Antibiotics Flashcards
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
- LARGER THE INDEX THE BETTER
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:
- inhibit cell wall synthesismost common
- Inhibit protein synthesis second most common
- Inhibit nucleic acid function or production
- Disrupt metabolic pathways, like folate metabolism
- 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
- absence of target from the host: high therapeutic indexes
- permeability differences: bacteria take it up, our cells dont
- 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 _______.
- bacteriostatic
- bactericidal
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
- 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
- no
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?
- indifference: 2 drugs have no effect on eachother
- Additive response: response is the same as the sum of the 2 drugs individually
- Synergistic response: response is greater than the sum of the two drugs used individually
- antagonistic response: response is less than sum of the two drugs used individually
2 drug examples of synergism
- Bactrim: Sulfamethoxazole (inhibits production of THF-acid, but not utilization of current pool)+ Trimethoprim (prevents use of THF-acid pool, but not its synthesis)
- 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
- location: some drugs cannot cross BBB and some bacteria are intracellular
- 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
- presence of foreign bodies and obstructions: adhere to objects and make biofilms
- drug resistance
5 general mechanisms of drug resistance
- enzymatic inactivation of the antibiotic
- Inadequate or decreased uptake of the drug into the microbe (mutate porins)
- Increased efflux of the antibiotic out of the microbe (active transport)
- Alteration of drug target (mutations in PBPs)
- 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?
-hospital
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
- transpeptidase
Penicillins bind to __________, so these enzymes are also referred to as __________.
- transpeptidase
- penicillin binding proteins (PBPs)
Beta lactams are competitive inhibitors of __________ and inhibit its function. What is the result of this?
- transpeptidase
- 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?
- bactericidal
- 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
- Natural penicillins
- Penicillinase-resistant penicillins
- 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
- Methicillin
- Oxacillin
- Naficillin
- Cloxacillin
- Docloxicillin
* *VERY NARROW SPECTRUM**
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
- Ampicillin
- Amoxicillin
- Carbenicillin
- 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?
- immediately
- 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
- Beta-lactamases are produced that destroy the drug
- Transpeptidases (major PBP) acquires a mutation the prevents drug binding
- 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
- clavulanate
- sulbactam
- tazolbactram
List 4 common combinations of penicillins and beta-lactamase inhibitors
- Amoxicillin-clavulanate = Augmentin
- Ampicillin-sulbactam
- Piperacillin-tazolbactam= Zosyn
- 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.
- Strep
- Meningococci
- Spirochetes
- Most other gram positive anaerobes
- NOT STAPH
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
- empiric therapy: given for proven or suspected infection, but organism not identified
- Definitive therapy: given for proven identification and based on a causative organism
- Prophylaxis: given to prevent infection
Hypersensitivity to penicillins are ______ mediated.
-IgE
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
- pseudomonas
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?
-bactericidal
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 ________.
-enterococci
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 _________.
- Cefazolin
- Cefadroxil
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?
- Cefipime
- 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
- Cafadroxil
- Cefazolin
- Cephalexin
2nd generation cephalosporin commonly used at Penn
- Cefuroxime
Name the 4 3rd generation cephalosporins used at penn
- Cefixime
- Cefotaxime
- Ceftazidime
- Ceftriaxone
What 3rd generation cephalosporin is used to treat pseudomonas?
-Ceftazidime
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
- Imipenem
- Meropenem** commonly used at Penn and restricted**
- Ertapenem
- Doripenem
Are Carbapenems bacteriostatic or bacterocidial? How are they administered?
- bactericidal
- 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?
-glycopeptide
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
Daptomycin
- 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
- MRSA
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
- Macrolides**
- Aminoglycosides**
- Tetracyclins
- Chloramphenicol
What are the 4 macrolides commonly used at penn?
- Azithromycin
- Clarithromycin
- Clindamycin
- Erythromycin
Mechanism of macrolides
-reversibly bind to 50S ribosome and prevent protein elongation
Are macrolides bactericidal or bacteriostatic?
-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
- URTI
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.
- 60S,40S
- 50S,30S
6 commonly used aminoglycosides
- streptomycin
- gentamicin
- tobramycin
- amikacin
- neomycin
- spectinomycin
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
- Gentamicin
- Tobramycin
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
- enzyme modification of the drug: typically on plasmids and results in high-level resistance
- reduced uptake or decreased cell permeability: intermediate resistance since block is not complete
- 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
- nephrotoxicity: relatively common (10-20%), generally reversible toxicity, appears assoc. with high trough levels (lowest levels of drug seen in plasma)
- 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 _______.
-synergy
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
- tetracyclin
- doxycycline
- minocycline
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?
-tetracyclins
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
- levofloxacin
- norfloxacin
- Cirpofloxacin
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
-Anthrax
-GNR including pseudomonas
-
Levofloxacin is active against many _________.
-penicillin-resistant pneumococci
How are fluoroquinolines administered?
- PO
- 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
-Flagyl
Is metronidazole bacteriostatic or bactericidal?
-bactericidal
Mechanism of action of metronidazole
-inhibits DNA replication, causes DNA breaks and secondary mutations
Metronidazole is administered as a _________. What does this mean?
- pro-drug
- 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 ________.
- anaerobes
- 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 _______.
-sulfonamide
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.
-anaerobic
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
- hypersensitivity
- 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
- Penicillins
- Cephalosporins
- Carbapenems
List the 1 class of drug that targets the cell membrane
-Glycopeptides/polypeptides
List the 4 classes of drugs that target protein synthesis
- Macrolides
- Aminoglycosides
- Tetracyclins
- Chloramphenicol
List the 3 classes of drugs that target nucleic acid synthesis
- Quinolones
- Rifampin
- Metronidazole
List the class of drugs that targets antimetabolites
- Sulfonamides
- Trimethoprim
