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Pharm 2 > Principles of Antibacterial Therapy > Flashcards

Principles of Antibacterial Therapy Flashcards

1
Q

Why not use Augmentin for everything?
(4)

A
  • Cost ($10/15 vs $50)
  • 3x more side effects
  • Resistance
  • In the person exposed,
    primarily
  • Stewardship
  • Analogy – moving from
    studio/1BR apartment
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2
Q

Why risk using amoxicillin rather than clindamycin?
Risk of using amoxicillin:
* No risk if the reaction is (4)

A

GI, headache, yeast infection, family history

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3
Q
  • Any non-SJS rash history to amoxicillin, re-exposed to amoxicillin –% tolerate with no subsequent reactions
  • Risk of a severe reaction is –%
  • Risk for sever reaction if initial ‘allergy’ was immediate onset, –%
A

93-94
0.001
0.29

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4
Q

Risk of Clindamycin
* Among oral antibiotics commonly
prescribed by dentists, — has
the highest fatal (2.9/million
prescriptions), serious (233.2/million
prescriptions), and overall (337.3/million
prescriptions) ADR rates

A

clindamycin

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5
Q

Among oral antibiotics commonly
prescribed by dentists, clindamycin has
the highest fatal (2.9/million
prescriptions), serious (233.2/million
prescriptions), and overall (337.3/million
prescriptions) ADR rates.
* — any other dental antibiotic
* >– times higher than amoxicillin
* — has the lowest fatal
(0.1/million prescriptions), serious
(11.9/million prescriptions), and overall
(21.5/million prescriptions) ADR rates

A

Double
15
Amoxicillin

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6
Q

Risk of C. difficile
Infection By Antibiotic
* Clindamycin —fold increased risk
* Augmentin —fold
* Cephalexin (Keflex) —fold
* Amoxicillin —fold
* Penicillin —fold

A

25
8.5
3
2
1.8

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7
Q

–% mortality rate
within 30 days of
initial CA-CDI
– of patients with
recurrent CDI die
within 6 months

A

1.3
1/3

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8
Q

Functional Gastrointestinal Sequelae Is Common
* –% of subjects with C.
difficile later identified with one
functional gastrointestinal
disorder
* 1 additional case of functional
gastrointestinal disorder for
every – diagnoses of C. difficile

A

14.1
12

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9
Q

Longer exposure to antibiotics and multiple antibiotics increases —

A

risk

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10
Q

Proton Pump Inhibitors Double Risk for CDI
CDI — as high in patients
prescribed a PPI + antibiotic versus
antibiotic alone (OR 2.2; 95% CI
1.52-3.23)
Exposure to PPI prior to initial CDI
event — risk of recurrence
(OR 2.02; 95% CI 1.59–2.55)

A

twice
doubles

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11
Q

May consider for higher risk individuals:
(5)

A
  • 65yo+
  • recent hospitalization or nursing home
  • weak immune system (HIV/AIDS, cancer, or
    taking immunosuppressive drugs)
  • previous C. diff infection
  • taking proton pump inhibitors
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12
Q

Penicillin Class Considerations Review
(4)

A
  • Spectrum of Activity
  • Penicillin covers…
  • Amoxicillin covers…
  • Augmentin covers if…
  • Early vs. Progressed
  • Diarrhea
  • Costs
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13
Q

Cephalosporins
* Most — do not reduce activity of cephalosporins

A

beta-lactamases
* Active against Gram negatives producing b-lactamase

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14
Q
  • Several “Generations”
  • Each successive generation includes more Gram—- activity
A

negative

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15
Q

Cephalosporins
(5)

A
  • Most beta-lactamases do not reduce activity of cephalosporins
  • Several “Generations”
  • Limited side effect profile
  • Safely tolerated in penicillin intolerance history
  • Poor against anaerobes
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16
Q

1st Generation Cephalosporins
* Excellent GRAM POSITIVE Coverage – (2)
* some gram negative activity:
(2)

A

Strep. spps. & Staph aureus

  • Proteus, E. coli, and Klebsiella (PEcK)
  • Limited oral gram negatives- NO P. gingivalis
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17
Q

1st Generation Cephalosporins
Orals
(2)

A

 cephalexin (Keflex™)
 cefadroxil (Duricef™)

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18
Q

2nd Generation Cephalosporins
* Still excellent GRAM POSITIVE Coverage – (1)
* Some additional gram negatives:
(2)

A

Strep. spps.

