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Pharm 2 > Principles of Antibacterial Therapy > Flashcards

Principles of Antibacterial Therapy Flashcards

1
Q

Normal Flora of Mouth
(5)

A

› Viridans Group Streptococci
› Other Strep spps.
› Lactobacillus
› Actinomyces spps.
› Prevotella spps.

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2
Q

Gram Positive organisms:
(4)

A
  • Bulk of oral bacteria
  • Primarily cocci or irregular shape (pleomorphic)
  • Oxygen tolerance varies from facultative anaerobes to strict anaerobes
  • Cell wall has thick peptidoglycan layer
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3
Q

Three important genera:

A
  • Actinomyces -
  • Lactobacillus -
  • Streptococcus -
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4
Q
  • Actinomyces -
A

facultative anaerobe; periodontal pockets, dental plaques, on carious teeth

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5
Q
  • Lactobacillus -
A

facultative anaerobe; produce lactic acid; role in dentine caries rather than
enamel caries

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6
Q
  • Streptococcus -
A

facultative anaerobic cocci; produce lactic acid some implicated in caries

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7
Q

Streptococci Species in the Oral Cavity
› Oral streptococci are referred to as …
› Isolated from all sights of the mouth, each species has specific properties for
colonizing different oral sites
› Large proportion of resident microflora

A

viridans streptococci (Streptococcus viridans)

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8
Q

The Bad
Strep mutans:

A
  • Acidogenic (acid producing) and aciduric
    (acid tolerant) species
  • Highly associated with caries (+++)
  • Bacterial communities collected from
    dentin carious lesions contain notorious
    acidogenic and aciduric species, including S.
    mutans, Scardovia wiggsiae, Parascardovia
    denticolens, and Lactobacillus salivarius
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9
Q

The Good
Strep mitis, S. sanguinis:

A
  • First oral organisms detected in newborn
    infants (primary colonizers)
  • Commensals
  • Peroxigenic (produce hydrogen peroxide)
    inhibits the growth of S. mutans and
    Porphyromonas gingivalis, and other oral
    pathogens.
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10
Q

Gram Negative organisms
* Many Gram-negative bacteria found in the mouth, especially in
…
* Range of oxygen tolerance but most important …
* Some fermentative, produce — which other organisms use acids as an
energy source, others produce — which break down tissue
* Cell wall different to Gram positive with a …

A

established/subgingival plaque
strict or facultative anaerobes
acids, enzymes
thin peptidoglycan layer, has B-
lactamase which breaks down penicillin, also has LPS/endotoxin

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11
Q

Gram Negative in the Oral Cavity
(7)

A
  • Porphyromonas:
  • Prevotella:
  • Fusobacterium:
  • Actinobacillus/Aggregatibacter:
  • Treponema:
  • Neisseria
  • Veillonella
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12
Q
  • Porphyromonas:
A

P. gingivalis major periodontal pathogen

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13
Q
  • Prevotella:
A

P. intermedia a periodontal pathogen

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14
Q
  • Fusobacterium:
A

F. nucleatum periodontal pathogen

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15
Q
  • Actinobacillus/Aggregatibacter:
A

A.actinomycetemcomitans associated with
aggressive periodontitis

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16
Q
  • Treponema:
A

group important in acute periodontal conditions i.e ANUG

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17
Q

Bacteriostatic –

A

Arrests growth of organism
* Must have active immune system

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18
Q

Bactericidal –

A

Kill the organism
* Neutropenic, Meningitis, Endocarditis

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19
Q

Bactericidal
(2)

A
  • Cell Wall Inhibitors
    *Inhibit DNA
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20
Q
  • Cell Wall Inhibitors
    (3)
A

*Beta Lactams
*Penicillins
*Cephalosporins

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21
Q

*Inhibit DNA
(2)

A

*Fluoroquinolones
*Metronidazole

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22
Q

Bacteriostatic
* Protein Synthesis Inhibitors
(3)

