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Antimicrobial Agents Flashcards

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1
Q

The addition of what class of antibacterial drug to penicillins is classified as synergistic?

A

Aminoglycosides

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2
Q

The addition of what class of antibacterial drug to penicillins is classified as antagonistic?

A

Tetracyclines

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3
Q

Name the classes of antimicrobial agents that inhibit bacterial cell wall synthesis

A
  • Penicillins
  • Cephalosporins
  • Imipenem/meropenem
  • Aztreonam
  • Vancomycin
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4
Q

Name the classes of antimicrobial agents that inhibit bacterial protein synthesis

A
  • Aminoglycosides
  • Chloramphenicol
  • Macrolides
  • Tetracyclines
  • Linezolid
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5
Q

Name the classes of antimicrobials that inhibit nucleic acid synthesis

A
  • Fluoroquinolones

- Rifampin

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6
Q

Name the classes of antimicrobials that inhibit folic acid synthesis

A
  • Sulfonamides
  • Trimethoprim
  • Pyrimethamine
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7
Q

What are the primary mechanisms of resistance to penicillins and cephalosporins?

A
  • Beta lactamases
  • PBP changes
  • Porin changes
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8
Q

What is the primary mechanism of resistance to aminoglycosides?

A

-Formation of enzymes that inactivate drugs via conjugation reactions that transfer acetyl, phosphoryl, or adenylyl groups

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9
Q

What are the primary mechanisms of resistance to macrolides and clindamycin?

A
  • Formation of methyltransferases that alter drug binding sites on the 50s subunit
  • Active transport out of cells
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10
Q

What is the primary mechanism of resistance to tetracyclines?

A

-Increased activity of transport systems that pump drugs out of the cell

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11
Q

What are the primary mechanisms of resistance to sulfonamides?

A
  • Change in sensitivity to inhibition of target enzyme
  • Increased formation of PABA
  • Use of exogenous folic acid
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12
Q

What are the primary mechanisms of resistance to fluoroquinolones?

A
  • Change in sensitivity to inhibition of target enzymes

- Increased activity of transport systems that promote drug efflux

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13
Q

What are the primary mechanisms of resistance to chloramphenicol?

A

Formation of inactivating acetyltransferases

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14
Q

What is the specific MOA of beta lactam drugs (penicillins and cephalosporins)?

A

Beta-lactam ring bind to PBPs to irreversibly inhibit transpeptidase (enzyme used for cross linking of the bacterial cell wall)

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15
Q

What are the subgroups of the penicillins?

A
  • Very narrow spectrum (least gram neg coverage for penicillins)
  • Narrow spectrum
  • Broad
  • Very broad (most gram negative coverage for penicillins)
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16
Q

What is the ONLY subgroup of penicillins that are beta-lactamase resistant?

A

The very narrow spectrum penicillin group are beta lactamase resistant-nafcillin, oxacillin, and methicillin

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17
Q

Very narrow spectrum penicillins

A
  • Beta-lactamase resistant

- Nafcillin, oxacillin, and methicillin

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18
Q

The very narrow spectrum penicillins are used to treat what infections?

A

Known or suspected staph (MSSA/non-MRSA) infections-osteomyelitis, skin infections (abscesses), endocarditis

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19
Q

Narrow spectrum penicillins

A
  • Beta lactamase sensitive

- Penicillin G and penicillin V

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20
Q

The narrow spectrum penicillins are used to treat what infections?

A
  • Streptococci - strep pharyngitis
  • Pneumococci
  • Meningococci
  • Treponema palllidum (penicillin G)
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21
Q

Broad spectrum penicillins

A
  • Aminopenicillins-Amoxicillin and ampicillin

- Beta lactamase sensitive

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22
Q

Broad spectrum penicillins (ampicillin or amoxicillin) can be used to treat what infections?

A
  • Gram positive cocci such as strep (not staph)
  • E. coli
  • Pneumonia-strep pneumo, H. Influenzae
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23
Q

Amoxicillin is used to treat what infections?

A
  • Otitis media/sinusitis-strep pneumo, H. influenzae, and moraxella catarrhalis
  • Borrelia burgdorferi
  • Helicobacter pylori
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24
Q

Ampicillin is used to treat what infections?

