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Boards First Aid and Kaplan > Antimicrobial Agents > Flashcards

Antimicrobial Agents Flashcards

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
Q

Very broad spectrum penicillins

A
  • Ticarcillin and piperacillin

- Beta lactamase sensitive

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26
Q

Very broad spectrum penicillins can be used to treat what infections?

A

-Increased activity against gram negative rods-Pseudomonas aeruginosa! (Nosocomial infections, empiric treatment of sepsis)

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27
Q

Name the beta lactamase inhibitors and what they are used for

A
  • Clavulinic acid and sulbactam

- Suicide inhibitors that enhance the activity of penicillins by inhibiting beta lactamase

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28
Q

What are the possible side effects of penicillins?

A
  • 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)
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29
Q

Identify mechanisms and examples of each of the different types of drug hypersensitivity reactions

A
  • 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
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30
Q

What is the MOA of cephalosporins?

A

Bind to PBPs to inhibit transpeptidase (identical to penicillins, mechanisms of resistance identical as well)

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31
Q

First generation cephalosporins and what are they used for?

A
  • Cefazolin, cephalexin
  • Spectrum-gram positive cocci (strep, MSSA/not MRSA), E. coli, Klebsiella, and some proteus species
  • Common use in surgical prophylaxis
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32
Q

Second generation cephalosporins and what are they used for?

A
  • Cefotetan, cefaclor, cefuroxime

- Spectrum-increased gram negative coverage, including some anaerobes

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33
Q

Third generation cephalosporins and what is the route of administration for each?

A
  • Ceftriaxone (IM)
  • Cefotaxime (parenteral)
  • Cefdinir and cefixime (oral)
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34
Q

What are the third generation cephalosporins used for?

A
  • Gram positive and gram negative cocci (neisseria gonorrhea)
  • Plus many gram negative rods
  • Important for empiric management of meningitis and sepsis
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35
Q

Fourth generation cephalosporin and what is its route of administration and other important characteristics?

A

Cefepime (IV)-even wider spectrum and resistant to most beta lactamases

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36
Q

Which classes of cephalosporins enter the CNS?

A
  • Cefuroxime (2nd gen)
  • Third gen
  • Fourth gen
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37
Q

What is ceftaroline and what is it used for?

A
  • An unclassified (5th gen) cephalosporin

- Can bind to the most often seen mutation of the PBP in MRSA

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38
Q

What are the specific organisms that are not covered by cephalosporins?

A
  • Listeria
  • Atypicals (chlamydia, mycoplasma)
  • MRSA
  • Enterococci
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39
Q

How are penicillins and cephalosporins eliminated from the body?

A
  • Penicillins and cephalosporins are eliminated by active tubular secretion - modify dose in renal dysfunction
  • Secretion is blocked by probenecid
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40
Q

Why should you avoid ceftriaxone in neonates?

A
  • Ceftriaxone is largely eliminated in the bile

- Neonates have low biliary metabolism -> sludging

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41
Q

If a patient has a rash to penicillin what should you treat them with?

A

Cephalosporin

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42
Q

What are the possible side effects of cephalosporins?

A
  • Wide range but rashes and drug fever most common

- Positive Coombs test but rarely hemolysis

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43
Q

If a patient has anaphylaxis to penicillin what should you treat them with?

A

Non-beta lactam

  • For gram positive orgs-> macrolides
  • For gram neg orgs -> aztreonam
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44
Q

Imipenem and meropenem MOA?

A
  • Same as penicillins and cephalosporins

- Resistant to beta lactamases

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45
Q

Imipenem and meropenem can be used to treat what infections?

A
  • Gram positive cocci
  • Gram negative rods (enterobacter, pseudomonas)
  • Anaerobes
  • Important in-hospital agents for empiric use in severe unidentified infections (very broad spectrum)
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46
Q

What must be administered with imipenem?

A

Imipenem is given with cilastatin-a renal dehydropeptidase inhibitor-inhibits imipenem’s metabolism to a nephrotoxic metabolite

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47
Q

How are imipenem and meropenem eliminated from the body?

A

Renal elimination -> decrease dose in renal dysfx

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48
Q

What are the possible side effects of imipenem and meropenem?

