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Medical Microbiology II - 4336 > Test 2: Antibiotics > Flashcards

Test 2: Antibiotics Flashcards

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1
Q

Antibiotics

A

Substance produced by a
microorganism that inhibits or kills other microorganisms

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2
Q

Antimicrobial agents

A

Chemical substance
produced either by a microorganism or
synthetically that can kill or suppress
microorganisms.

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3
Q

Antimicrobial agents may be described by what

A

*Bacteriostatic – inhibits bacterial growth
without killing
*e.g. tetracycline, erythromycin, Trimethoprim
*Bactericidal – kills bacteria
*e.g., aminoglycosides, beta-lactams,
vancomycin

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4
Q

What are types of Bacteriostatic drugs

A

Tetracycline, Erythromycin, and Trimethoprim

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5
Q

What are types of Bactericidal drugs

A

Aminoglycosides, Beta-Lactams, Vancomycin

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6
Q

Antimicrobial agents requirements

A

For an antibiotic to affect the growth
of a microbial cell it must
(i) enter the cell and reach the site of action,
(ii) bind to a target molecule involved in an
essential cell process,
(iii) markedly inhibit this process.

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7
Q

Antimicrobial resistance

A

is the ability of
a microorganism to withstand that
agent

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8
Q

Antimicrobial susceptibility

A

means that an
agent can kill (or inhibit growth of) the
organism at a specific concentration.
This is the MIC

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9
Q

activity of the microbial agent is

A

The degree and mode of
action of an antimicrobial agent

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10
Q

Spectrum of activity

A

its effective
against a large variety of organisms–
has broad spectrum
* Active against both gram-positive &
gram-negative; also, unidentified
pathogen
* Disadvantage: kills normal flora

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11
Q

Minimum Inhibitory concentration MIC

A

of an antibacterial agent is defined as the
maximum dilution of the product that
will still inhibit the growth of a test
microorganism.

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12
Q

Minimal bactericidal concentration

A

is defined as greater than or equal
to 99.9% reduction of visible colony
forming units of a bacterial or fungal
suspension.

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13
Q

MIC=MBC when

A

The concentration where there is no growth after incubation

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14
Q

how do you treat the person when MIC=MBC

A

Give antibiotics in high amounts and give for a longer period of time

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15
Q

MIC= what test tube

A

The high dilution without growth

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16
Q

Breakpoint

A

Concentration of
an antibiotic which defines in vitro whether a
species or group of species is susceptible or
resistant to an antibiotic/antimicrobial.

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17
Q

Breakpoint separates or defines

A

The interpretive category ( S,I, or R)

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18
Q

In breakpoint take in to account

A

wild type distribution of MICs
(wild type-those that do not have acquired
resistance or selected resistance mechanisms)

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19
Q

Other important implementations of Breakpoint

A
  • Pharmacokinetics/pharmacodynamics
  • Clinical outcome studies
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20
Q

Cell wall inhibitors

A
  • Beta-lactams: contain beta-lactam ring
    1. Penicillins
    2. Cephalosporins
    3. Carbapenems
  • Fosfomycin: inhibits enzyme at first step of
    cell wall synthesis
  • Glycopeptides/lipoglycopeptides
    1. Vancomycin
    2. Teicoplanin
  • Monobactam
    1. Aztreonam
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21
Q

Types of Beta-Lactams

A

Penicillins, Cephalosporins, and Carbapenems

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22
Q

Beta-lactams contain a

A

Beta-lactam ring

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23
Q

Fosfomycin inhibits

A

Enzyme at first step of cell wall synthesis

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24
Q

Gylcopeptides/lipoglycopeptides types

A
  1. Vancomycin
  2. Teicoplanin
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25
Q

Monobactam types

A

Aztreonam

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26
Q

Desirable properties of agents

A
  • Non-toxic; limited side-effects
  • Able to enter cell
  • Specific target
  • Sufficient concentration
  • Spectrum
  • Soluble in body fluids; remain active
  • Limited development of resistance
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27
Q

Beta lactams share a common

A

Beta-lactam rings

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28
Q

Bata-lactams principle mode of action

A

Inhibition of cell wall synthesis

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29
Q

Additions to the beta-lactam ring determine

A

whether the agent is a penicillin, cephem,
carbapenem, or monobactam.