A
  • Listeria
  • Anaerobic infections (aspiration pneumonia)
  • Enterococcus
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25
Very broad spectrum penicillins
- Ticarcillin and piperacillin | - Beta lactamase sensitive
26
Very broad spectrum penicillins can be used to treat what infections?
-Increased activity against gram negative rods-Pseudomonas aeruginosa! (Nosocomial infections, empiric treatment of sepsis)
27
Name the beta lactamase inhibitors and what they are used for
- Clavulinic acid and sulbactam | - Suicide inhibitors that enhance the activity of penicillins by inhibiting beta lactamase
28
What are the possible side effects of penicillins?
- Hypersensitivity (types 1-4 possible), skin rash (type 4) common - GI distress (NVD), especially ampicillin - Jarish-Herxheimer rxn (fever, myalgia) in tx of syphilis (expected)
29
Identify mechanisms and examples of each of the different types of drug hypersensitivity reactions
- Type 1-IgE mediated, rapid onset, anaphylaxis, angioedema, laryngospasm - Type 2-IgM and IgG Abs fixed to cells-vasculitis, neutropenia, + Coombs test - Type 3-Immune complex formation-vasculitis, serum sickness, interstitial nephritis - Type 4-urticarial and maculopapular rashes, SJS
30
What is the MOA of cephalosporins?
Bind to PBPs to inhibit transpeptidase (identical to penicillins, mechanisms of resistance identical as well)
31
First generation cephalosporins and what are they used for?
- Cefazolin, cephalexin - Spectrum-gram positive cocci (strep, MSSA/not MRSA), E. coli, Klebsiella, and some proteus species - Common use in surgical prophylaxis
32
Second generation cephalosporins and what are they used for?
- Cefotetan, cefaclor, cefuroxime | - Spectrum-increased gram negative coverage, including some anaerobes
33
Third generation cephalosporins and what is the route of administration for each?
- Ceftriaxone (IM) - Cefotaxime (parenteral) - Cefdinir and cefixime (oral)
34
What are the third generation cephalosporins used for?
- Gram positive and gram negative cocci (neisseria gonorrhea) - Plus many gram negative rods - Important for empiric management of meningitis and sepsis
35
Fourth generation cephalosporin and what is its route of administration and other important characteristics?
Cefepime (IV)-even wider spectrum and resistant to most beta lactamases
36
Which classes of cephalosporins enter the CNS?
- Cefuroxime (2nd gen) - Third gen - Fourth gen
37
What is ceftaroline and what is it used for?
- An unclassified (5th gen) cephalosporin | - Can bind to the most often seen mutation of the PBP in MRSA
38
What are the specific organisms that are not covered by cephalosporins?
- *L*isteria - *A*typicals (chlamydia, mycoplasma) - *M*RSA - *E*nterococci
39
How are penicillins and cephalosporins eliminated from the body?
- Penicillins and cephalosporins are eliminated by active tubular secretion - modify dose in renal dysfunction - Secretion is blocked by probenecid
40
Why should you avoid ceftriaxone in neonates?
- Ceftriaxone is largely eliminated in the bile | - Neonates have low biliary metabolism -> sludging
41
If a patient has a rash to penicillin what should you treat them with?
Cephalosporin
42
What are the possible side effects of cephalosporins?
- Wide range but rashes and drug fever most common | - Positive Coombs test but rarely hemolysis
43
If a patient has anaphylaxis to penicillin what should you treat them with?
Non-beta lactam - For gram positive orgs-> macrolides - For gram neg orgs -> aztreonam
44
Imipenem and meropenem MOA?
- Same as penicillins and cephalosporins | - Resistant to beta lactamases
45
Imipenem and meropenem can be used to treat what infections?
- Gram positive cocci - Gram negative rods (enterobacter, pseudomonas) - Anaerobes - Important in-hospital agents for empiric use in severe unidentified infections (very broad spectrum)
46
What must be administered with imipenem?
Imipenem is given with cilastatin-a renal dehydropeptidase inhibitor-inhibits imipenem's metabolism to a nephrotoxic metabolite
47
How are imipenem and meropenem eliminated from the body?
Renal elimination -> decrease dose in renal dysfx
48
What are the possible side effects of imipenem and meropenem?
