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Flashcards in Antibiotics Deck (190):

Antibiotics are based on naturally occurring compound but are modified chemically to do what?

-extend their range of action
-improve potency and pharmacokinetics
-avoid resistance mechanisms


Narrow vs. broad spectrum antibiotics

N: specific against a few bacteria
B: active against many different bacterial types


Define therapeutic index

-lowest dose that is toxic to the patient divided by the dose used to typically treat a patient


3 general types of adverse events from ABx

-allergic reactions: hypersensitivity to a specific drug
-toxic effects: can be drug specific
-Suppression of normal flora: one reason to use narrow-spectrum ABx


How do disinfectants differ from antibiotics?

-disinfectants (detergents, peroxide) have a NONSPECIFIC mechanism of action and so are BROADLY active and not tolerated by the host
-usually need higher concentration relative to antibiotics due to lack of specificity
-remember: ABx have specific spectrum of activity that is related a specific mechanism of action


5 major mechanisms by which antibiotics work:

1. inhibit cell wall synthesis**most common**
2. Inhibit protein synthesis **second most common**
3. Inhibit nucleic acid function or production
4. Disrupt metabolic pathways, like folate metabolism
5. Disrupt cell membrane (Not cell wall, cell membrane)


ABx that target the bacterial cell wall work best against _________ bacteria while ABx that target cell membrane typically work best against ________ bacteria.

-gram positive where cell wall is far more prominent
-gram negative where cell membrane is on outer surface


3 mechanisms that confer selectivity to antibiotics

1. absence of target from the host: high therapeutic indexes
2.permeability differences: bacteria take it up, our cells dont
3.structural differences in the target: different ribosome size


Drugs that gain selectivity by permeability differences need to be given by IV, not the mouth...why?

-our cells will not pick up the drug, so it cannot reach infections internally


Bacteriostatic vs. bactericidal antibiotics

-Static: reversibly inhibit bacterial growth; growth resumes when drug is removed
-cidal: kill bacteria; usually requires bacteria to be growing actively


Drugs that target metabolic processes typically fall into (bacteriostatic/bactericidal) categories. Drugs that target the cell wall or membrane tend to be _______.



Define Minimum Inhibitory Concentration

-lowest concentration of an antibiotic that effectively inhibits growth of a microorganism


2 ways to test susceptibility of bacteria to various antibiotics

1. Tube dilution assay for antibiotic sensitivities
2. Disc diffusion method


Tube dilution assay for antibiotic sensitivies

-bacteria are gown in small cultures in the presence of different concentrations of antibiotics
-tells you sensitivies of a given bacterial isolate to a range of drug concentrations


Disc diffusion method for antibiotic sensitivies

-bacterial isolate is spread over plate and grown into "bacterial lawn"
-small antibiotic impregnanted discs are placed on the agar, and drug diffuses in
-if isolate is not sensitive, it will continue to grow, but if it is sensitive, you will see clear area around disk


In a disk diffusion method, the width of the clear area is related to the _______. Does this procedure inform us if the drug is bacteriostatic or bactericidal?

-MIC: minimum inhibitory concentration


Generally, we prescribe one drug whenever possible and it is usually the simplest to minimize evolution of drug resistance. What are some cases when 2 or more ABx will be prescribed?

-chronic infections
-emergencies: cannot wait for cultures to come back
-mixed infections
-drug synergies


What are the 4 possible outcomes that can arise if more than 1 drug is being used?

