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Therapeutics > Rational Antimicrobial Selection > Flashcards

Rational Antimicrobial Selection Flashcards

1
Q

The initial selection of antimicrobial therapy may be ___, prior to documentation and identification of the offending organism.

A

Empirical

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2
Q

Empirical antimicrobial therapy selection should be based on:

A

1) The patient’s history and physical examination

2) Results of Gram stains or other rapidly performed tests on specimens from the infected site

3) Knowledge of the most likely offending organism for the infection in question

4) Institution’s local microbial susceptibility patterns

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3
Q

What are the most important factors in determining the choice of antimicrobial therapy?

A

1) Identification of the pathogen
2) Its antimicrobial susceptibility

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4
Q

What are ‘infected materials’?

A

1) Blood
2) Sputum
3) Urine
4) Stool
5) Abscess, wound, or sinus drainage
6) Spinal fluid
7) Joint fluid

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5
Q

Infected materials must be sampled BEFORE starting antimicrobial therapy for two reasons:

A

1) A Gram stain might reveal positive or negative stain bacteria, and an acid-fast stain might detect mycobacteria

2) The premature use of antimicrobials can suppress the growth of pathogens = false-negative cultures results.

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6
Q

Blood cultures should be performed in which patient?

A

The acutely ill and febrile patient

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7
Q

What should be done when a pathogenic microorganism is identified?

A

1) Antimicrobial susceptibility testing should be performed
2) Specific definitive antimicrobial therapy should be administered ASAP

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8
Q

A variety of factors must be considered when selecting presumptive therapy:

A

1) The severity and acuity of the disease
2) Local epidemiology and antibiogram
3) Patient’s history and host factors
4) Factors related to the drug(s) to be used
5) The necessity for using multiple agents

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9
Q

Are antibiotic susceptibilities the same or different across hospitals?

A

Different

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10
Q

What is the most important part of the patient’s history when trying to find a suitable antibiotic?

A

The place where the infection was acquired

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11
Q

____ can be exposed to potentially more resistant organisms because they are often surrounded by ill patients who are receiving antibiotics.

A

Nursing home patients

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12
Q

Which host factors are taken into consideration when determining which antimicrobial to give?

A

1) Allergy
2) Age
3) Pregnancy
4) Metabolic or Genetic Variation
5) Organ Dysfunction
6) Concomitant Drugs

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13
Q

Which drugs should be avoided in patients allergic to penicillin for immediate or accelerated reactions (anaphylaxis, laryngospasm)?

A

Cephalosporins

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14
Q

Can we use Cephalosporins if a patient gets a mild rash when taking penicillins?

A

Yes

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15
Q

Why is age an important host factor?

A

1) For identification of the likely etiologic agent
2) In the ability to eliminate the drug

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16
Q

Which functions are NOT
well developed in neonates?

A

Hepatic and liver functions

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17
Q

Neonates (especially when premature) can develop ___ when given sulfonamides.

A

Kernicterus

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18
Q

Why can neonates (especially when premature) develop kernicterus when given sulfonamides?

A

Because of displacement of bilirubin from serum albumin

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19
Q

The major change in the elderly is:

A

Decreased renal function

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20
Q

Neonates (especially when premature) can develop kernicterus when given __.

A

Sulfonamides

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21
Q

How are aminoglycosides excreted?

A

Renally

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22
Q

The elderly has increased adverse effects of which antimicrobials?

A

Those eliminated by the kidney

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23
Q

During pregnancy, the fetus is at risk of:

A

Drug teratogenicity

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24
Q

Which drugs are cleared more rapidly during pregnancy?

A

1) Penicillins
2) Cephalosporins
3) Aminoglycosides

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25
Q

Why are certain drugs cleared more rapidly during pregnancy?

A

Because of increases in:
1) Intravascular volume
2) GFR
3) Hepatic metabolic activities

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26
Q

The maternal serum antimicrobial concentrations are ~ 50% __(higher/lower) than in the nonpregnant state.

