Antimicrobials Flashcards
Penicillin G (IM/IV), V (oral) mechanism
Binds transpeptidases –> blocks cross-linking of peptidoglycans (cell wall)
- Also activates autolytic enzymes
- Penicillinase sensitive
**Prototype B-lactam antibiotics
Penicillin G, V use
Gram + cocci, rods, gram neg cocci, spirochetes
- Mostly: S. pneumo, S. pyogenes, Actinomyces
Tox: hypersensitivity rxn, hemolytic anemia
Resistant: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)
Amoxicillin, Ampicillin mechanism
Amox (oral), amp (IV)
- Binds transpeptidase, blocks cross link of peptidoglycans
- Combines with clavulanic acid to protect from B-lactamase
Amoxicillin, Ampicillin use
Extended-spectrum penicillin "Amp/amox HELPSS kill enterococci" - H. influenza - E. coli - Listeria - Proteus - Salmonella - Shigella - Enterococci
Tox: hypersensitivity rxn, rash, C. diff
Resistance: penicillinase in bacteria (B-lactamase, cleaves B-lactam ring)
Oxacillin, nafcillin, dicloxacillin mechanism
- Binds transpeptidase, blocks cross link of peptidoglycans
- Penicillinase-resistant penicillins (bulky R group blocks B-lactamase from binding B-lactam ring)
- Narrow spectrum
Oxacillin, nafcillin, dicloxacillin use
S. aureus (except MRSA)
- “Naf for staph”
Tox: hypersensitivity rxn, interstitial nephritis
Ticarcillin, piperacillin mechanism
Antipseudomonals
- Binds transpeptidase, blocks cross link of peptidoglycans
Ticarcillin, piperacillin use
Pseudomonas spp + gram-neg rods
- Susceptible to B-lactamase, use w/ B-lactamase inhibitors
Tox: hypersensitivity rxn
B-lactamase inhibitors
CAST
- Clavulanic Acid
- Sulbactam
- Tazobactam
*Add to penicillin abx to protect from destruction from B-lactamase
Cephalosporins (Gen I-V) mechanism
B-lactam drugs that inhibit cell wall synthesis
*Less sensitive to penicillinases
Those NOT covered are LAME:
- Listeria
- Atypicals (chlamydia/mycoplasma)
- MRSA (except 5th gen = ceftaroline)
- Enterococci
1st generation cephalosporins
Cefazolin, cephalexin
- Gram + cocci and PEcK (Proteus, E. coli, Klebsiella)
- Use prior to surgery to prevent wound infections (S. aureus)
2nd generations cephalosporins
Cefoxitin, cefaclor, cefuroxime
- Gram + cocci and HEN PEcKS - (H. influneza, Enterobacter, Neisseria, Proteas, E. coli, Klebsiella, Serratia)
3rd generation cephalosporins
Ceftriaxone, cefotaxime, ceftazidime
- Serious gram neg resistant to other B-lactams
- Ceftriaxone = meningitis/gonorrhea
- Ceftazidime = pseudomonas
4th generation
Cefepime
- Incr activity against pseudomonas + gram pos
5th generation
Ceftaroline
- Broad spectrum gram pos and gram neg organisms
- Includes MRSA, not pseudomonas
Azotrenam mechanism
Monobactam, resistant to B-lactamases
- Prevents peptidoglycan cross-linking by binding pencillin-binding protein 3
- Synergistic with aminoglycosides
Azotrenam use
Gram neg rods only (none for gram +)
- Good for those w/ penicillin allergy and renal insuffic (can’t tolerate aminoglycosides)
Tox: GI upset, non-toxic
*No cross-allergenicity w/ penicillins
Carbapenems mechanism
Imipenem, meropenem, ertapenem, doripenem
- Broad spectrum, B-lactamase resistant
- Give with cilastatin (inhib renal dehydropeptidase I) - decr inactivation in renal tubules
Carbapenem use
Gram + cocci, gram neg rods, anaerobes (wide spectrum)
- Significant side effects –> only use for life threatening infections
Tox: GI distress, skin rash, CNS tox (sz) at high plasma levels
*Mirapenem = decr sz risk, stable to dehydropeptidase I
Vancomycin mechanism
Inhibits cell wall peptidoglycan formation by binding D-ala portion of cell wall precursors
- This is the main component of gram + cell wall!
- pay back 2 D-alas (dollars) for vandalizing (vanc)*
Vancomycin use
Gram pos only!
