Micro Ch 20 Smart Book

What is the therapeutic window of a drug?

the range between the dose used therapeutically and the toxic dose

The Kirby-Bauer disc diffusion test is routinely used to determine ______.

the susceptibility of a given bacterial strain to an assortment of antimicrobial drugs

What is the therapeutic index of a drug?

the toxicity of a given drug expressed as the lowest dose toxic to the patient divided by the dose typically used for therapy

An advantage of the cephalosporins is ______.

their chemical structure makes them resistant to inactivation by certain β-lactamases

The relative toxicity of a given medication to humans is expressed as the __________ index.

therapeutic

All of the following accurately describe the tetracyclines EXCEPT ______.

they are equally toxic to eukaryotic and prokaryotic cells and so must be used only as a last resort

The selective toxicity of the tetracyclines is because ______.

they bind to the prokaryotic 30S ribosomal subunit

The fluoroquinolones are synthetic drugs that inhibit one or more of a group of enzymes called , which maintain the supercoiling of DNA within the bacterial cell.

topoisomerases

By reversibly binding to the 50S ribosomal subunit, the macrolides prevent the continuation of .

translation

A patient has a urinary tract infection. Why is this a good example of an infection that can usually be treated well with bacteriostatic antimicrobials, e.g., sulfa drugs?

Once bacterial growth is stopped, urination can usually be counted on to flush the pathogens.

To treat a case where the patient's defenses are unlikely to clear an infection, which would be the more appropriate choice of an antimicrobial drug, one that is bactericidal or bacteriostatic?

One that is bactericidal.

What are some ways in which physicians and other healthcare workers can help to slow the emergence and spread of antimicrobial resistance? (3)

Only prescribe suitable antibiotics if appropriate. Increase their efforts to identify the cause of a given infection. Educate patients about the proper use of prescribed drugs in order to increase compliance.

An antimicrobial medication is added to a culture of bacteria. The medication weakens the cell wall of the microbes, causing them to swell and burst due to osmotic pressure changes. Which of the following antimicrobials was most likely used?

Penicillin

Modifications in the - proteins (PBPs) prevent the beta-lactam antibiotics from binding to them.

Penicillin-Binding

How can changes in the porin proteins in the outer membrane of Gram-negative bacteria result in resistance to antimicrobials?

Porins selectively permit small molecules to enter the periplasm; changes in these porins can prevent certain drugs from entering.

Why is combination therapy effective in preventing the rise of mutants resistant to antibiotics?

The chance of a cell simultaneously developing mutational resistance to multiple drugs is extremely low.

Sulfa drugs are frequently prescribed for urinary tract infections. They prevent bacteria in the bladder from growing so that urination can more effectively eliminate them. In terms of their antimicrobial action, this means sulfa drugs are ______.

bacteriostatic

When considering their antimicrobial mechanism, drugs that inhibit bacterial growth but do not kill the organisms are referred to as .

bacteriostatic

Because of its activity against members of the genus Mycobacterium, rifampin is primarily used to treat ______.

tuberculosis Hansen's disease (leprosy)

In many parts of the world, particularly in developing countries, antimicrobial drugs are available on a non-prescription basis. All of the following are examples of problems that might arise from this approach EXCEPT ______.

drugs will make the people taking them resistant to the effects of the antimicrobials, making them useless in the future

Resistance to antimicrobials can result from the alteration of existing genes via spontaneous mutation, or via horizontal transfer from another organism.

gene

One of the main categories of MRSA is known as HA-MRSA. It stands for -associated methicillin-resistant Staphylococcus aureus.

healthcare or hospital

Human cells lack the enzyme targeted by the sulfonamides involved in folate synthesis. This suggests that these drugs should have a therapeutic index.

high

Because of concerns about antibiotic resistance, the CDC published a document that lists the most serious threats, categorizing them by ______.

level: urgent, serious, and concerning

The macrolides are not effective against members of the family Enterobacteriaceae because _______.

macrolides do not pass through the outer membrane of these bacteria

A bacterial enzyme that adds a methyl group to an rRNA molecule of the 50S ribosome confers resistance to ______.

macrolides, lincosamides, and streptogramins

In the case of changes to the target that result in drug resistance, they would most commonly arise from ______.

minor structural changes in the target, which prevent the drug from binding

Antibacterial medications that inhibit protein synthesis in prokaryotes target the 70S ribosome. However, of human cells possess ribosomes similar to those of bacteria, which might account for some of the toxicity observed with some of these drugs.

mitochondria

True or false: Most antibacterial medications interfere with metabolic pathways.

