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Disease and Defense class of 2019 > Unit 4 Pharm > Flashcards

Unit 4 Pharm Flashcards

1
Q

MIC

A

minimal inhibitory concentration

lowest concentration of antibiotic that prevents visible bacterial growth

low MIC is not necessarily best for bug, choose the most narrow spectrum first

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2
Q

MBC

A

minimal bactericidal concentration

derived from MIC testing
lowest concentration of the antibiotic that kills 99.9% or the original innoculum in a given time
must have less than 10 colonies for plate
used to determine whether certain drug is considered bactericidal or bacteriostatic against bacteria

Bactericidal: have MBC concentrations equal or above MIC
Bacteriostatic: antibiotics have MBC concentrations higher than MIC concentration

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3
Q

D test

A
  • need to associate with cross resistance for 3 antibiotic families: macrolides, lincosamides, group B streptogrammins
  • all bind same site on 23S rRNA of 50S
  • erm resistance is constitutive (always expressed) or inducible
  • when MLSb phenotype is due to constitutive erm gene on inducible type
  • expression of respective erm gene requires induction by some of the drugs in the 3 families
  • strains with inducible phenotype show resistance to inducing drugs
  • are sensitive to non-inducing drugs
  • treatment failures have happened in the last 10 years when clindamyacin was used fro MRSA infections caused by inducible erm resistance gene
  • strains appear susceptible to clinda, but resistant to macrolides
  • initially improve on clinda, then regress days/weeks into therapy
  • isolated organisms are clinda resistant
  • mutations change erm expression from inducible to constitutive
  • occur spontaneously at high frequency
  • clindamyacin treatment selects fro survival and growth of resistant subpopulations and treatment failure
  • D test identifies isolates that have inducible iMLSb genotype
  • Em disk is placed next to a clindamyacin disk, allows EM to diffuse out and induce erm expression in adjacent cells
  • results in asymmetric zone of inhibition around clinda disk, smaller zone adjacent to Em and larger zone on distal side
  • positive D test means its possible but not certain that its clindamyacin resistant
  • may still be sensitive to clinda
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4
Q

bactericidal

A

cell membrane-homeostasis destroyed
DNA disruption
cell wall disruption

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5
Q

zone of hemolysis

A
  • larger the zone of inhibited bacterial growth, the more susceptible the organism is to the antimicrobial
  • size of zone varies depending on various factors
  • size shows if resistant, intermediate, susceptible organisms
  • zone size corresponds to MIC values below clinically attainable serum conc. are susceptible
  • resistant is is MIC values above clinically attainable serum concentration of antimicrobial
  • intermediate is isolates where zone size measurements are not clear.
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6
Q

cocci negative-neisseria

A

3rd gen cephalosporin (ceftriaxone)

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7
Q

gram + cocci-most

A

pen v/g
clinda
macro
doxy (comm. acquired)

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8
Q

gram + cocci-

s. pneumo
s. pyo

A

amox

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9
Q

gram + cocci- MSSA

A

1st ceph
amox+clav
clind
macro

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10
Q

gram + cocci-MSSA

A

doxy
tmr-smx
clinda
vanco

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11
Q

gram - rods-most ecoli

A 
aminoglycosides
amox
amox+clav
1st ceph
tmp-smx
nitro
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12
Q

gram - rods-resistant ecoli

A

amino

cip-levo*

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13
Q

gram - rods-pseudomonas

A

amino
cip-levo
pip-taz
(3rd ceph)

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14
Q

anerobes-most

A

pip-taz
clind
penicillins

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15
Q

anerobes-c. diff

A

metro

vanco

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16
Q

anerobes- bacteroides

A

pip-taz

clinda

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17
Q

atypical-myco/chlamyd

A

doxy* (not preg/

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18
Q

cidal or static?

penicillins

A

cidal

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19
Q

cidal or static?

cephalosporins

A

cidal

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20
Q

cidal or static?

vanco

A

cidal

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21
Q

cidal or static?

carbapenems

A

cidal

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22
Q

cidal or static?

aminoglycosides

A

cidal

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23
Q

cidal or static?

