Antimicrobial Therapy Flashcards

1
Q

Antimicrobial therapy

folic acid synthesis

A
  • Sulfonamides
  • Trimethoprim
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2
Q

Antimicrobial therapy

DNA Topoisomerases

A
  • Fluoroquinolones
  • Quinolone
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3
Q

Antimicrobial therapy

damages DNA

A

Metronidazole

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4
Q

Antimicrobial therapy

mRNA synthesis

A

Rifampin

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5
Q

Antimicrobial therapy

protein synthesis (50S)

A
  • Chloramphenicol
  • Clindamycin
  • Linezolid
  • Macrolides
  • Streptogramins
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6
Q

Antimicrobial therapy

protein synthesis (30S)

A
  • Aminoglycosides
  • Tetracyclines
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7
Q

Antimicrobial therapy

cell wall synthesis (peptidoglycan cross linking)

A
  • penicillinase-sensitive penicillins
  • penicillinase-resistant penicillins
  • antipseudomonals
  • cephalosporins
  • carbapenems
  • monobactams
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8
Q

Antimicrobial therapy

cell wall synthesis (peptidoglycan synthesis)

A

Glycopeptides

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9
Q

Penicillin G, V

administration

A
  • prototype ß-lactam antibiotics
  • penicillin G - IV & IM
  • penicillin V - oral
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10
Q

Penicillin G, V

mechanism

A
  • bind PBPs (transpeptidases)
  • block transpeptidase cross-linking of peptidoglycan
  • activate autolytic enzymes
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11
Q

Penicillin G, V

clinical use

penicillinase

A
  • gram (+) organisms
    • S. pneumoniae, S. pyogenes, Actinomyces
  • N. meningitidis, T. pallidum
  • bactericidal: gram (+) cocci, gram (+) rods, gram (-) cocci, spirochetes
  • penicillinase sensitive
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12
Q

Penicillin G, V

toxicity

A
  • hypersensitivity rxns
  • hemolytic anemia
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13
Q

Penicillin G, V

resistance

A

penicillinase in bacteria cleaves ß-lactam ring

type of ß-lactamase

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14
Q

Ampicillin, amoxicillin

mechanism

A
  • same as penicillin
  • wider spectrum
  • penicillinase sensitive
  • combine w/ clavulanic acid to protect against ß-lactamase
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15
Q

Ampicillin, amoxicillin

clinical use

A

HELPSS kill enterococci

  • extended-spectrum penicillin
  • Haemophilus influenzae
  • E. coli
  • Listeria monocytogenes
  • Proteus mirabilis
  • Salmonella
  • Shigella
  • enterococci
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16
Q

Ampicillin, amoxicillin

toxicity

A
  • hypersensitivity rxns
  • rash
  • psuedomembranous colitis
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17
Q

Ampicillin, amoxicillin

resistance

A
  • penicillinase in bacteria cleaves ß-lactam ring
  • ß-lactamase
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18
Q

Oxacillin, nafcillin, dicloxacillin

mechanism

A
  • same as penicillin
  • narrow spectrum
  • **penicillinase resistant **
    • bulky R group
    • blocks access of ß-lactamase to ß-lactam ring
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19
Q

Oxacillin, nafcillin, dicloxacillin

clinical use

A

S. aureus (except MRSA)

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20
Q

Oxacillin, nafcillin, dicloxacillin

toxicity

A
  • hypersensitivity rxns
  • interstitial nephritis
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21
Q

Ticarcillin, piperacillin

mechanism

A
  • same as penicillin
  • extended spectrum
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22
Q

Ticarcillin, piperacillin

clinical use

A
  • Pseudomonas spp.
  • gram-negative rods
  • susceptible to penicillinase
  • **use w/ ß-lactamase inhibitors **
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23
Q

