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Pharm Antimicrobials

Colonization presence of an organism on or within the tissue, NOT resulting in an immune response or destruction of tissue (ex MRSA in nose)
Infection presence of an organism on or within the tissue resulting in an immune response and/or destruction of the tissue
synergy any combination of antimicrobials that when used together, increases the killing of an organism beyond that of either used alone (1+1=3)
antagonism : any combination of antimicrobials that decreases killing of an organism beyond that obtained from either used alone (1+1=0)
potentiation a drug which has no effect enhances the effect of a second drug (0+1=2)
What does a bacteriostatic antibiotic require for effective killing of organisms? ability to inhibit growth and replication of bacteria. Body’s immune system required to immobilize and kill the organism.
Selective Toxicity Ability of drug to injure a target cell or target organism without injuring other cells or organisms that are in intimate contact with the target (disrupt cell wall, inhibit enzyme unique to bacteria, disrupt bacterial protein synthesis)
List two methods by which antimicrobial agents may be classified. By Organism and by mechanism of action
Narrow spectrum active only against few bugs
Broad Spectrum active against a variety of bugs
List four methods by which pathogens may be classified - Gram Stain - Shape (Cocci/bacilli) - Need for Oxygen (aerobic/anaerobic) - Site of residence in host cells (intra/extracellular) -
Gram Positive retain initial hematoxylin blue/purple- cell wall relatively simple - thick layers of peptidoglycan on top of cytoplasmic membrane, favors antibiotic entry, especially charged compounds
Gram positive cocci staph, strep pneumonia, strep pyogenes
gram positive rods bacillus, listeria, clostridium (anaerobic)
Gram Negative resist hematoxylin; take on red-pink eosin counterstain): cell wall more complex: - periplasmic space (enzymes) and outer membrane with lipopolysaccharides (endotoxins) and porin channels on top of cytoplasmic membrane - challenge to drug entry
gram negative cocci H. influenza, neisseria, h. pylori
gram negative rods escherichia, shigella, salmonella, klebsielle, enterobacter, proteus, psuedomonas
Empiric Therapy need culture and sensitivity results but may treat before test results are available. Drug selection must be based on clinical evaluation and knowledge of which microbes are likely to cause an infection at a particular site
Discuss three factors to consider when making choices about an agent for empiric therapy. 1) Identify Infecting Organism 2) Determine Drug Susceptibility 3) Determine Host factors, such as site of infection and status of defenses that may modify drug choice, route, or dosage
List three drugs that provide particularly good coverage for anaerobes - 2nd generation cephalosporins - carbapenems - tetracyclines - flagyl**
What drug classes make up the β-lactam family? - Penicillins - Cephalosporins - Carbapenems - Monobactams - B-Lactamases
List three ways in which bacteria acquire resistance to β-lactam antimicrobials 1) Inactivation of antibiotic by B- lactamase (Penicillinases) (most common) 2) Modification of target PBP’s (so penicillins/b lactams cant bind) 3) Presence of Efflux pump 4) Impaired penetration of drug to target PBP’s
Describe why β-lactam antibiotics are ineffective if the microorganism has β-lactamase enzymes. a. Beta lactamases are enzymes that cleave the beta-lactam ring, rendering PCN inactive
Narrow Spectrum Penicillins: penicillin G, Penicillin V, antistaphylococcal penicillins
Broad Spectrum Penicillins ampicillin, amoxicillin
extended spectrum penicillins piperacillin, ticarcillin, aziocillin (antipsuedomonal)
What is the main adverse effect seen with penicillins? - most serious adverse reactions due to hypersensitivity o rashes most common reaction o ampicillin rash- in 50-100% patients with EBV - Anaphylaxis: 1/10,000 patients
Which generation cephalosporin is most effective against gram positive? 1st generation
Which generation is most effective against gram negative? 5th generation
Cephalosporins should be avoided for which subgroup of patients who describe themselves as penicillin allergic? patients with severe anaphylaxis to penicillins
Are penicillins or cephalosporins more stable to β-lactamases? cephalosporins
Name the classes that inhibit cell wall synthesis. BETA LACTAMS (Penicillin, Cephalosporins, Cabapenems, monobactams), GLYCOPEPTIDES (vancomycin)
1 generation cephalosporins - spectrum best activity against gram positive organisms, no ability to reach CSF.