A

Lower

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27
Q

__(Decreased/Increased) dosages of certain compounds might be necessary to achieve therapeutic levels during late pregnancy.

A

Increased

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28
Q

Patients with impaired blood flow may NOT absorb drugs given by ___ well.

A

Intramuscular injection

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29
Q

What will influence therapy of infectious diseases in a variety of ways?

A

Inherited or acquired metabolic abnormalities

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30
Q

Patients who are slow acetylators of __ are at greater risk for peripheral neuropathy

A

Isoniazid

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31
Q

Patients who are slow acetylators of isoniazid are at greater risk for ___.

A

Peripheral neuropathy

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32
Q

Patients with severe deficiency of ___ can develop significant hemolysis when exposed to dapsone, sulfonamides, nitrofurantoin, nalidixic acid, and antimalarials.

A

Glucose-6-phosphate dehydrogenase

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33
Q

Patients with severe deficiency of glucose-6-phosphate dehydrogenase can develop
significant hemolysis when exposed to which drugs?

A

1) Dapsone
2) Sulfonamides
3) Nitrofurantoin
4) Nalidixic acid
5) Antimalarials

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34
Q

Which antiretroviral drug is associated with severe hypersensitivity reaction (fever, rash, abdominal pain, and respiratory distress) in the presence of human leukocyte antigen allele HLAB*5701?

A

Abacavir

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35
Q

The antiretroviral drug Abacavir is associated with severe hypersensitivity reaction (fever, rash, abdominal pain, and respiratory distress) in the presence of:

A

Human leukocyte antigen allele HLAB*5701

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36
Q

Which antibiotics should be adjusted in severe liver disease?

A

1) Clindamycin
2) Erythromycin
3) Metronidazole
4) Rifampin

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37
Q

Significant accumulation can occur when both liver and renal dysfunction are present for which drugs?

A

1) Nafcillin
2) Sulfamethoxazole
3) Cefotaxime
4) Piperacillin

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38
Q

Administration of Isoniazid with phenytoin can result in phenytoin toxicity due to:

A

Inhibition of Phenytoin metabolism by Isoniazid

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39
Q

Administration of Isoniazid with Phenytoin can result in __ toxicity.

A

Phenytoin

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40
Q

Drugs that possess similar adverse effect profiles can produce ___ adverse effects.

A

Enhanced

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41
Q

Which drugs are aminoglycosides?

A

1) Gentamicin
2) Amikacin
3) Tobramycin
4) Neomycin
5) Streptomycin

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42
Q

Aminoglycosides have major drug interactions with:

A

1) Neuromuscular blocking agents
2) Nephro- and Oto-toxins

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43
Q

What happens if you give aminoglycosides with Neuromuscular blocking agents?

A

Additive NMJ block

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44
Q

Which drugs are nephro and oto toxic?

A

1) Amphotericin
2) Cisplatin
3) Cyclosporine
4) Furosemide
5) NSAIDs
6) Radiocontrast media
7) Vancomycin

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45
Q

Amphotericin B has major drug interactions with:

A

Nephrotoxins such as:
1) Aminoglycosides
2) Cidofovir
3) Cyclosporine
4) Foscarnet
5) Pentamidine

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46
Q

Chloramphenicol decreases metabolism of:

A

1) Phenytoin
2) Tolbutamide
3) Ethanol

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47
Q

Foscarnet given with ___ increases risk of severe nephrotoxicity/hypocalcemia.

A

Pentamidine IV

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48
Q

Foscarnet given with Pentamidine IV increases risk of:

A

Severe nephrotoxicity/hypocalcemia

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49
Q

Isoniazid decreases metabolism of:

A

1) Carbamazepine
2) Phenytoin

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50
Q

Isoniazid given with Carbamazepine/Phenytoin can cause:

A

1) Nausea
2) Vomiting
3) Nystagmus
4) Ataxia

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51
Q

Why shouldn’t Macrolides/azalides be given with Digoxin?

