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Bugs & Drugs I
antibiotics
32
Other
Undergraduate 2
04/03/2007

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Term
Gram Positive Envelope
Definition
2 Layers
-Plasma membrane
-Peptidoglycan layer: thick; 60-90%
-Lipoteicholic acid & telchic acid
Term
Gram Negative Envelope
Definition
3 Layers
-Plasma membrane
-Peptidoglycan layer: thin; 1-20% (inner-periplasmic space)
-Outer membrane
Term
Inhibitors of Cell Wall Synthesis (bactericidal)
Definition
Penicillins, Cephalosporins, Monobactam, Carbapenems
Term
Interfere w/ Bacterial Cell Membranes
Definition
Daptomycin
Term
Bactericidal inhibitors of protein synthesis
Definition
Aminoglycosides, Quinupristin/dalfopristin
Term
Bacteriostatic inhibitors of protein synthesis
Definition
Clindamycin, Linezolid, Macrolides, Tetracyclines, Tigecycline
Term
Mechanisms of resistance
Definition
-Enzyme which degrades drug (beta lactamases-Penicllins)
-Change target proteins
-Reduce drug uptake (i.e. efflux pumps)
-Synthesis of compounds to antagonize drug action (Sulfonamides)
Term
Mechanisms by which resistance is acquired
Definition
Spontaneous mutation: Generally confers resistance to 1 org.

Conjugation: Most w/ Gram- bac, frequently results in multiple drug resistance; not org specific.
Term
Causes of antibiotic resistance
Definition
-Over prescribing, inappropriate drug used, too little of a drug or probiotics in animal feed
Term
Superinfection
Definition
New infection that occurs during course of treatment for a primary infection; more common w/ broad spectrum drugs
Term
Drug Selection
Definition
-Match the drug w/ the bug; do a culture to identify G+/-.
-Drug susceptibilites: minimum inhibitory conc. (sensitive, intermediate, resistant)
-Host factors: Immune system, site of infection (antibiotic must be present at 4-8X the MIC to be effective)
-Age, pregnancy & lactation,allergies, AE's, genetic factors (G6PD deficiency)
Term
Dose and Duration
Definition
Duration dept on host defense, site of infection, identity of infecting org.
- Dose should provide conc > or = to MIC
Term
Drug Combinations
Definition
Synergism: beta-lactam+aminoglycoside + sulfonamide+trimethoprim

Additive: aminoglycoside+fluroquinolone

Antagonsim: bacteriostatic+bactericidal
Term
Indications for Combination Therapy
Definition
-Initial therapy of severe infection (etiology unknown)
-Mixed infections
-Prevention of resistance (TB, 4drugs)
-Decreased toxicity (syn effect)
-Enhanced antibacterial action
Term
Disadvantages of Combination Therapy
Definition
-Increased risk of toxic/allergic reaction
-Possible antagonism
-Increased risk of superinfection
-Selection of drug-resistant org's
-Increased cost
Term
Misuse of antimicrobial drugs
Definition
-Attempted treatment of untreatable infection (cold/virus)
-Treatment of fever of unknown origin
-Improper dosage
-Tx in the absence of aqeduate bacteriologic info
-Omission of surgical drainage (abcess)
Term
Penicillins (PCNs): IV PO
Cell Wall Active
Definition
-MOA: binds to penicillin-binding proteins (PBPs) leading to bactericidal inhibition of transpeptidases.
-Resistance: beta-lac, altered PBPs
-Interactions: probenecid, bacteriostatics
-A.E: Anaphylaxis, rash/hives, seizures w/high dose, GI intolerance, blood dyscrasias, interstitial nephritis, elevated liver enzymes, hypo/hyperkalemia
Term
Penicillin G&V (N)
Definition
Spectrum: Gram+, anaerobes, spirochetes (Treponema pallidum)
-Pen V: oral
-Pen G: IM/IV
DOC for strep throat (s. pyogenes), syphillis, dental work
Term
Antistaphylococcal PCNs
(Penicllinase-resistant PCNs) (N)
Definition
Spec: staph & strep
DOC for staphylococcal infections
(Nafcillin,Dicloxacillin)
Term
Aminopenicillins (B)
Definition
-Same as PCNs w/ some Gram- coverage
-Inactivated by betalactamases
(Ampicillin, amoxicillin)
-UTI: proteus, e. coli
Term
Antipseudomonal PCNs (extended-spectrum)
(B)
Definition
Spectrum: same as aminopenicllins + p. aeruginosa & enterobacteriacea
-Inactivated by beta-lac.
-DOC for pseudomonal infections.
(Piperacillin, Ticarcillin)
Term
PCNs + beta-lactamase inhibitor (B)
Definition
-When you need to use a specific drug.
-Spectrum: Gram+/-, anaerobes
-Amoxicillin/clavulanate (PO)
-Ampicillin/sulbactam, pipercillin/tazobactam, ticarcillin/clavulanate (IV)
Term
Cephalosporins
Definition
MOA: same as PCNs, bactericidal
Resistance: enzymes(1-3 gen)
Interactions: alcohol, warfarin (nMTT side chain), probenacid
-A.E: allergic reactions, bleeding, biliary sludging.
Term
Cephalosporins: Generations
Definition
1st: (N) Gram +; indicated for strep/staph infections, surgical prophylaxis, UTI

