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Module 7: Multisystem > Antibiotics > Flashcards

Antibiotics Flashcards

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1
Q

What makes an antibiotic bacteriostatic?

A

They inhibit growth reversibly (prevents further replication)

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2
Q

How do bacteria become resistant to tetracyclines?

A
  1. Decreased uptake (often due to mutations in the OmpF porin)
  2. Efflux from the bacterial cell; actively pump drug out of cell before it’s able to bind to 30S ribosomal subunit
  3. Elongation factor-like proteins that protect 30S subunit
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2
Q

What are characteristics of Ketolides?

A

Inhibitors of Translocation

First ketolide approved by FDA: Telithromycin

New family of antimicrobials structurally related to macrolides

Mechanism:
binding within exit tunnel of 50S subunit, thus blocking exit of nascent polypeptides
Strongly binds simultaneously to two domains of subunit (macrolides only bind to one)

Bactericidal or bacteriostatic depending on bacterium

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3
Q

What are the aminopenicillins?

Which is has greater oral availability?

A

Ampicillin

AmOxicillin (greater Oral availability)

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4
Q

Clinical use of Metronidazole

A

GET GAP on the Metro

Giardia
Entamoeba
Trichomonas
Gardnerella
Anaerobes (Bacteriodes, C. diff)
H. Pylori

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4
Q

Side effect of linezolid?

A

Bone Marrow suppression

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5
Q

What are the carbapenems?

A

Imipenem/cilastatin
Meropenem

beta-lactamase resistant

Cilastatin inhibits renal dehydropeptidase I and decreases inactivation of the drug in renal tubules

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5
Q

What’s the toxicity of vancomycin?

A

Well tollerated in general

does NOT have many problems

Nephrotoxicity
Ototoxicity
Thrombophlebitis

Redman syndrome preventable with slow infusion rate and antihistamines

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5
Q

Clinical use of tetracyclines?

A

Borrelia burdorferi
M. pneumonia
Rickettsia
Chlamydia

Demeclocycline- ADH agoinst acts as a Diuretic in SIADH

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6
Q

Penicillin is bactericidal for:

A

Gm+ cocci

Gm+ rods

Gm- cocci

Spirochetes

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6
Q

What is the clinical use of Fluoroquinolones?

A

Gm- rods of urinary and GI tracts

Pseudomonas
Neisseria

some Gm+ organisms

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7
Q

What are characteristics of Lincomycin and Clindamycin?

A

Inhibitors of Peptidyl Transferase:
Narrow Spectrum

Bacteriostatic

Mechanism:
Similar to chloramphenicol

Selective Toxicity:
Very effective for treatment of G+ bacterial infections
Clindamycin: Very effective for staphylococcal and anaerobic G- infections

Resistance:
Methylation of 23S ribosomal RNA which prevents drug binding to 50S subunit

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7
Q

What’s the clinical use of trimethoprim?

A

SMX-TMP used for treating UTIs

Shigella
Salmonella
PCP

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8
Q

What are some beta-lactam antibiotics?

A

Penicillin (G, V)
Methicillin, nafcillin, dicloxacillin (penicillinase-resistant)
Ampicillin, amoxicillin (aminopenicillins)
Ticarcillin, carbenicillin, piperacillin (antipseudomonals)
Cephalosporins
Aztreonam
Carbapenem

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8
Q

What antibiotics cause photosensitivity?

A

Sun Too Quick

Sulfonamides
Tetracyclines
Quinolones

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9
Q

How do bacteria become resistant to beta-lactam antibiotics?

A
  • Inactivation through beta-lactamases
  • Altered PBP (mecA-PBP2a)
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10
Q

What antibiotics target Formation of initiation complexes in bacteria?

A
  1. Linezolid
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11
Q

What are characteristics of Tetracyclines?

