Treatment of Bacterial Infections - Ch 87-93 Flashcards

1
Q

What is Chemotherapy?

A

Drugs that are β€œselectively toxic” to invading microorganisms that have minimal effect on host

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2
Q

Necrotizing fasciitis

A

β€œFlesh-eating disease”
Caused by variety of bacteria

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3
Q

Infections

A

Invasion and multiplication of organisms
Infections may be caused by foreign bacteria or normal flora (e.g. in immunocompromized
patients)

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4
Q

Colonization of the body by normal flora

A

Not usually harmful, can help in controlling growth of potentially pathogenic organisms

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5
Q

What causes implications for the action of antibacterials?

A

Gram-positive or Gram-negative cell wall

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6
Q

What are antibacterial drugs?

A

Either kill or slow down the growth of bacteria

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7
Q

What are the 2 subgroups of antibacterial drugs?

A

Bactericidal
Bacteriostatic

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8
Q

Bactericidal

A

Drugs are directly lethal to bacteria at clinically
achievable concentrations

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9
Q

Bacteriostatic

A

Drugs can slow bacterial growth but do not cause
cell death

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10
Q

What is critical in helping the body control and eliminate infections?

A

Immune system

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11
Q

Host defences are especially important in what group of antibiotics?

A

Bacteriostatic

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12
Q

Superinfection

A

new microbes take over when antibacterials kill normal flora
- eg respiratory, genitourinary tract and GI tract
microbe resistant to drug action = difficult to treat

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13
Q

Opportunistic infections

A

Infections that would not normally harm an immunocompetent person
-Existing colonization becomes infections
-Can be viruses, fungi, bacteria or protozoa

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14
Q

Who is affected by opportunistic infections?

A

Immunocompromised patients

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15
Q

How many people die globally from antibacterial resistance?

A

5 million people

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16
Q

What enhances selection of mutant bacteria (resistance)?

A

Improper choice of antibiotics
The dose is too low
Dosing not continued for long enough
Improper use of antibacterial, e.g, to treat a viral infection
Prophylactic use of antibacterials, e.g. in animal feed

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17
Q

What host factors need to be taken into consideration when providing antibacterial therapy?

A

Host age, allergies, organ health, pregnancy, site of infection and person’s general health

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18
Q

What are allergic reactions?

A

Immune response
-GI upset is not an allergic reaction

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19
Q

What are the four common mechanisms of action of antibacterials?

A
  1. Disruption of critical metabolic reactions
  2. Interference with cell wall synthesis
  3. Interference with protein synthesis
  4. Interference with DNA replication
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20
Q

What mechanism of action do sulfonamides use?

A

Inhibit metabolism

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21
Q

What spectrum do Sulfonamides have?

A

Broad spectrum
(effective against gram-positive and gram-negative)

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22
Q

What type of antibacterial are sulfonamides?

A

Bacteriostatic

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23
Q

How do sulfonamides inhibit/disrupt metabolic reactions?

A

Prevent synthesis of folic acid

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24
Q

Examples of sulfonamides

A

Sulfamethoxazole
Sulfadiazine

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25
Q

What are sulfonamides combined with?

A

trimethoprim
e.g, co-trimoxazole
Bactrim or Septra for UTI and otitis media

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26
Q

Where do sulfonamides reach effective concentrations?

A

Urinary tract

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27
Q

What are other clinical uses of sulfonamides?

A

Upper respiratory tract infections
others e.g, malaria, chlamydia

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28
Q

If someone is allergic to 1 sulfa-drug does that allergy applie to other reivatives of sulfa-life drugs?

A

Yes
e.g, anti diabetic agents sulfonylureas
thiazide and loop diuretics (increase urine)

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29
Q

Can pregnant women take sulfonamides and why?

A

No it is linked to birth defects in the 1st trimester and close to end of pregancy may increase fetal bilirubin (kernicterus brain damage)

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30
Q

It is advised to take sulfonamides during breastfeeding?

A

No also infants less than 2 months should not ingest

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31
Q

What are some adverse effects of sulfonamides?

