Chapter 10 Flashcards
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
2
Q
use of a drug to prevent infection of a person at risk
A
prophylaxis
3
Q
the use of drugs to control infection
A
antimicrobial chemotherapy
4
Q
all-inclusive term for any antimicrobial drug, regardless of its origin
A
antimicrobials
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
6
Q
drugs that are chemically modified in the lab after being isolated from natural resources
A
semisynthetic drugs
7
Q
drugs produced entirely by chemical reactions
A
synthetic drugs
8
Q
narrow spectrum drugs
A
target specific microbes
9
Q
broad spectrum
A
target variety of microbes (gram pos and gram neg)
but can cause resistance
10
Q
antibiotics are originally metabolic products of _______ and _______
A
bacteria and fungi
11
Q
produced by microbes in order to reduce competition for nutrients and space in their habitat
A
antibiotics
12
Q
what bacteria genera and mold genera have the greatest number of antibiotics
A
Streptomyces and Bacillus
Penicillium and Cephalosporium
13
Q
before antimicrobial therapy begins, what three factors need to be considered?
A
- identity of microbe causing infection
- degree of the microbes susceptibility (sensitivity) to various drugs
- overall medical condition of the patient
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
15
Q
Kirby-Bauer technique
A
an agar diffusion test that provides useful data on antimicrobial susceptibility
- The surface of a plate of special medium is spread with test bacterium
- Small discs containing premeasured amounts of antimicrobial are dispensed onto the bacterial lawn
- After incubation the zone of inhibition surrounding the discs is measured and compared
16
Q
E-Test
A
provides additional information on drug effectiveness
17
Q
Zone of inhibition
A
roughly speaking, the larger the size of the zone, the greater the bacterium’s sensitivity to the drug
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)
19
Q
the smallest concentration (highest dilution) of a drug that visibly INHIBITS growth is called the
A
minimum inhibitory concentration (MIC)
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
21
Q
does a smaller therapeutic index indicate more of a risk or less?
A
MORE RISKY
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
23
Q
alcohol and cephalosporins have drug _____
A
interactions
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
25
drugs should kill or inhibit microbial cells without simultaneously damaging host tissues
selectively toxic
26
example of drugs with excellent selective toxicity
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
27
What are the five categories based on what metabolic targets antimicrobial drugs affect?
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
4. Inhibition of folic acid synthesis
28
Drugs that target the cell wall
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)
29
Drugs that target PROTEIN SYNTHESIS
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
30
Drugs that target FOLIC ACID SYNTHESIS
Sulfonamides
- interfere with folate metabolism by blocking enzymes required for synthesis of tetrahydrofolate
- Sulfamethoxazole, Silver sulfadiazine (burns, eye infections), Trimethoprim
31
Drugs that target DNA OR RNA
Fluoroquinolones
- inhibit DNA unwinding enzymes or helicases-> stopping DNA transcription
- Levofloxacin, Ciprofloxacin
Miscellaneous
-Rifampin
32
Drugs that target CYTOPLASMIC OR CELL MEMBRANES
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)
33
examples of gram neg bacteria
salmonellosis, plague, gonorrhea
34
List narrow spectrum penicillins
G (best drug choice when bacteria are sensitive; low cost; low toxicity)
V
Methicillin, nafcillin (poor absorption; growing resistance)
35
List broad spectrum penicillins
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
36
TRUE OR FALSE
| Biofilm inhabitants are often affected by the same antimicrobials that work against them when they are free living.
FALSE
| they are often unaffected by the same ones when they are in biofilms that would usually work when they are free living
37
Why can some antibiotics now work as well on biofilms?
