Microbiology - Chapter 10 - antimicrobial treatment

Some bacteria produce similar peptides. What are they called?

Bacteriocins and Iantibiotics

What causes drug resistnace?

Because of the genetic versatility and adaptability of microbial populations

How do allergies occur?

Because the drug acts as an antigen (a foreign material capable of stimulating the immune system) and stimulates an allergic response

Once therapy has begun, it is important to observe the patient's clinical response. Why?

Because the in vitro activity of the drug is not always correlated with its in vivo effect

What are the uses of Penicillin G?

Best drug of choice when bacteria are sensitive; low cost; low toxicity

What action to macrolide polyene antibiotics take?

Bind to fungal membranes, causing loss of selective permeability; extremely versatile Can be used to treat skin, mucous membrane lesions caused by Candida albicans Injectable form of the drug can be used to treat histoplasmosis and Cryptococcus meningitis

What is the spectrum of action of Amoxicillin?

Broad

What is the spectrum of action of Ampicillin?

Broad

What is one of the most useful ways of categorizing antimicrobials?

Broad-spectrum Narrow-spectrum

Subgroups of Fluoroquinolones

Ciprofloxacin, ofloxacin Levofloxacin

Other miscellaneous drugs that target protein synthesis

Clindamycin Quinupristin + dalfopristin (Synercid) Linezolid

******Which bacteria pose an *urgent threat*?

Clostridium difficile (C. diff) Carbapenem-resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae

What are fecal transplants used to treat?

Clostridium difficile infection and ulcerative colitis

The CDC has categorized resistant bacteria into three groups, termed "hazard levels." What are they?

Concerning Serious Urgent

What viral diseases that cannot be prevented highlights the need for more effective medications that control viral infections?

Epidemics of AIDS influenza even the "commonness" of the common cold

Subgroups of Macrolides

Erythromycin, clarithromycin, azithromycin

What are the challenges of antihelminthic drug therapy?

Flukes, tapeworms, and roundworms are much larger parasites than other microorganisms and, being animals, *have greater similarities to human physiology* The usual strategy of using drugs to block their reproduction is usually not successful in eradicating the adult worms

*List the drugs that target DNA or RNA*

Fluoroquinolones Other miscellaneous drugs that target DNA or RNA

What are the uses of Penicillin V?

Good absorption from intestine; otherwise, similar to Penicillin G

What are the uses of Amoxicillin?

Gram-negative infections; good absorption

What other diseases is metronidazole used for when given orally?

Has applications for infections by Giardia lamblia and Trichomonas vaginali

Why chloroquine and primaquine?

Have less toxicity to humans

What are the disadvantages of Amoxicillin?

Hydrolysis by penicillinase; allergies

What are the disadvantages of Penicillin V?

Hydrolysis by penicillinase; allergies

Which viral infections are regularly treated?

Infections with HIV, hepatitis B and C, and herpesviruse Influenza drugs are available but are not highly effective

What is the challenge in chemotherapeutic treatment of viruses?

Infectious agent relies on a host cell for the vast majority of its metabolic functions Disrupting viral metabolism requires disruption of cellular metabolism of host *selective toxicity with regard to viral infection is difficult to achieve because a single metabolic system is responsible for the well-being of both virus and host*

What action do allylamines take?

Inhibit enzyme critical for ergosterol synthesis Used to treat ringworm and other cutaneous mycoses

What action do exhinocandins take?

Inhibit fungal cell wall synthesis Used against Candida strains and aspergillosis

How are tube dilution tests performed?

1. First the antimicrobial is diluted serially in tubes of broth 2. Then each tube is inoculated with a small uniform sample of pure culture, incubated, and examined for growth (turbidity)

What are the steps towards the goal of chemotherapy

1. Identify the structural and metabolic needs of a living cell 2. Once those are identified: Methods of removing, disrupting, or interfering with these requirements can be used as potential antimicrobial strategies.

What are some common examples demonstrate how a disturbance in microbial biota leads to replacement biota and superinfection?

A broad-spectrum cephalosporin used to treat a urinary tract infection by Escherichia coli This will cure the infection, but it will also destroy the lactobacilli in the vagina that normally maintain a protective acidic environment there The drug has no effect, however, on Candida albicans, a yeast that also resides in normal vaginas Released from the inhibitory environment provided by lactobacilli, the yeasts proliferate and cause symptoms Candida can cause similar superinfections of the oropharynx (thrush) and the large intestine

What is fuzeon?

