Unit 3

How do you effectively treat an area?

Turn the bottle around to the back side, read the label and follow the directions.

How do you effectively treat an area? What do you have to consider?

Turn the bottle around to the back side, read the label and follow the directions.

sterile field

(a designated area that is kept free of all vegetative microbes, endospores, and viruses). Everything inside of the field is considered sterile and strict rules are in place to maintain that sterility.

Penicillin G

(natural antibiotic) is given through the parenteral route because it is destroyed by acid. It can be distributed throughout the body with high levels in the kidneys. It is active against Gram + and some Gram - organisms. The first member of this family that was discovered was penicillin G. -INJECTION

Penicillin V

(natural antibiotic) is not destroyed by acid so it can be administered orally. It is active against Gram + and some Gram - organisms. Similar to penicillin G. -ORALLY

three common methods for sterilization

-An autoclave uses heat and pressure to sterilize items. The combination of heat and pressure denature proteins and is sufficient to sterilize. -Incineration (dry heat sterilization) Incineration at very high temperatures destroys all microorganisms. -Filtration is size selection. There are a variety of different filters that can be used to physically remove microbes. Filter sizes of 0.22 micrometers is sufficient to remove bacteria and other larger cells. It is unreliable because of the potential presence of smaller organisms (viruses) and Mycoplasma spp (because they lack a cell wall and can squeeze through the filter).

Know methods of degerming and sterilization. (Autoclave, commercial sterilization, incineration, filtration, desiccation, disinfection, sanitization, refrigeration, antisepsis, etc.)

-Autoclave: uses heat and pressure to STERILIZE items. -Commercial: to reduce the number of microbes in its product. What comes out of commercialization is a DEGERMED product, not sterile. -Incineration: dry heat sterilization. Incineration at very high temperatures destroys all microorganisms. -Filtration: nearly sterilize the air that passes through -Desiccation: drying out -Disinfection: DEGERMING. the inactivation of microbes on a surface of a fomite. Disinfectants use chemical or physical means of removing microbes from nonliving items. -Sanitization: DEGERMING. refers to the cleansing of fomites to remove enough microbes to achieve levels deemed safe for public health. -Refrigeration: inhibits metabolism (slows or arrests cell division)

least resistant to most

-Least resistant 1. Enveloped virus 2. Gram Positive bacteria 3. Naked virus4. Gram negative bacteria 5. Mycobacterium spp 6. Endospores 7. Prions -Most resistant

Actions of microbial control agents - The 3 major targets of microbial control agents are

1. Cell membrane- leaky membranes are bad for microbes! 2. Proteins- no enzymes... no life. 3. Nucleic acids- destroy the blueprint and you destroy an organism's ability to live.

Stages of viral infection

1. Host cell recognition and binding. 2. Entry into the host cell 3. Taking over the host cell machinery 4. Producing new virions (virus particles) 5. Exit from the host cell

Mechanisms of Antibiotic resistance

1. Modification or degradation of the antibiotic. Beta lactamase destroys members of the penicillin family. 2. Target molecule is changed. Changes (via mutation) to the ribosome or penicillin binding proteins can stop antibiotics from binding/ inhibiting their target enzymes. 3. Decreased permeability or increased efflux. Gram negative cells have the selectively permeable outer membrane. Mycobacterium tuberculosis has the mycolic acid barrier. Pseudomonas aeruginosa uses efflux pumps to pump out antibiotics before they can find their cellular targets. In many cases, efflux pumps can remove several different classes of antibiotics. Biofilms reduce permeability by secreting a slime layer. 4. Enzyme bypass mechanisms. Sulfonamide resistance is obtained the target enzyme such that there is a sufficient amount of antimicrobial-free enzyme to carry out the proper enzymatic reaction.

Critical items

Critical items must be sterile because they will be used inside of the body, often penetrating tissues or the blood stream (examples: surgical instruments, catheters, IV fluids).

what are the major effects of giving patient strong broad spectrum antibiotics? What side effects usually occur?

A broad-spectrum antibiotic targets multiple groups of microbes. If the causative agent isn't known and it is best to use a broad-spectrum antibiotic. Broad-spectrum antibiotics greatly influenced the health of your normal flora and can leave you open to a superinfection (a secondary infection a patient that had a pre-existing infection). Side effects include a phototoxicity, teeth discoloration, and liver toxicity.

