ANTIBIOTICS-AN INVESTIGATORY PROJECT

Antibiotics are Chemical Substances that produce chemicals to produce new microorganisms in order to inhibit or surpress growth of other micoorganisms(Bacteria, Fungi or Protozoa)The termantibioticwas first used in 1942 bySelman Waksmanand his collaborators in journal articles to describe any substance produced by a microorganism that isantagonisticto the growth of other microorganisms in high dilution. With advances inmedicinal chemistry, most modern antibacterials aresemisyntheticmodifications of various natural compounds.[4]These include, for example, thebeta-lactam antibiotics, which include thepenicillins(produced by fungi in the genusPenicillium), thecephalosporins, and thecarbapenems. Compounds that are still isolated from living organisms are theaminoglycosides, whereas other antibacterialsfor example, thesulfonamides, thequinolones, and theoxazolidinonesare produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosyntheticorigin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms:Bactericidalagents kill bacteria, andbacteriostatic agentsslow down or stall bacterial growth.

History of AntibioticsHistory of antibiotics can be described in two segments as under:Early HistoryDuring ancient times; Greeks and Indians used moulds and other plants to treat infections. In Greece and Serbia, bread mould was traditionally used to treat wounds and infections. Warm soil was used in Russia by peasants to cure infected wounds. Sumerian doctors gave patients beer soup mixed with turtle shells and snake skins. Babylonian doctors healed the eyes using a mixture of frog bile and sour milk. Sri Lankan army used oil cake (sweetmeat) to server both as desiccant and antibacterial. MODERN HISTORYYearOriginDescription

1640EnglandJohn Parkington recommended using mold for treatment in his book on pharmacology

1870EnglandSir John Scott Burdon-Sanderson observed that culture fluid covered with mould did not produce bacteria

1871EnglandJoseph Lister experimented with the antibacterial action on human tissue on what he called Penicillium glaucium

1875EnglandJohn Tyndall explained antibacterial action of the Penicillium fungus to the Royal Society

1877FranceLouis Pasteur postulated that bacteria could kill other bacteria (anthrax bacilli)

1897FranceErnest Duchesne healed infected guinea pigs from typhoid using mould (Penicillium glaucium)

1928EnglandSir Alexander Fleming discovered enzyme lysozyme and the antibiotic substance penicillin from the fungus Penicillium notatum

1932GermanyGerhard Domagk discovered Sulfonamidochrysoidine (Prontosil )

During 1940's and 50's streptomycin, chloramphenicol, and tetracycline were discovered and Selman Waksman used the term "antibiotics" to describe them (1942).Reason for discovery: - this was the period of world war 2. So as to serve injured soldiers and to treat them quickly, scientists searched for new cure. Thus soon, after many new antibiotics were discovered.

THE DISCOVERY OF PENICILLINIn 1928, bacteriologist Alexander Fleming made a chance discovery from an already discarded, contaminated Petri dish. The mold that had contaminated the experiment turned out to contain a powerful antibiotic, penicillin. However, though Fleming was credited with the discovery, it was over a decade before someone else turned penicillin into the miracle drug for the 20th century.Penicillin(sometimes abbreviatedPCNorpen) is a group ofantibioticsderived fromPenicilliumfungi,[1]includingpenicillin G(IV use),penicillin V(oral use),procaine penicillin, andbenzathine penicillin(intramuscularuse).Penicillin antibiotics were among the first drugs to be effective against many previously serious diseases, such assyphilisand infections caused bystaphylococciandstreptococci. Penicillins are still widely used today, though misuse has now made many types of bacteriaresistant. All penicillins are-lactam antibioticsand are used in the treatment of bacterial infections caused by susceptible, usuallyGram-positive, organisms.Classification of antibioticsClassificationsA common scheme of classifications for antibiotics is drawn below:

Antibiotics can also be classified based on their chemical structure. A similar level of effectiveness, toxicity and side-effects is rendered by the antibiotics of same structural group. Broad spectrum antibiotics are effective against a broad range of microorganisms in comparison to narrow spectrum antibiotics. Bactericidal antibiotics kill the bacteria whereas bacteriostatic antibiotics halt the growth of bacteria.TYPES OF ANTIBIOTICSThese are the main classes of antibiotics. Penicillin such as penicillin and amoxicillin Cephalosporins such ascephalexin(Keflex) Macrolides such aserythromycin(E-Mycin),clarithromycin(Biaxin), andazithromycin(Zithromax) Fluoroquinolones such asciprofloxacin(Cipro),levofloxacin(Levaquin), andofloxacin(Floxin) Sulfonamides such as co-trimoxazole (Bactrim) andtrimethoprim(Proloprim) Tetracyclines such astetracycline(Sumycin, Panmycin) anddoxycycline(Vibramycin) Aminoglycosides such asgentamicin(Garamycin) andtobramycin(Tobrex)Most antibiotics have 2 names, the trade or brand name, created by the drug company that manufactures the drug, and a generic name, based on the antibiotic's chemical structure or chemical class. Trade names such as Keflex and Zithromax are capitalized. Generics such as cephalexin and azithromycin are not capitalized.