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

What is MCR-1?

A gene that has been found in bacteria Makes the bacteria resistant to colistin/polymyxin which is a last resort antibiotic fro drug-resistant pathogens Can be passed on to other bacteria which would make them resistant to any drug Being watched by the CDC

What is anaphylaxis?

An acute, overwhelming allergic response that develops rapidly and can be fatal

What is SNAPP?

An artificially engineered peptide Stands for structurally nanoengineered antimicrobial peptide polymer Has shown promise in killing multiple types of bacteria that have become resistant to other drugs

What is a superinfection?

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

Other miscellaneous drugs that target the cell wall

Bacitracin Isoniazid Vancomycin Fosfomycin tromethamine

What are persisters?

Bacteria that go to sleep when exposed to antibiotics and rev back up after antibiotic concentrations decrease

Both host and bacterial defense peptides have multiple activities against bacteria. What do they do?

Insert their membranes and also target other structures in the cells Other peptides target viruses

What action do azoles take?

Interfere with sterol synthesis in fungi Ketoconazole—cutaneous mycoses, vaginal and oral candidiasis, systemic mycoses Fluconazole—AIDS-related mycoses (aspergillosis, Cryptococcus meningitis) Clotrimazole and miconazole—used to treat infections in the skin, mouth, and vagina

What is the spectrum of action of Methicillin and Nafcillin?

Narrow

What is the spectrum of action of Penicillin G?

Narrow

What is the spectrum of action of Penicillin V?

Narrow

What are drug examples of allylamines?

Terbinafine, naftifine

Subgroups of Tetracyclines

Tetracycline

Mutations and horizontal transfer result in mutants that have acquired one of several mechanisms of drug resistance. The actual changes that take place inside the cell as a result of these gene changes mostly fall into five categories. What are the five mechanisms of drug resistance?

New enzymes are synthesized, inactivating the drug (occurs when new genes are acquired) Permeability or uptake of the drug into the bacterium is decreased (occurs via mutation) Drug is immediately eliminated (occurs through the acquisition of new genes) Binding sites for drugs are decreased in number and/or affinity (occurs via mutation or through the acquisition of new genes) An affected metabolic pathway is shut down, or an alternative pathway is used (occurs via mutation of original enzymes)

Allergic reactions have been reported for every major type of antimicrobial drug. What are the top two most common drugs that cause an allergic reaction?

Penicillin Followed by...Sulfonamides

What are the selected penicillins?

Penicillin V Penicillin G Methicillin and Nafcillin Ampicillin Amoxicillin Azlocillin, mezlocillin, ticarcillin

Why are inhabitants of biofilms more resistant to antibiotics?

The (often ionically charged) antimicrobial drugs can not penetrate the sticky extracellular material surrounding biofilm organisms More importantly: The different phenotype expressed by biofilm bacteria When secured to surfaces, they express different genes and therefore have different antibiotic susceptibility profiles.

What is another alternative diffusion system that provides additional information on drug effectiveness?

The E-test

What do broad-spectrum antimicrobials do to healthy biota?

The destroy the healthy biota (along with the pathogens)

Which drug do you choose when a series of drugs being considered for therapy have similar MIC?

The drug with the highest therapeutic index usually has the widest margin of safety

*List the cell wall inhibitors*

Penicillins Cephalosporins Carbapenems Other miscellaneous drugs that target the cell wall

Subgroups of Penicillin

Penicillins G and V Ampicillin, carbenicillin, amoxicillin Nafcillin, cloxacillin Clavulanic acid

*Look at figure 10.5*

Understand how natural selection causes the biofilm to become resistant

Which bacteria pose a *concerning threat*?

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

What is the spectrum of action of Azlocillin, mezlocillin, and ticarcillin?

Very broad

Do viral infection have *treatments* ?

Very few

"Threat Report" issued by the CDC in 2013 outlines a "potentially catastrophic" antibiotic resistance situation. What is the situation?

We may enter a postantibiotic era where some infection will be untreatable

Allergic reactions do not occur during the first time exposed to the drug. So what happens?

People who are allergic to a drug become sensitized to it during the first contact (usually without symptoms) Once the immune system is sensitized, a second (or later) exposure to the drug can lead to a reaction

What are host defense peptides?

Peptides of 20 to 50 amino acids that are secreted as part of the mammalian innate immune system They have names such as defensin, magainins, and protegrins.

