Unit 4 Control of Microorganisms

Host-microbe Interactions

- Contamination spill S. aureus on my hand. - Infection - next step when there is multiplication of the organism within the host (replicating). -Infestation - when discussing parasitic worms or arthropods (ectoparasites) - tapeworm infestation, louse infestation - Disease - state of health is disrupted. Infection turns more serious

Preventing Microbes from Acquiring Resistance

- High levels of abx in body to kill all pathogens - Synergism - additive effect: using 2 abx at same time that might work by different mechanisms. (ex. Augmentin - combination of amoxicillin and clavulanic acid) - Restrict usage to essential use only - Ban use of abx in animal feeds

How to determine how effective an agent (of destroying microbes) is?

- Length of time that agent is contact with the microorganisms (like disinfecting the lab bench and DON'T dry it off so chemicals are in contact with the microbes longer to do their job - Heat (put loop in incinerator for about 15 seconds) - Higher temps do much better - pH extremes are the best (very acidic or very basic solutions do a better job since most of the things we work with fall in the middle of the range - neutral) and will be more damaging to the microorganisms - Concentration of chemical agent (usually the higher the concentration, the better job it will do)Higher is bacterialcidal, lower is bacteriostatic. Alcohol sold in stores is an exception - usually about 70% so that it won't evaporate quickly. - Type and number of microorganisms (agent might work on one type, but not on another or not as well) - organic material (like puss on a wound that would need to be cleared and out of the way so reach the surface)

Modes of Antibiotic Resistance - The ability of the microorganism to remain unharmed even in the presence of the anti-microbial agent.

-Mutation - Presence of R plasmid (extra piece of DNA not in the chromosome) - Lateral gene transfer Enterococcus can transfer VRSA to staph and make it VRSA - Evasiveness (Mycobacterium tuberculosis hides in the lungs) . L forms -bacteria that have the ability to stop making their cell wall, abx doesn't work then it's discontinued so the L forms make their cell wall again - Development of enzymes - Change metabolic pathways - makes a detour

Chemical means of controlling microbes (1) Disinfectants and Antiseptics

-Phenols - damage the cell membrane, damage proteins,used for a while (Lister used carbolic acid). ex. Lysol, broad spectrum, stays active for a long time, triclosan found in antibacterial soaps, some kids toys, but problems is that microbes are becoming resistant to it creating highly resistant microorganisms. BEST to wash your hands with soap. - Halogens: chlorine, iodine, bromine. They impair protein synthesis, alter cell membrane. ex. iodine - used as tincture (iodine mixed with alcohol) or iodophor (iodine mixed with soap) with soap it's more of a slow release, longer contact with iodoi. Betadine is an iodophor (surgical scrub). Doesn't completely sterilize, endospores are generally resistant to it, but does do a good job.

5 ways antibiotics work (will be on lab report test) - need to know names of the examples

1. Inhibition of cell wall synthesis- Damages the bacteria, but does not harm the host bc we don't have cell walls. (Antifungals work this way,too.) Ex. of Abx or antimicrobials: a. Penicillins - Narrow spectrum - Effective against Gram + organisms, but also semi-synthetic penicillins (methicillin, amoxicillin, oxicillin) - these have a broader spectrum of activity b. Cephalosporins (Broad spectrum often used on pts. allergic to PCN )- is a true Abx derived from a soil fungus, BUT it is also semi-synthetic because there are a lot of cephalosporins (cefotetan, cefepime) Most that start with cef or ceph c. Polypeptide drugs (Narrow spectrum effective against Gram +) Vancomycin is very potent, but has side effects: kidney damage, hearing loss, large molecule - too large to fit through the pores in Gram - organisms) . Bacitracin is in Triple Abx cream. Triple Abx cream Bacitracin is a polypeptide drug and so it's effective against Gram + organisms Summary of all above - if a bacteria can't synthesize its cell wall, it will not do well. Sometimes it pops the cell wall.

