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MS 2 - Unit 6 > Pharmacology - Antimicrobial Therapy II & III - Jeffrey Steele > Flashcards

Pharmacology - Antimicrobial Therapy II & III - Jeffrey Steele Flashcards

1
Q

What cephalosporins cover Pseudomonas?

A

Cefepime

Ceftazidine

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2
Q

Use: Ceftaroline (5th gen)

A

MSSA, MRSA
E. faecalis
S. pneumoniae

Complicated SSTI
Approved for CAP

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3
Q

Class: Avibactam

A

Novel beta-lactamase inhibitor

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4
Q

Use: Ceftolazone/Tazobactam

A

Pseudomonas and non-beta-lactamase producing enterobacteriaceae;
Complicated UTI;
Complicated intra-abdominal infection

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5
Q 
Class:
Imipenem-cilastatin;
Meropenem;
Ertapenem;
Doripenem
A

Carbapenems

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6
Q

What carbapenem is not recommended for use against Pseudomonas?

A

Ertapenem

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7
Q

What carbapenem is recommended for use against E. faecalis?

A

Imipenem

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8
Q

Use: Carbapenems

A 
cUTI;
cIAI;
CAP;
Bone and SSTI;
Bacterial meningitis, post-surgical (Miripenem) meningitis
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9
Q

What class of antibiotics is most likely to cause seizures (1%)?

A

Carbapenems

Often in patients with renal dysfunction, when drug is used in high doses

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10
Q

What Carbapenem is most effective against Pseudomonas?

A

Doripenem

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11
Q

Class: Aztreonam

A

Monobactam

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12
Q

Spectrum: Aztreonam

A

Gram negs only - Enterobacteriaceae and Pseudomonas

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13
Q

Class: Vancomycin

A

Glycopeptide

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14
Q

MOA: Vancomycin

A

Inhibits late stages of cell wall synthesis
– Binds to the D-Ala-D-Ala terminus of the nascent peptidoglycan pentapeptide
– Inhibits transglycosylase preventing elongation of peptidoglycan and cross-linking

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15
Q

Spectrum: Vancomycin

A 
MRSA
MSSA (less effective than beta-lactam)
Coag-neg staph ie Staph epidermidis;
Strep;
Enterococci;
Bacillus spp; Corynebacterium spp;
–  Peptostreptococcus 
–  Actinomyces
–  Propionibacterium 
–  Clostridium
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16
Q

Does Vancomycin have gram neg activity?

A

No

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17
Q

If MRSA is suspected, such as in a purulent cellulitis, what drug is recommended?

A

Vancomycin

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18
Q

Uses: Vancomycin

A

– SSTI, Especially when MRSA is suspected (purulent cellulitis)
• Bacteremia & Endocarditis
– Caused by Enterococcus, MRSA, coagulase-negative Staph
• Meningitis & Ventriculitis
– Community-acquired (for cephalosporin-resistant S. pneumoniae) – Hospital-acquired (for skin flora, MRSA)
• Pneumonia
– HAP, HCAP
• Bone & Joint Infection
• Neutropenic Fever
• Surgical prophylaxis
• C. difficile colitis (ORAL FORM ONLY)

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19
Q

Side effects: Vancomycin

A 
•  Nephrotoxicity
–  Concomitant nephrotoxins, e.g aminoglycosides, amphotericin
•  Infusion reactions
–  Redman syndrome
•  Secondary to histamine release
•  Maculopapular rash –  SJS, TEN
•  Drug fever
•  Phlebitis
•  Neutropenia
•  Thrombocytopenia
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20
Q

Only use PO Vancomycin for:

A

C. Diff colitis, because it’s a big molecule –> poorly absorbed

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21
Q

MOA: Daptomycin

A

Insertion into the gram-positive cell membrane causing depolarization and ultimate cell death

• Disclaimer: unique MOA. Not a cell-wall active agent

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22
Q

Spectrum: Daptomycin

A

MSSA, MRSA, VISA
Strep
Enterococci including VRE
Has activity against gram pos anaerobes

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23
Q

Does Daptomycin have gram neg activity?

A

NO

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24
Q

Why is Daptomycin not effective for use in pneumonia?