Spectrum of activity

A narrow spectrum antibiotic targets only a specific group of microbes. For example, penicillin works well on Gram positive but not very well on Gram negative microbes. If the pathogen causing an infection has been identified, it is best to use a narrow-spectrum antimicrobial and minimize collateral damage to the normal flora. A broad-spectrum antibiotic targets multiple groups of microbes. For example, Tetracyclines target gram positive microbes ,Gram negative microbes, Chlamydias and Rickettsias (pathogens we will discuss in the next unit). If the causative agent isn't known, then it is best to use a broad-spectrum antibiotic.

AZT

AZT, a nucleotide analog stops the reverse transcription step, in HIV's life cycle.

Acyclovir

Acyclovir (also known as Zovirax) mimics a nucleotide and stops DNA replication. Acyclovir and its derivatives are frequently used for the treatment of herpes virus infections, including genital herpes, chickenpox, shingles, Epstein-Barr virus infections, and cytomegalovirus infections. Acyclovir can be administered either topically or systemically, depending on the infection.

Antimicrobial agent

Agent that kills or inhibits the growth of microorganisms.

High-efficiency particulate air (HEPA) filters

Air is commonly filtered through high efficiency particulate air (HEPA) filters. HEPA filters have effective pore sizes of 0.3 micrometers, which is small enough to remove bacterial, endospores and many, but not all viruses. HEPA filters nearly sterilize the air that passes through.

ethanol and isopropanol

Alcohol. Alcohols can either be used as disinfectants or antiseptics. The work by denaturing proteins and disrupting membranes. The most commonly used alcohols for disinfection are ethyl alcohol (ethanol) and isopropyl alcohol (isopropanol, rubbing alcohol).

Alcohols

Alcohols can either be used as disinfectants or antiseptics. The work by denaturing proteins and disrupting membranes. The most commonly used alcohols for disinfection are ethyl alcohol(ethanol) and isopropyl alcohol (isopropanol, rubbing alcohol). Of the two, isopropanol works slightly better but they both work within seconds, to degerm an area. They are effective against bacteria and fungi, enveloped viruses. Endospores and naked viruses are resistant

Alcohol

Alcohols require water, in order to denature and cause protein agglutination (which is how they cause cytolysis). At 100%, alcohol will not effectively kill microbes. The most effective alcohol concentrations are between 60-95%. -Cytolysis and protein denaturation

Aminoglycosides

Aminoglycosides cause the misreading of the mRNA. This misreading of the message causes mistakes in the amino acids that are inserted into the new polypeptide chains. This, in effect, causes incorrect protein folding, which leads to agglutination that kills the cell. Examples of drugs in this group include streptomycin and neomycin. Aminoglycosides are more effective against Gram negatives, than Gram positives. The cell wall is the barrier for them.

Cide/static

Antibiotics can either kill or inhibit the growth of microbes. When they kill, we use the suffix "-cide" or "-cidal." If the inhibit the growth, we use the suffix "-static" or "-stasis." Although these drugs don't kill the pathogens, they do allow time for the host's immune system to clear the infection, while minimizing the damage due to microbial growth. One of the most important factors in choosing between the two options is the state of the patient's immune system. Healthy individuals can be given both "cidal" or "static" drugs. "Static" drugs are not ideal for immunocompromised patients.

Testing the Effectiveness of Antimicrobials - The Kirby-Bauer disk diffusion test

As the bacterial inoculum grows, antibiotic diffuses from the circular disk into the agar and interacts with the growing bacteria. Antibacterial activity is observed as a clear circular zone of inhibition around the drug-impregnated disk, similar to the disk-diffusion assay.

members of the penicillin family are combined with beta lactamase inhibitors, in order to increase their activity in microbes that possess beta lactamase . . .

Augmentin (amoxicillin and clavulanate) is an antibiotic used to treat bacterial infections, such as sinusitis, pneumonia and bronchitis. Clavulanate is a beta lactamase inhibitor.

Bacitracin

Bacitracin blocks the export of cell wall components, thus stopping cell wall synthesis. It has a very low therapeutic index, making it very toxic to your cells. Bacitracin is effective against a wide range of bacteria, including gram-positive organisms found on the skin, such as Staphylococcus and Streptococcus. Although it may be administered orally or intramuscularly in some circumstances, bacitracin has been shown to be nephrotoxic (damaging to the kidneys). -one of three antibiotics that is found in NEOSPORIN -STOPS THE EXPORT OF CELL WALL COMPONENTS

Inhibit cell wall synthesis

Beta lactams: penicillins, cephalosporins, carbapenems, vancomycin, bacitracin

Copper, nickel, and zinc

Copper is being used in a variety of ways to control microbial growth. In under developed countries, diarrhea is a killer. In some cases, water is stored in copper lined pots, to reduce the incidence of diarrheal diseases/deaths. Copper sulfate is used as an algicide in swimming pools and fish tanks. Copper coatings on door handles help control the transmission of disease that is caused by these fomites.