A

Inhibitors of recognition:

Broad Spectrum

Bacteriostatic

Hydrophobic

Used to Treat:
Chlamydia, Mycoplasma, Rickettsia (intracellular pathogens)
and certain G+ and G- bacterial infections

Selective Toxicity: high affinity uptake of drugs by acterial cells and increased targeting of 70S

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12
Q

What are the characteristics of Aminoglycosides?

A

Inhibitors of activated tRNA recognition:

Broad Spectrum (G+/-)
Bactericidal
Target specific proteins in the 30S ribosomal subunit

Selective Toxicity: 1. 30S vs 40S subunit
2. actively transported into bacteria, not euks.

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12
Q

What are Positive and Negative aspects of aminoglycoside therapy?

A

Positive: Rapid bactericidal effect
Broad spectrum
effective against Pseudomonas (notoriously antibiotic resistance)

Negative: Resistance
Ototoxicity and nephrotoxicity
Antagonized by anaerobiasis
low pH
ineffective against intracellular bacteria
induce biofilm production

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12
Q

What causes grey baby syndrome?

A

Chloramphenicol

Premature neonates because they lack UDP-glucuronyl transferase, the drug builds up in the fetus, displacing bilirubin.

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12
Q
A
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13
Q

What are the characteristics of aztreonam?

A

monobactam resistant to B-lactamases

Synergistic with Aminoglycosides

No cross allerginicity with penicillins

Can use in patients with renal insufficiency

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14
Q

When do bactericidal drugs have a higher efficacy than bacteriostatic?

A

When the body’s defenses are insufficient to clear the invading agents.

i.e. bacterial endocarditis, bacterial meningitis, and infections in patients with low circulating neutrophils (agranulocytopenia)