streptogamins

A

cidal

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24
Q

cidal or static?

fluoroquinolones

A

cidal

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25
Q

cidal or static?

nitrofurantoin

A

cidal

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26
Q

cidal or static?

sulfonamides

A

cidal

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27
Q

cidal or static?

metronidazole

A

cidal

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28
Q

cidal or static?

macrolides

A

static

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29
Q

cidal or static?

tetracyclines

A

static

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30
Q

cidal or static?

clindamycin

A

static

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31
Q

cidal or static?

chloramphenicol

A

static

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32
Q

cidal or static?

oxazolidinones

A

static

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33
Q

routes of administration:

penicillin V

A

oral

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34
Q

routes of administration:

penicillin G

A

parenteral

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35
Q

routes of administration:

dicioxacillin

A

parenteral, oral

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36
Q

routes of administration:

amoxicillin

A

oral

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37
Q

routes of administration:

ampicillin

A

oral, parenteral

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38
Q

routes of administration:

piperacillin

A

parenteral

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39
Q

routes of administration:

ticaracillin

A

parenteral

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40
Q

routes of administration:

cefazolin

A

paraenteral

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41
Q

routes of administration:

cephalexin

A

oral

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42
Q

routes of administration:

cefuroxamine

A

oral, parenteral

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43
Q

routes of administration:

ceftriaxone

A

parenteral

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44
Q

routes of administration:

cefazidime

A

oral, parenteral

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45
Q

What is not renally eliminated?

A

D(Q) CRIMES

Doxycycline: non-renally eliminated tetracycline
Quinolones: Ciprofloxacin renal but CYP450 inhibitor

Clindamycin: non-renally eliminated
Rifampin: inducer of P450 - potential for hepatotoxicity
Isoniazid: genetic polymorphism - potential for hepatotoxicity
Metronidazole: drug-drug interaction with alcohol due to inhibition of aldehyde metabolism (Antabuse reaction)
Erythromycin-like: drug-drug interactions due to inhibition of P450 (Clar-Ery not Azi)

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46
Q

resistance: penicillins

A
  • production of penicillinase via a plasmid (MSSA)
  • modification of PBPs (MRSA)
  • inability to penetrate (pseudomonas)
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47
Q

resistance: cephalosporins

A
  • MRSA
  • Pseudo
  • B fragillis
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48
Q

resistance: vanco

A

modification of terminal peptidoglycan motif (S. aureus and enterococcus)

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49
Q

resistance: macrolides

A
  • methylation of 50S ribosomes via MDR gene (S pneumo and flu)
  • multidrug efflux via MDR
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50
Q

resistance: tetracyclines

A
  • changes in transport in and out of cells

- proteins that block tetracycline binding (MDR)

51
Q

resistance: clindamycin, aminoglycosides

A
  • anerobes require O2

- chemical modification of drug to block action (may be plasmid mediated in gram neg)

52
Q

resistance: fluoroquinolones

A
  • point mutations on DNA gyrase
  • impermeable cells
  • Qnr proteins that protect gyros
  • acetyltransferase can modify drug
53
Q

resistance: nitrofurantoin

A

-pseudomonas

54
Q

resistance: metranidazole

A

nitromidazole reductase

55
Q

resistance: trimethoprim-sulfamethoxazole

A
  • escape mechanisms via methionine, purines, thymine

- acquired via increases in PABA or altered DHPS or DHFR

56
Q

intrinsic resistance

A

-occurs just because of natural properties of bacteria

57
Q

acquired resistance

A
  • develops via genetic mutation or by acquisition of new genes
  • new genetic material mediating antibiotic resistance is spread from cell to cell by mobile genetic elements (plasmids, transposons, bacteriophages)
58
Q

major mechanisms of resistance

A
  • inactivate/modify the drug
  • alter antibacterial target
  • reduce ability of drug to get to the target
59
Q

reducing antibiotic success

A

-specific growth states (e.g.: growth in a biofilm, aerobic conditions, stationary phase) can negatively impact susceptibility