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30
Q

Commonly used beta-lactum ring agents are due to their

A

broad spectra
of antibacterial activity, safety profiles, and proven
clinical efficacy

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31
Q

if the drug name begins with ceph or cillin, or penem

A

it is a beta lactam

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32
Q

Beta-lactam ring is similar to

A
  • Structurally similar to acyl-D-alanyl-D-
    alanine (substrate for linear
    glycopeptide in cell wall)
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33
Q

Beta lactam ring binds to

A

Bind to penicillin binding proteins
(PBPs)causing cell death
* PBPs cross-link cell walls
* PBPs essential for survival

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34
Q

all bacteria have pores and they are called

A

Porins or small pores

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35
Q

Glycopeptides/ Lipoglycopeptides are for what type of bacteria

A

gram positive bacteria

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36
Q

Glycopeptides- Vancomycin and teicoplanin what molecules and do not

A
  • Large molecules
  • Do not bind PBPs
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37
Q

Glycopeptides ( Vancomycin and Teicoplanin) bind

A

to precursors of cell wall synthesis
* Form a hydrogen bond with terminal D-alanyl-D-
alanine moiety of NAM/NAG peptides.
* Interferes with ability of PBP to incorporate precursors into cell wall

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38
Q

Lipoglycopeptides( oritavancin, Dalbavancin, Telavancin are Structurally similar to

A

vancomycin—
have addition of hydrophobic group

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39
Q

Lipoglycopeptides( oritavancin, Dalbavancin, Telavancin)

A

-Structurally similar to vancomycin—
have addition of hydrophobic group
Allows for binding to cell membrane—
increasing inhibition of cell wall
synthesis
* Also, increase permeability and
polarize cell membrane potential
* Can be affective for Vancomycin
Intermediate Staphylococcus aureus
(VISA).

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40
Q

Vancomycin mechanism of Action

A

Inhibits cell wall synthesis by binding to the D-ala-D-ala terminal of the
growing peptide during cell wall synthesis

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41
Q

Vancomycin use

A
  • For treatment of serious infections caused
    by β-lactam-resistant gram-positive
    microorganisms or if patient is allergic to β-
    lactam drugs
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42
Q

Vancomycin use for Prophylaxis for

A

endocarditis or
implantation of prostheses. Prophylaxis
should be discontinued after a maximum of
two doses.

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43
Q

Vancomycin use for what if unresponsive to what

A

for Pseudomembranous colitis if unresponsive to metronidazole

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44
Q

Vancomycin use is discouraged if

A
  • Routine surgical prophylaxis
  • Empiric therapy (unless evidence of Gram
    -positive infection or prevalence of MRSA
    is high)
  • Treatment of a single positive blood
    culture
  • Continued use after susceptibility report
  • Eradication of MRSA colonization
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45
Q

Inhibitors of cell membrane function

A

Polymyxin and Lipopeptides

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46
Q

Polymyxin description

A
  • Cyclic lipopeptides
  • Polymixin B and Colistin
  • Act as detergents (interacting with phospholipids)
  • Results in leakage of macromolecules from bacterial cells
  • Also human cell membranes 
  • Toxicity issues (neurotoxicity and nephrotoxicity)
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47
Q

Polymyxin acts like what

A

A detergent( Interacts with phospholipids)
- results in leakage of macromolecules from bacteria cells

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48
Q

Polymyxin are what lipopeptides

A

Cyclic

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49
Q

What are the types of Cyclic lipopeptides

A

Polymixin B and Colistin

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50
Q

How is Polymyxin toxic

A

Damage cell membranes
- Toxicity includes Neurotoxicity and Nephrotoxicity

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51
Q

Daptomycin can Bind to and

A
  • Binds to and disrupts Gram positive cell membrane
  • Inserts hydrophobic tail into membrane
  • Increases permeability, killing the cell
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52
Q

Daptomycin is what type

A

Lipopeptides

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53
Q

Polymyxin B can combined with

A

neomycin and bacitracin
as a topical antimicrobial
preparation

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54
Q

Colisitin was used between

A

1952 and 1980 for Gram negative rod infections

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55
Q

Colistin causes in humans

A

Renal toxicity and replaced by other antibiotics with less toxicity

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56
Q

Colistin is used for

A

Multi-drug resistant GNR and is a last line of defense

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57
Q

Daptomycin (DAP) is potent against

A

Gram postive cocci including resistant strains such as MRSA (Methicillin Resistant Staphylococcus
aureus) and
* VRE (Vancomycin Resistant Enterococcus sp.