A
  • GI distress
  • Drug fever (partial cross allergenicity with penicillins)
  • CNS effects, including seizures with imipenem in overdose or renal dysfx
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49
Q

What is the MOA of aztreonam?

A
  • Same as penicillins and cephalosporins

- Resistant to beta lactamases

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50
Q

What are the uses of aztreonam?

A

IV drug used for gram negative rods

-No cross allergenicity with penicillins/cephalosporins

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51
Q

What is the mechanism of resistance used by MRSA?

A

Modified transpeptidase

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52
Q

What is the MOA of vancomycin?

A

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
Q

What is the spectrum of use for vancomycin?

A

Gram positive ONLY

  • MRSA
  • Enterococci
  • C difficile (backup drug)
54
Q

What is the drug of choice for C difficile infection?

A

Metronidazole

55
Q

What are the pharmacokinetics of vancomycin?

A
  • 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
Q

What are the possible side effects of vancomycin?

A
  • Red man syndrome-histamine release
  • Ototoxicity (usually permanent, additive with other drugs)
  • Nephrotoxicity (mild but additive with other drugs
57
Q

What is the mechanism of resistance used by enterococci to become resistant to vancomycin (VRE)?

A

D-ala is replaced by D-lactate

58
Q

Which protein synthesis inhibitor antibiotics inhibit formation of the initiation complex?

A
  • Aminoglycosides (30S)

- Linezolid (50S)

59
Q

Which protein synthesis inhibitor antibiotics inhibit amino acid incorporation and how do they do this?

A

Tetracyclines (30S)-block the attachment of aminoacyl tRNA to acceptor site

60
Q

Which protein synthesis inhibitor antibiotics inhibit formation of the peptide bond and how does it do this?

A

Chloramphenicol (50S)-inhibits the activity of peptidyl transferase

61
Q

Which protein synthesis inhibitor antibiotics inhibit translocation and how do they do this?

A

-Macrolides and clindamycin-Inhibit translocation of peptidyl-tRNA from acceptor to donor site

62
Q

What characteristic of bacteria causes innate resistance to aminoglycosides?

A

Aminoglycosides accumulate intracellularly in microorganisms via an O2-dependent uptake -> anaerobes are innately resistant

63
Q

What are examples of aminoglycoside abx?

A
  • Gentamicin, tobramycin, and amikacin - often used in combinations
  • Streptomycin
64
Q

Aminoglycosides are mainly used to treat what type of bacteria?

A

Gram negative rods

65
Q

What is streptomycin used for?

A
  • Tuberculosis

- DOC for bubonic plague and tularemia

66
Q

What are the pharmacokinetics of aminoglycosides?

A
  • Polar compounds - not absorbed orally or widely distributed into tissues
  • Renal elimination is proportional to GFR, major dose reduction needed in renal dysfx
67
Q

What are the possible side effects of aminoglycosides?

A
  • Nephrotoxicity
  • Ototoxicity
  • Muscle weakness (may enhance effects of muscle relaxants)
68
Q

What is a good way to remember the key characteristics of aminoglycosides?

A

amiNOglycosides

  • Nephro, Ototoxicity
  • Need Oxygen
  • Neg Orgs (rods)
69
Q

Explain the once daily dosing of aminoglycosides

A

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
Q

What is the spectrum of treatment of tetracyclines?

A

“Broad spectrum” abx

  • Chlamydia
  • Mycoplasma
  • H pylori
  • Rickettsia, borrelia burgdorferi (“Tets for ticks”)
  • Brucella, vibrio, and treponema (backup drug)
71
Q

What are some specific examples of tetracyclines and what are they used for?

A
  • 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
Q

What are the pharmacokinetics of tetracyclines?

A
  • 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
Q

What are the possible side effects of tetracyclines?

A
  • Tooth enamel dysplasia and decreased bone growth in children (avoid)
  • Phototoxicity (demeclocycline, doxycycline)
  • Vestibular dysfx (minocycline)
  • Liver dysfx in pregnancy at high doses
74
Q

What is chloramphenicol used for?

A
  • Meningitis in third world countries (not widely available in the US)
  • Backup drug for salmonella typhi, B fragilis, rickettsia, and bacterial meningitis
75
Q

What are the main side effects of chloramphenicol?

