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Name the 6 general Cell Wall Synthesis Inhibitors (two general classes)
- Beta-Lactams: penicillins, cephalosporins, carbapenems, monobactams (all inhibit transpeptidases)
- Others: vancomycin (transglycosylase), fosfomycin (enolpyruvate transferase)
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Name the 9 general Protein Synthesis Inhibitors
- Aminoglycosides: 30S; block initiation complex, misread mRNA template, block A=>P translocation
- Spectinomycin: 30S; similar to aminoglycosides without mRNA misreads
- Tetracyclines/Glycylcyclines: 30S; block aminoacyl-tRNA binding to A site
- Macrolides/Ketolides/Lincosamides: 50S; block A=>P translocation
- Linezolid: 50S; block ribosome initiation complex formation
- Chloramphenicol: 50S; block P=>A transpeptidation
- Streptogramins: 50S; quinupristin/dalfopristin (A=>P translocation/conformational change respectively)
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Name the 4 general Inhibitors of Nucleic Acid Synthesis or Function
- Sulfonamides: cytoplasmic; inhibit dihydropteroate synthetase (purine synth)
- Trimethoprim: cytoplasmic; inhibit dihydrofolate reductase (purine synth)
- Fluoroquinolones: cytoplasmic; inhibit topoisomerases II (G-) and IV (G+)
- Metronidazole: DNA; direct damage via free nitrogen radical
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Name the main bactericidal drugs/classes (7 single agents and 2 combos)
- Beta-Lactams (cell wall synth)
- Vancomycin/Fosfomycin (cell wall synth)
- Aminoglycosides (protein synth 30s)
- Quinupristin-Dalfopristin (protein synth 50s)
- Sulfonamide-Trimethoprim (purine synth)
- Fluoroquinolones (topoisomerase)
- Metronidazole (DNA)
- Isoniazid (anti-mycobacterial)
- Rifampin (anti-mycobacterial)
- Pyrasinamide (anti-mycobacterial)
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Name the 6 main bacteriostatic drugs/classes
- Tetracyclines (protein synth 30s)
- Macrolides (protein synth 50s)
- Clindamycin (protein synth 50s)
- Chloramphenicol (protein synth 50s)
- Linezolid (ribosome formation)
- Sulfonamides (purine synth)
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Define concentration-dependent killing.
Significant increase in bacterial killing as [drug] increases; give high doses once per day for rapid killing.
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Define time-dependent killing.
Do not increase rate of killing as [drug] increases; rate of killing is proportional to time the [drug] remains above Minimum Bactericidal Concentration.
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Define post-antibiotic effect.
When drugs (e.g. aminoglycosides, fluoroquinolones) maintain persistent suppression of growth after [drug] has fallen below Minimum Inhibitory Concentration; often only require one dose per day.
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Define/compare MIC vs MBC.
- MIC: minimum inhibitory concentration; lowest concentration that inhibits growth; related to postantibiotic effect
- MBC: minimum bactericidal concentration; lowest concentration that kills; related to concentration dependent killing and time-dependent killing
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Compare concentration-dependent killing and time-dependent killing.
- Concentration: given in high and fewer (daily) doses to get better kill; includes aminoglycosides, fluoroquinolones, carbapenems
- Time: higher doses not more effective, given in smaller doses over time to maintain regular concentration; includes B-lactams, macrolides, clindamycin, linezolid
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List the 5 classes of β-lactam related drugs, general MOA, efficacy, susceptibility, and resistance.
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
- β-lactamase inhibitors
- All inhibit penicillin-binding proteins, most importantly transpeptidases for final peptidoglycan x-linking, and many can activate autolytic enzymes to further precipitate lysis.
- They exhibit time-dependent killing and are bacteriocidal.
- Susceptibility depends on outer cell membrane and peptidoglycan thickness.
- Natural or acquired (via plasmid); through β-lactamase, mutations in PBPs, decreased permeability, or active efflux.
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List 4 classes of penicillins and their drugs.
- Standards: penicillin G, benzathine penicillin
- Penicillinase resistant: nafcillin, dicloxacillin, methicillin
- Amino: ampicillin, amoxicillin
- Antipseudomonal: piperacillin
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List the 1 β-lactamase inhibitor and some general properties.
Clavulanate: inhibits a wide variety of β-lactamases; given with amino penicillins to extend their spectrum (+amoxicillin = augmentin).
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List 4 classes of cephalosporins and their drugs.
- 1st Gen: cefazolin (IM/IV), cephalexin (oral), 1=L
- 2nd Gen: cefuroxime, cefoxitin, cefotetan (IM/IV)
- 3rd Gen: cefotaxime, ceftriaxone, ceftazidime (IM/IV), 3=T
- 4th Gen: cefepime (IM/IV), 4=P
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List 2 carbapenems.
