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Pediatric Pharmacology Exam 2 > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Natural Prevention

A
  • Anatomical/Physiological barriers
    • Skin
      • pH
      • Barrier
    • Lungs
      • Ciliary clearance
    • Stomach
      • Lower stomach pH
  • Innate immunity
    • Non-specific
  • Adaptive immunity
    • Takes several days to develop response
    • Long-term memory of a specific pathogen
  • Modulating immune system:
    • GCSF
    • Immuneglobulins
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2
Q

Infection definition

A
  • Infection: An invasion of any host organism by disease-causing organisms
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3
Q

Micro-organisms classification

A
  • Bateria
  • Fungi/Mold
  • Viruses
  • Parasites
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4
Q

Antibiotic Classification

A
  • Antibacterial
  • Antifungal
  • Antiviral
  • Antiparasitic
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5
Q

Increased Risk of Infection

A
  • Age
  • Nutrition
  • Pregnancy
  • Decreased defense barriers (ex. Severe burns)
  • Cancer, HIV, other infections
  • Immunocompromised
  • Immunization history
  • Indwelling catheters
  • Corticosteroids
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6
Q

Considerations of Treatment – General

A
  • General considerations
    • Cost
    • Insurance formulary
    • Administration considerations (IV vs. PO, q24 vs. q8)
    • Patient population (antibiogram)
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7
Q

Considerations of Treatment – medication consideration

A

Medication considerations

  • Combination therapy (synergy)
  • Antibiotic susceptibility
  • Empiric Therapy
  • Targeted “narrower” treatment
  • Diagnostic tests
  • PK/PD parameters
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8
Q

Considerations of Treatment - patient

A

Patient considerations

  • Age
  • Immune function
  • Allergies
  • Response to antibiotics (improving or worsening)
  • Adverse events (ADRs)
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9
Q

Antibacterial Testing

Diagnostic testing

A
  • Gram Stain
    • Gram (+) vs. Gram (-)
  • Cultures
    • Growth of causative infection taken from site of infection
    • Susceptibility
  • Serology
    • Titers or antibodies measured
  • CBC
    • Elevation (or decrease) in WBC
  • PCR testing
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10
Q

Obtaining Cultures

A
  • Ideally should always be done BEFORE starting antibiotic therapy
  • Depending on infection concern, multiple cultures should be drawn simultaneously
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11
Q

Antibiotic Pharmacokinetic and Pharmacodynamic Concepts

A
  • Pharmacokinetics and Pharmacodynamics of Antibacterial Agents
    • Best antibiotic choice may depend on the different PK and PD properties
      • Example: Daptomycin
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12
Q

Medication considerations – antibiotics

A
  • Pharmacodynamics
  • Pharmacokinetics
  • Tissue penetration
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13
Q

Routes of Admin

A
  • Bioavailability
  • Severity of infection
  • Location of infection
  • Organ function
  • Drug levels required
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14
Q

Bactericidal

A
  • Destroy microbes
  • Example: Penicillin
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15
Q

Bacteriostatic

A
  • Inhibit the growth of bacteria but do not kill them
  • Need immunologic response to eliminate organisms
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16
Q

Pharmacodynamic Efficacy – Both

A
  • Some antibiotics exhibit bactericidal and bacteriostatic properties depending on concentration in the blood
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17
Q

Spectrum of Activity

Narrow vs. Broad

A
  • Narrow spectrum
    • Active against limited groups of pathogens
    • Generally, may only work against gram (-) or gram (+) organisms but not both
  • Broad spectrum
    • Active against wide range of pathogens
    • Often used for empiric therapy
    • Generally, has activity against both gram (-) and gram (+) organisms
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18
Q

Time-dependent kinetics

A

Relies on the amount of time the serum concentration remains above the MIC

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19
Q

Concentration-dependent kinetics

A
  • Relies on the highest concentration in the serum reached, must greatly exceed the MIC
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20
Q

Post antibiotic effect (PAE)

A
  • Delayed regrowth of bacteria following antibiotic exposure
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21
Q

Aerobic

A

Grow and live in the presence of oxygen

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22
Q

Anaerobic

A

Grow and live in the absence of oxygen

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23
Q

Gram Positive

A
  • Thick peptidoglycan cell wall
  • Cocci
  • Bacilli
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24
Q