A
  • Dose dependent bone marrow suppression (common)
  • Aplastic anemia (common)
  • Gray baby syndrome in neonates (decreased glucuronyl transferase)
76
Q

Name the 3 macrolides

A

Azithromycin, clarithromycin, erythromycin

77
Q

What is the spectrum of treatment for macrolide abx? Mnemonic?

A

-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
Q

Azithromycin is specifically used to treat what type of pneumonia and what types of bacteria cause this pneumonia?

A

Azithromycin is used to treat “walking pneumonia” caused by:

  • Mycoplasma pneumoniae
  • Legionella
  • Chlamydia pneumoniae
79
Q

Azithromycin and clarithromycin are used to treat what type of pneumonia and what types of bacteria cause this type of pneumonia?

A

Azithromycin and clarithromycin are used to treat community acquired pneumonia caused by:

  • Strep pneumo
  • H influenzae
  • M catarrhalis
80
Q

What are the diseases caused by chlamydia trachomatis and what can be used to treat them?

A
  • Urethritis and cervicitis-tx with azithromycin

- Neonatal conjunctivitis and pneumonia-oral erythromycin

81
Q

The neonatal conjunctivitis caused by neisseria gonorrhoeae can be treated with?

A

Erythromycin

82
Q

What can be used to treat babesiosis?

A

Clindamycin and atovaquone

83
Q

What can be used to treat diphtheria?

A

Erythromycin

84
Q

What can be used to treat cat scratch disease and what organism causes this?

A

Azithromycin can be used to treat cat scratch disease caused by bartonella henslae

85
Q

What drug should be administered at a CD4 count < 50 for MAC prophylaxis?

A

Azithromycin

86
Q

What is the important pharmacokinetic property of macrolides?

A

They are p450 inhibitors (clarithromycin and erythromycin)

-ACE your macrolides

87
Q

What are the possible side effects of macrolides?

A
  • Gastrointestinal distress (stimulate motilin receptors)
  • Reversible deafness
  • Increased QT interval
88
Q

Which macrolide could be used to treat diabetic gastroparesis?

A

Erythromycin (or use metoclopramide)

89
Q

If you suspect pelvic inflammatory diseases what types of bacteria should you suspect and what abx should you give to cover both?

A

Give ceftriaxone for neisseria and azithromycin for chlamydia

90
Q

Clindamycin

A

Not a macrolide, but has the same mechanisms of action and resistance

91
Q

What is the spectrum of treatment for clindamycin?

A

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
Q

What is the main side effect of clindamycin?

A

Pseudomembranous colitis (most likely cause)

93
Q

What can be used to treat VRSA?

A

Linezolid

94
Q

What antibiotics are contraindicated in pregnancy?

A
  • Fluoroquinolones
  • Aminoglycosides
  • Tetracyclines
  • Sulfonamides
95
Q

What are the main antibiotics that can cause phototoxicity?

A

“FoToS”

  • Fluoroquinolones
  • O*
  • Tetracyclines
  • O*
  • Sulfonamides
96
Q

What enzyme is inhibited by sulfonamides?

A 
Dihydropteroate synthetase (pteridine and PABA accumulate)
-This reaction/enzyme are only found in bacteria
97
Q

What enzyme is inhibited by trimethoprim and pyrimethamine (and methotrexate-used in RA and cancer)?

A 
Dihydrofolate reductase (dihydrofolic acid accumulates)
-This reaction/enzyme are found in human and bacterial cells
98
Q

Sulfonamides and trimethoprim are classified as?

A

Antimetabolites-substance that inhibits cell growth by competing with or substituting for a natural substrate in an enzymatic process

99
Q

What is sulfsalazine and what are the breakdown products and what are they used for?

A

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
Q

What types of bacteria can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?

A
  • 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
Q

What type of fungus can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?

A

Pneumocystis jiroveci-MC opportunistic infx in AIDS pts

102
Q

What type of protozoa can be treated with trimethoprim-sulfamethoxazole (cotrimoxazole)?

A

Toxoplasma gondii (sulfadiazine and pyrimethamine)

103
Q

What are the pharmacokinetics of sulfonamides?