A

Pulmonary surfactant inactivates the drug

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25
Q

Use: Daptomycin

A

SSTI
Staph aureus bacteremia and endocarditis;
Osteoarticular infection;
Enterococcal infections

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26
Q

Side effects: Daptomycin

A

Paresthesia
Peripheral neuropathy;
Eosinophilic pneumonia;
CPK elevation and possible skeletal muscle damage

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27
Q

Class: Gentamicin (IV)

A

Aminoglycosides

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28
Q

Class: Tobamycin (IV/inh)

A

Aminoglycosides

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29
Q

Class: Amikacin (IV/inh)

A

Aminoglycosides

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30
Q

Class: Streptomycin (IM)

A

Aminoglycosides

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31
Q

MOA: Aminoglycosides

A

Bind to the 30S subunit of bacterial ribosomes and interfere with an initiation complex between mRNA (messenger RNA) and the 30S subunit, inhibiting protein synthesis

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32
Q

Spectrum: Aminoglycosides

A

Gram-negative
– Enterobacteriaceae & Pseudomonas
• Gram-positive
– Synergy with cell wall active agent against Enterococcus. CANNOTGIVEAS MONOTHERAPY

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33
Q

What aminoglycoside is recommended for use against mycobacteria and Nocardia?

A

Amikacin

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34
Q

Do aminoglycosides have activity against anaerobes?

A

No

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35
Q

Side effects: Gentamicin, Amikacin

A

Nephrotixicity;
Ototoxicity - risk increased with loop diuretics;
Neuromuscular damage

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36
Q

Class: Minocycline (IV/PO)

A

Tetracycline

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37
Q

MOA: Tetracyclines

A

Passive diffusion through porins in gram- negative organism;

Bind to 30S ribosomal subunit preventing protein synthesis

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38
Q

What drug class is recommended for atypical organisms such as Chlamydia pneumoniae and Mycoplasma pneumoniae?

A

Tetracyclines

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39
Q

What drug class is recommended for spirochetes such as Borrelia burgdorferi, Leptospira, and Treponema pallidum?

A

Tetracyclines

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40
Q

What drug class is recommended for the rickettsiae?

A

Tetracyclines

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41
Q

Spectrum: Tetracyclines

A 
Atypical Organisms
–  Chlamydia pneumoniae –  Mycoplasma pneumoniae
•  Spirochetes
–  Borrelia burgdorferi –  Leptospira
–  Treponema pallidum
•  Rickettsiae
•  Gram positive
–  S. pneumoniae (although resistance may be an issue) –  CA-MRSA
•  Gram negative –  H. influenzae
–  Neiserria spp.
•  Rapidly growing Mycobacteria
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42
Q

Uses: Tetracyclines

A 
Tick-borne illness (DOC) 
–  Lyme disease
–  Ehrlichiosis
–  Anaplasmosis
•  CAP
–  Patients with low risk of S. pneumoniae resistance
•  SSTI caused by CA-MRSA
•  Combination therapy for H. pylori
•  Prophylaxis
–  Exposure to anthrax, tularemia, plague, Q fever, brucellosis
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43
Q

Side Effects: Tetracyclines

A 
Photosensitivity;
Hyperpigmentation
Blue discoloration of skin;
Nephrotoxocity;
Neurotoxicity with Minocycline;
Erosive esophagitis
44
Q

Why should tetracyclines not be given to children?

A

Discoloration of teeth AND inhibition of bone growth in infants (reversible)

45
Q

What kind of neurotoxicity occurs with tetracyclines?

A

Vertigo, Tinnitus;

Pseudotumor cerebri with prolonged use

46
Q

What kind of nephrotoxicity can occur with tetracycline use?

A

Expired tetracycline resulting in reversible Fanconi-like syndrome (doesn’t happen with current formulation)

47
Q

What drugs should be avoided when tetracyclines are administered?

A

Antacids
Sucralfate
Multivitamins
Iron

48
Q

Class: Tigecycline

A

Glycylcycline

49
Q

MOA: Tigecycline

A

9-glycl substitution enables tigecycline to overcome two major types of resistance
– Efflux pumps
– Ribosomal protection

50
Q

Spectrum: Tigecycline

A

Broad-spectrum;

gram-negative, gram-positives, anaerobes (includes MRSA, VRE & Acinetobacter)

51
Q

What 4 gram negative bugs canNOT be treated with Tigecycline?

