Antibiotics (Sheehy) Flashcards
What is the structure of Penicillins made of?
Thiazolidine Ring Beta Lactam Ring
How Do Penicillins kill bacteria?
Interfere with Transpeptidation Rxn
Inhibit Cell Wall Synthesis
(MUST BE ACTIVELY GROWING)
How are Penicillins rendered inactive?
Beta Lactamases
How are Pencillins able to kill Gram-Negative Bacteria?
They enter them through Porins
What are the (3) methods of Penicillin Resistance?
1) Altering Porin Channels
2) Altering structure of Pencilin Binding Protein
3) Increasing efflux of penicillin out
What is the Original Penicillin?
Penicillin G
What is Penicillin G able to kill?
S. Pneumonia
S Pyogenes
S Viridans
N Meninigitids
Spirochetes (T Pallidum, C. Perferingens)
(BEST AGAINST GRAM POSITIVES, GRAM NEGATIVE COCCI, AND NON-BETA LACTAMASE PRODUCING ANEAROBES)
What is a key adverse effect to taking Penicillins?
Hypersensitivty to Beta Lactam Ring
– life threatening anaphylaxis
– GI Symptoms - N/V/D
What are the Aminopenicillins?
Ampicillin, Amoxicillin
How do we normally make aminopenicillins more effective?
By combining them with Beta Lactamase Inhibitors
(IE: Amoxicilin Clauvulinic Acid) 850-150 mg
What do Aminopenicillins kill?
(What about with Beta Lactamase inhibitors?)
Gram Positives
Some Gram Negatives: E Coli, Enterics (Proteus, Salmonella, Shigella)
[with the combo of beta lactamase inhibitors)
H Influenzae
E Coli
Klebsiella spp
Proteus spp
B Fragilis
What are the drugs of Pencillinase Resistant Pencillins?
Nafcillin, Oxacillin, Dicloxacillin (Methicillin – but not in US)
How are drugs like Nafcillin, Oxacillin, Dicloacillin better than the previous Pencillins?
They have decreased susceptibility to Beta Lactamase
All Pencillins are:
Bactericidal
What do Pencillinase Resistant Pencillins kill?
What are they Resistant too?
S. Aureus
S Epidermidis (have poor gram positive coverage)
Resistant to MRSA and MRSE
What are the Antipseudomonal Penicillins?
Piperacillin (a uriedopenicillin – no carboxypenicilins are in the US)
What are Antipseudomonal Penicillins good for?
Targeting P. Aeurginosa - most effective against dividing bacteria
What is Piperacillin (a Antipseudomonal Penicillin) combined with?
Tazobactam (Beta Lactamase inhibitor)
What does the combo Penicillin Piperacillin/Tazobactam target?
P Aeuroginosa
S Aureus
Enterococcus faecalis
Klebsiella Pneumonia
E Coli
H Influenzae
B Fragilis
Which Penicillin has the broadest spectrum of all Penicillins?
Piperacillin (Antipseudomonal Penicillin)
How do Cephalosporins kill bacteria?
Cell Wall Inhibitor
Inactivate Transpeptidase
Best in Rapidly Proliferating Bacteria
Bactericidal
What is the base structure of Cephalosporins?
7-aminocephalosporanic acid (very similar to penicillin)
Main ways bacteria have evaded Cephalosporins?
Altering Porins
Altering structure of transpeptidase
Increase Efflux Pumps
Beta Lactamases (IE: Klebsiella and E Coli)
What is the general rule of the generations of Cephalosporins?
1st Gen – good against Gram +
3rd Gen – good against Gram -
2nd Gen – Ok against both +/-
What is the main Hypersensitivity for Cephalosporins?
to the Beta Lactam Ring – with a Maculopapular rash that develops several days after therapy.
(accompanied with Eosinophilia and Fever)
What are the 1st Gen Cephalosporins?
Cefazolin
Cephalexin
What are the 1st gen Cephalosporins active against?