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58
Q

Daptomycin large size prevents

A

it from penetrating gram negative organisms outer membrane

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59
Q

Daptomycin is not useful in

A

treatment of respiratory infections
- lung surfactant binds the drug, inactivating it

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60
Q

Inhibitors of protein synthesis

A
  • Aminoglycosides
  • Macrolide-lincosamide-
    streptogramin (MLS)
  • Ketolides
  • Oxazolidinones
  • Chloramphenicol
  • Tetracyclines
  • Glycylglycines
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61
Q

Amino-glycosides types

A

tobramycin, gentamicin, amikacin

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62
Q

Aminoglycosides are

A

broad spectrum

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63
Q

Aminoglycosides inhibit protein synthesis by

A
  • Irreversibly binds protein receptors on bacterial 30S
    ribosome
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64
Q

Amino-glycosides are used with and have an increased

A
  • Often used with beta-lactam (synergistic effect)
  • Bacterial uptake increased
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65
Q

Aminoglycosides inhibit what bacteria

A
  • Wide variety of GN organisms and certain GP –e.g. Staph.
    aureus
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66
Q

Aminoglycosides can not inhibit what

A
  • Anaerobic bacteria cannot take these agents up intracellularly –
    so typically not active
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67
Q

What should be monitored during therapy with Amino-glycosides

A
  • Blood levels must be monitored during therapy
  • Nephrotoxicity
  • Auditory and Vestibular Toxicity
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68
Q

Macrolide group
Macrolide=

A

Macrolide-lincosamide-streptogramin
* Macrolide=erythromycin, azithromycin,
clarithromycin

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69
Q

The macrolide group is generally what activity

A
  • Generally bacteriostatic, but can be
    bactericidal if infective dose is low and drug
    concentration is high
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70
Q

The Macrolide group binds to

A
  • Binds the 23S ribosomal RNA on the 50S
    ribosomal subunit
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71
Q

The Macrolide group disrupts what and has uptake difficulties with what

A
  • Disrupts the growing peptide chain by
    preventing translocation
  • Uptake difficulties with G- bacteria
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72
Q

Lincosamide type

A

Clindamycin

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73
Q

Clindamycin binds the blank and interferes with blank

A

50s subunit ribosomal subunit
- prevents elongation ( Interferes with peptidyl transfer)

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74
Q

Clindamycin has what activity

A

gram positive activity and is Bactericidal or bacteriostatic
-* Activity against anaerobic Gram positive and
some anaerobic Gram negative

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75
Q

Clindamycin is associated with an increased risk of

A

C.diff infections

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76
Q

Streptogramin-
Quinupristin/dalfopristin are what

A

(Synercid)
1. Synergistic (either is static; combination is cidal

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77
Q

Streptogramin-
Quinupristin/dalfopristin 1st step

A

First, dalfopristin binds to the ribosomal
50S unit changing the conformation of the
ribosome.

78
Q

Streptogramin-
Quinupristin/dalfopristin 2nd step

A

-Increasing the affinity of quinupristin that
in turn binds to the bacterial ribosome
-This double binding interrupts protein
synthesis and blocks bacterial growth

79
Q

Oxazolidinones types

A
  • Linezolid (trade name = Zyvox) and tedizolid
  • Relatively new class of antibacterial agents
  • Synthetic
80
Q

Oxazolidinones inhibit protien synthesis through

A

protein synthesis through a unique
mechanism
* Binds the 23S ribosomal RNA of the 50S
subunit, prevents the formation of a
functional 70S initiation complex. This
prevents bacterial translation and replication.
* New mechanism=no cross resistance with other drugs

81
Q

Oxazolidinones inhibit what organisms

A
  • Gram positives and Mycobacteria
82
Q

Chloramphenicol action, inhibits what organisms, and are is associated with what

A
  • inhibits protein synthesis by binding the 50S subunit—inhibits
    transpeptidation
  • Gram negative and Gram positive activity
  • Toxicity (Bone marrow—aplastic anemia)
83
Q