Physical means of eliminating microbes (5) Examples of dessication:

1. salt - changes the concentration gradient so that the water has to leave (think of internal concentration vs. external concentration of salt - the water follows the salt - called OSMOSIS). Cell will shrivel up. Draws moisture out of microbes, too, preserves it makes it last longer. - dried meats 2. sugar - works the same way, Osmosis - Think of the dried fruit (after a week would you eat a piece of pineapple or the one that has been dried) 3. clothes dryer - even on warm dry, but the drying portion gets all the moisture out (lice) 4. sun drying - raisins, tomatoes

Exotoxins (con't)

2. Cytotoxins affect cells. Ex. hemolysins: break down RBC's and hemoglobin and lose iron. Leukocidins: Kills WBC's. Staph and strep can produce cytotoxins that can produce hemolysins and leukocidins. 3. Enterotoxins -( Intestines) They act on gus tissue, stomach. ex. s. aureus produce enterotoxins, common cause of food poisoning bc it's such a common organism - on the skin, etc. Vomiting and diarrhea. Vibrio cholerae Gram - produces enterotoxins, cause ionic imbalance in the intestines,

5 ways antibiotics work (will be on lab report test) - need to know names of examples

2. Disruption of cell membrane function generally effective against Gram - - if the cell membranes become distorted, it's not going to allow for cellular contents to be lost, organism won't be able to bring things in properly. So knowing that Gram - cell wall/membrane would be so effective against Gram - BECAUSE they have lipopolysaccharide, which is part of the outer membrane which looks like is a phospholipid bi-layer. So the Gram - organisms basically have two membranes. They have the regular cell membrane and the outer membrane. So if it "disrupts" the membranes, it will work well on Gram - a. Polymyxin B - narrow spectrum, eff. against Gram - , in a triple antibiotic

5 ways antibiotics work (will be on lab report test) - need to know names of examples

3. Inhibition of protein synthesis - generally there is some toxicity with these types of Abx. Review ribosomes: site of protein synthesis, bacterial ribosomes (structure is 70S ribosomes, Large subunits is 50-S small is 30-S are different from eukaryotic ribosomes (80-S with subunits of 60- and 40). So these abx act on the 50 or 30 subunits of the prokaryotic ribosome. Only can affect the mitochondria and most of these abx can't get in to the mitochondria ( COULD damage it because our mitochondria is 70S ribosomes) a. Chloramphenicol very potent abx use to be used to treat meningitis bc it crossed the blood/brain barrier, but now there are safer alternatives.

5 ways antibiotics work (will be on lab report test) - need to know names of examples

4. Inhibition of nucleic acid synthesis - the enzymes that bacteria use to synthesize their nucleic acids of DNA or RNA are somewhat different than the enzymes used in eukaryotes like us. You can target nucleic acid synthesis as a way killing microorganisms. a. Quinolones/fluoroquinolones (ciproflaxacin, levoflaxacin) - Broad spectrum, used for UTI's, systemic conditions incl. anthrax. Levo is expensive (levoquin) effective but some organisms are resistant to it. b. Rifamycins (rifampin) narrow spectrum, are anti-MYCObacterial - effective mycobacterium (waxy cell wall).

Selective toxicity

Ability of an agent to be toxic to the microbe but not to the host. (Paul Ehrlich was looking for the magic bullet - found it for a while in salvarsan while treating syphillis.)

Viricide

Agent that inactivates viruses.

Sporocide

Agent that kills bacterial endospores.

Fungicide

Agent that kills fungi.

Bacteriacidal

Agent that kills the bacteria.

Bacteriostatic

Agent that stops the growth of the microorganism (bacteria).

Chemical means of controlling microbes (2) Disinfectants and Antiseptics

Alcohols - generally mixed with water bc if they are too high concentration they evaporate quickly. They are lipid solvents so they dissolve membranes. Do a good job, but some drawbacks as antiseptic. - Because they evaporate so fast even when diluted, using them on skin, they don't get deep down into the pores. - When used on wounds, they can actually cause coagulation of certain proteins, which can trap the bacteria underneath so that they don't come in contact with the alcohol, slows healing. - Some bacterial endospores can survive in alcohol for a long time, some can survive in 70% ethanol for over 20 years.

