Antibiotic Lecture Notes PDF

Antibiotics: Chloramphenicol Tetracyclines Aminoglycosides Rifamycins Aminocyclitols: Lincosamides , Macrolides CHLORAMPHENICOL Interfere with microbial protein synthesis , by making their way into the bacteria and attaching to the ribosomes , this renders the bacteria unable to produce v...

Antibiotics: Chloramphenicol Tetracyclines Aminoglycosides Rifamycins Aminocyclitols: Lincosamides , Macrolides CHLORAMPHENICOL Interfere with microbial protein synthesis , by making their way into the bacteria and attaching to the ribosomes , this renders the bacteria unable to produce vital proteins. Bacteriostatic - @ low doses [inhibits action of [penicillins + cephalosporins] Bactericidal - @ high doses [high concentrations]  MAJOR CONCERN :  It works by binding to ribosomes in sensitive bacteria and disrupting bacterial protein synthesis  Chloramphenicol can also affect the mitochondrial function in the bone marrow cells of mammals, temporarily damaging production of bone marrow cells  It can produce a serious and fatal aplastic anemia in humans  IT IS NOT USED IN FOOD ANIMALS!!  Liver metabolization of chloramphenicol is POOR in CATS…excreted via kidneys/bile ANTIMICROBIAL ACTIVITY  Gram +ves  Gram-ves  rickettsia  chlamydia  +/- mycoplasma  has a good ability to penetrate fluids/tissue: prostrate , eye , CNS CAP CONSIDERATIONS:  Resistance can be a problem ; also cross resistance with other Ab’s.  Are synergistic with tetracycline antibiotic group  Rapid absorption (all tissues)  IM , IV , Oral ; IV dosing needs to be 4-5 times per day b/c of absorption.  Some CAP may be excreted unchanged via the kidneys , therefore useful in urinary tract infections. CAP PHARMACOKINETICS : T1/2 = 1 hour or less in horse T1/2 = 6+ hours for foals T1/2 = 5-6 hours cats (much lower doses than dogs) T1/2 = 3-4 hours dogs  Common Chloramphenicols 1) Azramycine® , Centracol® , Chlor Palm® , Chlor Tablets® , Karomycin Palmitate®, Rogar Mycine® , Zoommycetine® Palmitate…  Tablets , Oral Suspension , Injection  Well absorbed (esp. oral) & widely distributed  Florfenicol (Nuflor ®)  Related to the chlorampheicols but changes have been made, it is a thiamphenicol derivative  can be safely used in cattle for respiratory disease and pneumonia, also treats foot rot  2 X IM injections @20mg/kg , 48 hrs apart ; or 1 X SQ high dose 1 injection @40mg/kg  Withdrawal time is 38  Florfenicol (Nuflor ®) NOTE: Intramuscular injection may result in local tissue reaction which persists beyond 28 days. This may result in trim loss of edible tissue at slaughter. Tissue reaction at injection sites other than the neck is likely to be more severe.  Zeleris® approved in 2020 Medicinal Ingredient Florfenicol, meloxicam Indication For therapeutic treatment of bovine respiratory disease, with accompanying pyrexia, associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni susceptible to florfenicol in beef and non- lactating dairy cattle.  Bacteriostatic  Have been in use for many years and therefore there is much resistance to them  They bind to bacterial ribosomes and prevent transfer RNA from linking to ribosomes this disrupts protein synthesis  Inhibit bacterial cellular function and division but do not cause immediate bacterial destruction  Bacteria actively take up tetracycline and concentrate it within the cell – a good thing! MAJOR CONCERNS :  There is variable absorption amongst the tetracyclines  Older ones are hydrophilic [tetracycline + oxytetracycline]  Newer ones are lipophilic [doxycycline + minocycline]  tetracycline & oxytetracycline can be chelated  Chelated = bound to …and precipitate out of solution ; specifically Ca++ , Mg++ , Fe++ , Cu++. Old vs New Old Tetracyclines New Tetracyclines  Tetracycline  Doxycycline  Oxytetracycline  Minocycline  Longer half life  Broader spectra of action  Better penetration of tissues ANTIMICROBIAL ACTIVITY :  Gram+’ves  A unique property of tetracyclines is their  gram-’ves ability to accumulate  rickettsial diseases within mammalian cells and reach organisms that  ehrlichiosis hide within the mammalian cell.  