03a: Antibacterial Agents Flashcards
List the four sites of antibiotic action.
- Cell wall synthesis
- Protein synthesis
- Nucleic acid synthesis
- Folic acid synthesis
List the classes of antibiotics that target cell wall synthesis. Star the beta lactams
- Penicillins*
- Vancomycin
- Beta-Lactamase Inhibitors
- Cephalosporins*
- Carbapenems*
Penicillin is (bactericidal/bacteriostatic) and (time/conc)-dependent.
Bactericidal; time-dependent
Mechanism of action of beta lactams is (stim/inhib) of (X), followed by bacterial cell (Y).
Inhibition;
X = PBPs (cross link peptide chains of peptidoglycan)
Y = lysis (via osmotic P or autolysins)
Natural penicillins, such as (X), primarily target gram (pos/neg) (aerobes/anaerobes) and is treatment of choice for which situations/infections?
X = penicillin G
Gram-pos aerobes (strep);
- Strep (GAS pharyngitis)
- Syphilis
Extended spectrum penicillins differ from natural penicillins in that they have greater:
access/ability to penetrate through O.M. of gram negatives
Aminopenicillins, such as (X), have coverage similar to penicillin G with (more/less) coverage for:
X = ampicillin; more
- Enterococcus
- Listeria
- Enterobacteriaceae
T/F: Aminopenicillins have very broad range of coverage for gram positives.
False
T/F: Penicillinase-resistant penicillins have very broad range of coverage for gram positives.
True
Drug of choice for endocarditis prophylaxis (i.e. via enterococcus).
Aminopenicillins (ex: ampicillin)
T/F: Most penicillins must be given by IV or IM to achieve adequate levels.
True (degraded by gastric acid)
T/F: Penicillins distribute well into most tissues, particularly bone/CSF.
False - less so in bone/CSF, though CSF levels are 5-20% of serum levels
Penicillins are mainly excreted (changed/unchanged) via which route?
Unchanged;
Renal (rapid)
Most common adverse effect of penicillins.
Hypersensitivity (3-10%), though anaphylaxis is rare
T/F: There may be cross-reactivity between penicillins and cephalosporins, but not other beta-lactams.
False - can be cross-reactivity between any of those
Beta-Lactamase Inhibitor example.
Clavulanic acid
Cephalosporins have which mechanism of action?
They’re beta-lactams! Similar to penicillins (inhibit PBPs)
(X) is a first-generation cephalosporin that acts primarily on which type of bacteria?
X = cefazolin
Gram-positive aerobes (ex: strep, MSSA)
(X) is a second-generation cephalosporin that acts primarily on which type of bacteria? (Y) is also a second-gen drug, but with additional activity against (Z).
X = cefuroxime
Gram-pos (mainly Strep, less Staph) and Gram-neg aerobes;
Y = cefoxitin
Z = gram-neg anaerobes
Which cephalosporin would you likely use to treat respiratory infections and community acquired pneumonia?
Cefuroxime (second generation)
(X) is a third-generation cephalosporin that acts primarily on which type of bacteria?
X = ceftriaxone Gram pos (mainly Strep, less Staph) and gram neg aerobes (less than fourth gen)
Which cephalosporin would you likely use to treat strep pneumo and gram negative infections?
Gen 3 (ceftriaxone)
Which cephalosporin would you likely use to treat hospital-acquired Pseudomonas?
Gen 4 (cefepime)
T/F: Gen 4 cephalosporins have no gram-positive acitivty.
False - similar to Gen 1 activity
T/F: Cephalosporins have no activity against anaerobes.
False - Cefoxitin(a gen 2) does against gram-neg anaerobes
Aside from (X), the pharmacokinetics of cephalosporins are similar to (Y) drugs.
X = ceftriaxone (longer half-life and biliary excretion) Y = penicillins
T/F: Cephalosporins have adverse effects/toxicity overall similar to penicillins.
True
Carbapenems have which mechanism of action?
They’re beta-lactams! Similar to penicillins (inhibit PBPs)
Carbapenems: (X) is combined with (Y) to prevent:
X = imipenem Y = cilastatin
Imipenem brakdown to nephrotoxic product
List the three mechanisms that pathogens use for antimicrobial resistance.
- Efflux of drug
- Alteration of drug
- Degradation of drug
(X) are broad-spectrum agents, generally reserved for documented resistance activity. These agents work on gram (pos/neg) (aerobes/anaerobes).
X = carbapenems
Gram pos and neg aerobes and anaerobes
Most common adverse effect of carbapenems are:
GI disturbances
T/F: Vancomycin is a beta-lactam that’s bactericidal and time-dependent.
Partly false - it’s a glycopeptide (not beta-lactam)
Spectrum of vancomycin is gram (pos/neg) (aerobes/anaerobes).
Gram pos aerobes and anaerobes (including MRSA)
Vancomycin primarily used for which two scenarios?
- MRSA
2. Pt with anaphylaxis to beta-lactams
“Red man syndrome” can be seen with infusion of (X) drug too rapidly.
X = vancomycin
List the classes of antibiotics that target protein synthesis.
- Aminoglycosides
- Tetracyclines
- Macrolides
- Clindamycin
Aminoglycosides, such as (X), have which mechanism of action?
X = gentamicin
Bind (irreversibly) to 30S ribosome (causing misreading)
Gentamicin activity is (bactericidal/bacteriostatic) and (time/conc)-dependent. Its spectrum of activity mainly includes gram (pos/neg) (aerobes/anaerobes).
Bactericidal;
Conc-dependent
Gram neg (and limited gram pos) aerobes
Distribution of gentamicin is primarily into which body compartment?
Extracellular (highly polar); no CNS penetration
Adverse effects of gentamicin.
