Exam 2 11/2 Antimicrobial Therapy Flashcards
Previous Exam question
What part of the bacteria is most important to maintain osmotic pressure?
Cell wall
Wrong answer is cell membrane
Previous exam question
Which cells recognize virally infected cells?
CD8/CTL
Recognize MHC I (endogenous antigens, check inside cell)
Previous exam question
Which immune cell does both phagocytosis and antigen presentation?
Macrophages
Neutrophils do phagocytosis but do not do APC!
Narrow Spectrum
Limited activity; works against small subset of bacteria
Broad spectrum
Work against greater variety of bacteria
________ agents inhibit bacterial replication
Bacteriostatic
________ agents kill bacteria
Bactericidal
Why is it important to consider minimum bactericidal concentration (MBC)?
Too many bacteria would be killed, including commensal bacteria (which are good for us and also help to prevent infections)
Minimum bactericidal concentration
lowest concentration of an antibacterial agent required to kill a particular bacterium
What is the goal of antimicrobial chemotherapy?
Selective toxicity - can be given to humans with reasonable safety while having toxic effects on specific microorganisms
Antibacterial is a broad class of:
Antimicrobials
Penicillin binding proteins
membrane-associated proteins involved in the biosynthesis of peptidoglycan
Different bacteria have different _____, which makes them have different susceptibility to beta lactams
PBPs
Beta lactam antibiotics block active site of ____ in order to prevent ____
PBPs, transpeptidase, etc.; cell wall synthesis
List the 5 beta-lactam antibiotics
- penicillins
- cephalosporins
- cephamycins
- carbapenems
- monobactams
Penicillins consist of a beta lactam ring (___-membered ring) bound directly to thiazolidine, a ___ -membered ring
4; 5
What differentiates various penicillins?
Different R groups
(Ex. Penicillin, amoxycillin, etc)
True or false: Beta lactam antibiotics are all cell wall inhibitors, but not all cell wall inhibitors are beta lactams
True - for example, vancomycin works against cell wall but is not a beta lactam
True or false: cephalosporins contain a beta lactam ring
True
_____ are composed of a beta lactam ring (4M) fused with dihydrothiazine ring (6M)
Cephalosporins
Which antibiotic is similar to cephalosporins?
Cephamycins
Cephalosporins and cephamycins are both resistant to:
Many beta lactamases
Many gram-negatives are now developing resistance via _______________ which is conferred by ___________________
- beta-lactamase (bacterial enzymes)
- R (resistance)-plasmid
Carbapenems are a broad/narrow spectrum β-lactam antibiotic
Broad
TEST QUESTION: Monobactams are a broad/narrow spectrum β-lactam antibiotic
Narrow
Monobactams are active against ______. ______ and ______ are resistant
Aerobic gram negatives; anaerobes and gram positives
What antibiotic is widely used in dentistry?
Penicillins
All penicillins share problem of _________
Allergy
1 most reported drug allergy
Penicillin
Minor reaction to penicillin that is most common _____; second most common ____
GI upset; rashes
True or false: with a penicillin allergy, severe reactions are common such as anaphylaxis and seizure
False - severe reactions are rare
_____ of patients are sensitive to penicillin - why?
10%; cross reactivity to cephalosporins and other beta lactam antibiotics
What are the ways that bacteria show resistance to beta lactams - which method is most common/easiest?
- block interaction of PBP and antibiotic
- modification of binding
- hydrolysis by beta lactamase (Most common)
How many beta lactamases or penicillinases exist that confer resistance to beta lactams?
About 200
There are 4 main classes of β-lactamases/penicillinase.
1. What is the most common?
2. Which class is the most resistant?
- Class A
- Class C (extended spectrum Beta lactamases)
Penicillinases have minimal activity against _______
Cephalosporins
What organisms produce Class A beta lactamases?