Tetracycline/ Doxycycline is a

A

broad spectrum antibiotic
- bacteriostatic
- toxic to upper GI and causes cutaneous phototoxicity and Photoallergenic immune reactions

84
Q

Tetracycline/ Doxycycline binds to and inhibits what organism

A
  • Bind 30S subunit; incoming tRNAs –
    amino acid complexes cannot bind to
    the ribosome.
  • G+, G-, intracellular bacterial
    pathogens
85
Q

Glycylglycines are

A
  • Semisynthetic tetracycline derivative
  • Tigecycline
  • have GI side effects
86
Q

Glycylglycines inhibit what and are not affected by what

A

Inhibits protein synthesis
* Reversibly binds the 30S ribosomal subunit
* Not affected by most common
tetracycline resistance mechanisms

87
Q

Inhibitors of DNA and RNA synthesis

A
  • Fluoroquinolones
  • Metronidazole
  • Rifampin
88
Q

Fluoroquinolones bind to and interfere with

A

Bind to and interfere with DNA gyrase and topoisomerase
(involved in bacterial supercoiling)

89
Q

Fluoroquinolones inhibit what organisms, human side effects, and are what mode of action

A
  • Bactericidal
  • Broad spectrum-Gram positive and Gram negative,
    but resistance has developed.
  • Side effects = affects in tendons (Tendonitis and rupture)
90
Q

types of Fluoroquinolones

A
  • Nalidixic acid= older drug
    Ciprofloxacin, levofloxacin,
    Ofloxacin, norfloxacin (UTI),
    Moxifloxacin
91
Q

Metronidazole disrupts what, requires what atmosphere, and is potent against

A
  • Disrupts helical structure of DNA
  • Activation requires reduced
    atmosphere (anaerobic)
  • Most potent against anaerobes
    and microaerophilic organisms
92
Q

**Metronidazole kills

A
  • kills both C. difficile
  • Also Trichomonas and other
    amoebae
93
Q

Rifampin characteristics

A
  • Semisynthetic
  • Binds RNA polymerase; inhibits
    synthesis of RNA
  • Better for Gram positive
94
Q

Rifampin develop what, has what type of mutations, and is used with

A
  • Develops resistance quickly
  • Spontaneous mutations—rifampin-
    insensitive RNAP
  • Used in combination with other
    drugs
95
Q

Inhibitors of Other Metabolic
Processes

A
  • Sulfonamides
  • Trimethoprim
  • Nitrofurantoin
96
Q

Sulfonamides characteristics

A
  • Also disrupts bacterial folic acid pathway
    (different enzyme inhibited)
  • Active against wide variety of Gram
    positive and negative except P.
    aeruginosa
97
Q

Trimethoprim

A
  • Disrupts folic acid pathway
  • Can combine with sulfonamide for better
    activity
  • Active against several Gram positive and
    negative except P. aeruginosa
98
Q

Trimethoprim binds to dihydrofolate reductase to inhibit

A

Dihydrofolic acid —-> Tetrahydrofolic acid ( active form of folic acid)

99
Q

Sulfonamide inhibits what enzyme

A

Para-aminobenzoic acid

100
Q

Nitrofurantoin characteristics

A
  • Activated by bacterial flavoproteins
    (nitroreductase). Reduced reactive intermediates
    damage ribosomes and other macromolecules such
    as DNA, RNA and proteins.
  • Good activity for most Gram positive and Gram
    negatives that cause UTI (not P. aeruginosa)
  • Only for urinary tract infections.
101
Q

Clinical Resistance

A

loss of antimicrobial
susceptibility to the extent that the agent is no
longer effective for clinical use.

102
Q

Microorganism- mediated antimicrobial resistance

A

– due to genetically encoded traits
Where a bacteria transfers resistance to another bacteria

103
Q

Examples of intrinsic resistance

A
  1. Pseudomonas: poor diffusion through
    cellular envelope and efflux pumps
  2. Vancomycin cannot penetrate gram-
    negative cell wall
  3. Enterococcus: cephalosporins cannot bind
    PBPs
  4. All Klebsiella pneumoniae produce a
    beta-lactamase that inactivates ampicillin
104
Q

Anaerobic bacteria versus aminoglycosides

A
  • Lack of oxidative metabolism to drive uptake of
    aminoglycosides
105
Q

Gram-positive bacteria versus aztreonam (beta-lactam)

