Anti-Infective Drugs & Antimicrobials

Anti-Infective Drugs: An Overview

• Microorganisms are widespread, some can cause disease.
• Around 100 antimicrobial drugs have been developed since the early 1900s.
• The first of these drugs were Sulfa drugs used in WWII.

Classifying Bacteria

• Gram-positive bacteria stain dark blue or purple.
• Gram-negative bacteria stain pink or red.
• Special staining is needed to ID some bacteria.
• Bacteria with similar staining respond to similar antimicrobial treatments.

Types of Antimicrobials

• Bactericidal agents kill bacteria and are used for severe, life-threatening infections.
• Bacteriostatic agents inhibit bacterial growth, allowing the body to kill the bacteria.
• Avoid mixing bacteriostatic and bactericidal drugs because it prevents bactericidal drugs from working

Resistance and Prudent Use

• Bacterial resistance can complicate antimicrobial treatments.
• Avoid indiscriminate antimicrobial use to reduce resistance development.
• Bacterial identification and sensitivity testing guides antimicrobial therapy.
• In vitro efficacy may not translate to in vivo results.
• Minimum Inhibitory Concentration (MIC) indicates the drug amount needed to inhibit growth.

Treatment Considerations

• Antimicrobials should be reserved for at-risk individuals with more than mild infections.
• Asepsis should not be compromised when antimicrobials are available.
• Use antimicrobials based on definitive diagnosis and choose the most specific antibiotic.
• Exercise caution using antimicrobials in food animals to avoid drug residue.

How Antibiotics Act

• Inhibition of cell wall synthesis will allow water into the cell causing it to explode
• Animal cells are not harmed since they lack a cell wall.
• Damage to the cell membrane will alter cell permeability which also leads to water entering the cell causing rupture
• Inhibition of protein synthesis prevents cell division.
• Interference with metabolism impedes essential bacterial processes.
• Impairing nucleic acid production hinders cell function and division.

Gaining Antibiotic Resistance

• Resistance occurs when bacteria change to reduce or eliminate antibiotic effectiveness.
• Improper drug usage includes using them for viral infections, wrong dosage, or inadequate duration.
• Bacteria can mutate, allowing it to resist antibiotics and become predominant as a result.
• Resistance genes can be acquired through plasmid transfer from resistant bacteria.
• Cross-resistance occurs when resistance to one antibiotic confers resistance to others with a similar mechanism.

Prevention of Resistant Infections

• Hospitals can be a source of resistant infections.
• Preventing close contact with sick patients can help.
• Hand washing can help limit the spread of resistant bacteria
• Antibiotic choice should be based on culture and sensitivity testing whenever possible.

Penicillins

• Discovered in 1928 by Sir Alexander Fleming, penicillins are bactericidal.
• Many formulations settle and require shaking before use.
• Oral preparations must be appropriately mixed to prevent dilution.
• Most penicillins require refrigeration.
• Oral preparations are only stable for 7-14 days.
• They can be indentified by the suffix -cillin.
• Penicillins are effective against anaerobes.

Penicillin Pharmacokinetics

• Oral penicillin absorption occurs in the stomach and small intestine.
• Injectable penicillin is rapidly absorbed at the injection site.
• Kidneys primarily excrete penicillins.
• Observe withdrawal times due to excretion in milk.

Penicillin Pharmacodynamics

• Penicillins bind to penicillin-binding proteins (PBPs) on the bacterial membrane.
• Binding PBPs increases osmotic pressure, causing the cell to burst.
• Some bacteria produce beta-lactamase (penicillinase), increasing penicillin resistance.
• Some penicillin forms resist beta-lactamase.
• Gram-positive bacteria are usually susceptible, while gram-negatives have a coating that reduces PBP permeability.