Gram-negative rods, Escherichia, Klebsiella
B-lactamase inhibitors
- clavulanic acid
- sulbactam
- tazobactam
Augmentin
Clavulanic acid + amoxicillin
(blocks penicillinase and transpeptidase)
Pharmacokinetics - what is bioavailability
A measure of the extent of drug absorption for a given drug and route (from 0% to 100%)
Penicillins and cephalosporins: excretion
Renal (mostly unchanged > 80%)
Half life 30-90 min
Vancomycin works against what bacteria
Streptomyces orientalis
Vancomycin has a different mechanism way of inhibiting cell wall formation, instead of disrupting the β-lactam ring it binds:
Terminal D-ala-D-ala residues on gram-positive organisms
Some bacteria (Lactobacillus, Enterococcus faecalis) have Intrinsic resistance to Vancomycin: instead of D-ala-D-ala residues at the terminus they have
D-alanine-D-serine
True or false: MRSA have acquired resistance to vancomycin and are now VRSA
True - plasmid genes confer VanA and VanB
Bacitracin is a _____ inhibitor and is effective against
polypeptide cell wall inhibitor; gram-positive - blocks bactoprenol
Vancomycin is a _____ inhibitor
Glycopeptide cell wall inhibitor
Bacitracin should be applied as ____ only
Topical
Should not be ingested because it blocks enolase
Polymixin is a _____ inhibitor
Polypeptide cell wall inhibitor
Polymixin disrupts ____ so it is effective against gram-negative bacteria
LPS
Polymyxin is _____________ so it is mainly for topical use
Excretion is _____________
nephrotoxic; renal
Isoniazid is a ______ inhibitor
Mycobacteria cell wall inhibitor
Ethionamide is a derivative of
Isoniazid
Isoniazid blocks synthesis of:
Mycolic acid
(works against Mycobacteria tuberculosis)
Ethambutol is a _____ inhibitor
Mycobacteria cell wall inhibitor
Ethambutol blocks:
Arabinogalactan synthesis (cell wall)
Cycloserine is a _____ inhibitor
Mycobacteria cell wall inhibitor
Cycloserine inhibits:
Other cell wall synthesis enzymes like D-alanine-D-alanine synthetase and alanine racemase
Alanine racemase is used in:
Mycolic acid synthesis
Isoniazid excretion and metabolism
Excretion - renal
Metabolism - hepatic (50-90%)
____ has a bimodal half life depending on ____.
50% of black and white individuals have a ____ half life, whereas 90% asians/Inuits have a ____ half life.
Isoniazid; race; Longer (3 hour); Shorter (1 hour)
Name the cell wall inhibitors that work against mycobacteria
Isoniazid, Ethionamide, Ethambutol, Cycloserine
Aminoglycosides are _____ inhibitors
Protein synthesis
Protein synthesis inhibitors (7)
- aminoglycosides
- tetracyclines
- macrolides
- chlorampenicol
- clindamycin
- streptagramins
- fusidic acid
Streptomycin is a(n) _____
Aminoglycoside
Aminoglycosides bind irreversibly to ____
30S ribosome
Aminoglycosides are effective against ____ bacteria, but ____ are generally resistant
Aerobes; anaerobes
Aminoglycosides are toxic to:
Ear and kidney
Ototoxicity.Chochleotoxicity
Tetracyclines are _____ inhibitors
Protein synthesis (30S)
Tetracyclines spectrum
Broad spectrum
Tetracyclines should be avoided in which people?
Children under 8 years old
Pregnant/lactating women
Those who have received tetracycline treatment may develop:
Unsightly tooth staining
Linezolid is used to treat:
Penicillin and vancomycin resistant staphylococci, streptococci, enterococci
Erythromycin, azythromycin, and clarithromycin are:
Macrolides
Macrolides are _____ inhibitors
Protein synthesis (50S)
Linezolid is a _____ inhibitor
Protein synthesis inhibitor
First choice for penicillin allergic patients?
Macrolides (erythromycin)
Chloramphenicol binds:
50S ribosome
Chloramphenicol cannot be given in high doses or for a long time because:
They cause bone marrow aplasia (toxic)
Clindamycin binds
50S ribosome
Which antibiotic can treat VRSA and VRE (vancomycin resistant S. aureus/enterococcus)?
Streptagramins
Streptagramins bind
50S
Fusidic acid blocks what ribosome
50S ribosome
Erythromycin has contraindications with:
Liver disease (hepatitis)
Erythromycin metabolism and excretion
Hepatic (>95%), bile
Nucleic acid inhibitors (3)
- metronidazole
- quinolones
- rifampin
Is metronidazole bacteriostatic or bactericidal?