A

– Pseudomonas
– Proteus
– Providencia
– Morganella

52
Q

Side effects: Tigecycline

A

• GI
– Significant nausea (~25%), vomiting (18%), diarrhea
• Transaminitis
• Increased mortality
– Black Box warning regarding
– Use in situations when alternative agents are not suitable

53
Q

Class: Azithromycin (IV/PO)

A

Macrolide

54
Q

Class: Clarithromycin (PO)

A

Macrolide

55
Q

Class: Erythromycin (IV/PO)

A

Macrolide

Not used much anymore

56
Q

Class: Macrolides

A

Reversible binding to 50S subunit of ribosome

57
Q

Spectrum: Macrolides

A 
•  Gram-positive
–  S. pneumoniae (significant resistance)
–  Significant resistance in β-hemolytic strep
•  Gram-negative
–  H. influenzae, M. catarrhalis
•  Atypicals
–  Legionella, Chlamydia, Mycoplasma
•  Anaerobes
–  Actinomyces
58
Q

Uses: Macrolides

A

• Uncomplicated upper & lower respiratory tract infections
– Usually in patients without prior antibiotics due to risk of resistant S. pneumoniae
• Mycobacterial infection – M. avium (seen in HIV crowd)
• H. pylori (clarithromycin>azithromycin) in combination with other agents

59
Q

Side effects: Macrolides

A 
•  GI
–  Erythromycin>azithromycin,clarithromycin – Abdominal cramps, N/V, diarrhea
•  Thrombophlebitis (IV) –  Erythromycin
•  Cardiac
–  QT-prolongation
       •  Torsades de pointes
60
Q

Class: Clindamycin

A

Lincosamide

61
Q

MOA: Clindamycin

A

Binding to 50S ribosomal subunit preventing protein synthesis

62
Q

Are Clindamycin effective against gram neg bugs?

A

NO, Gram pos only

63
Q

Why is Clindamycin indicated for use in TSS Strep?

A

Mitigates toxin production

64
Q

Side effects: Clindamycin

A
  • Diarrhea (up to 20% of patients)

* Pseudomembranous colitis

65
Q

Class: Linezolid (IV/PO)

A

Oxazolidinones

66
Q

Class: Tedizolid (PO)

A

Oxazolidinones

67
Q

MOA: Oxazolidinones (Linezolid, Tedizolid)

A

Binds to 23 S ribosomal RNA of the 50S subunit inhibiting protein synthesis

68
Q

Why should Linezolid be avoided in the treatment of Staph aureus bacteremia?

A

• Vancomycin or daptomycin are recommended as 1st- line therapy

69
Q

Use: Linezolid

A

– Enterococcal infection including bacteremia
– Nosocomial pneumonia caused by S. aureus
– CAP caused by S. aureus
– SSTI

70
Q

Use: Tedizolid

A

SSTI

71
Q

T/F: Linezolid has gram negative activity.

A 
FALSE
Linezolid use is:
–  Staphylococci
•  S. aureus (MRSA, MSSA) 
•  Coagulase-negative
–  Enterococci including VRE
–  Streptococci
72
Q

Side effects: Linezolid

A 
•  Hematologic toxicity
•  Reversible myelosuppression
–  Thrombocytopenia (most common)
–  Anemia
•  MitochondrialToxicity
–  Peripheral neuropathy, optic neuropathy –  Lactic acidosis
•  Serotonin Syndrome (SS)
–  Inhibition of MAO can result in SS when given with serotonergic agents
73
Q

Name the three nucleic acid synthesis inhibitors.

A

Fluoroquinolones;
Metronidazole;
Rifamycins

74
Q

Class:
– Rifampin
– Rifabutin
– Rifaximin

A

Rifamycin - Nucleic acid synthesis inhibitors

75
Q

Class:
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin

A

Fluoroquinolones - Nucleic acid synthesis inhibitors

76
Q

Class: Metronidazole

A

No technical class - Nucleic acid synthesis inhibitor

77
Q

MOA: Fluoroquinolones

A
  • Inhibit DNA gyrase

* Inhibit topoisomerase IV

78
Q

What are the ONLY oral antipseudomonal agents?

A

Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin

79
Q

Spectrum: Fluoroquinolones

A

– S. pneumoniae
• levofloxacin & moxifloxacin;
– Enterobacteriaceae
– H. influenzae
– P. aeruginosa: Ciprofloxacin & levofloxacin
– Atypicals (Legionella, Chlamydia, Mycoplasma);
• Mycobacterium

80
Q

Resistance in what bugs is an issue for Fluoroquinolone use?

A

Resistance in Enterobacteriaceae problematic

81
Q

What is the antibiotic of choice for anthrax?

A

Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin

82
Q

What is the recommended adjunctive therapy in MDR pulmonary TB?

A

Fluoroquinolones
– Ciprofloxacin
– Levofloxacin
– Moxifloxacin

83
Q

T/F: Fluoroquinolones are just as effective PO as IV.

A

True

Good drug for transitioning out of the hospital

84
Q

Avoid Ciprofloxacin in conjunction with what drugs?