- GI distress - Drug fever (partial cross allergenicity with penicillins) - CNS effects, including seizures with imipenem in overdose or renal dysfx
49
What is the MOA of aztreonam?
- Same as penicillins and cephalosporins | - Resistant to beta lactamases
50
What are the uses of aztreonam?
IV drug used for gram negative rods | -No cross allergenicity with penicillins/cephalosporins
51
What is the mechanism of resistance used by MRSA?
Modified transpeptidase
52
What is the MOA of vancomycin?
Vancomycin binds at the D-ala D-ala muramyl pentapeptide to inhibit transglycolase (enzyme involved in elongation of peptidoglycan chains) -Does not interfere with PBPs
53
What is the spectrum of use for vancomycin?
Gram positive ONLY - MRSA - Enterococci - C difficile (backup drug)
54
What is the drug of choice for C difficile infection?
Metronidazole
55
What are the pharmacokinetics of vancomycin?
- Used IV and orally (not absorbed) in colitis - Enters most tissues (bone) but not CNS - Eliminated by renal filtration (important to decrease dose in renal dysfx)
56
What are the possible side effects of vancomycin?
- Red man syndrome-histamine release - Ototoxicity (usually permanent, additive with other drugs) - Nephrotoxicity (mild but additive with other drugs
57
What is the mechanism of resistance used by enterococci to become resistant to vancomycin (VRE)?
D-ala is replaced by D-lactate
58
Which protein synthesis inhibitor antibiotics inhibit formation of the initiation complex?
- Aminoglycosides (30S) | - Linezolid (50S)
59
Which protein synthesis inhibitor antibiotics inhibit amino acid incorporation and how do they do this?
Tetracyclines (30S)-block the attachment of aminoacyl tRNA to acceptor site
60
Which protein synthesis inhibitor antibiotics inhibit formation of the peptide bond and how does it do this?
Chloramphenicol (50S)-inhibits the activity of peptidyl transferase
61
Which protein synthesis inhibitor antibiotics inhibit translocation and how do they do this?
-Macrolides and clindamycin-Inhibit translocation of peptidyl-tRNA from acceptor to donor site
62
What characteristic of bacteria causes innate resistance to aminoglycosides?
Aminoglycosides accumulate intracellularly in microorganisms via an *O2-dependent* uptake -> anaerobes are innately resistant
63
What are examples of aminoglycoside abx?
- Gentamicin, tobramycin, and amikacin - often used in combinations - Streptomycin
64
Aminoglycosides are mainly used to treat what type of bacteria?
Gram negative rods
65
What is streptomycin used for?
- Tuberculosis | - DOC for bubonic plague and tularemia
66
What are the pharmacokinetics of aminoglycosides?
- Polar compounds - not absorbed orally or widely distributed into tissues - Renal elimination is proportional to GFR, major dose reduction needed in renal dysfx
67
What are the possible side effects of aminoglycosides?
- Nephrotoxicity - Ototoxicity - Muscle weakness (may enhance effects of muscle relaxants)
68
What is a good way to remember the key characteristics of aminoglycosides?
ami*NO*glycosides - *N*ephro, *O*totoxicity - *N*eed *O*xygen - *N*eg *O*rgs (rods)
69
Explain the once daily dosing of aminoglycosides
Antibacterial effects depend mainly on peak drug level (rather than time) and continue with blood levels less than MIC-a post-antibiotic effect (PAE) -Toxicity depends on both blood level and the time that such levels are greater than a specific threshold (i.e. Total dose)
70
What is the spectrum of treatment of tetracyclines?
"Broad spectrum" abx - Chlamydia - Mycoplasma - H pylori - Rickettsia, borrelia burgdorferi ("Tets for ticks") - Brucella, vibrio, and treponema (backup drug)
71
What are some specific examples of tetracyclines and what are they used for?
- Doxycycline-particularly useful in prostatitis (reaches high levels in prostatic fluid) - Minocycline-in saliva and tears at high concentrations and used in the meningococcal carrier state
72
What are the pharmacokinetics of tetracyclines?
- Kidney for most (decrease dose in renal dysfx) - Liver for doxycycline - Chelators-tetracyclines bind divalent cations (Ca-avoid milk, Mg, and Fe) which decreases their absorption
73
What are the possible side effects of tetracyclines?
- Tooth enamel dysplasia and decreased bone growth in children (avoid) - Phototoxicity (demeclocycline, doxycycline) - Vestibular dysfx (minocycline) - Liver dysfx in pregnancy at high doses