A
  • Lack of penicillin-binding protein (PBP) targets that bind
106
Q

Gram-negative bacteria versus vancomycin

A
  • Lack of uptake resulting inability to penetrate outer
    membrane
107
Q

Pseudomonas aeruginosa versus sulfonamides,
trimethoprim, tetracycline, or chloramphenicol

A
  • Lack of uptake - ineffective intracellular concentrations
108
Q

Klebsiella spp. versus ampicillin (a beta-lactam) targets

A
  • Production of enzymes (beta-lactamases) that destroy
    ampicillin before it reaches its PBP target
109
Q

Aerobic bacteria versus metronidazole

A
  • inability to anaerobically reduce drug to its active form
110
Q

Enterococci versus aminoglycosides

A
  • Lack of sufficient oxidative metabolism to drive uptake of
    aminoglycosides
111
Q

Enterococci versus aminoglycosides

A
  • Lack of sufficient oxidative metabolism to drive uptake of
    aminoglycosides
112
Q

Enterococci versus all cephalosporin antibiotics

A
  • Lack of PBPs that effectively bind
112
Q

Enterococci versus all cephalosporin antibiotics

A
  • Lack of PBPs that effectively bind
113
Q

Lactobacilli and Leuconostoc spp. versus vancomycin

A
  • Lack of appropriate cell wall precursor target
114
Q

Lactobacilli and Leuconostoc spp. versus vancomycin

A
  • Lack of appropriate cell wall precursor target
115
Q

Stenotrophomonas maltophilia versus carbapenems (beta
-lactam)

A
  • Production of enzymes (beta-lactamases) that destroy
    carbapenem before it reaches PBP targets
116
Q

Acquired Resistance characteristics

A
  • Mutations
  • Horizontal gene transfer:
  • Transformation
  • Transduction
  • Conjugation
  • Often Plasmid mediated
    Important:
  • We test for acquired
    resistance not intrinsic
    resistance.
117
Q

Frequent Methods of Resistance

A
  • Enzymatic degradation
  • Decreased uptake
  • Increased efflux
  • Altered target
117
Q

Frequent Methods of Resistance

A
  • Enzymatic degradation
  • Decreased uptake
  • Increased efflux
  • Altered target
118
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems, etc.)

1.) Enzymatic destruction ( Beta- lactamases)

A
  • Most common method of resistance
  • Thousands of different types of beta-lactamases
  • Some beta-lactamases are encoded on mobile genetic
    elements (e.g. plasmids) and others are encoded on
    chromosomes.
119
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems

Class A subset a - Extended spectrum beta lactamases

A
  • Significant impact clinically
  • Confers resistance to penicillin, cephalosporins, and
    aztreonam
  • Derived from the narrow-spectrum beta-lactamases
    (TEM-1, TEM2 or SHV-1, OXA, CTX-M and GES
    ensyme)
  • Klebsiella, E. coli and enterobacteria
120
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems

class A subset b. Carbapenemases

A
  • High level clinical impact
  • Aztreonam is variable depending on the genotype
    CRE, CRO, MDRO
  • Serine beta-lactamase
  • KPC (Klebsiella pneumonia carbapenemases: Resistant to all
    penicillins, cephalosporins, carbapenems, and aztreonam
121
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems

Class B

A

-Metallo-beta-lactamases (MBLs) requires zinc at active
site
-to hydrolyze all beta-lactams NDM, IMP and VIM

122
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems

Class C

A

AmpC: hydrolyze most cephalosporins except cefipime,
cephamycin (cefoxitin, cepotetan), aztreonam and penicillin.

123
Q

Resistance to Beta Lactams (penicillins,
cephalosporins, carbapenems

Class D

A

Oxacillinases (OXAs) OXA 48 and OXA 23 like. Resistant to
all penicillins, cephalosporins, carbapenems, and
aztreonam

124
Q
  1. Altered antibiotic target (mutations in PBPs)
A

Lower affinity binding
mecA confers resistance in Staphylococcus sp. and
Streptococcus sp. (e.g. MRSA)

125
Q

MRSA

A
  • Methicillin resistant Staphylococcus aureus
125
Q

MRSA

A
  • Methicillin resistant Staphylococcus aureus
126
Q

MRSA what is tested, other characteristics

A
  • Cefoxitin resistance can be used as a screen
  • PBP 2A latex agglutination tests
  • PCR to detect genes
  • mecA – most common
  • mecC – newer variant identified in England
  • Limited data on prevalence in the US
127
Q

