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Respiratory II > Overview of Antimicrobial Agents Lecture > Flashcards

Overview of Antimicrobial Agents Lecture Flashcards

1
Q

Drug Classes

A

Natural Penicillins

Anti-staphylococcal Penicillins

Aminopenicillins

Anti-pseudomonal Penicillins

First Generation Cephalosporins
Second Generation Cephalosporins

Third Generation Cephalosporins

Fourth Generation Cephalosporins

Carbapenems

Monobactams

B-lactamase Inhibitors

Glycopeptides

Lipopeptides

Fluoroquinolones

Aminoglycosides

Tetracyclines/Glycylcyclines

Macrolides/Ketolides

Lincosamides

Oxazolidinones

Metronidazole

Sulfonamides/Trimethoprim

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2
Q

Natural Penicillins

A

Penicillin G (IV, IM)

Penicillin V (PO)

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3
Q

Anti-staphylococcal Penicillins

A

Oxacillin (IV, IM)

Dicloxacillin (PO)

Nafcillin (IV, IM)

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4
Q

Aminopenicillins

A

Ampicillin (PO, IV, IM)*

Amoxicillin (PO)*

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5
Q

Anti-pseudomonal Penicillins

A

Piperacillin (IV)

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6
Q

First Generation Cephalosporins

A

Cefazolin (IV, IM)

Cephalexin [Keflex] (PO)

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7
Q

Second Generation Cephalosporins

A

Cefoxitin (IV)

Cefuroxime (PO, IV, IM)

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8
Q

Third Generation Cephalosporins

A

Ceftriaxone [Rocephin] (IV, IM)*

Ceftazidime (IV, IM)*

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9
Q

Fourth Generation Cephalosporins

A

Cefepime (IV, IM)*

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10
Q

Carbapenems

A

Imipenem/cilastatin (IV)

Meropenem (IV)*

Ertapenem (IV, IM)*

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11
Q

Monobactams

A

Aztreonam (IV, IM, INH)

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12
Q

B-lactamase Inhibitors

A

Ampicillin-sulbactam (IV)*

Amoxicillin-clavulanic acid [Augmentin] (PO)*

Piperacillin-tazobactam (IV)*

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13
Q

Glycopeptides

A

Vancomycin (PO, IV)*

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14
Q

Lipopeptides

A

Daptomycin (IV)

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15
Q

Fluoroquinolones

A

Ciprofloxacin [Cipro] (PO, IV, topical)

Levofloxacin (PO, IV, topical)*

Moxifloxacin (PO, IV, topical)

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16
Q

Aminoglycosides

A

Tobramycin (IV, IM, INH, topical)

Gentamicin (IV, IM, topical)*

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17
Q

Tetracyclines/Glycylcyclines

A

Minocycline (PO, IV)

Doxycycline (PO, IV) *

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18
Q

Macrolides/Ketolides

A

Clarithromycin (PO)

Azithromycin [Zithromax, Z-pak] (PO, IV, topical)*

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19
Q

Lincosamides

A

Clindamycin [Cleocin] (PO, IV, IM, topical)*

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20
Q

Oxazolidinones

A

Linezolid (PO, IV)

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21
Q

Metronidazole

A

Metronidazole [Flagyl] (PO, IV, topical)

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22
Q

Sulfonamides/Trimethoprim

A

Sulfamethoxazole/trimethoprim (PO, IV)

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23
Q

Introduction to anitmicrobials

A

265,500,000 courses of outpatient antibiotics prescribed in 2011

842 prescriptions per 1000 persons

Most common categories: penicillins and macrolides

Top 5 drugs:

Azithromycin

Amoxicillin

Amoxicillin-clavulanate

Ciprofloxacin

Cephalexin

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24
Q

Microorganisms & Antimicrobials

A

Bacteria = Antibacterial

Virus = Antiviral

Fungus = Antifungal

Parasite = Antiparasitic

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25
Q

Appropriate Antimicrobial Therapy

A

Ask yourself whether an antimicrobial agent is warranted:

Is an antimicrobial indicated based on clinical

findings?

