General Infectious Disease Concepts/Resources Learning Objectives: 1. Distinguish between foundational infectious disease concepts including gram positive and negative bacteria, bacteriostatic and bactericidal antibiotics, and peak and trough concentrations 2. List common gram positive and gram negative bacteria 3. List common bacteriostatic and bactericidal antibiotics 4. Identify infectious disease resources and educational materials available to pharmacy students Helpful Resources (flash cards on access pharmacy, guidelines, Dipiro cases in workbook, etc) Access pharmacy cases virtual cases CAP and others Access pharmacy cases pharmacotherapy Casebook and Care plans pick any infectious disease and walk through a case, answer questions, start a treatment plan Access pharmacy study tools Flashcards Access pharmacy DiPiro Casebook for additional cases (see examples in other ID materials provided) TLDR pharmacy antibiotics sheet Clinical Key for bacteria in particular Sanford Guide to Antimicrobial Therapy May be beneficial to create your own pocket cards for dosing/renal dosing of commonly used antibiotics for your own learning and quick reference Instructions on how to access the Dipiro handbook: Access pharmacy pharmacotherapy: a pathophysiologic approach, 10e select the chapter of interest look for this message at the top of the chapter (ex from chapter on CNS infections): Click on the link to go to the Dipiro handbook Provides the most relevant information from Dipiro book in a condensed fashion Gram positive bacteria: Thick peptidoglycan layer that contains teichoic and lipoteichoic acids Turn purple; stain gets trapped in a thick, cross-linked, mesh-like structure (the peptidoglycan layer) which surrounds the cell Streptococcus Staphylococcus Enterococcus Listeria Clostridium Lactobacillus
Gram negative bacteria: Thin peptidoglycan layer and an outer membrane that contains lipopolysaccharide, phospholipids, and proteins Do not retain the crystal violet stain Cells must be counterstained with safranin and turned red Neisseria Acinetobacter Haemophilus Bacteroides Fusobacterium Pseudomonas Enterobacteriaceae Atypical Bacteria Neither gram-positive nor gram-negative by classification Most often will come up in cases of respiratory infections Chlamydophila Coxiella Legionella Mycoplasma Rickettsiaceae Fungi: Aspergillus Blastomyces Candida Coccidiodes Cryptococcus Histoplasma Pneumocystis (think Pneumocystis pneumonia (PCP)) Sporothrix Ringworm (can be caused by many species including Trichophyton, Microsporum, and Epidermophyton) Anaerobic Organisms: Gram-negative: Bacteroides (most common): Intra-abdominal infections Fusobacterium: Abscesses, wound infections, pulmonary and intracranial infections
Porphyromonas: Aspiration pneumonia and periodontitis Prevotella: Intra-abdominal and soft-tissue infections Gram-positive: Actinomyces: Head, neck, abdominal, and pelvic infections and aspiration pneumonia Clostridia: Intra-abdominal infections, soft-tissue infections, food poisoning, botulism, tetanus, and C. difficile-induced diarrhea Peptostreptococcus: Oral, respiratory, and intra-abdominal infections Propionibacterium: Foreign body infections (i.e. in a cerebrospinal fluid shunt, prosthetic joint, or cardiac device) Lactobacillus Minimum Inhibitory Concentration (MIC): The concentration that inhibits visible bacterial growth at 24 hours of growth in specific media, at a specific temperature, and at a specific carbon dioxide concentration Minimum bactericidal concentration (MBC): The concentration of a drug that results in a 1,000-fold reduction in bacterial density at 24 hours of growth in the same specific conditions Bactericidal antibiotic: Kills and decreases number of viable bacteria Classes: Penicillins Cephalosporins Fluoroquinolones (ciprofloxacin) Glycopeptides (vancomycin) Monobactams Carbapenems Linezolid (for strep) Daptomycin Nitroimidazoles Rifampin Bacteriostatic antibiotic: Stops growth and replication of bacteria, which lets the host eliminate the pathogen Classes: Macrolides Tetracyclines Trimethoprim Sulfonamides Chloramphenicol Linezolid
C. diff-causing antibiotics: High Risk: Clindamycin highest risk! Fluoroquinolones Aztreonam and carbapenems Cephalosporins Augmentin Moderate Risk: Macrolides Sulfonamides/trimethoprim Penicillins Troughs/peaks/dosing **May vary according to individual institution** Vancomycin Initial IV dosing in all patients should be based on actual body weight (ABW), and subsequent dosing should be adjusted based on serum trough concentrations and renal function Calculations may be indicated for patients with altered pharmacokinetics (morbid obesity, burns, critical illness, unstable renal function, pregnancy, cystic fibrosis, etc.) IV dose for adults: 15 to 20 mg/kg/dose (rounded to the nearest 250 mg; usual max: 2 g/dose initially) every 8 to 12 hours (typically 15 mg/kg/dose q 12 hours for initial dose in normal renal function, nonobese patients) Every 8 hrs usually reserved for patients <40 yo with good/stable renal function Loading dose (used in complicated infections in seriously ill patients to rapidly achieve target concentrations): 25 to 30 mg/kg (typical max initial dose 2000 mg) Typical goal trough concentration ranges are 10-15 mcg/ml or 15-20 mcg/ml depending on the infection (may be lower for certain SSTIs) Hemodynamically stable patients: draw trough concentrations at least once-weekly; hemodynamically unstable patients: draw trough concentrations more frequently If renal function is poor or unstable, draw trough concentrations more frequently Draw trough concentration just before the administration of a dose at steady-state conditions (generally occurs 30 minutes before the fourth dose)