Frequently Used Penicillin Formulations

• Procaine penicillin G is injectable, inactivated by stomach acid. It is not given orally and is injected IM in horses and cattle, and SQ in dogs and cats.
• Oral amoxicillin is available as a suspension, tablets, or capsules (Amoxi-drops®).
• Ampicillin is available in IV and SQ forms (Polyflex®).
• Benzathine penicillin is long-acting but not absorbed by horses.
• Ticarcillin is often used intrauterine in horses.
• Amoxicillin-clavulanate (Clavamox®) reduces resistance by combining a beta-lactam with a beta-lactamase inhibitor and is considered a potentiated drug.

Uses for Penicillin

• Penicillin treats infections caused by penicillin-susceptible organisms like Streptococcus sp. and Staphylococcus sp.
• Often combined with other antibiotics to broaden the spectrum against gram-negative and anaerobic bacteria.

Adverse Effects of Penicillin

• Anaphylactic reactions (hives, respiratory distress, collapse, death) can occur, and epinephrine is needed immediately.
• Procaine reaction (excitement, ataxia, vocalization) can occur if procaine enters the microvasculature.
• Spectrum: targets gram-positive Staphylococcus and Streptococcus.
• Gram negatives w/ LPS reduces PBP permeability.
• Superinfections can occur especially in hind gut fermentors and with rabbits and Pastuerella

Cephalosporins

• These are bactericidal and used primarily in small animal medicine.
• Older drugs use "ceph-" spelling, while newer drugs use "cef-".

Cephalosporin Pharmacokinetics

• Cephalosporins are given parenterally due to poor GI absorption.
• They distribute well to tissues and fluids, except the CNS.
• Elimination occurs via the kidneys through glomerular filtration and tubular secretion; hepatic metabolism also occurs.
• Doses should be adjusted for patients with renal failure.

Cephalosporin Pharmacodynamics

• Similar to penicillin they bind to PBPs, and some can penetrate the bacterial cell.
• Cephalosporins are susceptible to beta-lactamases (cephalosporinases).
• Primary activity targets gram-positive organisms.
• Cephalosporins are grouped into four generations with increasing spectrum against Gram-negative organisms.
• First generation drugs have broad-spectrum gram-positive bactericidal activity but can be inactivated by beta-lactamase.
• Second-generation drugs have a broader spectrum against gram-negative bacteria.
• Third-generation drugs have an even broader gram-negative spectrum and are generally resistant to beta-lactamase.
• Fourth-generation drugs are also active against Pseudomonas aeruginosa.

Frequently Used Cephalosporin Formulations

• Cephalexin oral capsules effectively treat gram-positive skin organisms and are first-generation drugs but can cause stomach upset, blood dyscrasia development, hemolytic anemia
• Cefazolin IV, a first-generation drug, is frequently used intraoperatively for orthopedic procedures, but are at a high risk for infection.
• Ceftiofur (Naxcel®, Excenel®) is a third-generation drug with zero milk withdrawal for cattle and is administered IV, SQ, or IM.
• Ceftiofur crystalline free acid (Excede®) is SQ for cattle and IM for horses and swine, with long-acting activity dependent on the species and requires specific instructions.
• Cefovecin (Convenia®) is a third-generation drug given SQ that binds to plasma proteins for long-acting effect and lasts 7-14 days.
• Cefpodoxime (Simplicef®) is a third-generation drug given orally once daily.

Uses of Cephalosporins

• Skin infections (pyoderma).
• Bovine mastitis.
• Respiratory infections in horses, cattle, sheep, and swine.
• Bovine respiratory disease and foot rot.
• Equine Streptococcus equi.
• Swine respiratory disease.
• Urinary tract infections.

Adverse Effects of Cephalosporins

• Cephalosporins are generally well-tolerated, but allergic reactions and blood dyscrasias (AIHA) may occur rarely.
• Diarrhea in horses can been seen when given in high doses.

