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Antibiotic toolkit Flashcards

info from the lecture and uptodate : https://www.uptodate.com/contents/penicillin-antistaphylococcal-penicillins-and-broad-spectrum-penicillins#H2

1
Q

What are antibiotics derived from?

A

Antibiotics are derived from living organisms (e.g., penicillin).

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2
Q

What are chemotherapeutic agents?

A

Chemotherapeutic agents are synthesized drugs.

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3
Q

What are the two main mechanisms of antibiotic action?

A

Concentration-dependent killing and time-dependent killing.

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4
Q

Which antibiotics are typically associated with concentration-dependent killing?

A

Aminoglycosides and quinolones.

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5
Q

What is the key characteristic of concentration-dependent killing?

A

Higher antimicrobial concentrations kill bacteria more rapidly.

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6
Q

What is the significance of the Area Under the Curve (AUC) in concentration-dependent antibiotics?

A

A larger AUC/MIC ratio correlates with better bacterial eradication.

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7
Q

What is the Minimum Inhibitory Concentration (MIC) in a concentration-time graph for antibiotics?

A

The lowest concentration of the antibiotic required to inhibit visible growth of a bacterium.

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8
Q

What correlates with better bacterial eradication for concentration-dependent antibiotics?

A

A larger AUC/MIC ratio.

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9
Q

Why is careful dosing important for concentration-dependent antibiotics?

A

To ensure peak concentrations are sufficiently high to achieve the desired therapeutic effect.

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10
Q

What can result from under-dosing concentration-dependent antibiotics?

A

Ineffective treatment and the risk of developing antibiotic resistance.

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11
Q

Which antibiotics are typically associated with time-dependent killing?

A

Beta-lactams.

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12
Q

What is the key characteristic of time-dependent killing?

A

The effectiveness is related to the duration the drug concentration remains above the MIC.

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13
Q

What percentage of the dosing interval should time-dependent antibiotics remain above the MIC for effective treatment?

A

40-60%, ideally 95-100% for certain infections like meningitis.

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14
Q

Why is it important not to skip doses of time-dependent antibiotics?

A

To maintain drug concentrations above the MIC and ensure therapeutic effectiveness.

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15
Q

What is the importance of maintaining drug concentration above the MIC?

A

It maximizes the drug’s efficacy and helps achieve a successful treatment .

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16
Q

How do concentration-dependent and time-dependent antibiotics differ in their dosing strategies?

A

Concentration-dependent antibiotics require higher peak concentrations, while time-dependent antibiotics require consistent levels above the MIC.

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17
Q

list drugs that fall under beta lactams

A
  1. Penicillins
  2. Cephalosporins
  3. Carbapenems
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18
Q

What is the primary action of β-lactams?

A

They act on the bacterial cell wall.

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19
Q

What type of killing action do β-lactams exhibit?

A

Time-dependent bactericidal action.

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20
Q

What is a notable characteristic of the therapeutic index of β-lactams?

A

They have a wide therapeutic index but can be CNS toxic at maximal doses.

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21
Q

What is the main adverse effect associated with β-lactams?

A

Hypersensitivity.

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22
Q

How are most β-lactams eliminated from the body?

A

They are primarily eliminated by renal tubular secretion.

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23
Q

What is the most common mechanism of resistance to β-lactams?

A

Resistance mediated by β-lactamases.

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24
Q

Can resistance mediated by β-lactamases be overcome by using higher doses of β-lactams?

A

No, it cannot be overcome by using higher doses.

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25
Q

Which types of bacteria commonly produce β-lactamases in the community?

A

Most aerobic Gram negatives, anaerobes, and staphylococci.

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26
Q

What are extended spectrum β-lactamases (ESBLs) and where are they commonly found?

A

ESBLs are produced by aerobic Gram negatives in hospitals, resulting in high-level resistance to all penicillins and cephalosporins.

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27
Q

What is the second mechanism of resistance to β-lactams?

A

Mutations in penicillin-binding proteins (PBPs), such as in S. pneumoniae, which usually leads to low-level resistance that can be overcome by higher doses.

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28
Q

What types of bacteria is penicillin primarily active against?

A

Gram-positive bacteria and spirochaetes.

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29
Q

What are the primary clinical uses of penicillin?