Hemobartenella  Protozoan infections CONSIDERATIONS :  Excreted via the kidney & liver , largely unchanged  Oxytet. has good absorption IM [more reliable concentrations than oral adm.]  Tetra. is better absorbed per os  Oxy./Tetra. Are both hydrophilic and therefore have low [ ] in CNS  Doxy./Mino. Are lipophilic and therefore will cross the BBB.  Because of their ability to chelate , Oxy./Tetra. will bind with the minerals of developing tooth enamel  Avoid use in animals ~ 4-16 weeks of age  They are a broad spectrum antibiotic and therefore we can get superinfection  Powder from broken capsules or partially chewed tablets may adhere to the esophagus injure the tissue and cause inflammation  This may result in formation of a scar +/or stricture  SHORT ACTING INTERMEDIATE LONG ACTING ACTING* tetracycline demecloycycline doxycycline oxytetracycline minocycline Water Soluble Lipid Soluble Lipid Soluble *Not common in vet medicine  Common Tetracyclines 1) Vibramycin® (Doxycycline)  2nd generation  Tx : hemobartonella , Rocky Mountain Spotted Fever , Leptospirosis , Borreliosis Common Tetracyclines  Approved species  The Bee  Common Tetracyclines  Liquamycin® , Bio-Mycin 200® (Oxytet)  Large animals  Never give tetracycline IV to a horse  Tetracycline: extra label drug use in small animals  Tetracyn®  Achromycin®  Sumycin® AMINOGLYCOSIDES  Inhibit protein synthesis and therefore bacterial cell division.  They are ‘mostly’ bactericidal (dose related)  All administered parenterally (hydrophilic) (except for Neomycin) MAJOR CONCERNS :  Nephrotoxic (100% excreted via kidney) NEOMYCIN is the most toxic  Ototoxic [rare – risk greater if on a diuretic]  they remain mostly in extracellular fluid ANTIMICROBIAL ACTIVITY :  although considered broad spectrum , used primarily to treat gram-’ve  Gentamycin is the most nephrotoxic so monitor the urine for casts  Also prolong the interval btw. dosing ; this allows [ ] in blood to drop to sub toxic level  Clinical Application o 4 yr. old cat with large draining abscess over lumbar region from an attack by a dog 4 weeks previously o Pseudomonas susceptible to gentamicin was cultured from the wound o The wound was lavaged with gentamicin solution twice within 24 hours o Cat was anaesthetized and the wound cleaned – cat recovered uneventfully from anaesthesia o Gentamicin was administered 2.2 mg/kg q12h , subcutaneously o 3 days later cat showed signs of elevated BUN o (blood urea nitrogen) & creatinine o U-SG was 1.008 o Urine sediment contained RBC’s WBC’s and casts o Because gentamicin nephrotoxicosis was suspected the gentamicin was stopped and IV fluids were started o Ampicillin was used in place of the gentamicin o Unfortunately the signs of renal toxicosis continued and at owner’s request the cat was euthanized o Necropsy confirmed necrosis of the proximal convoluted tubule o The combination of gentamicin flushed directly onto the wound and subsequent SQ administration of gentamicin prevented the plasma concentrations from decreasing below 2.0 µg / ml  Common Aminoglycosides 1) Gentocin® (Gentamicin sulfate)  IV , IM and SC = sting! PO is OK  Keep animal well hydrated Acute serious infections! Gentamicin sulfate and betamethasone Topagen® spray Superficial skin lesions Theraderm® Cream Steroid and gentamicin Common Aminoglycosides 1) Biosol® (Neomycin)  PO , topical  Not absorbed well systemically  Common Aminoglycosides 1) Amiglyde-V® (amikacin sulfate) Intrauterine ED50 = 5 mg/kg : LD50 = 250 mg/kg Effective where Gentamicin & Neomycin are not RIFAMYCINS Rifampin®️ Rifadin®️ Rimactane®️  Not an aminoglycoside  Red-orange coloured but used almost urine,tears and saliva exclusively in horses and almost always combined (+sweat) in horses with  An aminoglycoside  Wear gloves !  