1. indifference: 2 drugs have no effect on eachother
2. Additive response: response is the same as the sum of the 2 drugs individually
3. Synergistic response: response is greater than the sum of the two drugs used individually
4. antagonistic response: response is less than sum of the two drugs used individually


2 drug examples of synergism

1. Bactrim: Sulfamethoxazole (inhibits production of THF-acid, but not utilization of current pool)+ Trimethoprim (prevents use of THF-acid pool, but not its synthesis)

2. Augmentin: amoxicillin (extended spectrum penicillin)+ beta-lactamase inhibitor clavulanic acid


Drug example of antagonistic response

-penicillin and erythromycin
-erythomycin is bacteriostatic and slows bacterial growth that is necessary for penicillin (bacterocidal) to function properly
-if E is used first, it will make subsequent application of the cell wall inhibitors less effective


Name 4 issues that can limit successful antimicrobial therapy

1. location: some drugs cannot cross BBB and some bacteria are intracellular
2. abscess formation and necrosis: decreased circulations in the area of an abscess will limit drug concentrations; low nutrients may slow bacterial growth that makes some ABx less effective
3.presence of foreign bodies and obstructions: adhere to objects and make biofilms
4. drug resistance


5 general mechanisms of drug resistance

1. enzymatic inactivation of the antibiotic
2. Inadequate or decreased uptake of the drug into the microbe (mutate porins)
3. Increased efflux of the antibiotic out of the microbe (active transport)
4. Alteration of drug target (mutations in PBPs)
5. Altered metabolic pathways (new enzyme expression)


Many bacteria, as a form of resistance, produce an enzyme called a beta lactamase that does what?

-cleaves the beta-lactam ring present in penicillins, cephalosporins, and carbapenems


Are community acquired or hospital acquired bacterial infections more likely to be resistant to drugs?



If you know what bacterium is causing the infection, you should prescribe drugs that are as ____________. When would you want to do the opposite?

-narrow spectrum as possible
-if life threatening, you need to treat more broadly since you can't run the risk of guessing wrong


Gram positive vs. gram negative structure

+: thick, exposed peptidoglycan layer
-: thinner peptidoglycan layer that is beneath an outer membrane


Peptidoglycan has repeating units of disaccharides that are crosslinked to each other via ________. What catalyzes formation of these cross-linked?

-peptide bonds


Penicillins bind to __________, so these enzymes are also referred to as __________.

-penicillin binding proteins (PBPs)


Beta lactams are competitive inhibitors of __________ and inhibit its function. What is the result of this?

-do not destroy existing cross-links but prevent formation of new ones; causes weak points at growth sites and become fragile


In general, Beta-lactam ABx are more effective against what type of bacterial cells?

- gram-positives because the cell wall is exposed
-those that are effective against G(-) cells must cross the cell membrane


Beta-lactams are __________ and work more effectively against rapidly/slowly growing bacteria?

-rapidly growing bacteria


What do the 3 classes of penicllins have in common? Describe this feature

-common structure of the beta-lactam ring
-4 sided ring with a nitrogen in it


Are penicillins the only ABx to have a beta-lactam ring?

-no; cephalosporins, carbapenems, and monobactams
-different side groups can alter the properties of the drug


Penicillins, cephalosporins, and carbepenems are drug classes that ALL contain a beta-lactam ring and target ________.

-bacterial cell wall
-called beta-lactam antibiotics


Name the 3 classes of penicillins

1. Natural penicillins
2. Penicillinase-resistant penicillins
3. Extended spectrum penicillins


List the 2 natural penicillins and how they are taken

-Penicillin G: inactivated by low pH so given by IV
-Penicillin V: acid stable, so can be taken PO


List the 5 penicillinase-resistant penicillins

1. Methicillin
2. Oxacillin
3. Naficillin
4. Cloxacillin
5. Docloxicillin


What is unique about penicillinase-resistant penicillins?

-they are resistant to beta-lactamases and were developed to combat Staph


Give the 4 examples of extending spectrum penicillins

1. Ampicillin
2. Amoxicillin
3. Carbenicillin
4. Pipericillin


What is unique about extending spectrum penicillins?

-must improved activity against gram-negatives, but less effective against gram positives


Extended spectrum penicillins are often used in conjunction with ____________.

-beta lactamase inhibitors


Penicillins are safe drugs, but have one significant side effect. Name it and describe a little bit about its risk.

-hypersensitivity reactions
-can be severe, causing anaphylaxis and can become more severe if a person is exposed to these drugs multiple times
-can include hives, maculopapular-measles-like, include itchy skin, wheezing swollen lips, etc


Anaphylactic reactions to penicillins occur _________ and include what symptoms? What symptoms do they not include?