(INJUSTICE) . . . actually
S Aurues and most Gram + (VERY GOOD)
Moraxella Catarhallis, K Pneuomonia, E Coli, Proteus Mirabilis (OK)
NOT: MRSA, Enterococci, S Epidermidis, B Fragilis
What are the 2nd Gen Cephalosporins?
(What subclass is also in this group?)
Cefurixome
Cefaclor
Cefprozil
Cefamycins – Cefotetan, Cefoxitin
What do the 2nd Gen Cephalosporins Kill?
Expanded Gram Neg Coverage
– including Klebsiella, H Influenzae, N Meningitidis, S Pneumoniae
NOT: Serratia, B Fragilis
What do the Cephamycins kill?
B Fragilis
Serratia
NOT: H Influenzae
[Cephamycins are resistant to Beta Lactamases]
What do 2nd Gen Cephalosporins NOT cover?
NO Coverage of: Enterococci
Cefotetan (a Cephamycin) has what adverse effect?
Hypoprothrombinemia and bleeding due to the methylthiotetrazole group on its structure
What should you never take with Cefotetan?
Alcohol
What are the 3rd Generation Cephalosporins?
Cefotaxime, Cefixime, Cefdnir, Ceftibuten, Ceftazdime, Ceftriaxone, Cefpodoxime Proxetil, Cefditoren Pivoxil
What are the 3rd Gen Cephalosporins active against?
(JUSTICE) . . . no? too much?
Neisseria spp, Haemophilus spp,
NOT: Enterobacter spp (anything that has consitutive expression of beta lactase)
What is the only 3rd Gen Cephalosporins that is active against P Aeruginosa?
Ceftazidime
What are the 2 prodrugs in the 3rd Ceph family?
Cefpodoxime Proxetil and Cefditoren Pivoxil – hydrolyzed to active forms
Cefixime, Cefpodoxime Proxetil, Cefdinir, Ceftibuten are active against what?
E Coli
H Influenzae
P Mirabilis
S Pyogenes
Ceftriaxone may cause what?
Jaundice in Neonates
Gall Stones (Biliary Pseudolithiasis)
What are the 4th Gen Cephalosporins?
Cefepime
What are the 4th Gen Cephalosporins active against?
. . . . you wanted me to say it. . . .
Enterobacter, Pseudomonas
BAD: B Fragilis
What are the 5th Gen Cephalosporins?
Ceftaroline Fosamil
Ceftolozane (usually with Tazobactam)
The 5th Gen Cephalosporins are good against?
MRSA, Pseudomonas, S. Pneumoniae
NOT: B Fragilis
What are the Carbapenems?
Ertapenem
Meropenem
Doripenem
Imipenem
How do Carbapenems work?
(by working duh . . .)
Inhibiting Transpeptidase, Inhibiting Cell Wall (decreasing cross linking), Resistant to Beta Lactamases
How do Bacteria resist Carbapenems?
by “Carbon” loading them with so much food?!?! (No you silly goose)
Shrink Down Porin Channels
Upreg of Carbapenemases
What are Carbapenems good against?
Gram Neg Bacteria
Imipenem (a Carbapenem) is active against what?
(Its WIDE SPECTRUM) Gram Positives Anaerobes Most Gram Neg Rods (with P Aeruginosa)
IE: Listera, Staphylococci (including MRSA) Enterococci (NOT: Enterococcus Faecium) Streptococci (including Penicillin resistant S Pneumoniae) Enterobacteriacae, Acinetobacter spp, B Fragilis
What Bacteria are resistant to Imipenem (a Carbapenem)?
Stenotrophomonas Maltophillia
Burkholderia Cepacia
Clostridium Difficile
MRSA (some strains)
Enterococcus Faecium
Doripenem and Meropenem (Carbapenems) are more active against what?
Gram Neg
(less active with Gram Positives IE: Enterococcus)
They are also not degraded by Renal Dipeptidase Enzymes
Ertapenem (a Carbapenem) is not active against what?
P Aeruginosa
Acinetobacter spp (less active against Enterococcus)
What are the adverse effects of Imipenem use? (a Carbapenem)
Skin Rash
Diarrhea
Vomiting
Nausea
Renal Failure, Seizures (at high levels of the drug)
What is the structure of the Monobactams?
they have a Monolithic Beta Lactam Ring
What is the Monobactams that we need to know?