  • Morexella, Haemophilus, Enterobacter, Neisseria
    (More HEN PEcK)
  • Still overall limited oral gram negative- YES P. gingivalis
    RX: Cefuroxime 500mg po BID x 5 days
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19
Q

2nd Generation Cephalosporins
Orals
(3)

A

 cefaclor (Ceclor™)
 cefuroxime (Ceftin™)
 cefprozil (Cefzil™)

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20
Q

Cephalexin Considerations
* Compared to Amoxicillin
* Pro:
* Con:
* Compared to Augmentin
* Pro:
* Con:

A
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21
Q

*Individuals allergic to amoxicillin may receive cephalexin as long as the reaction
was not

A

anaphylactic-like.

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22
Q

Metronidazole (Flagyl)
●Bactericidal against all —
 Bacteroides spps. and Fusobacterium
●Breaks DNA structure directly through production of —
●

A

obligate ANAEROBES
free radicals
Antiprotozoal: amoeba (Entamoeba), Trichomonas, Giardia.

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23
Q

Metronidazole
Adverse Reactions:
(4)

A
  • Metallic taste, dry mouth
  • Dark urine
  • Skin rashes
  • Disulfiram reaction? (headache, flushing, N/V)
    avoidance of alcohol no longer required
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24
Q

CYP2C9 Inhibitor: DRUG INTERACTIONS
(3)

A

ÞWarfarin
ÞLithium
ÞPhenytoin

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25
Q

Consistent INR elevations
observed with Warfarin’s BFFs
(3)

A

 Bactrim
 Flagyl
 Fluconazole

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26
Q

Warfarin Interactions
CYP2C9 Culprit
(3)

A

› TMP-SMX
› Metronidazole
› Fluconazole

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27
Q

Empiric Warfarin Dose Reduction
* Retrospective, cohort study in a pharmacist-managed anticoagulation clinic
* Anticoagulation patients initiating metronidazole
* Preemptive dose reduction (PDR) of warfarin vs increased monitoring
* Mean warfarin PDR 34.6% ± 13.4%
* PDR patients had no significant increase in INR (p=0.61)
* Mean INR difference +1.28 (p=0.01), monitoring vs PDR
* INR values >4.0 (PDR 0% vs. increased monitoring 46%, p=0.05)

Suggests benefit of —% preemptive reduction in mean daily warfarin
dose for patients started on concomitant CYP2C9 inhibitor

A

30%-35

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28
Q

Metronidazole (Flagyl)
●General Medical Uses:
(2)
●Resistance is not a problem. Given (2)

A

 Deep space abscesses
 Gastrointestinal infections

IV or orally

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29
Q

Metronidazole (Flagyl)
DENTAL USES:
(3)

A

●Combined w/ -Lactams - 1st Line for serious orofacial
infections
 “poor man’s Augmentin”
●Management of refractory or progressive periodontitis.
●Rx: Metronidazole 500mg po Q8h x 5days, #15

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30
Q

General Antibiotic Mechanisms of Action
Non-Cell Wall Active
(5)

A

Ribosome, protein synthesis inhibition
* Macrolides
* Clindamycin
* Doxycycline
DNA inhibition
* Metronidazole
* Trimethoprim-sulfamethoxazole

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31
Q

General Antibiotic Mechanisms of Action
Cell Wall Active
(3)

A
  • -Lactams
  • Penicillins
  • Cephalosporins
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32
Q

Protein Synthesis Inhibitors
(3)

A
  • Clindamycin – STATIC
  • Macrolides - STATIC
  • Tetracyclines – STATIC
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33
Q

Clindamycin (Cleocin™) – IV and PO
Activity for Gram Positives and Anaerobes
(3)

A
  • Strep. & Staph. including MRSA
  • Anaerobic gram negatives: Actinomyces, Bacillis, Bacteroides (increasing resistance)
  • No aerobic gram-negatives
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34
Q