What are resistance (R) factors?

Plasmids containing antibiotic resistance genes Such traits are "lying in wait" for an opportunity to be expressed and to confer adaptability on the species

Subgroups of Polymyxins

Polymyxin B Daptomycin

*List the drugs that target cytoplasmic or cell membranes*

Polymyxins (Collstins)

What are the disadvantages of Methicillin and Nafcillin?

Poor absorption; allergies; growing resistance

What should the physician consider before prescribing an antibiotic?

Preexisting conditions that might influence the activity of the drug or the response of the patient History of allergy to a certain class of drugs Underlying liver or kidney disease Infants, the elderly, and pregnant women require special precautions Intake of other drugs can result in increased toxicity or failure of one or more drugs Some drug combinations have synergistic effects, may allow for reduced dosages

What are probiotics?

Preparations of live microorganisms that are fed to animals and humans to improve the intestinal biota

Other miscellaneous drugs that target DNA or RNA

Rifampin

What is antibiotic associated colitis?

Serious and potentially fatal conditions caused by oral therapy with tetracyclines, clindamycin, and broad-spectrum penicillins and cephalosporins

Describe the characteristics of the ideal drug

Should be easy to administer, yet be able to reach the infectious agent anywhere in the body Be toxic to the infectious agent, while being nontoxic to the host Should remain active in the body as long as needed, yet be safely and easily broken down and excreted

What does chromosomal drug resistance stem from?

Spontaneous random mutations in bacterial populations

Subgroups of aminoglycosides

Streptomycin

Subgroups of Sulfonamides

Sulfamethoxazole Silver sulfadiazine Trimethoprim

*List the drugs that target folic acid synthesis*

Sulfonamides

How are antimicrobial agents classified?

With regard to their: origin range of effectiveness whether they are naturally produced or chemically synthesized

What are the uses of Ampicillin?

Works on gram-negative bacilli

Can drugs fight microbes when spontaneous random mutations in a community changes microbial sensitivity?

Yes, with higher doses of drugs However, *some* microbes result in complete loss of sensitivity

Where are the greatest number of current antibiotics derived from?

a bacteria in the genera Streptomyces and Bacillus from molds in the genera Penicillium and Cephalosporium

What percentage of people taking an antimicrobial drug experience some type of serious adverse reaction to it?

a least 5%

What does praziquantel do?

a treatment for various tapeworm and fluke infections

What does ivermectin do?

a veterinary drug now used for strongyloidiasis and oncocercosis in humans

What drugs are the most toxic to human cells?

act upon a structure common to both the infective agent and the host cell such as the cytoplasmic membrane (ex. amphotericin B, used to treat fungal infections) *As the characteristics of the infectious agent become more and more similar to those of the host cell, selective toxicity becomes more difficult to achieve, and undesirable side effects are more likely to occur

What are antimicrobials?

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

When should identification of infectious agents from body specimens occur? Why?

as soon as possible - before any antimicrobial drug is given so that it happens before the drug reduces the number of the infectious agent

The Kirby-Bauer procedure is less effective for what kind of bacteria?

bacteria that are anaerobic, highly fastidious, or slow-growing (Mycobacterium).

What do mebendazole and albendazole do?

broad-spectrum antiparasitic drugs used for several types of roundworm intestinal infestations

What is the goal of antimicrobial drugs?

disrupt the cell processes or structures of bacteria, fungi, and protozoa inhibit virus replication interfere with the function of enzymes required to synthesize or assemble macromolecules destroy structures already formed in the cell should be *selectively toxic*

What is the goal of chemotherapy?

disrupt the structure or function of an organism to the point where it can no longer survive

What are synthetic drugs?

drugs produced entirely by chemical reactions

What are semisynthetic drugs?

drugs that are chemically modified in the laboratory after being isolated from natural sources

What is quinine?

extracted from the bark of the cinchona tree, was the principal treatment for malaria for hundreds of years, but it has been replaced

Gene transfers are extremely frequent in nature. Where do the genes come from?

from totally unrelated bacteria, viruses, and other organisms living in the body's normal biota and the environment.