2nd:(B) Gram+, some g-, some anaerobes; indicated for upper respiratory tract infections, intraabdominal, surgical prophylaxis

3rd: (B) G->G+, good CNS penetration; indicated for pneumonia & meningitis

4th: (B) G+ & G-, good CNS penetration
Term
Carbapenems (VB)
Definition
MOA:similar to PCN, bactericidal
A.E: GI, seizures, allerigic reaction/rash
Indications: mixed or complicated infections, resistant pathogens
(not MRSA)
Term
Monobactam (N)
Definition
MOA: Similar to PCN, bactericidal
Spectrum: ONLY G-
-No cross reactivity w/ PCNs (for those w/ anaphylaxis to PCN)
Term
Vancomycin
Definition
MOA: inhibits cell wall formation, bactericidal. IV/PO
A.E: Infusion-related reactions due to histamine release (red man syn)
Nephrotoxicity (trough conc) & ototoxicity (peak conc)--therapeutic drug monitoring
-Spectrum: MRSA, serious G+ infections in pts w/ PCN allergy, PO for c. dif infections
Term
Daptomycin (N)
Definition
MOA: disrupts cell plasma membrate & results in cell death
-IV
-A.E: muscle toxicity, GI
Spectrum: MRSA, G+ skin infections, endocarditis, pts w/ PCN allergy
Term
Aminogylcosides
Protein synthesis inhibitors
Definition
MOA: bactericidal
-nephrotoxicity, ototoxicity, NM blockade (tx drug monitoring essential!)
-Increased risk of nephrotoxicity assoc w/ elderly, preexisting kidney disease, concurrent nephrotoxic drugs, duration >10 days. Toxicity assoc w/ total accum dose.
Mechanism of resistance: bac enzymes.
Spectrum: all G-, G+ synergy w/ gemtamicin.
Interactions: nephro/ototoxic drugs, neuromuscular drugs.
Term
Tetracyclines (B)
Definition
MOA: bacteriostatic; inhibit protein syn.
Resistance: decrease drug uptake, increase drug inactivation.
Spectrum: Staph, Strep, some G- & anaerobes, atypicals, MRSA, spirochetes, Borrelia burgdorferi, Rickettsia
A.E: teeth staining (not for children <8 or pregnancy), photosensitivity, dizziness, tinnitus (minocycline)
Interactions: Calcium, iron, mag, aluminum, zinc.
Indications: Rocky Mt syn, Chlamydia trachomatis, atypical pneumonia, Lyme disease, anthrax, acne, periodontal disease
Term
Tigecycline (B)
Definition
MOA: inhibit protein syn-bacteriostatic
Spec: Staph, strep, MRSA, VRE, G- (not s. aeruginosa) anaerobes
-N/V, tooth discoloration; not for those <8 or pregnancy.
Interactions: warfarin
-Indications: complicated skin infections, intraabdominal infections.
Term
Macrolides (B)
Definition
MOA: inhibit protein syn-bacteriostatic
Resistance: efflux pump, modifaction of target ribosomes.
Spec: Stap, strep,some G- & anerobes, atypicals, Chlamydia trachomatis
A.E: GI UPSET, OTc prolongation, superinfection of bowel
Interactions: CYP drugs w/ eryth&clarith (warfarin, carbamez, statins, theophylline)
Indications: bronchitis, sinusitus, CAP, dental, Chalm. trach, B pertussis, H. pylori
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