-difficulty breathing, decreased blood pressure leading to dizziness and weak pulse, swelling of throat and tongue
-Nausea and vomiting are NOT allergic reactions to the drug


Before administering a penicillin, what do physicians have to do?

-ask if there is a history of having taken these drugs before/allergies to medications


Any allergic reaction to penicillin can occur quickly, but more commonly _____________________.

-it takes a while, sometimes a day or two


3 mechanisms of Beta-lactam resistance

1. Beta-lactamases are produced that destroy the drug
2. Transpeptidases (major PBP) acquires a mutation the prevents drug binding
3. Gram negatives can have membrane pumps that remove drug from pepiplasmic space


Describe the function of Beta-lactamase inhibitors

-little or no antimicrobial activity on their own, but can make beta lactam antibiotics more effective by binding to and inactivating beta lactamases


List 3 beta lactamase inhibitors

1. clavulanate
2. sulbactam
3. tazolbactram


List 4 common combinations of penicillins and beta-lactamase inhibitors

1. Amoxicillin-clavulanate = Augmentin
2. Ampicillin-sulbactam
3. Piperacillin-tazolbactam= Zosyn
4. Ticarcillin-clavulanate= Timentin


When are natural penicillins the drug of choice and when are they not used?

-drug of choice for community-acquired Strep, pneumococci, meningococci
-treatment of choice for syphilis (a spirochete)
-NOT effective against STAPH due to drug resistance


What genra of bacteria are natural penicillins not effective against and why?

-Staph!!! due to drug resistance


What is Staph's method of resistance against natural penicillins? What is then used to treat them and are issues arising in this?

-beta lactamases
-use beta-lactamase resistant penicillins (oxacillin, methicillin, naficillin) but many strains are now resistant to these drugs--MRSA
-now try to use oxacillin to treat Staph but this resistance is now rising


Characteristics of Ampicillin and Amoxicillin.

-extended spectrum penicillins
-similar to natural penicillins but can cross the membranes of some gram negatives and inactivate their transpeptidase enzymes


What are Ampicillin and Amoxicillin commonly prescribed for?

-uncomplicated urinary tract infections, otitis media, and uncomplicated community acquired penumonia, H. influenza, Lyme disease, and listeria meningitis


Characteristics and issue with Ticarcillin, Mexlocillin, and Piperacillin

-extended spectrum penicillins
-nice coverage of gram negatives, but at expense of not hitting gram positives as effectively
-still sensitive to beta lactamases, which is a huge issue


What class of penicillins are often coadministered with beta lactamase inhibitors?

-extend spectrum penicillin


Summary of categories of bacterium natural penicillins are good at fighting against.

-Most other gram positive anaerobes


Why is selective toxicity crucial to antibiotics?

-due to specific mechanism of action, are typically well-tolerated by the host but lethal to harmful micrones


Define disinfectant and give 4 characteristics

- an agent, such as heat, radiation, or a detergent, that destroys, neutralizes, or inhibits the growth of disease-carrying microorganisms
-Nonspecific spectrum of action
-Nonspecific mechanism of action
-Not tolerated by host
-Usually need high concentrations due to lack of specificity


Are bactericidal or bacteriostatic drugs better?

-often believed that bactericidal is more beneficial, though massive bacterial death can enhance inflammatory response
-bactericidal drugs are clearly better for meningitis and endocarditis


Efflux systems can be shared between bacteria via exchange of _________.

-Pathogenicity islands


3 ways antibiotics are used

1. empiric therapy: given for proven or suspected infection, but organism not identified
2. Definitive therapy: given for proven identification and based on a causative organism
3. Prophylaxis: given to prevent infection


Hypersensitivity to penicillins are ______ mediated.