Tetracyclines

• Tetracyclines are bacteriostatic but may be bactericidal at high concentrations.
• Active against Mycoplasma, Chlamydia, Borrelia burgdorferi, Leptospira sp., Toxoplasma, and Ehrlicia as well as many positive and negative bacteria.
• Generic names end in -cycline or brand names end in -mycin. They mostly treat tick borne diseases.
• May be given parenterally or orally.
• Inactivated by antacids and dairy products.

Tetracycline Pharmacokinetics

• They are distributed throughout the tissue and can sometimes penetrate the CNS,.
• Most are eliminated in active form by glomerular filtration but can also be eliminated through biliary excretion.
• Use with caution in renal disease.

Tetracycline Pharmacodynamics

• Tetracyclines act to inhibit protein synthesis, impeding bacterial cell division and should not be placed with bactericidal drugs.

Frequently Used Tetracycline Formulations

• Doxycycline treats tick-borne diseases, respiratory infections, and Mycoplasma hemofelis.
• Doxycycline- Doxirobe® gel treats periodontal disease and is a vet formulation
• Tetracycline (LA-200, Biomycin) are injectables for bovine respiratory disease.
• Tetracycline- Terramycin® is a water-soluble powder for poultry.
• Chlortetracycline boluses a treatment for calf scour.
• Oxytetracycline treats bovine respiratory disease, foot rot and Equine Erlichia.

Uses for Tetracycline

• Ocular chlamydia and conjunctivitis.
• Respiratory infections.
• Bacterial enteritis.
• UTIs.
• Rickettsial diseases.
• Flexural limb deformities.

Adverse Effects of Tetracycline

• Possible renal toxicity and permanent staining of young animal teeth.
• Drug-induced fever in cats can occur.
• Esophageal stricture in cats if "dry pilled".

Aminoglycosides

• They are bactericidal and end in suffixes -micin or -mycin; however, not all "-mycins" are aminoglycosides.
• Exhibit primary effect against gram-negative organisms, but is lovery against anaerobes
• Used cautiously in reptiles and birds with IV fluids to reduce nephrotoxicity risk.
• May cause nephrotoxicity and ototoxicity.

Aminoglycosides Pharmacokinetics

• Aminoglycosides are poorly absorbed through the GI tract, so most are given parenterally.
• They are distributed throughout the bloodstream and distributed to the extracellular fluid, but do not reach the bile, CSF, respiratory secretions, prostatic or ocular fluid.
• Elimination occurs through glomerular filtration into the urine.
• They can accumulate in high levels in the renal cortex, making normal renal function necessary for use.

Aminoglycosides Considerations

• Levels of creatinine should be monitored before and during treatment to watch for potential signs of nephrotoxicity due to their accumulation properties
• Monitoring creatine is necessary to ensure drugs aren't accumulating
• Drug concentrates in the inner ear, which can potentially cause ototoxicity that is vestibular or auditory

Aminoglycosides Action

• Very similarly to tetracyclines, aminoglycosides also inhibit protein synthesis and bacterial cell division.

Considerations for Aminoglycosides Use

• Broad spectrum drugs should only be used for certain gram-negative infections even though these drugs have a broad spectrum.
• These have a poor activity against streptococcal infections and anaerobic bacteria.

Formulations of Aminoglycosides

• Gentamicin is great for equine orthopedic infections but must be given IV in combination with penicillin; it is combined with ampicillin for treatment of sepsis in small animals.
• Otomax® and Malotic® are topical formulations of Gentamicin and are used in combination of steroids and antifungals in treating otitis.
• Amikacin is delivered via a IV or injected as a regional limb perfusion.

