AB Flashcards
What is an example of an antibiotic with a high chemotherapeutic index value? Low value?
Penicillin – high
Aminoglycosides – lower
MIC and MBC related to which type of agents?
MIC: minimum inhibitory concentration
MBC: minimum bactericidal concentration
Name 3 bacteriostatic drugs:
Chloramphenicol, clindamycin, macrolides
Name 3 bactericidal drugs:
Penicillin & cephalosporin, vancomycin, rifampin
Direct toxic damage caused by the following drugs:
Aminoglycosides – kidney, nerves
Chloramphenicol – bone marrow
Vancomycin – kidneys
Antifungal drugs – liver
Tetracycline – teeth (avoid in children under 8)
Quinolones – bones and cartilage (especially Achilles tendon)
Cephalosporin – may cause gall stones
Which are the beta-lactam antibiotics?
Penicillin, cephalosporin, carbapenem, monobactam
What is the penicillin mechanism of action?
Penicillin molecules bind penicillin binding protein & transpeptidation is inhibited, cell wall synthesis is blocked so autolytic enzymes are activated
Which penicillin generation is acid sensitive? What is the consequence?
Ist, only injectable
Which bacteria lacks a cell wall and therefore is resistant to penicillin?
Mycoplasm tb
Which bacteria are resistant to penicillin due to beta-lactamase production?
Staphylococcus, Neisseria, enteric bacteria (ESBL)
Which bacteria are resistant to penicillin due to lack or alteration of binding protein
Streptococcus pneumoniae, MRSA
Which penicillin derivative is a narrow spectrum antibiotic, primarily to gram + cocci and bacilli? How is it administered?
Penicillin G, paraenterally
Which penicillin is used to treat oral infections?
Penicillin V (has higher serum concentration)
What are penicillin derivatives (G, V) effective against?
Streptococcus, Neisseria, Treponema, Bacillus anthracis
What are the penicillin with extended spectrum and what are they effective against?
Aminopenicillins: wide spectrum, G+/-
Carboxypenicillin: Proteus, Pseudomonas (ineffective against S. aureus, enterococcus)
Ureidopenicillin: Pseudomonas
ALL are sensitive to beta-lactamase
Give examples of beta lactamase inhibitors:
Clavulanic acid, sulbactam, tazobactam (Unasyn, Augmentin)
Which penicillin derivatives are penicillinase (=beta-lactamase) resistant? What is their downside?
Methicillin, oxacillin, cloxacillin, nafcillin
Less effective
What are mechanisms of cephalosporin resistance?
Difficult penetration, lack of penicillin binding protein, broken down by beta-lactamase enzyme
What is the cephalosporin spectrum?
Broad, bactericidal
What are the synthetic derivatives of cephalosporins?
1st gen – Gram + cocci 2nd gen – Gram - 3rd gen – Gram - 4th gen – Gram + and gram - 5th gen - MRSA (ceftarolin), pseudomonas (ceftobiprole)
What are monobactams (aztreonam) used for?
Gram-negative aerobic bacteria: neisseria, pseudomonas
What are carbapenems (impenem, meropenem) used for?
Gram + and Gram - (mostly for MDR bacteria, but ineffective against MRSA)
Which are the glycopeptide antibiotics?
Vancomycin, teicoplanin
glycopeptide antibiotics
What is a side effect? Why are they important?
Oto- and nephrotoxicity
Used against MRSA, VRE
glycopeptide antibiotics
What is their spectrum? Mode of action?
- Narrow – only against gram + b/c CANNOT cross outer membrane and penetrate inside because too big, bacteria, bactericidal
- Bind terminal D-ala-D-ala (D-ala-D-lactate) and block crosslink with pentagylcin bridge to inhibit cell wall synth
What is fosfomycin spectrum, what is it used for? What is its mechanism?
Broad, UTI (single dose)
Inhibits early stage synthesis of peptidoglycan
What is bacitracin and what is it used for?
Polypeptide, inhibits peptidoglycan synthesis (translocation of precursor across membrane), effect against gram - and gram + (especially MRSA!)
Which are protein synthesis inhibitors? Which ribosomal subunit do they act on?
30S: Aminoglycosides, tetracyclines
50S: chloramphenicol, macrolides (streptogramins, linezolid)
Some examples of aminoglycosides?
Streptomycin (used against TB), gentamicin (used parenterally or in eye drops), neomycin (eye drops)
How do aminoglycosides work?
Bind 30S subunit, don’t allow tRNA to bind ribosome which is bactericidal
What is the resistance mechanism of aminoglycosides?