Have appropriate cultures been obtained?

What is the most likely causative organism?

What must be done to prevent secondary

exposure?

Is there clinical evidence or established guidelines

that have determined antimicrobial therapy

provides a clinical benefit?

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26
Q

Organism Identification

A

Most valuable, time tested method for immediate ID of bacteria = gram stain

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27
Q

Gram-Positive vs. Gram-Negative

A
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28
Q

Peptidoglycan

A
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29
Q

Susceptibility Testing

A

›Susceptible: Likely to inhibit pathogenic microorganism

›

Intermediate: May be effective at higher dosage, more frequent administration, or in specific body site

›

Resistant: Not effective at inhibiting growth of microorganism

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30
Q

Susceptibility Testing

Minimum inhibitory concentration (MIC):

A

›Minimum inhibitory concentration (MIC): lowest concentration of drug required to inhibit growth

› Breakpoints established by Clinical and Laboratory

Standards Institute (CLSI)

›

Types of Susceptibility Tests

› Dilution Tests

› Disk Diffusion

› Optical Diffusion

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31
Q

›Susceptibility Testing

Dilution Tests

A
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32
Q

Susceptibility Testing

›Disk Diffusion

A
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33
Q

Susceptibility Testing

›Clinical and Laboratory Standards Institute (CLSI) Breakpoints

A

›Clinical and Laboratory Standards Institute (CLSI) Breakpoints

› Example: antibiotic X

34
Q

Antibacterial Spectrum

A

›Narrow-spectrum = Act on a single or a limited group of microorganisms

›

Extended-spectrum = Active against gram-positive bacteria but also against significant number of gram-negative bacteria

›Broad-spectrum = Act on a wide variety of bacterial species, including both gram-positive and gram-negative

35
Q

Bacteriostatic vs. Bactericidal

A

›Bacteriostatic: arrests growth and replication of bacteria (limits spread of infection)

›

Bactericidal: kills bacterial

› Concentration-dependent killing: rate and extent of

killing increase with increasing drug concentrations

›

Time-dependent killing: activity continues as long as

serum concentration above minimum bactericidal

concentration

36
Q

Concentration-Dependent

A
37
Q

Time-Dependent

A
38
Q

Bacteriostatic vs. Bactericidal

›This concept is relative

A

›This concept is relative

› Certain drugs are –cidal against specific bacteria

while –static against others

›

Drug-drug enhancement or synergism

› Gentamicin – ineffective against enterococci in the

absence of a cell-wall inhibitor

›Combining penicillin with gentamicin leads to bactericidal activity

39
Q

Bacteriostatic vs. Bactericidal

Graphically

A
40
Q

Antimicrobial Selective Toxicity

A
41
Q

Antimicrobial Classification

A

›Antimicrobials classified based on:

› Class and spectrum of microorganisms it kills

› Biochemical pathway it interferes with

› Chemical structure

42
Q

Site of Antibacterial Action

A
  • ›Cell wall synthesis
  • ›Cell membrane synthesis
  • ›Protein synthesis
  • ›Nucleic acid metabolism
  • ›Function of topoisomerases
  • ›Folate synthesis
43
Q

Cell Wall Inhibitors

A
44
Q

β-Lactams

A

›Penicillins

›Cephalosporins

›Monobactam

›Carbapenems

45
Q

β-Lactam Mechanism of Action

A

Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis

46
Q

β-Lactamase Inhibitors

A

›Amoxicillin + clavulanic acid, ticarcillin + clavulanic acid, ampicillin + sulbactam, piperacillin + tazobactam

›

MOA: prevent destruction of B-lactam antibiotics

47
Q

Inhibition of Cell Wall Synthesis

A
48
Q

Fluoroquinolone Mechanism of Action

A

Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils

49
Q

Inhibitors of Protein Synthesis

A

Formation of initiation complex

Amino-acid incorporation

Formation of peptide bond

Translocation

50
Q

Aminoglycosides

A
51
Q

Tetracyclines

A
52
Q

Macrolides

A
53
Q

Sulfonamides and Trimethoprim

A

Inhibit folic acid synthesis; block sequential steps in pathway

54
Q

Β-Lactams

A

›MOA: structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit transpeptidation