Ticarcillin, piperacillin

toxicity

A

hypersensitivity rxns

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24
Q

ß-lactamase inhibitors

A

CAST

  • Clavulanic Acid
  • Sulbactam
  • Tazobactam
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25
Cephalosporins mechanism
* ß-lactams * **inhibit cell wall synthesis ** * less susceptible to penicillinases * bactericidal
26
1st generation cephalosporins
**cefazolin, cephalexin ** * gram (+) cocci * PEcK * Proteus mirabilis * E. coli * Klebsiella
27
\_\_\_\_\_\_\_ used prior to surgery to prevent S. aureus wound infections.
Cefazolin
28
2nd generation cephalosporins
**cefoxitin, cefaclor, cefuroxime ** * gram (+) cocci * HEN PEcKS * Haemophilus influenzae * Enterobacter aerogenes * Neisseria spp. * Proteus mirabilis * E. coli * Klebsiella pneumoniae * Serratia marcescens
29
3rd generation cephalosporins
**ceftriaxone, cefotaxime, ceftazidime ** * serious gram (-) infections resistant to other ß-lactams * Ceftriaxone - meningitis & gonorrhea * Ceftazidime - Psuedomonas
30
4th generation cephalosporins
**cefepime** * increased activity against Pseudomonas & gram (+) organisms
31
5th generation cephalosporins
**ceftaroline** * broad gram (+) & gram (-) organism coverage * MRSA, not Pseudomonas
32
Cephalosporins toxicity
* hypersensitivity rxns * vitamin K deficiency * low cross-reactivity w/ penicillins * increased nephrotoxicity of aminoglycosides
33
Aztreonam mechanism
* monobactam * resistant to ß-lactamases * **prevents peptidoglycan cross-linking** * **binds PBP** * synergistic w/ aminoglycosides * no cross-allergy w/ penicillins
34
Aztreonam clinical use
* gram (-) rods only * penicillin-allergic patients * patients w/ renal insufficiency who can't tolerate aminoglycosides
35
Aztreonam toxicity
* usually non-toxic * occasional GI upset
36
Carbapenems
* Imipenem * Meropenem * Ertapenem * Doripenem
37
Carbapenems mechanism
Imipenem * broad-spectrum, ß-lactamase resistant * admin w/ _cilastatin_ * inhibitor of renal dehydropeptidase I * decreased inactivation of drug in renal tubules
38
Carbapenems clinical use
* gram (+) cocci, gram (-) rods, anaerobes * wide spectrum * **life-threatening infections or when other drugs have failed ** * Meropenam has decreased risk of seizures
39
Carbapenems toxicity
* GI distress * skin rash * CNS toxicity (seizures)
40
Vancomycin mechanism
* inhibits cell wall peptidoglycan formation * binds D-ala-D-ala * bactericidal
41
Vancomycin clinical use
* gram (+) only * serious, multidrug-resistant organisms * MRSA, enterococci, C. difficile
42
Vancomycin toxicity
**NOT** trouble-free * **N**ephrotoxicity * **O**totoxicity * **T**hrombophlebitis * diffuse flushing * red man syndrome
43
Vancomycin resistance
* aa modification of D-ala-D-ala to D-ala-D-lac
44
Protein synthesis inhibitors * 30S inhibitors * 50S inhibitors
Buy **AT 30**, **CCEL** (sell) at **50** * 30S inhibitors * Aminoglycosides * Tetracyclines * 50S inhibitors * Chloramphenicol, Clindamycin * Erythromycin (macrolides) * Linezolid
45
Aminoglycosides
GNATS * **G**entamicin * **N**eomycin * **A**mikacin * **T**obramycin * **S**treptomycin
46
Aminoglycosides mechanism
* bactericidal * **inhibits formation of initiation complex ** * misreading of mRNA * blocks translocation * requires O2 (aerobes)
47
Aminoglycosides clinical use
* severe gram (-) rod infections * synergistic w/ ß-lactam antibiotics
48
\_\_\_\_\_\_\_\_ for bowel surgery.
Neomycin
49
Aminoglycosides toxicity
NNOT * **N**ephrotoxicity * **N**euromuscular blockade * **O**totoxicity * **T**eratogen
50
Aminoglycosides resistance
* bacterial transferase enzymes inactivate drug * acetylation * phosphorylation * adenylation
