Antibacterials Flashcards
B-lactams MOA:
Inhibit PBPs, which catalyze cell wall crosslinks. Competitive and irreversible.
B-lactams MOR:
- B-lactamase (most prevalent).
2. Altered PBP (MRSA).
B-lactams SEs:
Allergic reactions: Anaphylaxis, rash.
Diarrhea, enterocolitis.
Seizures (rare).
Penicillin G and V:
- GM+ anaerobes (B-lactamase negative Strep).
- Syphilis
- Neisseria meningitidis (behind Ceftriaxone).
Oxacillin:
- B-lactamase-producing staphylococci.
- MSSA
Amoxicillin:
- B-lactamase-negative GM+ (Streptococcus, listeria).
- GM- (Haemophilus)
- First-line treatment for otitis media.
Ampicillin:
-Same as amoxicillin, plus treats meningitis (Neisseria, Listeria), GI infections.
Ticarcillin:
- Broad GM- effectiveness, including pseudomonas aeruginosa.
- Often used with a B-lactamase inhibitor to hit anaerobes.
Piperacillin:
- Broad GM- effectiveness, including pseudomonas and klebsiella (ticarcillin-resistant)
- Often used with a B-lactamase inhibitor.
2 B-lactamase inhibitors:
- Clavulanic acid.
2. Tazobactam
Cephalosporins spectrum of activity:
1st generation: best for GM+
2nd generation: more GM- activity.
3rd generation: best for GM -
Cefazolin:
- 1G
- GM+
- Surgical prophylaxis against skin flora.
Cephalexin:
- 1G
- Oral form of Cefazolin.
Cefuroxime:
- Only 2nd gen to penetrate CSF.
- Best of 2nd gen against Haemophilus.
Cefoxitin:
- 2G
- Cefuroxime plus added benefits against anaerobes such as Bacteroides.
Ceftriaxone:
- 3G
- 1st line against gonorrhea, meningitis (Neisseria).
Ceftazidime:
- 3G
- Active against Pseudomonas.
Cefepime:
- 4G
- Similar spectrum to Ceftazidime, except more resistant to type I B-lactamases.
- Empirical treatment of serious inpatient infections.
Imipenem use and side effects:
-Broad-spectrum.
-Resistant to many B-lactamases, including ESBLs.
-Not effective against MRSA.
-Give with cilastatin, a renal peptidase inhibitor.
-Use if mixed or ill-defined infection, those not responsive to other drugs.
Side effects: Hypersensitivity, seizures, dizziness, confusion, GI effects.
Aztreonam:
-Used against GM- aerobic rods.
-Resistant to many B-lactamases.
-Can be used in those with known hypersensitivities to penicillins.
Side effects: seizures, GI effects, anaphylaxis, transient EKG changes.
Vancomycin MOA:
MOA: Inhibits cell-wall synthesis: by interfering with cross-linking and elongation of the peptidoglycan chains.
Vancomycin uses:
GM+ ONLY.
- First line against HA-MRSA.
- Severe C diff infections (behind metronidazole).
Vancomycin SEs:
- “Red neck” syndrome.
- Nephrotoxicity.
- Phlebitis.
- Ototoxicity.
Fosfomycin MOA:
Inactivates enolpyruvyl transferase, an early stage cell wall synthesis enzyme.
Fosfomycin uses:
-Uncomplicated UTIs caused by E. coli, enterococcus.
Bacitracin MOA:
Interferes with lipid carrier that exports early cell wall components through the cell membrane.
Bacitracin uses:
Topical agent against GM+
Polymyxins MOA:
Cationic detergents that bind LPS in the outer membrane of GM-
Polymyxin B:
Topical agent against GM-, pseudomonas.
Daptomycin MOA:
Binds to bacterial cytoplasmic membrane, causing rapid membrane depolarization.
Daptomycin uses:
-Complicated skin infections (Staph. Aureus, streptococcus, enterococcus).
Quinolones MOA & MOR:
MOA: Inhibits bacterial DNA gyrase, thus interfering with replication and repair.
MOR: 1. Altered DNA gyrase.
- Decreased permeability.
- Combo of the two.
Quinolones misc:
AUC killers.
Quinolones SEs and contraindications:
- Contraindicated in those with seizure disorders, pregnancy, children.
- EKG irregularities.
- Athropathy, tendon rupture.
Name the quinolones:
- Norfloxacin
- Ciprofloxacin
- Moxifloxacin
Norfloxacin:
UTIs (achieve therapeutic concentrations only in the UG region).
Ciprofloxacin:
UTIs, infectious diarrhea, skin infections, bone and joint infections, chlamydia.
Moxifloxacin:
- Better GM+ spectrum than most quinolones.
- Respiratory infections (NOT strep throat).
- CA pneumonia, bacterial bronchitis.
Nitrofurantoin MOA, use, SEs:
MOA: Nitroreductase enzyme converts drug to reactive compounds which can damage DNA.
Use: Lower UTIs.
SEs: -Peripheral neuropathy.
- Pulmonary fibrosis in elderly.
- GI upset.
Rifampin MOA:
Inhibitor of RNAP, thereby inhibiting RNA synthesis.