Clindamycin (Cleocin™) – IV and PO
Clinical advantages
(2)

A
  • PVL toxin inhibition
  • Biofilm inhibition/penetration
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35
Q

Clindamycin (Cleocin™) – IV and PO
Disadvantages
(3)

A
  • C. difficile infection
  • Clindamycin oral suspension unpleasant taste
  • High doses of oral clindamycin (>450 mg Q6H) may cause esophagitis
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36
Q

Clindamycin (Cleocin™) – IV and PO
Additional Dental Advantages
(2)

A

●High penetration into saliva, gingival tissues, and bone
●Minimal renal concerns

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37
Q

Clindamycin (Cleocin™) – IV and PO
●In dentistry:

A

Late or severe endodontic infections & abscesses
with severe PCN allergy
■Rx: Clindamycin 150mg po TID x 5days, #15
■May use 300mg – likely more GI side effects; reserve
for SEVERE infections

38
Q

Movement Away from
Use in ‘Allergies’
Single dose clindamycin associated with
significant rates of fatal and nonfatal
ADRs
* Amoxicillin : 0 fatal and 22.62 non-fatal
ADRs per million prophylactic courses
* Clindamycin : 12.6 fatal and 149.1 non-
fatal ADRs per million prophylactic courses
Review of Minnesota CA-CDI, 15% of
cases had antibiotics prescribed for
dental procedures
* Cases 5x more likely to be prescribed
clindamycin (P < 0.001

A

clindamycin is no longer recommended to be prescribed for dental tx

39
Q

— is no longer recommended for antibiotic prophylaxis for a dental procedure

A

clindamycin

40
Q

Greater Reliance on Cephalosporins in Allergies
Fatal anaphylaxis from a single dose of a cephalosporin in patients
with no history of a serious reaction <

A

1 per 1 million doses

41
Q

Tetracyclines
- Tetracycline (Achromycin), Doxycycline (Vibramycin), Minocycline (Minocin)
(5)

A
  • MOA: Bind to 30S subunit of Ribosome
    ● Bacteriostatic
    ● Broad spectrum activity but mostly for gram positives
    ● Requires active transport into cells- source of resistance
    ● Chelate/Bind divalent cations.
  • Binds with Ca++, Mg++, antacids, iron or multivitamins.
    ● No renal or hepatic adjustment
  • cleared totally unchanged in fecal excretion
42
Q

Limited Risk for C. difficile as Respiratory Agent
Meta-analysis, antibiotic class and risk CA-CDI
* Tetracyclines demonstrated

A

no increased risk (OR, 0.92) vs no antibiotic
exposure

43
Q

Doxycycline Tooth Discoloration in Pediatrics
(3)

A

No tetracycline-like staining observed in any of the exposed children’s teeth
(0/58), and no significant difference in tooth shade versus controls (P = .20)
* Low concern for tooth discoloration for doxycycline
* May consider overall doxycycline exposure for child

44
Q

Doxycycline Considerations
(7)

A
  • Tooth Discoloration:
  • Avoid during pregnancy
  • GI upset
  • Erosive esophagitis – avoid taking at bedtime, drink full glass of water
  • Peak plasma concentration may be reduced ~20% by high-fat meal or milk
  • Phototoxicity (skin rashes) may occur
  • Renal/hepatic disease patients can use doxycycline
45
Q
  • Tooth Discoloration:
A

Updated recommendations from the American
Academy of Pediatrics permit doxycycline for ≤21 days in children of all ages

46
Q
  • GI upset
  • More common with —-
  • — less acidic, better tolerated
A

hyclate salt
Monohydrate

47
Q

Tetracyclines
Dental Uses:

A

Periodontal only.
●No longer used for odontogenic infections due to resistance:
■Management of localized juvenile periodontitis (Aggressive Periodontitis) – Aggregatibacter
actinomycetemcomitans (AA) –make -lactamase
■AA sensitive to Tetracyclines, Fluoroquinolones, Bactrim™… ?Augmentin.
■Additive Effects:
Concentrates in the gingival crevice extremely well, 7–20 times more than any other drug
Anticollagenase
Anti-inflammatory
Inhibition of bone resorption
Promotes reattachment