Gram Negative

A
  • Thin peptidoglycan cell wall
  • Addition of a thick outer lipid membrane
  • Coccobacilli
  • Cocci
  • Bacilli
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25
* Minimum Inhibitory Concentration (MIC)
* The lowest concentration of an antibacterial agents to prevent growth * Predicts bacteriological response to therapy
26
Testig for susceptibility is defined by...
Clinical laboratory standard institute (CLSI) Some bacteria are inherently resistant to certain classifications
27
* CLSI Breakpoints –
* Sensitive * Intermediate * Resistant
28
Beta-Lactams General
* Generally considered ‘broad spectrum’ antibiotics * Gram (+) * Gram (-) * Anaerobes * Pseudomonas
29
Beta-Lactam Classifications
* Penicillins * Extended-Spectrum Penicillin (ESPCN) * ß-Lactam/ß-Lactamase Inhibitors * Cephalosporins * Carbapenems * Monobactam
30
Beta-Lactams Mechanism of Action
* Bactericidal * Binds to cell wall and inactivates Penicillin Binding Proteins (PBPs) * Interferes with the last step of bacterial wall synthesis * Time dependent killing
31
Penicillins General
* Natural penicillins * Aminopenicillins * Penicillinase-Resistant Synthetic Penicillins (PRSPs) * Extended-Spectrum Penicillins (ESPCN) * Beta-Lactam/Beta-Lactamase Inhibitors
32
Natural Penicillin Clinical use
* Clinical use * Pneumococcal and streptococcal infections * Drug of Choice (DOC) for syphilis * Prophylaxis of enapsulated organisms
33
Penicillin IM Oral
IM=Penicillin G Oral = Penicillin VK
34
Aminopenicillin Clinical Use
* Minimal activity against Gram (-) * Clinical Use * DOC for enterococcal infections * Community-acquired respiratory infections * Otitis media
35
Aminopenicillin IV/IM Oral
IM/IV = ampicillin (IV/IM), ampicillin (IV/IM) Oral = ampicillin, amoxicillin
36
**_Penicillinase-Resistant Synthetic Penicillins (PRSPs)_** **_Clinical Use_**
* No enterococcal coverage * No coverage of Methicillin Resistant S. Aureus (MRSA) * Clinical Use * DOC for beta-lactamase (penicillinase) positive
37
PRSPs IV/IM agent Oral agent
IV/IM = oxacillin, nafcillin Oral = dicloxacillin, dicloxacillin
38
**_Extended-Spectrum Penicillin_** **_Clinical Use_**
* Pseudomonasaeruginosa * Usually in combination with an aminoglycoside * Monotherapy okay for UTI * Enterococcalactivity * Goodanaerobicactivity
39
Extended-Spectrum Penicillin IV formulation
* Only available as IV formulation * Piperacillin * Ticarcillin
40
Extended spectrum penicillin is used in combination with
B-lactamase inhibitor
41
**_B-Lactamase Inhibitor_**
* The beta-lactamase inhibitor restores the activity of the beta- lactam component in the presence of beta-lactamase * Increases spectrum of activity
42
Selected B-Lactamase Producing Organisms
Staph aureus (Not MRSA) H. influenza Most anaerobes Many gram negative bacilli
43
B-Lactam -- Mixed Infections
Respiratory infections Abdominal infections Skin/soft tissue infections Bite wound infections Resistant UTIs
44
B-Lactams IV/IM Agents
IV/IM * Piperacillin/Tazobactam (Zosyn) * Ampicillin/Sulbactram (unasyn) * Ticarcillin/Clavulanate (Timentin) Oral * Amoxicillin/clavulanate (Augmentin) -- depending on infection * SAME^ * N/A (change antibiotic class)
45
PCN ADE
* Rash (usually delayed) * Seizures (rare) * Abdominal discomfort * Neutropenia * Fever (drug-induced fever) * Acute renal failure (AKI) * Elevated LFTs (oxacillin and nafcillin)
46
PCN CLINICAL PEARLS
* Generally considered broad spectrum * Increasing rates of resistance seen * Specifically Enterobacteriaceae * Common with failure to narrow therapy * Common with prolonged duration of use * Should not be used for MRSA infections
47
Cephalosporins Generations
* 1st generation * 2nd generation * Enteric * Respiratory * 3rd generation * Non-pseudomonal * Pseudomonal * 4th generation
