Micro LO 4


Describe the most important mechanism explaining how bacteria become antibiotic resistant. Describe at least one other mechanism of antibiotic resistance.


Transferring of plasmids -> bact become resistant toantibiotics. Plasmids passed around are �R-factors� (�r� stands for �resistance�): - enzymes (to break down antibiotic) - pumps (allow bact to pump out antibiotic)Bact also become resistant by: 1) forming biofilms (bact at bottom don�t come into contact w antibodies)2) mutate (selecting antibiotic-resistant bact)3) change structure of what antibiotic (abx) is targeting -> may remove cell walls 4) metabolic pathways


State where antibiotics were first isolated from and how semi-synthetic and synthetic agents improve on these antibiotics.


abx first isolated from bact. & fungi -> anti (against) and biotic (life). Bact and fungi kill off whatever�s growing in their area. Bact and fungi were original sources.Take �natural� abx -> modify them in the lab -> get �semi-synthetics� (aka: second generation). Want increased range and stability or increasing bacteriocidal abilities.


Define bactericidal, bacteriostatic and bacteriolytic agents. Describe broad spectrum vs. narrow spectrum antibiotics and the advantages and disadvantages of each.


bacteriocidal: �killing� the bact.bacteriostatic: stop bact from dividing (gentler on your flora than bacteriocidal; also lets your body see the bact and mount an immune response. CONS: if someone�s immunocompromised, they won�t be able to kill the bact)bacteriolytic: �lyses� bact. � makes them leakybroad spectrum Ab: Gram +/- CONS: Damages pt flora.narrow spectrum Ab: Gram � (like enteric bact after abdominal surgery). If you have myco. TB, you�ll get super narrow spectrum. CONS: if you give wrong abx, you�ve just allowed the real bact to grow one week more.A broad-spectrum antibacterial drug can inhibit a variety of gram-positive and gram-negativebacteria, whereas a narrow-spectrum drug is active only against a limited variety of bacteria.


Describe the MIC test. Is a higher or a lower MIC test desirable? How does this compare with an agar diffusion method? The MBC test?


- MIC: Minimal Inhibitory Concentration. Use for Bacteriostatic activity: Level of antimicrobialactivity that inhibits the growth of an organism. This is determined in vitro by testing a standardized concentration of organisms against a series ofantimicrobial dilutions. The lowest concentration that inhibits the growth of the organism is referred to as the minimum inhibitory concentration (MIC). - MBC: Use for Bactericidal activity: Level of antimicrobial activity that kills the test organism. This is determined in vitro by exposing a standardized concentration of organisms to a series of antimicrobial dilutions. The lowest concentrationthat kills 99.9% of the population is referred to as the minimum bactericidal concentration (MBC).- Kirby-Bauer test: agar diffusion test. Make a lawnof bact. Buy Ab disks and you �plop� them on -> look for clearing around the disk, called �zone of inhibition�. Get some drug-resistant bact. in zones of inhibition!


List the 9 desirable properties of antibiotics.


soluble � can it �get to� infectionslowly breaks down/slowly excreted � only have to take this guy once a day, rather than 6 times a day selectively toxic � leaves flora alonepH stableNOT create an allergyDrug resistance RARESmall doseBacteriocidal vs bacteriostatic preferenceActive and stable in pus


Define synergistic and antagonistic effects of antibiotics and selective toxicity.


synergistic: two things work together and you get more effect than you would from one thing onit�s own� like prescribing two Abs togetherantagonistic: two drugs cancel each other outdentists should avoid combination therapy


Penicillin V Oral & Penicillin G parenteral


Target: cell wallClass: B-lactam MO: Interferes w cross-linking of peptidoglycanUses: Gram + bact & Gram - cocci * B-lactamase gene on R factors* Staph is resistant!


Methicillin, Cloxacillin, Oxacillin


Target: cell wallClass: B-lactamMO: interferes w cross-linking of peptidoglycanUses: 2nd generation penicillin Staph infxns*B-lactamase resistant (penicillinase-resistant)* Anti-staphylococcal penicillins (but MRSA has emerged)


Ampicillin & amoxicillin


Target: cell wallClass: B-lactamMO: interferes w cross-linking of peptidoglycanUses: 3rd generation penicillin. More effective against Gram - bacilli* "extended spectrum penicillins"; common dental prophylaxis* ampicillin: sulbactam & amoxicillin: clavulanate (augmentin) have B-lactamase inhibitors


Cephalosporin


Target: cell wallClass: B-lactamMO: interferes w cross-linking of peptidoglycansUses: BROAD spectrum. 4th generation (each generation is broader spectrum)* effective against some Gram -; more resistant to B-lactamase* antabuse reaction. 10% of penicillin allergic


Imipenem


Target: cell wallClass: B-lactam CarbapenemsMO: interferes w cross-linking of peptidoglycan Use: BROAD spectrum* resistant to B-lactamase* given w cilistatin to decrease toxicity