False

True or false: Physicians and healthcare workers are helpless in slowing the emergence and spread of antimicrobial resistance. The real problem is patients improperly using these lifesaving medications.

False

In the picture showing results from a Kirby-Bauer method for determining drug susceptibility, the strain is most susceptible to which drug?

The answer cannot be fully determined from the information provided.

Eukaryotic cells have 80S ribosomes. Prokaryotic cells, however have ribosomes, composed of a 50S and 30S subunit. The structure of these prokaryotic ribosomes is different enough from the eukaryotic ones that they can be selectively targeted by antibacterial drugs.

70S

True or false: There are no useful antimicrobials that inhibit nucleic acid synthesis because the processes are essentially the same in both eukaryotic and prokaryotic cells, making the drugs too toxic to humans.

False

True or false: To prevent the spread of antibiotic resistance, scientists recommend that everyone stop using the medications for a period of five years.

False

True or false: Viruses are very effectively treated with antibiotics.

False

True or false: In some cases, resistance genes may have originated from the soil microbes that naturally produce that antibiotic.

True

Surveys indicate that far too many people believe that antibiotics are effective against viruses, often seeking prescriptions to "cure" viral infections. Why should antibiotics never be taken for viral infections? (2)

Antibiotics are not effective against viruses. Misuse of antibiotics only selects for antibiotic-resistant bacteria in the normal microbiota.

Explain how drug resistance develops in bacteria and ultimately limits the usefulness of all known antimicrobials.

Antimicrobials kill or inhibit sensitive organisms, providing a selective advantage to resistant strains; these strains spread in the population.

Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to methicillin as well as nearly all other - drug

B-Lactam

Consider the following antibiotics and their common uses. Based on these uses, which most likely has a low therapeutic index?

Bacitracin, used in topical ointments

Which organization recently published a document that lists the most serious threats with respect to antibiotic resistance?

CDC

What is the function of penicillin-binding proteins (PBPs)?

Catalyze the formation of peptide bridges between adjacent glycan strands in the final stages of peptidoglycan synthesis.

There are two categories of MRSA strains. The one called CA-MRSA refers to __________ acquired methicillin-resistant Staphylococcus aureus.

Community

Which steps must be taken to prevent the spread of antimicrobial resistance? (3)

Countries around the world must make important policy decisions about the appropriate uses of the medications The general public must take responsibility for the appropriate use of the medications. Physicians must take responsibility for the appropriate use of the medications.

The systems that bacteria use to transport damaging compounds out of a cell are called .

Efflux Pumps

Which of the following are steps that patients can take to help slow the emergence and spread of antimicrobial resistance? (3)

Finish the entire course of medications. Do not skip a scheduled dose of a drug. Carefully follow the instructions that accompany their prescriptions, even if inconvenient.

Penicillin G interferes with bacterial cell wall synthesis. Therefore, what would you expect its therapeutic index to be, and why?

High, because it targets a vital biochemical process in bacteria that does not exist in human cells.

Sulfa drugs have a high therapeutic index, meaning they have low toxicity. Why is this?

Human cells lack the enzyme that binds these medications.

Resistance can result from structural changes in efflux pumps, changing the range of drugs that can be pumped out. Why is resistance that develops by this mechanism particularly worrisome?

It might allow an organism to become resistant to several drugs simultaneously.

In terms of treating infections in humans, why is the bacterial cell wall such a good drug target for antimicrobials?

It is unique in containing peptidoglycan; antimicrobials that interfere solely with peptidoglycan synthesis do not affect eukaryotic cells.