A

It is the drug of choice for streptococci, syphilis and other spirochaetes, enterococci, Listeria, and Actinomyces.

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30
Q

What is a significant limitation of penicillin regarding resistance?

A

Penicillin is susceptible to β-lactamase.

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31
Q

What are the two forms of penicillin ( the natural penicillins )and their routes of administration?

A

Penicillin G (IV) and Penicillin V (oral, but poorly absorbed).

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32
Q

How long does long-acting injectable benzathine penicillin last?

A

It lasts for 21 days.

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33
Q

What are aminopenicillins and their routes of administration?

A

Aminopenicillins include ampicillin (only useful IV) and amoxicillin (oral and well absorbed).

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34
Q

How has the spectrum of activity for aminopenicillins changed over time?

A

They were initially broad-spectrum agents, but resistance has become widespread.

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35
Q

What additional coverage do aminopenicillins provide compared to penicillin?

A

They provide coverage for Haemophilus, except for those strains that produce β-lactamase (about 15%).

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36
Q

Why are aminopenicillins recommended for respiratory infections?

A

They have excellent activity against S. pneumoniae.

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37
Q

What distinguishes broad-spectrum penicillins?

A

Their activity against gram-negative bacilli.

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38
Q

What are the classifications of broad-spectrum penicillins?

A

Second-generation (ampicillin, amoxicillin), third-generation (carbenicillin, ticarcillin), and fourth-generation (piperacillin).

  • with the second generation resistance has increased
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39
Q

Why are ampicillin and amoxicillin not stable to beta-lactamases?

A

They are susceptible to degradation by these enzymes.

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40
Q

Which bacteria are broad-spectrum penicillins active against?

A

They are active against the majority of strains of Escherichia coli, Proteus mirabilis, Salmonella, Shigella, and Haemophilus influenzae.

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41
Q

What is a key feature of cloxacillin regarding resistance?

A

Cloxacillin resists β-lactamase produced by Staphylococci.

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42
Q

How does flucloxacillin compare to cloxacillin in terms of absorption?

A

Flucloxacillin is better absorbed orally than cloxacillin.

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43
Q

What types of bacteria are cloxacillin and flucloxacillin effective against?

A

Both are effective only against Gram-positive bacteria

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44
Q

For what types of infections are cloxacillin and flucloxacillin widely used?

A

They are widely used for skin and soft tissue infections.

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45
Q

What are the antistaphylococcal penicillins?

A

Nafcillin, oxacillin, cloxacillin, and dicloxacillin.

must know : Cloxacillin

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46
Q

What is the primary action of antistaphylococcal penicillins?

A

They inhibit penicillinase-producing staphylococci.

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47
Q

Against which type of staphylococci are antistaphylococcal penicillins inactive?

A

They are inactive against oxacillin-resistant staphylococci.

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48
Q

For strains of Staphylococcus aureus sensitive to oxacillin, which antibiotics are preferable to vancomycin?

A

Antistaphylococcal penicillins or cefazolin

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49
Q

Why are antistaphylococcal penicillins or cefazolin preferred over vancomycin for sensitive S. aureus strains?

A

Vancomycin is less active against S. aureus than beta-lactams in in vitro and clinical studies.

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50
Q

What are the available forms of penicillin?

A

Penicillin is available in IV, oral, and depot IM forms.

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51
Q

Name two penicillins that are resistant to β-lactamase.

A

Cloxacillin and flucloxacillin.

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52
Q

What is a commonly used oral penicillin?

A

Amoxicillin.

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53
Q

What are β-lactamase inhibitors

A

They are irreversible inhibitors of β-lactamases, which are enzymes that confer resistance to β-lactam antibiotics.

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54
Q

Name two common β-lactamase inhibitors.

A

Clavulanate and tazobactam.

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55
Q

How do β-lactamase inhibitors work in combination with β-lactams?

A

They can reverse resistance to β-lactam antibiotics when combined with them.

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56
Q

What is an example of a combination of a β-lactam and a β-lactamase inhibitor?

A

Amoxicillin-clavulanate.

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57
Q

What types of infections is amoxicillin-clavulanate effective against?

A

It has broad-spectrum activity against community-acquired Gram-positive, Gram-negative, and anaerobic infections.

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58
Q

What is another example of a β-lactam combined with a β-lactamase inhibitor?