Gentamicin Conventional adult dosing: IM, IV: 3 to 5 mg/kg/day in divided doses every 8 hours Extended interval dosing: IV: 5 to 7 mg/kg/day once every 24 hours (adjusted based on serum concentrations) Can extend interval further for renal dysfunction Extended interval has shown similar efficacy and reduces costs, improves ease of administration and concentration monitoring, and possibly decreases nephrotoxicity (based on animal models) Hartford nomogram helps determine the initial dosing interval based on serum concentrations after initial drug administration For aminoglycoside weight-based dosing: If actual BW < IBW, use actual BW If actual BW > IBW by 120-130% (depends on institution), use adjusted BW Otherwise use IBW Draw peak 30 minutes after 30-minute infusion has been completed or 1 hour after IV injection Draw trough immediately before next dose is due Levels are typically obtained before and after the third dose in conventional dosing Peak therapeutic levels Sepsis, pneumonia, other serious infections: 6 to 8 mcg/ml Life-threatening infections: 8 to 10 mcg/ml UTIs including pyelonephritis: 4 to 6 mcg/ml Synergy against gram-positive organisms: 3 to 4 mcg/ml Trough therapeutic levels Serious infections: 0.5 to 1 mcg/ml Life-threatening infections: 1 to 2 mcg/ml Synergy against gram-positive organisms: <1 mcg/ml
Antibiograms An antibiogram is an overall profile of antimicrobial susceptibility testing results of a specific microorganism to a battery of antimicrobial drugs Antibiograms help guide the clinician and pharmacist in selecting the best empiric antimicrobial treatment in the event of pending microbiology culture and susceptibility results Useful in detecting resistance patterns of microorganisms in the region The higher the percentage displayed on the table, the better the coverage of that drug of the organism shows percentage that is susceptible to antimicrobial agent Time-Dependent Antibiotics The inhibitory effect can be effective because their concentration exceeds the MIC for the microorganism. Hence, these antibiotics are referred to as time-dependent antibiotics. For time-dependent drugs, the pharmacodynamic parameter can be simplified to the time that serum concentrations remain above the MIC during the dosing interval Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) Clindamycin Macrolides (erythromycin, clarithromycin) Oxazolidinones (linezolid) Concentration-Dependent Antibiotics Drugs that have high concentrations at the binding site which eradicates the microorganism These drugs are considered to have a different kind of bacterial killing, named concentration-dependent killing. For concentration-dependent agents, the pharmacodynamic parameter can be simplified as a peak/mic ratio Aminoglycosides and quinolones Mechanisms of Resistance 1. Decreased penetration: prevents antibiotic from penetrating bacterial cell, decreasing the intracellular concentration of the antibiotic a. Cell wall changes b. Biofilm production c. Porin channel changes or loss 2. Enzymatic modification: enzyme produced by the bacteria destroys the antibiotic before it has a chance to reach its site of activity or even enter the cell a. Beta-lactamase production b. Aminoglycoside-modifying enzymes c. Methylation 3. Target site changes: a change occurs that leads to an elimination or modification of the antibiotic s site of activity such that it cannot work a. Ribosomal modifications
4. Active efflux: efflux pumps in the bacteria pump the antibiotic out of the cell, decreasing intracellular concentrations a. Tetracycline efflux b. Fluoroquinolone efflux Further Resources: Link to ID Stewardship: https://www.idstewardship.com/basics-bactericidal-versus-bacteriostatic-antibiotics/ Link to Clinical Key: https://www.clinicalkey.com/#!/content/book/3-s2.0- B9780323299565000124?scrollTo=%23hl0000494 Link to UpToDate for Vancomycin: https://www.uptodate.com/contents/vancomycin-druginformation?search=vancomycin%20dosing&source=search_result&selectedtitle=1~148&usag e_type=default&display_rank=1# Link to UpToDate for Gentamicin: https://www.uptodate.com/contents/gentamicin-systemic-druginformation?search=gentamicin&source=search_result&selectedtitle=1~142&usage_type=defa ult&display_rank=1#f8107222 NEW DRUG references: Zerbaxa, Avycaz, and Vabomere comparison: https://www.idstewardship.com/comparison-avycaz-vabomere-zerbaxa/ http://www.pharmacytimes.com/contributor/monica-v-golik-mahoney-pharmd-bcps-aqid/2015/03/superheroes-of-gram-negative-bacteria Isavuconazole (Cresemba): https://academic.oup.com/cid/article/61/10/1558/301996