MRSA's method of resistance to penicillins

-transpeptidase acquires a mutation that prevents drug bindings


Staph's method of resistance to penicillins

-beta lactamases


Mechanism of action of beta lactamase inhibitors

-irreversibly bind and inactivate certain beta-lactamases


Is amoxicillin or ampicillin used more?

-amoxicillin because it can be used 3 times a day instead of 4, and it is absorbed better


Extended spectrum penicillins with the addition of a beta-lactamase inhibitor have activity against _______.

-improved activity against staph and gram negatives


Compare cephalorsporins mechanism of action to the penicillins. What are some differences?

-same mechanism: inhibit peptidoglycan synthesis via PBPs--bactericidal
-wider antibacterial spectrum
-resistance to many beta-lactamases
-improved pharmacokinetics


Are cephalosporins bactericidal or bacteriostatis?



How do cephalosporins ring structures compare to penicillins?

-both have beta lactam rings, but cephalosporins are connected to a 6-member ring while penicillins are connected to a 5 member ring


In general, cephalosporins are resistant to _______ produced by __________ and common gram-negatives.

-beta-lactamases produced by staph


Cephalosporins do NOT cover ________.



Cephalosporin drugs have been described as "generations" from first generation (oldest) to fourth. Newer generations have better _______________.

-gram-negative coverage and poorer gram + coverage


Like penicillins, cephalosporins can induce ____________.

-hypersensitivity reactions
-5% of patients with penicillin reactions have reactions to cephalosporins as well


1st generation cephalosporins start with "ceph" except for ________ and _________.



What types of bacteria are cephalosporin (1st gen) active against and what are they commonly prescribed for?

-very active against gram positives including Staph (except MRSA)
-moderate use against some gram negatives, esp. E. coli and Klebsiella
-used for community acquired UTIs and respiratory infections
-Cefazolin is used for surgical prophylaxis


For what instances are 1st generation cephalosporins commonly prescribed?

-community acquired UTIs and respiratory infections
-Cefazolin for surgical prophylaxis


When are 2nd generation cephalosporins prescribed?

-otitis media in children
-increased activity, esp. against gram negatives including H. influenzae
-respiratory infections, UTIs


3rd generation cephalosporin activity

-less activity against G+, more effective G- coverage


What are 3rd generation cephalosporins prescribed for?

-management of hospital-acquired (G-) bacteremia, inpatient pneumonia and UTIs
-some can penetrate CNS!!! unlike 1st and 2nd generation)
-gonococcal infections


Single dose of __________ is used for gonococcal infections. It is also used to treat meningitis

-Ceftriaxone, a 3rd generation cephalosporin


________ is the only licensed 4th generation cephalosporin in the US. What activities does it have?

-enhanced activity to enterobacter, citrobacter, and pseudomonas
-can be used when resistance is seen to a 3rd generation drug


Side effects of Cephalosporins

-overall relatively safe since drugs that target cell wall have a very high therapeutic index
-hypersensitivity reactions just like penicillin
-patients with significant PCN allergies should NOT be given cephalosporins, but you can risk it if PCN allergies are mild
-greater incidence of GI problems due to better gram negative coverage- can lead to C. difficile colonization and colitis


3 mechanisms of resistance to cephalosporins

-Same to penicillin!
1. beta lactamases
2. increased efflux from periplasmic space of gram negatives
3. change the target; mutate PBPs so they dont bind ABx well


As you increase the generation of cephalosporins, you increase the ________ coverage.

-gram negative


3 common first generation cephalosporins used at Penn

1. Cafadroxil
2. Cefazolin
3. Cephalexin


2nd generation cephalosporin commonly used at Penn

1. Cefuroxime


Name the 4 3rd generation cephalosporins used at penn

1. Cefixime
2. Cefotaxime
3. Ceftazidime
4. Ceftriaxone


What 3rd generation cephalosporin is used to treat pseudomonas?



Carbapenems mechanism of action; how is it similar to penicillins? how is it different?