- Nephrotoxicity (reversible)
2. Ototoxicity (auditory/vestibular; irreversible)
Tetracyclines, such as (X), have which mechanism of action?
X = doxycycline
Bind (reversibly) to 30S ribosome (causing misreading)
Doxycycline activity is (bactericidal/bacteriostatic) and (time/conc)-dependent.
Bacteriostatic;
Time-dependent
Gentamicin works (intra/extra)-cellularly. It is transported via which mechanisms?
Intracellularly (on 30S ribosome)
- Porin channels (passive)
- Active transport (oxygen dependent)
Gentamicin is less effective in (aerobic/anaerobic) and (acidic/basic) conditions. Why?
Anaerobic, acidic;
Decreased transport (which is oxygen-dependent)
(X) drugs are often used in combo with others (in sick, high-risk patients), while waiting for tests to ID illness.
X = Gentamicin (aminoglycosides)
For optimal bactericidal effects, Gentamicin must have Cmax: MIC ratio of:
10:1 (conc-dependent)
Doxycycline has generally broad spectrum of gram (pos/neg) coverage, but (resistance/adverse effects) pose issues.
Both (pos and neg aerobes and anaerobes);
Both acquired resistance and adverse effects are problematic
Oral absorption of doxycyline is (fair/poor) and it distributes into (most/only select) tissues. How is it eliminated?
Fair (but decreased by simultaneous ingestion of certain minerals);
Most;
Undergoes glucoronidation, then excreted in urine and bile
Doxycycline is contraindcated in which patient population? Why?
Children under 8 due to photosensitivity (rash) and tooth/bone discoloration
Doxycycline most common adverse effect.
GI disturbances
Macrolides, such as (X), have which mechanism of action?
X = azithromycin
Reversibly bind 50S ribosome
Azithromycin is (bactericidal/bacteriostatic) and (time/conc)-dependent. Its coverage is similar to that of (X) drug, but with less gram (Y) coverage.
Depends on dose and organism;
Time-dependent
X = penicillins
Y = anaerobic
T/F: Azithromycin has activity against T. pallidum and chlamydia.
False - only chlamydia
T/F: Azithromycin has activity against H. flu and Legionella.
True
T/F: Azithromycin is used in resp tract infections, such as against mycoplasma.
True
Oral absorption of azithromycin is (fair/poor) and it distributes into (most/only select) tissues. How is it eliminated?
Fair (some food interactions;
Most (except CSF);
Metabolized by liver; excreted in bile and urine
Clindamycin has which mechanism of action?
Binds 50S ribosome and inhibits protein synthesis
Clindamycin is (bactericidal/bacteriostatic) and covers (broad/narrow) range of gram (pos/neg) bacteria.
Bacteriostatic;
Broad (gram pos aerobes and anaerobes)
Clindamycin has (fair/poor) oral absorption and distributes into (most/only select) tissues. It’s excreted (changed/unchanged) in (bile/urine).
Fair;
Most (except CSF);
Changed (inactivated metabolites);
Bile and urine
Most common adverse effect of Clindamycin.
GI tolerability
List the two antibacterial drug classes that act as Nucleic Acid structure inhibitors.
- Quinolones
2. Metronidazole
Generation (1/2/3/4) of quinolones are no longer used.
Gen 1
Anaerobic activity is seen in gen (1/2/3/4) quinolones.
Gen 4
Quinolones have (fair/poor) oral absorption and distributes into (most/only select) tissues. It’s excreted (changed/unchanged) in (bile/urine).
Fair;
Most;
Unchanged in urine
The major “hole” in cephalosporin coverage is (X) bacterial species.
X = ENTEROCOCCUS
Monobactam drugs, such as (X), have similar mechanism to (Y) drugs but with gram (pos/neg) spectrum only.
X = aztreonam
Y = penicillins
Only gram-neg
T/F: Patient with penicillin allergy can be given aztreonam.
True - it’s a monobactam
For (X) class of drugs, think DRUG INTERACTIONS.
X = macrolides
(X) class of drugs covers atypical bacteria in their spectrum.
X = macrolides
Linezolid is (bactericidal/bacteriostatic) and has which mechanism of action?
Bacteriostatic;
Binds 50S ribisome
Linezolid has mainly gram (pos/neg) spectrum of activity. In clinical practice, it’s primarily used against which bacteria?
Gram positive aerobes;
MRSA and VRE infections
Levofloxacin is part of (X) drug class. It’s (bactericidal/bacteriostatic) and (time/conc)-dependent.
X = quinolones
Bactericidal;
Conc-dependent
(X) drugs are considered the “last line of defense” in the community setting.
X = quinolones
Levofloxacin mechanism of action.
Inhibits topoisomerases (enzymes that maintain DNA supercoiling)
T/F: Quinolone oral bioavailability is equal to IV bioavailability.
Essentially true! Excellent oral absorption
T/F: Quinolones prove ineffective in hospital-acquired infections.
False - cover pseudomonas and atypicals
Metronidazole is in (X) class of drugs. It’s (bactericidal/bacteriostatic) and (time/conc)-dependent. What’s the mechanism?
X = nitroimidazole
Bactericidal; conc-dep
Enters cell and is reduced to cytotoxic product
Spectrum of metronidazole is:
ANAEROBES
Gold standard drug for anaerobic infections, especially gram-neg.
Metronidazole (used for “below diaphragm” anaerobes)
Above diaphragm: typically gram (pos/neg) anaerobes. And below diaphragm?
Gram-pos above; gram-neg below
Gold standard #2 drug for anaerobic infections, especially gram-pos.
Clindamycin (used for “above diaphragm” anaerobes)
“Metallic” taste is side effect of which drug?
Metronidazole