51
Tetracyclines
* Tetracycline * Doxycycline * Minocycline
52
Tetracyclines mechanism
* bacteriostatic * binds 30S & prevents attachment of aminoacyl tRNA * limited CNS penetration
53
\_\_\_\_\_\_\_\_ is fecally eliminated & can be used in patients w/ renal failure.
Doxycycline
54
Do not take tetracyclines w/ \_\_\_\_\_\_, \_\_\_\_\_, or \_\_\_\_-containing preparations b/c divalent cations inhibit its absorption in the gut.
* milk (Ca2+) * antacids (Ca2+, Mg2+) * iron
55
Tetracyclines clinical use
* Borrelia burgdorferi * M. pneumoniae * Rickettsia & Chlamydia (intracellular) * treats acne
56
Tetracyclines toxicity
* GI distress * _discoloration of teeth & inhibition of bone growth _ * children * photosensitivity * contraindicated in pregnancy
57
Tetracyclines resistance
decreased uptake or increased efflux out of bacterial cells by _plasmid-encoded transport pumps _
58
Macrolides
* Azithromycin * Clarithromycin * Erythromycin
59
Macrolides mechanism
* inhibit protein synthesis * **block translocation ** * bind 23S rRNA of 50S ribosomal subunit * bacteriostatic
60
Macrolides clinical use
* atypical pneumonias * Mycoplasma * Chlamydia * Legionella * STDs * Chlamydia * gram (+) cocci * Strep in patients allergic to penicillin
61
Macrolides toxicity
**MACRO** * **G**I Motility issues * **A**rrhythmia (prolonged QT) * acute **C**holestatic hepatitis * **R**ash * e**O**sinophilia * Increases serum conc of theophyllines, oral anticoagulants
62
Macrolides resistance
methylation of 23S rRNA-binding site
63
Chloramphenicol mechanism
blocks peptidyltransferase at 50S ribosomal subunit
64
Chloramphenicol clinical use
* meningitis * Haemophilus influenzae * Neisseria meningitidis * Streptococcus pneumoniae * rocky mountain spotted fever * Rickettsia rickettsii * limited use due to toxicity (but low cost)
65
Chloramphenicol toxicity
* anemia (dose dependent) * aplastic anemia (dose independent) * **gray baby syndrome ** * premature infants * lack liver UDP-glucuronyl transferase
66
Chloramphenicol resistance
plasmid-encoded acetyltransferase inactivates the drug
67
Clindamycin mechanism
blocks peptide transfer (translocation) at 50S ribosomal subunit
68
Clindamycin clinical use
* anaerobic infections (Bacteroides, Clostridium perfringens) in... * aspiration pneumonia * lung abscesses * oral infections * invasive group A strep infection
69
\_\_\_\_\_\_ treats anaerobes _above_ the diaphragm. \_\_\_\_\_\_ treats anaerobes _below_ the diaphragm.
Clindamycin Metronidazole
70
Clindamycin toxicity
* Pseudomembranous colitis (C. diff overgrowth) * fever * diarrhea
71
Sulfonamides
* sulfamethoxazole (SMX) * sulfisoxazole * sulfadiazine
72
Sulfonamides mechanism
* inhibit folate synthesis * PABA antimetabolites inhibit dihydropteroate synthase * bacteriostatic
73
Sulfonamides clinical use
* gram (+) * gram (-) * Nocardia * Chlamydia * triple sulfas or SMX for simple UTI
74
Sulfonamides toxicity
* hypersensitivity rxns * hemolysis if G6PD deficient * nephrotoxicity (tubulointerstitial nephritis) * photosensitivity * kernicterus in infants * displace other drugs from albumin (warfarin)
75
Sulfonamides resistance
* altered enzyme (bacterial dihydropteroate synthase) * decreased uptake * increased PABA synthesis
76
Trimethoprim mechanism
inhibits bacterial DHFR bacteriostatic
77
Trimethoprim clinical use
* **combination w/ sulfonamides (TMP-SMX)** * sequential blockade of folate synthesis * combination used for UTIs, Shigella, Salmonella, PCP pneumonia treatment & prophylaxis, toxoplasmosis prophylaxis
78
Trimethoprim toxicity
* megaloblastic anemia * leukopenia * granulocytopenia
79
Fluoroquinolones