MAJOR ANTIBIOTICSGeneric Name(S)StrengthDosage FormICD Code

Daptomycin500mgInjectionY40.9

Meropenem125mg/Vial, 250mg/Vial, 500mg/Vial, 1000mg/VialInjectionY40.9

Nitrofurazone0.2%/1gmCream, Ointment, PowderY56

Polymyxin, Bacitracin and Neomycin3.5gm,Eye Drops, OintmentY40.9

Procaine/ Penicillin600,000 to 1,000,000 units/dayInjectionY40.0

Rifaximin200mg, 550mg, 400mgTablets

Roxithromycin50mg, 150mgTabletsY40

Sisomicin3mg/3mlEye dropsY40

Spiramycin0.375 MIU x 5 mL x 60mlSuspensionY40

Sultamicillin250mg, 375mgTabletsY40

Teicoplanin200mg, 400mg/vialInjectionY40

Telavancin250 or 750mg/vialInjectionY40

Telithromycin400mgTabletssY40

CephalosporinsGeneric Name(S)StrengthDosage FormICD Code

Cefaclor250mg, 500mgCapsuleY40.1

Cefaclor125mg/5ml, 187mg/5ml, 250mg/5ml, 375mg/5mlSuspensionY40.1

Cefadroxil500mg, 1gCapsule,TabletY40.1

Cefamandole1g, 2g/VialInjectionY40.1

Cefazolin1g/50mlInjectionY40.1

Cefdinir300mgCapsuleY40.1

Cefdinir125mg/5mlSuspensionY40.1

Cefditoren200 and 400mg.TabletsY40.1

Cefepime500mg, 1g, 2g/VialInjectionY40.1

CefetametY40.1

Cefixime100mg/5mlSuspensionY40.1

Cefoperazone Sodium Injection10 g/VialInjectionY40.1

Cefotaxime500mg, 1g, 2g/VialInjectionY40.1

Cefotetan1g, 2g/VialInjectionY40.1

Cefoxitin1g, 2g, 10g/VialInjectionY40.1

CefpiromeY40.1

Cefpodoxmine Proxetil100g, 200gTablets, Oral SuspensionY40.1

Cefprozil250mg, 500mgTabletY40.1

Cefprozil125mg/5ml, 250mg/5mlSuspensionY40.1

Ceftaroline Fosamil Injection400g, 600g/VialInjectionY40.1

Ceftazidime1g, 2g, 10g/VialInjectionY40.1

Ceftibuten400mgCapsules and Oral SuspensionY40.1

Ceftriaxone500mg, 1g/VialInjectionY40.1

Cefuroxime125mg/5ml, 250mg/5mlSuspensionY40.1

Cefuroxime axetil125mg, 250mg, 500mgTabletY40.1

Cephalexin250mg, 500mgCapsule, TabletY40.1

Cephalexin125mg/5ml, 250mg/5mlSuspensionY40.1

Cephradine250mg, 500mgCapsuleY40.1

Cephradine125mg/5ml, 250mg/5mlSuspensionY40.1

FluoroquinolonesGeneric Name(S)StrengthDosage FormICD Code

Gatifloxacin200-mg and 400-mgTablets , Injection,Y40.8

Lomefloxacin400mgTabletY40.8

Pefloxacin400mg, 0.3%/5ml, 400mg/100ml, 100mg/50mlTablet, Drop, InjecionY40.8

Sparfloxacin100mg, 200mgTabletsY40.8

Generic Name(S)StrengthDosage FormICD Code

Y40.3

Azithromycin1000mgPacketY40.3

Azithromycin250mg, 600mgTabletY40.3

Azithromycin100mg/5ml, 200mg/5mlSuspensionY40.3

Azithromycin2g/60mlSuspensionY40.3

Clarithromycin250mg, 500mgTabletY40.3

Clarithromycin125mg/5ml, 250mg/5mlSuspensionY40.3

Clarithromycin500mgTabletY40.3

Erythromycin250mg, 333mg, 500mgCapsule, TabletY40.3

Erythromycin40mg/ml, 200mg/5ml, 400mg/5mlDrops, SuspensionY40.3

Erythromycin Estolate250mgCapsuleY40.3

Erythromycin Estolate125mg/5ml, 250mg/5mlSuspensionY40.3

Erythromycin Ethylsuccinate200mg, 400mgChewtab, TabletY40.3

Erythromycin Ethylsuccinate/Sulfisoxazole40mg/ml, 200mg/5ml,400mg/5mlSuspensionY40.3

Erythromycin Stearate250mg, 500mgTabletY40.3

Fidaxomicin200mgTabletY40.3

Troleandomycin250mgCapsulesY40.3

MacrolidesMonocyclic Beta-lactam AntibioticGeneric Name(S)StrengthDosage FormICD Code

Aztreonam1 g/vial, 2 g/vialInjectionY40.1

Doripenem500mg/1vialInjectionY40.1

penicillinsGeneric Name(S)StrengthDosage FormICD Code

Amoxicillin250mg, 500mgCapsuleY40.0

Amoxicillin50mg/ml, 125mg/5ml, 200mg/5ml, 250mg/5ml, 400mg/5mlDrops, SuspensionY40.0

Amoxicillin125mg, 200mg, 250mg, 400mgChewable TabletY40.0

Amoxicillin and Clavulanate Potassium250mg/125mg, 1000mg/62.5mgTabletY40.0

Amoxicillin and Clavulanate Potassium500mg/125mg, 875mg/125mgTabletY40.0

Amoxicillin and Clavulanate Potassium125mg/31.5mg, 25mg/62.5mgChewable TabletY40.0

Amoxicillin and Clavulanate Potassium200mg/28.3mg, 400mg/57mgChewable TabletY40.0

Amoxicillin and Clavulanate Potassium125mg/31.25mg/5ml, 250mg/62.5mg/5mlSuspensionY40.0

Amoxicillin and Clavulanate Potassium200mg-28.5mg/5ml, 400mg-57mg/5ml,SuspensionY40.0

Amoxicillin and Clavulanic acid125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL, 125-mg, 200-mg , 250-mg, 400-mg , 500-mg, 875-mgTablets, Oral SuspensionY40.0

Ampicillin250mg, 500mgCapsuleY40.0

Ampicillin125mg/5ml, 250mg/5mlSuspensionY40.0

Ampicillin and Sulbactam1.5 g, 3 g vialsInjectionY40.0

BacampicillinY40.0

Bacitracin (Neomycin/Polymyxin B) Opthalmic1/2 ozOintmentY40.0

Dicloxacillin250mg, 500mgCapsuleY40.0

Mezlocillin sodiumY40.0

Oxacillin Injection1gm, 2gmInjectionY40.0

Oxacillin Injection1gm/50ml, 2gm/50mlInjectionY40.0

Penicillin VK250mg, 500mgTabletY40.0

Penicillin VK125mg/5ml, 250mg/5mlSuspensionY40.0

Piperacillin/Tazobactam4000mg/500mg/Vial, 1000mg/125mg/Vial, 2000mg/250mg/VialInjectionY40.0

