1. Classification of antibacterial drugs 1.1 Classification according to the antibacterial spectrum and application of drugs 1. The main antibacterial drugs against Gram-positive bacteria include: penicillins, cephalosporins, macrolides, lincosamides, bacitracin wait. 2. The main antibacterial drugs against Gram-negative bacteria include: aminoglycosides and polymyxins. 3. Broad-spectrum antibacterial drugs include: fluoroquinolones, tetracyclines, amide alcohols, etc. 4. Antifungal and antibacterial drugs include: amphotericin B, nystatin, clotrimazole, itraconazole, fluconazole, etc. 5. Antiparasitic antibacterial drugs include: ivermectin, abamectin, monensin, salinomycin, maduramycin, etc. 1.2. Classification according to chemical structure 1. β-lactam penicillins: fungicides during breeding season, penicillin, ampicillin, amoxicillin, oxacillin, piperacillin sodium, dicloxacillin, etc. Cephalosporins: ceftaxime, cefadroxil, cefotaxime, ceftriaxone sodium, cephalexin, ceftiofur, etc. 2. Aminoglycosides streptomycin sulfate, apramycin sulfate, gentamicin sulfate, amikacin (amikacin sulfate), neomycin sulfate, spectinomycin sulfate, etc. 3. Tetracyclines Oxytetracycline, Tetracycline, Chlortetracycline, Doxycycline, Metacycline, Minocycline, etc. 4. Amino alcohols such as thiamphenicol, florfenicol, etc. 5. Macrolide erythromycin, roxithromycin, erythromycin thiocyanate, kitasamycin tartrate, tylosin, tilmicosin, tediroxin, gamimycin, etc. 6. Lincomycin, a lincosamide. 7. Polypeptide bacitracin, colistin, antibacterial peptides, etc. 8. Polyene nystatin, amphotericin B, etc. 9. Phosphorus-containing polysaccharides such as flavomycin, carbamycin, and erythromycin are mainly used as feed additives. 10. Polyether ion monensin, salinomycin, etc. 1.3. Synthetic antibacterial drugs 1, sulfasulfadiazine , sulfamethoxazole, sulfamidine, sulfamethoxine sodium, sulfaquinazoline, sulfachloropyrazine sodium, sulfadimethoxine sodium, sulfamethoxine Sodium etc. Highly sensitive to Streptococcus, Pneumococcus, Salmonella, Corynebacterium pyogenes, etc.; completely ineffective against Spirochetes, Mycobacterium tuberculosis, Rickettsia, viruses, etc. 2. Antibacterial synergist TMD, DVD, etc. 3. Furans such as furazolidone. 4. Quinolones Norfloxacin, Ciprofloxacin, Enrofloxacin, Pefloxacin, Ofloxacin, Dafloxacin, etc. 5. Other compound antibacterial drugs carbadox, isoniazid, berberine, etc. 6. Metronidazole , metronidazole, dimeridazole, etc. 7. Antiviral drugs interferon, transfer factor, astragalus polysaccharide, etc. 2. Incompatibility 1. Penicillins such as ampicillin sodium, amoxicillin, and penicillin G potassium [increased efficacy of compatibility] streptomycin, neomycin, polymyxin, quinolones; [decreased efficacy of compatibility] tilmicosin, Doxycycline, Florfenicol; [compatibility failure] aminophylline, sulfonamides, VC-polyphosphate, roxithromycin. 2. Tetracyclines Tetracycline , doxycycline, doxycycline, chlortetracycline [compatibility enhancement] tylosin, tiamulin, TMP; [compatibility failure] aminophylline. 3. Cephradine, cephalexin , cephalexin, cephalosporins, cephalosporins, cephalosporins, and cephalosporins [increased efficacy of compatibility] neomycin, gentamicin, quinolones, colistin sulfate; [decreased efficacy of compatibility] aminophylline, VC, sulfonamides, roxigenin Erythromycin, doxycycline, florfenicol; [increased compatibility with nephrotoxicity] cephalosporin II, diuretics. 4. Macrolides roxithromycin, erythromycin thiocyanate, and tilmicosin [increased efficacy of compatibility] gentamicin, neomycin, florfenicol; [decreased efficacy of compatibility] Lincomycin [compatibility failure] sodium chloride , calcium chloride; [increased compatibility toxicity] kanamycin, sulfonamides, aminophylline. 5. Aminoglycoside antibiotics neomycin sulfate, gentamicin, kanamycin, streptomycin [enhanced efficacy of compatibility] ampicillin sodium, cephradine, cephalexin, doxycycline, TMP; [decreased efficacy of compatibility] VC, Florfenicol. 6. Polymyxins [increased compatibility efficacy] doxycycline, florfenicol, cephalexin, roxithromycin, tilmicosin, quinolones; [increased compatibility toxicity] atropine, cephalosporin, Mycin, Gentamicin. 7. Quinolones ofloxacin, enrofloxacin, ciprofloxacin, norfloxacin [compatibility enhancement] cephalosporins, ampicillin, streptomycin, neomycin, gentamicin, sulfonamides; 【Compatibility reduces curative effect】tetracycline, doxycycline, florfenicol, furans, roxithromycin. 8. Sulfonamides [Increased compatibility efficacy] TMP, neomycin, gentamicin, kanamycin; [decreased compatibility efficacy] cephalosporins, ampicillin sodium; [ enhanced compatibility toxicity] florfenicol, roxithromycin. 9. Amino alcohols thiamphenicol and florfenicol [increased compatibility efficacy] neomycin, doxycycline, colistin; [decreased compatibility efficacy] cephalosporins, ampicillin sodium; [increased compatibility toxicity] card Namycin, quinolones, sulfonamides, furans, streptomycin. The vitamin folic acid, B12, can affect red blood cell production. 10. Aminophylline [reduced efficacy of compatibility] quinolones; [ineffectiveness of compatibility] VC, doxycycline, epinephrine. 11. Lincomycin [compatibility enhancement] metronidazole; [compatibility decrease efficacy] roxithromycin, tilmicosin; [compatibility failure] sulfonamides, aminophylline. 