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15
What are the clinical uses for 3rd Gen cephalosporins?
CefTriaxone, cefotaxime, ceftazidime Serious Gm- infections resistant to other B-lactams Ceftriaxone-meningitis and gonorrhea Ceftazidime- Pseudomonas
15
Clinical use of chloramphenicol?
Meningitis H. influenzae N. meningitidis S. pneumoniae
16
What are the 3 mechanisms of action of Streptomycin?
1. **Misreading**: at low concentrations, or in case of ribosomes engaged in elongation, we see insertion of incorrect AA 2. **Cyclic Polysomal Blockade**: 70S complex forms but is unstable and falls apart; results in cell death due to inability to make proteins 3. **Faulty outer Membrane Proteins**: Translational misreading results in mutant membrane proteins that cause bacterial membrane to be leaky, thus more drug is taken into cell and acts at 30S subunit
17
What organisms are not covered by Cephalosporins?
LAME Listeria Atypicals (Chlamydia, Mycoplasma) MRSA Enterococci
19
What are the antipseudomonals?
Ticarcillin Carbenicillin Piperacillin TCP: Takes Care of Pseudomonas
20
What is the clinical use of carbapenems?
Broad Spectrum Gm+ cocci Gm- rods Anaerobes GI distress, skin rash, and CNS toxicity (seizures) at high levels limit use of Imipenem to 2nd tier or life threatening infections Meropenem has reduced risk of seizures at high plasma levels and is dihydropeptidase I resistant
21
What's the clinical use of Clindamycin?
Anaerobic infections above the diaphram Bacteroides fragilis Clostridium perfrigens aspiration pneumonia S. aureus osteomyelitis
22
Clinical use of sulfonamindes
Gm+ Gm- Nocardia Chlamydia Triple sulfas or SMX for simple UTI
22
What's the mechanism of Metronidazole?
Forms free radical toxic metabolites in the bacterial cell that damages DNA Bactericidal, antiprotozoal
24
What bacteria are treated with Streptogramins?
Staphylococci Streptococci *Enterococcus faecium* (Restricted for treating vancomycin-resistant forms)
25
What are the clinical uses for 2nd Gen cephalosporins?
cefoxitin, cefaclor, cefuroxime Gm+ cocci HEN PEcKS H. influenzae Enterobacter aerogenes Neisseria spp. Proteus mirabilis E. coli Klebsiella pneumonia Serratia marcescens
26
What's the MOA mechanism of beta-lactam antibiotics?
1. Bind penicillin-binding proteins 2. Block transpeptidase cross-linking of peptidoglycan 3. Activate autolytic enzymes
26
What's the mechanism of Trimethoprim?
inhibits bacterial dihydrofolate reductase Causes megaloblastic anemia, leukopenia, granulocytopenia (may be fixed with folic acid supplementation)
27
What are characteristics of Chloramphenicol?
An inhibitor of Peptidyl transfer: Broad Spectrum Bacteriostatic Mechanism: Binds reversibly to 50S ribosomal subunit and alters the tRNA structure blocking peptidyl transfer Selective Toxicity: Cannot enter mitochondria Does not bind to host 60S subunit Resistance: plasmid-encoded acetyltransferase that catalyze the acetylation of -OH groups; preventing 50S binding
28
What are the characteristics of Linezolid?
- Only clinically significant drug taht inhibits formation of 70S complex - First of new class of antibiotics called **oxazolidinones** - prevents formation of N-formylmethionyl-tRNA-mRNA-70S ribosomal ternary complex **Activity:** Bacteriostatic for Staphylococci and enterococci Bactocidal for Streptococci NOT approved for catheter-related blood stream, catheter-site, or gram(-) infections
30
What are the 4 steps of peptide chain synthesisn and which antibiotics target each step?
1. Recognition: - Aminoglycosides - Spectinomycin - Tetracyclines 2. Peptidyl Transfer: - Chloramphenicol - Lincomycin - Clindamycin 3. Translocation: - Macrolides - Ketolides - Streptogramins 4. Release: - None
32
Clinical use of Aminoglycosides?
Gm- rods Neomycin for bowel surgury
34
What are the penicillinase-resistant penicillins used for clinically?
S. aureus (not MRSA) "Use naf(cillin) for staph"
35
What antibiotics are included in the family of Aminoglycosides?
Streptomycin Kanamycin Tobramycin Gentamycin Neomycin Amikacin Paramomycin
37
Clinical use of Penicillin
Gm+ (Staph pneumoniae, pyogenes; Actinomyces) Treponema pallidum
37
What's the clinical use of vancomycin?
Gm+ only Serious multidrug resistant organisms S. aureus Enterococci C. difficile
38
What are the B-lactamase inhibitors?
CAST Claulanic Acid Sulbactam Tazobectam Added to penicillins to prevent beta-lactamase destruction
39
What is the mechanism of Macrolides?
Not entirely clear, but likely to: 1. Prevent elongation 2. prevent release of empty tRNA 3. blockage of transpeptidation
41
What are the clinical uses for 1st Gen cephalosporins?
