Term
| Selective Toxicity is achieved by using drugs that are directed against targets which are: |
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Definition
Present in pathologic cells, but not in host cells
Similar, but not identical, in pathologic cells and host cells
Shared by pathologic and host cells, but differ in importance in the two |
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Term
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Definition
| inhibit pathologic cell growth while having a limited impact on host cells |
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Term
| Minimum Inhibitory Concentration (MIC) |
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Definition
| lowest drug concentration that inhibits microbial growth after an 18-24 hour incubation in vitro. |
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Term
| Minimum Bactericidal Concentration (MBC) |
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Definition
| lowest drug concentration at which 99.9% of microbes are killed after an 18-24 hour incubation in vitro. |
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Term
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Definition
MBC is much greater than its MIC
require host defense mechanisms to eradicate the infection after they have halted growth of the pathogen |
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Term
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Definition
MBC is close to its MIC
can eradicate infections in hosts that are immunocompromised
Usually bactericidal drugs require pathogens to be actively growing to exert their killing effect, so mixing a bacteriostatic and bacteriocidal drug often leads to a bacteriostatic effect |
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Term
| Concentration Dependent Killing |
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Definition
- Some bactericidal drugs, such as aminoglycosides and fluoroquinolones
-Maximizing the peak drug levels of these drugs enhances their killing effect
-exhibit a post-antibiotic effect |
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Term
| post-antibiotic effect (PAE) |
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Definition
| pathogen growth is inhibited even after the drug concentration drops below the MBC; as a result, these drugs can be given infrequently (once-a-day) and still be effective |
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Term
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Definition
-Some bactericidal drugs
-the effectiveness of the drug is dependent only on the amount of time that the drug is present above its MBC.
- These drugs may or may not have a PAE.
- Examples include the beta-lactams, vancomycin, isoniazid, pyrazinamide, and rifampin |
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Term
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Definition
- Reflects an absence or inaccessibility of the drug target
- Responsible for the resistance of bacteria to anti-fungal drugs, most bacteria to isoniazid, gram-negatives to penicillin G, and fungi to rifampin
- The outer membrane of gram negatives acts as a permeability barrier which confers innate resistance to many drugs |
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Term
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Definition
Arises spontaneously
- Does not require prior exposure to the drug
- Anti-microbial drugs inhibit the growth of susceptible bacteria and select for the growth of the pre-existing resistant bacteria; selection like this also takes place in cancer cell populations |
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Term
| Acquisition of Drug Resistance can occur by: |
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Definition
- Spontaneous mutation of the bacterial chromosome; examples include methicillin-resistant Staph aureus (MRSA), penicillin-resistant Strep pneumoniae (PRSP), and drug resistant TB; chromosomal mutations in different genes are acquired independently of each other
- Transfer of mutant genes among plasmids and bacteria (through transduction, transformation, and conjugation); drug resistance is transferred from plasmid to plasmid by transposons and from bacterium to bacterium by plasmids; often plasmids carry multiple drug resistance genes |
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Term
| Methods to reduce Incidence of Antibacterial Drug Resistance include: |
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Definition
- Use of antibacterials only in appropriate settings and the use of narrow spectrum drugs instead of broad spectrum drugs
- Limiting use of antibiotics in livestock feed
- Availability of antibiotics by prescription only
- Use of drug combinations against certain pathogens like HIV and TB
- Discovery of new drugs that target known resistance mechanisms and/or have novel molecular targets |
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Term
| Empirical therapy is used when? |
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Definition
| when delaying treatment risks serious morbidity or poses a danger to public health |
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Term
| Steps to Administering Empirical Antibiotic Therapy |
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Definition
1) Make clinical diagnosis of infection
2) Make a presumptive bacteriological diagnosis, considering both the site of infection and the patient’s immune status
3) Acquire samples for the lab before starting therapy
4) Choose drugs that cover the most likely organisms
5) Alter the drug therapy once a definitive microbiological diagnosis is made |
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Term
| Prophylactic Antibacterial Therapy |
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Definition
- Use of antibiotics to prevent colonization by an infectious organism or to prevent disease after colonization has occurred
- Most likely to be effective if it is used to prevent infection by a single organism
- Should be limited in duration, employ therapeutic drug levels, and should only be used where efficacy has been documented
- Commonly used in preventing infection in close contacts of patients with TB, meningococcal disease, or gonorrhea, recurrences of rheumatic fever, and some cases of CMV, HSV, and HIV; also may be useful in preventing endocarditis in high risk patients who undergo dental procedures |
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Term
| Which drugs exhibit concentration dependent killing? |
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Definition
| Aminoglycosides & fluoroquinolones |
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Term
| anti-cancer drugs' method of action is what? |
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Definition
-inhibit processes such as DNA synthesis, mitosis, & cell cycle progression which are shared by normal and neoplastic cells
-very toxic
-have low therapeutic indices |
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Term
| Anti-cancer drugs are especially toxic to what? |
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Definition
| The GI tract, bone marrow, and hair follicles |
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Term
| Anti-cancer drugs have a high or low therapeudic index? |
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Definition
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Term
| For any drug, do MIC and MBC vary from pathogen to pathogen? |
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Definition
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Term
Drugs that do not (or have very little) effects on host cells have a high or low therapeutic index?
