Module G

Question 1

List the 4 classifications of antibiotic agents

Answer 1

1. Cell wall synthesis inhibitors
2. Protein synthesis inhibitors
3. Nucleic acid synthesis inhibitors (antifolates, quinolones, etc.)
4. Cell membrane synthesis inhibitors

Question 2

Compare and contrast the actions of bacteri/fungicidal and bacteri/fungistatic agents

Answer 2

both types of agents are antimicrobial and inhibit the cellular processes of bacteria or fungi

bacteri/fungicidal agents kill the susceptible organisms and reduce the number of organisms in the body

bacteri/fungistatic agents inhibit growth of susceptible organisms so that their number remains constant after administration.

Question 3

Explain why administration of bactericidal agent is usually preferable to a bacteristatic agent

Answer 3

Bactericidal agents kill the susceptible pathogen and rapidly reduce its numbers in the body. This leads to a more rapid resolution of symptoms, less dependence on immune function, and a lower likelihood of the pathogen developing resistance

Question 4

Describe the advantages of narrow-spectrum drugs over broad spectrum, and explain when broad-spectrum drugs would be preferred

Answer 4

Narrow-spectrum drugs act on fewer microbes and are less likely to disturb the normally bodily flora, so they generally have fewer adverse effects.

Broad-spectrum drugs are preferable when there is a serious infection where the pathogenic organism haas not yet been identified.

Question 5

Describe the metric used to define microbial sensitivity to a drug

Answer 5

Minimum Inhibitory Concentration (MIC) is the minimum concentration of a drug required to inhibit growth of a pathogen in a nutrient medium. The lower the MIC, the more sensitive the pathogen is to the drug

Question 6

Describe the ways in which pathogens become resistant to drugs

Answer 6

• Innate resistance already exists when the pathogen is first exposed to the drug. ex: gram negative bacteria tend to be resistant to penicillins
• Acquired immunity can be through mutation/selection or transferrable resistance
• Mutation occurs randomly and is more likely to confer resistance to inappropriately managed infections (drug concentration too low, therapy terminated early, therapy too long).
• Transferrable resistance occurs when microbes exchange plasmids containing resistance-conferring genes. This leads to multidrug resistance

Question 7

Describe factors important in selection of antimicrobial therapy

Answer 7

• Host Factors: Allergies, pregnancy, renal/hepatic failure, age
• Microbial Factors: If the organism is known, an appropriate narrow-spectrum antibiotic should be used. Empiric therapy may be initiated based o an educated guess of the pathogenic organism (based on knowing what organisms tend to cause which infections). Broad-spectrum antibiotics may be preferred in serious infections where the causative organism is unknown
• Pharmacokinetic factors: A drug should be selected that promotes compliance (easy dosing) and that maximizes concentration in the effected tissues

Question 8

Describe combination drug therapy and compare its benefits to monotherapy

Answer 8

combination drug therapy is treatment with multiple antimicrobials. It is useful in mixed infections (more than one pathogen), in empiric therapy, or to take advantage of drug interactions (additive, synergistic, indifferent)

Monotherapy with a narrow-spectrum drug is preferred when the causative organism is known because it is less expensive and less likely to produce adverse reactions

Question 9

Describe prophylactic use of antimicrobials

Answer 9

• not common any more because injudicious use of antimicrobials contributes to resistance-formation
• is used to prevent infections during invasive procedures
• is used to prevent disease transmission (malaria, TB, meningococcal infections

Question 10

The structural difference between gram-positive and gram-negative bacteria is:

Answer 10

the presence of an outer trilaminar membrane in gram-negative bacteria. Lipopolysaccharrides in this outer membrane act as endotoxins

Question 11

List the 4 classes of Beta-lactam antibiotics

Answer 11

• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams

Question 12

The first type of antibiotic that was isolated and used to treat systemic bacterial infections is

Answer 12

Penicillins

Question 13

Group the penicillins according to efficacy spectrum

Answer 13

Penicillin G and V are narrow-spectrum. Amoxycillin and ampicillin are extended-spectrum, having some activity against gram-negative (in addition to gram-positive) bacteria

Question 14

Describe the most common form of resistance to penicillins

Answer 14

most commonly due to expression of penicillinase/beta-lactamase which cleaves the lactam ring

Question 15

Describe the MOA of beta-lactam drugs

Answer 15

Penicillins bind to PBPs (penicillin binding proteins) irreversibly, inhibitng the cell’s ability to produce peptidoglycans for cell wall formation, causing cell death

Question 16

The most common adverse reaction to penicillins is

Answer 16

allergic/anaphylactic reactions

Question 17

Describe the role of beta-lactamase inhibitors in antimicrobial therapy and give an example

Answer 17

beta-lactamse inhibitors like clavulinic acid inhibit penicillinase/beta-lactamse and prevent the breakdown of the lactam ring, protecting the drugs from inactivation by resistant bacteria. They are often given as a mixed formulation with a beta-lactam drug and are especially useful against staphylococci (MRSA)

Question 18

The largest and most widely used group of antibiotics is:

Answer 18

cephalosporins

Question 19

Describe advantages of cephalosporins over penicillins

Answer 19

cephalosporins are less susceptible to degradation by beta-lactamase and have a broader spectrum (effective against both gram-positive and gram-negative bacteria).