QuinolonesGeneric Name(S)StrengthDosage FormICD Code

Balofloxacin100mgTabletsY41.8

Ciprofloxacin250mg, 500mg, 750mgTabletY41.8

Ciprofloxacin250mg/5ml, 500mg/5mlSuspensionY41.8

Garenoxacin MesylateY41.8

Levofloxacin250mg, 500mgTabletY41.8

Nalidixic Acid125mg, 300mg, 150mg, 300mg/5mlTablet, Suspension, SyrupY41.8

SulfonamidesGeneric Name(S)StrengthDosage FormICD Code

Y41.0

Sulfadiazine500mgTabletY41.0

Sulfisoxazole500mgTabletY41.0

Sulfisoxazole500mg/5mlSuspensionY41.0

Sulfisoxazole/Erythromycin Ethylsuccinate600mg+200mg/5mlSuspensionY41.0

Sulfisoxazole/Phenazopyridine500mg + 50mgTabletY41.0

Trimethoprim/Sulfamethoxazole80mg/400mgTabletY41.0

Trimethoprim/Sulfamethoxazole40mg+200mg/5mlSuspensionY41.0

Trimethoprim/Sulfamethoxazole DS160mg/800mgTabletY41.0

TetracyclinesGeneric Name(S)StrengthDosage FormICD Code

Demeclocycline150mg, 300mgTabletY40.4

Doxycycline50mg, 100mgCapsule, Tablet,Y40.4

Doxycycline25mg/5ml, 50mg/5mlSuspension, SyrupY40.4

Minocycline50mg, 75mg, 100mgCapsuleY40.4

Oxytetracycline250mg, 500mg, 50mg/1ml, 10mg/1gm, 30mg/1gmCapsule, Injection, OintmentY40.4

Tetracycline250mg, 500mgCapsule, TabletY40.4

Tetracycline125mg/5mlSuspensionY40.4

WORKING OF ANTIBIOTICSWhen should you take antibiotics?Antibiotics are prescribed for illnesses caused by bacteria, not by viruses. The common cold and flu are caused by viruses, not by bacteria. Antibiotics do not work against viruses. When used prudently, antibiotics are a powerful medical tool to thwart bacterial diseases. Prudent use includes taking antibiotics only for diagnosed bacterial infections and following the precise directions on the prescript.What is the proper dosage?Prescriptions are written to cover the time needed to help your body fight all the harmful bacteria. If you stop your antibiotic early, the bacteria that have not yet been killed can restart an infection.

Leftover antibiotics are not a complete dose, and they will not work to kill all your disease causing bacteria. Taking partial doses can select for the bacteria that are resistant. Always talk to your doctor because your symptoms may not be caused by bacteria. If you do have another bacterial infection, a complete dose of the appropriate antibiotic is needed to kill all the harmful bacteria.

How safe are antibiotics?Antibiotics are generally safe and should always be taken as prescribed by your doctor; however, Antibiotics may alter the effectiveness of other medications and cause side effects or allergic reactions. Antibiotics can kill most of the bacteria in your body that are sensitive to them, including good bacteria. By destroying the bacterial balance, it may cause stomach upsets, diarrhea, vaginal infections, or other problems. If you take antibiotics unnecessarily you may contribute to the development of antibiotic resistance. If you become sick and your bacteria are resistant to your prescribed antibiotic, your illness lasts longer and you may have to make return office and pharmacy visits to find the right drug to kill the germ. For more serious infections it is possible that you would need to be hospitalized or could even die if the infection could not be stopped. Also, while the resistant bacteria are still alive, you act as a carrier of these germs, and you could pass them to friends or family members.How does a physician decide which antibiotic to prescribe?

The type of antibiotic your doctor prescribes to treat your infection depends on the type of bacteria causing that infection. Most bacteria fall into two types: Gram-positive and Gram-negative. These classifications are based, basically, on the type of cell wall that the bacteria has. Gram-positive bacteria -- such as Streptococcus -- have thin, easily permeable, single-layered cell walls. Gram-negative bacteria -- such as E. coli -- have thicker, less penetrable, two-layer cell walls. For an antibiotic to successfully treat a bacterial infection, it needs to be able to penetrate either or both types of bacterial cell walls.What should women know before taking antibiotics? Antibiotics often lead to a vaginal yeast infection. Because antibiotics kill the normal bacteria in the vagina, yeast no longer have competition for food and grow rapidly. Yeast cells begin attacking tissues in the vagina, usually causing one or all of the following symptoms: itching, burning, pain during sex and vaginal discharge. If you think you have a yeast infection, consult a physician. Antibiotics may reduce the efficacy of birth control pills.