quaternary ammonium salts (quats)

Cationic detergents include an important class of disinfectants and antiseptics called the quaternary ammonium salts (quats). Since they are amphipathic, they can insert themselves in the membrane and cause cytolysis. Quats can kill bacteria, fungi, protozoans and enveloped viruses. They cannot destroy endospores. Benzalkonium chloride is an example of a quat that can be found in a variety of items, including mouth washes and hand sanitizers. Roccal is another example of a quat. It requires ten minutes to be effective, but it kills a variety of microbes.One disadvantage of quats is that some strains of Pseudomonas can break them down and use them for nutrients, if they contain the right dissimilation plasmid.

Chloramphenicol

Chloramphenicol inhibits protein synthesis by inhibiting the formation of the peptide bond between amino acids. It is one of only a few antibiotics that can cross the blood-brain barrier. One possible side effect is anemia. Chloramphenicol reduces the number of blood cells produced by bone marrow and this eventually leads to a deficit. If it occurs during treatment, the treatment stops, and the effects are reversed. In some cases, anemia occurs, via an unknown mechanism, after treatment has completed and aplastic anemia occurs (a lethal loss of blood cell production). Another possible serious side-effect is gray baby syndrome. -STOPS PEPTIDE BOND FORMATION -CAN CAUSE APLASTIC ANEMIA

Know the difference between cidal and static. Also know all of the terms used to describe these effects on different types of organisms

Cidal: it kills Static: inhibits the growth Bactericide = kills bacteria Fungicide = kills fungi Viricide = inactivates viruses Algicide = kills algae Sporicide = destroys endospores Bacteriostatic = inhibits bacterial growth

Cresols

Cresols (methylated phenols) and o-phenylphenol were active ingredients in various formulations of Lysol

Also know if they sterilize or just degerm

Degerm: sterilization, disinfection, antisepsis and sanitization. Sterilize: autoclave, incineration, HEPA filters nearly sterilize.

Detergent

Detergents contain synthetic surfactant molecules with both polar and nonpolar regions that have strong cleansing activity but are more soluble, even in hard water, and, therefore, leave behind no soapy deposits

Ethylene oxidase

Ethylene oxide is a type of alkylating agent that is used for gaseous sterilization. It is highly penetrating and can sterilize items within plastic bags such as catheters, disposable items in laboratories and clinical settings (like packaged Petri dishes), and other pieces of equipment. -denatures proteins through alkylation -gaseous sterilant -toxic, carcinogenic?, explosive

Sterilizing gases

Ethylene oxide is a type of alkylating agent that is used for gaseous sterilization. It is highly penetrating and can sterilize items within plastic bags such as catheters, disposable items in laboratories and clinical settings (like packaged Petri dishes), and other pieces of equipment. Ethylene oxide exposure is a form of cold sterilization, making it useful for the sterilization of heat-sensitive items.

Eukaryotic pathogens

Eukaryotic pathogens are harder to treat than bacterial pathogens because they are so similar to our cells. Much of their metabolism is similar, if not identical to ours. They have 80S ribosomes, which are also present in our cells. Selective toxicity is hard to obtain, treatment times can be long and side effects can be severe.

Why can't we cure HIV?

Evolution

Fungi infections

Fungal infections in hospitals are on the rise. They now make up ~9% of nosocomial infections. This is mainly because of the rise in the number of people with HIV/AIDS. These immunocompromised patients are likely to develop fungal infections, like thrush (caused by Candida albicans) and certain types of pneumonia (caused by Pneumocystis).

Which antibiotics work better on Gram negative microbes versus Gram positive microbes?

Gram negative:Tetracyclines, polymyxins, Gram positive: penicillin, tetracyclines,

betadine

HALOGEN. Betadine is a brand of povidone-iodine commonly used as a hand scrub by medical personnel before surgery and for topical antisepsis of a patient's skin before incision.

Chlorine

Halogen. Chlorine is another halogen commonly used for disinfection. When chlorine gas is mixed with water, it produces a strong oxidant called hypochlorous acid. Hypochlorous acid destroys all types of molecules by breaking bonds.

Iodine

Halogen. Iodine works by oxidizing cellular components, including sulfur-containing amino acids, nucleotides, and fatty acids, and destabilizing the macromolecules that contain these molecules.