60
Q

porins

A
  • outer membrane gram negative bacteria
  • form channels to allow selective uptake of nutrients/compounds
  • changes in configuration adversely affect uptake
61
Q

efflux pumps

A
  • eliminate substrates from cytoplasm
  • originate as mechanisms to get rid of toxic substances
  • can be present in + or -
  • can be specific or general (multi-drug resistance)
62
Q

peptidoglycan as resistance mechanism

A
  • backbone of 2 sugars with cross linking peptide bridge
  • formed by precursors and 5 attached aa
  • cross link, driven by cleavage of peptide aa
  • things that cross link are PBPs (penicillin binding proteins)
  • altered PBPs are a moving target
63
Q

beta lactam resistance

A
  • peptidoglycans are made by PBPs (perform transpeptidase, transglycoslyase reaction)
  • involved in sythesis and growth
  • beta lactam antibiotics bind and inactivate the TRANSPEPTIDASE reaction of PBPs. inhibit CROSS LINKING and synthesis.
  • resistance comes from:
    1. modifying drug-destroy with beta lactamase
    2. modify target-alter PBPs
    3. prevent interaction with target-porin channel mutation, efflux mechanism
64
Q

beta lactamases

A
  • enzymes that inactivate beta lactam antibiotics
  • split amide bond of beta lactam ring
  • encoded by chromosomal or transferrable genes
  • found in + and -
  • broad spectrum beta lactamases are found in gram - bacteria
65
Q

narrow spectrum beta lactamase

A
  • hydrolize penicillin antibiotics
  • not much activity against cephalosporins, carbapenems
  • found in + and -
  • occur frequently or less commonly
66
Q

ESBLs (extended spectrum beta lactamases)

A
  • arose 1980s
  • mutants of TEM1, 2 and SHV1. 1-4 aa substitutions
  • ability to attach cephalosporins
  • found on plasmids, mobile, can disseminate
  • found almost exclusively in gram negative rods, prevalence is low
67
Q

ampC-encoded beta lactamase

A
  • ampC is a chromosomally located gene in gram neg organisms
  • encodes for beta lactamase that is capable of hydrolyzing penicillins, 1-3 cephs
  • not inhibited by beta lactamase inhibitors
  • found in some gram neg rods: enterobacter, pseudomonas
  • is inducible or constitutive
  • normal conditions, is expressed in small amounts, can be induced in some beta lactams
  • some mutations can lead to constitutive expression
68
Q

enterobacter in inducible state

A

ampicillin–R
cefazolin–R
bug is resistant since both induce amp C

69
Q

enterobacter with mutation to express ampC

A 
ampicillin--R
cefazolin--R
ceftriaxone--R
ceftazidime--R
piper/taz--R
ertapenem--S
now all third gens are degraded by ampC since expressed all the time
70
Q

what does mutation of ampC mean clinically

A

mutational events lead to permanent expression of ampC during therapy.

71
Q

carbapenems and carbapenemases

A
  • beta lactam antibiotics
  • broad spectrum against gram neg rods, used in hospitalized patients with resistant infections
  • plasmid mediated, found in gram negative rods like Klebsiella, ecoli, enterobacter
  • some gram negative organisms can become resistant to carbapenems without a carbapenemase
72
Q

altered penicillin binding proteins (PBPs)

A
  • produce a PBP that has reduced affinity for beta lactamase drug
  • mutation of existing genes, but acquisition of new PBP genes or new pieces of PBP genes is more important
  • has mecA, mosaic
  • generally change slowly over time, so resistance slowly proceeds
73
Q

mecA PBPs

A
  • seen in staph
  • encodes for low affinity PBP called PBP2a
  • resistance to all beta lactam agents
  • makes MRSA
74
Q

mosaic PBPs

A
  • in strep and neisseria
  • pick up pieces genetic material
  • genes encoding can become mosaics over time
  • encode then for markedly reduced beta lactam antibiotic affinity
75
Q

vanco resistance

A

-stage 2 synthesis
-vanco targets precursor molecule, binds d-ala region
resistance comes from:
1. modifying target (entero does this though plasmid acquisition), unrecognizable precursor
2. preventing drug target interaction: binds free vance in existing peptide wall (mostly in S. aureus)