Beta-Lactam/Beta Lactamase Inhibitor
Drugs mode of actions

A
  • Inhibitor binds beta-lactamase allowing, beta-lactam to
    work
  • Older generation were suicide inhibitors
  • Most have no intrinsic antibacterial activity
  • Exception - Sulbactam is active against Acinetobacter
128
Q

Beta-Lactam/Beta Lactamase Inhibitor
Drugs examples

A
  • Amoxicillin/clavulanic acid
  • Ampicillin/sulbactam
  • Piperacillin/tazobactam
129
Q

Vancomycin Resistance
* VRE – Enterococcus

A
  • vanA, vanB, vanC, vanD, and vanE
129
Q

Beta-Lactam/Beta Lactamase Inhibitor
Drugs newer generation

A
  • Ceftolozane/tazobactam
  • Ceftazidime/avibactam
130
Q

Vancomycin Resistance

Intrinsic

A
  • Enterococcus casseliflavus/flavescens and
    gallinarum
  • Low-level
131
Q

Vancomycin Resistance

  • Acquired resistance (vanA most common)
A
  • Enterococcus faecalis, faecium, raffinosus,
    avium, and durans
  • Altered target - Alteration in the molecular
    structure of cell wall precursor components
    decreases binding of vancomycin, allowing cell
    wall synthesis to continue.
132
Q

Aminoglycoside Resistance

Enzymatic

A
  • Modification of aminoglycoside
  • Decreased affinity to bind the 30S ribosome
  • Allows translation to continue
133
Q

Aminoglycoside Resistance

Altered target

A
  • Mutations in ribosomal targets (rare)
134
Q

Aminoglycoside Resistance

Decreased uptake

A
  • Porin (OMP) mutations
135
Q

Fluoroquniolone resistance

A
  • Decreased uptake
  • Altered target
  • Mutations in DNA gyrase or
    toposiomerase
  • Efflux
136
Q

Resistance to Trimethoprim

A
  • Bacteria need to make their own folic acid
  • Use a vital pathway that involves the
    enzyme dihydrofolate reductase.
  • Trimethoprim inhibits this bacterial
    enzyme
  • some bacteria bypass this step by acquiring a
    new enzyme that bypasses the old, inhibited
    dihydrofolate reductase.
  • The new enzyme comes from (you guessed it)
    plasmids.
137
Q

Goals of tests

A
  • Determine the best option for treatment
  • Relevant testing
    Standardization
  • Environmental factors must be minimized
  • Optimize growth conditions
  • Optimize antimicrobial integrity
  • Maintain reproducibility/consistency
138
Q

In vitro standardization

Bacterial Inoculum

A

0.5 Macfarland

139
Q

In vitro standardization

medium ( Mueller Hinton agar or broth

A
  • agar depth ~4mm
  • Cation concentration – too high can cause a decrease in
    zone sizes
  • pH – neutral ~7.4
  • Thymidine concentration – should not interfere with
    detection of tetracycline and sulfonamide resistance
    (can cause inhibition if concentration to high)
140
Q

In vitro standardization

Incubation time and temperature

A

35 C, 16-18 hours

141
Q

In vitro standardization

Concentrations of antimicrobial agent

A
  • Follow CLSI concentrations or FDA package insert
    concentrations
142
Q

Inoculum Standardization

A

 A 0.5 McFarland Standard contains
about 1.5 x 108 CFU/mL (used for disk diffusion and E-test)
 Broth dilution methods are standardized using
5 x 105 CFU/mL.