Tincture of iodine

Halogen. Iodine works by oxidizing cellular components, including sulfur-containing amino acids, nucleotides, and fatty acids, and destabilizing the macromolecules that contain these molecules. It is often used as a topical tincture (iodine + alcohol), but it may cause staining or skin irritation.

Fluorine

Halogen. The halogen fluorine is also known to have antimicrobial properties that contribute to the prevention of dental caries (cavities). Fluoride is the main active ingredient of toothpaste and is also commonly added to tap water to help communities maintain oral health.

Zinc oxide

Heavy metal. Zinc oxide is found in topical antiseptic creams such as calamine lotion, diaper ointments, baby powder, and dandruff shampoos.

Heavy metals

Heavy metals kill microbes by binding to proteins, causing them to denature, and inhibiting enzyme activity. They display oligo dynamic activity (highly effective at super low concentrations). Heavy metals do not have good selective toxicity, as they are toxic to us as well. Mercury, silver, copper, nickel, and zinc -oligo dynamic activity- highly effective at low concentrations -denatures proteins

Disk diffusion test

It is important to be able to test the effectiveness of a treatment on a particular microbe so that we can choose the best method. In order to do this, we use the disk diffusion test. As the inoculated microbes grow, they will either be influenced by the active ingredient, or not. If they are not influenced, the microbes will grow up to the disk. If they are influenced by the active ingredient, there will be a clearing around the disk. This clearing is called a zone of inhibition. Measurement are taken to determine levels of resistance. This same method can be used for assessing antibiotic resistance/sensitivity.

Noncritical items

Items that may contact but do not penetrate the patient are noncritical items (examples: bed linens, furniture, crutches, stethoscopes, blood pressure cuffs). These need to be cleaned but not highly disinfected, although certain types of patient infections may warrant a higher level of disinfection of these items.

Algicide

Kills algae

ethambutol

Like Isoniazid, ethambutol influences the mycolic acids barrier of Mycobacterium. Ethambutol works slightly differently than Isoniazid. Ethambutol prevents the incorporation of mycolic acid into the cell wall, preventing the formation of the barrier. The mycolic acid barrier is a great barrier. Once it is compromised, other treatments can kill the weakened Mycobacterium cells. Ethambutol is also used in conjunction with rifampin or streptomycin -STOPS MYCOLIC ACID INCORPORATION INTO THE CELL WALL.

Lincosamides

Lincosamides, like clindamycin stop protein synthesis (by inhibiting translocation) and are particularly active against streptococcal and staphylococcal infections. Precautions must be taken during treatment with clindamycin because it increases the risk of C-diff mediated colitis by four-fold.

Macrolides

Macrolides are bacteriostatic drugs that stop proteins synthesis. Erythromycin was the first macrolide and it works by stopping ribosome translocation. (carried around by the immune system cells). Azithromycin lasts longer (along a single dose/day) and is commonly used in Z-pak form (3 day treatment).

Mercury

Mercury compounds like mercuric chloride are mainly bacteriostatic and have a very broad spectrum of activity. In recent decades, the use of such compounds has diminished because of mercury's toxicity. It is toxic to the central nervous, digestive, and renal systems at high concentrations.

Nucleid acid synthesis Metronidazole (Flagyl)

Metronidazole (Flagyl) interferes with DNA replication by breaking DNA molecules. It mainly works on anaerobic microbes because they process it into its toxic form. Aerobic microbes do not have the enzymes to do this, so they are unaffected. Metronidazole is also active against protozoans

what do you know about mycoplasma and how would it influence which antibiotic you choose to treat an infection that is caused by this group of microbes?

Mycoplasma is a genus of bacteria that lack a cell wall around their cell membranes. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis.

Neomycin

Neomycin is found in Neosporin

Why is hydrogen peroxide considered a poor antiseptic but a great disinfectant?

One disadvantage of using hydrogen peroxide as an antiseptic is that it also causes damage to skin that may delay healing or lead to scarring. It is not considered a good antiseptic because of the presence of catalase.

Effectiveness of antimicrobial treatments: Things to consider

Organic material, temperature, pH

Antagonism

Other drugs will negate the activity of one another

antagonism

Other drugs will negate the activity of one another

Know the effects of penicillin on vegetative versus nonvegetative cells. When does it work best? If I give a bacteriostatic antibiotic before giving penicillin, how does that influence penicillin's ability to work?

Penicillin targets cell wall synthesis so they will only influence vegetative cells, since non-vegetative cells are not undergoing cell wall synthesis. If these antibiotics work, the cells will die via osmotic lysis (when conditions are appropriate).

Roccal

Surfactant/quat. Roccal is another example of a quat. It requires ten minutes to be effective, but it kills a variety of microbes.