A

– Macrolides
– Clindamycin
– Doxycycline

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23
Q

‘Cidal’ agents better for patients with

A

immunosuppression and severe disease

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24
Q
  • Concentration dependent
A
  • Higher concentration, more
    extensive/faster kill. Maximize peak
    concentation
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25
Q
  • Post-antibiotic effect
A
  • Bacterial suppression after antibiotic
    concentrations fall below MIC
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26
Q
  • Time dependent
A
  • The more time above the MIC, more
    inhibition. Maximize duration of
    exposure above MIC
    Affects how antibiotics are dosed
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27
Q

Concentration dependent
(2)

A
  • Higher concentration = greater killing
  • fluoroquinolones, metronidazole
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28
Q

Time-dependent killing
(2)

A
  • Concentrations need to be reinforced, leading to more dosing
  • More exposure = more killing
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29
Q
  • More exposure more killing
  • No PAE: 1
    • Some PAE: 3
A

Beta-lactams
clindamycin, azithromycin, tetracyclines

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30
Q

Optimizing Cephalexin Dosing
Usual dosage range:

A

250 to 1,000mg every 6 hours
or 500mg every 12 hours

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31
Q

— Dependent Drug: works best the longer concentrations stay above —
Half-life:
Excretion:

A

Time,MIC
approximately 1-hour for adults
Urine 80-100% as unchanged drug in 6-8 hours

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32
Q

Cellulitis:
Cystitis:

A

500mg 4 times daily
500mg twice daily

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33
Q

Suggests minimum —
hours of subtherapeutic
blood concentrations
with Q12hr dosing

A

4-6

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34
Q

Penicillin Allergy Problem
* Results in significantly more (3)

A

vancomycin, clindamycin, &
fluoroquinolones

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35
Q
  • Collateral damage associated with reported penicillin allergy
  • —% higher cost of antibiotics
  • Increase length of hospitalization, average — more total hospital days
  • Increased drug-resistant organisms
  • —% increased risk of MRSA infections
  • —% more VRE infections
  • —% increased risk of C. difficile infection
A

63-158
0.59
69
30.1
26

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36
Q

Penicillin Allergy Statistics
~–% of US outpatients & –% inpatients self-report penicillin allergy
* Studies have found —% of penicillin allergic patients tolerate penicillins
* –% test positive for penicillin allergy using skin testing

A

10
15
80-90
10

37
Q
  • Study of 5,201,036 individuals
  • 1,840,830 exposed to 3,837,003 courses of oral penicillins
  • 17 cases of anaphylaxis with oral penicillin (—%; 1 in 225,706 exposures)
  • 172,840 individuals exposed to 237,404 courses of parenteral penicillins
  • 3 cases of anaphylaxis with parenteral penicillin (0.00126%; 1 in 79,134)
  • 18,122 (0.44%) new penicillin ‘‘allergy’’ reports within 30 days of penicillin course
A

0.00044

38
Q

Adverse Drug Reaction Versus Allergy
Type A [Side Effect] - common
(3)

A
  • Predictable (pharmacologic action), Dose Related, Can Affect Anyone
  • Overdose - Hepatic failure (acetaminophen)
  • Side Effect - Nephrotoxicity (with aminoglycosides); diarrhea (amoxicillin)
39
Q

Type B [Allergy] - uncommon
(2)

A
  • Unpredictable (hypersensitivity reaction), Not dose related, Cannot affect anyone
  • Anaphylaxis; photoallergy
  • Antibody or T-cell Stimulation
40
Q

“Allergic-like” or “Pseudo-allergic” Reactions
(2)

A
  • Resemble allergic reactions; NOT Immune-mediated
  • Vancomycin ‘Redman Syndrome’; Morphine rash
41
Q

Low-Risk Penicillin Allergy Assessment
Low-Risk
(9)

A

Non-Hive Rash
Itching
Hive Rash*
Diarrhea
Vomiting
Nausea
Runny Nose
Cough
Family Hx of Allergy