Changing receptor on ribosome – mutation
Breaking down by enzymes – encoded on plasmids
Efflux pump
Side molecule can’t penetrate into cell (aerobic)
What are side effects of aminoglycosides?
Oto and nephrotoxic, neurotoxic at high doses
Which was the first broad spectrum antibiotic (against gram - and +)
Cloramphenicol
What is the mechanism of chloramphenicol?
Binds 50S subunit of ribosome, so peptidyl transferase is inhibited
What is the side effect of chloramphenicol?
Defective bone marrow function, gray-syndrome, aplastic anaemia
What is the resistance mechanism of chloramphenicol?
Acetyl-transferase
Which antibiotics disrupt the cell membrane?
Polymixins, lipopeptides
Which is the mode of action of the macrolide antibiotics?
Binds 50S subunit of ribosome, bacteriostatic
Bind peptidyl transferase center
What is the spectrum of macrolides?
Gram + cocci, legionella, mycoplasma, chlamydia trachomatis
What is the resistance mechanism of macrolides?
Target modification
Efflux pump
What is the side effect of tetracyclines? What is their resistance mechanism?
Forms complex with Ca2+ which colorizes enamel, shouldn’t be used in children!
Mutations
Which antibiotic is good to use against intracellular bacteria? Which bacteria?
Tetracycline, chlamydia, mycoplasma, rickettsia
What is the action of clindamycin? What is it an antagonist of?
50 S subunit
Macrolides
Which bacteria is linezolid NOT effective against?
Gram negative
What are streptogramins effective against?
VRE and VRSA
Which antibiotics inhibit nucleic acid synthesis?
Quinolons
Inhibitors of folate synthesis
Metronidazol
RNA synthesis inhibitor (Rifampin
Inhibitors of folic acid synthesis include:
P-amino-benzol-sulfonamides – p-Amino benzoic acid (PABA) antagonist
Trimethoprim – dihydrofolate reductase inhibitor
Which antibiotic inhibits DNA gyrase enzyme?
Nalidix acid and fluoroquinolons (inhibit DNA gyrase enzyme)
What is the original compound in quinolons?
Nalidixic acid
Rifamycin B (rifampin) mechanism and spectrum?
mRNA synthesis inhibition, Gram + cocci, mycobacterium (URT infections)
Mechanism of action of nitroimidazole – metronidazole? Limitations?
Damages DNA – no DNA synth
Bactericidal, effective only in anaerobic conditions
Spectrum of polymyxin and mode of action?
Narrow, gram -, bactericidal
Binds membrane phospholipids and inhibits membrane transport
Which antibiotic that alters membrane functions is antifungal and toxic (therefore has to be administered locally)?
Nystatin (steroid of membrane binding disintegrates PM)
When do we use daptomycin? Why is it limited?
Used against vancomycin resistant enterococci and staphylococcal infections
ONLY active against gram + (b/c cannot cross outer membrane of gram negatives)
Mechanisms of daptomycin:
Mutations in genes that involve synthesis of phosphatidylglycerol
Some phenotypes of staphylococcus aureus with VISA phenotype are less susceptible b/c of thicker wall less access
Which antibiotics should be completely avoided in pregnancy and young children?
Quinolon
Which are some important “synergies” or combinations of antibiotics that can be used?
Sumetrelim: TMX (tetramethoprim) + SMX (sulfamethoxazole)
Synercid: quinopristin + dalfopristin
Penicillin + gentamycin
Which antibiotics are contraindicated to be used together?
Beta-lactams and macrolides
Ciprofloxacin+ tetracycline
Which antibiotics can be used to treat MRSA?
Vancomycin, teicoplanin
Bacitracin
5th generation cephalosporin (cephtarolin)
Which are the problem bacteria/problems associated with the following straings:
Staph. Aureus
Enterococcus faecalis, faecium
Mycobacterium TB
Staph. Aureus – MRSA, VRSA
Enterococcus faecalis, faecium – VRE
Mycobacterium TB – MDR, XDR
Which are the carbapenem resistant gram-negative bacteria?
Acinobacter baumanni, pseudomonas aeruginosa, Klebsiella spp, stenotrophomonas maltophila Enterobacteriaceae
What do extended spectrum beta lactamases (ESBL) do? Which type of bacteria are they?
Hydrolyze penicilins, cephalosporins
Do not hydrolyze carbapenems, monobactams
Gram negative
What does metallo beta-lactamase do? Which type of bacteria are they?
Hydrolyze carbapenems
Gram negative bacteria
What are other antibiotics that work through enzyme inactivation?