-same as penicillins: inhibit PBPs
-wider antibacterial spectrum than other beta lactamases, resistance to beta-lactamases, improved pharmackkinetics


4 carbapenems commonly used

1. Imipenem
2. Meropenem** commonly used at Penn and restricted**
3. Ertapenem
4. Doripenem


Are Carbapenems bacteriostatic or bacterocidial? How are they administered?

-usually given IV


What types of bacterial are carbapenems effective against?

-gram positive, gram negative, aerobic, and anaerobic bacteria
-typically cover everything except enterococci


When are carbapenems administered?

-often used as empiric therapy for critically ill patients
-last resort for E. Coli and Klebsiella infections


Where are carbapenems metabolized? By what enzyme and can this be blocked?

-Kidney by dehydropeptidase
-blocked by cilastatin, which is sometimes coadministered


Why is the use of carbapenems so controlled?

-we dont want overuse as resistance to them so far is rare


Resistance to carbapenems

-Carbapenemases (beta lactamases) have been found in enteric bacteria


How do carbapenems penetrate gram negative rods?

-bia OprD porins
-carbapenem resistant pseudomonas aeruginosa mutants lack OprD


In summary, beta lactam drugs are generally more active against __________ bacteria, with variable coverage of ___________ bacteria.

-gram positive
-gram negative


Beta lactam side effects summary

-hypersensitivity is major side effect, along with GI disturbances with more potent cephaloporins


What type of molecule is vancomycin?



Function of vancomycin

-interactions with D-alanine-D-alanine termini of the pentapeptide side chains interfering with formation of bridges between peptidoglycan chains
**Thus it works a step BEFORE beta-lactams in preventing transpeptidation**


Is there cross resistance to vancomycin and beta-lactams?

-no; though V inhibits cell wall synthesis, it does so differently than beta-lactams


How is vancomycin usually administered?

-IV due to poor absorption from intestinal tract, unless you are trying to treat a GI infection


What coverage is vancomycin best at providing?

-excellent gram positive coverage against Staph and Strep
-NO gram negative coverage


Why does vancomycin not providing gram negative coverage make sense?

-it is a glycopeptide and is too big to pass through porins in the gram negative membranes


Compare vancomycin and oxacillin effectiveness against MRSA

-vancomycin is inferior to oxacillin, but V is still used


What is vancomycin prescribed for?

-Staph and Strep infections
-MRSA and othwr beta-lactam resistant gram positive organisms
-oral form used for C. difficile colitis


Vancomycin can cause a hypersensitivity reaction; rarely this can be more severe, leading to what is called ____________. In general, it is well tolerated but must be infused slowly. What else can it cause?

-Red Man Syndrome with a red rash on the face, neck, and trunk
-occurs monutes after administration due to secondary mast cell degranulation and histamine release
-can also cause thrombophlebitis


Bacitracin, like vancomycin, is a ________.

-peptide; although, B is technically a mixture of cyclic peptides


How does bacitracin function?

-inhibits cell wall synthesis by preventing the transport of peptidoglycan precursors across the bacterial cytoplasmic membrane


How is bacitracin used and what is it most effective against?

-only used topically; toxicity issues if taken orally
-most effective against gram-positives


Where is bacitracin a common ingredient?

-in non-prescription first-aid ointments



-lipophilic peptide that disrupts the membranes of gram positives
-can be given IV


Daptomycin is approved for _____________ infections and is active against _________.

-gram positive skin infections and S. aureus bacteremia


What is the target of many antimicrobials that function by inhibiting protein synthesis?

-prokaryotic ribosome
-it is different enough from the eukaryotic ribosomes responsible for selective toxicity


4 drugs comprising class of antimicrobials that act via inhibiting protein synthesis

1. Macrolides**
2. Aminoglycosides**
3. Tetracyclins
4. Chloramphenicol


What are the 4 macrolides commonly used at penn?

1. Azithromycin
2. Clarithromycin
3. Clindamycin
4. Erythromycin


Mechanism of macrolides

-reversibly bind to 50S ribosome and prevent protein elongation


Are macrolides bactericidal or bacteriostatic?



Macrolides have broad activity against __________ and some _______.