12. Sulfonamides [increased compatibility efficacy] TMP, neomycin, gentamicin, kanamycin; [decreased compatibility efficacy] cephalosporins, ampicillin sodium. 3. Precautions and principles of veterinary drug use Safe, correct and rational use of veterinary drugs to effectively prevent and treat livestock and poultry diseases is the basic common sense that every breeder should master. 3.1. Diagnosis Correct diagnosis of epidemic disease is the premise of correct treatment, and the effect of treatment is the verification of diagnosis. Only by correct diagnosis and prescribing the right medicine reasonably can a satisfactory curative effect be obtained. For diseases of unknown cause, drug abuse is strictly prohibited. 3.2. Course of treatment and administration time The use of drugs must have a sufficient course of treatment. The length of the course of treatment depends on the severity of the disease, because the growth and reproduction of pathogens have a certain process. If the curative effect is too short, some pathogens can only be temporarily suppressed and cannot be eliminated. Once the drug is stopped, The suppressed bacteria will re-grow, multiply, and more serious symptoms will appear. In general, the drug can be stopped after the symptoms disappear, but when antibiotics are used to treat certain infectious diseases, in order to consolidate the therapeutic effect, it is necessary to continue to use the drug for a period of time after the symptoms disappear. Some chronic diseases require long-term medication. In order to reduce adverse reactions, medication should be prescribed according to the course of treatment. In addition, the application of some drugs at the right time can improve their drug efficacy. As for the administration time, it needs to be considered from the aspects of drug properties, absorption, drug stimulation to the stomach, animal tolerance and the time when the drug effect occurs. consider. 3.3. Dosage of the drug Usually, the drug is absorbed by the body and can only play a role in treating diseases when it reaches an effective concentration. If the dosage of the drug is too small, the effective concentration cannot be reached, the disease cannot be effectively controlled, and drug resistance is likely to occur; if the dosage is too large, after exceeding a certain concentration, the curative effect cannot be increased, resulting in waste of drugs and toxicity to the body. Therefore, the frequency, dose and course of treatment should be reasonably arranged according to the duration of the effective concentration in the blood. In addition, some drugs have different dosages and different pharmacological effects, and the dosage of the drugs should be reasonably controlled according to the specific situation. 3.4. Drug interactions In clinical practice, two or more drugs are often used in combination, with the purpose of improving efficacy, reducing or avoiding toxic reactions, and preventing and delaying the emergence of drug-resistant strains. When using veterinary drugs, the synergistic effect of the drugs should be fully utilized, and incompatibility should be paid attention to. For example, aminoglycoside drugs should not be compatible with erythromycin and other drugs, nor should they be compatible with muscle relaxants to prevent toxicity enhancement. 3.5. Drug resistance and allergic reactions Drug resistance refers to the development of drug resistance by pathogens, and the second refers to the development of drug resistance in animal organisms. After continuous and repeated administration of certain drugs, the response of pathogens and animal organisms to the drugs decreases, resulting in drug resistance. This requires timely replacement of drugs according to the progress of the animal's disease. An allergic reaction is an abnormal phenomenon that occurs in an individual animal after the application of a certain drug. Therefore, care should be taken when using veterinary drugs. 3.6. The species, age, gender and individual differences of animals Because the species, age, sex and body weight of the sick animals are different, even to the same drug, their sensitivity and therapeutic effect are also different, and the reaction is not obvious. Therefore, special attention should be paid when using veterinary drugs, and the specific situation should be treated on a case-by-case basis. 3.7. Pathological conditions and functional conditions of animals The pathological conditions and functional conditions of animals are different, and the responses to drugs are also different. Generally, the effect of drug treatment is more obvious under pathological conditions. 3.8. Comprehensive prevention and control measures Acute and chronic diseases in animals are often accompanied by dysfunction of multiple organs and systems throughout the body. In the course of clinical treatment, adhere to the method of combining traditional Chinese and Western medicine, while applying antibiotics, pay attention to strengthening the regulation of electrolytes and body pH balance. In the process of preventing and treating diseases in animals, it is required to be familiar with the pharmacology, toxicology, medicinal properties, indications, usage, dosage, and matters that should be paid attention to in use of various drugs. When selecting veterinary drugs, the principles of broad-spectrum efficiency, safety, convenience, economy and applicability, and harmlessness to humans should be followed.

