Microbiology - Antimicrobials (1) Flashcards
1
Q
Antimicrobial therapy (179)
A
2
Q
Penicillin G, V
- Examples
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Examples
- Penicillin G (IV and IM form), penicillin V (oral).
- Prototype β-lactam antibiotics.
- Mechanism
- Bind penicillin-binding proteins (transpeptidases).
- Block transpeptidase cross-linking of peptidoglycan.
- Activate autolytic enzymes.
- Clinical use
- Mostly used for gram-positive organisms (S. pneumoniae, S. pyogenes, Actinomyces).
- Also used for N. meningitidis and T. pallidum.
- Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes.
- Penicillinase sensitive.
- Toxicity
- Hypersensitivity reactions, hemolytic anemia.
- Mechanism of resistance
- Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.
3
Q
Ampicillin, amoxicillin (aminopenicillins, penicillinase-sensitive penicillins)
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Mechanism
- Same as penicillin.
- Bind penicillin-binding proteins (transpeptidases).
- Block transpeptidase cross-linking of peptidoglycan.
- Activate autolytic enzymes.
- Wider spectrum
- Penicillinase sensitive.
- Also combine with clavulanic acid to protect against β-lactamase.
- AMinoPenicillins are AMPed-up penicillin.
- AmOxicillin has greater Oral bioavailability than ampicillin.
- Same as penicillin.
- Clinical use
- Extended-spectrum penicillin—Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
- Coverage: ampicillin/amoxicillin HELPSS kill enterococci.
- Toxicity
- Hypersensitivity reactions; rash; pseudomembranous colitis.
- Mechanism of resistance
- Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.
4
Q
Oxacillin, nafcillin, dicloxacillin (penicillinase-resistant penicillins)
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Same as penicillin.
- Bind penicillin-binding proteins (transpeptidases).
- Block transpeptidase cross-linking of peptidoglycan.
- Activate autolytic enzymes.
- Narrow spectrum
- Penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.
- Same as penicillin.
- Clinical use
- S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).
- “Use naf (nafcillin) for staph.”
- Toxicity
- Hypersensitivity reactions, interstitial nephritis.
5
Q
Ticarcillin, piperacillin (antipseudomonals)
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Same as penicillin.
- Bind penicillin-binding proteins (transpeptidases).
- Block transpeptidase cross-linking of peptidoglycan.
- Activate autolytic enzymes.
- Extended spectrum.
- Same as penicillin.
- Clinical use
- Pseudomonas spp. and gram-negative rods
- Susceptible to penicillinase
- Use with β-lactamase inhibitors.
- Toxicity
- Hypersensitivity reactions.
6
Q
β-lactamase inhibitors
A
-
CAST
- Clavulanic Acid
- Sulbactam
- Tazobactam
- Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).
7
Q
Cephalosporins (generations I, II, III, IV, V)
- Mechanism
- Organisms typically not covered by cephalosporins
- Clinical use
- 1st generation
- 2nd generation
- 3rd generation
- 4th generation
- 5th generation
- Toxicity
A
- Mechanism
- β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.
- Bactericidal.
- Organisms typically not covered by cephalosporins
- LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
- Exception: ceftaroline covers MRSA.
- Clinical use
- 1st generation (cefazolin, cephalexin)
- Gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae.
- PEc_K_.
- Cefazolin used prior to surgery to prevent S. aureus wound infections.
- Gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae.
- 2nd generation (cefoxitin, cefaclor, cefuroxime)
- Gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
- HEN PEc_KS_.
- Gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
- 3rd generation (ceftriaxone, cefotaxime, ceftazidime)
- Serious gram-negative infections resistant to other β-lactams.
- Ceftriaxone—meningitis and gonorrhea.
- Ceftazidime—Pseudomonas.
- 4th generation (cefepime)
- Increase activity against Pseudomonas and gram-positive organisms.
- 5th generation (ceftaroline)
- Broad gram-positive and gram-negative organism coverage, including MRSA
- Does not cover Pseudomonas.
- 1st generation (cefazolin, cephalexin)
- Toxicity
- Hypersensitivity reactions, vitamin K deficiency.
- Low cross-reactivity with penicillins.
- Increased nephrotoxicity of aminoglycosides.
8
Q
Aztreonam
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- A monobactam
- Resistant to β-lactamases.
- Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3.
- Synergistic with aminoglycosides.
- No cross-allergenicity with penicillins.
- Clinical use
- Gram-negative rods only—no activity against gram-positives or anaerobes.
- For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.
- Toxicity
- Usually nontoxic; occasional GI upset.
9
Q
Carbapenems
- Examples
- Mechanism
- Clinical use
- Toxicity
A
- Examples
- Imipenem, meropenem, ertapenem, doripenem.