A

Piperacillin-tazobactam.

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59
Q

What combination includes amoxicillin and a β-lactamase inhibitor?

A

Amoxicillin-clavulanate.

60
Q

How are cephalosporins categorized?

A

They are developed in successive generations.

61
Q

What is the spectrum of activity for 1st generation cephalosporins?

A

The spectrum is largely limited to Streptococci and Staphylococci.

62
Q

Name two examples of 1st generation cephalosporins

A

Cefazolin (IV) and Cephalexin (PO).

63
Q

What additional coverage do 2nd generation cephalosporins provide compared to 1st generation?

A

They cover Haemophilus and community-acquired Gram negatives.

64
Q

Name an example of a 2nd generation cephalosporin

A

Cefuroxime (available in both PO and IV forms).

65
Q

What additional infections do 3rd generation cephalosporins cover?

A

They cover typhoid, spirochetes, and have good CSF penetration.

66
Q

Name two examples of 3rd generation cephalosporins.

A

Cefotaxime and Ceftriaxone.

67
Q

What is a notable characteristic of Ceftazidime among 3rd generation cephalosporins?

A

It is effective against Pseudomonas but is poor for Streptococci.

68
Q

Name an example of 3rd generation cephalosporins

A

Cefepime

69
Q

What is Cefazolin used for?

A

It is used at inductionn for surgical prophylaxis and for serious staphylococcal infections

70
Q

How is Ceftriaxone administered and what is its excretion route?

A

Ceftriaxone is administered IV or IM daily and is mainly excreted via bile.

71
Q

What is the spectrum of Ceftriaxone?

A

It covers community-acquired Gram+ (including most S. pneumoniae) and Gram- bacteria.

72
Q

What are the clinical uses of Ceftriaxone?

A

It is the empiric drug of choice for bacterial meningitis, typhoid, and gonorrhea, and is useful for serious community infections.

73
Q

What are carbapenems known for?

A

They have an extremely broad spectrum covering most hospital-acquired Gram+, Gram-, and anaerobes.

74
Q

When are carbapenems typically used?

A

They are used only for nosocomial infections.

75
Q

What is a limitation of carbapenems?

A

They are not active against cloxacillin-resistant Staphylococci and are very expensive.

76
Q

What is the incidence of β-lactam hypersensitivity reactions with penicillins?

A

The incidence is between 1 to 6%.

77
Q

What is the most common type of rash associated with β-lactam hypersensitivity?

A

Maculopapular rash, which usually occurs after 72 hours and is often due to amoxicillin.

78
Q

What is the risk of anaphylaxis with β-lactam antibiotics?

A

Anaphylaxis occurs mostly with parenteral administration and is rare, with an incidence of 0.01 to 0.05%.
occurs within 1 hour

79
Q

What symptoms can occur within 72 hours of β-lactam hypersensitivity?

A

Angioedema, urticaria, and bronchospasm.

80
Q

What is the cross-reactivity rate between cephalosporins and penicillins?

A

The cross-reactivity is less than 5%, and it is lowest with 3rd generation cephalosporins (<1%).

81
Q

What should be done if a patient has an IgE-mediated reaction to penicillins?

A

The entire class should be avoided, and desensitization may be considered in exceptional cases.

82
Q

What should be done if a patient has penicillin allergy if hypersensitivity
reaction was not IgE mediated?

A

can use cephalosporins

  • Cross reaction between cephalosporins & penicillins <5%, lowest with 3rd generation (<1%)
83
Q

What is the primary action of glycopeptides?

A

What is the primary action of glycopeptides?

84
Q

What type of killing do glycopeptides exhibit?

A

Time-dependent killing.

85
Q

Are glycopeptides absorbed orally?

A

No, they are not absorbed orally.

86
Q

What type of bacteria do glycopeptides cover?

A

They only cover Gram-positive bacteria.

87
Q

Which specific bacteria are glycopeptides especially effective against?

A

They are especially effective against cloxacillin-resistant Staphylococci.

88
Q

What is an example of a glycopeptide?

A

Vancomycin.

89
Q

What is essential when administering vancomycin?

A

Slow IV infusion is essential to prevent red man syndrome

90
Q

what is a red man syndrome ?