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)
38
A lipopeptide that is effective in deep tissue infections with resistant bacteria
- has shown success in biofilm infection treatment
Daptomycin (Cubicin)
39
what is a risk because of the similarity between fungal and human cells?
often means that drugs toxic to fungal cells are also capable of harming human tissues
40
Macrolide polyenes
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
41
Azoles
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
42
Echinocandins
Agents used to treat fungal infections
Ex: Micafungin, caspofungin
- inhibit fungal cell wall synthesis
- used against Candida strains and aspergiollosis
43
Allylamines
Agents used to treat fungal infections
Ex: Terbinafine, naftifine
- inhibit enzyme critical for ergosterol synthesis
- used to treat ringworm and other cutaneous mycoses
44
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)
Quinine
45
malaria parasite
Plasmodium
46
why is no single drug universally effective for malaria?
because there are several species of plasmodium, and many stages in its life cycle
47
Artemisinin
a drug which originates from a plant called sweet wormwood; is a staple for malaria tx
48
Metronidazole (Flagyl)
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
49
Other drugs besides Metronidazole that antiprotozoal activities
Quinacrine (a quinine-based drug)
Sulfonamides
Tetracyclines
50
what do the most effective drugs against helminths do?
immobilize, disintegrate, or inhibit the metabolism in all stages of the life cycle
51
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
Albendazole
52
antihelminthic drug used to treat strongyloidiasis and onchocerciasis in humans
Ivermectin
53
antihelminthic drug used to treat various tapeworm and flukeworm infections
Praziquantel
54
What are the three major modes of action of agents that treat viral infection?
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
Enfuvirtide (Fuzeon)
Inhibition of virus entry
| -blocks HIV by preventing the binding of viral proteins to cell receptor, thereby preventing fusion of virus with cell
56
Amantadine (Symmetrel)
inhibition of virus entry
| -blocks entry of influenza by interfering with fusion of virus with cell membrane
57
Acyclovir, Ribavirin, Remdesivir, Nevirapine, etc.
inhibition of nucleic acid synthesis
58
Indinavir, Saquinavir, Zanamivir, Oseltamivir
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
10.3
| An adaptive response in which microorganisms begin to tolerate an amount of a drug that would normally be inhibitory
drug resistance
60
whether antibiotics are present or not, microbes become newly resistant to a drug after one of the following two events:
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
Potential third mechanism of acquiring drug resistance that is a phenotypic adaptation
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
additional option by fungi for antibiotic resistance
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
heritable change in gene expression that does not involve change in the gene itself but chemical additions to it
epimutation
64
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
Epigenetic
65
drug resistance that is found on chromosomes usually results from what
random mutations in bacterial populations
66
drug resistance occurring through horizontal transfer originates from
plasmids called resistance (R) factors that are transferred through conjugation, transformation, or transduction.
67
Mechanisms of drug resistance
How does new enzymes being synthesized and inactivating the drug occur?
occurs when new genes are acquired
68
Mechanisms of drug resistance
How does the permeability and uptake of a drug into the cell being decreased occur?
occurs via mutation
69
Mechanisms of drug resistance
How does the drug being immediately eliminated occur?
occurs through the acquisition of new genes
| many bacteria possess multidrug-resistant pumps that actively transport drugs out of cells
70
Mechanisms of drug resistance
How does the number of binding sites for drugs being decreased in affinity and/or number occur?
occurs via mutation or through acquisition of new genes
71
Mechanisms of drug resistance
How does an affected metabolic pathway being shut down or an alternative pathway being used occur?
occurs via mutation of original enzymes
72
Examples of Urgent Threat (hazard level) resistant bacteria
C. diff
Carbapenem-resistant Eterobacteriaceae
Drug-resistant Neisseria gonorrhea
73
Examples of Serious Threats (hazard level) drug resistant bacteria
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
Examples of Concerning Threats (hazard levels) of drug resistant bacteria
Vancomycin-resistant Staphylococcus aureus (VRSA)
Erythromycin-resistant Group A Streptococcus
Clindamycin-resistant Group B Streptococcus
75
In the US alone 23,000 deaths annually are attributed to
infection with resistant bacteria
76
mcr-1 gene
gene that makes bacteria resistant to colistin (polymyxin), which is considered a last-resort antibiotic treatment for bacteria that are multi-drug resistant
77
RNA interference
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
Host defense peptides
peptides of 20-50 amino acids secreted as part of the mammalian innate immune system
79
Defensins, magainins, protegrins
Host defense peptides
80
Fuzeon
a drug used in HIV infections that is a peptide that inhibits fusion of the virus to human cells
81
some bacteria produce similar peptides called
Bacteriocins and lantibiotics
82
SNAPP
artificially engineered peptide polymer that has shown promise in killing multiple types of bacteria that have become resistant to other drugs
83
CRISPR system
provides hope that science may be capable of overcoming antibiotic resistance.