48
Q

Tetracyclines
 Low-dose systemic doxycycline for refractory agg. periodontitis
● Periostat™ (100 mg PO daily)
● Local application in adjunctive tx for resistant periodontitis:
(2)

A

 Atridox™ gel (doxycycline)
 Arestin™ (minocycline microspheres)

49
Q

Macrolides
Azithromycin, Clarithromycin, Erythromycin
* MOA:

A

Binds to 50S Ribosome (Static), prevents transpeptidation
* Time Dependent Killing Effect

50
Q

Macrolides
ERTHYROMYCIN: NOT USED
●Narrow spectrum:
■ Adverse effects: (4)
■ Strong inhibitor of — –many drug interactions.
■ Highest — prolongation risk among antimicrobials

A

LOTS of resistance
Prokinetic, GI disturbances, diarrhea, cramping
CYP3A
QTc

51
Q

Macrolides
Clarithromycin (Biaxin) –AVOID USE
Liver metabolism:

A

Moderate CYP3A inhibitor.
Prodrug: metabolized to active compounds
Less drug-drug interactions than
Erythromycin but more than azithromycin

●H.pylori – chronic dyspepsia, peptic ulcer
development, and gastric cancer
 Triple Therapy (PPI, amox, clarith) or Quadruple (PPI,
amox, Flagyl, and bismuth)
●Taste Disturbances: Metallic taste

52
Q

MacroliCYP3A4 Suppression & Drug Interactions
(2)

A
  • Both Erythromycin and Clarithromycin slow CYP3A4
  • Azithromycin limited effect on CYP3A4
53
Q
  • Both Erythromycin and Clarithromycin slow CYP3A4
  • Accumulation of other drugs that are metabolized through 3A4
    (4)
A
  • Benzodiazepines
  • Transplant Drugs (cyclosporine, tacrolimus)
  • HIV Drugs
  • CCBs (amlodipine, diltiazem)
54
Q

Macrolides
Azithromycin (ZPack; Zithromax) – IV and PO
(2)

A

● Improved infected tissue penetration and half life
- Concentrates in tissues, phagocytes, & fibroblasts giving it a long half-life.
● No phase I metabolism.
- Eliminated unmetabolized – no drug interactions
- Long half-life (60hrs) - qday dosing.
- Must use loading dose. (2x)

55
Q

Macrolides
Azithromycin (ZPack; Zithromax) – IV and PO
Side Effects:
(2)

A
  • Possible reversible tinnitus with large doses
  • Liver reports – jaundice, necrosis, failure
56
Q

Macrolides
Dental uses:

A

Used in odontogenic and periodontal infections in early, non-abscess
infections as 2nd alternative or in severe penicillin allergies

■ No activity against Bacteroides, common in dental abscesses
■ Alternative antibiotic in odontogenic infections.
■ Less effective than - Lactams (2nd choice)
■ Overall limit use due to already high resistance rates.
■ 50% of viridans group Streptococci resistant

57
Q

Macrolides
Prescriptions:
Orofacial Infection:
Perio Infection:

A

500mg, then 250mg PO Daily x 4 days
500mg PO Daily x 5 days

58
Q

Drug Selection Factors
(6)

A
  • Common pathogens = Empiric Therapy Targets
  • Site of Infection
  • Ability to penetrate infection site
  • Patient Allergies and Drug Adverse Reactions (Tolerance)
  • Renal and Hepatic Function, Patient’s Age
  • Clearance and Metabolism of Antibiotics
  • Concomitant Medications (drug interactions) and Past Medical History
  • Pregnancy or Breastfeeding
59
Q

Teratogen –

A

Agent that can potentially cause a birth defect or negatively alter cognitive and
behavioral outcomes
* Physical, cognitive, behavioral

60
Q

Teratogenicity
Determinants –
(4)

A
  • Dose of toxicant
  • Half-life of toxicant
  • Placental permeability
  • Stage of development
61
Q

Pregnancy and Lactation
* Good Safety
(4)
* Avoid
(4)