Antibacterials like daptomycin and polymyxin B essentially make holes in the bacterial membrane. Why, in terms of the function of the membrane, is this deadly to bacteria?

It makes the membranes no longer selectively permeable.

Why is combination therapy required for treating tuberculosis?

Large numbers of bacteria are found in an active infection, so it is likely that at least one has developed spontaneous resistance to a drug.

In the context of antimicrobials, MRSA stands for - Staphylococcus aureus.

Methicillin-Resistant

Genes encoding resistance to antimicrobial drugs can spread to different strains, species, and even genera, most commonly through conjugative transfer of .

R or resistance plasmids or factors

What is the primary benefit of the newer aminoglycosides binding to several sites on the ribosome?

Resistance due to spontaneous mutation is unlikely.

When an antimicrobial drug has several different targets or has multiple binding sites on a single target, resistance through spontaneous mutation is less likely to occur. Why is this?

Several different mutations are required to prevent binding of the drug.

Which of the following statements regarding antibiotics, antibiotic use, and viruses are true? (3)

Taking antibiotics will not cure the common cold or any other viral illness. People may mistakenly believe that antibiotics are effective against viruses and often seek prescriptions to "cure" viral infections. Misuse of antibiotics may select for antibiotic-resistant bacteria in the normal microbiota.

Why are many Gram-negative bacteria intrinsically resistant to certain drugs?

The lipid bilayer of their outer membrane prevents certain drugs from entering.

Broad-spectrum antimicrobials are effective against a wide range of bacteria, so they are more likely than narrow-spectrum antimicrobials to be able to clear a given infection. Why are they not simply used all the time instead of narrow-spectrum antibiotics?

They are more likely to disrupt the normal microbiota that plays an important role in excluding pathogens.

Which of the following correctly describe how R plasmids contribute to resistance in microbial populations?

They can spread to different strains, species, or even genera via conjugative transfer. They often carry several different resistance genes, each one encoding resistance to a specific antimicrobial drug.

Effective antimicrobial drugs would need to demonstrate selective toxicity. What does this mean?

They cause greater harm to microbes than to the human host.

A broad-spectrum antimicrobial is most likely effective against ______.

a wide range of both Gram-positive and Gram-negative bacteria

All of the following are true statements regarding treatment of tuberculosis EXCEPT ______.

development of drug-resistant strains is uncommon

Certain bacteria are inherently resistant to the effects of some antimicrobials. Inherent resistance is called resistance.

intrinsic or innate

When a patient fails to complete the prescribed course of antibiotics, or skips a scheduled dose of a drug, this can change the population of microorganisms by all the following mechanisms EXCEPT ______.

it will decrease the development of resistance, since the microbes will have less exposure to the drugs that select for resistance

If a bacterium is resistant to the macrolides, lincosamides, and streptogramins, it most likely produces an enzyme that ______.

modifies an rRNA molecule of the 50S ribosomal subunit

In general, the later generations of cephalosporins are _____ effective against Gram-negative bacteria and _____ susceptible to destruction by some β-lactamases.

more; less

Although antimicrobial resistance can result from the acquisition of new genes, it can also be due to the altering of existing genes via spontaneous .

mutation or mutations

Antibiotics are _________ effective against viruses.

not or never

Just a single specific base-pair change in the gene encoding a ribosomal protein alters the target enough to make the cell resistant to the antibiotic ______.

streptomycin

Infections caused by Salmonella strains resistant to antibiotics have been linked to farm animals whose feed was supplemented with ______.

the same antibiotics

A gene codes for an enzyme that chemically modifies an aminoglycoside, rendering the drug inactive. The gene encoding that enzyme is thought to have originally come from ______.

the same species of Streptomyces that produces the drug

Which of the following statements are true regarding the use of antimicrobials with low therapeutic index? (3)

The concentration in the patient's blood must be carefully monitored to ensure it does not reach a toxic level. They can sometimes be used for topical applications, e.g., as first-aid antibiotic skin ointments. They are sometimes used when all other options are unavailable due to strains of bacteria that are resistant to multiple antibiotics.

