Antibiotics & Microbial Resistance Mechanisms Flashcards
1
Q
This is the term for “lethal to bacteria.”
A
Bactericidal
2
Q
This is the term for “inhibits growth but is not lethal.”
A
Bacteriostatic
3
Q
This is the term for “lowest concentration of antibiotic able to inhibit bacterial growth in a liquid media.”
A
Minimal Inhibitory Concentration (MIC)
4
Q
This is the term for “the concentration of antibiotic that blocks all bacterial growth on plated samples.”
A
Mean Bactericidal Concentration (MBC)
5
Q
T/F: MBC inhibits growth but bacteria may still be alive.
A
False, MIC does that.
6
Q
This is the term for “organisms that a particular agent is active against.”
A
Spectrum (Narrow vs. Broad)
7
Q
This is the term for “microbes that are NOT inhibited by clinically achievable concentrations of an antibiotic.”
A
Resistance
8
Q
This is the term for “antibiotic given based on probable microbial etiology – educated guess.”
A
Empiric Therapy
9
Q
This is the term for “specific antimicrobial therapy based on a known pathogen.”
A
Specific Therapy (isolation and identification of organism)
10
Q
This is the term for culture data that suggests the organism came from the skin or environment and does not represent true infection.
A
Contaminant
11
Q
This is the term for development of a new flora at an anatomic site that does not clinically fit with an infection at that site.
A
Colonization
12
Q
Antibiogram
A
Log of what antiobiotics kill what bacterias. Gives the ranking of how many bugs are apparent/popular in this hospital.
13
Q
Important Bacterial Pathogens
Gram (+)
A
Aerobes:
- Staphylococcus
- Streptococcus
- Listeria
- Bacillus
- Cornybacterium
Anaerobes
- Clostridium
- Bacteroides
14
Q
Important Bacterial Pathogens
Gram (-)
A
- E. coli
- Klebsiella
- Proteus
- Pseudomonas
- Enterobacter
- Haemophilus
- Neisseria
- Salmonella
15
Q
What antibiotics target the bacterial cell wall?
A
- Beta-lactams (Penicillins, Cephalosporins, Carbapenems, Monobactams)
- Gycopeptides (Vancomycin)
16
Q
What antibiotics target protein synthesis?
A
- Aminoglycosides
- Tetracyclines
- Macrolides
- Clindamycin
- Oxazolidinones
17
Q
What antibiotics target nucleic synthesis?
A
- Quinolones
- Folate inhibitors
- Metronidazole
18
Q
What antibiotics target cell membrane?
A
Daptomycin
19
Q
If you needed to cover a life threatening infection with 2 antibiotics how would you choose them?
A
You wouldn’t!
20
Q
Characteristics of Gram Positive Bacterial Cell Wall. (This is review, we should know the basics)
A
- cytoplasmic lipid membrane
- thick peptidoglycan layer
* teichoic acids and lipoteichoic acids are present, which serve to act as chelating agents, and also for certain types of adherence. - capsule polysaccharides (only in some species)
- flagellum (only in some species)
21
Q
Characteristics of Gram Negative Bacterial Cell Wall. (This is review, we should know the basics)
A
- Cytoplasmic membrane
- Thin peptidoglycan layer (which is present in much higher levels in Gram-positive bacteria)
- Outer membrane containing lipopolysaccharide (LPS, which consists of lipid A, core polysaccharide, and O antigen) outside the peptidoglycan layer
- Porins exist in the outer membrane, which act like pores for particular molecules
- There is a space between the layers of peptidoglycan and the secondary cell membrane called the periplasmic space
- The S-layer is directly attached to the outer membrane, rather than the peptidoglycan
- If present, flagella have four supporting rings instead of two
- No teichoic acids or lipoteichoic acids are present
- Lipoproteins are attached to the polysaccharide backbone.
- Most do not sporulate
22
Q
MOA of Beta-Lactams
A
Inhibits Transpeptidation, blocks cross-lining of peptidoglycan units.
- Beta lactams look like Ala-Ala ***This is important
- Binds PBPs irreversibly
23
Q
Important facts to know about Beta- Lactams
A
- Bactericidal
- Bacteria must be synthesizing new cell wall for this to be effective
- So… antagonized by bacteriostatic antibiotics
- Kill bacteria by osmotic lysis
- -Water enters cell from extracellular space and causes rupture
- Will not work on mycoplasma sp.