Beta lactamase

An enzyme that some bacteria produce that breaks the beta lactam ring of an Abx. makes it inactive

Other Antimicrobials

Antifungals: Treat fungal infections. Difficult to find a point of selective toxicity (best place to attack it) because they have the same make-up as us (ribosomes, membranes, enzymes...), they DO have cell walls so that is a point of selective toxicity because it's something different that we DON't have. - amphotericin B - clotrimazole - OTC - Miconazole - OTC - Ketoconazole - griseofulvin

Other Antimicrobials

Antiprotozoans - chloroquine - treat Malaria (caused by Plasmodium) so it's used against Plasmodium - metronidazole (flagyl) ** is also an antibiotic and is used against anaerobic bacteria Antihelminths (worms) - Piperazine - paralyzes the worm - ivermectin - paralyzes the worm

Other Antimicrobials

Antivirals: Viruses are hard to target without harming the host because they are inside the cells and possibly in the genome. - Tamiflu - influenza, inhibits the NA spike has to do with how the influenza gets out of the host cell, Tamiflu targets the spikes so it can't spread - Acyclovir- herpes - Interferon - naturally occurring substance that our bodies produce, it's produced to be used as a treatment. Inhibits the spread of viruses to new cells. Not a cure. - AZT -1st drug approved for treating HIV, affects the enzyme reverse transcriptase, the enzyme that makes RNA into DNA - Norvir - HIV. Blocks a protease enzyme (proteases are enzymes that break proteins down). The virus has to break certain proteins for the virus to mature and spread to other cells.

Kirby Bauer Method (Disc diffusion method)

Bacteria may reach a concentration of the abx that is too high for the bacteria to continue growing: zone of inhibition, measure mm diameter. Smallest zone is 6 mm

Chemical means of controlling microbes (9) Disinfectants and Antiseptics

Benzoyl peroxide is antiseptic effective against anerobic bacteria, esp. acne. One of the bacteria in acne is Proprioni bacterium acnes which is anaerobic bacteria lives deep in pores, not a problem unless it goes crazy, multiplies.

Antiseptic

Chemical agent that can be used on external tissues to inhibit microbial growth or destroy the organisms. - Listerine

Disinfectant

Chemical agent used on inanimate surfaces (i.e., a table) to destroy microbes or inhibit their growth. - Lysol

Antibiotics

Chemical agents that are used to either inhibit or kill bacteria. *True definition is that the chemical being used is derived from another microorganism. - Penicillin is a true antibiotic because it comes FROM penicillium, which is a microorganism. - The ones manufactured in a laboratory (synthesized in the lab from chemicals) are still called antibiotics, but they are "synthetic" antibiotic or semi-synthetic (made in part in lab from chemicals and part from microorganism that is tweaked in the lab), not a TRUE antibiotic, not derived from a microorganism.

5 ways antibiotics work (will be on lab report test) - need to know names of examples

Chris' notes about chemical reactions: A - B - C - D - E - F - G altogether this is a metabolic pathway, reactants are the starting substances of a chemical reaction then you have the product. B is reactant and C is product, but it continues moving to the right. All can be reactants, B - E are products, B C D are both so they are called intermediates or metabolites. SO: 5. Action as antimetabolites - The antibiotics mimic one of the metabolites (this is called molecular mimicry, where the molecule is very simil a. Sulfonamides - The Abx mimics a substance PABA, bacteria have long metabolic pathway and final product is folic acid. They make it and need it to survive. WE need it to survive. Green leafy vegetables. One of the steps along the way is PABA. They mimic PABA and then replace PABA so the pathway can't continue, can't make folic acid and the bacteria dies. Ex. is Bactrim-trimethoprim sulfamethoxazole - broad spectrum, UTI's

E-test method

Combination of diffusion and the dilution in some ways. Strip is impregnated with abx, but different concentrations all the way down the strip low to high. And it's listed on the strip. Instead of a circle, it makes an elliptical shape. Instead of measuring diameter, measure where the zone of inhibition meets the strip to get the MIC (minimum inhibitory concentration). This one you actually get a numeric value. (.64 for ex. is a concentration of antibiotic)

Means of Damaging Bacterial Cells

Damage cell membrane - Causes loss of cell contents - Inability to bring in nutrients Denatures proteins (which are involved in everything inside the cell, chemical reactions are catalyzed by enzymes and generally enzymes are proteins) Disrupts nucleic acids (prevent replication)

Pathogenicity - organism's capability to produce disease (sometimes people interchange this with virulence, but virulence is the degree of pathogenicity: to what extent)

Depends upon: - its ability to invade host - Number of invading microbes (some you only need 1 microbe, some you need a lot more) - Ability to multiply in host (not all viruses are suited to be in a human host, so it won't be pathogenic: feline leukemiavirus) - Ability to avoid damage from host defenses (some produce capsules which prevent the immune system from phagocytize it - engulf it) OR the tuburcles that are produced.