Peroxides

Peroxygens are strong oxidizing agents that can be used as disinfectants or antiseptics. The most widely used is hydrogen peroxide (H2O2). Hydrogen peroxide breaks molecules apart. If enough damage is done, it can kill microbes. It has broad-spectrum activity, working against gram-positive and gram-negative bacteria, fungi, viruses, and endospores. -One disadvantage of using hydrogen peroxide as an antiseptic is that it also causes damage to skin that may delay healing or lead to scarring. -It is not considered a good antiseptic because of the presence of catalase.

Hydrogen peroxide

Peroxygens are strong oxidizing agents that can be used as disinfectants or antiseptics. The most widely used is hydrogen peroxide (H2O2). Hydrogen peroxide breaks molecules apart. If enough damage is done, it can kill microbes. It is not considered a good antiseptic because of the presence of catalase. Many organisms possess this enzyme that breaks hydrogen peroxide down into water and oxygen. This is why you see bubbling when you apply it to a wound.

phenolics

Phenolics tend to be stable, persistent on surfaces, and less toxic than phenol. They inhibit microbial growth by denaturing proteins and disrupting membranes. -DISRUPT MEMBRANES - CYTOLYSIS -DENATURE PROTEINS EX: TRICLOSAN, LYSOL

Increase in Plasma membrane permeability

Polymyxin B and Polymyxin E (colistin) binds to the cell membrane making it more permeable.This is used mostly for resistant Gram negative organisms that are difficult to treat. The thick cell wall ofGram + organisms does not allow this drug to gain access to the cell membrane so it has little effect onGram + organisms. Polymyxin B is found in Neosporin. Oral colistin was historically used only for bowel decontamination to prevent infections originating from bowel microbes in immunocompromised patients or for those undergoing certain abdominal surgeries. Polymyxins are more effective against Gram negatives, than Gram positives. The cell wall is the barrier for them.

Disrupt membranes

Polymyxin B, colistin

Benzalkonium chloride

Quat/surfactant. Benzalkonium chloride is an example of a quat that can be found in a variety of items, including mouth washes and hand sanitizers.

Nucleid Acid Synthesis

Quinolones and Fluoroquinolones are broad spectrum antibiotics that inhibit DNA gyrase. DNA gyrase activity is essential for DNA replication. Nalidixic acid, a quinolone, stops DNA replication by stopping DNA gyrase. Ciprofloxacin and levofloxacin are effective against a broad spectrum of gram-positive or gram-negative bacteria, and are among the most commonly prescribed antibiotics used to treat a wide range of infections, including urinary tract infections, respiratory infections, abdominal infections, and skin infections. Side effects associated with different fluoroquinolones include phototoxicity, neurotoxicity, cardiotoxicity, glucose metabolism dysfunction, and increased risk for tendon rupture.

beta lactamase

Resistance came about because of the spread of an enzyme, in the microbial population. This enzyme was beta lactamase (also called penicillinase). Beta lactamase breaks the beta lactam ring and destroys penicillin's activity.

Ribavirin

Ribavirin is another nucleotide analog that stops both DNA and RNA synthesis (via unclear mechanisms). It is primarily used for the treatment of the RNA viruses like hepatitis C (in combination therapy with interferon) and respiratory syncytial virus. Possible side effects of ribavirin use include anemia and developmental effects on unborn children in pregnant patients

Nucleid acid synthesis Rifampin

Rifampin inhibits RNA synthesis and is commonly used to treat leprosy and tuberculosis because both are caused by organisms of the Genus Mycobacterium. These organisms are slow growers so therapeutic treatments are given over several months.

Inhibit nucleic acid synthesis

Rifamycin (STOPS TRANSCRIPTION), Fluoroquinolones

Ritonavir

Ritonavir stops the viral life cycle by inhibiting HIV protease activity.

Semi critical items

Semi critical items do not typically need sterilization but need a high level of disinfection. They may contact mucous membranes or non-intact skin but do not penetrate tissues (example: GI endoscopes).

Sepsis

Sepsis is a condition of contamination (which is our normal environment) If sepsis occurs in a patient, it can result in high fever, increased heart and respiratory rates, shock and possibly death.

Silver

Silvadene cream is commonly used to treat topical wounds and is particularly helpful in preventing infection in burn wounds.

What are the limitations of filtration?

Size selection

synergism

Some drugs will interact and increase the activity of one another

Synergism

Some drugs will interact and increase the activity of one another.