76
Q

enterococcus resistance to vanco

A
  • genes encoded on plasmids

- change the d-ala to d-lactate

77
Q

staph resistance to vanco

A
  • moderate reduction in susceptibility
  • don’t have genes that mediate vance resistance, they have perturbations in cell wall synth
  • thicker peptidoglycan layers
  • less cross linking
  • vanco gets bound up in the wall, and there is less free to bind the precursor molecules
  • develop in prolonged vanco therapy
78
Q

quinolone resistance

A

-quinolones target bacterial enzymes DNA gyros and topoisomerase4
resistance comes from:
1. modifying drug (rare)
2. modifying target through aa changes (DNA mutations) (majority of cases)
-mutations result in aa substitutions in quinolone resistance determining region (QRDR)
-make enzyme less sensitive to inhibition, reduce affinity
-mutations are easy to select for during therapy
3. prevent drug target interaction via efflux and porin mutations (less common)

79
Q

resistance to macrolides

A
  • macrolides inhibit bacterial protein synthesis by binding 50S subbing of bacterial ribosome
  • prevents chain elongation
  • resistance comes from
    1. modify drug (rare)
    2. modify target (common) prevents macrolide binding to ribosome. mediated by term gene. found on plasmids/transposons
  • dimethylation by term
  • erm regulation induced by macrolides only (not by clindamycin)
  • constituent expression tests resistant to macrolides and cloned
  • inducible test sensitive then become constitive
    3. prevent drug-target interaction (common), efflux pumps
80
Q

aminoglycoside resistance

A

-not used much anymore due to toxicity
resistance due to:
1. modifying drug (classic mechanism).
2. modify target (common). methylate 16s rRNA. plasmids
-modifying enzymes do N-acetylation, O-nucleotidylation, O-phosphorylation
3. prevent drug target interaction. uptake depends on sufficient electrochemical gradient. aerobic bacteria (with no aerobic respiratory chain) don’t have gradient necessary, so they are resistant to aminoglycosides

81
Q

Cell Wall Synthesis Inhibitors

A

Penicillins:
Narrow  Penicillin V, Penicillin G
β-lactamase resistant  Dicloxacillin
Extended spectrum  Amoxicillin-(clavulanate), Ampicillin
Antipseudomonal  Piperacillin-(tazobactam)

Cephalosporins:
*1st  Cephalexin, Cefazolin
3rd  Ceftriaxone

Vancomycin

82
Q

Protein Synthesis Inhibitors

A

Macrolides:
Azithromycin
Clarithromycin
Erythromycin

Tetracyclines:
Doxycycline
Tetracycline

Clindamycin

*Aminoglycosides:
Tobramycin
Gentamicin

83
Q

Inhibitors of DNA Function

A

Fluoroquinolones:
Ciprofloxacin
Levofloxacin
Moxifloxacin

Nitrofurantoin

Metronidazole

84
Q

Inhibitors of Intermediary Metabolism

A

Sulfonamides  Sulfamethoxazole

Trimethoprim

Trimethoprim-Sulfamethoxazole

85
Q

Bactericidal agents

A

Preferred in severe infections

Act more quickly, often irreversible with sustained effect

Can compensate for patients with an impaired host defense

Required for treatment of infections in located in immune sanctuaries (CNS-endocarditis infections)

86
Q

Bactericidal mechanisms

A

Inhibition of cell wall synthesis

Disruption of cell membrane function

Interference with DNA function or synthesis

87
Q

bacteriostatic mechanisms

A

Inhibition of protein synthesis (except AGs  -cidal)

Inhibition of intermediary metabolic pathways

88
Q

Narrow spectrum

A

effect against either gram + or gram –

Most effective on susceptible organism

Less disturbance of host flora

89
Q

Extended spectrum

A

effect against gram + and gram –

90
Q

Broad spectrum

A

effective against gram + and gram – and atypical

Sacrifice efficacy for greater scope of activity for initial empiric treatment

More likely to cause superinfections

91
Q

Tetracyclines - Adverse Reactions

A

Yeast (candidal) overgrowth: Disturbance of normal gut flora can lead to thrush and vaginitis