- NO cell wall
24
Q
Talk to me about Penicillin G
A
- Gram (+) organisms and spirochetes
- Acid sensitive (no oral)
- Least toxic and least expensive
- Benzathine PCN (Bicillin)- long acting form about 7-10 days in the body IM
25
Talk to me about Penicillin V
- Chemical modification of penicillin G
- Acid stable can be given orally
- Covers mouth flora and Strep throat
26
Talk to me about Beta Lactamase Resistant Penicillins
- Methicillin, nafcillin, and oxacillin
- Active against lactamase producing S.aureus (MSSA)
- Mostly used in cellulitis (Streptococcus)
* **Not inactivated by Beta-lactamases
27
Aminopenicillins:
| Amoxicillin
- Oral
- Taste great -- kids
- Otitis media and sinusitis (Moraxella, H. influenza, and Streptococcus)
28
Aminopenicillins:
| Amoxicillin/Clavulanate (Augmentin)
- Beta lactamase producing Moraxella and H. influenza
- Use as tx for failed otitis or sinusitis
- Clavulanate inhibits beta lactamases
29
Aminopenicillins:
| Ampicillin
- IV only
| - Used for Listeria and Enterococcus
30
Aminopenicillins:
| Ampicillin-Sulbactam (Unasyn)
If worried about Beta-lactam producing bacteria
31
Carboxy/Ureido PCNs (Extended Spectrum)
- Ticarcillin-clavulanate (Timentin)
- Pipercillin-tazobactam (Zosyn)
- - Covers Pseudomonas, Bacteroides, and Enterobacter
- - Anaerobic (intra-abdominal infections and gynecologic infections)
*** Can also be used for life or limb threatening skin infections with both gram + and – organisms.
32
Which PCN is best for MSSA?
Oxacillin (narrowest spectrum to kill this)
33
Which PCN is best for Strep Throat?
Amoxicillin +/- Clav
34
Which PCN is best for Pseudomonas?
Pipercillin, Ticarcillin
35
Which PCN is best for Enterococcus?
Ampicillin
36
Which PCN is best for Intra-abdominal/polymicrobial?
Ampicillin + Sulbac
| Pipercillin, Ticarcillin
37
Which PCN is best for Beta lactamase producing bacteria?
Oxacillin
Amoxicillin + Clav
Ampicillin + Sulbac
38
Cephalosporins
- Classified based on generations (1st, 2nd, 3rd,and 4th)
- Each generation has expanded gram negative spectrum
- More gram (-) coverage
- Less gram (+) coverage (except for 4th gen)
- Mechanism of action the same as for penicillin
* ** Looks like Ala-Ala
39
1st Generation Cephalosporins
Cefazolin (Ancef) -- IV
Cephalexin (Keflex) -- PO
1. Cover mostly Gram (+) cocci
- Therapeutic value = high activity against gram (+) organisms
- Surgical Prophylaxis
- MSSA (Ineffective against MRSA)
- Streptococcus pyogenes (Especially pharyngitis and cellulitis)
2. Few gram negatives
- E. coli, Klebsiella, and Proteus
40
2nd Generation Cephalosporins
Cefoxitin (Mefoxin)
Cefaclor (Ceclor)
- Less gram-positive coverage
- More active against gram negatives
- - H. flu, Enterobacter, Moraxella, Klebsiella, Neisseria, E. coli, and Proteus
- - Increased anaerobic coverage (Mefoxin)
Intra-abdominal infections and PID
Think abdomen/pelvis infection for this generation
*Not the most popular cephalosporin
41
3rd Generation Cephalosporins
Ceftriaxone (Rocephin)
Cefotaxime (Claforan)
- Less gram (+) coverage – but ok for Strep
- Wider gram (-) spectrum and activity
- - Neisseria, H. influenzae, Moraxella, Shigella and Salmonella
- - Hospitalized Community acquired pneumonia
- - Good CSF penetration
-- Preferred tx for meningitis (Neisseria meningitidis, Streptococcus pneumonia, Haemophilus influenzae)
42
4th Generation Cephalosporins
Cefepime (Maxipime)
- Useful for nosocomial infections
- Good spectrum against gram (-) organisms (Adds Pseudomonas)
- Unlike others still maintains gram (+) ****
- MSSA and Streptococcus sp.
- Ideal for suppressed immune system b/c broad spectrum
43
Carbapenems
Imipenem (Primaxin)
Meropenem (Merrem)
Ertapenem (Invanz)
- Mechanism of action same as penicillin
- Broadest spectrum of all the Beta-lactams
- Gram positive/negative aerobes and anaerobes
- Penetrates tissues well
- Resistant to Beta-lactamases
- - Empiric tx of mixed aerobic and anaerobic infections or nosocomial infections
- - Can be used for empiric sepsis treatment
- - Usually reserved for critically ill
44
Monobactams
Aztreonam (Azactam)
- Only for gram negative infections
- Will not work on anaerobes
- Spares some gut flora
- Good empiric therapy when combined with antibiotic that covers gram positives
- Can be used in PCN allergic patient
45
Which Cepahalsporin and Bactams would you use to best treat MSSA?
