Chapter 10 Flashcards

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1
Q

Characteristics of ideal antimicrobial drugs

A
  • toxic to microbe but not host
  • microbicidal
  • does not lead to resistance
  • readily delivered to site of infection
  • remains potent long enough/not broken down/excreted prematurely
  • remains active in tissues and body fluids
  • does not disrupt host’s health by causing allergies and superinfection
  • relatively soluble
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2
Q

use of a drug to prevent infection of a person at risk

A

prophylaxis

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3
Q

the use of drugs to control infection

A

antimicrobial chemotherapy

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4
Q

all-inclusive term for any antimicrobial drug, regardless of its origin

A

antimicrobials

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5
Q

substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms; generally the term is used for drugs targeting bacteria and not other types of microbes

A

antibiotics

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6
Q

drugs that are chemically modified in the lab after being isolated from natural resources

A

semisynthetic drugs

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7
Q

drugs produced entirely by chemical reactions

A

synthetic drugs

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8
Q

narrow spectrum drugs

A

target specific microbes

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9
Q

broad spectrum

A

target variety of microbes (gram pos and gram neg)

but can cause resistance

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10
Q

antibiotics are originally metabolic products of _______ and _______

A

bacteria and fungi

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11
Q

produced by microbes in order to reduce competition for nutrients and space in their habitat

A

antibiotics

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12
Q

what bacteria genera and mold genera have the greatest number of antibiotics

A

Streptomyces and Bacillus

Penicillium and Cephalosporium

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13
Q

before antimicrobial therapy begins, what three factors need to be considered?

A
  1. identity of microbe causing infection
  2. degree of the microbes susceptibility (sensitivity) to various drugs
  3. overall medical condition of the patient
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14
Q

drug sensitivity testing

A

involve exposing a pure culture of the microbe to several different drugs and observing the effects of the drug on growth

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15
Q

Kirby-Bauer technique

A

an agar diffusion test that provides useful data on antimicrobial susceptibility

  1. The surface of a plate of special medium is spread with test bacterium
  2. Small discs containing premeasured amounts of antimicrobial are dispensed onto the bacterial lawn
  3. After incubation the zone of inhibition surrounding the discs is measured and compared
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16
Q

E-Test

A

provides additional information on drug effectiveness

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17
Q

Zone of inhibition

A

roughly speaking, the larger the size of the zone, the greater the bacterium’s sensitivity to the drug

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18
Q

Tube dilution tests

A

the antimicrobial is diluted serially in tubes of broth

each tube is then inoculated with a small uniform sample of pure culture, incubated, and then examined for growth (turbidity)

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19
Q

the smallest concentration (highest dilution) of a drug that visibly INHIBITS growth is called the

A

minimum inhibitory concentration (MIC)

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20
Q

defined as a ration of the dose of the drug that is toxic to humans compared to its minimum effective (therapeutic) dose.

A

therapeutic index

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21
Q

does a smaller therapeutic index indicate more of a risk or less?

A

MORE RISKY

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22
Q

what should the physician consider before prescribing antimicrobials?

A
  • preexisting medical conditions
  • allergies
  • underlying liver/kidney disease (depends where the drug is metabolized/excreted)
  • infants, elderly, (gastro /organ absorption) and pregnant women (placental barrier) require special precautions
  • other drugs currently taking
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23
Q

alcohol and cephalosporins have drug _____

A

interactions

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24
Q

what are the goals of antimicrobial drugs

A

disrupt cell processes, disrupt structures of bacteria, fungi, and protozoa, or to inhibit virus replication

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25
Q

drugs should kill or inhibit microbial cells without simultaneously damaging host tissues

A

selectively toxic

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26
Q

example of drugs with excellent selective toxicity

A

those that block the synthesis of the cell wall in bacteria e.g. penicillins

-they have low toxicity and few direct effects on human cells b/c human cells lack the chemical peptidoglycan

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27
Q

What are the five categories based on what metabolic targets antimicrobial drugs affect?