- Imipenem: hydrolyzed by dehydropeptidase-1 (DHP-1), must be given with cilastatin (DHP1 inhibitor)
- Meropenem: not degraded by DHP1
- Both have broad spectrum against G+, G-, and anaerobes; resistant to most β-lactamases.
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List 1 monobactam and its properties.
Aztreonam: no activity against G+ and anaerobes; resistant to G- β-lactamases; tolerated by penicillin/cephalosporin allergics; used for nosocomial Pseudomonas infections
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List 2 other cell wall inhibitors.
- Vancomycin: no activity against G-; parenteral admin; flushing and hypotension after rapid IV; DOC for MRSA, used for C. difficile enterocolitis, combo with aminoglycosides for Enterococcal endocarditis and ceftriaxone for pneumococcal meningitis
- Fosfomycin: inhibits enolpyruvate transferase (NAG to NAM synth, early step); active against G+ and G-
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List the 6+1 drugs that bind the 30S ribosomal subunit and block initiation complex formation and A=>P translocation.
- Aminoglycosides - bactericidal, concentration-dependent killers with long post-antibiotic effect used primarily against G- aerobes
- Streptomycin: generally less active, but highly effective for Yersinia, Mycobacterium, and Francisella
- Gentamycin: commonly used against G-, combo with β-lactams for synergy
- Tobramycin: esp. active against P. aeruginosa, combos with piperacillin
- Amikacin: highest resistance to aminoglycoside inactivators
- Neomycin: primarily topical, otherwise nephrotoxic
- Paromomycin: good for protozoa (esp. Entamoeba, Cryptosporidium, Taenia)
- Spectinomycin: does not cause mRNA misreading! Used as alternative N. gonorrhea treatment.
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Name the 3+1 drugs that bind to the 30S subunit and block aminoacyl tRNA binding to the A site.
- Tetracyclines - broad spectrum, especially useful for atypicals, anaerobes, G+ bugs, G- rods, and protozoa; bacteriostatic; resistance can arise easily
- Tetracycline
- Doxycycline
- Demeclocycline
- Glycylcyclines - same as tetracyclines, but bugs exhibit less resistance to tigecycline
- Tigecycline
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Name the 1 drug that binds to the 50S subunit and inhibits transpeptidation.
Chloramphenicol: broad spectrum, but many side effects, toxicities, and drug interactions coupled with widespread resistance; can cause bone marrow suppression and gray-baby syndrome
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Name 3+1 drugs that bind the 50S subunit and inhibit tRNA translocation.
- Macrolides - bacteriostatic, good against G+s, anaerobes, and atypicals; clar- and azithromycin broader and more effective
- Erythromycin: low bioavailability, inhibits CYP450
- Clarithromycin: improved acid stability over erythro
- Azithromycin: also acid stable, doesn't inhibit CYP450
- Clindamycin: lincosamide, not macrolide; Bacteroides fragilis treatment
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Name the drug that binds to the 50S subunit and blocks formation of initiation complex.
Linezolid: bacteriostatic drug with poor activity on G-; reserved for vancomycin and multi-drug resistant bugs (Enterococcus faecium, S. aureus) and nosocomial S. aureus pneumonia
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Name the 2 streptogramins.
- Quinupristin/Dalfopristin - bactericidal combo with long post-antibiotic effect; active against G+ cocci, inactive against G-; used for VRSA and VREF
- Quinupristin: binds 50S to prevent A=>P translocation
- Dalfopristin: binds 50S and induces conformational change
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Name 4 drugs that block topoisomerase II and IV.
- Fluoroquinolones - concentration-dependent bactericidals with post-antibiotic effect; resistance is uncommon
- Ciprofloxacin: potent against Pseudomonas, DOC for anthrax
- Ofloxacin: chlamydial urethritis/cervicitis
- Levofloxacin: community acquired pneumonias
- Moxifloxacin: good for anaerobes; poor activity against Pseudomonas
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Name 3 drugs that block dihydropteroate synthetase.
- Sulfonamides - bacteriostatic; prevents PABA -> dihydropteroate, inhibiting purine synth
- Sulfamethoxazole: often combined with trimethoprim (aka bactrim or cotrimoxazole, TMP-SMZ)
- Sulfadiazine: topical, active against bacteria and fungi
- Sulfasalazine: ulcerative colitis and rheumatoid arthritis
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Name the drug that blocks dihydrofolate reductase.
Trimethoprim: prevents purine synth; bacteriostatic, much more potent than sulfonamides; cidal when combo'd 1T:5S with sulfamethoxazole
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Name the drug that causes DNA damage through nitrogenous free radical formation.
Metronidazole: cidal prodrug converted by anaerobics that donate electrons from ferredoxins; teratogenic
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Name 2 urinary antiseptics.
- Methenamine: converted to formaldehyde at urine pH ( < 5.5); cannot use with sulfonamides
- Nitrofurantoin: intermediates formed by susceptible bacs that damage DNA, rapidly excreted in urine
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