Aztreonam
What does Aztreonam (a Monobactam) inhibit?
It inhibits the gram-negative specific subtype of the transpeptidase enzyme –> Bacterial cell wall loses rigidity –> bacteria dies
Is Aztreonam susceptible to Beta Lactamases?
YES! It still has a Beta Lactam ring
What does Aztreonam (Monobactam) have no activity against?
No activity against Gram Positives or Anaerobes
What does Aztreonam have activity against?
(only Gram Negs, and Aerobes) Enterobacteriaceae and P. Aeruginosa, H Influenza (A lot like Ceftazidime – 3rd gen cephalosporin)
What patients can take Aztreonam?
Penicillin Allergic patients (beta lactamase allergic people can take this drug) Sometimes skin rashes occur but not often
What are the main Glycopeptides? What are the main Lipoglycopeptides?
Glyco: Vancomycin
Lipo: Telavancin, Dalbavancin, Oritavancin
How do Glycopeptides and Lipoglycopeptides work?
By being Cell wall synthesis inhibitors
- They bind to D-Alanyl-D-Alanine terminus with high affinity
- they inhibit transglycosylase
– no cross linking of peptidoglycans Lipoglyco- improve on this and dimerize and embed their lipid structures in to the cell wall. (Increases Potency)
What do Oritavancin and Telavancin (Lipoglycopeptides) do specifically?
Disrupt the bacterial membrane allowing them to have a more rapid bactericidal effect
What species are resistant to Glycopeptides?
Enterococci spp (esp – E Faecium) Resistance is on a transposon – so its scary!
Vancomycin (a Glycopeptide) is active against what?
Gram + like: Ampicillin Resistant Enterococci, Penicillin Resistant Streptococci, MRSA
What bacteria are resistant to Vancomycin (a Glycopeptide)
Erysipelothrix, Leuconostoc, Pediococcus, Lactobacillus ALL GRAM NEG Bacilli and Mycobacteria are resistant
Can Lipoglycopeptides and Glycopeptides go through porins?
NO! They are too big to penetrate the outer membrane of Gram Neg
How can Vancomycin be effective systemically?
Give it in an IV, not orally
What are the Key Adverse effects of Lipoglycopeptides and Glycopeptides?
Red Man Syndrome – Hypotension, Tachycardia, and flushing
THIS IS NOT AN ALLERGY – its just a interaction with mast cells
Nephrotoxicity is another more serious issue
What are the Beta Lactamase Inhibitors?
Clauvulinic Acid
Sulbactam
Tazobactam
What do you do with Beta Lactamase Inhibitors?
You pair them with other antibacterial (because they are weak alone) and not all are inhibited by beta lactamases) Very few adverse effects – look to the main drug for problems
Beta Lactamase Inhibitors extend coverage for what main bacteria?
Aminopenicillin attacks on: H Influenzae, E Coli, Klebsiella, Proteus, B Fragilis
What are the Oxazolidinones?
Linezolid
Tedizolid
What do Oxazolidinones act mainly against?
Gram Positive Bacteria
Enterococci, Streptococci, Staphylcocci,
Gram + anaerobic cocci, L Monocytogenes, Corneybacterium spp, Nocardia spp, Good for Resistant strains: MRSA, penicillin resistant S pneumoniae
(POOR COVERAGE of Gram -)
How do Oxazolidinones act against bacteria?
Bind to the P site on the 50S ribosome, and prevent the formation of the fMet tRNA complex. (they are Bacteriostatic, but are Bactericidal against Streptococci)
How do bacteria become resistant to Oxazolidinones?
Point mutations on the 23S rRNA (takes mutations on two or more 23S rRNAs) A Methyltransferase that can modify the Ribosome and alter binding (this is transferable between bacteria – BAD)
What are the 3 different categories of Adverse effects of Oxazolidinones?
Myelosuppression
Mitochondrial Toxicity
Drug-Drug Interactions
Explain Myelosuppression of Oxazolidinones?