A

Integumentary allergies
Blood adverse effects
GI adverse effects

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32
Q

What are some adverse effects affecting the skin caused by sulfonamides?

A

Stevens-johnson syndrome
Photosensensitivty

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33
Q

What are some blood adverse effects caused by sulfonamides?

A

(bone marrow depression)
Agranulocytosis, thrombocytopenia, aplastic anemia

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34
Q

What are GI adverse effects caused by sulfonamides?

A

Nausea and vomiting

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35
Q

Who discovered Beta-lactam antibacterials?

A

Sir Alexander Fleming (1928)
-Discovered Staphylococcus aureus was destroyed by the mold Penicillium notatu β€”> penicillin

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36
Q

What percent of S. aureus is resistant to penicillin now?

A

95%

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37
Q

What mechanism of action do Beta-lactam antibacterials use?

A

Inhbit cell wall enzyme responsible for peptidoglycan synthesis

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38
Q

What kind of antibacterial are Beta-lactams?

A

Bactericidal

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39
Q

What are the 4 groups of Beta-lactam antibacterials?

A

Penicillins
Cephalosporins
Monobactams
Carbapenems

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40
Q

What do all Beta-lactam antibacterials have in common?

A

Beta-lactam ring in their structures

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41
Q

What groups of Beta-lactams are commonly used in Canada?

A

Penicillins
Cephalosporins
Carbapenems

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42
Q

What are the 2 min subgroups of penicillins?

A

Naturally occurring
Semi-synthetic

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43
Q

What are Naturally occurring penicillin sensitive to?

A

Beta-lactamase

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44
Q

What are semi-synthetic penicllin resistant to?

A

Beta-lactamase

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45
Q

What kind of spectrums do semi synthetic penicillin have?

A

Broad or extended

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46
Q

What are broad spectrum semi-synthetic penicillins called?

A

Aminopenicillins

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47
Q

What are extended semi-synthetic penicillins called?

A

Anti-pseudomonal penicillins

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48
Q

What are the 2 narrow-spectrum (natural) penicillins that are still commonly used?

A

Penicillin G and Penicillin V

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49
Q

Example of beta-lactamase-resistant penicillin?

A

Cloxacillin

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50
Q

Examples of aminopenicillins (broader-spectrum)

A

Amoxicillin (more acid-stable), ampicillin

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51
Q

Examples of anti-pseudomonal penicillins (extended-spectrum)

A

Ticarcillin, piperacillin

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52
Q

Anti-pseudomonal penicillins can even be used against which bacteria?

A

Pseudomonas aeruginoas
-affects mostly ill people e.g, immunocompromized, cystic fibrosis

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53
Q

Pseudomonas aeruginosas opportunistic infections?

A

Respiratory tract
Ears
Eyes
CNS
UTI
Endocarditis

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54
Q

Describe the mechanism of action of Penicillins

A
  • Penicillins enter the bacteria
  • Inside the cell they bind to penicillin- binding proteins
  • Normal cell wall synthesis is disrupted
  • Bacteria cells rupture
  • Penicillins do not kill other cells in the body
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55
Q

What kind of antibacterial are penicillins?

A

Bactericidal

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56
Q

Depending on which type of penicllin, penicillins are active against most of which type of bacteria?

A

Most gram-positive
-Only some gram-negative

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57
Q

Why is there resistance to Penicillins?

A

Some bacteria produce enzymes capable of destroying penicillins

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58
Q

What enzyme do bacteria produce that causes resistance?

A

Beta-lactamases which splits the Beta-lactam ring

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59
Q

What is used in combination with penicillins?

A

Beta-lactamase inhibitors
(helps with resistance)

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60
Q

Examples of Beta-lactamase inhibitors

A

Clavulanic acid (amoxicillin + clavulanic acid)
Tazobactam (piperacillin + tazobactam)

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61
Q

How can Penicillins be administered?

A

PO, IM, IV

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62
Q

Penicillin G administration

A

IV or IM

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63
Q

Penicillin V administration

A

PO

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64
Q

Adverse effects of Penicillin

A

GI problems
-Nausea, vomiting, diarrhea, pain
(generally well tolerated)
Allergic reactions

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65
Q

What is the most common cause of drug allergy?