* ciprofloxacin * norfloxacin * levofloxacin * ofloxacin * sparfloxacin * moxifloxacin * gemifloxacin * enoxacin * nalidixic acid (quinolone)
80
Fluoroquinolones mechanism
* inhibit DNA gyrase (topoisomerase II) & topoisomerase IV * bactericidal must NOT be taken w/ antiacids
81
Fluoroquinolones clinical use
* gram (-) rods of urinary & GI tracts * includes Pseudomonas * Neisseria * some gram (+)
82
Fluoroquinolones toxicity
* GI upset * superinfections * skin rashes * headache * dizziness * less common: tendonitis, tendon rupture, leg cramps, myalgias * contraindicated in pregnant women, nursing mothers, children \<18 YO --\> possible damage to cartilage * prolonged QT interval * tendon rupture in \>60 YO & patients taking prednisone
83
Fluoroquinolones resistance
* chromosome-encoded mutation in DNA gyrase * plasmid-mediated resistance * efflux pumps
84
Metronidazole mechanism
* free radical toxic metabolites in bacterial cell that damage DNA * bactericidal * antiprotozoal
85
Metronidazole clinical use
**GET GAP ** * Giardia * Entamoeba * Trichomonas * Gardnerella vaginalis * Anaerobes (Bacteroides, C. difficile) * H. Pylori (triple therapy) * metronidazole + PPI + clarithromycin
86
Metronidazole toxicity
* disulfiram-like rxn w/ alcohol * severe flushing * tachycardia * hypotension * headache * metallic taste
87
Antimycobacterial drugs * M. tuberculosis * M. avium-intracellulare * M. leprae
* M. tuberculosis * Prophylaxis: Isoniazid * Treatment: RIPE * Rifampin * Isoniazid * Pyrazinamide * Ethambutol * M. avium-intracellulare * Prophylaxis: azithromycin, rifabutin * Treatment: azithromycin/clarithromycin + ethambutol * M. leprae * Prophylaxis: N/A * Treatment: dapson & rifampin (T); + clofazimine (L)
88
Isoniazid mechanism
* decreases synthesis of mycolic acids * bacterial catalase-peroxidase needed to convert to active metabolite
89
Isoniazid toxicity
**INH** **I**njures **N**eurons & **H**epatocytes * neurotoxicity * hepatotoxicity * pyridoxine (vit B6) can prevent neurotoxicity, lupus
90
Rifamycins
* Rifampin * Rifabutin
91
4 R's of Rifampin
Rif**amp**in r**amp**s up CYP450, **but** rifa**but**in does not * **R**NA polymerase inhibitor * **R**amps up microsomal CYP450 * **R**ed/orange body fluids * **R**apid resistance if used alone
92
Rifamycins \_\_\_\_\_ favored over _____ in patients w/ HIV infection due to less CYP450 stimulation.
rifabutin rifampin
93
Pyrazinamide mechanism
* uncertain * **thought to acidify intracellular environment ** * conversion to pyrazinoic acid * effective in acidic pH of phagolysosomes (TB engulfed by macrophages)
94
Pyrazinamide clinical use toxicity
* Mycobacterium tuberculosis * Hyperuricemia, hepatotoxicity
95
Ethambutol mechanism
decreases carb polymerization of mycobacterium cell wall by blocking _arabinosyltransferase_
96
Ethambutol clinical use toxicity
* Mycobacterium tuberculosis * Optic neuropathy (red-green color blindness)
97
antimicrobial prophylaxis endocarditis w/ surgical or dental procedures
penicillins
98
antimicrobial prophylaxis gonorrhea
ceftriaxone
99
antimicrobial prophylaxis history of recurrent UTIs
TMP-SMX
100
antimicrobial prophylaxis meningococcal infection
ciprofloxacin rifampin (children)
101
antimicrobial prophylaxis pregnant woman carrying group B strep
ampicillin
102
antimicrobial prophylaxis prevention of gonococcal or chlamydial conjunctivitis of the newborn
erythromycin ointment
103
antimicrobial prophylaxis prevention of postsurgical infection due to S. aureus
cefazolin
104
antimicrobial prophylaxis prophylaxis of strep pharyngitis in child w/ prior rheumatic fever
oral penicillin
105
antimicrobial prophylaxis syphilis
benzathine penicillin G