Physical means of eliminating microbes (4)

Dessication (drying) when you're drying something out, you separate the cell wall from the cell membrane, break membranes (which changes the osmotic pressure, when you change osmotic pressure you draw moisture out of the cell. Pretty effective, however, viruses and most endospores are resistant to this and some vegetative cells can be resistant.

Measurements of Disinfectant Effectiveness (2)

Disc Diffusion Test: Streak plate with a lawn of bacteria, put discs on plate with various disinfectants (antiseptic or antibiotic) on the plate before growth starts. Whatever is on the disc will diffuse through the media, highest concentration is in the center of the disc and gets weaker as the diameter grows. Sometimes it will STOP the bacteria from growing there is no growth in the zone of inhibition. Measure the diameter of the zone, refer to chart to find out if bacteria is susceptible, intermediate or resistant to the material on the disc.

Chemical means of controlling microbes (6) Disinfectants and Antiseptics

Ethylene oxide is a gas that will inactivate proteins, it's a gas sterilant, does completely sterilize, does a good job. BUT, in pure form it's explosive so would want to use in a 20% concentration, also is carcinogenic - need to use it in a well ventilated area and take proper precautions, takes time to do it's job - not fast

Exotoxins

Exotoxins are produced primarily by Gram + organisms, but there are few Gram - that produce them. They are produced inside of the cell and released. More powerful than endotoxins. They are proteins. 1. Neurotoxins - exotoxins that affect the nervous system (botulinum toxin produced by Clostridium botulinum, causes paralysis of muscles while in flacid state - MOST POTENT NEUROTOXIN) (Clostridium tetani PRODUCES the neurotoxin, too.)** Will be on test.

Physical means of eliminating microbes (3)

Filtration - Good for liquids and for gases, esp. large quantities. - HEPA filter (High efficiency particulate air) used to remove microbes that are very small (.3 micrometers in size, recall that E. coli is about 1 micrometer) end up with sterile or almost sterile air or water passes through the filter and the filter stops mosts things - air, vacuum, and in cabinets - laminer air flow cabinets (hood) Helps people working with nasty microbes to get them filtered out so they're not inhaled. Most hoods also have ultraviolet light attached to use after working.

HIV treatment

HART - Highly active anti-retroviral therapy. It means using lots of different anti-virals that target the virus from different angles in hopes that it keeps the viral load down.

Physical means of eliminating microbes (1)

Heat (denatures proteins and breaks membranes) - Dry heat will completely sterilize (incinerator, passing over the Bunsen burner) - Moist heat (boiling water, but doesn't completely sterilize, some viruses and some bacterial endospores that can survive boiling) . autoclave (they DO sterilize, uses steam which is very hot - like a pressure cooker - +the pressure will + the temp)

Chemical means of controlling microbes (4) Disinfectants and Antiseptics

Heavy Metals - silver, mercury, copper, zinc - Silver nitrate is a solution that has been added to the eyes of newborns (use to, now use Abx drops like for Neisseria gonorrhea transmission for birth). Silvadine used for burn victims - very expensive. - Mercury use to be used as mercurachrome antiseptic, red color on scrapes, etc. (could lead to mercury poisoning) - Copper sulfate is used as an algacide in water, however, EPA has been evaluating it bc it may be an environmental hazard. Hand sanitizer "x-gel" does not use alcohol, it uses copper. - Zinc oxide is a fungicidal agent used in paints to prevent fungal contamination (disinfectant) -Zinc chloride can be found in mouthwashes (antiseptic)

Chemical means of controlling microbes (7) Disinfectants and Antiseptics

Hydrogen peroxide - H2O2, most people use it as an antiseptic, but not good used that way. (good to gargle or use for swimmer's ear) It can slow healing and our cells have the enzyme catalase so they can break down H2O2 into water and oxygen, which does nothing. Better as a disinfectant (chefs use it). Good for puncture wounds if you can get it down into the wound before it's broken down. Because the anaerobic bacteria do not have enzyme catalase.

Sterilization

Killing or removing ALL microorganisms, including inactivating bacterial endospores and inactivating viruses.

MIC (minimum inhibitory concentration)

Lowest concentration of antibiotic that inhibits the growth of the bacteria.