Most commonly Thrombocytopenia (Tenzolid may have less of this problem)
Explain Mitochondrial Toxicity of Oxazolidinones?
Lactic Acidosis, Optic Neuritis, Peripheral Neuropathy can develop in patients taking Linezolid. Linezolid should not be used for Long Term Treatment
Explain Drug-Drug Interactions of Oxazolidinones?
Linezolid is a weak inhibitor of MAO – this causes interactions with SSRIs – can lead to serotonin syndrome
What is Serotonin Syndrome with taking Oxazolidinones?
Life Threatening, can manifest as Headaches, palpitations, and hypertensive crisis.
What are the main Macrolides and Ketolides to know?
Macrolides: Erythromycin, Clarithromycin, Azithromycin, Fidaxomicin Ketolide: Telithromycin
What is Fidaxomicin (a Macrolide) used to treat?
C Difficile colitis
How do Macrolides and Ketolides kill bacteria?
- Protein Synthesis Inhibitors Bind reversibly to 50S ribosomal subunit prevents translocation of tRNA from the A site to the P site
- Elicit Conformational change in Bacterial ribosome this can indirectly inhibit transpeptidation
(BOTH Macrolides and Ketolides are Bacteriostatic)
What are the 4 main mechanisms of resistance to Macrolides and Ketolides?
1) Active Drug Efflux
2) Ribosome is shielded or protected from them (by Methylase enzymes)
3) Degradation of the drug
4) Mutations to the 50S subunit can occur
Erythromycin (a Macrolide) has good activity against what?
(warning: its a hefty amount)
(I don’t blame you for skipping past this card – I will too)
Erythromycin has good activity against streptococci, pneumococci, staphylococci. In addition, erythromycin is active against: C. jejuni, M. pneumoniae, Legionella pneumophila, C. trachomatis, Chlamydophila psittaci, Chlamydophila pneumoniae, H. pylori and the gram-positive bacilli including Clostridium perfringens, Corynebacterium diphtheriae, and L. monocytogenes. Some gram-negatives are also susceptible to erythromycin and these include Bartonella spp., Quintana spp., Neisseria spp., Rickettsia spp., and Treponema pallidum.
(I don’t blame you for skipping past this card – I will too)
What are Erythromycin (a Macrolide) not good against?
Mean words spoken about them by other antibiotics — noooo
Most Aerobic Enteric Gram Neg Bacilli
What is Azithromycin (a Macrolide) active against?
Azithromycin is active against Moraxella catarrhalis, Chlamydia spp. (highly active), L. pneumophila, B. burgdorferi, M. pneumoniae, and H. pylori. Azithromycin is less active than erythromycin and clarithromycin against streptococci and staphylococci.In contrast, azithromycin is more active against H. influenzae.
What is Clarithromycin (a Macrolide) active against?
Clarithromycin is more potent than erythromycin against sensitive streptococci and staphylococci. In addition, clarithromycin is active against same bacteria highlighted with azithromycin. Like azithromycin, Clarithromycin is also active against H. influenzae.
What is Fidaxomycin (a Macrolide) active against? (don’t skip this one — its short)
C Difficile (in GI Tract)
What is Telithromycin (a Ketolide) active against?
similar to azithromycin and clarithromycin but with better attacking power of S Pneuominae and S Aureus Macrolide resistant strains
What are the most common adverse affects of Macrolids and Ketolides?
Diarrhea, Nausea, Vomiting, and Anorexia Hepatotoxicity (with prolonged Eryhthromycin, Clarithromycin and Azithromycin use)
What are the signs of hypersensitivity to Macrolides and Ketolides?
Skin Eruptions, Eosinophilia, and Fever
What are the main drugs of Streptogramins? (and their percentages?)
Streptogramin A –> Dalfopristin (70%)
Streptogramin B –> Quinupristin (30%)
always are in a combined ratio
How do Streptogramins attack bacteria?