Rifampin uses:
- Primarily for treatment of pulmonary TB.
- Prophylaxis of meningococcal meningitis, haemophilus influenza.
- Part of combination therapy for leprosy.
Rifampin SEs:
- Orange urine, tears, sweat.
- Strongly induces CYP3A.
Fidaxomicin uses:
- 3rd line for C diff (behind metronidazole, vancomycin).
- Only hits clostridium, so useful for allowing patient to restore normal gut flora.
- Less recurrence of C diff than vanco and metronidazole.
Fidaxomicin MOA:
Inhibitor of RNAP, thereby inhibiting RNA synthesis.
Metronidazole uses:
- C diff enterocolitis.
- Combination therapy for H. pylori.
- Gardnerella vaginalis.
Metronidazole MOA:
Anaerobes reduce the nitro group, resulting product disrupts DNA.
Metronidazole SEs:
- Long-term treatment: leukopenia, neutropenia.
- Bacterial and fungal superinfections (Candida).
Aminoglycosides MOA:
Transported into bacteria by an energy-requiring aerobic process. Binds to several ribosomal sites, stopping initiation, causes premature release of ribosome from mRNA, and mRNA misreading.
Aminoglycosides uses:
- More effective against GM- than GM+, but when using against GM+, use with quinolone or cell wall inhibitor.
- Use only against serious infections because of toxicity.
Aminoglycosides misc:
- Concentration-dependent killing.
- -Post-antibiotic effect: sustained activity for several hours after aminoglycoside concentration has dropped below effective levels. Allows for less frequent dosing.
- -Do not mix B-lactams with aminoglycosides in vitro – will inactivate the drug.
Name the aminoglycosides:
- Gentamicin
- Tobramicin
- Amikacin (most broad spec)
Name the tetracyclines:
- Minocycline
2. Doxycycline
Tetracyclines MOA:
Blocks protein synthesis by binding to the 30S ribosomal subunit, preventing attachment of aminoacyl-tRNA to the acceptor site.
Tetracyclines MOR:
- Efflux pumps.
Cross-resistance.
Tetracyclines uses:
- Preferred agents for rickettsia, chlamydia, Mycoplasma, Ureaplasma, Borrelia.
- Ca++ inhibits absorption.
Tigecycline MOA:
Same as the tetracyclines, but binds additional sites on ribosomes.
Tigecycline uses:
- Used against many GM+, including MRSA.
- A few GM-, but NOT pseudomonas.
Chloramphenicol MOA:
Blocks protein synthesis: Inteferes with binding of aminoacyl-tRNA to 50S subunit, and inhibits peptide bond formation.
Chloramphenicol uses:
Broad spec – only use in serious cases.
-Alternative agent for meningitis, brain abscesses.
Chloramphenicol SEs:
- Bone marrow depression, can progress to a fatal aplastic anemia.
- Grey baby syndrome.
- Optic neuritis.
Macrolides MOA:
Block protein synthesis by binding to the 50S ribosomal subunit, blocking the translocation step.
Macrolides SEs:
-Increases risk of arrhythmias and cardiac arrest (QT prolongation).
Erythromycin uses:
- Enhances GI motility.
- Primarily against GM+ (Staph and Strep)
- Also against Chlamydia, mycoplasma, bordetella, campylobacter.
- Interferes with CYP3A metabolism of other drugs.
Clarithromycin:
- Better kinetics than erythromycin (less frequent dosing).
- Less GI motility.
- Somewhat wider spectrum.
- Uses are same as erythromycin
- Also part of combination therapy for H pylori.
- Also used for MAC treatment, prophylaxis.
Azithromycin:
- Respiratory infections.
- Gonorrhea (ceftriaxone + azithromycin or doxycycline).
Clindamycin MOA:
Same as macrolides, but not a macrolide.
Clindamycin uses:
- Inhibits most GM+ cocci, and many anaerobes, incl. Bacteroides fragilis.
- Suppresses bacterial toxin production (Strep and Staph).
Linezolid MOA:
Blocks protein synthesis by binding to the 50S ribosomal subunit, interfering with the formation of 70S initiation complex.
Linezolid uses:
- 1st line against CA-MRSA.
- VRE
- Staph
- Strep
Linezolid SEs:
- Bone marrow depression.
- Non-selective inhibitor of MAO (avoid foods with tyramine).
Sulfonamides MOA:
Inhibit folate synthesis in bacteria by competitive inhibition of dihydropteroate synthase.
Sulfonamides SEs:
- Renal damage from crystalluria.
- Inhibit CYP2C9 – potentiates action of other drugs (Warfarin).
TMP/SMX:
UTIs, bacillary dysentery, typhoid fever.
Silver sulfadiazine:
Use on burn wounds.
Trimethoprim uses:
Given in conjunction with sulfamethoxazole – combined effects are bactericidal.
Used for UTIs, URIs and otitis media.
-Also for Pneumocystis jiroveci.
Trimethoprim MOA:
Inhibit folate synthesis in bacteria by competitively inhibiting dihydrofolate reductase.
Trimethoprim SEs:
Bone marrow suppression.