A

Penicillin

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66
Q

What reaction do people with allergies to penicillin display?

A

Skin rashes
Subcutaneous edema (e.g, lips)
Also can be fatal

67
Q

Cephalosporins are derivatives of what?

A

Semisynthetic derivatives from Cephalosporium fungus

68
Q

Cephalosporins are structurally and pharmacologically related to what?

A

Penicillins

69
Q

What kind of antibacterial are cephalosporins?

A

Bactericidal

70
Q

How are cephalosporins named?

A

Based on generations
1st gen β€”> 5th gen
(introduction to clinical use)

71
Q

With the newer generations of cephalosporins, what happens?

A

Better gram-negative coverage
Better Beta-lactamase resistance

72
Q

First Generation cephalosporins examples?

A

Cefazolin
Cephalexin
Cefadroxil
used for Surgical prophylaxis, URIS, otitis media

73
Q

How is cefazolin administered?

A

IV

74
Q

Cefazolin is excellent on which kind of bacteria?

A

Gram-positive

75
Q

How is cephalexin administered?

A

PO

76
Q

Second genration cephalosporins are good against which kind bacteria?

A

Gram-positive
Better gram-negative coverage than first gen

77
Q

Second generation cephalosporins examples?

A

Cefuroxime
Cefoxitin

78
Q

How is cefuroxime administered?

A

PO
-For surgical prophylaxis

79
Q

How is cefoxitin administered?

A

IV and IM

80
Q

THird-gen cephalosporins are better against which bacteria than previous generations?

A

Gram-negative

81
Q

Examples of third-gen cephalosporins?

A

Cefotaxime
Cefixime

82
Q

How does cefotaxime work?

A

Easily passes meninges and diffuses into CSF to treat CNS infections
e.g, meningitis

83
Q

How is Cefotaxime administered?

A

IV and IM

84
Q

How is Cefixime administered?

A

PO
-Best oral cephalosporin against gram-negative

85
Q

What drug is the only PO 3rd generation?

A

Cefixime

86
Q

How do fourth gen antibacterials compare to 3rd gen?

A

fourth generation have a broader spectrum, especially against gram-positive

87
Q

Example of fourth gen cephalosporins?

A

Cefepime

88
Q

Example of fifth gen cephalosporin

A

Ceftaroline
-MRSA infections

89
Q

What are the adverse effects of cephalosporins?

A

Similar to penicillins (GI)
Patients with a history of allergy to penicillin have cross-hypersensitivity to cephalosporins

90
Q

Describe the spectrum of Carbapenems?

A

Broad-spectrum
Work against gram-positive, gram-negative and anaerobic

91
Q

Carbapenems are effective against which infections?

A

Mixed infections
-NOT MRSA

92
Q

How are all carbapenems administered?

A

Parentally
-Not PO

93
Q

Examples of Carbapenems

A

Imipenem
Meropenem

94
Q

Whata re carbapenems reserved for?

A

Severe, complicated body cavity and connective tissue infections
-Last resort antibacterial when something can’t be treated by a narrower drug

95
Q

What is the name of a combination carbapenem drug?

A

Imipenem-cilastin

96
Q

What does cilastin do in combination with imipenem?

A

Inhibits breakdown of imipenem in kidney

97
Q

What is the type of bacteria that are resistant to Carbapenems?

A

Carbapenem-resistant Enterobacteriaceae (CRE)
-Resistant against most antibacterials
-Cause difficult to treat oppurtunistic infections

98
Q

What are the enzymes called that break down Carbapenems?

A

KPC: Klebsiella pneumoniae carbapenemase

NDM: New Delhi Metallo-beta-lactamase

99
Q

What is the class of drugs that are large in size?

A

Macrolides

100
Q

Examples of Macrolides?

A

Erythromycin (protypical)
Azithromycin
Clarithromycin

101
Q

What are macrolides mechanisms of action?

A

Inhibits protein synthesis by binding to 50S portion of the ribosome

102
Q

Describe the spectrum of macrolides?