Considerations for Aminoglycoside Adverse Effects

• Contraindicated for animals with renal insufficiency
• Should not be used in combination with neuromuscular blocking agents
• Aminoglycosides are not approved for use in food animals, and can disrupt the intestinal flora resulting in diarrhea, which is potentially life threatening for horses in particular

Fluoroquinolones

• Relatively new with a bactericidal action
• Has a -floxacin suffic
• Commonly approved for used among larger animals like: cattle, dogs, cats, turkeys and chickens

Pharmacokinetics of Fluoroquinolones

• Available for oral and parenteral administration
• Absorbed into the tissue and body fluids
• Metabolism occurs in the liver and occurs via the kidneys into urine or through bile into the intestines

Pharmacodynamics of Fluoroquinolones

• Wide bactericidal action is achieved through the inhibition or interference of the bacterial enzyme DNA-gyrase
• Broad gram-positive and gram-negative activity

Specific Formulations of Fluoroquinolone

• Enrofloxacin, known as Baytril®, can be delivered via oral and parenteral administration
• Marbofloxacin is known as Zeniquin®Orbifloxacin, known as Orbax® can be given as a ophthalmic preparation
• Ciproflaxin is Cipro® and is only reserved for animals

Clinical Uses of Fluoroquinolones

• Great for treating skin and soft tissue infections
• Treats respiratory infections and UTIs
• Can also treat bovine respiratory disease, but there's little activity against anaerobes

Adverse Effects of Fluoroquinolones

• Adverse effects can include blister or cyst-like that appears during rapid growth, and is more common for smaller breeds.
• Adverse effects include blindness in older cats given fluoroquinolones at high doses.

Considerations for Fluoroquinolone Use

• Not determined in breeding cats and dogs
• Always adhere to withdrawal times in food and animals
• ELDU use is prohibited

Chloramphenicol General Information

• Bacteriostatic
• Available in tablet, capsule, ophthalmic formulations
• Functions as a four quadrant antibiotic- with activity against gram positive and negative aerobes/anaerobes.

Considerations for Chloramphenicol Use

• Banned in food animals because it runs the risk of causing anaplasic anemia
• Readily absorbed into the tissue and body fluids.
• Metabolized by the liver and excreted through the kidneys into the urine.
• Inhibits bacterial protein synthesis

Factors that can affect Chloramphenicol Use

• Metabolized by specific liver enzyme group
  • Other drugs compete for this enzyme group
  • Phenobarbital and primidone (anticonvulsants)
  • Pentobarbital (anesthetic/euthanasia)
  • Use with caution with these drugs

Clinical Use for Chloramphenicol

• Second line antibiotic
• Bacterial respiratory tract infections
• UTI
• Enteritis
• Bacterial conjunctivitis
• Has good penetration of the CNS, prostate and eye

Chloramphenicol Side Effects

• Staff should avoid inhaling powder and wash hands after handling
• Possible blood dyscrasias in cats
• Prohibited from use in food animals
• Not recommended for use in breeding dogs
• Should not be used in combination with the bactericidal penicillin, streptomycin or cephalosporins

Florfenicol Background and Effects

• With a bacteriostatic action, Florfenicol provides broad spectrum activity for Nuflor®, a food animal antibiotic.
• The drug can also penetrate the CNS; however, the drug can cause transient inappetence, decreased water consumption and diarrhea.
• Labeled for IM use in cattle 20 months of age or older. It also lacks the component that causes bone marrow toxicity in humans.

Macrolides

• With a bactericidal or bacteriostatic action, the primary target is against gram-positive bactera
• Inhibiting bacterial protein synthesis, they bind to the 50s subunit of the ribosomes
• Will distribute throughout the body, but not the CNS

Macrolide Clinical Uses

• Erythromycin commonly treats respiratory infections and is used in conjunction with rifampin for Rhodococcus equi.
• Another macrolide known called Tilmicosin- Micotil®, treats respiratory disease in cattle and is fatal in humans even though it is used to battle respiratory disease
• Other macrolides are Tylosin-Tylan which when mixed with water, is soluble and used to treat for chronic clostridial colitis in small animals for poultry
• Tulathromycin (Draxxin) treats Bovine Respiratory Infections

Adverse Effects of Macrolides

• Azithromycin is also a macrolide, known as Zithromax used to treat respiratory infections and Bartonellosis
• Diarrhea, vomiting a common symptom esp erythromycin
• Severe diarrhea in horses is common
• Injecting IM can have a painful injection