A
  1. Inhibition of cell wall synthesis
  2. Inhibition of nucleic acid (RNA and DNA) structure and fx
  3. Inhibition of the ribosome in protein synthesis
  4. Interference with cytoplasmic membrane structure or fx
  5. Inhibition of folic acid synthesis
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28
Q

Drugs that target the cell wall

A

Penicillins
-natural form used to treat gram-pos cocci, some gram-neg bacteria (meningococci, syphilis, spirochetes)

Cephalosporins

  • Cefazolin
  • Cefaclor
  • Cephalexin

Carbapenems

  • Aztreonam (narrow-spectrum)
  • Doripenem
  • Imipenem

Miscellaneous (Vancomycin, Bacitracin, Isoniazid(tuberculosis), Fosfomycin tromethamine)

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29
Q

Drugs that target PROTEIN SYNTHESIS

A

Aminoglycosides
-Streptomycin (broad spectrum-gram neg rods, gram pos, bubonic plague, tuberculosis)

Tetracyclines

  • block the attachment of tRNA on the A acceptor site and stop further protein synthesis
  • tetracycline

Glyclycyclines

  • Tigecycline
  • effective against bacteria that have become resistant to Tetracyclines

Macrolides

  • inhibit translocation of the subunit during translation (erythromycin)
  • azithromycin, clarithromycin
  • relatively broad spectrum, semisynthetic, AIDS treatment

Miscellaneous

  • Linezolid
  • Quinupristin + dalfopristin
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30
Q

Drugs that target FOLIC ACID SYNTHESIS

A

Sulfonamides

  • interfere with folate metabolism by blocking enzymes required for synthesis of tetrahydrofolate
  • Sulfamethoxazole, Silver sulfadiazine (burns, eye infections), Trimethoprim
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31
Q

Drugs that target DNA OR RNA

A

Fluoroquinolones

  • inhibit DNA unwinding enzymes or helicases-> stopping DNA transcription
  • Levofloxacin, Ciprofloxacin

Miscellaneous
-Rifampin

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32
Q

Drugs that target CYTOPLASMIC OR CELL MEMBRANES

A

Polymyxins (colistins)

  • interact with membrane phospholipids distort cell surface and cause leakage of protein and nitrogen bases
  • Polymyxin B
  • Daptomycin (most active against gram-pos bacteria)
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33
Q

examples of gram neg bacteria

A

salmonellosis, plague, gonorrhea

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34
Q

List narrow spectrum penicillins

A

G (best drug choice when bacteria are sensitive; low cost; low toxicity)
V
Methicillin, nafcillin (poor absorption; growing resistance)

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35
Q

List broad spectrum penicillins

A

Ampicillin - work on gram-neg bacilli

Amoxicillin - work on gram-neg infections; good absorption

VERY BROAD:
Azlocillin, Mezlocillin, Ticarcillin - effective against Pseudomonas species; low toxicity compared with aminoglycosides

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36
Q

TRUE OR FALSE

Biofilm inhabitants are often affected by the same antimicrobials that work against them when they are free living.

A

FALSE

they are often unaffected by the same ones when they are in biofilms that would usually work when they are free living

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37
Q

Why can some antibiotics now work as well on biofilms?

A

cannot easily penetrate the sticky extracellular material surrounding biofilm

*b/c of the different phenotype expressed by biofilm bacteria (different genes are expressed and therefore there are different antibiotic susceptibility profiles than if the microbes were free living)

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38
Q

A lipopeptide that is effective in deep tissue infections with resistant bacteria
- has shown success in biofilm infection treatment

A

Daptomycin (Cubicin)

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39
Q

what is a risk because of the similarity between fungal and human cells?

A

often means that drugs toxic to fungal cells are also capable of harming human tissues

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40
Q

Macrolide polyenes

A

Agents used to treat fungal infections
ex: Amphotericin B

  • bind to fungal membranes, causing loss of selective permeability
  • can be used to treat skin, mucous, membrane lesions caused by Candida albicans
  • injectable form of drug can be used to treat histoplasmosis and Cryptococcus meningitis
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41
Q

Azoles

A

Agents used to treat fungal infections
Ex: Ketoconazole. Fluconazole, Clotrimazole, Miconazole

  • interferes with sterol synthesis in fungi
  • Ketoconazole -> cutaneous mycoses, vaginal and oral candidiasis, systemic mycoses
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42
Q

Echinocandins

A

Agents used to treat fungal infections
Ex: Micafungin, caspofungin

  • inhibit fungal cell wall synthesis
  • used against Candida strains and aspergiollosis
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43
Q

Allylamines

A

Agents used to treat fungal infections
Ex: Terbinafine, naftifine

  • inhibit enzyme critical for ergosterol synthesis
  • used to treat ringworm and other cutaneous mycoses
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44
Q

principal tx for malaria for hundreds of years; extracted from the bark of the cinchona tree

-has since been replaced by synthesized quinolones (less toxicity)

A

Quinine

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45
Q

malaria parasite

A

Plasmodium

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46
Q

why is no single drug universally effective for malaria?