A

broad spectrum
-Most Gram-positive, some gram-negative

103
Q

What group of antibacterials are macrolides?

A

Both bacteriostatic and bactericidal
-Depends on concentration and bacterial susceptibility

104
Q

Macrolides are used as alternatives to what when an allergic reaction occurs?

A

Beta-lactam allergies

105
Q

Macrolides are used an alternatives to what when resistance forms?

A

Penicillin resistance

106
Q

Are macrolides ever used in combination?

A

Yes
e.g, azithromycin and clarithromycin
used in combination for people with HIV/AIDS for opportunistic infections

107
Q

What infections are Macrolides used to treat?

A
  • Respiratory, skin and soft tissue
  • Strep infections
  • Streptococcus pyogenes (group A beta-hemolytic streptococci)
  • Mild to moderate URI (upper respiratory infections)
  • Haemophilus influenzae
  • Spirochetal infections
  • Syphilis and Lyme disease
  • Gonorrhea, Chlamydia, Mycoplasma
108
Q

What are the adverse effects of macrolides?

A

GI disturbances (nausea, vomiting, diarrhea)
Cardiac dysrhythmia (Long Q-T)

109
Q

Adverse effects of azithromycin and clarithromycin specifically?

A

Fewer drug-drug interactions (theophylline, warfarin, cyclosporine)
Little to no inhibition of CYP enzymes

110
Q

Describe the spectrum of Tetracyclines?

A

Broad-spectrum
-Gram positive, gram-negative

111
Q

What is the mechanism of action of tetracyclines?

A

Inhibits protein synthesis
-Binds to 30S portion

112
Q

What group of antibacterials is Tetracyclines?

A

Bacteriostatic

113
Q

Examples of Tetracyclines?

A

Tetracycline
Doxycycline
Minocycline
Demeclocycline

114
Q

What specific bacteria can Tetracycline be used to treat?

A

Mycoplasma, Rickettsia, Chlamydia, Syphilis
Protozoa

115
Q

What do Tetracyclines bind to?

A

Metal ions
Ca 2+, Mg 2+, iron and aluminum

found in, milk products, supplements, some laxatives most antacids

116
Q

What happens when Tetracyclines bind with metal ions?

A

Insoluble complexes form called Chelation

117
Q

What happens if Tetracyclines are taken with dairy products, antacids and iron salts?

A

Reduces absorption of tetracyclines

118
Q

Do NOT use Tetracyclines in which populations?

A

Children less than 8 years old
Pregnancy/breast feeding

119
Q

Why should young kids/pregnant women not take Tetracyclines?

A

Have a strong affinity for calcium which causes…
-Discoloration of permanent teeth and enamel in fetuses and kids
-Retards fetal skeletal development during pregnancy

120
Q

What other adverse effects do tetracyclines have?

A

GI disturbances (direct irritation, distrubs gut flora)
Photosensitivity

121
Q

Alteration in intestinal flora caused by tetracyclines may result in what?

A

Superinfection (overgrowth of new, non-susceptible organisms such as Candida)
Diarrhea
Pseudomembraneous colitis (C. Diff) colon infection

122
Q

Tetracyclines are antagonistic to which bacterials?

A

Bacteriocidal antiacterials so must be times for use usually at least an hour apart

123
Q

What are the 2 forms of Aminoglycosides?

A

Natural and semisynthetic

124
Q

What are Aminoglycosides produced from?

A

Streptomyces

125
Q

Aminoglycosides were the first antibacterial effect against what?

A

Gram-negative bacteria

126
Q

What group of antibacterials are Aminoglycosides?

A

Bactericidal

127
Q

What mechanism of action do Aminoglycosides use?

A

Prevents protein synthesis
(or causes abnormal protein synthesis)

128
Q

Aminoglycosides are used against which bacteria?

A

Mostly gram-negative and some gram-positive

129
Q

Examples of Aminoglycosides?

A

Gentamicin
neomycin
streptomycin
tobramycin
amikacin

130
Q

What are some examples of gram-negative bacteria that aminoglycosides are effective against?