After testing to determine the susceptibility of an organism to various drugs, what are important considerations when choosing a drug to use?

The drug should act against as few other bacteria as possible. The drug should act against the pathogen.

True or false: A Gram-negative rod that does not produce an ESBL (extended-spectrum β-lactamase) would likely be treated with a carbapenem.

False

True or false: Susceptibility of a pathogen to a specific antimicrobial drug is almost always predictable.

False

A group of medications called the - drugs are preferred for use against species of Mycobacterium, because they are the most effective as well as the least toxic.

First-Line

Which of the following antimicrobials inhibit nucleic acid synthesis?

Fluoroquinolones, rifamycins, and metronidazole

Rifamycins are antibiotics that bind to _______ of bacteria thus preventing _______.

RNA polymerase; transcription

_______, an inhibitor of transcription, is primarily used to treat tuberculosis and to prevent meningitis in people exposed to Neisseria meningitidis.

Rifampin

When a previously sensitive organism develops resistance through spontaneous mutation or horizontal gene transfer, this is an example of resistance.

acquired

Antimicrobial medications that have a high therapeutic index are ______(a) toxic, whereas those with a low therapeutic index are ______(b) toxic.

(a) Less (b) More

Consider narrow-spectrum and broad-spectrum antimicrobials. Match each in terms of advantages and disadvantages with the appropriate description. Broad-spectrum advantage: Broad-spectrum advantage: drop zone empty. Broad-spectrum disadvantage: Broad-spectrum disadvantage: drop zone empty. Narrow-spectrum advantage: Narrow-spectrum advantage: drop zone empty. Narrow-spectrum disadvantage:

Broad-spectrum advantage: Broad-spectrum advantage: Drop zone Useful for treating acute, life-threatening diseases when immediate antimicrobial therapy is essential and there is no time to culture and identify the pathogen correct Toggle Button Unavailable. Useful for treating acute, life-threatening diseases when immediate antimicrobial therapy is essential and there is no time to culture and identify the pathogen Broad-spectrum disadvantage: Broad-spectrum disadvantage: Drop zone More likely to disrupt the normal microbiota that play an important role in excluding pathogens correct Toggle Button Unavailable. More likely to disrupt the normal microbiota that play an important role in excluding pathogens Narrow-spectrum advantage: Narrow-spectrum advantage: Drop zone Less likely to disrupt the normal microbiota that play an important role in excluding pathogens correct Toggle Button Unavailable. Less likely to disrupt the normal microbiota that play an important role in excluding pathogens Narrow-spectrum disadvantage: Narrow-spectrum disadvantage: Drop zone The pathogen must be identified and tested for susceptibility to the antibiotic correct Toggle Button Unavailable. The pathogen must be identified and tested for susceptibility to the antibiotic

Drugs such as streptomycin for which a single point mutation causes resistance are sometimes used in combination with one or more other drugs. This way, if any cell spontaneously develops resistance to one drug, another drug will still kill it. This approach is called .

Combination Therapy

After sulfa drugs and penicillin were introduced, people hoped such drugs would eliminate most bacterial diseases. Unfortunately, this has not happened. Why is this?

Drug resistance limits the usefulness of all known antimicrobials.

The figure shows results from the - disc diffusion test for determining the susceptibility of a given bacterial strain to a variety of antimicrobial medications.

Kirby-Bauer

Antibacterial drugs that bind to the 70S ribosome inhibit prokaryotic protein synthesis. What organelle in a human cell might also be targeted, possibly accounting for some of the toxicity observed with some of these drugs?

Mitochondria

If a strain of Mycobacterium tuberculosis proves resistant to the preferred and most effective drugs, the - drugs should be used, even though they are either less effective or have greater risk of toxicity.

Second-Line

Medically useful antimicrobial drugs exhibit _________ __________, meaning they cause greater harm to microbes than to the human host.

Selective toxicity

What are two ways that changes in efflux pumps can lead to resistance to an antimicrobial?