A

because there are several species of plasmodium, and many stages in its life cycle

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47
Q

Artemisinin

A

a drug which originates from a plant called sweet wormwood; is a staple for malaria tx

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48
Q

Metronidazole (Flagyl)

A

anti-protozoal drug
;effective in treating severe intestinal infections and hepatic disease caused by Entamoeba histolytica

;orally it can treat Giardia lamblia and Trichomonas vaginalis

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49
Q

Other drugs besides Metronidazole that antiprotozoal activities

A

Quinacrine (a quinine-based drug)

Sulfonamides

Tetracyclines

50
Q

what do the most effective drugs against helminths do?

A

immobilize, disintegrate, or inhibit the metabolism in all stages of the life cycle

51
Q

broad spectrum antiparasitic drug used for several types of roundworm infestations; works in intestines to inhibit the fx of the microtubules or worms, eggs, and larvae = parasite can no longer utilize glucose = death

A

Albendazole

52
Q

antihelminthic drug used to treat strongyloidiasis and onchocerciasis in humans

A

Ivermectin

53
Q

antihelminthic drug used to treat various tapeworm and flukeworm infections

A

Praziquantel

54
Q

What are the three major modes of action of agents that treat viral infection?

A
  1. Barring penetration of the virus into the host cell
  2. Blocking the transcription and translation of viral molecules
  3. Preventing the maturation of viral particles
55
Q

Enfuvirtide (Fuzeon)

A

Inhibition of virus entry

-blocks HIV by preventing the binding of viral proteins to cell receptor, thereby preventing fusion of virus with cell

56
Q

Amantadine (Symmetrel)

A

inhibition of virus entry

-blocks entry of influenza by interfering with fusion of virus with cell membrane

57
Q

Acyclovir, Ribavirin, Remdesivir, Nevirapine, etc.

A

inhibition of nucleic acid synthesis

58
Q

Indinavir, Saquinavir, Zanamivir, Oseltamivir

A

inhibition of viral assembly and release

  • stop action of virus and result in inactive/noninfectious viruses
  • block exit of influenza viruses from host cells
59
Q

10.3

An adaptive response in which microorganisms begin to tolerate an amount of a drug that would normally be inhibitory

A

drug resistance

60
Q

whether antibiotics are present or not, microbes become newly resistant to a drug after one of the following two events:

A
  1. Spontaneous mutation in critical chromosomal genes
    or
  2. Acquisition of entire new genes or sets of genes via horizontal transfer from another species
61
Q

Potential third mechanism of acquiring drug resistance that is a phenotypic adaptation

A

recent studies suggest that bacteria can “go to sleep” when exposed to antibiotics, meaning they will slow or stop their metabolism so that they cannot be harmed by the antibiotic
-> and they can then rev back up after the antibiotic concentration decreases

sometimes these bacteria are called “persisters”

62
Q

additional option by fungi for antibiotic resistance

A

a small regulatory RNA called interfering RNA (RNAi), has been found to temporarily bind to a genetic sequence which silences the gene and the target of the antibiotic resistance is not manufactured by the fungus, thus allowing it to temporarily resist the drug

-> the fungus can later express the gene when the antibiotic is no longer present

63
Q

heritable change in gene expression that does not involve change in the gene itself but chemical additions to it

A

epimutation

64
Q

refers to “above the gene”, specifically additions to the DNA that do not change the gene but can change its expression

ie. reversible mechanism that fungus undergo r/t drug resistance

A

Epigenetic

65
Q

drug resistance that is found on chromosomes usually results from what

A

random mutations in bacterial populations

66
Q

drug resistance occurring through horizontal transfer originates from

A

plasmids called resistance (R) factors that are transferred through conjugation, transformation, or transduction.