A
  • Hepatically acetylated (conjugation)
  • Renally excreted metabolites cause crystalluria
  • High protein binding (kernicterus in neonates, avoid in 3rd trimester)
104
Q

What are the possible side effects of sulfonamides?

A
  • Hypersensitivity (rashes, SJS)
  • Hemolysis in G6PD def.
  • Phototoxicity
105
Q

What is stevens johnson syndrome and what are the symptoms?

A

A type of erythema multiforme-hemorrhagic crusting of the lips and oral mucosa

106
Q

What is the main possible side effect of trimethoprim/ pyrimethamine?

A

Bone marrow suppression (leukopenia)

107
Q

What are examples of fluoroquinolones?

A

Ciprofloxacin, levofloxacin, and other “-floxacins”

108
Q

What is the MOA of fluoroquinolones?

A

Interfere with DNA synthesis
-Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV (responsible for separation of replicated DNA during cell division)

109
Q

What are the main clinical uses for fluoroquinolones?

A
  • 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
Q

Which specific fluoroquinolone is used for drug resistant pneumococci?

A

Levofloxacin

111
Q

What are the pharmacokinetics of fluoroquinolones?

A
  • Fe and Ca limit their absorption
  • Eliminated by kidney via filtration and active secretion (inhibited by probenecid)
  • Reduce dose in renal dysfx
112
Q

What are the main side effects of fluoroquinolones?

A
  • Tendonitis, tendon rupture
  • CNS effects (insomnia, dizziness, headaches)
  • Inhibit chondrogenesis (C/I in children)
113
Q

What are the main therapy combinations for H pylori GI ulcers?

A
  • Omeprazole (PPI) + clarithromycin + amoxicillin (usually)

- Bismuth + metronidazole + tetracycline (BMT regimen)

114
Q

What is the MOA of metronidazole (unclassified antibiotic)?

A

It is converted to free radicals by ferredoxin, binds to DNA and other macromolecules

115
Q

What type of bacteria does metronidazole treat?

-Mnemonic?

A

Anaerobic gram negative bacteria

  • Bacteroides (DOC)
  • Clostridium (DOC in pseudomembranous colitis)
  • Gardnerella (DOC)
  • H pylori
116
Q

Metronidazole also treats what protozoa?

A
  • Giardia
  • Trichomonas
  • Entamoeba
117
Q

What are the side effects of metronidazole?

A
  • Metallic taste

- Disulfiram-like effect

118
Q

What are the 4 main drugs used to treat tuberculosis?

A
  • Isoniazid
  • Rifampin
  • Ethambutol
  • Pyrazinamide
  • streptomycin can also be used
119
Q

What is the MOA of isoniazid?

A
  • Inhibits mycolic acid synthesis (unique to TB)

- Prodrug (requires conversion by catalase)

120
Q

What is the mechanism of resistance to isoniazid?

A

High level resistance-deletions in katG gene (encodes the catalase needed for activation)

121
Q

What are the possible side effects of isoniazid?

A
  • Hepatitis
  • Peripheral neuritis (use vitamin B6)
  • Sideroblastic anemia (use vitamin B6)
  • SLE in slow acetylators
122
Q

What is the MOA of rifampin?

A

-Inhibits DNA-dependent RNA polymerase (nucleic acid synthesis inhibitor)

123
Q

What are the possible side effects of rifampin?

A
  • Hepatitis
  • Induction of p450
  • Red orange metabolites (tears, sweat, urine)
124
Q

What is the MOA of ethambutol?

A

Inhibits synthesis of arabinogalactan (cell wall component)

125
Q

What are the possible side effects of ethambutol?

A

-Dose dependent retrobulbar neuritis -> decreased visual acuity and color blindness

126
Q

What are the possible side effects of pyrazinamide?

A
  • Hepatitis

- Hyperuricemia (everybody gets this)

127
Q

Clinical correlate pg 189 in pharm book-INH prophylaxis?

A

?

128
Q

What is the prophylaxis treatment for mycobacterium avium complex (MAC)?

A

-Prophylaxis-azithromycin or clarithromycin

129
Q

What are the abx that can be used to treat anthrax?

A
  • Fluoroquinolones
  • Penicillins
  • Tetracyclines

Boards First Aid and Kaplan (19 decks)

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