A

Increased Digoxin bioavailability

52
Q

Macrolides/azalides should NOT be given with:

A

Digoxin

53
Q

Metronidazole with ethanol (drugs containing ethanol) cause:

A

Disulfiram-like reaction

54
Q

Metronidazole should not be given with ___ because of disulfiram-like reaction.

A

Ethanol (drugs containing ethanol)

55
Q

Penicillins/Cephalosporins should NOT be given with:

A

1) Probenecid
2) Aspirin

56
Q

Why should Penicillins/Cephalosporins NOT be given with Probenecid or Aspirin?

A

Blocked excretion of β-lactams

57
Q

Quinolones have major drug reactions with:

A

1) Classes Ia and III antiarrhythmics
2) Multivalent cations (antacids, iron, sucralfate, zinc, vitamins, dairy products)
3) Citric acid
4) Didanosine

58
Q

What happens if you give Quinolones with Classes Ia and III antiarrhythmics?

A

Increased QT interval

59
Q

What happens if you give Quinolones with Multivalent cations (antacids, iron, sucralfate, zinc, vitamins, dairy products), Citric acid, or Didanosine?

A

Decreased absorption of Quinolones

60
Q

Rifampin increases metabolism of:

A

1) Azoles
2) Cyclosporine
3) Oral contraceptives
4) Warfarin
5) Protease inhibitors
6) Methadone
7) Tacrolimus
8) Propranolol

61
Q

Sulfonamides should not be given with:

A

1) Sulfonylureas
2) Phenytoin
3) Warfarin

62
Q

Sulfonamides given with Sulfonylureas, Phenytoin, or
Warfarin cause:

A

Displacement from binding to albumin

63
Q

Tetracyclines have major drug reactions with:

A

1) Antacids
2) Iron
3) Calcium
4) Sucralfate
5)Digoxin

64
Q

Tetracyclines given with Antacids, iron, calcium, or sucralfate cause:

A

Decreased absorption of tetracycline.

65
Q

Tetracyclines given with Digoxin cause:

A

Increased digoxin bioavailability

66
Q

Important drug parameters to be considered are the:

A

1) Minimal Inhibitory Concentration (MIC)
2) Time the concentration is above MIC

67
Q

Aminoglycosides exhibit ______, which allows a once-daily aminoglycosides administration.

A

Concentration-dependent bactericidal effects

68
Q

Which drugs are given as a single large daily dose to maximize the peak/MIC ratio?

A

Aminoglycosides

69
Q

Aminoglycosides possess a what kind of effect?

A

Post-antibiotic

70
Q

What is the Post-antibiotic effect?

A

Persistent suppression of organism growth after concentrations decrease below the MIC

71
Q

What appears to contribute to the success of high-dose, once-daily administration of aminoglycosides?

A

Post-antibiotic effect

72
Q

Fluoroquinolones exhibit:

A

Concentration-dependent killing activity

73
Q

Optimal killing by Fluoroquinolones appears to be characterized by:

A

The AUC/MIC ratio

74
Q

β-Lactams display ___ effects.

A

Time-dependent bactericidal

75
Q

The important pharmacodynamic relationship for β-Lactams is:

A

The duration that drug concentrations exceed the MIC

76
Q

How can you administer β-lactams in ways that appear to be correlated with positive outcomes?

A

1) Frequent small doses
2) Continuous infusion
3) Prolonged infusion

77
Q

One important factor in treating an infection is:

A

The presence of the antimicrobial agent in an active form and at adequate concentration at the site of infection

78
Q

Drugs that have low biliary fluid concentrations are NOT useful in the treatment of:

A

1) Cholecystitis
2) Cholangitis

79
Q

Drugs that do NOT reach significant concentrations in the CSF should NOT be used in
treatment of:

A

Bacterial meningitis

80
Q

Which factors can high
concentrations of certain drugs?