What does a small ratio mean?

greater the potential for toxic drug reactions example: TI of 1.1 is riskier than TI of 10

What is hepatoxicity?

liver damage

What are the four main drug groups currently in use to treat fungal infections?

macrolide polyene antibiotics the azoles the echinocandins allylamines

What viral diseases are prevented because of vaccinations?

measles, mumps, and hepatitis

What time of tubes are usually used?

miniaturized tubes called wells in 96-well plates

What is neurotoxicity?

nervous system damage

What does the compound pyrantel do?

paralyzes the muscles of intestinal roundworms Because of this, the worms are unable to maintain their grip on the intestinal wall and are expelled along with the feces by the normal peristaltic action of the bowel

What does horizontal transfer resistance stem from?

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

What are other approaches to controlling infections?

probiotics prebiotics fecal transplants

What are other drugs with antiprotozoal activities?

quinacrine (a quinine-based drug), sulfonamides, and tetracyclines.

What are scientist worried about when it comes to antibiotics?

we are dangerously close to a *postantibiotic era* where the drugs we have are no longer effective

Resistance can be intrinsic or acquired. What does this mean?

*intrinsic resistance:* It is called intrinsic when it is a fixed trait of a microbe (ex: all microbes are intrinsically resistant to antibiotics they themselves produce) *acquired resistance:* Resistance to a drug by a microbe that was previously sensitive to the drug

The steps of how antibiotic resistance occurs

1. Lots of bacteria. A few are drug resistant. 2. Antibiotics kill bacteria causing the illness, as well as good bacteria protecting the body from infection 3. The drug-resistant bacteria are now allowed to grow and take over 4. Some bacteria give their drug-resistance to other bacteria, causing more problems

Which groups of bacteria need antimicrobial sensitivity testing? Why?

1. Staphylococcus species 2. Neisseria gonorrhoeae 3. Streptococcus pneumoniae 4. Enterococcus faecalis 5. the aerobic gram-negative intestinal bacilli

How is the Kirby-Bauer test performed?

1. the surface of a plate of special medium is spread with the test bacterium 2. small discs containing a premeasured amount of antimicrobial are dispensed onto the bacterial lawn 3. After incubation, the zone of inhibition surrounding the discs is measured and compared with a standard for each drug

Some *fungi* have an additional option for becoming antibiotic-resistant, as discovered in 2014. What is this option?

A small regulatory RNA known as interfering RNA—or RNAi—has been found to bind to a genetic sequence temporarily When it is bound, the gene is silenced and the target of the antibiotic is not manufactured by the fungus thus rendering it temporarily resistant to that drug This allows the fungi to express the gene later when the antibiotic is no longer present

What is artemisinin?

A staple for malaria treatment in most parts of the world

What is metronidazole (Flagyl)?

A widely used amoebicide It is effective in treating mild and severe intestinal infections and hepatic disease caused by Entamoeba histolytica

What are the disadvantages of Azlocillin, mezlocillin, and ticarcillin?

Allergies; susceptible to many beta-lactamases

*List the drugs that target protein synthesis*

Aminoglycosides Tetracyclines Glycylcyclines Macrolides Other miscellaneous drugs that target protein synthesis

What are drug examples of macrolide polyene antibiotics?

Amphotericin B (shown above in gray)

What is antibiotic associated colitis known as? What is caused by?

C. diff or Clostridium difficile Caused by the overgrowth of the endospore-forming bacterium Clostridium difficile

What are the disadvantages of Penicillin G?

Can be hydrolyzed by penicillinase; allergies occur; requires injection

What are the disadvantages of Ampicillin?

Can be hydrolyzed by penicillinase; allergies; only fair absorption

What are current widely used antimicrobial drugs are divided into?

Categories based on which metabolic targets they affect (DNA/RNA/proteins/cytoplasmic membrane that make up a new cell wall)

Subgroups of cephalosporins

Cefazolin Cefaclor Cephalexin, cefotaxime Ceftriaxone Cefepime Cegtaroline

The major side effects fall into one of three categories. What are they?

Direct damage to tissues through toxicity Allergic reactions Disruption in the balance of normal microbial biota *The damage can be short term and reversible or permanent, and it ranges in severity from cosmetic to lethal*

What are some quick initial methods for detecting and perhaps even identifying *bacteria or fungi*?

Direct examination of: body fluids sputum stool

Subgroups of Carpapenems

Doripenem, imipenem Aztreonam

What are the uses of Azlocillin, mezlocillin, and ticarcillin?

Effective against Pseudomonas species; low toxicity compared with aminoglycosides

What are some biofilm treatment strategies that have been developed?