A

Red Man Syndrome is a side effect of some antibiotics, like vancomycin. It causes symptoms like redness and itching of the skin, usually on the upper body and neck. It can also lead to low blood pressure

91
Q

What are the potential toxicities associated with glycopeptides?

A

They are mildly nephrotoxic and ototoxic (toxic to the ear ).

92
Q

Why is it important to measure glycopeptide concentration?

A

It is important to measure concentration in renal failure and for selected organisms.

93
Q

What type of bacteria are aminoglycosides potent against?

A

They are potent against aerobic Gram-negative bacilli.

94
Q

What is the mechanism of action of aminoglycosides?

A

They are bactericidal inhibitors of protein synthesis.

95
Q

What type of killing do aminoglycosides exhibit?

A

Concentration-dependent killing.

96
Q

How do aminoglycosides interact with β-lactams?

A

They can have synergy with β-lactams, although this is rarely necessary.

97
Q

Why must aminoglycosides be given parenterally?

A

They are polar compounds with poor tissue penetration

98
Q

Where are aminoglycosides concentrated in the body?

A

They are concentrated in urine.

99
Q

What is the recommended dosing strategy for aminoglycosides?

A

Single daily dosing is best due to the post-antibiotic effect.

100
Q

When should aminoglycoside concentrations be measured?

A

If treatment lasts more than 3 days or in cases of renal failure.

101
Q

What is a common use of gentamicin?

A

It is used for serious community infections, such as pyelonephritis.

102
Q

How is gentamicin used in polymicrobial infections?

A

It can be combined with β-lactams for synergy, particularly in enterococci and streptococcal endocarditis.

103
Q

What is a key toxicity associated with aminoglycosides?

A

Ototoxicity, which can affect cochlear and vestibular functions.

104
Q

What are the characteristics of cochlear ototoxicity?

A

It often presents as high-tone deafness initially and can be irreversible.

105
Q

What type of nephrotoxicity is associated with aminoglycosides?

A

The nephrotoxicity tubular ,and it is generally reversible.

106
Q

In which populations should aminoglycosides be avoided?

A

They should be avoided in the elderly or those with chronic kidney disease (CKD).

107
Q

name an amoniglycoside

A

Amikacin

108
Q

Explain aminoglycoside toxicity

A

Related to prolonged elevated trough concentrations
* Ototoxicity
– Cochlear – high tone deafness initially
– Vestibular
– Irreversible in many cases
* Nephrotoxicity
– Tubular toxin
– Reversible
– Avoid in elderly or CKD

109
Q

What enzymes do quinolones target?

A

They target DNA enzymes, specifically gyrase and topoisomerase IV.

110
Q

What type of killing do quinolones exhibit?

A

Concentration-dependent killing.

111
Q

How are first-generation quinolones characterized in terms of absorption and spectrum?

A

They are poorly absorbed and have a limited spectrum, primarily targeting Gram-negative aerobes, with resistance arising readily (e.g., nalidixic acid)

112
Q

What is the absorption and spectrum of second-generation fluoroquinolones?

A

They are well absorbed and effective against Gram-negative aerobes, including Pseudomonas, but are poor for Gram-positive bacteria.

113
Q

What is the spectrum of third-generation fluoroquinolones?

A

They are well absorbed and cover both Gram-positive (especially Streptococci) and Gram-negative bacteria (except Pseudomonas).

114
Q

What are some common toxicities associated with quinolones?

A

Toxicities include rashes, CNS effects (headache, dizziness, excitation, seizures), and tendonitis.

115
Q

Why is the use of quinolones in children limited?

A

Their use is limited due to animal toxicity, although they may be used for restricted indications.

116
Q

How does resistance to quinolones generally occur?

A

Resistance typically arises from mutations in the target genes.

117
Q

For what types of infections are quinolones recommended?

A

They are recommended only for serious infections due to recent toxicity concerns.

118
Q

What is the drug of choice among second-generation quinolones?

A
  • Ciprofloxacin is the drug of choice for bacterial dysentery, pyelonephritis, and prostatitis.
  • Alternative to aminoglycosides
  • Typhoid (resistance is increasing
119
Q

What is a notable use of third-generation quinolones like moxifloxacin?

A

They are used for multidrug-resistant tuberculosis (MDR TB) and Alternative for respiratory tract infections (only if severe beta lactam allergy), cover atypical pneumonia agents as well as conventional
bacterial causes of community-acquired pneumonia

120
Q

What are macrolides used as an alternative for?