Question 20

Compare first-generation to later-generation cephalosporins

Answer 20

later generation cephalosporins generally are more effective against gram-negative bacteria and are less susceptible to beta-lactamase activity

Question 21

Cephalosporins generally _____ (can / can not) be used in patients with mild allergic reactions to penicillins

Answer 21

Can

cephalosporins should be avoided in patients with confirmed anaphylactic reactions to penicillins

Question 22

common adverse effects of cephalosporins are

Answer 22

• generally safe
• hypersensitivity reactions may occur, and there may be cross-sensitivity with penicillins
• may cause bleeding due to platelet dysfunction

Question 23

Describe characteristics of carbepenem antibiotics

Answer 23

• beta-lactam antiobiotics
• broad spectrum against gram positive and gram negative bacteria
• resistant to many beta-lactamases
• IV-only
• generally used for serious, systemic, and multi-drug resistant infections
• may be combined with cilastin to extend duration of action

Question 24

what is cilastin used for in antibiotic therapy

Answer 24

extends duration of action of some carbepenem antibiotics

Question 25

patients that are allergic to penicillins ___ (may / may not) be treated with carbepenems

Answer 25

may not! contrast this to cephalosporins which often can be administered to patients with mild penicillin allergies

Question 26

Name a bacterial cell wall synthesis inhibitor that is not a beta-lactam

Answer 26

vancomycin

Question 27

Describe the use of vancomycin in antibiotic therapy

Answer 27

* very effective against many gram-positive and some gram-negative bacteria * Useful in treatment of antibiotic resistant bacteria (MRSA) * most useful in treatment of skin infections * Generally IV only

Question 28

what is the significance of vancomycin resistance?

Answer 28

bacteria that are resistant to vancomycin are often resistant to all other common forms of antibiotics

Question 29

Name three common classes of antibiotics that target bacterial protein synthesis

Answer 29

aminoglycosides, tetracyclines, and macrolides

Question 30

Decribe the general mechanism of action of aminoglycosides and explain why they are bacterioselective in their action

Answer 30

aminoglycosides bind to the 30s ribosomal subunit and cause an incorrect amino acid insertion, leading to inhibition of protein formation. They do not interact with human ribosomes which have a 40s subunit instead of a 30s subunit

Question 31

What class of bacteria are must susceptible to treatment with aminoglycosides

Answer 31

gram negative aerobic organisms ## Footnote *streptomycin is the first-line treatment for TB*

Question 32

What routes are available for administration of aminoglycosides

Answer 32

IV or topical

Question 33

List common adverse effects of aminoglycoside (streptomycin, gentamycin, etc.) administration

Answer 33

ototoxicity and nephrotoxicity

Question 34

Describe the spectrum and general clinical uses of tetracyclines

Answer 34

broad-spectrum **bacteriostatic** antibiotics Generally used to manage infections by small pathogens (rickettsia, mycoplasma pneumonia, lyme disease spirochetes). May be used to treat severe acne

Question 35

Common adverse reactions to tetracyclines include:

Answer 35

* discolouration of teeth * increased skin sensitivity to light * nephrotoxicity * hepatotoxicity

Question 36

Explain a reason why tetracycline resistance is increasing worldwide

Answer 36

heavy prophylactic use in agriculture

Question 37

Describe common clinical uses of macrolides (erythromycin, azithromycin)

Answer 37

used in management of gram-positive upper respiratory infections and community acquired pneumonias

Question 38

Explain why a patient with COPD may be prescribed macrolides

Answer 38

macrolides may be prescribed prophylactically if the patient is at risk of acute COPD exacerbation due to pneumonia

Question 39

Describe common clinical uses of clindamycin and its classification as an antimicrobial

Answer 39

clindamycin is a uniquely-structured protein-synthesis inhibitor that does not belong to the tetracyclines, aminoglycosides, or macrolides. It is important in the mangement of MRSA and penicillin-resistant bacteria also useful in mangement of C. Perfrigens, the cause of gas gangrene.

Question 40

Name the two main categories of nucleic acid sythesis inhibitors

Answer 40

Antifolates and fluoroquinolones

Question 41

What are the two classes of antifolate antibiotics? How are they related?

Answer 41

sulfonamides (sulfa drugs) and trimethoprim both classes inhibit folate metabolism, but at different steps in the pathway. They are often given together to produce a synergistic effects

Question 42

What are the two classes of antifolate drugs and what are the most common adverse reactions to these drugs?

Answer 42

sulfonamides (sulfa drugs) and trimethoprim the most common adverse effect is allergic reaction. Sulfa drugs can cause life-threatening skin reactions

Question 43

What are two major advantages of fluoroquinolones?