48
**_1st Generation Cephalosporin_** **_Clinical uses_**
* Primarily for GPC infections * EXCEPT: Enterococcus * Garden-variety gram (-) bacillary infections (PECK) * Proteus * E. Coli * Klebsiella
49
Cephalosporins 1st generation IV/IM -- Oral
IV/IM * Cefazolin (IV) Oral * Cephalexin * Cefadroxil
50
**_2nd Generation Cephalosporins_**
* Enteric Cephalosporins * Only available as IV/IM formulations * Cefoxitin * Cefotetan
51
2nd generation ceph Clinical uses
* Anaerobic coverage (Bacteroides fragilis) * Enhanced GNR activity, but not GPC activity * Surgical prophylaxis (colorectal, abdominal)
52
2nd generation ceph Enteric cephalosporins
Available agents -- cefoxitin (IV/IM) Clinical use * Surgical prophylaxis (colorectal, abdominal) Spectrum of activity * Anaerobic coverage (Bacteroides fragilis) * Enhanced GNR activity (lacks GPC activity)
53
2nd generations cephalosporins Respiratory Available agent, clinical use, Spectrum of activity
Available agents -- Cefuroxime (IV/IM/PO) Clinical Use * Lower respiratory tract infections Spectrum of Activity * Streptococcus pneumonia * H. Influenza
54
3rd Generation Cephalosporins Spectrum of Activity
* Enhanced Gram (-) activity * Activity against PCN-resistant pneumococcus * Ceftazidime effective against Pseudomonas
55
3rd Generation Cephalosporins Clinical use
* Community Acquired Pneumonia (CAP) * Meningitis * Gonorrhea
56
3rd Generation Cephalosporins Benefit
* Once daily dosing (ceftriaxone and forms)
57
3rd Generation Cephalosporin IV/IM Oral
IV/IM agents * Cefotaxime * Ceftriaxone (Rocephin) * Ceftazidime * Cefotaxime Oral * Cefpodoxime (Vantin) * Cefixime (Suprax) * Cefdinir (Omnicef)
58
4th Generation Cephalosporins Clinical Use
* Best cephalosporin for GNR * Any serious infection
59
4th Generation Cephalosporin Spectrum of Activity
* Exhibits excellent gram (+) and gram (-) activity * Covers Staphylococcus, Streptococcus, P. aeruginosa * IV/IM Agent
60
4th Generation Cephalosporin Oral Agent Equivalent
* Can sometimes be used even if isolate is resistant Cefepime (IV/IM) * None to 3rd generation cephalosporins
61
4th generation IV/IM Oral
IV/IM -- cefepime Oral -- none
62
Cephalosporin ADE
* Rash (usually delayed) * Seizures (rare) * Abdominal discomfort * Neutropenia * Fever (drug induced fever) * Biliary sludging (ceftriaxone)
63
Cephalosporin Clinical Pearls
* Use in caution in patients with PCN allergies * ~10% cross sensitivity * Coverage changes with change in generation * GPC * GNR * Pseudomonas
64
Carbapenems General
* Broadest spectrum of all antibiotics * Potential cross sensitivity for PCN allergies * ~15%
65
Carbapenems Spectrum of Activity
* Pseudomonas infections
66
Carbapenems Clinical Use
* Serious infections with multiple resistant bacteria * Febrile neutropenia * Monotherapy for polymicrobial infections
67
Organisms intrinsically resistant to carbapenems (7)
* MRSA * E. faecium * Stenotrophomonas * Burkholderia * Chlamydia * Mycoplasma * Corynebacterium
68
Carbapenems IV/IM
Imipenem Meropenem Doripenem Ertapenem (IV/IM)
69
**_Monobactam (Aztreonam)_** **_Spectrum of Activity_**
* NO activity against GPC or anaerobes * ONLY active against GNR * No apparent cross-reactivity in ß-lactam allergic patients
70
Aminoglycosides Mechanism of Action
* Bactericidal * Concentration dependent killing * Inhibits protein synthesis at 30s ribosome
71
Aminoglycosides Spectrum of Activity
* Gram Negative Rod infections * Used in combination for gram (+) organisms (i.e. endocarditis) * GI bacterial overgrowth
72
Aminoglycosides Clinical Use
* Gram (-) infections * Poor penetration in to abscesses
73
Aminoglycosides Specific Agents
* Amikacin * Greatest risk of toxicity * Tends to defer resistance compared to gentamicin and tobramycin * Gentamicin * Tobramycin * Pseudomonal coverage than gentamicin * (Streptomycin)