Serum killing power

Measures how effective the antibiotic is during treatment. Would have to know exactly what microorganism caused the infection and have to have the exact organism from that pt. (ex. S. aureus comes in many strains). Have to know abx they are on - get blood sample, use the serum (liquid) portion, spin it down, add a bacterial suspension to the serum (the EXACT bacterium that was causing their infection), incubate, look for turbidity. If it's turbid the abx is not enough or the wrong one.

Narrow spectrum

More limited than broad spectrum. It will be effective against a small number of maybe even just one type of pathogen. You know what the microorganism is and you want to use the Abx that will treat it and target it, you don't want to harm host normal flora. (You could end up wth an opportunistic infection and you could increase the likelihood of resistant microorganisms popping up.)

Communicable disease Non-communicable disease

Note: infectious disease is simply any disease caused by an infectious agent (bacterium, virus, prion, fungus, protozoan, helminth) Communicable disease - Contagious-easily spread from person to person (ex. influenza, HIV) - Not contagious-not easily spread from person to person (ex. Lyme disease, Tetanus: Clostridium tetani) Non-communicable disease - Never contagious

Opportunistic infections

Opportunists are transient or normal. Cause infections due to certain conditions that allow them to thrive. (vaginal yeast infection usually ok, but other bacteria get in when ex. lactobacillus decreased from Abx.) and C. diff. 1. Immunocompromised individuals (very young or very cold, malnourished, pregnant, other diseases (AIDS), some drugs 2. Introduction of organism into unusual sites 3. Disturbing normal microflora with antibiotics

Chemical means of controlling microbes (5) Disinfectants and Antiseptics

Organic acids - Sorbic acid or benzoic acid (food preservatives) block enzyme function, prevent food from being contaminated esp. with fungi Glutaraldehydes - is one of the only liquids with sterilizing capability, so doesn't just reduce the number of microbes, but it's a liquid that can potentially completely sterilize. Formaldehydes - is a gas, IS an excellent sterilant. Formalin (3% formahaldehyde gas mixed in aqueous solution (gas + liquid) used to preserve biological samples (now they use something less hazardous). In clinical setting, samples from different dept. in the hospital and sometimes it would go to the lab in formalin when it was not supposed to be. Can't culture something that's been in it because it kills everything.

Microflora

Organisms that live in you or on you and are nonpathogenic Normal microflora - Generally permanent No normal microflora is NOT in stomach - acid Blood - will not find microflora (blood as WBC's protected by immune system) Brain - CNS microbes can't there, if they DO, serious health issues Transient microflora - may be present for a small time period, can be pathogenic or non-pathogenic - temporary Cut yourself with a knife in the kitchen might go into blood, they are there for a brief period. Opportunists are transient in this case.

Chemical means of controlling microbes (8) Disinfectants and Antiseptics

Ozone - O3 (oxygen is O2) ozone is formed by passing oxygen through a high voltage discharge, like lightning. Helps protect from UV light. Ozone being broken down (partially due to CFC's), seeing skin cancers. Ozone can be used to purify water, in some purification systems, not quite as unpleasant as chlorine in pools, drinking.

Endotoxins

Part out of the outer membrane of Gram - organisms. Endotoxin is the same as the lipopolysaccharide. Endotoxins are released from Gram - bacteria when the bacteria dies when the cell wall breaks down. Endotoxins generally cause bp to drop, fever, DIC (Disseminated intervascular coagulation) your body throws tiny clots, all clotting factors are being used up, then you have bleeding issues. The endotoxin release causes ENDOTOXIC SHOCK.

Physical means of eliminating microbes (2)

Pasteurization (gentle heating -not boiling), doesn't necessarily kill everything. The purpose is to decrease the population enough to prevent or slow spoilage. (milk - will last longer and have less potential harmful things) . Flash heats (AKA high temp. short time) ex. heat milk for 15 secs. at about 72 degrees Celsius (100 degree C is boiling) . Holding method (AKA classic method) 63 degrees C for 30 mins. . UHT (ultra high temperature) starts 74 degrees C, goes up to 140 deg. C., then back down to 74 : ALL IN 3 seconds. COMPLETELY STERILIZES - Used in shelf milk (Parmalat, coffee creamers that don't need refrigeration)

Virulence Factors

Pili for attachment, surfaces, to cells Capsules protect bacteria from phagocytosis Enzymes (bacteria produce) -Gelitinase - Coagulase forms clots, S. aureus around itself and hide - Hyaluronidase - breaks down hyaluronic acid that acts like a glue holding cells together, can break through the cells then - Streptokinase - breaks clots, microbes spread further Toxins - some bacteria produce toxins poisonous to other organisms, toxins spread through blood called toxemia

What is the most narrow spectrum Abx?