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SOME ANTIBIOTICS WITH THEIR FUNCTIONS

A STUDY

ANTIBIOTIC RESISTANCE

Can you imagine a day when antibiotics don't work anymore? It's concerning to think that the antibiotics that we depend upon for everything from skin and ear infections to life-threatening bloodstream infections could no longer work. Unfortunately, the threat of untreatable infections is very real.Antibiotic resistance occurs when germs outsmart drugs. In today's healthcare and community settings, we are already seeing germs stronger than the drugs we have to treat them. This is an extremely scary situation for patients and healthcare workers alike.So, what is fueling antibiotic resistance, you may ask? We're finding that the widespread overuse and incorrect prescribing practices are significant problems. In addition to driving drug resistance, these poor practices introduce unnecessary side effects, allergic reactions, and serious diarrheal infections caused byClostridium difficile. These complications of antibiotic therapy can have serious outcomes, even death.According to CDC'sNational Healthcare Safety Network, a growing number of healthcare-associated infections are caused by bacteria that are resistant to multiple antibiotics. These include: MRSA, vancomycin-resistantEnterococcus, extended-spectrum cephalosporin-resistantK. pneumonia(andK. oxytoca),E. coliandEnterobacterspp., carbapenem-resistantP. aeruginosa, carbapenem-resistantK. pneumonia(andK. oxytoca),E. coli, andEnterobacterspp

HOW TO PREVENT SUCH CONDITION:-Patients can: Ask if tests will be done to make sure the right antibiotic is prescribed. Take antibiotics exactly as the doctor prescribes. Do not skip doses. Complete the prescribed course of treatment, even when you start feeling better. Only take antibiotics prescribed for you; do not share or use leftover antibiotics. Antibiotics treat specific types of infections. Taking the wrong medicine may delay correct treatment and allow bacteria to multiply. Do not save antibiotics for the next illness. Discard any leftover medication once the prescribed course of treatment is completed. Do not ask for antibiotics when your doctor thinks you do not need them. Remember antibiotics have side effects. Prevent infections by practicing good hand hygiene and getting recommended vaccines.

View Larger GraphicHealthcare providers can: Prescribe antibiotics correctly get cultures, start the right drug promptly at the right dose for the right duration. Reassess the prescription within 48 hours based on tests and patient exam. Document the dose, duration and indication for every antibiotic prescription. Stay aware of antibiotic resistance patterns in your facility. Participate in and lead efforts within your hospital to improve prescribing practices. Follow hand hygiene and other infection control measures with every patient.Healthcare Facility Administrators and Payers Can:To protect patients and preserve the power of antibiotics, hospital CEOs/medical officers can: Adopt an antibiotic stewardship program that includes, at a minimum, thischecklist:1. Leadership commitment: Dedicate necessary human, financial, and IT resources.2. Accountability: Appoint a single leader responsible for program outcomes. Physicians have proven successful in this role.3. Drug expertise: Appoint a single pharmacist leader to support improved prescribing.4. Action: Take at least one prescribing improvement action, such as requiring reassessment within 48 hours to check drug choice, dose, and duration.5. Tracking: Monitor prescribing and antibiotic resistance patterns.6. Reporting: Regularly report to staff prescribing and resistance patterns, and steps to improve.7. Education: Offer education about antibiotic resistance and improving prescribing practices. Work with other health care facilities to prevent infections, transmission, and resistance.DRAWBACKS OF ANTIBIOTICS1. They have side effects that can sometimes prove to be more difficult to manage than the ailment they are meant to cure.2. They destroy friendly bacteria along with disease-causing bacteria. The body needs friendly bacteria for a number of processes like detoxification, easy elimination of wastes and cleansing of the blood and the liver.3. Over-use of antibiotics lead to their becoming ineffective due to bacterial mutation. Simply stated, it means that certain bacteria get used to a particular antibiotic and start using it for their own benefit. Penicillin and tetracycline are classic examples of how antibiotics become redundant for killing some bacterium.4. Children who receive broad-spectrum antibiotics during their first year of life are at increased risk of developing childhood asthma.5. Broad Spectrum antibiotics may give rise to drug resistance.6. Antibiotics at are constant threat of vaginal infections and may cause malfunctioning of reproductive organs.