Bactericidal
Metronidazole blocks _____ in all _____
DNA synthesis; strict anaerobes
Rifampin blocks:
RNA polymerase (inhibits RNA synthesis)
If you need to treat mycobacteria resistant to Isoniazid, you can prescribe:
Rifampin
Rifampin is bactericidal/bacteriostatic? It is very active against _____
Bactericidal; aerobic, gram-positive cocci
Rifampin increases p450 CYP enzymes, which increase clearance for ____ (contraindication)
anti-HIV medications
Someone with HIV and has Mycobacteria, they would likely be taking Isoniazid and anti-HIV drugs so they cannot be given ____
Rifampin
Quinolones/fluoroquinolones inhibit
DNA gyrases/topoisomerases –> inhibit DNA replication
Anti-metabolites (2)
- sulfonamides
- trimethoprim
Sulfonamides inhibit ______. Poses potential complications with ____
Folic acid synthesis; pregnancy
Folic acid is needed to make
Purines and pyrimidines (Dna synthesis)
Trimethoprim inhibits ______ and is contraindicated in ____
dihydrofolate reductase; pregnancy
Why is antibiotic resistance a problem in dentistry?
Oral bacteria (streptococci) may develop cross resistance to both penicillins and cephalosporins
_____ rapidly acquires resistance while ____ rarely do so
S. aureus; S. pyogenes
Resistance to some antibiotics like ____ is virtually unknown, whereas strains resistant to other drugs like ____ readily emerge
Metronidazole; penicillin
Methicillin is relatively resistant to:
beta-lactamases
Almost all S. aureus is sensitive to ____. However, ___ is emerging so vancomycin must be used instead. However, reports of ____ are not detected so linezolid or streptogramins must be used instead
Methicillin; MRSA; VRSA
Types of resistance
- primary (intrinsic) resistance
- acquired resistance
- cross-resistance
Order of operation for antibiotic prescribing
- Penicillin
- Methicillin
- Vancomycin
- Linezolid
- Streptagramins
Primary (intrinsic) resistance
- naturally resistant to the drug
- vancomycin ineffective in D-alanine-D-serine bacteria
Acquired resistance
- mutation or gene transfer
- Rifampin ineffective against RNA polymerase mutation
- beta lactamase transfer (R-plasmid)
Cross-resistance
- resistance to one drug confers resistance to related drugs (R-plasmids)
- penicillin and cephalosporin resistance
Mechanisms of resistance
- altered target - lower affinity for antibacterial but still functional
- altered uptake - increasing impermeability or increased efflux of drug out of cell
- drug inactivation - enzymes which modify or destroy the antibacterial agent
Only documented plasmid to transfer in free-living environments
NDM-I (superbug)
KPC
Klebsiella pneumoniae carbapenemase (superbug, ESBL)
Four main treatments to reduce rejection of transplant
- methotrexate
- cyclosporin
- tacrolimus
- glucocorticoids (prednisone)
Methotrexate (MTX) is often used in
chemotherapy and autoimmune disorders
Methotrexate competitively inhibits
Dihydrofolate reductase (DHFR)
Methotrexate inhibits ____ binding
IL-1 beta
IL-1
inflammation
Pharmacologic immunosuppression can present ____ and treat _____
graft vs host disease (GVHD); autoimmune disease
Methotrexate is a treatment for
GVHD, autoimmune disorders (decreases inflammation)
What drugs interact with methotrexate?
- penicillin (decreases elimination of MTX which can kill them)
- aminoglycosides (reduce absorption of MTX)
- NSAIDs have potentially fatal interactions
- nitrous oxide induces hematologic toxicity of MTX
Cyclosporins are mainly used to treat ____ and prevent ____
Autoimmune diseases; GVHD
Cyclosporin inhibits?
IL-2 and T-lymphocyte activity
Tacrolimus interacts with
Macrolides
Tacrolimus inhibits ____ production
IL-2
Which is a more potent immunosuppressant - tacrolimus or cyclosporin?
Tacrolimus
Tacrolimus is used to treat/prevent:
autoimmune disease; GVHD
What drugs have contraindications with tacrolimus?
- macrolides (erythromycin)
- azoles )fluconazole)
Tacrolimus is nto used with what patients?
Hep B/C patients
Tacrolimus competed for:
CYP3A - cytochrome P450 liver enzymes
Tacrolimus is influenced by _____. _____ make non-functional CYP3A5 protein, increasing risk of drug toxicity
Genetics; CYP3A5 G/G
Glucorticoids (prednisone) treats _____; what effects does it have
Overactive immune diseases (high doses = immunosuppression)
- may result in T-cell or humoral immune deficiency, neutropenia
Glucocorticoids inhibit what cytokines?
IL-1, IL-2, IL-4, IL-6, IL-8