Aminoglycoside (N-acetyltransferase, O-phosphotransferase, O-adenylotransferase)
Chloramphenicol (acetyltransferase)
Which are antibiotic resistance problems seen in gram + bacteria?
MRSA – methicillin resistant staphylococcus aureus
PRP – penicillin resistant pneumococcus
VRE – vancomycin resistant enterococcus
Why is MRSA resistant to all beta-lactams?
PBP2a has low affinity to all beta-lactams
What does vancomycin bind in its process of inhibiting cell wall synthesis?
D-alanine D-alanine
Which kinds of bacteria are resistant to vancomycin?
All gram-negative bacteria!
Why can’t vancomycin be given per os? When should it be given per os?
No absorption in GI
To kill gram + bacteria in GI that overgrow after other antibiotics were taken
What is the mechanism of vancomycin resistance? (VRE)
Vancomycin can’t bind to the D-ala-D-lactate structure
What are the most important MDR bacteria?
ESKAPE: Enterococcus, S. aureus, Klebsiella, Acinetobacter, p. aeruginosa, Enterobacter spp.
What are the fundamental mechanisms of extrinsic (acquired) resistance?
- Receptor is absent
- Resistance against the antibiotic which was produced by themselves
- Cell wall barrier (gram negatives) or lack of a cell wall (mycoplasma)
- Lack of a transport system
- Antibiotic concentration is low at the receptor
How is resistance described clinically?
MIC is higher than maximal dose tolerable by the host
Which type of resistance results from the following:
Absence of sterols in cell membrane of bacteria
Mycoplasms have no cell wall
Isoniazid inhibits synthesis of mycolic acid
Gram-negative bacteria have complex cell wall
Some bacteria need energy from the membrane potential to be absorbed
- Absence of sterols in cell membrane of bacteria resistance to antifungal polyenes (amphotericin B, nystatin)
- Mycoplasms have no cell wall beta-lactams are ineffective
- Isoniazid inhibits synthesis of mycolic acid only works on mycobacteria, nothing else has mycolic acid in cell walls
- Gram-negative bacteria have complex cell wall penicillin G can’t reach penicillin-binding-protein
- Some bacteria need energy from the membrane potential to be absorbed inhibition of transport results in resistance to aminogylcosides
What is virulence?
The degree of pathogenicity of a microbe, depends on presence/absence of certain structures, exotoxins and endotoxins
Which bacteria are toxin producing?
Clostridium tetani, Corynebacterium diphtheriae
Which bacteria produce the following toxins?
Neurotoxins, Cyotoxins
Neurotoxins – clostridium botulinum, tetani
Cyotoxins – staphylococci, streptococci, clostridia toxins (cause non-specific necrosis)
What is a superantigen?
Binds MHC class II molecules at a location outside the groove normally bound by antigenic peptides, then binds part of the beta-chain of the T-cell which can trigger T—cell activation
What is the function of non-toxic virulence factors:
Capsule: macrophages and neutrophils can’t phagocytose
Flagella: motility, chemotaxis
Pili (fimbrae): adherence
Biofilm: binding of prosthetic devices
Invasin: provides most direct and efficient manner of host cell invasion
Extracellular enzymes: antiphagocytic effect (coagulase, haemolysins, proteases), fascilitate invasion (streptokinase, collagenase, hyaluronidase)
Why are there only vaccines for viruses and bacteria?
Immune responses against them are antibody mediated
What are the types/components of vaccines?
Inactivated, attenuated, toxoid, subunit, conjugate
Which vaccine contains pathogens grown in culture and destroyed by chemical, heat, radioactivity or antibiotics? Examples?
Inactivated vaccines
Cholera, bubonic plague, pertussis
Which vaccine contains live pathogens? Examples?
Attenuated
Typhoid, TB (BCG - modified strain), typhus
What Is a toxoid vaccine? Examples?
Contains bacterial toxin components that have been inactivated (chemically or by heat)
Botulism, tetanus, diphtheria
What is a subunit vaccine? How can they be made more immunogenic and T-dependent?
Contains a subcomponent of the pathogenic organism (proteins or polysaccharides)
Conjugation with proteins
Which vaccines contain capsular polysaccharide?
- HiB, haemophilus influenzae type B
- Prevenar 13/Pneumovax 23
- Meningococcus vaccines (against ACWY – not B)
Which infections require passive immunity?
Diphtheria, tetanus, measles, rabies, botulism
What are examples of anti-phagocytotic substances on the bacterial surface?
Polysaccharide capsules M protein and fimbrae Surface slime (polysaccharides) O antigen associated with LPS K antigen of E coli Cell bound or soluble protein A