1st Gen. Cephalosporin
46
Which Cepahalsporin and Bactams would you use to best treat UTI?
- 1st Gen. Cephalosporin (if out pt.)
| - 3rd Gen. Cephalosporin (if hosp. or pyelonephritis/hematuria)
47
Which Cepahalsporin and Bactams would you use to best treat Pseudomonas?
- Gen. Cephalosporin
| - Imipenem/Meropenem
48
Which Cepahalsporin and Bactams would you use to best treat Gram Negative Only?
- Aztreonam
| - 3rd Gen. Cephalosporin
49
Which Cepahalsporin and Bactams would you use to best treat Neutropenic fever?
4th Gen. Cephalosporin
| Imipenem/Meropenem (good second choice)
50
Which Cepahalsporin and Bactams would you use to best treat Severe PCN allergy?
Aztreonam
51
Which Cepahalsporin and Bactams would you use to best treat Sepsis (polymicrobial)?
Imipenem/Meropenem
| 4th Gen. Cephalosporin (Reasonable, but not best)
52
Glycopeptide Abx
Vancomycin
- Mechanism of action different than Beta-lactams
- Inhibits transpeptidation step (same as Beta-lactams)
- Binds directly to the Ala-Ala residues versus B-lactams that looks like Ala-Ala
- Blocks the access of PBP’s to these residues
- Results in inhibition of peptidoglycan synthesis
- Useful for gram (+) bacteria only
- Most often reserved for drug resistant bacteria (MRSA, staph epidermidis, Sensitive Enterococcus, Streptococcus)
- Oral use only for C. difficile colitis (Only after failed therapy with Metronidazole or severe case)
- Resistance is occurring
1. VRE –(Vanco Resistant Enterococcus)
2. VRSA – (Staph Aureus)
53
Inhibitors of Protein Synthesis
1. Aminoglycosides (Gentamycin, Tobramycin)
2. Tetracyclines (Tetracycline, Doxycycline)
3. Macrolides (Erythromycin, Azithromycin, Clarithomycin)
4. Clindamycin
5. Oxazolidinones (Linezolid)
54
Aminoglycosides
Gentamicin
Tobramicin
Amikacin
1. Bactericidal against aerobic gram negative pathogens
2. Inhibit protein synthesis
- - Binds to 30S subunit
- - Inhibition of initiation complex
- - Misreading of mRNA
3. No activity against anaerobes
- - Lack oxidative phosphorylation
4. IV forms only
Toxicity: Renal, 8th cranial nerve
- Activity is concentration dependent – hard to dose
- Post antibiotic effect – 1-3 hrs after antibiotic is gone
- Synergy with beta lactams (cell wall and protein synthesis)
- Activity against:
1. P. aeruginosa
2. Tularemia (rabbit fever)
3. Enterococci + beta lactam
4. Yersinia (plague)
55
Tetracyclines
Tetracycline
Doxycycline (Vibramycin)
Tigecycline (Tygacil)
Wide spectrum – works against:
- Intracellular organisms (Rickettsia and Chlamydia, Lyme disease)
- Cell wall deficient organisms (Mycoplasma)
- Binds to 30S subunit (Prevents the binding of tRNA to ribosome)
- Bacteriostatic
- Not given to children or during pregnancy (Discoloration of teeth)
Tigecycline
- Think for drug resistant organisms (For MRSA, VRE)
- Bacteroides and Clostridium- severe intra-abdominal infections
- Severe skin infections
56
Macrolides
Erythromycin
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
- Binds to 50S subunit (Blocks the translocation of tRNAs)
- Bacteriostatic
Erythromycin
- - Mostly gram + organisms
- - Similar spectrum to Pen V (strep and staph)
- - If allergic to PCN this is a good choice
Azithromycin
- - Enhanced gram (-) coverage
- - Good Chlamydia and Mycoplasma
- - Good coverage for community acquired-- pneumonia, otitis, sinusitis – not for in hospital infections
- - Strep resistance increasing
57
Inhibitors of Nucleic Acid Synthesis
1. Quinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin)
2. Folate Inhibitors (Sulfonamides, Trimethoprim)
3. Metronidazole
58
Quinolones (General)
Ciprofloxacin (Cipro)
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
- Inhibits DNA replication
- Blocks DNA gyrase and topoisomerase (Coiling in DNA-gyrase)
- Unlinking daughter DNA strands (topoisomerase)
59
2nd Generation Quinolones
Ciprofloxacin
- Expanded gram (-) coverage
- Treatment for travelers diarrhea, UTI and prostatits
- Covers gram negatives such as H. flu, P. aeruginosa, E. coli, Enterobacter, Proteus, Klebsiella, Shigella and Salmonella