Inhibit Protein Synthesis by binding to 50S Ribosomal subunit Quinupristin
– inhibits polypeptide elongation/early term of protein Dalfopristin
– binds to nearby site, causing conformational change // impedes polyp chain formation
How do Bacteria cause resistance to Streptogramins? (3)
1) Enzymatic inactivation of Dalfopristin (Strepto A)
2) Binding site of Quinipristin can be altered (Strepto B)
3) Both can be subjected to efflux
What are Streptogramins active/and not active against?
NOT active against GRAM NEG Bacteria Active against: gram positive cocci including resistant streptococci, penicillin-resistant S. pneumoniae, and methicillin resistant staphylococci. In addition, quinupristin/dalfopristin is active against M. pneumoniae, C. pneumoniae, and Legionella spp.
What are the problems associated with taking Streptogramins?
Infusion site reactions – with pain and arthralgia-myalgia syndrome
What are the main Tetracylcines and Glycylcyclines?
Tetracyclines: Doxycycline, Tetracycline, Minocycline, Demeclocycline
Glycycyclines: Tigecycline
How do Tetra and Glycylcyclines attack bacteria?
Protein synthesis inhibitors Bind the the 30S ribosomal subunit - prevent tRNA from binding to the A site
How do Bacteria make resistance to Tetra and Glycylcyclines?
1) Reduced Intracellular Concentration
a – energy dependent efflux path
b – glycyclines are able to overcome tetracycline resistance by these efflux pumps
2) Upreg of a protein that dislodges them from their target
3) Inactivated enzymatically
What do Tetracyclines attack? (this is a lot, just know the 1 spirochete and generals of the other)
GOOD: Gram +, Anaerobes: IE: Chlamydiae, Mycoplasmas, Rickettsiae (MRSA), Streptococcus pyogenes, Streptococcus pneumoniae, Bacillus anthracis, Listeria monocytogenes, Haemophilus influenzae, Vibrio cholera, and Helicobacter pylori. Ureaplasma spp., Coxiella burnetii, Mycoplasma pneumoniae, Rickettsia spp., Chlamydia spp., Legionella spp., and Plasmodium spp. and 1 spirochete: T Pallidum
What are Tetracyclines not good against?
Inactive against: Pseudomonas, Proteus, Providencia
What do Glycylcyclines attack?
same as tetracycline, but with added activity against bacteria resistant to tetracyclines Tigecycline has much greater activity against enterococci, enterobacteriaceae, Acinetobacter spp., and B. fragilis. Pseudomonas, Proteus, and Providencia spp. are still resistant to tigecycline.
What are the Adverse effects of Glycylcyclines and Tetracyclines?
GI Irritation and effects on bone and teeth (can lead to an risk of C Difficile) Develops a brown discoloration of teeth NO use for pregnant women – can hurt the babies bone and teeth
What are the Aminoglycosides?
Streptomycin
Gentamycin
Tobramycin
Amikacin
Neomycin
Paromomycin
How do Aminoglycosides inhibit bacteria? (3 ways)
Bind to the 30S subunit and inhibit protein synthesis 3 ways: 1) Inhibit imitation of protein by fixing the 50S and 30S ribosomal subunit to the AUG 2) they also inhibit continuation of Translation/ early termination 3) Introduce errors into protein synthesis – nonfunctional proteins
(They are BACTERICIDIAL)
How do Aminoglycosides get into bacteria?
Through Outer membrane porin channels, relying on the electrical gradient
How are Bacteria becoming resistant to Aminoglycosides?
1) Enzymatic Inactivation of aminoglycocides
2) Intracellular Transport of Aminoglycosides (due to mutation of porins)
3) Mutations of 30S subunit prevent binding
What are the susceptible bacteria to Aminoglycosides?
Enterobacter spp., E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia spp., and Acinetobacter baumanii.
(NEVER USE ALONE TO TREAT A GRAM + BACTERIA)
What are Aminogylcosides almost always combined with?
Beta Lactam Antibiotic
What does this Combo of Beta Lactam Antibiotic and Aminoglycosides provide coverage for?
Listeria
Viridans
Enterococci
Stapylcocci
What are the Adverse effects of Aminoglycosides?
Nephrotoxic and Ototoxic (Vestibular Damage, Loss of Balance, Ataxia, Vertigo)
What are the Fluoroquinolones?