143
Q

media

Mueller Hinton broth

A
  • Purchased commercially
  • pH, cation concentration, thymidine content controlled by
    manufacturer
144
Q

media

NaCL is needed for

A

MRSA

145
Q

media

Blood MH is needed for

A

Viridans Streptococcus or Streptococcus
pneumoniae

146
Q

media

Chocolate MH is needed for

A

N. meningitidis

147
Q

media

Haemophilus test medium is used for

A

Haemophilus

148
Q

Incubation requirements

A
  • After test is set up, DO PURITY CHECK
  • 350, non-CO2
  • Can use CO2 for fastidious (Neisseria, Haemophilus,
    streptococci)
149
Q

Microbroth dilution

A
  • Usually MH broth
  • Serially dilute antimicrobial agent in tubes or
    wells
  • Add organism suspension: final
    concentration is 5 x 105 (dilution of 0.5
    McFarland)
  • Incubate
  • Read MIC
150
Q

Agar dilution

A
  • Incorporate antimicrobial agent in semi-liquid agar
    at varying concentrations
  • Inoculate bacterial suspensions on surface of agar
  • Incubate
  • Read MIC
151
Q

Disk diffusion ( Kirby Bauer)

A
  • 0.5 McFarland
  • MH Media
  • Can test multiple drugs
  • Use antimicrobial agent impregnated disks
  • Agent diffuses into agar: concentration gradient
  • Incubate
  • Measure zone diameters, correlate to S, I, R
  • No MICs
  • Storage of disks
  • Must be stored at proper temperature
  • Frequently requires -20C
152
Q

Antimicrobial Susceptibility Test
Methods: Interpretive Breakpoints

A
  • Establishing zone
    diameter interpretive
    breakpoints
  • Hundreds of samples
    tested and zone of diameter
    correlated with MICs to get
    ranges
153
Q

the E test

A
  • 0.5 McFarland
  • MH Media
  • Gradient diffusion
  • Antibiotic concentration changes along the strip
  • Can obtain MIC
154
Q

Advantages and disadvantages of broth dilution

A
  • A: can obtain MIC
  • D: amt. of tubes/pipetting, time consuming, not as
    reproducible
155
Q

Advantages and disadvantages of micro dilution

A
  • Microdilution
  • A: better reproducibility, ease of inoculation, can test
    many drugs at once
  • D: skipped wells, expensive, less choice of drugs
156
Q

Advantages and disadvantages of Kirby Bauer

A
  • A: easy and cheap, more choices of drugs
  • D: lots of variables
157
Q

Advantages and disadvantages of E test

A
  • A: ease of use and reading, can test organisms
    that don’t grow well in broth systems
  • D: more expensive
158
Q

types of automated AST

A

-Vitek
- microscan

159
Q

Vitek

A
  • Small card
  • Microdilution in tiny wells
  • Algorithm based MICs generated by software
  • Cannot see what is happening
  • 8-24 hour results
  • Has more limitations because of algorithm
160
Q

Microscan

A
  • Microdilution in microtiter plate
  • Lyophilized version of reference method
  • Can be read by instrument or manually
  • 16-48 hour results
161
Q

QC

A
  • Daily/weekly
  • IQCP (Individualized Quality Control Plan)
    required for weekly testing
  • New lot/new test
  • Use ATCC strains
  • QC strains are found in package insert or CLSI
    Manual (M100)
162
Q

Common test battery

Enterobacteriaceae

A
  • Beta lactams including: ampicillin, cephalosporins, and
    carbapenems; aminoglycosides; fluoroquinolones
163
Q

Common test battery

Pseudomonas

A
  • Other beta lactams such as Piperacillin, ceftazidime(3rd
    generation cephalosporin) and cefepime (4th generation
    cephalosporin), and carbapenems), and aminoglycosides,
    fluoroquinolones
164
Q

Common test battery

Staphylococcus

A
  • Pen & Amp, erythromycin, clindamycin, fluoroquinolones,
    vancomycin, doxycycline, trimethoprim/sulfa.
165
Q

Clinical reporting

A
  • CLSI has recommendations for reporting by
    drug/bug combo
  • FDA indications also important
  • Body site and infection specificity
  • Not all drugs are cleared to treat all types of
    infections in all sites
  • Reporting should be determined by
    laboratory with input from Pharmacy and
    Infectious Disease Physicians
166
Q

Antibiogram

A
  • Provides guidance for empiric treatment
  • Provides guidance on resistance patterns in a particular
    hospital or system
167
Q

Alternative Approaches for MRSA

Oxacilin agar screen

A
  • Technique to ensure detection of heteroresistant
    populations (MSSA and MRSA)
  • In conventional testing: 5% NaCl, 35o, 24 hours
168
Q

Alternative Approaches for MRSA

PBP2a detection

A
  • Detect using latex agglutination or
    immunochromatographic membrane tests
169
Q

