Antibiotics Flashcards
What makes an antibiotic bacteriostatic?
They inhibit growth reversibly (prevents further replication)
What are characteristics of Ketolides?
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
What are the aminopenicillins?
Which is has greater oral availability?
Ampicillin
AmOxicillin (greater Oral availability)
Side effect of linezolid?
Bone Marrow suppression
Clinical use of tetracyclines?
Borrelia burdorferi
M. pneumonia
Rickettsia
Chlamydia
Demeclocycline- ADH agoinst acts as a Diuretic in SIADH
What is the clinical use of Fluoroquinolones?
Gm- rods of urinary and GI tracts
Pseudomonas
Neisseria
some Gm+ organisms
What’s the clinical use of trimethoprim?
SMX-TMP used for treating UTIs
Shigella
Salmonella
PCP
What antibiotics cause photosensitivity?
Sun Too Quick
Sulfonamides
Tetracyclines
Quinolones
How do bacteria become resistant to beta-lactam antibiotics?
- Inactivation through beta-lactamases
- Altered PBP (mecA-PBP2a)
What antibiotics target Formation of initiation complexes in bacteria?
- Linezolid
What are characteristics of Tetracyclines?
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
What are the characteristics of aztreonam?
monobactam resistant to B-lactamases
Synergistic with Aminoglycosides
No cross allerginicity with penicillins
Can use in patients with renal insufficiency
When do bactericidal drugs have a higher efficacy than bacteriostatic?
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)
Clinical use of chloramphenicol?
Meningitis
H. influenzae
N. meningitidis
S. pneumoniae
What are the 3 mechanisms of action of Streptomycin?
- Misreading: at low concentrations, or in case of ribosomes engaged in elongation, we see insertion of incorrect AA
- Cyclic Polysomal Blockade: 70S complex forms but is unstable and falls apart; results in cell death due to inability to make proteins
- 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
What organisms are not covered by Cephalosporins?
LAME
Listeria
Atypicals (Chlamydia, Mycoplasma)
MRSA
Enterococci
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
What are the antipseudomonals?
Ticarcillin
Carbenicillin
Piperacillin
TCP: Takes Care of Pseudomonas
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
What’s the clinical use of Clindamycin?
Anaerobic infections above the diaphram
Bacteroides fragilis
Clostridium perfrigens
aspiration pneumonia
S. aureus osteomyelitis
What’s the mechanism of Metronidazole?
Forms free radical toxic metabolites in the bacterial cell that damages DNA
Bactericidal, antiprotozoal
Clinical use of sulfonamindes
Gm+
Gm-
Nocardia
Chlamydia
Triple sulfas or SMX for simple UTI
What bacteria are treated with Streptogramins?
Staphylococci
Streptococci
Enterococcus faecium
(Restricted for treating vancomycin-resistant forms)
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
What’s the mechanism of Trimethoprim?
inhibits bacterial dihydrofolate reductase
Causes megaloblastic anemia, leukopenia, granulocytopenia
(may be fixed with folic acid supplementation)
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
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
What’s the MOA mechanism of beta-lactam antibiotics?
- Bind penicillin-binding proteins
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
What are the 4 steps of peptide chain synthesisn and which antibiotics target each step?
- Recognition:
- Aminoglycosides
- Spectinomycin
- Tetracyclines - Peptidyl Transfer:
- Chloramphenicol
- Lincomycin
- Clindamycin - Translocation:
- Macrolides
- Ketolides
- Streptogramins - Release:
- None
What causes grey baby syndrome?
Chloramphenicol
Premature neonates because they lack UDP-glucuronyl transferase, the drug builds up in the fetus, displacing bilirubin.
Clinical use of Aminoglycosides?
Gm- rods
Neomycin for bowel surgury
What are Positive and Negative aspects of aminoglycoside therapy?
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
What are the penicillinase-resistant penicillins used for clinically?
S. aureus
(not MRSA)
“Use naf(cillin) for staph”
What antibiotics are included in the family of Aminoglycosides?
Streptomycin
Kanamycin
Tobramycin
Gentamycin
Neomycin
Amikacin
Paramomycin
What are the characteristics of Aminoglycosides?
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.
What’s the clinical use of vancomycin?
Gm+ only
Serious multidrug resistant organisms
S. aureus
Enterococci
C. difficile
What are the B-lactamase inhibitors?