A

Theophylline –> Seizure

Tizanidine –> Hypotension

85
Q

MOA: Metronidazole

A

Interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis

86
Q

Spectrum: Metronidazole

A 
•  Anaerobes 
–  B. fragilis
–  Clostridial species including difficile
•  Protozoa
–  Trichomonas
–  Giardia
–  Entamoeba histolytica
87
Q

Side effects: Metronidazole

A
  • Metallic taste
  • Minor GI disturbances
  • Peripheral neuropathy (with long-term use or very high doses)
  • Disulfiram reaction with alcohol
88
Q

Use: Metronidazole

A
  • C. difficile diarrhea
  • Intra-abdominal infections in combination with other agents
  • Surgical prophylaxis in colon surgery (with other agents)
  • Trichomoniasis
89
Q

MOA: Rifamycins

A

Bind to DNA-dependent RNA polymerase inhibiting RNA synthesis

90
Q

T/F: Rifamycins such as Rifampin inhibit biofilms.

A

True

91
Q

Spectrum: Rifamycin

A 
•  Gram-positive 
–  Staphylococci 
–  Streptococci 
–  C. difficile
–  Listeria
•  Gram-negative 
–  H. influenzae 
–  N. meningitidis 
–  H. pylori
•  Mycobacterium
92
Q

Use: Rifampin

A

– M. tuberculosis infection
– Other Mycobacterium infections
– Adjunctive treatment in prosthetic valve endocarditis (S. aureus) and for prosthetic joint infection
– Prophylaxis N. meningitidis

93
Q

Use: Rifaximin

A

– Hepatic encephalopathy
– Recurrent C. difficile
– Traveler’s diarrhea

94
Q

Side effects: Rifampin

A

– Rifampin-associated flulike syndrome • Onset is latent
– Thrombocytopenia, hemolysis
– Renal failure
– Transaminitis
• Increased incidence of hepatotoxicity when combined with INH
or pyrazinamide

95
Q

Rifampin interacts with what liver enzymes, lowering the concentration of other drugs?

A

3A4*
1A2
2C
2D6

96
Q

What are the main anti-TB drugs?

A
  • Isoniazid (INH)
  • Pyrazinamide
  • Ethambutol
97
Q

Side effects: Isoniazid

A 
•  Hepatitis
–  10-20% of patients have asymptomatic minor transaminitis 
•  Neurotoxicity
–  Peripheral neuropathy
•  Pyridoxine can alleviate 
–  Memory loss, psychosis
•  Hypersensitivity reactions
98
Q

Class: Trimethoprim-Sulfamethoxazole (Bactrim)

A

Bacterial anti-metabolites

99
Q

MOA: Trimethoprim-Sulfamethoxazole

A

Sulfamethoxazole: Interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from paraaminobenzoic acid (PABA)

Trimethoprim: inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway

100
Q

What are the two drugs of choice for listeria?

A

Ampicillin;

Trimethoprim-Sulfamethoxazole

101
Q

What is the drug of choice for Stenotrophomonas (hosp)?

A

Trimethoprim-Sulfamethoxazole

102
Q

Is Trimethoprim-Sulfamethoxazole effective against anaerobes?

A

NO

103
Q

Spectrum: Trimethoprim-Sulfamethoxazole

A 
•  Gram-Positive
–  CA-MRSA/MSSA
–  S. pneumoniae
•  Not ideal for β-hemolytic strep
–  Listeria
•  Gram-Negative
–  Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, etc.)-resistance varies
–  DOC-Stenotrophomonas
•  Toxoplasmosis, Nocardia, Pneumocystis
104
Q

Uses: Trimethoprim-Sulfamethoxazole

A
  • Prophylaxis & treatment Pneumocystis jiroveccii pneumonia
  • Toxoplasmosis encephalitis
  • Urinary tract infection
  • Listeria meningitis
  • CA-MRSA
105
Q

Side effects: Trimethoprim-Sulfamethoxazole

A

RASH - SJS, TEN possible also
more common in HIV patients;

• Hematologic
– Bone marrow suppression (usually at higher doses)
• Renal
– Pseudo-renal failure: TMP can inhibit creatinine secretion
– AIN from sulfamethoxazole
– Hyperkalemia-TMP essentially acts as a K+ sparing diuretic

106
Q

Avoid warfarin when administering what antibiotic?

A

Trimethoprim-Sulfamethoxazole

Warfarin (inhibition of CYP 2C9 by TMP/SMX) leading to increase in INR

MS 2 - Unit 6 (34 decks)

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