A

Pseudomonas spp
E. coli
Proteus spp
Klebsiella spp
Serratia spp

131
Q

Are aminoglycosides used in combination?

A

Yes with other antibacterials for synergistic effect

132
Q

Where are aminoglycosides poorly absorbed?

A

Through GI Tract

133
Q

How are aminoglycosides administered?

A

Parenterally (IV or IM)

134
Q

When are aminoglycosides given PO?

A

To decontaminate the GI tract before surgical procedures or enema

135
Q

Aminoglycosides are drugs with _________ __________!!

A

Serious toxicities

136
Q

What types of toxic effects do aminoglycosides cause?

A

Ototoxicity
Nephrotoxicity

137
Q

Ototoxicity

A

Affects the ear
Auditory impairment e.g, Tinnitus, deafness
Vestibular impairments e.g, balance problems, dizziness, vertigo

138
Q

Is Ototoxicity reversible?

A

No it is irreverisble

139
Q

How is aminoglycosides Ototoxicity made worse?

A

If other ototoxic drugs are given e.g, Loop diuretics

140
Q

Nephrotoxicity

A

Affects the kidney
Causes kidneys to detriorate

141
Q

Who is extremely affected by nephrotoxicity?

A

Neonates
People with pre-existing renal conditions
-measure proteinuria, serum creatinine levels, BUN

142
Q

Is Nephrotoxicity reversible?

A

Yes it is reversible

143
Q

You must monitor what to prevent toxicities caused by aminoglycosides?

A

Plasma drug levels

144
Q

Theres is an additive effect for nephrotoxicity if used with what?

A

Vancomycin
Cyclosporine (immunosuppressant)
Amphotericin B (antifungal)

145
Q

What mechanism of action do Quinolones/Fluroquinolones use?

A

Affect DNA replication
Alters DNA of bacteria by preventing proper supercoiling

146
Q

Examples of Quinolones?

A

Ciprofloxacin
Norfloxacin
gemifloxacin
levofloxacin
gatifloxacin

147
Q

What is a very effective and most commonly used quinolone?

A

Ciprofloxacin

148
Q

How is Ciprofloxacin administered?

A

PO

149
Q

What group of antibacterials are quinolones?

A

Bactericidal

150
Q

Describe the spectrum of Quinolones?

A

broad spectrum
-Gram-negative (major use)
-Some gram-positive

151
Q

Do quinolones affect human DNA?

A

NO

152
Q

What infectiosn are treated with quiniolones?

A

UTI
Lower resp. tract infections
Bone and joint infections
Infectious diarrhea
Skin infections
STDs
Anthrax!!!!!!!!!!!!

153
Q

What adverse effects do quinolones have?

A

GI distrubances (nausea, vomiting, diarrhoea)
Skin (rashes)
CNS (headache, dizziness)

154
Q

What drugs do quinolones have interactions with that cause CYP inhibition?

A

Theophylline (asthma drug)
Warfarin

155
Q

What reduces oral absorption of Quinolones?

A

Antacids
Iron, zinc, calcium-containing preparations
-Drugs should be given 1-2 hours before consuming those preparations

156
Q

What is the mechanism of action of Vancomycin?

A

Inhibits cell wall syntehsis

157
Q

What group of antibacterials is Vancomycin?

A

Bactericidal

158
Q

Vancomycin have a different what to Beta-lactams?

A

Different protein targets

159
Q

How is Vancomycin administered?

A

IV and PO

160
Q

Iv administration of Vancomycin is used to treat what?

A

MRSA and other gram-positive infections

161
Q

Oral administration of Vancomycin is used to treat what?

A

Pseudomembranous colitis (C. diff)

162
Q

What is increasing in regards to Vancomycin use?

A

Vancomycin resistance

163
Q

What infusion rate (over 1 hour ) related adverse effects does Vancomycin have?

A

Flushing syndrome possible

164
Q

What adverse effects does Vancomycin have?

A

Fever, chills and phlebitis (inflamed vein at injection)
Ototoxicity
Nephrotoxicity