74
Aminoglycosides Dosing
* Requires narrow therapeutic monitoring * Interval dosing can be traditional or extended
75
Aminoglycosides Toxicity (associated with long-term use and acute toxicity)
* Nephrotoxicity (renal tubular damage) * Ototoxicity (Irreversible hearing loss)
76
Sulfonamides (Sulfamethoxazole) AKA...
Folic acid metabolism inhibitors
77
Sulfonamides (Sulfamethoxazole) Mechanism of Action Bacteriocidal vs. static?
* Bacteriostatic * Inhibits cell growth via interfering with folic acid synthesis * Generally abbreviated as ‘sulfa’ medications
78
Sulfonamides (Sulfamethoxazole) Spectrum of Activity Drug of choice for (3)
* Gram (-) & gram (+) * MSSA & MRSA * Drug of choice for: Stenotrophomonas, Nocardia, & Pneumocystis jiroveci pneumonia (PCP)
79
**_Sulfonamides (Sulfamethoxazole)_** **_Clinical Use_**
* UTI (treatment and prophylaxis) * Respiratory tract infections * PCP prophylaxis * Abdominal infections * Cellulitis
80
**_Sulfonamide ADE (7)_**
* Rash * Photosensitivity * Nephrotoxicity * Obstructive uropathy * Neutropenia * Thrombocytopenia * Hyperkalemia
81
Sulfamethoxazole/Trimethoprim (Bactrim®, Co-trimoxale®,SMX/TMP) IV/PO information Clinical Pearls (2); PCP dosing, allergies
* Only available in combination with trimethoprim * Available as IV and PO * IV has short stability and requires more frequent dosing * PO dosing is typically q12 * Clinical Pearls * PCP ppx dosing is TIW (FSS, MWF, etc) * Watch for sulfa allergies
82
Fluoroquinolones General and MOA
* Broad spectrum of activity against GNR * Poor anti-anaerobic activity * Mechanism of Action * Bactericidal * Inhibits topoisomerase IV and DNA gyrase
83
Fluoroquinolones Spectrum of Activity (4)
* Broad spectrum of activity against GNR * Variable Pseudomonal & Streptococcal activity * Covers MSSA but not MRSA reliably * E coli
84
Fluoroquinolones Clinical Use
* Poor anti-anaerobic activity * UTI * STD
85
**_Fluoroquinolones_** **_Available Agents_**
* Ciprofloxacin (CIPRO) * IV/PO otic and optic suspension * Best for pseduomonal activity * Levofloxacin (Levaquin) * IV/PO * Moxifloxacin (Avelox) * IV, PO * Ofloxacin (ocular suspension) Decision which FQ may be dictated by patient's insurance
86
Fluoroquinolones ADE
* Photosensitivity * Seizures(rare) * Abdominal discomfort * QTc interval prolongation * CNS stimulation * BBB for: * Tendon ruptures * Peripheral neuropathy * CNS effects
87
**_FQs Clinical Pearls_**
* Ideal oral antibiotic if broad spectrum is needed * Caution with BBB * Watch for increasing rates of resistance * Avoid in pregnancy and lactation * Requires renal dose adjustment * Polyvalent metallic cationic adsorptive interactions * Avoid taking with foods and/or medications with metallic cautions
88
Tetracyclines Mechanism of Action
* Bacteriostatic * Inhibits 30s and 50s ribosomal subunits in susceptible bacteria
89
Tetracyclines Spectrum of Activity
* Stenotrophamonas (minocycline) * MSSA, MRSA * Mycoplasma pneumonia * Lots more...
90
Tetracyclines CLinical Use
* Community-acquired respiratory tract infections * STDs (chlamydia) * Lime disease and Rickettsial diseases * Malaria prophylaxis * Acne
91
Tetracyclines Available Agents
* (all have IV & PO formulations) * Minocycline\* * Tetracycline * Doxycycline \* \* Used more orally than tetracycline
92
Tetracycline ADE
* Photosensitivity * Abdominal discomfort * Stained teeth (cosmetic) * Absorption may be decreased with foods and metallic cations
93
Macrolides Mechanism of Action
* Bacteriostatic * Binds to 50s ribosomal subunit to inhibit RNA synthesis
94
Macrolides Spectrum of Activity
* H. pylori * Atypical pathogens * Legionella * Mycoplasma * Chlamydia pneumoniae
95