Cefazolin, cephalexin Gm+ Cocci PEcK Proteus mirabilis E. coli Klebsiella pneumoniae
42
What antibiotics target the amino acid activation of bacteria?
None - there are NO clinically significant inhibitors of AA activation (possibly due to the fact that prokaryotic and eukaryotic processes are so similar)
44
How do many antibiotics specifically target bacteria, and not humans?
They target bacterial ribosomes and inhibit protein synthesis
45
What makes an antibiotic bactericidal?
They kill microorganisms rapidly
46
What are the sulfonamides?
Sulfamethoxazole (SMX) sulfisoxazole sulfadiazine PABA antimetabolites inhibit dihydropteroate synthetase
47
How do bacteria become resistant to Aminoglycosides?
1. Altered target in 30s ribosomal subunit 2. Decreased cellular uptake 3. Enzymatic modifications of the aminoglycoside (typically by enzymes coded on transposons or plasmids) Gentamicin specifically has: Potential sites for acetylation Potential sites of adenylylation or phosphorylation - both of which alter the antibiotic activity, rendering it useless
48
What is the mechanism of action of Vancomycin?
Binds D-ala, D-ala portion of cell wall precursors inhibiting mucopeptide formation Bacteriocidal
50
What are penicillinase resistant penicillins?
Methicillin Nafcillin Dicloxacillin
52
What are characteristics of Macrolides?
Inhibitors of Translocation: Characterized by macrocyclic lactone structure Medium Spectrum Bacteriostatic Treatment: infections caused by *Mycoplasma, Legionella, Chlamydia,* and *Campylobacter* and G+ bacteria in patients allergic to penicillins Azithromycin and Clarithromyin: certain Mycobacteria
53
Clinical use of Macrolides
Atypical Pneumonias (mycoplasma, chlamydia, legionella) URIs STDs Gm+ cocci Neisseria
54
What are some broad-spectrum antibiotics?
Amoxicillin Carbapenems Piperacillin/tazobactam Fluoroquinolones Streptomycin Tetracycline Chloramphenicol
56
What's the clinical use of Ticarcillin, carbenicillin, and piperacillin?
Pseudomonas spp. Gm- rods Use with beta-lactamase inhibitors
58
What's the clinical use of aminopenicillins?
Ampicillin, Amoxicillin HELPSS kill enterococci Extended spectrum penicillin Haemophilus influenzae E. Coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella enterococci
59
What are characteristics of Streptogramins?
Inhibitors of Translocation: Class of natural cyclic peptide antibiotics produced by certain subspecies of Streptomyces Mechanisms: **Dalfopristin:** binds to 50S subunit; prevents elongation and facilitates binding of quinupristin to 50S **Quinupristin**: premature release of peptide chains from ribosome **Synercid** (quinupristin+dalfopristin) Alone = bacteriostatic Together = bactericidal
61
What are the protein systhesis inhibitors?
Target bacterial ribosome (70S) buy AT 30, CCEL (sell) at 50 Aminoglycosides Tetracyclines Chloramphenicol, Clindamycin Erythromycin Linezolid
62
What are characteristics of Spectinomycin?
Inhibitor of Recognition: Bacteriostatic Causes formation of unstable 70S initiation complexes (does not cause misreading or inhibit polysomal ribosomes) Exclusively for treatment of gonorrhea caused by beta-lactamase-producing gonococci or to treat gonorrhea in patients allergic to penicillins
63
What are two common antibiotics in the Macrolide family?
Azithromycin and Clarithromycin | (modified forms of erythromycin)
64
Antibiotics to avoid in pregnancy:
Clarithromycin-embryotoxic Sulfonamides-kernicterus Aminoglycosides-ototoxic Fluoroquinolones-cartilage damage Metronidazole-mutagenesis Tetracyclines-discolored teeth, bone growth problems Ribavinin-teratogen Griseofulvin-teratogen Chloramphenicol- "gray baby" Countless SAFe Moms Take Really Good Care
65
Toxicity of Sulfa drugs?
hypersensensitivity hemolysis if G6PD nephrotoxicity photosensitivity kernicterus in infants displace drugs from albumin
66
Explain the tenants of selective toxicity
Characteristics of antibiotics that reduce side-effects: - Absence of target from host - permeability differences (effective [antibiotic] is too low to cause side effects in humans) - structural differences in target
67
What bugs is Aztreonam used against?
Gm- rods only no activity against Gm+ or anaerobes
69
What is the mechanism of action for tetracyclines?
Tetrcyclines bind to 30S ribosomal subunit and inhibit bindign of aa-tRNA to the A site
70
What contributes to Macrolide resistance?
1. Methylation of 23S RNA of teh 50S subunit; which prevents binding of drug 2. Hydrolysis of lactone ring by and esterase 3. Efflux of drug
71
That's the mechanism of quinolones?
-floxacins inhibit DNA gyrase (topoisomerase II) Bactericidal

Module 7: Multisystem (15 decks)

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