Structural changes in the pumps can influence the range of drugs that can be pumped out. A cell can increase production of the efflux pumps, thereby ejecting the drug faster.

Considering that all cells synthesize proteins, how is it possible to selectively target prokaryotic protein synthesis with antibacterials?

The structure of the prokaryotic 70S ribosome is sufficiently different from the eukaryotic 80S ribosome.

Which of the following accurately describe narrow-spectrum antimicrobials?

Their use causes less disruption to the normal microbiota. They affect a limited range of bacteria. Their use requires that the pathogen be identified and tested for susceptibility.

Consider the group of enzymes that catalyze the formation of peptide bridges between adjacent glycan strands, an essential step in the final stages of peptidoglycan synthesis. Why are these enzymes commonly called penicillin-binding proteins (PBPs)?

They bind penicillin and were initially discovered during experiments to study the effects of the medication.

There are a few antibacterial medications that interfere with cell membrane integrity. How do they lead to bacterial cell death?

They cause the cells to leak.

What characteristic of Mycoplasma species gives them intrinsic (innate) resistance to penicillin and other antimicrobials with the same target?

They lack a cell wall and are therefore resistant to drugs that interfere with peptidoglycan synthesis.

Why do antimicrobials that target the bacterial cell wall usually have a very high therapeutic index?

They target peptidoglycan synthesis, which is only found in bacteria, not eukaryotic cells, so they have low toxicity.

What best explains why the first-line drugs are generally given in combination of two or more to patients who have active tuberculosis, caused by Mycobacterium tuberculosis?

To reduce the chance that resistant mutants will develop.

True or false: When a streptomycin-sensitive strain is grown in streptomycin-free medium to a population of 109 cells, at least one cell in the population probably has the particular single base-pair mutation in the gene encoding a ribosomal protein that makes the cell streptomycin-resistant.

True

In terms of their antimicrobial action, drugs that kill bacteria are said to be .

bactericidal

Antimicrobials that are effective against a wide range of bacteria are known as - antimicrobials.

broad-spectrum

You have discovered a new antibiotic and determined that its chemical structure is very similar to that shown in the figure. This tells you that this antibiotic most likely targets ______.

cell wall (peptidoglycan) synthesis

Sulfonamides and related compounds, collectively referred to as sulfa drugs, interfere metabolically with the growth of many Gram-positive and Gram-negative bacteria. They accomplish this via inhibition of the pathway for folate biosynthesis.

competitive

The β-lactam antibiotics (e.g., penicillin) bind to a group of enzymes called penicillin-binding proteins (PBPs), preventing them from catalyzing the formation of peptide bridges between adjacent glycan strands. This binding is an example of inhibition.

competitive

What are four common mechanisms of acquired resistance to antimicrobial medications?

decreased uptake of the drug production of a drug-inactivating enzyme increased elimination of the drug alteration in the target molecule

All of the following are examples of mechanisms of acquired antimicrobial drug resistance EXCEPT ______.

development of a mutation in response to an antimicrobial

Penicillinase and chloramphenicol acetyltransferase are both examples of ______.

enzymes produced by bacteria that chemically modify a specific drug, interfering with its function

Among the most useful antibacterial medications that interfere with metabolic pathways are the biosynthesis inhibitors: sulfonamides and trimethoprim.

folate

A bactericidal drug is best described as a drug that ______.

kills bacteria

Some bacteria resist the effects of certain β-lactam antibiotics by synthesizing a β-, an enzyme that breaks the critical β-lactam ring, destroying the activity of the antibiotic.

lactamase

An advantage of the carbapenems is that they are resistant to most β-.

lactamases

In the context of antimicrobials, extended-spectrum β- (ESBLs) inactivate a wide variety of drugs, including both the penicillins and the cephalosporins.

lactamases or lactamase

Erythromycin and clarithromycin are _______ antibiotics that inhibit _______ synthesis.

macrolide; protein

Antimicrobials that affect a limited range of bacteria are - antimicrobials.

narrow-spectrum

You are studying an antimicrobial medication that has a structure similar to that shown in the figure. The presence of the β-lactam ring suggests to you that this antibiotic is likely most closely related to ______.