Streptomycin

Streptomycin was one of the first antibiotics that was used to treat tuberculosis. -causes the misreading of the mRNA -not commonly used because of hearing loss -cidal because of protein agglutination

Inhibit the 70S ribosome

Streptomycin, tetracyclines, Erythromycin, chloramphenicol

Sulfonamides

Sulfonamides are agents that stop the synthesis of folic acid, a precursor for nucleotide synthesis.Sulfanilamide is an example of a competitive inhibitor. Competitive inhibitors bind to the active site of an enzyme and block the substrate from entering.

Surfactants

Surface-active agents, or surfactants, are a group of chemical compounds that lower the surface tension of water. Surfactants are the major ingredients in soaps and detergents

Soap

Surfactants. Soaps are salts of long-chain fatty acids and have both polar and nonpolar regions, allowing them to interact with polar and nonpolar regions in other molecules. Their amphipathic nature allows them to interact with the oils on the skin. This allows them to lift and remove skin contaminants. Their main degerming action is to mechanically carry away the microbes.

pHisohex

The bisphenol hexachlorophene, a disinfectant, is the active ingredient in pHisoHex, a topical cleansing detergent widely used for handwashing in hospital settings. pHisoHex is particularly effective against gram-positive bacteria, including those causing Staphylococcal and Streptococcal skin infections. pHisoHex was formerly used for bathing infants, but this practice has been discontinued because it has been shown that exposure to hexachlorophene can lead to neurological problems.

Commercial sterilization

The canning industry uses commercial sterilization to reduce the number of microbes in its product. THIS IS AN INAPPROPRIATE USE OF THE TERM "STERILIZATION." What comes out of commercialization is a degermed product, not sterile. The main purpose of commercial sterilization is to destroy the endospores (survival structures) of Clostridium botulinum.

Carbapanems

The carbapenems also have a beta lactam ring. They also work to inhibit cell wall synthesis by binding to enzymes involved in cell wall synthesis. Their structure is different from the other beta lactams and that gives them a high level of resistance to beta-lactamase. They have low therapeutic indices, so in many cases they are reserved as last line of defense drugs for those microbes that are hard to kill. They are commonly used to treat infections caused by Pseudomonas aeruginosa but are ineffective against MRSA. The carbapenem family includes a variety of semisynthetic drugs (imipenem, meropenem, and doripenem) that provide very broad-spectrum activity against gram-positive and gram-negative bacterial pathogens.

Cephalosporins

The cephalosporins also have the beta lactam ring but they are structurally different from the penicillins. This structural difference makes them less susceptible to beta lactamases. Cephalosporins also bind to penicillin binding proteins that synthesis the peptidoglycan cell wall, thus stopping cell wall synthesis. They are bactericidal because when they work, they cause osmotic lysis, in their target cell. The first generation was effective against Gram positive bacteria (narrow spectrum), but improvements have made the subsequent generations into more broad-spectrum antibiotics. Some members of the cephalosporin family can cross the blood-brain barrier. Cephalosporinases do exist and are capable of deactivating members of the cephalosporin family -MULTIPLE GENERATIONS -INITIAL GENERATIONS NARROW SPECTRUM -LATER GENERATIONS EXTENDED TO BROAD SPECTRUM

isoniazid

The drug isoniazid has long been used in combination with rifampin or streptomycin in the treatment of tuberculosis. Isoniazid prevents the synthesis of mycolic acid, which is essential form ycobacterial cell walls. Possible side effects of isoniazid use include hepatotoxicity, neurotoxicity, and hematologic toxicity (anemia). -STOPS MYCOLIC ACID SYNTHESIS

Mechanisms of antibiotics CELL WALL

The first major target is the cell wall. The major role of the cell wall is to prevent osmotic lysis. Many of the drugs that target the cell wall, target cell wall synthesis. This means that they will only influence vegetative cells, since non-vegetative cells are not undergoing cell wall synthesis. If these antibiotics work, the cells will die via osmotic lysis (when conditions are appropriate).

Halogens

The halogens consist of Iodine, Chlorine, and Fluorine. Theses active ingredients are good at killing a variety of different microbes, including Bacteria, Fungi, most endospores, some viruses. They have good activity against Mycobacterium and can be sporicidal at higher concentrations. -IODINE: DENATURES PROTEINS -TINCTURE: INDINE MIXED WITH ALCOHOL -IODOPHOR: IODINE + ORGANIC MOLECULE -CHLORINE: BREAKS DOWN ALL MOLECULES

Metabolism

The last major target is metabolism. There are a variety of type of metabolism that are influenced by antibiotics. Some target DNA replication or transcription. Others influence specific essential metabolic pathways.