(eg: B-lactams that inhibit bacterial cell wall synthesis) |
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Definition
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Term
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Definition
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Term
| A drug with MBC close to MIC |
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Definition
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Term
| This type of drugs requires host immune response to eradicate infection after the drug has halted growth of the pathogen |
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Definition
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Term
| This type of drug is useful in immunocompromised hosts |
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Definition
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Term
| This type of drug usually requires pathogens be actively growing to exert killing effect |
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Definition
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Term
| bacteriostatic + bactericidal drugs used together = what type of response? |
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Definition
| bacteriostatic, because the bactericidal drugs require that the pathogen be growing to exert their killing effect |
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Term
| How is the killing effect maximized for concentration-dependent drugs? |
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Definition
| Maximizing the peak drug levels |
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Term
| Drugs that can be given infrequently (ie, once a day) may exhibit this |
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Definition
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Term
| Most drugs exhibit what type of killing (time or concentration dependent)? |
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Definition
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Term
| Time dependent killing drugs' efficacy is dependent on ? |
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Definition
| the amount of time the drug is present above its MBC |
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Term
| Examples of time-dependent killing drugs |
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Definition
B-lactams
vancomycin
isoniazid
pyrazinamide
rifampin |
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Term
| Pathogen resistance can be either: |
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Definition
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Term
| This type of resistance reflects an absence or inaccessibility of the drug target |
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Definition
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Term
| This type of resistance is responsible for the resistance of bacteria to anti-fungal drugs, most bacteria to isoniazid, gram-negatives to penicillin G, and fungi to rifampin |
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Definition
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Term
| The outer membrane of Gram negatives acts as a permeability barrier to confer this type of resistance to many drugs |
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Definition
| innate resistance (because drug target is not accessible) |
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Term
| This type of resistance arises spontaneously |
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Definition
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Term
| Is prior exposure to a drug required for acquired resistance to be present? |
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Definition
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Term
| MRSA resistance arose from ? |
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Definition
| spontaneous mutation of the bacterial chromosome |
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Term
| PRSP resistance arose by ? |
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Definition
| spontaneous mutation of the bacterial chromosome |
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Term
| drug-resistance TB arose by ? |
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Definition
| spontaneous mutation of the bacterial chromosome |
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Term
True or False:
Chromosomal mutations in different genes are acquired independently of each other. |
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Definition
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Term
| Mutant genes are spread between bacteria and plasmids via: |
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Definition
| transduction, transformation, and conjugation |
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Term
| plasmid-plasmid and bacterium-bacterium drug resistance is transfered by ? |
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Definition
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Term
| Do plasmids carry multiple drug resistance genes? |
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Definition
Yes, they can.
Therefore, selection of an organism that is multi-drug resistant can occur by using only one anti-microbial, if resistance is plasmid-based. |
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Term
| Prophylactic antibiotic therapy is most effective: |
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Definition
| to prevent infection by a single organism |
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Term
| Prophylactic antibacterial therapy is commonly used for those in close contact of patients with: |
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Definition
TB, meningococcal disease, gonorrhea, recurrences of rheumatic fever, CMV, HSV, HIV
may also be useful in preventing endocarditis in high-risk patients who undergo dental procedures |
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