Β-lactam  Doxycycline  Sometimes combined  with clarithromycin This is because there is widespread resistance to rifampin RIFAMYCINS Rifampin®️ Rifadin®️ Rimactane®️  Gram positive  Resistance to rifamycin's  Mycobacteria may develop rapidly as a 1- step process  A few gram negative  For this reason they are  Anaerobes always administered in  Chlamydia combination with other  microbials Several viruses*  penicillin, erythromycin,  *@ high concentrations miconazole, amphotericin B  Lincosamide’s Macrolides  Lincomycin®  Tilmicosin (Micotil®)  Clindamycin (Antirobe®)  Erythromycin  Spectinomycin / Pirlimycin  Tylosin®️ (like) Inhibit bacterial protein synthesis Inhibit bacterial protein synthesis Bacteriostatic or bactericidal Bacteriostatic  Lincosamides Macrolides  The pharmacokinetics Lincomycin®  Tilmicosin of lincosamides have not been extensively  Erythromycin  Clindamycin (Antirobe®) studied in veterinary species  Spectinomycin / Pirlimycin  Tylosin®️ (like) Inhibit bacterial protein synthesis Inhibit bacterial protein synthesis Bacteriostatic or bactericidal Bacteriostatic  Common Lincosamides: Antirobe® 1) Antirobe® , Antirobe Aqua drops® (Clindamycin)  Good for bacteria that prove resistant to penicillins and cephalosporins  Expensive , added benefit works on anaerobic bacteria: skin/dental infections  Capsules = dogs , Aqua drops® = cats + dogs Oral Liquid – dogs/cats Oral Capsule – dogs/cats Injectable – dogs/cats  Common Lincosamides: Lincocin® 2) Lincocin® (Lincomycin)  Dogs = URTI , skin , nephritis & metritis  Cats = abscesses  Swine and poultry  Common Macrolides: 1) Erythro-36® , Erythro-200® , Erythro-Dry Cow® , Gallimycin® (Erythromycin)  Cattle, swine , chicken for growth ; ‘pink-eye’ in cattle  Potential hepatotoxin has been incriminated in immune-mediated thrombocytopenia  Good for respiratory disease  Has a prolonged withdrawal time  3 weeks for cattle  Common Macrolides 4) Tylocine , Tylan (LA) [Tylosin]  bronchitis, , tracheobronchitis , pneumonia and has been used to manage colitis in dogs and cats  PO  Common Macrolides 4) Trobicin® , Spectam (LA)® [Spectinomycin]  A drug used in similar situations as aminoglycosides because it is less toxic  Synergistic with lincomycin  Micotil 300® Active ingredient: tilmicosin (macrolide) Micotil 300, an injectable tilmicosin drug, is administered to treat respiratory disease in cattle and sheep. It has been associated with 2,200 reports in the U.S. of adverse events involving human exposure, most of them from accidents, according to FDA information. At least 16 of the 25 deaths associated with Micotil 300 likely were by suicide. "This drug has been shown to have toxic effects on the human heart," the FDA announcement states. "In some cases of exposure, people required hospitalization and prolonged medical care; some people have died despite receiving medical care." In a message, FDA spokeswoman Lindsay Dashefsky said the drug's manufacturer, Elanco, has implemented online training and adjusted the product to improve handling, among other changes since the drug was approved in 1992. In May 2017, the Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health issued recommendations on preventing deaths and injuries from Micotil 300. NIOSH recommends that veterinarians consider prescribing medications without toxic effects on humans, administer Micotil 300 only with appropriate animal restraint, ensure that people