Principles of Microbiology — Gram Staining

1. Heat Fix the Bacteria - so you have some bacteria on a petri dish and pick up a small amount and smear it on a slide. Those bacteria can still slide off, so we quickly run the slide over a flame to fix (glue) the bacteria in place. This does kill the bacteria but does not burst the cell (if you run the slide through the flame quick enough).
2. Apply the primary stain: Crystal Violet - In water, it dissociates into CV+ and quickly penetrates through the cell wall. The CV+ is attracted to the negative components of the peptidoglycan layer. Now the cells are purple.
3. Apply the mordant: Iodide - a mordant is a chemical that fixes a dye into a substance (like cotton). In this case, the iodide associates with the CV+ and glues it within the peptidoglycan layer.
4. Apply the decolorizer: Alcohol/Acetone - in order to get a contrast stain, you want to wash the CV out of the cells that hold onto it loosely. When alcohol/acetone is applied to the cells, it penetrates and washes away the CV-I complex in the thin peptidoglycan layer. So in gram-negative cells, you’ve just washed all the CV out of the cell (it's now colorless).Gram-positive bacteria however dehydrate in the presence of alcohol/acetone. The large peptidoglycan layers resist washing away and will remain (with the CV-I complex). Thus gram-positive bacteria remain purple.
5. Apply the counterstain: Safranin - Safranin is also a positive charged dye and will adhere to both cell walls. In gram-positive, the safranin is unnoticeable (hides underneath and blends with the CV) while gram-negative are dyed pink.