A

1) Acidic pH
2) WBC products
3) Various enzymes

81
Q

Body fluids where drug concentration data are
clinically relevant include:

A

1) CSF
2) Urine
3) Synovial fluid
4) Peritoneal fluid

82
Q

Parenteral therapy is indicated in:

A

1) Febrile neutropenia
2) Meningitis
3) Endocarditis
4) Osteomyelitis

83
Q

Severe pneumonia often is treated initially with __(oral/IV) antibiotics then switched to __(oral/IV) therapy with clinical improvement.

A

IV; Oral

84
Q

Which patient illnesses treated in the ambulatory setting can receive oral therapy?

A

1) URTIs (pharyngitis,
bronchitis, sinusitis, and otitis media)
2) Lower respiratory tract infections
3) Skin and soft-tissue
infections
4) Uncomplicated UTIs
5) Selected STDs

85
Q

Antibiotics associated with CNS toxicities, when not dose-adjusted for renal function, include:

A

1) Penicillins
2) Cephalosporins
3) Quinolones
4) Imipenem

86
Q

Reversible nephrotoxicity is classically associated with:

A

1) Aminoglycosides
2) Vancomycin

87
Q

Irreversible ototoxicity can occur with:

A

Aminoglycosides

88
Q

Hematologic toxicities occur with prolonged use of:

A

1) Nafcillin (Neutropenia)
2) Piperacillin (Platelet
dysfunction)
3) Cefotetan (Hypoprothrombinemia)
4) Chloramphenicol (Bone marrow suppression, both idiosyncratic and dose-related toxicity)
5) Trimethoprim (Megaloblastic anemia)

89
Q

Prolonged use of Nafcillin causes:

A

Neutropenia

90
Q

Prolonged use of Piperacillin causes:

A

Platelet dysfunction

91
Q

Prolonged use of Cefotetan causes:

A

Hypoprothrombinemia

92
Q

Prolonged use of Chloramphenicol causes:

A

Bone marrow suppression

93
Q

Prolonged use of Trimethoprim causes:

A

Megaloblastic anemia

94
Q

Which drugs cause photosensitivity?

A

1) Azithromycin
2) Quinolones
3) Tetracyclines
4) Pyrazinamide
5) Sulfamethoxazole
6) Trimethoprim

95
Q

Many antibiotics have been implicated in causing
diarrhea and colitis secondary to ___ superinfection!!!!!!

A

Clostridium difficile

96
Q

Which drugs cause QT prolongation?

A

1) Macrolides/azalide
2) Fluoroquinolones

97
Q

Which drugs cause Stevens-Johnson syndrome?

A

1) Fluoroquinolones
2) Sulfonamides and trimethoprim

98
Q

Patients who fail to respond to antimicrobial therapy over 2-3 days require:

A

A thorough reevaluation

99
Q

Causes of antimicrobial therapy failure?

A

1) The disease is NOT infectious or is nonbacterial in origin
2) There is an undetected pathogen in a polymicrobial infection
3) Factors directly related to drug selection, the host, or the pathogen
4) Laboratory error in identification, susceptibility testing, or both

100
Q

Antimicrobial therapy failures caused by Drug Selection?

A

1) Inappropriate selection of drug, dosage, or route of administration

2) Reduced absorption of a drug, resulting in subtherapeutic concentrations

3) Accelerated drug elimination = low concentrations

4) Poor penetration into the site of infection

5) Chemical inactivation of the drug at the site of infection

101
Q

Which “diseases” can cause accelerated drug elimination?

A

1) Cystic fibrosis
2) Pregnancy

102
Q

Which sites have poor penetration into the site of infection?

A

1) CNS
2) Eye
3) Prostate gland

103
Q

Reduced absorption of a drug, resulting in subtherapeutic concentrations, can be caused by:

A

1) GI disease (short-bowel syndrome)
2) Drug interactions

104
Q

Antimicrobial therapy failures caused by Host Factors?

A

1) Immunosuppression
2) The need for surgical drainage of abscesses or removal of foreign bodies, necrotic tissue, or both.

105
Q

Which infections will NOT be effectively treated without surgical procedures?

A

1) Abscesses
2) Removal of foreign bodies, necrotic tissue, or both.