67
Q

Mechanisms of drug resistance

How does new enzymes being synthesized and inactivating the drug occur?

A

occurs when new genes are acquired

68
Q

Mechanisms of drug resistance

How does the permeability and uptake of a drug into the cell being decreased occur?

A

occurs via mutation

69
Q

Mechanisms of drug resistance

How does the drug being immediately eliminated occur?

A

occurs through the acquisition of new genes

many bacteria possess multidrug-resistant pumps that actively transport drugs out of cells

70
Q

Mechanisms of drug resistance

How does the number of binding sites for drugs being decreased in affinity and/or number occur?

A

occurs via mutation or through acquisition of new genes

71
Q

Mechanisms of drug resistance

How does an affected metabolic pathway being shut down or an alternative pathway being used occur?

A

occurs via mutation of original enzymes

72
Q

Examples of Urgent Threat (hazard level) resistant bacteria

A

C. diff
Carbapenem-resistant Eterobacteriaceae
Drug-resistant Neisseria gonorrhea

73
Q

Examples of Serious Threats (hazard level) drug resistant bacteria

A

Multidrug-resistant Acinetobacter
Drug-resistant Campylobacter
Fluconazole-resistant Candida (a fungus)

Extended spectrum Beta-lactamase-producing Enterobacteriaceae

Vancomycin-resistant Enterococcus
Multidrug-resistant Pseudomonas aeruginosa
Drug-resistant non-typhoidal Salmonella
Drug-resistant Salmonella typhi
Drug-resistant Shigella
Methicillin-resistant Staphylococcus aureus (MRSA)
Drug-resistant Streptococcus pneumoniae
Drug-resistant tuberculosis
74
Q

Examples of Concerning Threats (hazard levels) of drug resistant bacteria

A

Vancomycin-resistant Staphylococcus aureus (VRSA)
Erythromycin-resistant Group A Streptococcus
Clindamycin-resistant Group B Streptococcus

75
Q

In the US alone 23,000 deaths annually are attributed to

A

infection with resistant bacteria

76
Q

mcr-1 gene

A

gene that makes bacteria resistant to colistin (polymyxin), which is considered a last-resort antibiotic treatment for bacteria that are multi-drug resistant

77
Q

RNA interference

A

refers to small pieces of RNA that regulate the expression of genes

*being exploited in attempt to the shut down the metabolism of pathogenic microbes

78
Q

Host defense peptides

A

peptides of 20-50 amino acids secreted as part of the mammalian innate immune system

79
Q

Defensins, magainins, protegrins

A

Host defense peptides

80
Q

Fuzeon

A

a drug used in HIV infections that is a peptide that inhibits fusion of the virus to human cells

81
Q

some bacteria produce similar peptides called

A

Bacteriocins and lantibiotics

82
Q

SNAPP

A

artificially engineered peptide polymer that has shown promise in killing multiple types of bacteria that have become resistant to other drugs

83
Q

CRISPR system

A

provides hope that science may be capable of overcoming antibiotic resistance.

-system found in bacteria that can cause very specific cuts in genes

84
Q

Teixobactin

A

antibiotic that inhibits cell wall synthesis using a unique mechanism, and MOST STRIKINGLY: bacteria seem unable to or at least are very slow to develop resistant to the drug

85
Q

name a clear advantage of bacteriophage tx

A

its extreme specificity of the phages, only one species of bacterium in affected, leaving the normal inhabitants of the body alone.

86
Q

nutrients used to stimulate the growth of favorable biota in the intestine

A

Prebiotics

87
Q

Preparations of live microbes used as preventative or therapeutic measure to displace or compete with potential pathogens

;fed to animals and humans to improve intestinal biota

A

Probiotics

88
Q

is postbiotic diarrhea considered a drug toxicity, an allergic reaction, or neither?