Flourinated analogs of Quinolone nalidixic acid
Moxifloxacin
Ciprofloxacin
Ofloxacin
Gatifloxacin
Gemifloxacin
Levofloxacin
What are the groups of Fluoroquinolones and there respective bacteria?
Norf, Cipro, Levo, Oflo, Eno, Lome, Peflo – improved activity against Gram +
Gemi, Moxi, Dati, – superior activity of Gram +
Moxi – has action against Anaerobes
What were the problems with some Fluoroquinolones?
Phototoxicity and QT Prolongation
How do Flooroquinolones work?
They inhibit transcription and replication of bacterial DNA
INHIBIT Topoisomerase II (DNA Gyrase)
How are bacteria becoming resistant to Fluoroquinolones?
1) Mutations to quinolone binding site on topoisomerase IV or DNA gyrase
2) Drug Efflux
3) Upreg of proteins that protect the enzymes
What are the primary organisms Fluoroquinolones are active against?
Fluoroquinolones are potent bactericidal agents against Campylobacter spp., Enterobacter spp., Shigella spp., Salmonella spp., Proteus spp., Klebsiella spp., and E. coli. Fluoroquinolones are also active against intracellular microorganisms including Legionella spp. and Chlamydia spp.
Levofloxacin is the __ Isomer of Ofloxacin and has exceptional activity against ___ bacteria (Strep Pneumoniae)
L Isomer
Gram + Bacteria
Ciprofloxacin is best against __ bacteria (P Aeruginosa)
Gram - Bacteria
A 3rd group of Fluoroquinoloes are active now: (Moxifloxacin) and is active against what?
Effective against some Anaerobes INCREASED activity against Gram +’s – S Pneumoniae and some staph
What are the complications of Fluoroquinolones?
Abdominal Discomfort, Nausea, Vomiting,
ACHILLES TENDON RUPTURE (rare, but testable)
Moxifloxacin (3rd gen Flouro) – causes QT prolongation, torsades de pointes arrhthymia
What is the one Sulfonadmide and Benzylpyrimidine?
TMP/SMX (Bactrim) (Sulfamethoxazole-Trimethoprim)
How does TMP/SMX work?
it inhibits steps in the tetrahydrofolate biosynthetic pathway
How does resistance to TMP/SMX work?
SMX Resistance
1) Changes to the Bacterial Tetrahydrofolate bio pathway
2) Bacterial overproduction of PABA
3) Reduced Binding
4) Decrease med entry into bacteria (permeability)
TMP Resistance
1) Reduced bacterial permability
2) Upreg of dihydrofolate reductase
3) reduced binding affinity
Can Trimethoprim be given as a mono therapy?
YES! but rarely – for UTI
What bacteria are resistant to Trimethoprim?
P Aeruginosa
B Fragilis
Enterococci
What bacteria are susceptible to TMP/SMX?
A SHIT TON (look in the packet)
What are the consequences of TMP/SMX use?
Anemia, Leukopenia, Granulocytopenia Nausea, Vomting, Photosensitivty, Fever, Uricaria (hives), Skin Rashes Stevens-Johnson Syndrome
What are the main Polymyxins?
Colistimethate (Polymyxin B)
Colistin (named Polymyxin E – for topical use)
(was discovered from the Bacillus Polymyxa)
How do Polymyxins act against bacteria?
disrupt the phospholipid membrane bind to and inactivate endotoxin
ARE BACTERICIDAL
What bacteria are resistant to Polymyxins?
Extensively drug resistant strains of; Klebsiella, Acinetobacter, Neisseria, Burkholderia, Stenotrophomonas spp Gram + Bacteria (because they don’t have an outer membrane like Gram Neg) Anaerobes
What bacteria are Polymyxins active against?
Enterobacteriaceae
Pseudomonas spp
Acinetobacter spp
Proteus spp
Serratia spp
(Good for superficial cuts and scraps)
What are the problems with taking Polymyxins?
Nephrotoxicity
Slurred Speech
Vertigo
Paresthesias
Apnea
Muscle Weakness