Alternative Approaches for MRSA what molecular test

A
  • PCR
  • Detect mecA gene
170
Q

Oxacillin screen agar

A
  • -Resistance by penicillin binding proteins (PBP) via mecA gene
  • -Test oxacillin in lab (more stable) - if resistant, all
    cephalosporins are reported as resistant
  • -Newer method uses cefoxitin for greater sensitivity (usually
    cefoxitin disk)
171
Q

Oxacillin screen agar

A
  • -Resistance by penicillin binding proteins (PBP) via mecA gene
  • -Test oxacillin in lab (more stable) - if resistant, all
    cephalosporins are reported as resistant
  • -Newer method uses cefoxitin for greater sensitivity (usually
    cefoxitin disk)
172
Q

Oxacillin disk screen

A

– screen for
Streptococcus pneumoniae ( penicillin resistance)

173
Q

Enterococci screening test

A
  • Aminoglycoside screen – tests synergy of
    two drug classes
  • Synergy: Ampicillin + Gentamicin
  • Test for VRE (vancomycin agar screen)
174
Q

ChromAgar

A

Screening agar – used for determining MRSA
carriage in the nares

175
Q

Beta-lactamase

A
  • Use chromogenic cephalosporin (nitrocefin,
    cefinase)
  • Use for Staphylococcus, N. gonorrhoeae, H.
    influenzae, enterococci, sometimes
    Bacteroides sp.—NOT for enteric GNRs
176
Q

ESBL

A
  • Extended Spectrum Beta Lactamase
  • E. coli, K. pneumoniae and others
  • In vitro susceptibility not reliable for B-lactam
    drugs
  • Test using B-lactam inhibitor
    New Cephalosporin Breakpoint Released by CLSI in
    2010 made ESBL testing no longer required for Clinical
    Reporting
177
Q

ESBL Testing (rarely used now)

A

Look for ≥ 5 mm zone increase
CAZ, CAZ/CLA
CTX, CTX/CLA

178
Q

ESBL confirmation

A

-Can also use broth dilution:
-Look for ≥ 3 doubling dilution decrease with either
drug:
-e.g. ceftazidime MIC = 8 ug/mL
ceftazidime/clavulanate MIC = 1 ug/mL
-This is the basis for confirmation FDA-approved
commercial tests

179
Q

Reporting ESBL test

A
  • Report resistant for all penicillins, cephalosporins,
    and aztreonam regardless of in vitro status
  • Not cephamycins (cefoxitin/cefotetan)
180
Q

Detection methods for
Carbapenemases

  • Modified Carbapenem Inactivation Method (mCIM)
A
  • Incubate organism in water with 10ug disk of
    meropenem for 2 hours
  • Place disk on lawn of susceptible E. coli and look for
    presence or absence or zone of clearing
181
Q

Detection methods for
Carbapenemases

CarbaNP

A
  • Hydrolysis methods which detect carbapenem
    degradation products – color change
182
Q

Detection methods for
Carbapenemases

  • Lateral flow immunoassays
A
  • Detect carbapenemase enzymes using specific
    antibodies
183
Q

Detection methods for
Carbapenemases. Molecular methods

A

PCR) – detects genes

184
Q

Detection methods for
Carbapenemases

Modified Hodge test is no

A

no longer recommended

185
Q

D test

A
  • The erm gene product confers clindamycin
    resistance in S. aureus.
  • Clindamycin resistance is INDUCIBLE
  • Any Staphylococcus Or Beta Streptococcus that
    tests susceptible to clindamycin and NOT
    susceptible to erythromycin must have a D-Test
    performed
186
Q

Clindamycin Induction

A
  • To determine if S.
    aureus/MRSA is
    susceptible to Clindamycin
  • S. aureus/MRSA resistant
    to erythromycin and
    susceptible to clindamycin
    have to be tested
  • Zone around clindamycin
    disk will be blunted to
    form D if clindamycin can
    be induced by
    erythrothromycin to be
    resistant
187
Q

Limitations of Susceptibility/Resistance
Testing

A
  • In vitro/in vivo
  • Phenotypic vs. Genotypic
  • Diffusion of agent in tissues
  • Patient status
  • Virulence and pathogenicity of
    organism
  • Site & severity of infection

Medical Microbiology II - 4336 (20 decks)

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