CAST
Claulanic Acid
Sulbactam
Tazobectam
Added to penicillins to prevent beta-lactamase destruction
What is the mechanism of Macrolides?
Not entirely clear, but likely to:
- Prevent elongation
- prevent release of empty tRNA
- blockage of transpeptidation
Clinical use of Penicillin
Gm+ (Staph pneumoniae, pyogenes; Actinomyces)
Treponema pallidum
What are the clinical uses for 1st Gen cephalosporins?
Cefazolin, cephalexin
Gm+ Cocci
PEcK
Proteus mirabilis
E. coli
Klebsiella pneumoniae
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)
What are some beta-lactam antibiotics?
Penicillin (G, V)
Methicillin, nafcillin, dicloxacillin (penicillinase-resistant)
Ampicillin, amoxicillin (aminopenicillins)
Ticarcillin, carbenicillin, piperacillin (antipseudomonals)
Cephalosporins
Aztreonam
Carbapenem
How do many antibiotics specifically target bacteria, and not humans?
They target bacterial ribosomes and inhibit protein synthesis
What makes an antibiotic bactericidal?
They kill microorganisms rapidly
What are the sulfonamides?
Sulfamethoxazole (SMX)
sulfisoxazole
sulfadiazine
PABA antimetabolites inhibit dihydropteroate synthetase
How do bacteria become resistant to Aminoglycosides?
- Altered target in 30s ribosomal subunit
- Decreased cellular uptake
- 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
What is the mechanism of action of Vancomycin?
Binds D-ala, D-ala portion of cell wall precursors inhibiting mucopeptide formation
Bacteriocidal
What are characteristics of Lincomycin and Clindamycin?
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
What are penicillinase resistant penicillins?
Methicillin
Nafcillin
Dicloxacillin
Penicillin is bactericidal for:
Gm+ cocci
Gm+ rods
Gm- cocci
Spirochetes
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
Clinical use of Macrolides
Atypical Pneumonias (mycoplasma, chlamydia, legionella)
URIs
STDs
Gm+ cocci
Neisseria
What are some broad-spectrum antibiotics?
Amoxicillin
Carbapenems
Piperacillin/tazobactam
Fluoroquinolones
Streptomycin
Tetracycline
Chloramphenicol
What’s the toxicity of vancomycin?
Well tollerated in general
does NOT have many problems
Nephrotoxicity
Ototoxicity
Thrombophlebitis
Redman syndrome preventable with slow infusion rate and antihistamines
What’s the clinical use of Ticarcillin, carbenicillin, and piperacillin?
Pseudomonas spp.
Gm- rods
Use with beta-lactamase inhibitors
What are the carbapenems?
Imipenem/cilastatin
Meropenem
beta-lactamase resistant
Cilastatin inhibits renal dehydropeptidase I and decreases inactivation of the drug in renal tubules
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
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
Clinical use of Metronidazole
GET GAP on the Metro
Giardia
Entamoeba
Trichomonas
Gardnerella
Anaerobes (Bacteriodes, C. diff)
H. Pylori
What are the protein systhesis inhibitors?
Target bacterial ribosome (70S)
buy AT 30, CCEL (sell) at 50
Aminoglycosides
Tetracyclines
Chloramphenicol, Clindamycin
Erythromycin
Linezolid
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
What are two common antibiotics in the Macrolide family?
Azithromycin and Clarithromycin
(modified forms of erythromycin)
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
Toxicity of Sulfa drugs?
hypersensensitivity
hemolysis if G6PD
nephrotoxicity
photosensitivity
kernicterus in infants
displace drugs from albumin
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
What bugs is Aztreonam used against?
Gm- rods only
no activity against Gm+ or anaerobes
How do bacteria become resistant to tetracyclines?
- Decreased uptake (often due to mutations in the OmpF porin)
- Efflux from the bacterial cell; actively pump drug out of cell before it’s able to bind to 30S ribosomal subunit
- Elongation factor-like proteins that protect 30S subunit
What is the mechanism of action for tetracyclines?
Tetrcyclines bind to 30S ribosomal subunit and inhibit bindign of aa-tRNA to the A site
What contributes to Macrolide resistance?
- Methylation of 23S RNA of teh 50S subunit; which prevents binding of drug
- Hydrolysis of lactone ring by and esterase
- Efflux of drug
That’s the mechanism of quinolones?
-floxacins
inhibit DNA gyrase (topoisomerase II)
Bactericidal