• Coagulase - ability for bacteria to clot the blood. This a virulence factor (assist colonization of the body)
  • Coagulase positive bacteria = Staph. Aureus
    • Clotting protects it from being destroyed by the immune system
• Motility Agar - determines if bacteria has a flagella and can swim through the medium
  • Motile bacteria = E. coli
    • This could be why E. coli is the cause of UTI infections about 90% of the time
• Blood Agar Plates - tests bacteria’s ability to lyse (cut) sheep’s red blood cells
  • No hemolysis (gamma) - no notable hemolysis
  • Partial hemolysis (alpha) - bacteria has some ability to break down red blood cells
  • Complete hemolysis (beta) - clear ability to destroy red blood cells
    • Strep pyogenes is a classic B-hemolytic. It can cause hemorrhagic pneumonia (pneumonia with coughing up blood, yikes)

Yum, fungus

• Now, contemporaries knew that arsenic was poisonous, but Salvarsan was the first organic antisyphilitic treatment and was a huge improvement on the widely used inorganic mercury compounds. (it's a wonder how anyone survived.)
• Salvarsan was a success, that much shouldn’t be understated. It was described as Ehlrig’s “magic bullet” and became a mainstay in syphilis treatment. That being said, Salvarsan had a number of issues, particularly in its administration.
  • Firstly, the compound needed to be dissolved in several hundred milliliters of sterile water and could not be exposed to air. Only then could an injectable medication be administered to a patient. Due to its proclivity to oxidize, Salvarsan needed to be stored in sealed vials under a nitrogen atmosphere.
  • Both of these points forced Ehlrig to develop a drug that was safer and had a less complicated administration.
  • Oh yeah and its incredibly toxic: severe nausea and vomiting, deafness, rashes, liver damage, risk of limb necrosis, and other fun side effects.

• In 1912 Ehlrig released Neosalvarsan or compound 914. Neosalvarsan was markedly less toxic and more water soluble than Salvarsan.
• Both drugs were thought of great successes and Neosalvarsan was considered the primary treatment of syphilis. Ehlrig and his partner Sahachiro Hata received bad press for finding a cure for syphilis as many believed the disease to be a punishment for sin and immorality and shouldn’t be cured. Eventually, both were hailed as heroes in the medical community and received praises from most prominent microbiologists, physicians, and the public. In 1908, Elhrig and Hata would share the Nobel Prize in Physiology and Medicine. Ehlrig would die in 1915 and Hata would return to Japan as a renowned immunologist.
• By the 1920’s arsenic solidified as the primary treatment of syphilis. It was found that combining arsenic compounds with earlier mercury or bismuth treatments resulted in lower doses of all three.

• In 1930, Salvarsan’s metabolite oxyphenarsine was discovered. It would be marketed as Mapharsen.

Finally, Penicillin

• At Oxford’s School of Pathology, Howard Florey, Ernst Chain and Sir Willian Dunn worked to purify and identify the structure of penicillin. Unfortunately their research began in earnest in 1939 and the beginning of their research was stalled due to the war. In order to perform enough animal tests, they had to produce more than 500 liters of “mold juice” per week. Apparently they did so by employing “penicillin girls” who would inoculate and ferment culture vessels like baths, bedpans, milk churns, and food tins. Eventually they would invent a culture vessel. That mold filtrate was sent to Normal Heatley and Edward Abraham who extracted penicillin from the huge volumes of liquid.
• By 1940, the first animal experiments were beginning. They successfully showed that mice infected with streptococci bacteria could be cured with penicillin. The following year, Albert Alexander would become the first person treated with Penicillin after developing a life threatening infection on his face. They injected the drug and instantly Alexander started to improve. Unfortunately he would die a few days later because the supplies of medication ran out.

So are we gonna talk about chemistry?

• As a class, all penicillins work the same. The exposed and reactive amide is attacked by an alcohol residue found in the Transpeptidase enzyme. This enzyme is responsible for building and maintaining the peptidoglycan wall layer. By occupying the active site of the Transpeptidase, the enzyme is irreversibly inhibited, thus deactivating it. Ultimately, the bacteria is unable to repair its cell wall and bursts from lack of repairs.