Polymyxin or Isoniazid

Chemical means of controlling microbes (3) Disinfectants and Antiseptics

Quats (quaternary ammonium compounds) - (JUST KNOW QUATS) detergents that are attached to ammonia and they denature proteins and disrupt cell membranes. Good against gram + organisms. Found in things that are sudsy, ear piercing kits, some mouthwashes (Cepacol),

Physical means of eliminating microbes (6)

Radiation - Ionizing Ionizing: Gamma rays, x-rays, penetrate very well, break DNA into little pieces, can be used for medical lab equipment, helps to prevent spoilage in seafood, some meats are irradiated to prevent E. coli 0157H7, salmonella (after anthrax some mail was being irradiated that was sent to people that might have been a target) UV - non-ionizing, going to disrupt the replication of DNA by interrupting normal base pairing (causes thymine dimers or pyrimidine dimers where adjacent thymine will not bind to its complementary adenine, instead bind to each other and it disrupts DNA replication and transmission). - Problems: doesn't penetrate well or go around corners it doesn't really bend and it can damage your eyes. - Used in air ducts, ICU units.

What is the most broad spectrum Abx?

Tetracyclines

Therapeutic dosage level

The dosage level of the antimicrobial in which the pathogenic organism is eliminated and the host is not harmed.

Toxic dosage level

The level of an antimicrobial that's going to harm the host (do not want to give someone a dosage that meets or exceeds this level)

MBC (minimum bactericidal concentration)

The lowest concentration of abx that kills the microorganism. Take all the test tubes that show no growth and subculture each one to an agar plate and incubate the plates (because just bc you can't see it doesn't mean it's dead). Then figure out which ones were killed by the abx and which ones just stopped the growth. Where the minimum where there was NO growth.

Spectrum of activity

The range of different microbes that an antimicrobial is effective against - a range.

Mycotoxins

Toxins produced by fungi (molds) Lots of mycotoxins: ex. is Aflatoxins : Aspergillus flavus found in grains, nuts, that are stored for a long period.

Measurements of Disinfectant Effectiveness (1) (refer to notes I made too)

Use Dilution Test: Use stainless cylinders, coat them with bacteria and allow them to dry at 37 degrees until they are dried. Take the cylinders, you have tubes with different concentrations of disinfectants, dip the cylinders into the tubes for about 10 mins., rinse them, take cylinders and put in T.S. broth, incubate them 24 hours, look at the broth for turbidity and which has no turbidity. You would say that the highest dilution with no growth would be your use dilution rating

Commercial sterilization

Used in food preparation - simply enough heat to kill the endospores of Clostridium botulinum. Doesn't necessarily kill everything else, but does get rid of these spores, which can make people sick.

Chemotherapy

Using chemicals to treat various aspects of disease.

Dilution Method

Using test tubes or microwells like we used. Different concentrations of the abx in test tubes. Then add a known concentration of bacteria to the tubes, incubate then look for growth (turbidity) (button in the microtitre)

Broad spectrum

Will be effective against a wide range of different pathogens. Would use if you didn't know what the microorganism is but you want to begin treatment. Problems: could harm normal flora and it's going to increase the likelihood of resistant microorganisms popping up.

5 ways antibiotics work (will be on lab report test) - need to know names of examples

b. Aminoglycosides (amikacin, gentemycin, tobramycin, neomycin (is the 3rd in abx cream and is effective against Gram + AND Gram -), streptomycin - which is old and from a soil organism. Broad spectrum. c. Tetracyclines (tetracycline, doxycycline) BROAD spectrum used for many things (UTI, anthrax, Lyme or minor like acne) d. Macrolides (erythromycin, azithromycin) Erythromycin is narrow spectrum, good for Gram + . Azithromycin is broad spectrum and used quite a bit. AKA "z-pack", great only take about 5 days (2 in first day then once daily, easier to remember)