-gram positive
-some gram negatives


When are macrolides prescribed?

-first line agents for community acquired pneumonia and often drugs of choice for those allergic to penicillin
-good activity against strep pneumonia
-atypical pathogens like legionella, chlamydia, and mycoplasma
-skin infections not due to MRSA


Usual form of resistance to macrolides

-usually due to altered binding sites
- can also be due to hydrolysis of drug and enhanced efflux


Macrolide side effects

-no unusual side effects


Eukaryotic ribosome have _____ and _____ subunits, while prokaryotes have ____ and ______ subunits.



6 commonly used aminoglycosides



Mechanism of action of aminoglycosides

-IRREVERSIBLY binds to 30S ribosomal subunit
-causes distortion and malfunction of ribosome
-blocks initiation of translation
-causes misreading of mRNA


Are aminoglycosides bactericidal or bacteriostatic?

-bactericidal because they bind irreversibly


Are aminoglycosides effective against anaerobes? explain.

-no; penetration through membrane is an aerobic, energy-dependent process


Aminoglycosides are not effective against _____ and _______ unless...

-enterococci and streptococci
-UNLESS a Beta lactam drug is coadministered
-this allows aminoglycosides to enter cells that are often resistant


Typical uses of aminoglycosides

-good coverage against aerobic, gram negative rods (E. coli, Klebsiella, enterobacter, pseudomonas, shigella)
-usually reserves for serious gram negative infections (complicated UTIs with pylonephritis, penumonia and used with beta-lactam to cover G+ and G-, pseudomonas)


Are aminoglycosides used in everyday practice?

-no, issues with toxicity limit their use


How are aminoglycosides administered?

-not absorbed in the gut
-thus given IV or IM


What are the 2 most commonly used aminoglycosides



Why are aminoglycosides coadministered with beta lactams?

-beta lactams will damage cell wall and allow aminoglycosides to penetrate


Aminoglycoside resistance is increasing with _______ and _______.

-pseudomonas and enterococci
-incidence of resistance is low for other organisms


3 resistance mechanisms to aminoglycosides

1. enzyme modification of the drug: typically on plasmids and results in high-level resistance
2. reduced uptake or decreased cell permeability: intermediate resistance since block is not complete
3. Altered ribosome binding site: not common


Why are there such strict concerns over aminoglycosides?

-these drugs have a low therapeutic index, so you need to follow drug levels


2 common side effects of aminoglycosides

1. nephrotoxicity: relatively common (10-20%), generally reversible toxicity, appears assoc. with high trough levels (lowest levels of drug seen in plasma)
2. Ototoxicity: appears assoc with high peak levels, can cause tinnitus and permanent deafness due to loss of hair cells; may not be reversible


Aminoglycosides being used with beta-lactams is a good example of _______.



Why can administering aminoglycosides be of help to CF patients?

-important drug against pseudomonas which cause serious problems for patients with CF


3 common drugs used from tetracyclins



Mechanism of action for tetracyclins

-REVERSIBLY bind to 30S ribosomal subunit
-blocks attachment of tRNA to ribosome and prevents continuations of protein synthesis


Are tetracyclins bacteriostatic or bactericidal?

-bacteriostatic: reversibly! bind 30s


Common uses of tetracyclins

-good coverage of mycoplasma and chlamydia
-Drug of choice for lyme disease
-acne treatment


What class of drugs is the drug of choice for lyme disease?



3 common side effects of tetracyclins

-discolored teeth in children
-GI upset
-Phototoxic dermatitis


Who should NOT receive tetracyclins?

-children or pregnant women


Most common resistance mechanism to tetracyclins

-increased efflux from cells


Mechanism of action of chloramphenicol

-binds to 50S subunits
-prevents peptide bonds from forming and blocking protein synthesis


Chloramphenicol is effective against a VERY wide variety of organisms, but used as drug of last resort for life-threatening infections. Why?