42
Q

Low-Risk Penicillin Allergy Assessment
High-Risk [likely IgE or T-cell]
(5)

A

Lip/Facial Swelling
Breathing Difficulty/Wheezing
Skin Peeling
Mouth Blisters
Drop in Blood Pressure

43
Q

Urticaria | Hives
Affects –% of population at some point in their lives
* Viral infections cause >–% of all cases of acute hives in children

A

20
80

44
Q
  • 88 children (44 girls, 44 boys), average age 3.5 years (range, 0.5-14)
  • 47 patients (53.4 %) urticarial and 41 patients (46.6%) maculopapular
  • —% had no reaction following oral challenge
  • Observed skin reactions were similar to initial reactions
A

93.2

45
Q

597 questionnaires completed for children 4-18yrs reporting PCN allergy; 302
exclusively low-risk reactions
 100 low-risk reports underwent 3-tier testing
 Rash 97%
 Itching 63%
►–% tested negative for penicillin allergy

A

100

46
Q

All children with low-risk penicillin allergy history had negative results for

A

IgE
penicillin allergy using standard 3-tier testing process

47
Q

Low-risk allergy symptoms
– most commonly rash and itching –
likely do not represent true —

A

IgE allergy

48
Q

IgE-mediated
(5)

A
  • Onset minutes to hours
    into treatment course
  • Pruritic
  • Raised off the skin
  • Each lesion lasts <24 h
  • Fades without scarring
49
Q

Benign T-cell-mediated
(4)

A
  • Onset days into treatment
    course
  • Typically less pruritic than IgE-
    mediated reactions
  • Each lesion lasts >24 h
  • Fine desquamation with
    resolution over days to weeks
50
Q

Severe T-cell-mediated or
severe cutaneous
(4)

A
  • Onset days to weeks into
    treatment course
  • Mucosal and/or organ
    involvement
  • Blistering and/or skin
    desquamation
  • Usually requires
    hospitalization
51
Q

Low Risk
History
(4)
Action
(2)

A
  • Isolated reactions unlikely
    allergic (gastrointestinal
    symptoms, headaches)
  • Pruritus without rash
  • Remote (>10 years) unknown
    reactions without IgE features
  • Family history of Pcn allergy

› Prescribe amoxicillin course or
› Perform a direct amoxicillin
challenge under observation

52
Q

Medium Risk
History
(2)
Action
(2)

A
  • Urticaria or other
    pruritic rashes
  • Reactions with IgE
    features but not
    anaphylaxis

Skin test plus
amox challenge or
› Graded challenge

53
Q

High Risk
History
(4)
Action
(1)

A
  • Anaphylactic
    symptoms
  • Positive skin testing
  • Recurrent reactions
  • Reactions to multiple
    β-lactam antibiotics

Skin test plus amoxicillin
challenge

54
Q

Allergy Assessment
Questions to ask when assessing an allergy

A

 Describe reaction
 Administered PO or IV?
 How long ago did the reaction occur?
 Timing of reaction?
 Immediate (< 4hrs)
 Delayed (>24 hrs)
 Any treatment required?
 Use of penicillins or cephalosporins before reaction?
 Use of penicillins or cephalosporins since reaction?

55
Q

Time Elapse Since Adverse Response
Patients positive (skin test) for penicillin allergy
* 1-year later –% have a negative response
* 5-years later –% have a negative response
* 10-years later –% have a negative response

A

10-20
50
80

56
Q

65,915 penicillin ‘allergy’ patients exposed to 127,125 cephalosporin courses
» 3 cases (—%) of cephalosporin-associated anaphylaxis vs 7 cases in 845,923 courses
in patients with no history of penicillin allergy (0.0008%), not statistically more (p > 0.05)
J Allergy Clin Immunol. 2015