- Serious, multi-drug resistant organisms: MRSA, enteroccic, C. diff (oral)
Tox - well tolerated but NOT Really trouble free (Nephrotoxicity, Ototoxicity, Thrombophlebitis), diffuse flushing (Red man syndrome; pre-tx with antihistamine/slow infusion)
Resist: bacteria with D-ala D-ala –> D-ala D-lac modification
Inhibitors of cell wall synthesis
- Penicillin-sensitive penicillins: Pen G/V, amox, ampicillin
- Penicillin-resistant penicillins: oxacillin, nafcillin, dicloxacillin
- Antipseudomonas: ticarcillin, piperacillin
- Cephalosporins: 1 (cephazolin, cephelexin), 2 (cefoxitin), 3 (ceftriaxone), 4 (cefepime), 5 (ceftaroline)
- Carbapenems: imipenem, meripenem, (ertapenem/doripenem = new)
- Bind transpeptidase (needed to cross-link peptidoglycans)
- Azotreonam
- Binding pencillin-binding protein 3
- Glycopeptides (vancomycin, bacitracin)
- Binding precursor D-ala D-ala
Inhibitors of protein synthesis
Target smaller bacterial ribosome (70S made of 30S and 50S subunits) –> leaves human ribosome unaffected (80S)
30S inhibitors:
- A = aminoglycosides
- T = tetracyclines (bacteriostatic) –> block A-site tRNA binding (block aminoacyl-tRNA attachment)
50S inhibitors:
- C = chloramphenicol, clindamycin (bacteriostatic) –> peptidyl transferase
- E = erythromycin (macrolides); (bacteriostatic) –> translocation
- L = Linezolid (variable) –> block 50S
**“buy AT 30, CCEL (sell) at 50”
Aminoglycosides mechanism
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin (GNATs)
- Bactericidal –> binds 30S, inhibits initiation complex formation
- *Needs O2 for uptake (doesnt work against anerobes)
Aminoglycosides use
Severe gram neg rod infections
- Synergistic with B-lactam antibiotics
- Give neomycin for bowel surgery
Tox: NNOT - nephrotocixity (w/ cephalosporins), neuromusc blockade, ototoxicity (w/ loop diuretics), teratogen
**“Mean (aminoglycosides) GNATS caNNOT kill anaerobes”
Resist: bacterial transferase enzymes inactivate drug by acetylation, phosphorylation or adenylation
Tetracyclines mechanism
Tetracycline, doxycycline, minocycline
- Bacteriostatic –> binds 30S, prevent attachment of aminoacyl-tRNA
- Doxy elimated fecally (can use in renal pts)
- Don’t take milk, antacids or iron bc divalent cations inhibit gut absorption of tetracyclines
Tetracyclines use
- Borrelia burgforderi, M. pneumoniae,
- Rickettsia, chlamydia (good bc drug accum intracellularly, very effective)
- Acne
Tox: GI distress, discolored teeth/bone in growing kids/fetus (contranind in pregn), photosensitivity
Resist: decr uptake/incr efflux out of bacterial cells by plasmid-encoded transport pumps
Macrolides mechanism
Azithromycin, clarithromycin, erythromycin
- Block translocation (“macroSlides”) bc binding 23S rRNA of 50S
Macrolides use
- Atypical pneumonias (mycoplasma, chlamydia, legionella)
- STDs (chlamydia)
- Gram + cocci (strep infections if allergic to penicillins)
Tox: MACRO
- gastric Motility issues
- Arrhythmia from prolonged QT
- acute Cholestatic hepatitis
- Rash
- eOsinophilia
- Incr serum conc of theophyllines, oral anticoags
Resist: binding 23S rRNA binding site (drug can’t bind)
Chloramphenicol mechanism
Blocks peptidyltransferase at 50S –> this blocks transfer from A to P on ribosome
Chloramphenicol use
Meningitis (H. flu, Neisseria, S. pneumoniae), Rocky mountain spotted fever (rickettsia)
Tox: anemia (dose dependent, reversible), aplastic anemia (dose dep, irreversible), gray baby syndrome (premies bc lack liver UDP-glucuronyl transferase)
Resist: plasma-encoded acetyltransferase inactivates drug
Clindamycin mechanism
Blocks translocation (peptide transfer) at 50S
Clindamycin use
- Anaerobic infections (bacteriodes, clostridium) in aspiration pneumo, lung abscesses, oral infections
- Invasive group A strep
- *Treats anaerobes ABOVE diaphragm (metronidazole below)
Tox: C. diff, fever, diarrhea
Inhibitors of folic acid synthesis
- Sulfonamides - block dihydropteroate synthase
- Trimethoprim - block dihydrofolate reductase
Need this pathway to make DNA/RNA, proteins
Sulfonamides mechanism
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
- Inhibit folate syntheis (PABA to DHT): PABA antimetabolites inhibit dihydropteroate synthase
Sulfonamides use
Gram +, gram neg, Nocardia, Chlamydia
- Simple UTI - triple sulfa or SMX
Tox: hypersensitivity rxn, hemolysis if G6DP defic, nephrotoxic (tubulointerstitial nephritis), photosensitive, kernicterus in infants
Resist: altered enzyme (dihydropteroate synthase), decr uptake or incr PABA synthesis