Interrupting quorum sensing pathways (mediate communication between cells and may change phenotypic expression) Daptomycin (trade name: cubicin) - a lipopeptide that is effective in deep tissue infections with resistant bacteria has shown success Adding DNAse to antibiotics aids penetration through extracellular debris Since many biofilm infections can be found on biomaterials inserted in the body, such as cardiac or urinary catheters....impregnating devices with antibiotics prior to implantation (cannot be done with biofilm infections of natural tissues, such as the prostate or middle ear)

In the past, many physicians tended to use a "shotgun" antimicrobial therapy for minor infections. What does this mean?

Involves administering a broad-spectrum drug instead of a more specific narrow-spectrum one

What does C.diff do to the body?

It invades the intestinal lining Releases toxins that induce diarrhea, fever, and abdominal pain

Is the gene silencing epigenetic or epimutation? What does this mean?

It is an epimutation Heritable change in gene expression that does not involve change in the gene itself but chemical additions to it

Is the mechanism used by fungi to silence the target of the antibiotic with a RNAi epigenetic or epimutation? What does this mean?

It is epigenetic Refers to "above the gene," specifically additions to the DNA which do not change the gene but can change its expression

There may be a third mechanism of acquiring resistance to a drug. What is it?

It is phenotypic instead of genotypic Recent studies suggest that bacteria can "go to sleep" when exposed to antibiotics, meaning they will slow or stop their metabolism so they cannot be harmed by the antibiotic They can then rev back up after the antibiotic concentration decreases Sometimes these bacteria are called "persisters"

What was the spectrum of activity for the original penicillins like?

It was narrow-spectrum It was susceptible to microbial counterattacks

What are drug examples of azoles?

Ketoconazole, fluconazole, miconazole, and clotrimazole

Which organs are affected the most by drugs?

Liver (hepatotoxic) Kidneys (nephrotoxic) Gastrointestinal tract Cardiovascular system and blood-forming tissue (hemotoxic) Nervous system (neurotoxic) Respiratory tract Skin Bones and teeth

How horizontal transfers work:

Many bacteria also maintain transposable drug resistance sequences (transposons) that are duplicated and inserted from one plasmid to another or from a plasmid to the chromosome Chromosomal genes and plasmids containing codes for drug resistance are often faithfully replicated and inherited by all subsequent progeny

What drugs are used to treat helminth infections?

Mebendazole Albendazole Compound pyrantel Newer drugs: Praziquantel Ivermectin

What are drug examples of echinocandins?

Micafungin, caspofungin

How have penicillins evolved?

Molecule has been altered and improved upon over the years Later penicillins have overcome the limitations of the original molecule

What are tube dilution tests used to determine?

More sensitive and quantitative results

Which bacteria pose a *serious threat*?

Multidrug-resistant Acinetobacter Drug-resistant Campylobacter Fluconazole-resistant Candida Many more

Is there a universally effective drug? Why or why not?

No Because there are several species of Plasmodium (the malaria parasite) and many stages in its life cycle So no single drug is universally effective for every species and stage Furthermore, the geographical region where the malaria infection was acquired must be taken into account, as different parts of the world harbor strains of the parasite with differing drug resistances.

Do all bacteria require antimicrobial sensitivity testing?

No Some do and some don't

What is biota?

Normal microbial colonists of healthy body surfaces Normally consist of harmless or beneficial bacteria A few may be pathogens

What are the uses of Methicillin and Nafcillin?

Not usually susceptible to penicillinase

What is artemisinin combination therapy (ACT)?

Now recommended for the treatment of certain types of malaria today It involves the use of artemisinin with quinine derivatives or other drugs.

What are prebiotics?

Nutrients that encourage the growth of beneficial (good) microbes

How is CRISPR used?

One possible way to use it is as a method to: Treat antibiotic-resistant infections, together with an antibiotic Scientists in Israel delivered CRISPR packaged in a phage vector that only infected the offending bacteria CRISPR then destroyed the genes that were causing the resistance, allowing the antibiotics to be effective

Because drug toxicity to the host is a concern, what is the best drug to choose?

One with with high selective toxicity for the infectious agent and low human toxicity

Where does artemisinin come from?

Originally from a plant called sweet wormwood, used for centuries in Chinese traditional medicine

What happens when antimicrobials destroy beneficial resident species?

Other microbes that were once in small numbers begin to overgrow and cause disease

What kind of infection is malaria?

Protozoal

What is the CRISPR system?