-has rare, but deadly side effects
-aplastic anemia


Aplastic anemia

-rare, often fatal side effect of chloramphenicol
-bone marrow is wiped out


Give 2 examples when Chloramphenicol is used

-young children and pregnant women with Rocky Mountain Spotted Fever, which is usually treated with tetracyclins but can't use these with these people
-meningitis if organism not known and patient has penicillin allergy


Who should not be given chloramphenicol under any condition?

-neonates: they cannot metabolize the drug, resulting in high levels and vasomotor collapse


3 types of drugs that inhibit nucleid acid synthesis. Name them and if they work on DNA or RNA

DNA replication: quinolones/fluoroquinolones and metronidazole
RNA replication: Rifamycins


Quinolones target ________.

-DNA gyrase
-DNA gyrase nicks and reannels DNA to relieve supercoiling, and relieves tension as DNA is unwound during replication


Drugs that target DNA gyrase inhibit ________.

-DNA replication


Commonly used fluoroquinolones



What bacterium are fluoroquinolones not good against?

-gram positives or anaerobes


What are fluoroquinolones effective against?

-multi-drug resistant pseudomonas (Cipro is best)
-Enterics: E.coli, salmonella, shigella, campylobacter
-Complicated UTIs: usually caused by gram negs
-GNR including pseudomonas


Levofloxacin is active against many _________.

-penicillin-resistant pneumococci


How are fluoroquinolines administered?

-good tissue absorption


Resistance mechanism against fluoroquinolones

-due to mutations in drug binding site in gyrase


Side effects of fluoroquinolones

-generally safe, but can disrupt normal gut flora, increasing chance of getting C. difficile


Tradename of metronidazole



Is metronidazole bacteriostatic or bactericidal?



Mechanism of action of metronidazole

-inhibits DNA replication, causes DNA breaks and secondary mutations


Metronidazole is administered as a _________. What does this mean?

-it is inactive (or significantly less active) until it is metabolized in vivo into an active form
- in metronidazole, the nitrogroup is chemically reduced by bacterial oxidoreductases to become active


What enzymes create the active form of metronidazole?

-bacterial oxidoreductases
-it is activated INSIDE bacterial cells


Metronidazole is only active against ________.

-one of the most reliable anti-anaerobic agents available


Aside from anaerobes, metronidazole is also good against what other pathogens?

-good for C.difficile, behind vancomycin
-Protozoa: trichomonas, giardia, amebic infections


Resistance mechanisms against metronidazole

-decreased uptake into the cell
-reduced activation of the ABx


Mechanism of action of sulfonamides

-inhibit growth of gram + and gram - organisms through competitive inhibition of enzyme that aids in production of folic acid


What is sulonamides structurally similar to?

-para-aminobenzoid acid which is substrate in folic acid pathway


What is the basis of selective toxicity of sulfa-drugs?

-humans lack specific enzyme in folic acid pathway


Resistance mechanism to sulfa-drugs

-due to plasmid
-plasmid codes for enzyme that has lower affinity to drug


Trimethoprim mechanism of action

-inhibits folic acid production
-interferes with activity of enzyme following enzyme inhibited by sulfonamides


Trimethoprim is often used synergistically with _______.



Most common mechanism of resistance to trimethoprim

-plasmid-encoded alternative enzyme


Genes encoding resistance to sulfonamide and tripmethoprim are often ________.

-carried on the same plasmid


What is bactrim a combination of?

-trimethoprim and sulfamethaxazole


Bactrim has no _______ coverage.



What is bactrim good for?

-strep and H. flu (otitis media, sinusitis, bronchitis)
-gram negatives causing diarrhea: shigella, salmonella, E. coli
-pneumocystis (seen in AIDS patients)


Bactrim side effects

-don't give to patients taking warfarin (blood thinner) as it increases warfarin levels and can lead to bleeding


List the 3 classes of drugs that target the cell wall



List the 1 class of drug that targets the cell membrane



List the 4 classes of drugs that target protein synthesis



List the 3 classes of drugs that target nucleic acid synthesis



List the class of drugs that targets antimetabolites