Lincosamides Key Aspects

• Bacteriostatic/bactericidal depending on concentration
• Gram-positive and anaerobic spectrum
• Disrupts with bacterial protein synthesis by interfering with the binding the 50s ribosomal subunit
• Treats both mastitis and upper respiratory infections in some animals
• Clindamycin is approved for treating skin infections
• Will typically be metabolized in the kidneys- liver and kidney disorders can result in a need for dose reduction

Specific Lincosamide Medications

• Clindamycin and Lincomycin are the most common lincosamides, which treat infections.
• Lincosamides has a potential of a high resistance, but is commonly resistant to everything
• May cause gi stress

Vancomycin

• Has a bactericidal effect
• Can be more commonly known is use due to growing rise in antibiotic resistance to MRSA.
• Very effective gram-positive pathogens will get these drugs

Clinical Use of Vancomycin

• Given as a injection for resistance staph and strep
• orally only for difficult clostridium cases

Polymyxin B and Bacitracin

• Have a bacteriostatic effect and used in tandem with treatment for skin conditions
• Polymyxin-B works well with gram negative bacteria

Method of Action of Polymyxin B

• Applied topically and combined with other agents to create a stronger treatment for skin and eye conditions.
• The drug won't create a systematic uptake
• Some Polymxin formulations when injected directly could create a possibility for neurotoxicity

Sulfonamides

• Used in WW II, and very common among soldiers
• Can reduce bacteria effectively
• Only work while potentiated by other drugs

Pharmacokinetics of Sulfonamides

• Travel throughout the body well
• Some can act as a UTI drug, but consult veterinarian first

Specific Use for Sulfonamide Drugs

• Some form crystals in the urine and those who take it, will need plenty of water

More Information for Sulfonamide Medications

• Sulfadimethoxine is common among drugs and treats parasite infections with a loading dose.
• Sulfamethoxazole-Trimethoprim serves as an antibiotic tablets for cats and large farm animals

Side Effects

• Allergic reactions
• induced cataracts among Spaniels

Rifampin

• An antimicrobial combined with other antibiotics
• Targets and destroys RNA synthesis

Clinical Uses

Works well with younger horses and helps create a hyperthermia barrier

• Can cause different colors, so a veterinarian should advise with the safety

Nitrofurans

• Utilized topically and can be both bacterical or bacteristatic
• Utilized for skin problems and food based residue contamination

Nitroimidazoles-metronidazole

• Considered an antibacterial drug and good to destroy protozoa and used against anaerobic bacteria

Clincal Uses for Nitroimidazoles

• To treat protozoal infections- administer per rectum to the horse

Adverse Effects for Nitroimidazoles

• The drugs do pose some side effects- such as anorexia, diarrhea- or a dangerous neurotoxicity

Antifungals and its Clinical Uses

• Infections known as mycoses are classified into two different categories and is dived into 4 different options- polyene, imidazole, antimetabolic and superficial agents
• AntiFungal drugs are mostly static and can damage the kidney
• Systemic for systemic and localized problems

The Difference Between an Polyene Antibiotic vs Nystatin based medication

• Amphotericin B exhibits fungistatic and fungicidal properties and used for serious systemic issues
• Nystatin is a topical drug and is used for mucus membranes.

What Is Ketoconzaole

• A very broad antifungal for many different things. Will be mixed with monistat for treatment of yeast infections

Additional Information on Antifungal Medications

• Other antifungal can trigger an affect to the liver and heart and is considered oral and fungistatic
• Griseoufulvin is used on cats and dogs and can have many adverse effects

Antiviral Effects In Acyclovir

• A support tool as it targets cornea issues common in cats Other antivirues commonly used are Valacyclovir and Zovirax.

General Overview for Antiviral Medications

• Inhibits RNA-dependant conversion for viral RNA and helps reduce infection from FeLV.
• May assist in the pain that's perpetuated