Provides the first true hope that science may be capable of overcoming antibiotic resistance It is a system found in bacteria that can cause very specific cuts in genes Researchers turned this into a powerful genetic engineering tool

What drugs are used for malaria?

Quinine derivatives (chloroquine and primaquine) Artemisinin Artemisinin combination therapy

Researchers are taking novel approaches to developing new drugs that they hope can replace, and improve upon, the ones that are losing their effectiveness. What are some of these approaches?

RNA interference Defense peptides CRISPR Drugs from noncultivable bacteria Bacteriophages

Even when all of the information is in, the final choice of a drug is not always easy or straightforward. Why?

Read the hypothetical cases on page 281 About the cancer patient and elderly alcoholic patient

In general, how does natural selection lead to drug resistance in a biofilm?

The environmental factor (in this case, the drug) has put selection pressure on the population, allowing the more "fit" microbe (the drug-resistant one) to survive, and the population has evolved to a condition of drug resistance

Since fungal cells are eukaryotic, they present special problems in chemotherapy. What are some of these problems?

The great majority of chemotherapeutic drugs are designed to act on bacteria and *are generally ineffective in combating fungal infections* The similarities between fungal and human cells often mean that drugs toxic to fungal cells are also capable of harming human tissues. Only a few agents with special antifungal properties have been developed for treating systemic and superficial fungal infections

What can provoke the allergic response?

The intact molecule or by substances that develop from the body's metabolic alteration of the drug

What was considered a medical revolution in the 1940s?

The introduction of modern drugs to control infection

What is the antibiogram?

The profile of antimicrobial sensitivity created by the kirby-bauer test

What is the therapeutic index?

The ratio of the dose of the drug that is toxic to humans as compared to its minimum effective (therapeutic) dose

What is the minimum inhibitory concentration (MIC)?

The smallest concentration (highest dilution) of drug that visibly inhibits growth see figure 10.3

What has replace quinine?

The synthesized quinolones, mainly: chloroquine and primaquine

What are broad-spectrum drugs?

They are effective against more than one group of bacteria Ex. Tetracycline antibiotics

It is common for individuals in Latin America and Asia to self-medicate with antibiotics. What does this cause?

They are largely ineffectual and lead to drug resistance Also, responsible for emergence of drug-resistant bacteria that subsequently cause epidemics

Where do antibiotics come from?

They are natural metabolic products of bacteria and fungi Also, chemists have created new drugs by altering the structure of naturally occurring antibiotics, and they are actively searching for metabolic compounds with antimicrobial effects in species other than bacteria and fungi

Why have new and effective antibiotics been slow to come to the market?

They are not economically profitable for pharmaceutical companies They are still just as expensive and time-consuming to make

What is one of the major ways biofilm inhabitants differ from their planktonic counterparts?

They are often unaffected by the same antimicrobials that work against them when they are free-living

What are narrow-spectrum drugs?

They generally target a specific group Ex. Polymyxin

What have antimicrobial drugs done to infections? Have they eliminated infectious diseased?

They have reduced the incidence of certain infections No, they probably never will

How are probiotics beneficial?

They serve to replace microbes lost during antimicrobial therapy They simply augment the biota that is already there They are generally safe and effective Useful in the management of food allergies

How do mebendazole and albendazole function?

They work locally in the intestine to inhibit the function of the microtubules of worms, eggs, and larvae This means the parasites can no longer utilize glucose, which leads to their demise.

What are the consequences of the "shotgun" approach?

This has led to superinfections and other adverse reactions Caused the development of resistance in "bystander" microbes (normal biota) that were exposed to the drug as well, leading to the spread of resistant pathogens Growing awareness has led to the reduction of this practice

How is RNA interference being used?

This is being exploited in attempts to shut down the metabolism of pathogenic microbes

What are fecal transplants?

This procedure involves the transfer of feces from healthy patients via colonoscopy

Subgroups of Glycylcyclines

Tigecycline

What is the *goal of antimicrobial chemotherapy*? Why is this difficult to achieve?

To administer a drug to an infected person, which destroys the infective agent without harming the host's cells This is actually difficult to achieve because many (often contradictory) factors must be taken into account

Why are antibiotics made by producers?