A

0.002

57
Q

Penicillin-Cephalosporin Cross-Sensitivity
* Classic Teaching, –% Penicillin-Cephalosporin
cross-reactivity
* Based on studies in 1960s and 1970s
* 1980’s cephalosporin purification techniques
developed
* Early cephalosporins contaminated with
penicillins: derived from Acremonium mold

A

10

58
Q

Oral antibiotic associated adverse drug
reactions for penicillin skin test positive
individuals compared to penicillin skin test
negative individuals
* Matched for sex, age, and follow-up length
* All had at least one oral antibiotic post
penicillin skin test

Conclusion Statement:

A

‘Non-beta-lactam antibiotics were associated with more adverse drug
reactions than penicillins or cephalosporins, independently of the penicillin skin test result.
Cephalosporins can be used as safely or more safely than non-beta-lactam antibiotics in
penicillin skin test positive and negative individuals.

59
Q

Penicillin-Cephalosporin Side Chain Comparison
Beta-lactam antibiotics have shared beta-lactam rings and may have side chains that
are structurally identical or similar.
ñ Cross reactivity is highest for beta-lactams that share identical side chains.
ñ Cross reactivity theoretically higher if …

A

side chains are similar

60
Q

Penicillin-Cephalosporin Similar R-side Chain
Cephalosporins without similar side chains to penicillin considered low risk and safe
in patients with …
* A reaction may occur to a cephalosporin by coincidence
* Risk similar to developing a reaction to sulfonamide antibiotic
» Cephalexin (Keflex) has a similar side chain to amoxicillin
» Cephalosporins that DO NOT have similar side chains to —: IV Cefazolin
(Ancef); Cefuroxime (Ceftin); Cefdinir (Omnicef

A

reported history or positive skin test

penicillins

61
Q

Penicillin Allergy Summary
ñ — is rare; Penicillin-Cephalosporin cross-reactivity NOT 10%
ñ Review the documented allergy or Interview the patient

A

True allergy (IgE)

62
Q

ñ Family history of penicillin allergy, GI symptoms, headache, yeast infection
(2)

A

►Not Allergy
* Comfortable giving any penicillin or cephalosporin

63
Q

ñ Hive and non-hive rash reports [not SJS-like]
(3)

A

►Likely not Type-1 Allergy
* May give amoxicillin, especially with distant history and penicillin benign skin reaction
* Can use a cephalosporin without concern

64
Q

ñ Severe/high-risk reactions [e.g. SJS, Anaphylaxis-like, DRESS, Serum sickness]
(2)

A

►Type-1 or CTC Allergy
* Use an alternative antibiotic [reasonable to consider later generation cephalosporin]

65
Q

Beta-Lactams
(3)

A
  • Penicillins
    Cephalosporins
    Carbapenems
66
Q
  • Penicillins
    (4)
A
  • Penicillin
  • Amoxicillin/Ampicillin
  • Dicloxacillin
  • Piperacillin
67
Q
  • Cephalosporins
    (5)
A
  • Cephalexin (Keflex)
  • Cefuroxime (Ceftin)
  • Cefaclor (Ceclor)
  • Cefprozil (Cefzil)
  • Cefdinir (Omnicef)
68
Q
  • Carbapenems
    (4)
A
  • Ertapenem | Imipenem | Doripenem | Meropenem
69
Q

B-lactam Mechanism of Action
(3)

A

Binds and Inhibits Penicillin Binding Protein (PBP)
Results in bacterial cell wall dysfunction
Includes Penicillins, Cephalosporins, Carbapenems

70
Q

Beta-Lactams
(6)

A
  • MOA: Binds to Penicillin Binding Proteins (PBPs); block cell wall
    synthesis causing the walls to leak; lower cell death threshold
  • ALL BETA LACTAMS ARE BACTERICIDAL
  • Most used & effective antibiotics with least toxicity.
  • Side-chains account for differences: acid stability, absorption, spectrum,
    susceptibility to beta-lactamases
  • Cross placenta and distributed into breast milk
  • High renal excretion
71
Q

Resistance Mechanisms
– decrease abx uptake
(2)