• Penicillin G (1942) was the first penicillin to be discovered. This is the same chemical that Fleming discovered in his lab and it’s approval in 1942 ushered in the modern age of antibiotics. Penicillin G is a benzylpenicillin and is overall the simplest penicillin available. It is extremely cheap and so mild infections with susceptible bacteria can be treated with low cost high dose therapy. High doses are needed because of penicillin’s propensity to be broken by water. Likewise, highly nucleophilic side chains had the propensity to break penicillin too.

• Because of benzylpenicillin’s ability to cleave and deactivate easily in water, structural changes needed to be made to improve the stability of the beta-lactam pharmacophore. Penicillin V (phenoxymethyl penicillin) is the first improvement. The added electron withdrawing stabilizes the beta-lactam further increasing the overall stability. Because of this, Penicillin V became the first oral penicillin (Pen G would be given IV to avoid high dose loads).
• The success and tolerability of penicillin would replace Salvarsan as the mainstay therapy for syphilis and almost all other antibiotic regimens from then on. Because of penicillin, we no longer ingest toxic metals to cure infections.

Glory to the Resistance!

• The first penicillin-resistant antibiotic was Methicillin (1960). At the time of its introduction, it was the magic bullet able to kill multiple strains of beta-lactamase resistant bacteria. Its bulky dimethoxybenzoyl group was too large to fit into the beta-lactamase active site, thus preventing deactivation. Luckily, due to the distance of the side chain to the beta-lactam (and the bent shape), it was still able to fit inside the transpeptidase and kill the bacteria.
  • Almost immediately, bacteria become resistant to Methicillin and are now dubbed Methicillin Resistant Staphylococcus Aureus (MRSA) and account for some of the most deadly and virulent infections. Likewise modern bacteria are induced by Methicillin (increase resistance once exposed) and so it has been almost entirely replaced by its siblings: Nafcillin and Oxacillin (and a few others).

• Two drugs, Ampicillin (1961) and Amoxicillin (1971) are two penicillins with an R-phenylglycine moiety. This extremely electron withdrawing side chain heavily increases hydrolysing resistance and is believed to be the reason for increased gram-negative penetration.
  • Oh yeah, gram staining! Remember that gram-positive bacteria have a peptidoglycan layer that is exposed to the outside while gram-negative bacteria have a double layer. Penicillins naturally have a better spectrum because of that huge peptidoglycan layer in gram positive. Ampicillin’s and Amoxicillin’s real triumph is their ability to penetrate into gram negative bacteria.
• Another approach to beta-lactamase bacteria is to give a drug that specifically inhibits that enzyme. The discovery of beta-lactamase inhibitors also increases the potency and kill-ability of antibiotics. Clavulanic acid is a mold product that has terrible antibiotic activity BUT is an irreversible inhibitor of beta-lactamase. Sulbactam is a partial chemical synthesis from penicillins.
  • These two inhibitors are called “suicide substrates” because their job is to be deactivated (killed) thus inhibiting the resistance mechanism. While we are unsure what specifically makes beta-lactamase target the inhibitor over the penicillin, the result is increased amoxicillin and Ampicillin effect.
  • Currently, there are two combination products available. Augmentin (Amoxicillin/Clavulanate) and Unasyn (Ampicillin/Sulbactam)

How does Penicillin work?

The Macrolide Antibiotics

How do macrolides work?

• Azithromycin
• Clarithromycin
• Erythromycin
• Fidaxomicin
• Telithromycin

Penicillin vs. Azithromycin for Bacterial Infections

• Diarrhea
• Abdominal pain
• Rash
• Heartburn
• Nausea
• Itching

• Diarrhea
• Nausea
• Abdominal pain
• Vomiting
• Tongue discoloration
• Ringing in the ears (tinnitus)

Potential Bacterial Resistance of Penicillins vs. Azithromycin

How to save on Azithromycin