Liver / kidney toxicities: If pre-existing conditions

Drug Interactions

Antacids / Iron Supplements (metal ions): Decrease bioavailability by forming insoluble salts

Phenytoin / Barbiturates / Carbamazepine: Increased metabolism of doxycycline

Oral Anticoagulants: Increased anticoagulant effect

92
Q

Nitrofurantoin - Mechanism

A

Most commonly used urinary tract antiseptic

Not used for systemic infections - effective Cp cannot be obtained with safe doses

Since it concentrates in renal tubules, can be given orally to treat urinary tract infections (i.e., non-systemic)

Mechanism of Action

Reduced by bacterial enzymes to intermediates that damage bacterial DNA

Concentration dependent effect – generally bactericidal

Selectively toxic because mammalian enzymes don’t reduce nitrofurantoin as rapidly

93
Q 
Selective Distribution (accumulation)
Beneficial
A

Selective Distribution (accumulation)

Beneficial:
Clindamycin into bone (osteomyelitis)

Macrolides into pulmonary cells (URIs-pneumonia)

Tetracyclines into gingival crevicular fluid and sebum (periodontitis and acne)

Nitrofurantoin rapid excretion into urine (UTIs)

94
Q 
Selective Distribution (accumulation)
Potential for toxicity
A

Aminoglycosides bind cells of the inner ear and renal brush border  ototoxicity and nephrotoxicity

Tetracyclines bind Ca++ in developing bone and teeth  abnormal bone growth and tooth discoloration

95
Q

CNS distribution

A

Antibiotics vary substantially in ability to cross BBB

CNS penetration necessary to treating CNS infections effectively

3rd generation cephalosporins excellent - ceftriaxone

96
Q

Fetus distribution

A

Adverse effects if antibiotics cross the placental “barrier”

Rule of thumb: Oral antibiotics for systemic infections can also cross the placenta and have potential to harm the fetus

97
Q

Aminoglycosides - Mechanism of Action

A

Bind irreversibly to 30S ribosome altering interaction of mRNA with subunit

Produces inhibition of protein synthesis initiation

Breakup of polysomes

Misreading the code (? producing lethal proteins)

Bactericidal at clinically utilized concentrations

Actively transported into bacteria; requires O2 - thus NOT effective against anaerobic organisms

98
Q

Aminoglycosides - Adverse Reactions

A

Renal Toxicity (usually reversible when drug D/C’d)

25% of patients show mild impairment

Manifested by rising BUN and creatinine levels, proteinuria, oliguria, acute tubular necrosis

Followed by reduced glomerular filtration  resulting in further accumulation

Eighth nerve damage (often irreversible) - involves sensory receptors of the nerve - affects Ca++ fluxes

Auditory (0.5-12%): Tinnitus and high frequency hearing loss (outside normal speech)

Vestibular (1-3%): Dizziness, nausea / vomiting, vertigo

99
Q

Sulfonamides Spectrum  Clinical Uses

A

Gram positive cocci

Staph. aureus (community-acquired MRSA skin / skin structure infections [TMP/SMX]

Staph aureus  conjunctivitis [Sulfacetamide]

Gram-negative rods

E. coli, Klebsiella, Proteus, Enterobacter  uncomplicated urinary tract infections [TMP/SMX]

Atypical organisms [TMP/SMX]

Chlamydia  trachoma, community-acquired pneumonia, urethitis

100
Q

Cephalosporins - Adverse Reactions

A

Generally well tolerated due to high selective toxicity

Allergy / Hypersensitivity

Anaphylaxis, skin rashes, nephritis, hemolytic anemia - not as severe as with penicillins

Cross-reactivity with penicillins

101
Q

Cephalosporins

A

Mechanisms of action and resistance - similar to penicillins

Relative to penicillins (G and V), cephalosporins have:

Broader spectrum of action vs gram-negative bacteria

Less susceptibility to β-lactamases (penicillinases) but ESBLs are emerging

Less cross-reactivity in penicillin sensitive patients (1% or less)

102
Q

what should NEVER be given to patients with penicillin allergies?