Answer 43

* they have good broad-spectrum bactericidal activity * they are well absorbed orally and can often be given once-a-day

Question 44

fluoroquinolones can be identified by their generic names ending in:

Answer 44

-floxacin ## Footnote *ex: ciprofloxacin, levofloxacin, moxifloxacin*

Question 45

Describe how fluoroquinolones are commonly used and give an example of the class

Answer 45

* commonly used in empiric therapy due to their broad-spectrum efficacy and convenient pharmacokinetics * Generally reserved for serious infections that are resistant to other drugs * useful in UTI mangement due to high urine concentration

Question 46

why should fluoroquinolones only be used in adult patients

Answer 46

due to the potential adverse effects of tendonitis and tendon rupture

Question 47

Describe first and second line TB therapy

Answer 47

* 1st line: **PIRE** (**P**yrazinamide, **I**soniazid, **R**ifampin, **E**thambutol) * 2nd line: fluoroquinolones (cipro), amikacin, streptomycin

Question 48

Describe difficulties with effectively treating TB

Answer 48

* Often present with long periods of inactivity encased in granulomatous tissue, hindering antimicrobial access to microbes * Frequently incompletely eradicated so resistance rates are high * Requires a long duration (6-9 months) of treatment to fully eradicate pathogen from body

Question 49

Describe strategies for effectively managing TB

Answer 49

* aggressive management is required to kill bacteria rapidly * Combination therapy is essential * Patient isolation to limit disease transmission * Therapy must continue long after signs disappear to ensure total eradication of pathogen * **DOT** (directly observed therapy) is used to ensure compliance

Question 50

Describe drug resistance in TB

Answer 50

drug resistant TB strains are grouped as **MDR-TB** and **XDR-TB** **MDR-TB** (multi-drug resistant) strains are resistant to at least rifampin and isoniazid **XDR-TB** (extreme-drug resistant) strains are resistant toisoniazid and rifampin as well as second-line drugs (fluoroquinolones, streptomycin, etc.)

Question 51

List the three types of fungal infection

Answer 51

1. superficial 2. subcutaneous 3. systemic

Question 52

Most fungal infections are \_\_\_\_\_\_\_\_\_\_\_, and predominantly occur in immunocompromised or debilitated patients

Answer 52

opportunistic

Question 53

Most antifungal medications are effective against fungi and \_\_\_\_\_\_\_\_\_\_

Answer 53

protozoa

Question 54

The prototype antifungal is \_\_\_\_\_\_\_\_\_, and is most often used for severe infections due to its toxicity

Answer 54

amphoteracin B

Question 55

Compare nystatin to amphoteracin B for antifungal treatment

Answer 55

nystatin is only used for superficial infections whereas amphoteracin B is used for serious or systemic infections. Amphoteracin has higher toxicity than nystatin

Question 56

Pentamidine is primarily used to treat:

Answer 56

pneumocystis pneumonia in HIV patients

Question 57

The organism that is targeted by pentamidine is classified as a

Answer 57

fungus; *pneumocystis carinii* was previously believed to be a protozoan, but is now classified as a fungus

Question 58

pentamidine may be given by which routes

Answer 58

parenterally or inhalational

Question 59

antiviral therapy should be initiated _______ (before / after) signs of infection are present

Answer 59

before

Question 60

briefly describe how antivirals that are used against Herpes viruses have their effect, and give examples

Answer 60

they generally act as nucleoside analogues, causing errors in viral replication. Examples are **acyclovir** and **famciclovir**

Question 61

HIV is calssified as a \_\_\_\_\_\_\_\_

Answer 61

retrovirus

Question 62

Define HAART and describe components of HAART

Answer 62

HAART = Highly Active AntiRetroviral Therapy Usually composed of several NRTIs (nucleoside reverse transcriptase inhibtors) combined with a NNRTI

Question 63

Describe how NRTIs like zidovudine or aziothymidine have their effect in HAART

Answer 63

they mimic viral nucleosides and terminate nucleic acid synthesis

Question 64

NRTIs used in HAART have the common ending:

Answer 64

-dine ## Footnote *ex: zidovudine, aziothymidine*

Question 65

How do NNRTI protease inhibitors have their effect in HAART

Answer 65

they inhibit the action of HIV-1 protease which interferes with virion production. They are generally combined with 2 or more NRTIs

Question 66

How is Tamivir used clinically?

Answer 66

used in treatment of influenza A and B to treat and prevent viral spreading. Usual care for influenza is prophylactic by influenza vaccine

Question 67

Which forms of hepatitis can be treated by antiviral therapy?

Answer 67

Hepatitis B and C

Question 68

Why are trimethoprim and sulfamethoxazole given together as combination therapy, and what infection are they specifically indicated for?

Answer 68

The two antifolates have synergistic effects if given together, turning them from bacteriostatic to bactericidal. They are used to treat pneumocystis carinii pneumonia (PCP)