- Good pseudomonas coverage
*** Poor coverage for MRSA, enterococci, and pneumococci (Poor gram positive coverage).
60
3rd Generation Quinolones
Levofloxacin
Moxifloxacin
Gatifloxacin
- Same gram negative coverage as 2nd generation
- Expanded coverage of gram (+) -- S. pneumonia
- Recommended for community acquired pneumonia- outpatient therapy
- Covers “atypical” lung infections
- Can be used for skin infections gram +
61
Folate Inhibitors
Sulfonamides
Trimethoprim (Bactrim)
- Bacteria must synthesize folate (Purines and thymidine required for DNA)
- Humans cannot make folate (selective toxicity)
1. Sulfonamide
-- Competitive inhibitor of dihydropteroate synthetase
2. Trimethoprim
-- Blocks dihydrofolate reductase
3. Combined trimeththoprim-sulfamethoxazole =(Bactrim)
-- Blocks folate synthesis at two different steps (Prevents resistance)
Coverage for MRSA skin infections, Streptococcus, Listeria, UTI’s and PCP (PJP) prophylaxis/treatment in AIDS patients.
62
Metronidazole (Flagyl)
- Induction of breaks in DNA strands (Must be in anaerobic environment to work)
- Activity against bacteria and protozoans
- Limited to anaerobic bacteria
- -- C. difficile, bacterial vaginosis
- -- Trichomonas vaginalis infections
- -- Giardia
- -- Amoeba
63
Daptomycin (Cubicin)
- Depolarizes lipid cell membrane
- - Stops protein, DNA and RNA synthesis
- Enterococci (VRE), MRSA, and S.pyogenes
- Excellent for severe soft tissue infections
- Cannot be used for pneumonia
- - inactivated by surfactant
- Watch for rhabdomyolysis
- - Monitor CPK
64
Which is the best treatment for C. diff?
- Oral Vancomycin
| - Metronidazole (use this first clinically b/c less expensive)
65
Which is the best treatment for UTI?
- Trimethoprim/sulfa
| - Ciprofloxacin
66
Which is the best treatment for VRE?
Daptomycin
67
Which is the best treatment for Atypical Pneumonia?
- Quinolones
| - Macrolides
68
Which is the best treatment for Skin Infections (Staph and Strep not MRSA)?
- Levofloxacin
69
Which is the best treatment for Anaerobes?
- Metronidazole
Aminoglycosides are the worst option for this!
70
Which is the best treatment for MRSA?
Vancomycin
71
Which is the best treatment for Gram negative only?
Aminoglycosides
72
Strategy for Abx Use
1. Is there a bacterial infection?
2. Educated Guess of Pathogen(s)
3. Local susceptibility pattern
4. Previous abx exposure
5. Host Factors
6. Fine tune
73
Mechanisms of Resistance
1. Accumulation of barriers
- - Impermeability
- - Active Efflux Pumps
2. Alterations in target
- - Mutant PBP’s
3. Inactivation of antibiotic by bacterial enzyme
- - Beta lactamase producing bacteria
74
Accumulation of Barriers
1. Cell wall and outer membrane of gram (-) organisms
- - Limits the access of antibiotics to sites of action
- - Drugs must get inside cell and achieve suitable concentrations
- - Outer membrane porins restrict antibiotic entry (Pseusdomonas aerugonisa)
2. Some antibiotics must be transported inside cells
- - Anaerobes that lack oxidative pathways for the transport of aminoglycosides- (only work on aerobes)
3. Efflux pumps
- - Pumps that transport out tetracycline and fluoroquinolones
75
Altered Targets
1. Target is usually an enzyme or ribosome
2. Altered PBP’s
- - Penicillin resistant S. pneumonia
- - Changes in amino acid sequence
- - Point mutations (random)
3. MRSA
- - Acquires new genes for different form of PBP
- - Conjugation
4. Vancomycin resistance
- - Action of new enzyme (Substitutes lactate for alanine)
- - Ala-Ala changed to Ala-lactate
- - Vancomycin will not bind
76
Enzymatic Inactivation
1. Most robust of all mechanisms (Obtained by conjugation)
2. Beta-lactamases
- - Cleaves the -lactam ring
- - Inactivates the antibiotic
3. Modifying Enzymes
- - Aminoglycosides: Inactivates aminoglycosides by acetylation, phosphorylation or adenylation
77
Conjugation
The transfer of genetic material (plasmid) between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells.
78
Resistance Control
- Use abx conservatively and with specificity
- Adequate duration and dosage
- Select antimicrobials based on known sensitivities
- Use narrow spectrum if possible
- Limit prophylactic use
- Hand washing
- Isolate patients who have known resistant infection