›

›Resistance:

› Structural difference in PBPs

› Decreased PBP affinity

› Inability for drug to reach site of action (i.e. gram-

negative organisms)

› Active efflux pumps

› Drug destruction/inactivation by B-lactamases

55
Q

Natural Penicillins

A
  • ›Penicillin G (IV, IM), penicillin V (PO)
  • ›
  • ›Spectrum: highly effective against gram-positive cocci (GPC) but easily hydrolyzed by penicillinase
  • ›
  • ›Therapeutic use: narrow-spectrum, Streptococcus pneumoniae pneumonia and meningitis. Penicillin V for Streptococcus pyogenes pharyngitis, toxic shock, viridians streptococci endocarditis if susceptible, syphilis
56
Q

Anti-Staphylococcal Penicillins

A
  • ›Oxacillin (IV, IM), dicloxacillin (PO), nafcillin (IV, IM)
  • ›
  • ›Spectrum: penicillinase resistant; agents of first choice for Staphylococcus aureus (MSSA) and Staphylococcus epidermidis (MSSE) that are not methicillin resistant
  • ›
  • ›Therapeutic use: restricted to infections with known Staphylococcus sensitivity
57
Q

Aminopenicillins

A

›_Ampicillin*_ (PO, IV, IM), _amoxicillin*_ (PO)

›

›Spectrum: extended-spectrum; extends beyond gram-positive to gram-negative (Haemophilus influenzae, Escherichia coli, Proteus mirabilis), Listeria monocytogenes, susceptible meningococci, enterococci

›

›Therapeutic use: upper respiratory tract infections (S. pyogenes, S. pneumoniae, H. influenzae), sinusitis, otitis media, enterococcal infections

58
Q

Anti-Pseudomonal Penicillins

A

›Ticarcillin (IV), _piperacillin*_ (IV)

›

›Spectrum: extends spectrum to Pseudomonas aeruginosa, Enterobacter, and Proteus spp.

›

›Therapeutic use: serious gram-negative infections, hospital acquired pneumonia (HAP), immunocompromised patients, bacteremia, burn infections, UTI

59
Q

Penicillins

›Adverse effects:

A

›Adverse effects:

› Allergic reactions (0.7-10%)

› Anaphylaxis (0.004-0.04%)

› Nausea, vomiting, mild to severe diarrhea

› Pseudomembranous colitis

60
Q

1st-Generation Cephalosporins

A
  • ›Cefazolin (IV, IM), cephalexin (PO)
  • ›Spectrum: good gram-positive coverage, modest gram-negative (covers Moraxella, E. coli, Klebsiella pneumoniae, P. mirabilis), orally active anaerobes
  • ›Therapeutic use: skin and soft tissue infections (SSTIs), surgical prophylaxis
61
Q

2nd-Generation Cephalosporins

A

›Cefoxitin (IV), cefuroxime (PO, IV, IM)

›

›Spectrum: somewhat increased activity against gram-negative, but less active than 3rd-generation. Subset active against Bacteroides fragilis

›

›Therapeutic use: used in gram-negative mixed anaerobic (intra-abdominal infections, pelvic inflammatory disease, diabetic foot infections)

62
Q

3rd-Generation Cephalosporins

A
  • ›Ceftriaxone (IV, IM), ceftazidime (IV, IM)

›

  • ›Spectrum: less active against gram-positive, more active against Enterobacteriaceae (although resistance increasing due to B-lactamase producing strains)

›

  • ›Therapeutic use: serious gram-negative infections (Klebsiella, Proteus, Providencia, Serratia, Haemophilus), ceftriaxone DOC for all forms of gonorrhea & severe Lyme’s disease; meningitis. Ceftazidime covers Pseudomonas

›

63
Q

4th-Generation Cephalosporin

A
  • ›Cefepime (IV, IM)