2nd generation cephalosporins- spectrum enhanced activity against gram negative bacteria, does not reach CSF. Less active against gram positive. Used against H influenzae
Cephamycins not true 2d generation cephalosporins, activity against anaerobes -- cefoxitin, cefotetan
3rd generation cephalosporins- spectrum less activity against gram positives, but greater activity against gram negatives, can cross BBB (First line for meningitis)
4th generation cephalosporins- spectrum extended spectrum, good gram positive an dnegative
5th generation cephalosporins- spectrum multidrug resistant staph aureus, VRSA, strep pneumonia, respiratory gram negatives, COMMUNITY ACQUIRED BACTERIAL PNEUMONIA and acute kin infections
Carbapenems broadest spectrum of all beta lactams
Monobactams gram negative rods
Beta lactamase inhibitors Augmentin, Timentin, Unasyn, Zosyn
Glycopeptides: drug Vancomycin
Vancomycin: MOA cell wall synthesis inhibitor
Vancomycin- spectrum gram positive bacteria, MRSA
Vancomycin: uses sepsis, endocarditis caused by MRSA, meningitis with highly penicillin resistant pneumococcus
Red Man's Syndrome AE of vancomycin, infusion related flushing (slow infusion or increase dosin interval)
- What newer drug(s) is/are available to treat vancomycin resistant enterococci (VRE)? Linezolid (zyvox)
Protein synthesis Inhibitors (bacteriostatic) Tetracyclines, macrolides, "other.misc."
Protein synthesis inhibitors (bactericidal) aminoglycosides
Tetracylcines- spectrum bacteriostatic protein synthesis inhibitors, broad spectrum
Tetracyclines- use mycoplasma pneumonia, chlamydiae, rickettsiae.
Tetracyclines- adverse effects tooth discoloration/deformation of bones, photosensitivity
Macrolides- drugs Erythromycin, Azithromycin
Macrolides- spectrum bacteriostatic protein synthesis inhibitors, gram positives
Macrolides- uses diphtheria, chlamydia, CAP
Adverse effects of erythromycin GI, acute hepatitis
drug interacitons of erythromycin CYP inhibitors, can prolong QT interval, increase risk for sudden cardiac death
Other/Newer Bacteriostatic Protein synthesis inhibitors Clindamycin, Streptogramins, Linezolid
Clindamycin- clinical use head and neck infections
Streptogramins- clinical use gram positive, drug resistant staph and strep, VRE
Linezolid- use VRE
Aminoglycosides bactericidal protein synthesis inhibitors, block protein synthesis at 3 points in pathway
Are aminoglycosides well absorbed orally? polar- NO
Aminoglycosides- drugs gentamycin, neomycin, tobramycin, kanamycin, amikacin
Aminoglycosides-spectrum gram negative enteric bacteria (aerobic)
Aminoglycosides-clinical use bacteremia and sepsis
Aminoglycosides-adverse effects ototoxicity and nephrotoxicty
Antimetabolites- MOA inhibit folic acid synthesis (folic acid needed for DNA synthesis)
Antimetabolites- drugs Bactrim and Septra
Antimetabolites- Bactrim® and Septra® contain what two antimicrobial agents? What advantages result from giving these two agents in combination? Trimethoprim- Sulfamethoxazole, synergistic
Antimetabolites- adverse effects photosensitivity, Stevens johnson Syndrome
What is Stevens Johnson Syndrome? serious and potentially fatal skin and mucous membrane eruption
DNA Gyrase Inhibitors Fluoroquinolones - bactericidal
Fluoroquinolones - drugs ciprofloxacin, levofloxacin
Ciprofloxacin- spectrum more active against gram negatives
Levofloxacin- spectrum superior activity against gram positives
Describe two key pharmacokinetic advantages possessed by Fluoroquinolones high oral availability and wide distribution to tissues
Fluoroquinolones-uses UTI!!!, resp. infections
Fluoroquinolones- Adverse effects may prolong QT, tendonitis, arthritis, arthropathy
Metronidazole antiprotozoal with potent activity against anaerobes- used in GI tract infections
Amphotericin B broad spectrum antifungal, used for life threatening mycotic infections because of toxicity
azole antifungals less toxic than amphotericin B, topical and systemic use
4 drugs used for TB tx Isoniazid, Rifampin, Pyrazinamine, Ethambutol
Isoniazid- MOA inhibits synthesis of myco bacterium wall.