Macrolides Clinical Use
* Respiratory infections & community-acquired pneumonia * Skin and soft tissue infections * STDs
96
Macrolides Available Agents
* Erythromycin (EES) * Used largely in pediatric for pro-motility & enhance gastric emptying * Causes QT prolongation * Azithromycin * Clarithromycin
97
Macrolides ADE
* Abdominal discomfort * Ototoxicity (rare) * Taste disturbances
98
Macrolides Clinical Pearls
* Erythromycin is used more for its intestinal pro-motility agent * Decreased clearance of many drugs via CYP 450 inhibition * Not seen with azithromycin * Do not use clarithromycin during pregnancy * Pregnancy category C
99
Clindamycin Mechanism of Action
* Mechanism of Action * Bacteriostatic * Bacteriocidal * Inhibits protein synthesis by binding to 50s ribosomal subunit
100
Clindamycin Spectrum of Activity Clinical Use
* Spectrum of Activity * Aerobic GPCs * MRSA & MSSA * Anaerobic organisms * Clinical Use * Inhibits toxin release * Cellulitis
101
Lincodamide ADE
* Abdominal discomfort * Pseudomembranous colitis * Taste! * Capsules can be opened and dissolved
102
Metronidazole Mechanism of Action Spectrum of Activity
* Mechanism of Action * Bactericidal * Interacts with DNA to cause a loss of helical DNA structure and strand breakage * Spectrum of Activity * Clostridium difficile colitis * Anaerobic infections * Protozoal infections
103
Metronidazole Clinical Use
* STDs * Bacterial overgrowth
104
Metronidazole ADE
* Peripheral neuropathy * Taste disturbances * Disulfiram reaction * Seizures (rare) * Abdominal discomfort
105
Vancomycin Mechanism of Action Spectrum of Activity
* Mechanism of Action * Slowly bactericidal * Glycopeptide that Inhibits cell wall synthesis * Spectrum of Activity * Gram (+) organisms * C. difficile
106
Vancomycin Clinical Use
* Treatment of choice for MRSA * Empiric therapy for pneumococcal meningitis * Oral therapy for C. difficile colitis * In place of penicillin in patients with a PCN allergy
107
Vancomycin ADE
* Ototoxicity (rare) * Nephrotoxicity * (Red-man syndrome) * Neutropenia
108
VANCO ADME
* Requires serum level monitoring for efficacy and safety * Not orally absorbed
109
Linezolid Mechanism of Action
* Bacteriostatic in vitro * Bactericidal in vivo * Inhibits cell wall synthesis
110
Linezolid Clinical Use
* Vancomycin Resistant Enterococcus (VRE) * Systemic oral GPC-specific product is needed * Does not need renal adjustment
111
Linezolid ADE
* Thrombocytopenia * Peripheral neuropathy * Optic neuropathy * Lactic acidosis
112
Daptomycin Mechanism of action Spectrum of Activity
* Mechanism of Action * Bactericidal * Depolarizes cell wall * Spectrum of Activity * VRE * MRSA * VRSA
113
Daptomycin Clinical USe
* Skin & soft tissue infections * Endocarditis * AVOID in pneumonia
114
Daptomycin ADE
* CPK elevations * Myopathies * Avoid in combination with statins
115
* Azole Antifungal * Mechanism of Action
* Inhibits ergosterol synthesis (main sterol in fungal cell wall) therefore prevents cell wall growth
116
Azole Antifungal Available Agents
* Fluconazole * Ketoconazole (used topically) * Voriconazole
117
Azole Antifungal Spectrum of Activity * Fluconazole * Voriconazole
* Fluconazole * Candida * Cyptococcus, blastomyces, etc. * Voriconazole * Candida species * Aspergillus * Mold
118
Azole Antifungal Side effects
* Increase in LFTs * Abdominal pain, N/V (general well tolerated) * QT prolongation * Specific to voriconazole: * CNS hallucinations or visual disturbances * Increased SCr
119
Azole Antifungal Clinical Pearls
* Voriconazole requires therapeutic drug monitoring * Major interaction with CYP enzymes * CYP3A4 (strong inhibitor) * CYP2C9 & CYP2C19 (moderate inhibitor)
120

Pediatric Pharmacology Exam 2 (9 decks)

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