penicillin

All β-lactam antibiotics interfere with peptidoglycan synthesis by competitively inhibiting a group of enzymes that catalyze the formation of peptide bridges that cross-link adjacent glycan chains. These enzymes are commonly called - proteins.

penicillin-binding

An enzyme produced by some bacteria that destroys penicillin is .

penicillinase, beta lactamase, B-lactamase, or beta-lactamase

The proteins in the outer membrane of Gram-negative bacteria selectively allow small hydrophobic molecules to enter the periplasm. Changes in these proteins can therefore prevent certain drugs from entering.

porin or channel

Examples of acquired resistance include ______.

resistance resulting from horizontal gene transfer a spontaneous mutation resulting in resistance

The are antibiotics that block bacterial RNA polymerase from initiating transcription; rifampin is the most widely used example.

rifamycins

When treating Mycobacterium tuberculosis, second-line drugs may be used because they ______.

serve as an alternative when strains are resistant to the first-line drugs

When certain bacteria are said to have intrinsic (innate) resistance, this means they have ______.

some inherent property that makes them generally more resistant to the effect of some antimicrobials

Antibacterials that are structurally similar to para-aminobenzoic acid (PABA) and therefore competitively inhibit folic acid synthesis are the sulfonamides and related compounds, collectively referred to as drugs.

sulfa

Efflux pumps are ______.

systems that bacteria use to transport damaging compounds out of a cell

The macrolides prevent the continuation of translation by reversibly binding to ______.

the 50S ribosomal subunit

In the Kirby-Bauer disc diffusion test, what are factors that influence the size of a clearing zone of inhibition around a microbial disc?

the amount of the drug on the disc the stability of the drug the degree of susceptibility of the organism to the drug the molecular weight of the drug

Enzymes required for nucleic acid synthesis are the targets of some groups of antimicrobial drugs. Those that target topoisomerases in particular are ______.

the fluoroquinolones

Match each antibacterial medication with its appropriate mechanism of action. vancomycin fluoroquinolones daptomycin trimethoprim aminoglycosides

vancomycin vancomycin Drop zone cell wall (peptidoglycan) synthesis correct Toggle Button Unavailable. cell wall (peptidoglycan) synthesis fluoroquinolones fluoroquinolones Drop zone nucleic acid synthesis correct Toggle Button Unavailable. nucleic acid synthesis daptomycin daptomycin Drop zone cell membrane integrity correct Toggle Button Unavailable. cell membrane integrity trimethoprim trimethoprim Drop zone metabolic pathways (folate biosynthesis) correct Toggle Button Unavailable. metabolic pathways (folate biosynthesis) aminoglycosides aminoglycosides Drop zone protein synthesis correct Toggle Button Unavailable. protein synthesis

Beta-lactam antibiotics interfere with peptidoglycan synthesis. Based on this information, you can conclude the bacterial structure most likely targeted by these drugs is the cell .

wall

The range between the medication dose used therapeutically and the toxic dose is referred to as the therapeutic .

window

Consider the following classes of antibacterial medications. Match each each with its correct target. β-lactam drugs β-lactam drugs drop zone empty. rifamycins rifamycins drop zone empty. polymyxin B polymyxin B drop zone empty. sulfonamides sulfonamides drop zone empty. tetracyclines

β-lactam drugs β-lactam drugs Drop zone cell wall (peptidoglycan) synthesis correct Toggle Button Unavailable. cell wall (peptidoglycan) synthesis rifamycins rifamycins Drop zone nucleic acid synthesis correct Toggle Button Unavailable. nucleic acid synthesis polymyxin B polymyxin B Drop zone cell membrane integrity correct Toggle Button Unavailable. cell membrane integrity sulfonamides sulfonamides Drop zone metabolic pathways (folate biosynthesis) correct Toggle Button Unavailable. metabolic pathways (folate biosynthesis) tetracyclines tetracyclines Drop zone protein synthesis correct Toggle Button Unavailable. protein synthesis