›

  • ›Spectrum: extends beyond 3rd-generation, useful in serious infections in hospitalized patients. Effective against Pseudomonas

›

  • ›Therapeutic use: empirical treatment of nosocomial infections
64
Q

Cephalosporins

Adverse Effects:

A

›Adverse effects:

  • ›1% risk of cross-reactivity to penicillins
  • ›Diarrhea
65
Q

Carbapenems

A

›Imipenem/cilastatin (IV), meropenem (IV), ertapenem (IV, IM)

›

›Spectrum: aerobes & anaerobes; gram-positive, Enterobacteriaceae, Pseudomonas, Acinetobacter. Stenotrophomonas maltophilia is resistant.

›

›Therapeutic use: UTI, lower respiratory tract infection (LRTI), intra-abdominal, gynecological, SSTI, bone and joint infections

›

›Adverse effects:

›Nausea/vomiting (1-20%), seizures (1.5%), hypersensitivity

66
Q

Monobactam

A

›Aztreonam (IV, IM, INH)

›

›Spectrum: activity against gram-negative (Enterobacteriaceae, Pseudomonas, H. influenzae, gonococci), no activity against GPC or anaerobes

›

›Therapeutic use: patients who are allergic to B-lactams appear not to react to aztreonam à effective for gram-negative infections which would usually be treated with B-lactam

67
Q

Glycopeptides

A

›Vancomycin (PO, IV)

›

›MOA: inhibits cell wall synthesis binding with high affinity to D-Ala-D-Ala terminal of cell wall precursor units.

›

›Resistance: alteration of D-Ala-D-Ala target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may also occur

68
Q

Glycopeptides

›Spectrum:

›Therapeutic use:

›Adverse effects:

›

A

›Spectrum: broad gram-positive coverage – S. aureus (including MRSA), S. epidermidis (including MRSE), Streptococci, Bacillus, Corynebacterium spp., Actinomyces, Clostridium

›

›Therapeutic use: osteomyelitis, endocarditis, MRSA, Streptococcus, enterococci, CNS infections, bacteremia, orally for C. difficile

›

›Adverse effects:

›Macular skin rash, chills, fever, rash

›Red-man syndrome (histamine release): extreme flushing, tachycardia, hypotension

›Ototoxicity, nephrotoxicity (33% with initial trough > 20 mcg/mL)

69
Q

Fluoroquinolones

A

›MOA: concentration-dependent; targets bacterial DNA gyrase & topoisomerase IV.

›

›Spectrum: E. coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria, Pseudomonas aeruginosa, S. aureus (not MRSA), limited coverage of Streptococcus spp.

› _Levofloxacin*_, moxifloxacin, “respiratory fluoroquinolones” cover Streptococcus spp.

›

›Therapeutic use: UTI, prostatitis, STI (chlamydia, Neisseria gonorrhoeae), traveler’s diarrhea, shigellosis, bone, joint, SSTI infections, diabetic foot infections

70
Q

Fluoroquinolones

Adverse Effects:

A

›Adverse effects:

› GI 3-17% (mild nausea, vomiting, abdominal

discomfort)

› CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations)

›Rash, photosensitivity, Achilles tendon rupture (CI in children)

›

71
Q

Aminoglycosides

A

›Tobramycin (IV, IM, INH, topical), _gentamicin*_ (IV, IM, topical)

›

›MOA: concentration-dependent; binds 30S ribosomal subunit, disrupts normal cycle of ribosomal function

›

›Spectrum: aerobic gram-negative bacteria, limited action against gram-positive, synergistic bactericidal effects in gram-positive with cell wall active agent

›

›Therapeutic use: UTI (not uncomplicated), used if resistance to other agents, seriously ill patients, pneumonia (infective against S. pneumoniae and anaerobes), HAP, peritonitis, synergy in bacterial endocarditis, tobramycin inhalation in CF

72
Q

Aminoglycosides

Adverse Effects:

A

›Adverse effects:

  • ›Ototoxicity (may be as high as 25%)
  • ›Nephrotoxicity (8-26%)
  • ›Neuromuscular block and apnea
73
Q

