that the right drug, dose, and duration are selected when an antibiotic is needed DEFINITIONS Bactericidal – kills sensitive organisms so that number of viable organisms falls rapidly after exposure Bacteriostatic – inhibits growth of bacteria but does not kill them ANTIMICROBIAL SPECTRUM Narrow-spectrum – agent is active against a single species or limited group of pathogens Broad-spectrum – agent is active against a wide range of pathogens Extended-spectrum – agent falls in between (intermediate) MECHANISM OF ACTION All beta-lactam antibiotics interfere with bacterial cell wall synthesis Inhibition of bacterial transpeptidase (also called penicillin-binding protein) which inhibits peptidoglycan cross-linking making cell wall synthesis impossible Generally confers bactericidal activity PENICILLIN V Narrow-spectrum antibiotic Typically administered in an oral suspension Adverse effects include GI upset, nausea, vomiting, diarrhea, and rash. In rare instances can cause severe hypersensitivity reactions. Considered the drug of choice for Group A streptococcal pharyngitis PENICILLIN V Dosed by weight for adults and children People over 27 kg: 300 mg TID or 600 mg BID PO for 10 days People 27 kg or under: 40 mg/kg/day divided BID or TID for 10 days with a maximum daily dose of 750 mg. AMOXICILLIN An extended-spectrum penicillin Essentially a modified version of penicillin that results in greater activity against additional gram-negative bacteria Generally well tolerated but can cause the same adverse effects as penicillin V Typically used more often as it is more palatable than penicillin V AMOXICILLIN Dosed by body weight for all patients 50 mg/kg once daily or divided BID PO for 10 days with a maximum daily dose of 1000 mg. CEPHALOSPORINS A very large group of antibiotics The different generations are used to define their antimicrobial spectrum Have greater structural diversity which is more resistant to beta-lactamases and increases their range of antimicrobial activity CEFADROXIL A first-generation cephalosporin May be used if treatment failure with penicillin or in individuals with nonimmediate hypersensitivity to penicillins Adverse effects include GI upset, nausea, vomiting, diarrhea, hypersensitivity (some cross-reactivity with penicillins) CEFADROXIL Adults: 1 g/day PO as a single dose or divided BID for 10 days CEPHALEXIN A first-generation cephalosporin Same adverse effect profile as cefadroxil and may also be used if treatment failure with penicillins or in individuals with nonimmediate hypersensitivity to penicillins Also available as a suspension CEPHALEXIN Adults: 500 mg BID PO for 10 days Children: 40 mg/kg/day divided BID PO for 10 days with a maximum daily dose of 1000 mg. PROTEIN SYNTHESIS INHIBITORS Prokaryotic ribosomes are composed of a 30S and 50S subunit Eukaryotic mRNA translation proteins are far more complex than those in prokaryotic cells MACROLIDES Inhibit peptidyl transferase which functions to link amino acids together in the growing peptide chain Also interferes with translocation (movement of the nucleotide from the A position to the P position to allow for reading the next spot on the mRNA) Confers bacteriostatic activity AZITHROMYCIN An alternative for patients who are allergic to penicillin Less likely than other macrolide antibiotics to interact with other drugs Adverse effects include GI upset, nausea, vomiting, diarrhea, rash, QTc interval prolongation. AZITHROMYCIN Adults: 500 mg PO for one day, then 250 mg PO daily for 4 days. Children: 12 mg/kg PO for 5 days with a maximum daily dose of 500 mg. CLARITHROMYCIN An alternative for patients who are allergic to penicillin Same adverse effect profile as azithromycin Also available as a suspension Increases the levels of some common drugs like atorvastatin, lovastatin, simvastatin, and prednisone CLARITHROMYCIN Adults: 250 mg BID PO for 10 days Children: 15 mg/kg/day divided BID PO for 10 days with a maximum daily dose of 500 mg. LINCOSAMIDES Interfere with translocation like macrolides but do not inhibit peptidyl transferase Approximately 4 times more likely to cause Clostridium difficile infections compared to other antibiotics Generally bacteriostatic but can be bactericidal at high doses CLINDAMYCIN An alternative for patients who are allergic to penicillin May be used for treatment in symptomatic patients with multiple, recurrent episodes of pharyngitis Commonly causes diarrhea as an adverse effect. Increased risk of C. difficile colitis CLINDAMYCIN Adults: 300 mg TID PO for 10 days Children: 21 mg/kg/day divided TID PO for 10 days with a maximum daily dose of 900 mg GROUP A STREPTOCOCCUS PHARYNGITIS Antibiotic therapy is most beneficial for people who are at high risk of developing acute rheumatic fever and who have confirmed streptococcal infection Watchful waiting may be appropriate in patients at low risk for acute rheumatic fever as antibiotics have a minimal impact on the natural course of group A streptococcal pharyngitis GROUP A STREPTOCOCCUS PHARYNGITIS According to evidence, antibiotics reduce duration of symptoms by approximately 16 hours Given the small benefit antibiotic therapy could be withheld for 48 – 72 hours in adult patients with more severe symptoms Antibiotic therapy is not generally recommended for mild cases SAMPLE QUESTION Which of the following antibiotics is suitable for use in a patient with an immediate hypersensitivity reaction to penicillin? A. Amoxicillin B. Cephalexin C. Cefadroxil D. Azithromycin