Aztreonam


Target: cell wallClass: B-lactam MonobactamsMO: interferes w cross linking of peptidoglycansUses: NARROW spectrum aerobic, Gram -; resistant to B-lactamase* not widely used* given IV, IM, and inhaled


Vancomyocin


Target: call wallClass: NON-B-lactam GlycopeptideMO: Cell wall synthesis INHIBITORUses: Gram + bacteria; limited effect against Gram -* used for multidrug resistance bact (MRSA) and endocarditis


Bacitracin


Target: cell wallClass: topicalMO: stops cell wall synthesisUses: Gram + Staph AND Group A Strep* mostly topical* nephrotoxic if systemic - not well absorbed from GI


Isoniazid


Target: cell wallClass: Anti-TBMO: Inhibits mycolic acid synthesisUses: Mycobacterium tuberculosis*long treatment times needed


Rifampin & Rifabutin


Target: RNA synthesisClass: RifamycinsMO: transcription initiationUses: Mycobacterium TB*Hepatotoxic


Lincomycin, Clindamycin


Target: Protein SynthesisClass: LincosamidesMO: Translation inhibitor. Blocks 50 S ribosome; inhibits translocationUses: Anaerobic Gram + OR Gram - bacteria* pseudo-membranous colitis (from C. diff); common dental proph.* R factor that methylates rRNA and prevents abx binding to ribosomes


Erythromycin, Clarithromycin, Azithromycin


Target: protein synthesisClass: macrolidesMO: translation inhibitor. Binds 50 S ribosome.Uses: Gram + bact. Other anaerobes not killed at oral admin levels (why you choose penicillins)* GI problems. Ototoxic. Use if penicillin allergies. Effective against B lactamase + organisms* Increases theophylline levels. R factor that methylates rRNA and prevents abx binding to ribosomes


Streptomycin, Gentamicin, Tobramycin


Target: protein synthesisClass: AminoglycosidesMO: translation inhibitor. Blocks 30 S ribosomeUses: effective against Gram + and Gram - anaerobes & Gram - rods* requires oxygen for transport into bacteria; not effective against anaerobes* Given IV or IM. Damage 8th cranial nerve. Nephrotoxic


Tetracycline, Doxycycline, Minocycline


Targets: Protein synthesisClasss: TetracyclinesMO: translation inhibitor. Blocks 30 S subunit. Stops tRNA binding.Uses: BROAD spectrum: many Gram + and Gram -. Some Rickettsiae, Mycoplasma, and Chlamydia* discolors developing teeth. Photosensitivity. Used as mouthwash for 2ndary infxn w oral ulceration.* antacids, dairy, iron, and zinc reduce absorption. R factor that alters bacterial cell membrane and decreases permeability to abx.


Chloramphenicol


Target: protein synthesisClass: ChloramphenicolMO: Blocks 50 S ribosome. Inhibits peptidyl-transferaseUses: Some Gram + cocci, Gram - aerobes, anaerobes, Rickettsia, Chlamydia, Mycoplasma, and salmonella* bone marrow toxicity* limited use - severe Salmonella and B-lactam sensitive patients w bacterial meningitis


Nystatin, Amphotericin


Target: cell membraneClass: PolyeneMO: binds ergosterol in fungal cell membraneUses: Candida, Cryptococcus*FUNGAL cell membranes * these are anti-fungals; ergosterol is unique to fungi


Chlorhexidine


Target: cell membraneClass: antiseptic mouthwashMO: membrane disruptionUses: both Gram + and Gram - bact; more effective against Gram +* used as a surgical scrub and as a mouthwash. Mouthwash binds to oral tissues has persistent effect.* inactivated by SLS and MFP in toothpaste - don't use together


Polymyxin


Target: cell membraneClass: topicalMO: detergent actionUses: Gram - (binds LPS in cell wall)*skin, eye infxns* Neurotoxic, nephrotoxic, not GI stable if used internally


Metronidazole


Target: DNA synthesisClass: MetronidazoleMO: strict anaerobes are sensitive and some protozoaUses: anaerobes EXCEPT Actinomyces*often used to treat pseudo-membranous colitis*antabuse effect w alcohol


Ciprofloxacin


Target: DNA synthesisClass: quinolones, FluoroquinolonesMO: inhibit DNA gyrase-transcription inhibitorUses: Gram - rods, Neisseria some Gram +; not anaerobes*can damage cartilage and growing bone* not used in kids or in pregnancy


Sulfadiazine, Trimethoprim


Target: metabolismClass: SulfonamidesMO: blocks folic acid synthesis -> need folate for DNAUses: Gram + and Gram - Actinomyces, Nocardia, and Chlamydia*cause hemolytic anemia in patients w G6PD deficiency* allergy causer, renal toxicity. Trimethoprim: good for UTI b/c it's excreted in urine