A

CEPHALOSPORIN

103
Q

Cephalosporins - Classifications general

A

Five generations - originally based on activity against gram negative organisms

Now also consider resistance to cephalosporinases (4th) and activity against MRSA (5th)

104
Q

Cephalosporins - Classifications

First Gen

A

First - Cephalexin (po), Cefazolin (IV)

Spectrum like amoxicillin - gram + and gram  but rarely drugs of first choice

More stable than penicillins to many beta-lactamases

105
Q

Cephalosporins - Classifications

Second Gen

A

Second - Cefaclor (po), Cefuroxime (po, IV)

Gram + activity

106
Q

Cephalosporins - Classifications

3rd gen

A

Third - Cefdinir (po), Ceftriaxone (IV-IM)

Excellent activity against some gram + (S. Pneumoniae)

Expanded gram  vs 2nd gen (enteric gram bacilli)

Moderate antipseudomonal activity (ceftazidime)

107
Q

Clindamycin - Adverse Reactions

A

Pseudomembranous colitis

Toxigenic Clostridium difficile selected out during treatment (superinfection, 0.1-10%)

Probably no worse than some broader spectrum agents (amoxicillin-ampicillin, 2nd-3rd gen cephalosporins, FQs)

Common: Nausea, diarrhea (severe 2-20%), skin rashes

Rarely: Impaired liver function, neutropenia

108
Q

Clindamycin - Pharmacokinetics

A

Absorption
90% of oral dose absorbed - not affected by food

Distribution
Penetrates most tissues well - especially bone - but not well into CSF

Elimination
Metabolized by liver, then primarily biliary excretion

No dosage adjustment required in renal failure

Excreted in breast milk

109
Q

Tetracyclines - Adverse Reactions

A

Teeth and bone

Temporary depression of bone growth - permanent discoloration of teeth if given during development

Chelates to Ca++ in developing bone and teeth

Avoid use during latter half of pregnancy and in children under 8 years old (Pregnancy Risk Factor D)

GI disturbance: Nausea, vomiting, diarrhea common

Photosensitivity: Abnormal sunburn reaction

Yeast (candidal) overgrowth: Disturbance of normal gut flora can lead to thrush and vaginitis

Liver / kidney toxicities: If pre-existing conditions

Drug Interactions

Antacids / Iron Supplements (metal ions): Decrease bioavailability by forming insoluble salts

Phenytoin / Barbiturates / Carbamazepine: Increased metabolism of doxycycline

Oral Anticoagulants: Increased anticoagulant effect

110
Q

Fluoroquinolones - Mechanism

A

Target: Bacterial DNA gyrase and topoisomerase IV

DNA gyrase facilitates unwinding of DNA strands

Required for normal DNA replication - transcription and some aspects of DNA repair and recombination

Inhibition by quinolones is rapidly bactericidal (99.9% lethal within 2 hr)

111
Q

Fluoroquinolones - Adverse Reactions

A

Overall very well tolerated

GI (5-10%): N/V, diarrhea (C. difficile associated)

CNS: Dizziness, headache, insomnia, rarely seizures

Black Box Warning

3-4-fold ↑ risk of tendon rupture, but still rare, 1:10,000

Potential for arthropathies limits use in pregnancy and children

112
Q

Penicillins - Pharmacokinetics

absorption

A

Oral absorption varies depending on acid stability

Penicillin G poor and unreliable

Penicillin V and Amoxicillin excellent

Piperacillin and Ticarcillin and IV only

IM absorption dependent on salt form

Rapid from aqueous solutions

Delayed from suspensions (procaine - benzathine)

Use against organisms susceptible to low but sustained levels of Pen G (syphilis- endocarditis)

113
Q

Penicillins - Pharmacokinetics

distribution

A

Distribute throughout body water - penetrate into cells and tissues poorly (ionized at physiological pH)

Can enter inflamed tissues or membranes (CSF, joint, eye)