Penicillin family

The penicillins are also called the beta lactams, because they all possess this ring. This β-lactam ring is essential for drug activity. The penicillins act by binding to and inhibiting an enzyme that is involved in cell wall synthesis. Stopping this enzyme will lead to osmotic lysis in the affected cell, when conditions are appropriate. Most of the penicillins work well against the Gram positives, but not so well against the Gram negatives. The reason is because penicillins have a hard time making it across the Gram negative's selectively permeable outer membrane. They can still be used to treat Gram negative infections, but the dosage usually changes (higher).

70s ribosome

The second major target is the 70S ribosome. The ribosome synthesizes proteins and proteins are essential for life.

Extended-Spectrum β-Lactamase-Producing Gram-Negative Pathogens

The spectrum of β-lactams inactivated by ESBLs provides for resistance to all penicillins, cephalosporins, monobactams, and the β-lactamase-inhibitor combinations, but not the carbapenems. An even greater concern is that the genes encoding for ESBLs are usually found on mobile plasmids that also contain genes for resistance to other drug classes (e.g., fluoroquinolones, aminoglycosides, tetracyclines), and may be readily spread to other bacteria by horizontal gene transfer.

Sanitization

The term sanitization refers to the cleansing of fomites to remove enough microbes to achieve levels deemed safe for public health.

Tetracyclines

The tetracyclines are broad-spectrum antibiotics that inhibit proteins synthesis by preventing tRNAs from entering the ribosome. They are bacteriostatic, in nature. Some examples included oxycycline and tigecycline. Side effects include phototoxicity (increased risk for sunburn), teeth discoloration (especially in children under 8) and liver toxicity. -STOP TRNA ENTRY

Mycobacterium are hard to kill because of two reasons.

They have a slow rate of metabolism and they have a mycolic acid barrier. The mycolic acid is a fatty acid that is intertwined in the cell wall. It is super selectively permeable, so a lot of our treatments cannot penetrate it. It also allows Mycobacterium to persist in an environment by preventing desiccation (drying out).

what is the therapeutic index what does a high TI mean? Low TI?

This is a ratio of the effects on them/the effects on us. An anti-microbial with a high therapeutic index kills them I'll causing minimal damage, if any, to us. An anti-microbial with a low therapeutic index kills them and also causes damage to us.

Clostridium botulinum

This microbe produces a neurotoxin and causes botulism. This neurotoxin blocks the release of acetylcholine, which causes one of the main symptoms of botulism, flaccid paralysis.

how do you microbes gain resistance to antibiotics/treatments?

Through the process of cell replication, some bacteria develop mutations that makes them resistant to antibiotics.

therapeutic index

To measure selective toxicity, we use the therapeutic index. This is a ratio of the effects on them/the effects on us. An antimicrobial with a high therapeutic index kills them while causing minimal damage, if any, to us. An antimicrobial with a low therapeutic index kills them and also causes damage to us. Usually these types of drugs are withheld for the harder to treat cases (like multi-drug resistant microbes that do not respond to other treatments).

which enzyme increases HIV's genetic diversity

Transcriptase

Glycopeptides (Vancomycin)

Vancomycin is called the "LAST LINE" of defense against MRSA. VRSA is one of them that is a major concern because is some cases we do not have an antibiotic that will destroy this type of resistant microbe(IN SOME CASES). Vancomycin is not absorbed orally so it must be given via IV if the infection is not in the digestive tract. It can be toxic to the ears and kidneys which is why it is not used frequently. It works best on Gram + microbes. In most cases it is not active against most Gram -microbes because it can't effectively penetrate the outer membrane. Vancomycin prevents peptide cross linking of the peptidoglycan which leads to osmotic lysis in affected cells. -BLOCKS PEPTIDE CROSSLINKING -LAST LINE OF DEFENSE AGAINST MRSA

Fomites

We constantly come in contact with inanimate objects that help spread disease, called fomites (door knobs, toys, credit card machines at Walmart, grocery carts, etc.).