A
  • Cephalosporins, penicillins, clindamycin, azithromycin
  • Doxycycline – Ca++ chelation
  • Fluoroquinolones – kidneys/cartilage
  • Sulfamethoxazole/trimethoprim – various/kernicterus
  • Metronidazole in 1st Trimester – limited data
62
Q
  • Prophylactic Therapy
    (2)
A

–To prevent an infection
–i.e. Amoxicillin prior to dental work

63
Q
  • Empiric Therapy
    (2)
A

–To cover most likely pathogens
–i.e. Augmentin for acute periodontal abscess

64
Q
  • Directed Therapy
    (2)
A

–Target toward specific pathogen
–i.e. Cephalexin for MSSA skin infection

65
Q

When Are Antibiotics Indicated/ Recommended?
Yes
(4)

A
  • NUG – systemic symptoms or
    immunocompromised
  • Aggressive Periodontitis
  • Fascial space infection
  • Endo/Perio with systemic symptoms
66
Q

When Are Antibiotics Indicated/ Recommended?
No
(4)

A
  • Endodontic conditions
  • Chronic Periodontitis or Gingivitis
  • Periodontal Abscess
  • NUG – no systemic symptoms
67
Q

Consider Systemic Antibiotics
(5)

A

Signs/symptoms of systemic spread – pyrexia, malaise and worsening of general condition
Rapid onset and progress
Infection in immunocompromised patients
Swelling involving submental/submandibular or parapharyngeal spaces (potential airway compromise)
Presence of trismus indicates involvement of peri-mandibular spaces and is a serious sign

68
Q

Antibiotics in Odontogenic Infections
Antimicrobial agents are indicated if

A

fever and regional lymphadenopathy are
present, or when infection has perforated the bony cortex and spread into
surrounding soft tissue.

69
Q
  • Early Infection (< 3 days)
    ●Penicillin VK or Amoxicillin
    ●If recent mild/mod intolerance – —
    ●If severe allergy - —
    ●No Improvement (48 hrs)
    (4)
A

Ceftin
clindamycin

●B-lactamase producing? Anaerobic?
●Discontinue Penicillin –Switch to:
● Augmentin® or
●amoxicillin + metronidazole (cheaper but
bigger pill burden)

70
Q
  • Late Infection (abscess or > 3 days)
    think anaerobes and Gram negative
    (4)
A

●Augmentin®
-Amoxicillin + Metronidazole
-Cephalosporin + Metronidazole
-Severe allergy, Clindamycin

71
Q

Bacterial Infective Endocarditis (BIE):
85% are (2)
~5% caused by …

A

Infection of endocardium or valves from blood born bacteria.

Staphylococci spps & Streptococci spps

HACEK group Gram-Negatives
(Haemophilus spps, A. actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, Kingella kingae)

72
Q
  • HACEK are — with potential for infection.
A

oral flora

73
Q

Rationale for Prophylaxis
Pathogenesis involves following sequence of events:
(4)

A
  • Formation of a small thrombus on an abnormal endothelial surface
  • Bacteria access blood circulation (bacteremia)
  • Secondary infection of thrombus with bacteria circulating in bloodstream
  • Proliferation of bacteria resulting in cardiac vegetation on endothelial surface
74
Q
  • Formation of a small thrombus on an abnormal endothelial surface
    (2)
A
  • Surgical Intervention
  • Turbulent blood flow produced by congenital or acquired heart disease
75
Q

Antibiotic Prophylaxis & Infective Endocarditis

A

Meta-analysis of three case-control studies observed no statistically significant
association between IE cases and failure to use antibiotic prophylaxis (odds
ratio 0.59, 95% CI 0.27-1.30, P=0.14)
Antibiotic prophylaxis reduces bacteremia
› Meta-analysis of 21 trials of antibiotic prophylaxis observed a reduction in
post procedural bacteremia (RR 0.53, 95% CI 0.49-0.57, P<0.01).
The occurrence of bacteremia is crucial to initiate an episode of BIE, in theory
preventing or promptly treating transient bacteremia will prevent BIE

76
Q

Prophylaxis against IE is reasonable before dental procedures that involve
manipulation of gingival tissue, manipulation of the periapical region of
teeth, or perforation of the oral mucosa in patients with the following:
(5)