- Mechanism
- Imipenem
- A broad-spectrum, β-lactamase– resistant carbapenem.
- Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules.
- With imipenem, “the kill is lastin’ with cilastatin.”
- Newer carbapenems include ertapenem (limited Pseudomonas coverage) and doripenem.
- Imipenem
- Clinical use
- Gram-positive cocci, gram-negative rods, and anaerobes.
- Wide spectrum, but significant side effects limit use to life-threatening infections or after other drugs have failed.
- Meropenem has a decreased risk of seizures and is stable to dehydropeptidase I.
- Toxicity
- GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
10
Q
Vancomycin
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Mechanism
- Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors.
- Bactericidal.
- Clinical use
- Gram positive only—serious, multidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis).
- Toxicity
- Well tolerated in general—but NOT trouble free.
- Nephrotoxicity, Ototoxicity, Thrombophlebitis
- Diffuse flushing—red man syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate).
- Well tolerated in general—but NOT trouble free.
- Mechanism of resistance
- Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.
- “Pay back 2 D-alas (dollars) for vandalizing (vancomycin).”
11
Q
Protein synthesis inhibitors
- General
- 30S inhibitors
- 50S inhibitors
A
- General
- Specifically target smaller bacterial ribosome (70S, made of 30S and 50S subunits), leaving human ribosome (80S) unaffected.
- “Buy AT 30, CCEL (sell) at 50.”
-
30S inhibitors
- A = Aminoglycosides [bactericidal]
- T = Tetracyclines [bacteriostatic]
-
50S inhibitors
- C = Chloramphenicol, Clindamycin [bacteriostatic]
- E = Erythromycin (macrolides) [bacteriostatic]
- L = Linezolid [variable]
12
Q
Aminoglycosides
- Examples
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Examples
- Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin.
- “Mean” (aminoglycoside) GNATS caNNOT** kill anaerobes.**
- Mechanism
- Bactericidal
- Inhibit formation of initiation complex and cause misreading of mRNA.
- Also block translocation.
- Require O2 for uptake; therefore ineffective against anaerobes.
- A “initiates” the Alphabet.
- Clinical use
- Severe gram-negative rod infections.
- Synergistic with β-lactam antibiotics.
- Neomycin for bowel surgery.
- Toxicity
- Nephrotoxicity (especially when used with cephalosporins)
- Neuromuscular blockade
- Ototoxicity (especially when used with loop diuretics)
- Teratogen
- “Mean” (aminoglycoside) GNATS caNNOT** kill anaerobes.**
- Mechanism of resistance
- Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
13
Q
Tetracyclines
- Examples
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Examples
- Tetracycline, doxycycline, minocycline.
- Mechanism
- Bacteriostatic
- Bind to 30S and prevent attachment of aminoacyl-tRNA
- Limited CNS penetration.
- Doxycycline is fecally eliminated and can be used in patients with renal failure.
- Do not take with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because divalent cations inhibit its absorption in the gut.
- Clinical use
- Borrelia burgdorferi, M. pneumoniae.
- Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia.
- Also used to treat acne.
- Toxicity
- GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
- Contraindicated in pregnancy.
- Mechanism of resistance
- Decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.
14
Q
Macrolides
- Examples
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Examples
- Azithromycin, clarithromycin, erythromycin.
- Mechanism
- Inhibit protein synthesis by blocking translocation (“macroslides”)
- Bind to the 23S rRNA of the 50S ribosomal subunit.
- Bacteriostatic.
- Clinical use
- Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram-positive cocci (streptococcal infections in patients allergic to penicillin).
- Toxicity
- MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia.
- Increases serum concentration of theophyllines, oral anticoagulants.
- Mechanism of resistance
- Methylation of 23S rRNA-binding site prevents binding of drug.
15
Q
Chloramphenicol
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Mechanism
- Blocks peptidyltransferase at 50S ribosomal subunit.
- Bacteriostatic.
- Clinical use
- Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain spotted fever (Rickettsia rickettsii).
- Limited use owing to toxicities but often still used in developing countries because of low cost.
- Toxicity
- Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).
- Mechanism of resistance
- Plasmid-encoded acetyltransferase inactivates the drug.
17
Q
Sulfonamides
- Examples
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Examples
- Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine.
- Mechanism
- Inhibit folate synthesis.
- Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase.
- Bacteriostatic.
- Clinical use
- Gram-positive, gram-negative, Nocardia, Chlamydia.
- Triple sulfas or SMX for simple UTI.
- Toxicity
- Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin).
- Mechanism of resistance
- Altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis.