Tetracyclines/Glycylcyclines

A

›Minocycline (PO, IV), _doxycycline*_ (PO, IV), tigecycline (IV)

›

›MOA: bacteriostatic; binds 30S bacterial ribosome. Prevents access of aminoacyl tRNA to acceptor (A) site on mRNA ribosome complex

›

›Spectrum: wide range of aerobic/anaerobic gram-positive and -negative activity; effective for: Rickettsia, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia spp, Legionella, atypical mycobacterium, Plasmodium, Borrelia burgdorferi (Lyme’s disease), Treponema pallidum (syphilis)

›

74
Q

Tetracyclines/Glycylcyclines

›Therapeutic use:

›Adverse effects:

›

A

›Therapeutic use: CAP, atypical CAP coverage, community acquired SSTIs, community acquired MRSA, acne, Rickettsial infections (Rocky Mountain Spotted Fever), Q fever, anthrax

›

›Adverse effects:

  • ›GI (epigastric burning, nausea, vomiting, diarrhea)
  • ›Superinfections of C. difficile
  • ›Photosensitivity
  • ›Teeth discoloration
  • ›Thrombophlebitis
75
Q

Macrolides/Ketolides

A

›Clarithromycin (PO), _azithromycin*_ (PO, IV, topical)

›

›MOA: bacteriostatic; binds reversibly to 50S ribosomal subunit, inhibits translocation

›

›Therapeutic use: respiratory tract infections (spectrum S. pneumoniae, H. influenzae, and atypicals: Mycoplasma, Chalmydophilia, Legionella), alternative for otitis media, sinusitis, bronchitis, and SSTIs. Pertussis, gastroenteritis, H. pylori, Mycobacterial infections

›

76
Q

Macrolides/Ketolides

›Adverse effects:

›Drug interactions:

A

›Adverse effects:

  • ›GI (epigastric distress)
  • ›Hepatotoxicity
  • ›Arrhythmia
  • ›QT prolongation

›

Drug interactions: CYP3A4 inhibition – prolongs effects of digoxin, warfarin

77
Q

Lincosamides

A
  • ›Clindamycin (PO, IV, IM, topical)

›

  • ›MOA: binds 50S subunit of bacterial ribosome, suppresses protein synthesis
  • ›Spectrum: pneumococci, S. pyogenes, viridans Streptococci, MSSA, anaerobes (B. fragilis)

›

  • ›Therapeutic use: SSTIs, necrotizing SSTIs, lung abscesses, anaerobic lung and pleural space infections, topically for acne vulgaris

›

78
Q

Lincosamides

Adverse Effects:

A

›Adverse effects:

  • ›GI diarrhea (2-20%)
  • ›Pseudomembranous colitis (0.01-10%)
  • › -Due to C. difficile
  • ›Skin rashes (10%)
  • ›Reversible increase in aminotransferase activity
  • ›May potentiate neuromuscular blockade
79
Q

Oxazolidinones

A
  • ›Linezolid (PO, IV)

›

  • ›MOA: inhibits protein synthesis binding P site of 50S ribosomal subunit, prevents formation of initiation complexes

›

  • ›Spectrum: gram-positive Staphylococcus (MSSA, MRSA, VRSA), Streptococcus (penicillin resistant S. pneumoniae), enterococci (VRE), gram-positive anaerobic cocci, gram-positive rods (Corynebacterium, L. monocytogenes)

›

80
Q

Oxazolidinones

›Therapeutic use:

›Adverse effects:

››Drug interactions:

A

›Therapeutic use: VRE faecium (SSTI, UTI, bacteremia), nosocomial pneumonia caused by MSSA and MRSA, CAP, complicated/uncomplicated SSTI infections

›

›Adverse effects:

  • › Myelosuppression [thrombocytopenia
  • (2.4%),anemia, leukopenia]
  • › Headache
  • › Rash

›

›Drug interactions: weak, nonspecific inhibitor of monoamine oxidase

Respiratory II (14 decks)

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