-system found in bacteria that can cause very specific cuts in genes
84
Teixobactin
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
name a clear advantage of bacteriophage tx
its extreme specificity of the phages, only one species of bacterium in affected, leaving the normal inhabitants of the body alone.
86
nutrients used to stimulate the growth of favorable biota in the intestine
Prebiotics
87
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
Probiotics
88
is postbiotic diarrhea considered a drug toxicity, an allergic reaction, or neither?
Neither, it is a side effect caused by disruption of the gut microbiome and not a result of the drug harming human cells
89
fecal transplants
involves transfer of feces from a healthy patient via colonoscopy, establishing a rich microbiota in the intestines
90
Which medication could be used again gram-neg, gram-pos, and chlamydias, and rickettsias?
a. tobramycin
b. penicillin
c. tetracyclines
d. cephalosporins and sulfonamides
c. tetracyclines
91
10.4
| Three categories of major side effects of drugs
1. Direct damage to tissues through toxicity
2. Allergic reactions
3. Disruption in the balance of normal microbial biota
92
It is estimated that at least _% of all persons taking an antimicrobial drug experience some type of adverse effect.
5%
93
Drugs most adversely affect what organs?
```
Liver (hepatoxic)
Kidneys (nephrotoxic)
Gastrointestinal tract
Cardiovascular system and blood-forming tissue (hemotoxic)
Nervous system (neurotoxic)
Respiratory tract
Skin
Bones
Teeth
```
94
adverse reactions
Penicillin G
Rash, hives, watery eyes
95
adverse reactions
Carbenicillin
Abnormal bleeding
96
adverse reactions
Ampicillin
diarrhea and enterocolitis
97
Adverse reactions
Cephalosporins
inhibition of platelet fx
decreased circulation of WBC
nephritis
98
Adverse reactions
Sulfonamides
formation of crystals in kidney; blockage of urine flow
hemolysis
reduction in number of red blood cells
99
Adverse reactions
Polymyxin (Colistin)
kidney damage
weakened muscular responses
100
Adverse reactions
Quinolones (norfloxacin, ciprofloxacin)
headache, dizziness, tremors, GI distress
101
Adverse reactions
Rifampin
damage to hepatic cells
dermatitis
102
Adverse reactions (antifungals)
Amphotericin B
altered kidney function
103
Adverse reactions (antifungals)
Flucytosine
decreased number of white blood cells
104
Adverse reactions (antiprotozoal drugs)
Metronidazole
nausea, vomiting
105
Adverse reactions (antihelminthics)
Pyrantel
intestinal irritation
headache, dizziness
106
Adverse reactions (antivirals)
Acyclovir
seizures, confusion
| rash
107
Adverse reactions (antivirals)
Amantadine
nervousness, light-headedness
nausea
108
Adverse reactions (antivirals)
AZT
immunosuppression, anemia
109
the altered, usually exaggerated, immune response to an allergen. Also called hypersensitivity
allergy
110
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
allergy
111
what drug accounts for the greatest number of allergic reactions
penicillins
112
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
allergy
113
beneficial or harmless resident bacteria found on and/or in the human body
biota/microbiota
114
an infection occurring during antimicrobial therapy that is caused by an overgrowth of drug-resistant bacteria
superinfection
115
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
Clostridius difficile
116
drugs that prevent the formation of bacterial cell walls are
a. quinolones
b. penicillins
c. tetracyclines
d. aminoglycosides
b. penicillins
117
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
b. antibiotic
118
R factors are ______ that contain a code for ________
plasmids
| drug resistance
119
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
d. all the above are true
120
an antimicrobial drug with a _______ therapeutic index is better than one with a _______ therapeutic index.
high / low