SIDE EFFECTS OF ANTIBIOTICS- RESEARCH WORKNew research, undertaken at Harvard University, indicates how long-term treatment with common antibiotics can trigger harmful side effects.Doctors often prescribe antibiotics freely, thinking that they harm bacteria while leaving human tissue unscathed. A studied published in July 2013 suggests this is not the case.Theresearch studyhas found that certain antibiotics, when used over a prolonged period of time, can trigger a phenomenon calledoxidative stress. This effect is a condition in which human cells can be programmed into producing chemically reactive oxygen molecules. For the killing of the desired microorganism this is effective; however the damage caused to the DNA, enzymes and cell membranes of the bacteria can also affect the bodys own cells.

As well as killing bacteria, the oxidizing process can negatively affect parts of body cells calledmitochondria. These function to supply human cells with energy. This was seen with three common antibiotics: ciprofloxacin, ampicillin and kanamycin. Oxidative stress reflects an imbalance between reactive oxygen in the body and the bodys ability to readily detoxify the by-products or to repair the resulting damage.The concern was shown in studies on mice, where use of the three antibiotics led to signs that the lipids (fats) in the mice became damaged as well as leading to levels of glutathione, one of the body's natural antioxidants, to fall.Commenting on the findings, Dr. Don Ingber, head of the institute which led the study, is quoted by theAlternative Dailyas saying: "Doctors have known for years that antibiotics occasionally cause serious side effects and Jim's new findings offer not one but two exciting new strategies that could address this long-neglected public health problem."The researchers behind the study have speculated whether an antioxidant, such as N-acetylcysteine, could be used to reduce the impact of the antibiotic. However, this raises concerns about people consuming a potentially harmful chemical.The research was carried out by the Wyss Institute for Biologically Inspired Engineering at Harvard University under a team led by Dr. Jim Collins.

SIDE EFFECTS:-

Antibiotics are a family of medications used to treat bacterial infections, fungal infections and some parasites. Numerous side effects are associated with antibiotic use and extremely high doses of antibiotics can have severe consequences.Respiratory Side Effectsantibiotics can cause allergy-like symptoms such as wheezing and difficulty breathing. In severe cases taking too many antibiotics can prevent a person from breathing altogether. A severe allergy to antibiotics can lead to anaphylaxis, a condition characterized by swelling of the throat, the inability to breathe and extremely low blood pressure..Skin Side EffectsSide effects of an antibiotic overdose that affect the skin include skin rash, pale skin and bluish lips and fingernails.Intestinal Side Effects

Side effects of antibiotics that affect the intestines include an upset stomach and diarrhea. An antibiotic overdose can also cause nausea, abdominal pain and cramping.

Additional Side Effects

vaginal yeast infections in women as a common side effect of antibiotic therapy. More severe side effects include damage to the kidneys, liver, bone marrow and other organs. Severe reactions to an antibiotic overdose include fever, convulsions, chest pain and an increased risk of collapsing.

ANTIBIOTICS DURING PREGNANCY-BAD IDEA

Recent research shows children whose mothers took antibiotics during their pregnancy were more likely to develop asthma, compared to those whose mother did not take antibiotics Children predisposed to asthma due to their mother having the condition were twice as likely to develop asthma if their mother used antibiotics during the third trimester, compared to those whose mother did not use antibiotics

This suggests that women should try to avoid antibiotics during their pregnancy unless necessary and prescribed by a medical practitioner.

ANTIBIOTICS MAY AFFECT SPREM QUALITY

University of Nevada researchers revealed that tetracycline a common antibiotic, may have an effect not just on a males sperm viability, but his childrens sperm viability as well.Authors of the study administered the antibiotic tetracycline to a type of scorpion, and compared their reproductive function, sperm health, sperm count, and body size to scorpions that were not given the antibiotic. Next, the scientists observed these factors in the small scorpions offspring.They discovered that reproductive function and sperm health were significantly reduced up to 15% by tetracycline for both father and son.The findings implications may be more complex than they appear at first glance, because tetracycline is widely used in agriculture as an additive in animal feed. This suggests that more men may be affected by this than those prescribed the medication to fight infection.The researchers advise that individuals concerned about sperm quality and sexual health may want to consider choosing organic food products and talking to their doctor about appropriate antibiotic use, such as cutting back on tetracycline intake.