A
  1. Non-native cardiac valves
  2. Cardiac valves repaired with prosthetic material
  3. Previous IE
  4. Cardiac transplant with valvular regurgitation
  5. Pediatric - Unrepaired cyanotic congenital heart disease or repaired
    congenital heart disease, with residual shunts or valvular regurgitation
77
Q

Benefit in High-risk Patients
* Analysis of 3,774 patients with IE
* Prophylaxis for IDPs in high IE risk patients
resulted in over –% reduction in IE risk
(P < 0.002) compared with no prophylaxis
* Primary benefit in extractions (–% reduction)
and oral surgical procedures (>–% reduction)
* No benefit observed for other IDPs or in
moderate or low/unknown IE risk

A

70
87
90

78
Q

Avoid Antibiotic Prophylaxis
(7)

A

› Routine anesthetic injections through noninfected tissue
› Dental radiographs
› Placement of removable prosthodontic appliances
› Placement or adjustment of orthodontic appliances
› Placement of orthodontic brackets
› Shedding of deciduous teeth
› Bleeding from trauma to the lips or oral mucosa

79
Q

Normal Flora of Mouth
(5)

A

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

80
Q

Notable Changes in
2021 AHA Statement
* Consideration of adverse drug
reactions –
* Specific statement about —
allergies
* Consideration of drug resistance –
resistance rates for — higher
than for penicillin

A

clindamycin
penicillin
macrolides

81
Q

Allergies:
Amoxicillin Versus Cephalexin Versus Azithromycin
Amoxicillin for:
(6)

A

Non-allergic ADR Hx
Vomiting
Nausea
Runny Nose
Cough
Family Hx of Allergy

82
Q

Allergies:
Amoxicillin Versus Cephalexin Versus Azithromycin
Cephalexin for:
(4)

A

Low risk ADRs Hx
Diarrhea
Non-Hive Rash
Itching

83
Q

Allergies:
Amoxicillin Versus Cephalexin Versus Azithromycin
Azithromycin for:
(7)

A

High risk ADRs Hx
 Lip/Facial Swelling
 Breathing
Difficulty/Wheezing
 Skin Peeling
 Mouth Blisters
 Drop in Blood Pressure
 Hive Rash (per guidelines)

84
Q

Antibiotic Considerations
* Antibiotic should be prescribed and administered — procedure
* — dose only
* If patient forgets to take antibiotic before procedure, instruct to take within —
hours following procedure
* If procedure spans — days, a separate preventative dose is recommended
for each procedure

A

before
Single
2
multiple

85
Q
  • Invasive dental procedures cause bacteremia, which can be complicated by
A

IE in
those at increased risk of the disease

86
Q
  • Patients with (3) are at highest risk of IE
A

prosthetic heart valves, previous infective endocarditis, and some
types of congenital heart disease

87
Q
  • Patients undergoing procedures that involve (3)
    are at highest risk for bacteremia
A

manipulation of gingival tissue,
manipulation of the periapical region of teeth, or perforation of the oral mucosa

88
Q
  • — reduces the incidence of bacteremia, but no high level
    studies exist to confirm that this reduces the incidence of IE
A

Antibiotic prophylaxis

89
Q
  • Warn high risk patients undergoing high risk dental interventions of the risk of
    infective endocarditis. Offer these patients
A

antibiotic prophylaxis, and discuss
with them the risks and benefits of this option

90
Q
  • — prior to dental procedure preferred
A

Amoxicillin 2gm X1 dose 30-60mins

91
Q

Matched Case-Control study; 339 patients with PJI versus 339 without
* Reviewed dental procedure exposure in previous 6-24 months
* Controlled for potential confounder variables
* No increased risk of PJI following …
* Antibiotic prophylaxis in high- or low-risk dental procedures not associated
with reduced PJI risk (OR, 0.9; 95% CI, 0.5–1.6 and 1.2; 95% CI, 0.7–2.2)

A

high- or low-risk dental procedure not
administered antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4–1.6)

92
Q
A

Pharm 2 (13 decks)

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