Fungal cell membrane

We use cholesterol to regulate membrane fluidity. Fungi use ergosterols. This difference allows us some selective toxicity. Azoles target ergosterols and increase membrane permeability(causing cytolysis and cell death). Miconazole, ketoconazole, and clotrimazole are used to treat fungal skin infections (caused by dermatophytes) such as ringworm, specifically tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm)

semisynthetic antimicrobial

a chemically modified derivative of a natural antibiotic

bisphenol hexachlorophene

a disinfectant, is the active ingredient in pHisoHex, a topical cleansing detergent widely used for hand washing in hospital settings. pHisoHex is particularly effective against gram-positive bacteria, including those causing Staphylococcal and Streptococcal skin infections. pHisoHex was formerly used for bathing infants, but this practice has been discontinued because it has been shown that exposure to hexachlorophene can lead to neurological problems

synthetic antimicrobial

a drug that is developed from a chemical not found in nature

Oxacillin

a modified member of the penicillin family that is resistant to many penicillinase producing microbes. -RESISTANT TO BETA LACTAMASE

Ampicillin

an extended spectrum antibiotic that is commonly used in biotechnology. It works well against Gram positives and has increased activity against Gram - microbes, versus other penicillins. G+ and more G- than penicillin. Parenteral and oral. -EXTENDED SPECTRUM

antibiotic chemotherapy

any use of chemicals or drugs to treat disease

Why is C-diff resistant to alcohol?

because it can produce endospores, so you don't want to "foam out" using an alcohol-based hand sanitizer, after cleaning up that patient's diarrhea.

C-diff

causes colitis and diarrhea

Zinc chloride

commonly found in mouthwashes. Zinc oxide is found in topical antiseptic creams such as calamine lotion, diaper ointments, baby powder, and dandruff shampoos.

Ototoxic

damage to the ear

Nephrotoxic

damage to the kidneys

neurotoxic

damage to the nervous system

Aseptic

describes a contaminate free state (the desired condition in health care, where there are immunocompromised patients). In a clinical setting, doctors and nurses practice aseptic("sterile") techniques (a combination of protocols that collectively maintain sterility, or asepsis) to reduce the incidence of disease transmission.

Methicillin

designed to be penicillinase resistant. This strategy initially worked; however, microbes have discovered other mechanism by which methicillin resistance is achieved. **G+ only including B-lactamase producers. Parenteral

Sporicide

destroys endospores

where is VRE commonly found in hospitals?

doorhandles. These strains are typically spread among patients in clinical settings by contact with healthcare workers and contaminated surfaces and medical equipment.

Triclosan

found in antibacterial soaps, Colgate and many plastics. Your child's toys probably have this to prevent the spread of disease.

Viricide

inactivates viruses

Bacteriostatic

inhibits bacterial growth

Antisepsis

is the application of an antiseptic (an antimicrobial chemical that is safe to use on living skin or tissues). In addition to the characteristics of a good disinfectant, antiseptics must also be selectively effective against microorganisms and able to penetrate tissue deeply without causing tissue damage. Alcohol (ethanol or isopropanol) and hydrogen peroxide are commonly used antiseptics.

Bactericide

kills bacteria

Fungicide

kills fungi

STATIC

means inhibits the growth

CIDE

means it kills

zone of inhibition

plate clearing where bacteria could not grow

Amoxicillin

similar to ampicillin but a slight change in its structure allows better absorption in the intestines. Similar to ampicillin, Oral (better than ampicillin)

Sterilization

sterilization (the killing of all microbes, the inactivation of viruses and the destruction of all endospores) is the most complete.

phenolics

the chemical compounds found in antiseptic mouthwashes and throat lozenges. They inhibit microbial growth by denaturing proteins and disrupting membranes. They are effective against Mycobacterium spp, organisms that is hard to kill because of its very effective mycolic acid barrier. EXAMPLES: Cresols (methylated phenols) and o-phenylphenol were active ingredients in various formulations of Lysol.

Disinfection

the inactivation of microbes on a surface of a fomite. Disinfectants use chemicalor physical means of removing microbes from nonliving items. Ideally, disinfectants should be fast acting, stable, easy to prepare, inexpensive, and easy to use. After disinfection, the environment is not sterile because in many cases, non-vegetative cells/endospores survive.

route of administration

the method used to introduce a drug into the body. Drugs that can be administered orally are generally preferred because patients can more conveniently take these drugs at home. However, some drugs are not absorbed easily from the gastrointestinal (GI) tract. Sometimes, patients may not initially be able to take oral medications because of their illness (e.g. vomiting, intubation for respirator). When this occurs, and when a chosen drug is not absorbed in the GI tract, administration of the drug by a parenteral route (intravenous or intramuscularinjection) is preferred and typically is performed in health-care setting.

Degerming

the process of removing microbes from an area. Methods of degerming include sterilization, disinfection, antisepsis and sanitization. Sterilization can be accomplished through physical (high heat, pressure, and filtration) or chemical means (sterilants).

why is CRE hard to treat?

these pathogens develop resistance to carbapenems through a variety of mechanisms including production of carbapenemases, Active influx of carbapemems out of the cell, and or prevention of entry through porin channels.