A

Neither, it is a side effect caused by disruption of the gut microbiome and not a result of the drug harming human cells

89
Q

fecal transplants

A

involves transfer of feces from a healthy patient via colonoscopy, establishing a rich microbiota in the intestines

90
Q

Which medication could be used again gram-neg, gram-pos, and chlamydias, and rickettsias?

a. tobramycin
b. penicillin
c. tetracyclines
d. cephalosporins and sulfonamides

A

c. tetracyclines

91
Q

10.4

Three categories of major side effects of drugs

A
  1. Direct damage to tissues through toxicity
  2. Allergic reactions
  3. Disruption in the balance of normal microbial biota
92
Q

It is estimated that at least _% of all persons taking an antimicrobial drug experience some type of adverse effect.

A

5%

93
Q

Drugs most adversely affect what organs?

A
Liver (hepatoxic)
Kidneys (nephrotoxic)
Gastrointestinal tract
Cardiovascular system and blood-forming tissue (hemotoxic)
Nervous system (neurotoxic)
Respiratory tract
Skin
Bones
Teeth
94
Q

adverse reactions

Penicillin G

A

Rash, hives, watery eyes

95
Q

adverse reactions

Carbenicillin

A

Abnormal bleeding

96
Q

adverse reactions

Ampicillin

A

diarrhea and enterocolitis

97
Q

Adverse reactions

Cephalosporins

A

inhibition of platelet fx
decreased circulation of WBC
nephritis

98
Q

Adverse reactions

Sulfonamides

A

formation of crystals in kidney; blockage of urine flow

hemolysis

reduction in number of red blood cells

99
Q

Adverse reactions

Polymyxin (Colistin)

A

kidney damage

weakened muscular responses

100
Q

Adverse reactions

Quinolones (norfloxacin, ciprofloxacin)

A

headache, dizziness, tremors, GI distress

101
Q

Adverse reactions

Rifampin

A

damage to hepatic cells

dermatitis

102
Q

Adverse reactions (antifungals)

Amphotericin B

A

altered kidney function

103
Q

Adverse reactions (antifungals)

Flucytosine

A

decreased number of white blood cells

104
Q

Adverse reactions (antiprotozoal drugs)

Metronidazole

A

nausea, vomiting

105
Q

Adverse reactions (antihelminthics)

Pyrantel

A

intestinal irritation

headache, dizziness

106
Q

Adverse reactions (antivirals)

Acyclovir

A

seizures, confusion

rash

107
Q

Adverse reactions (antivirals)

Amantadine

A

nervousness, light-headedness

nausea

108
Q

Adverse reactions (antivirals)

AZT

A

immunosuppression, anemia

109
Q

the altered, usually exaggerated, immune response to an allergen. Also called hypersensitivity

A

allergy

110
Q

this reaction occurs b/c the drug acts as an antigen (a foreign material capable of stimulating the immune system) and stimulates an allergic response

A

allergy

111
Q

what drug accounts for the greatest number of allergic reactions

A

penicillins

112
Q

provoked by an intact drug molecule, or by substances that develop from the body’s metabolic alteration of the drug.

ex: in the case of penicillin, it is not the penicillin molecule itself that causes the reaction, but a product called benzylpenicilloyl

A

allergy

113
Q

beneficial or harmless resident bacteria found on and/or in the human body

A

biota/microbiota

114
Q

an infection occurring during antimicrobial therapy that is caused by an overgrowth of drug-resistant bacteria

A

superinfection

115
Q

oral therapy with some antimicrobials is associated with a serious and potentially fatal condition known as antibiotic-associated colitis, this is caused by an overgrowth of the endospore-forming bacterium

A

Clostridius difficile

116
Q

drugs that prevent the formation of bacterial cell walls are

a. quinolones
b. penicillins
c. tetracyclines
d. aminoglycosides

A

b. penicillins

117
Q

a compound synthesized by bacteria or fungi that destroys or inhibits the growth of other microbes is

a. synthetic drug
b. antibiotic
c. interferon
d. competitive inhibitor

A

b. antibiotic

118
Q

R factors are ______ that contain a code for ________

A

plasmids

drug resistance

119
Q

treating malarial infections is theoretically difficult b/c

a. the protozoal parasite is eukaryotic and therefore similar to human cells.
b. there are several species of Plasmodium
c. no single drug can target all life stages of Plasmodium
d. all the above are true

A

d. all the above are true

120
Q

an antimicrobial drug with a _______ therapeutic index is better than one with a _______ therapeutic index.

A

high / low