A

They are used as an alternative to penicillin for allergic patients with mild streptococcal and staphylococcal infections.

121
Q

Which atypical pneumonia agents are macrolides active against?

A

They are active against Legionella, Mycoplasma, and Chlamydophila.

122
Q

What are the drugs of choice among macrolides for H. pylori infections?

A

Clarithromycin and azithromycin.

123
Q

What is a recommended treatment for Chlamydia urethritis/cervicitis?

A

A single dose of azithromycin.

124
Q

What infections are macrolides the drugs of choice for in AIDS patients?

A

M. avium complex infections.

125
Q

list conditions or infections where macrolides are the drug of choice

A
  • H. pylori (clarithromycin/azithromycin)
    – Chlamydia urethritis/cervicitis (single dose azithromycin)
    – Pertussis
    – Chancroid
    – M. avium complex infections in AIDS (clarithromycin/
    azithromycin
126
Q

What is the mechanism of action of tetracyclines?

A

They inhibit protein synthesis by targeting the 30 S ribosome.

127
Q

How do tetracyclines exhibit resistance?

A

Resistance can occur through efflux or enzymatic breakdown.

128
Q

How does the absorption of tetracyclines vary?

A

Absorption varies, with doxycycline having excellent absorption, while absorption can be impaired by divalent cations

129
Q

What is a notable characteristic of tetracyclines regarding tissue penetration?

A

They have good intracellular penetration.

130
Q

What are some common toxicities associated with tetracyclines?

A

Toxicities include nausea/vomiting, photosensitivity, and teeth discoloration (avoid use in children under 8 years and during pregnancy).

131
Q

Tetracyclines are the drugs of choice for which conditions/ infections.

A

Drugs of choice
– Rickettsia
– Brucellosis
– Acne (low dose)

132
Q

What is the role of tetracyclines in malaria prophylaxis?

A

They are used for the prophylaxis of falciparum malaria

133
Q

Why are tetracyclines limited in usefulness as a single agent for respiratory infections?

A

Because Streptococcus pneumoniae often shows resistance to them.

134
Q

What are the components of cotrimoxazole?

A

Cotrimoxazole is a combination of sulfamethoxazole (a sulphonamide) and trimethoprim.

135
Q

How does cotrimoxazole work?

A

It blocks successive steps in the bacterial folate pathway, preventing nucleic acid synthesis.

136
Q

How is cotrimoxazole absorbed?

A

It is well absorbed orally.

137
Q

What is the main side effect of cotrimoxazole?

A

The main side effect is sulphonamide hypersensitivity, which can lead to severe skin rashes, including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

138
Q

Why is cotrimoxazole of minimal value outside of HIV?

A

Due to its toxicity and the high prevalence of resistance in community-acquired Gram negatives and Streptococcus pneumoniae.

139
Q

What are the therapeutic uses of cotrimoxazole in HIV infection?

A

It is the drug of choice for Pneumocystis jirovecii pneumonia, toxoplasmosis, and Cystoisospora belli diarrhea.

140
Q

What is the role of cotrimoxazole in primary prophylaxis for HIV patients?

A

It prevents Pneumocystis jirovecii pneumonia and reduces bacterial infections.

141
Q

What is a common reaction in HIV+ patients taking cotrimoxazole?

A

There is a much higher frequency of rash, especially with higher doses.
– Especially with higher doses
– Rechallenge/dose reduction often successful
(not if reaction was severe)

142
Q

What is metronidazole’s mechanism of action?

A

It is toxic to DNA, forming highly reactive nitro radicals through anaerobic metabolism involving Fe:S proteins.

143
Q

How is metronidazole administered?

A

It has good oral absorption and is also available as a rectal (PR) and intravenous (IVI) formulation.

144
Q

What are some common side effects of metronidazole?

A

It is well tolerated in short courses but can cause a metallic taste and a disulfiram-like effect (avoid alcohol). Long-term use may lead to neurotoxicity and neutropenia.

145
Q

What types of infections is metronidazole effective against?

A

It is a broad-spectrum anaerobe agent effective against cocci, Gram-negative bacilli, Gram-positive spore-forming bacilli, and certain protozoans like Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia.

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