Isoniazid- AE peripheral neuropathy (tx with Pyridoxine)
Rifampin - MOA inhibits TB RNA synthesis/protein synthesis
Rifampin- AE hepatotoxicity, red-orange body fluids
4 methods of antimicrobial resistance produce drug metabolizing enzymes (penicillinase), cease uptake of drugs, change in receptors, synthesize compounds that antagonize drug actions
How do microbes gain resistance? Genetic Alterations (spontaneous mutation), DNA transfer (conjugation from other microbes), altered expression of proteins in drug resistant organisms (modified targets)
Suprainfection (superinfection) new infection that appears during course of treatment for a primary infection. - develops when abx eliminate the inhibitory influence of normal flora, allowing a second infectious agent to flourish
Which antimicrobials are most often associated with superinfections? braod spectrum!, 3rd generation cephalosporins, clindamycin
What is first line to treat C. Diff? Metronidazole (flagyl)
Alternative to Flagyl for C. Diff tx vancomycin
List two antimicrobial classes that should not be given during pregnancy - fluoroquinolones - tetracyclines
Safe in pregnancy - Penicillins - Cephalosporins (category B) - Clarithromycin (category C) - Erythromycin (not estolate) - Azithromycin
List the 3 most common pathogens responsible for community acquired pneumonia (CAP), o Strep pneumoniae (gm +) o Mycoplasma pneumoniae (atypical) o H. influenzae (gm -)
What is the first- choice drug for empiric treatment of pneumonia in a hospitalized patient? Which class can be used for single agent therapy for this indication? Macrolide + Beta Lactam. Respiratory fluoroquinolone
List the two most common pathogens responsible for pharyngitis streptococcus pyogenes (group A beta hemolytic), viral
Tx of pharyngitis Penicillin, amoxicillin
First line therapy for Otitis media Amoxicillin or augmentin
Alternative therapy for Otitis media 2nd and 3rd generation cephalosporins
List the two most common pathogens responsible for Urinary tract infections E coli and pseudomonas
What is the first choice for complicated UTI treatment in women? a. How long should it be given (duration)? o 7-21 days Ciprofloxacin
What is the first choice therapy for uncomplicated urinary tract infection (UTI) in women? a. How long should it be given (duration)? o 3 days (lower rate of recurrent infection than single dose) o trimethoprim-sulfamethoxazole
First Choice drug for impetigo mupirocin, alternative azithromycin, clarithromycin, 2nd generation cephalosporins
MRSA- tx septra, bactrim, clindamycin, tatracylcines, rifampin, vancomycin, linezolid, daptomycin
First Line for E. Coli cephalosporins
First Line for Pseudomonas aeruginosa • Ciprofloxacin
First Line for Staphylococcus aureus Penicillinase Producing: penicillinase resistant penicillin Methicillin resistant: vancomycin with or without gentamycin/rifampin
first line for Haemophilus influenzae Meningitis: cephalosporin (3rd generation). Upper RTI/bronchitis: septra/bactrim
Created by: alexadianna
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