To inhibit the growth of other microorganisms in the same habitat (antagonism) antibiotic producers are able to enjoy less competition for nutrients and space

Other characteristics of the ideal drug

Toxic to the microbe but nontoxic to host cells Microbicidal rather than microbistatic Relatively soluble; functions even when highly diluted in body fluids Remains potent long enough to act and is not broken down or excreted prematurely Does not lead to the development of antimicrobial resistance Complements or assists the activities of the host's defenses Remains active in tissues and body fluids Readily delivered to the site of infection Reasonably priced Does not disrupt the host's health by causing allergies or predisposing the host to other infections

What is one of the most frequent drug reactions?

allergies

What is drug resistance?

an adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory one unfortunate outcomes of the use of antimicrobials

What is the Kirby-Bauer test?

an agar diffusion test that provides useful data on antimicrobial susceptibility

What is narrow-spectrum (limited spectrum)?

antimicrobials effective against a limited array of microbial type for example, a drug effective mainly against gram-positive bacteria

What is broad-spectrum (extended spectrum)?

antimicrobials effective against a wide variety of microbial type for example, a drug effective against both gram-positive and gram-negative bacteria

The currently used antiviral drugs were developed to target specific points in the infectious cycle of viruses. What are the three major modes of action?

barring penetration of the virus into the host cell, blocking the transcription and translation of viral molecules, and preventing the maturation of viral particles.

What do the best current drugs block?

block the actions or synthesis of molecules in microorganisms but not in vertebrate cells this means they have great selective toxicity

What is hemotoxicity?

blood damage

When are epidemiological statistics required to predict the most likely agent in a given infection?

if the infectious agent is not or cannot be isolated for example: Streptococcus pneumoniae accounts for the majority of cases of bacterial meningitis in children, followed by Neisseria meningitidis

Doctors begin therapy on the basis of what?

immediate findings in body fluids even on the basis of an informed best guess epidemiological statistics may be required to predict the most likely agent in a given infection (if the infectious agent is not or cannot be isolated)

What do the most effective antihelminthic drugs do?

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

Selecting the right antimicrobial treatment relies on testing what?

in vitro activity of various drugs against the isolated microbe in the laboratory

What are the categories of drugs based on which metabolic targets they affect?

inhibition of cell wall synthesis, inhibition of nucleic acid (RNA and DNA) structure and function inhibition of protein synthesis interference with cytoplasmic membrane structure or function inhibition of folic acid synthesis

What about testing for fungal or protozoal infections?

it is difficult and unnecessary because antimicrobial agents generally target all representatives of these groups

What is nephrotoxicity?

kidney damage

What are some reactions that can occur?

skin rash (hives) respiratory inflammation anaphylaxis

What is RNA interference?

small pieces of RNA that regulate the expression of genes

Whether antibiotics are present or not, microbes become newly resistant to a drug after one of two events occur. What are the two causes?

spontaneous mutations in critical chromosomal genes, or acquisition of entire new genes or sets of genes via horizontal transfer from another species. there may be a third mechanism

What are antibiotics?

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

What do some antibiotics do that worsens the biofilm?

t chemotherapy with some antibiotics—notably aminoglycosides—can cause bacteria to form biofilms at a higher rate than they normally would

What is an advantage of bacteriophage treatment?

the extreme specificity of the phages only one species of bacterium is affected, leaving the normal inhabitants of the body, and the body itself, alone (unlike antibiotics)

Before actual antimicrobial therapy can begin, it is important that at least three factors be known. What are the three factors?

the identity of the microorganism causing the infection the degree of the microorganism's susceptibility (also called sensitivity) to various drugs the overall medical condition of the patient

When antimicrobial treatment fails, the failure is due to one or more the following:

the inability of the drug to diffuse into that body compartment (the brain, joints, skin) resistant microbes in the infection that didn't make it into the sample collected for testing an infection caused by more than one pathogen (mixed), some of which are resistant to the drug in outpatient situations you have to also consider the possibility that the patient did not take the antimicrobials correctly

What is antimicrobial chemotherapy?

the use of drugs to control infection

Examples of drugs with excellent selective toxicity

they block the synthesis of the cell wall in bacteria ( ex. *penicillin* ) they have low toxicity and few direct effects on human cells because human cells lack the chemical peptidoglycan and are thus unaffected by this action of the antibiotic

What does it mean when a drug is selectively toxic?

they should kill or inhibit microbial cells without simultaneously damaging host tissues this concept of selective toxicity is central to antibiotic treatment

What is prophylaxis?

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

What is the MIC useful for?

useful in determining the smallest effective dosage of a drug and in providing a comparative index against other antimicrobials