106
Q

What is Intrinsic resistance?

A

When the antimicrobial agent never had activity against the bacterial species. (Naturally resistant)

107
Q

Bacteria that lack ___ will not respond to βlactam antibiotics.

A

Cell wall

108
Q

What is Acquired resistance?

A

When the antimicrobial agent was originally active against the bacterial species but the genetic makeup of the bacteria has changed so the drug can NO longer be effective.

109
Q

What are the mechanisms of acquired bacterial resistance?

A

1) Alteration in the target site
2) Change in membrane permeability
3) Expression of an efflux pump
4) Drug inactivation through either β-lactamases or aminoglycoside-modifying enzymes is the predominant mechanism of resistance!!

110
Q

The expression of β-lactamases can be:

A

1) Induced
2) Constitutive

111
Q

The increased resistance results from:

A

1) Continued overuse of antimicrobials in the community and in hospitals

2) Long-term suppressive antimicrobials for the prevention of infections in immunosuppressed patients

112
Q

Enterococci with multiple resistance patterns may be resistant to:

A

1) β-lactams
2) Vancomycin
3) Aminoglycosides
4) Tetracyclines
5) Ciprofloxacin
6) Clindamycin
7) Erythromycin
8) Quinupristin-dalfopristin

113
Q

Resistance to β-lactams can be caused by:

A

1) β-lactamase production
2) Altered penicillin-binding proteins [PBPs]
3) Both

114
Q

Resistance to Vancomycin can be caused by:

A

Alterations in peptidoglycan synthesis

115
Q

Resistance to Aminoglycosides can be caused by:

A

High levels of AGs-degrading enzymes

116
Q

Penicillin-Resistant Enterococci treatment?

A

Vancomycin + Gentamicin or Streptomycin

117
Q

Vancomycin-Resistant Enterococci (VRE) treatment?

A

1) Linezolid
2) Daptomycin
3) Tigecycline
4) Nitrofurantoin for UTI

118
Q

Enterococci with multiple resistance patterns treatment are susceptible to:

A

1) Imipenem
2) Teicoplanin

119
Q

Resistant Pneumococci are usually susceptible to:

A

1) Vancomycin
2) New Fluoroquinolones:
a) Moxifloxacin
b) Trovafloxacin)
3) Cefotaxime/Ceftriaxone

120
Q

Which antimicrobial agents have been used for resistant gram-positive bacteria?

A

1) Linezolid
2) Daptomycin
3) Telavancin (Semi-synthetic
derivative of Vancomycin)
4) Tigecycline (New Tetracycline)

121
Q

Enterobacter, Citrobacter, Serratia, and P. aeruginosa usually retain susceptibility to:

A

1) Fluoroquinolones
2) Aminoglycosides
3) Carbapenems

122
Q

Which patients are at high risk for drug failure?

A

Debilitated patients with:
1) Pulmonary infections
2) Abscesses
3) Osteomyelitis

123
Q

True or False: Antimicrobial combinations are often overused in clinical practice.

A

TRUE

124
Q

The unnecessary use of antimicrobial combinations may cause:

A

1) Increases toxicity
2) Increases costs
3) Reduced efficacy due to antagonism of one drug by another

125
Q

Antimicrobial combinations should be selected for one or more of the following reasons:

A

1) To provide broad-spectrum empiric therapy in seriously ill patients.
2) To treat polymicrobial infections
3) To decrease the emergence of resistant strains–tuberculosis.
4) To obtain enhanced inhibition or killing
5) To decrease dose-related toxicity by using reduced doses of one or more components of the drug regimen.

126
Q

Antimicrobial combinations chosen should cover:

A

The most common known or suspected pathogens but NOT cover all possible pathogens.

127
Q

The use of Flucytosine in combination with Amphotericin B for the treatment of Cryptococcal meningitis in non HIV-infected patients allows for:

A

A reduction in amphotericin B dosage with decreased Amphotericin B induced nephrotoxicity

Therapeutics (23 decks)

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