74
What is chloramphenicol used for?
- Meningitis in third world countries (not widely available in the US) - Backup drug for salmonella typhi, B fragilis, rickettsia, and bacterial meningitis
75
What are the main side effects of chloramphenicol?
- Dose dependent bone marrow suppression (common) - Aplastic anemia (common) - Gray baby syndrome in neonates (decreased glucuronyl transferase)
76
Name the 3 macrolides
Azithromycin, clarithromycin, erythromycin
77
What is the spectrum of treatment for macrolide abx? Mnemonic?
-Gram positive cocci (not MRSA) -Atypical orgs (chlamydia, mycoplasma, and ureaplasma) -Legionella pneumophila -Campylobacter jejuni -Mycobacterium avium complex (MAC) -H pylori -Bordetella pertussis "GAL CoMe Here Bitch"
78
Azithromycin is specifically used to treat what type of pneumonia and what types of bacteria cause this pneumonia?
Azithromycin is used to treat "walking pneumonia" caused by: - Mycoplasma pneumoniae - Legionella - Chlamydia pneumoniae
79
Azithromycin and clarithromycin are used to treat what type of pneumonia and what types of bacteria cause this type of pneumonia?
Azithromycin and clarithromycin are used to treat community acquired pneumonia caused by: - Strep pneumo - H influenzae - M catarrhalis
80
What are the diseases caused by chlamydia trachomatis and what can be used to treat them?
- Urethritis and cervicitis-tx with azithromycin | - Neonatal conjunctivitis and pneumonia-oral erythromycin
81
The neonatal conjunctivitis caused by neisseria gonorrhoeae can be treated with?
Erythromycin
82
What can be used to treat babesiosis?
Clindamycin and atovaquone
83
What can be used to treat diphtheria?
Erythromycin
84
What can be used to treat cat scratch disease and what organism causes this?
Azithromycin can be used to treat cat scratch disease caused by bartonella henslae
85
What drug should be administered at a CD4 count < 50 for MAC prophylaxis?
Azithromycin
86
What is the important pharmacokinetic property of macrolides?
They are p450 inhibitors (clarithromycin and erythromycin) | -ACE your macrolides
87
What are the possible side effects of macrolides?
- Gastrointestinal distress (stimulate motilin receptors) - Reversible deafness - Increased QT interval
88
Which macrolide could be used to treat diabetic gastroparesis?
Erythromycin (or use metoclopramide)
89
If you suspect pelvic inflammatory diseases what types of bacteria should you suspect and what abx should you give to cover both?
Give ceftriaxone for neisseria and azithromycin for chlamydia
90
Clindamycin
Not a macrolide, but has the same mechanisms of action and resistance
91
What is the spectrum of treatment for clindamycin?
Narrow spectrum - gram positive cocci (including community acquired MRSA) - Anaerobes including B fragilis (backup drug) - Concentration in bone has clinical value in osteomyelitis due to gram pos cocci
92
What is the main side effect of clindamycin?
Pseudomembranous colitis (most likely cause)
93
What can be used to treat VRSA?
Linezolid
94
What antibiotics are contraindicated in pregnancy?
- *F*luoroquinolones - *A*minoglycosides - *T*etracyclines - *S*ulfonamides
95
What are the main antibiotics that can cause phototoxicity?
"FoToS" - *F*luoroquinolones * O* - *T*etracyclines * O* - *S*ulfonamides
96
What enzyme is inhibited by sulfonamides?
``` Dihydropteroate synthetase (pteridine and PABA accumulate) -This reaction/enzyme are only found in bacteria ```
97
What enzyme is inhibited by trimethoprim and pyrimethamine (and methotrexate-used in RA and cancer)?
``` Dihydrofolate reductase (dihydrofolic acid accumulates) -This reaction/enzyme are found in human and bacterial cells ```
98
Sulfonamides and trimethoprim are classified as?
Antimetabolites-substance that inhibits cell growth by competing with or substituting for a natural substrate in an enzymatic process
99
What is sulfsalazine and what are the breakdown products and what are they used for?
Sulfsalazine is a prodrug used in ulcerative colitis and RA - Sulfsalazine is broken down by colonic bacteria into: - 5-aminosalicylic acid (UC) - Sulfapyridine (RA)
100
What types of bacteria can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?