114
Q

Penicillins - Pharmacokinetics

elimination

A

Most excreted as active drug via the kidney (t1/2

115
Q

Classes of Penicillins

Prototype Penicillins - narrow antimicrobial spectrum

A

Penicillin G - Prototypical penicillin

Powerful and inexpensive

BUT, hydrolyzed by acid and penicillinase enzyme

Used IV for hospitalized patients with serious infections

Penicillin V - Acid resistant penicillin

Better absorbed than penicillin G, but still incomplete

Preferred for oral therapy - higher reliability of absorption

Efficacy

116
Q

Classes of Penicillins

Penicillinase-Resistant Penicillins

A

Less potent against Pen G-sensitive organisms

Not substitutes for Pen G, except for PCNase-producers

Emergence of MRSA has greatly limited current clinical use

Methicillin is prototype, but no longer available - Nafcillin

NOTE: Acid resistance varies: Oxacillin and dicloxacillin good oral absorption

Relatively narrow spectrum agents: gram +/ cocci

NOTE: All other penicillin drugs are susceptible to penicillinase

117
Q

Classes of Penicillins

Extended Spectrum Penicillins

A

Increased hydrophilicity [due to NH2 or COOH]  penetration through porins of gram-negative organisms

NOT penicillinase-resistant  given w/β-lactamase inhibitors

	Amoxicillin and Ampicillin

Acid resistant, good oral absorption

Amoxicillin absorbed better  less frequent dosing-diarrhea

	 Piperacillin and Ticarcillin - anti-pseudomonal penicillins

Must be given parenterally

Useful in anaerobic infections caused by B. fragilis

Effective against Pseudomonas and enterococci (+ AG)

118
Q

gram positive vs gram negative with penicillins

A

gram positive: pen V/G

gram neg: amox-amp

119
Q

Vancomycin - Pharmacokinetics

A

Poor oral absorption, administered IV, except for GI tract indications (e.g., Clostridium difficile)

Excretion mainly through kidneys – requires dosage adjustment if renal impairment

120
Q

Macrolides - Spectrum  Clinical Uses (Azithromycin – Clarithromycin – Erythromycin)

A

Gram positive cocci (increasing resistance):
Streptococci (increasing resistance)  pneumonia, pharyngitis [All]

Staphylococci (MSSA)

Atypical organisms:
Chlamydia  trachoma, CA pneumonia, urethitis [Azi]

Mycoplasma pneumoniae  CA pneumonia [All]

121
Q

Macrolides - Adverse Reactions

A

GI Disturbances

Nausea, vomiting, diarrhea, anorexia

Direct stimulation of gut motility by erythromycin - less with azithromycin and clarithromycin

Hepatotoxicity: Reversible acute cholestatic hepatitis (estolate salt)

Prolongs QT interval  ventricular arrhythmias - use caution with other QT prolonging drugs

Drug Interactions: Clarithromycin - erythromycin metabolites can inhibit CYP450 enzymes [NOT azithromycin]

122
Q

Macrolides - Mechanism of Action

A

Binds 50S ribosomal subunit  blocks translocation of peptidyl tRNA from acceptor to donor site on ribosome  prevents peptide elongation - bacteriostatic (BUT)

Not actively transported - enters by passive diffusion

Weak base that is more active at alkaline pH

Selectively toxic - no binding to human 60S ribosome

Resistance

Altered target - methylation of 50S ribosome  prevents macrolide binding

Increasing for S. pneumonia and H. influenzae

Substrates for multi-drug efflux transporter (MDR gene)

Inactivation of drug not significant

123
Q

Metronidazole - Adverse Reactions

A

Most common: nausea, headache, dry mouth, metallic taste

Occasionally: vomiting, diarrhea, abdominal distress

Exacerbation of candidiasis  furry tongue, glossitis

Inhibits aldehyde dehydrogenase

Antabuse®-like effect (GI upset, vomiting, headache) if alcohol consumed within 3 days of metronidazole

Risk of severe reaction is low

Category B in pregnancy - but weigh benefit-risk

Conflicting evidence regarding teratogenicity in animals

Taken at all stages of pregnancy without adverse effects, but use during 1st trimester is not advised

Disease and Defense class of 2019 (9 decks)

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