A
  • efflux pumps
  • membrane permeability changes
72
Q

Resistance Mechanisms
– enzymatic modification/degradation
(3)

A
  • beta-lactamases
  • transferases
  • redox processes
73
Q

Resistance Mechanisms
– target modification
(3)

A
  • altered PBP
  • RNA modification
  • DNA gyrase mutation
74
Q

Resistance Mechanisms
– — overproduction

A

bacterial

75
Q

Beta-Lactamase =

A

degradative enzyme

76
Q

270.2 million antibiotic prescriptions were written in
the United States in 2016
Enough antibiotic courses for — out of every six
Americans to receive an antibiotic prescription in 2016

A

five

77
Q

Resistance Statistics
Respiratory Infections (acute otitis media; pneumonia)
* S. pneumoniae resistance to azithromycin >—% in U.S.
* S. pneumoniae resistance to amoxicillin ~—% in U.S.
* S. pneumoniae resistance to smx-tmp ~—% in U.S.
Urinary Tract Infections
* E. coli resistance to amoxicillin ~–% in U.S.
* E. coli resistance to smx-tmp ~–% in U.S.
* E. coli resistance to fluoroquinolones ~–% in U.S.

A

40
20
30

50
30
30

78
Q

Beta-Lactamase Inhibitors
(3)

A
  1. Clavulanate (Paired with Amoxicillin)
  2. Sulbactam (Paired with Ampicillin)
  3. Tazobactam (Paired with Piperacillin)
79
Q

Beta-Lactamase Inhibitors
● Mechanism of action:
(3)

A

■ Irreversibly bonds with beta-lactamase.
■ “Ties up” all beta- lactamase.
■ Allows the antibiotic to persist and extends
activity to B-lactamase producing pathogens

Extends coverage, more GramNegatives, anaerobes, & Staph.
 Bacteroides spps. (common to oral abscesses) produce B-Lactamases

80
Q

► Augmentin™- amoxicillin+clavulanate =
(2)

A

► Augmentin™- amoxicillin+clavulanate = more gram negatives, anaerobes, & Staph.:
●Dental infections with abscess or failed amoxicillin

81
Q

B-lactamase Resistance (MSSA) Versus MRSA
B-lactamase
› Produced by Gram + and Gram -
› Effects Penicillin and Amoxicillin

Can Use:
(2)

A

»Cephalosporins
»Amox-clavulanate

82
Q

B-lactamase Resistance (MSSA) Versus MRSA
MRSA = PBP Change
Produced by some Staph. aureus species
Can NOT use

A

ANY B-lactam Antibiotic

83
Q
  • B-Lactam(s) =
    (2)
A

Group of Antibiotics
* Have B-lactam ring as part of the structure

65

84
Q
  • B-Lactamase =
    (2)
A

enzyme released by bacteria
* Disables the B-lactam ring thus the antibiotic is
ineffective

85
Q
  • B-Lactamase Inhibitor = (2)
A

compound added to
B-Lactam antibiotic
* Disables the B-lactamase thus antibiotic is
effective again

86
Q

Therapeutic Spectrum
* Narrow -
* Extended Spectrum -
* Broad Spectrum -

A

act on single organism or type of organisms
ex. Penicillin

works on gram positives and also some gram negatives
ex. Amoxicillin-clavulanic acid

affect a wide variety of organisms.
ex. Clindamycin
› May cause “superinfections” of unaffected microbes or fungi

87
Q

Amoxicillin/Clavulanate
Pediatric Antibiotic Associated Diarrhea
* 35 articles reporting on 42 studies were included for analysis
* 33 trials reported on amoxicillin/clavulanate
* 6 trials on amoxicillin
* 3 trials on penicillin V
* In total, the 42 trials included 7729 children treated with an oral penicillin

250: Amoxicillin 250 mg /clavulanate 62.5mg per 5mL
Rate of
Diarrhea –%

A

25

88
Q
A

Pharm 2 (13 decks)

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