- DOC in Nocardia - Listeria (backup) - Gram negative infx-E coli (UTIs), salmonella, shigella, H influenzae - Gram positive infx-staph (incl. comm. acquired MRSA), strep
101
What type of fungus can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?
Pneumocystis jiroveci-MC opportunistic infx in AIDS pts
102
What type of protozoa can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?
Toxoplasma gondii (sulfadiazine and pyrimethamine)
103
What are the pharmacokinetics of sulfonamides?
- Hepatically acetylated (conjugation) - Renally excreted metabolites cause crystalluria - High protein binding (kernicterus in neonates, avoid in 3rd trimester)
104
What are the possible side effects of sulfonamides?
- Hypersensitivity (rashes, SJS) - Hemolysis in G6PD def. - Phototoxicity
105
What is stevens johnson syndrome and what are the symptoms?
A type of erythema multiforme-hemorrhagic crusting of the lips and oral mucosa
106
What is the main possible side effect of trimethoprim/ pyrimethamine?
Bone marrow suppression (leukopenia)
107
What are examples of fluoroquinolones?
Ciprofloxacin, levofloxacin, and other "-floxacins"
108
What is the MOA of fluoroquinolones?
Interfere with DNA synthesis -Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV (responsible for separation of replicated DNA during cell division)
109
What are the main clinical uses for fluoroquinolones?
- UTIs (particularly when resistant to cotrimoxazole) - STDs/PIDs-chlamydia, gonorrhea - Skin, soft tissue, and bone infections by gram neg orgs - Diarrhea to shigella, salmonella, E coli, and campylobacter - Anthrax
110
Which specific fluoroquinolone is used for drug resistant pneumococci?
Levofloxacin
111
What are the pharmacokinetics of fluoroquinolones?
- Fe and Ca limit their absorption - Eliminated by kidney via filtration and active secretion (inhibited by probenecid) - Reduce dose in renal dysfx
112
What are the main side effects of fluoroquinolones?
- Tendonitis, tendon rupture - CNS effects (insomnia, dizziness, headaches) - Inhibit chondrogenesis (C/I in children)
113
What are the main therapy combinations for H pylori GI ulcers?
- Omeprazole (PPI) + clarithromycin + amoxicillin (usually) | - Bismuth + metronidazole + tetracycline (BMT regimen)
114
What is the MOA of metronidazole (unclassified antibiotic)?
It is converted to free radicals by ferredoxin, binds to DNA and other macromolecules
115
What type of bacteria does metronidazole treat? | -Mnemonic?
Anaerobic gram negative bacteria - Bacteroides (DOC) - Clostridium (DOC in pseudomembranous colitis) - Gardnerella (DOC) - H pylori
116
Metronidazole also treats what protozoa?
- Giardia - Trichomonas - Entamoeba
117
What are the side effects of metronidazole?
- Metallic taste | - Disulfiram-like effect
118
What are the 4 main drugs used to treat tuberculosis?
- Isoniazid - Rifampin - Ethambutol - Pyrazinamide - streptomycin can also be used
119
What is the MOA of isoniazid?
- Inhibits mycolic acid synthesis (unique to TB) | - Prodrug (requires conversion by catalase)
120
What is the mechanism of resistance to isoniazid?
High level resistance-deletions in katG gene (encodes the catalase needed for activation)
121
What are the possible side effects of isoniazid?
- Hepatitis - Peripheral neuritis (use vitamin B6) - Sideroblastic anemia (use vitamin B6) - SLE in slow acetylators
122
What is the MOA of rifampin?
-Inhibits DNA-dependent RNA polymerase (nucleic acid synthesis inhibitor)
123
What are the possible side effects of rifampin?
- Hepatitis - Induction of p450 - Red orange metabolites (tears, sweat, urine)
124
What is the MOA of ethambutol?
Inhibits synthesis of arabinogalactan (cell wall component)
125
What are the possible side effects of ethambutol?
-Dose dependent retrobulbar neuritis -> decreased visual acuity and color blindness
126
What are the possible side effects of pyrazinamide?
- Hepatitis | - Hyperuricemia (everybody gets this)
127
Clinical correlate pg 189 in pharm book-INH prophylaxis?
?
128
What is the prophylaxis treatment for mycobacterium avium complex (MAC)?
-Prophylaxis-azithromycin or clarithromycin
129
What are the abx that can be used to treat anthrax?
- Fluoroquinolones - Penicillins - Tetracyclines
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