Antimicrobials

CHAPTER 14CHAPTER 14

Dr. Dipa Brahmbhatt VMD MpHDr. Dipa Brahmbhatt VMD MpH

dbrahmbhatt@vettechinstitute.edudbrahmbhatt@vettechinstitute.edu

Basic Terminology

• An antimicrobial is a chemical substance that has the capacity, in diluted solutions– To kill (biocidal activity) OR

• Attack something that micoorganism have but patient doesn’t

– Inhibit the growth (biostatic activity) of microbes• Attack both have but microorganism needs more of it

• Antimicrobials can be classified as:– Antibiotics– Antifungals– Antivirals– Antiprotozoals– Antiparasitics – Ch 15

Staphylococcus

Pathogenic Microorganisms

• Cause a wide variety of infections and illness in different organs or body systems

• May be classified as local or systemic– A localized infection may involve skin or an internal organ

and may progress into a systemic infection

– A systemic infection involves the whole animal and is more serious than a local infection

Pathogenic Microorganisms

Enter the body through:

• Integumentary

– Break through skin or mucous

membrane• Respiratory system

– Inhaling contaminated droplets

• GI tract

– Ingestion contaminated food and water

• Genitourinary

– Contaminated vaginal secretions, semen or urine

Antimicrobials

• Prokaryotic

– Fewer organelle & smaller than Euk.

– Cell wall

• +/- capsule

– Cell/ plasma membrane

– Nucleoid

– Cytoplasm

– Ribosomes

– +/-: pili, plasmids, flagellum

– Few have endospore

• Eukaryotic

– Cell / plasma membrane

– Nucleus

– Nucleolus

– Cytoplasm

– Mitochondria

– Golgi apparatus

– Endoplasmic reticulum

– Ribosomes

– Vacuoles

– Lysosomes

Boundary/ semi-permeable

•Controls cellular activity•Genetic material

NucleolusProduces RNA that Forms ribosomes

Semi-fluid medium with organelles

Energy producers

Chemical processor of the cell

Has ribosomes Syn. proteins

No ribosomeSyn. Lipids and some carbohydrates

Site of protein synthesis

Small, membrane boundOrganelles with food, water or metabolic waste

Digestive system of the cell

Not membrane bound

Smaller than Eukaryotic

Barrier againstphagocytosis

Hairlike protein extensionsAttach/communicate withOther cells

DNA outside chromosomeReplicate independentlyPass info via pilus

Mobility

FEW BACTERIA HAVE ABILITY TO PRODUCE ENDOSPORESPersists in variable environment

Antibiotics

• Antibiotics work only on bacteria and are described by their spectrum of action spectrum of action (range of bacteria for which the agent is effective)– Narrow-spectrum antibiotics work only on eithereither gram-positive or

gram-negative bacteria (not both)– Broad-spectrum antibiotics work on bothboth gram-positive and gram-

negative bacteria (but not necessarily all)

• Antibiotics can be classified as bactericidalbactericidal or bacteriostaticbacteriostatic– Bactericidals killkill the bacteria– Bacteriostatics inhibit the growth inhibit the growth or replication of bacteria

Gram stain Procedure

Staphlylococcus sp.Streptococcus sp.

Salmonella sp.Proteus sp.

Antimicrobials

• The goal of antimicrobial treatment is to render the microbe helpless (either by killing them or inhibiting their replication) and not to hurt the animal being treated

• Antibiotic treatment is accomplished by making sure that the infecting bacteria are susceptible to the antibiotic, that the antibiotic reaches the infection site and that the animal can tolerate the drug

Agar Diffusion Test

• A.k.a. Kirby-Bauer antibiotic sensitivity testing• Used to determine if a particular antibiotic is effective

against a particular bacterium.• Antibiotic-impregnated disks placed onto agar plates

containing bacteria being tested.• After incubation at proper temperature for the proper

time, zones of inhibition (clear zones) are measured and compared to a standardized chart to determine R.– R = resistant (antibiotic does not work); I = intermediate

(antibiotic may work); S = sensitive (antibiotic will work)

Broth Dilution Method

Minimum Inhibitory Concentration (MIC): Lowest conc. Of Antibiotic that visually inhibits growth of bacteria

EFFECTIVE ANTIBIOTIC

• Bacteria sensitive to antibiotic

• Proper dose of Ab.

• Get’s into infection site at high enough doses

How Do Antibiotics Work?

• Antibiotics work by a variety of mechanisms:– Inhibition of cell wall synthesis

• Bacteria have cell walls & animals don’t

• Bactericidal: growing and dividing not in developed

bacteria

– Damage to the cell membrane• Alters membrane permeability

• Bactericidal/static

• Loss of cellular substances

causes lysis of cell

How Do Antibiotics Work?

– Inhibition of protein synthesis

• In ribosomes

– RNA copy (of DNA), t RNA (AA’s)

– Disrupts linkage of AA’s

– Bactericidal/static

– Interference with metabolism

• Block enzymes / essential nutrients

– Can’t divide and cell death

• Bacteriostatic

– Impairment of nucleic acids

• Intefere with nucleic acid production– Can’t divide/ function properly

• Bactericidal

cidal

cidal

static

Considerations when using antibiotics

• Antibiotic resistance– Means that the bacteria survive and continue to multiply

after administration of the antibiotic

– Occurs when bacteria change in some way that reduces or eliminates the effectiveness of the agent used to cure or prevent the infection

– Causes• Drug not properly used (used for viral infection)

• Not admin. For proper length of time

• Not at proper dosage

Considerations when using antibiotics

• Antibiotic resistance dvlps. through

• Natural/Intrinsic resistance• Ab. Acts on enz. Systems or biological processes

not used by microorganism

• Acquired resistance: sensitive before• Bacterial mutation

– E.g. bacteria produce beta-lactamase, inactivates penicillin

• Bacteria acquiring genes that code for resistance– Plasmids

• Other means– Cross –resistance e.g. between Ab’s. with same actions: penicillins & cepalosporins

– Noscomial infections (sick patients and close contact)

– Handwashing

Considerations when using antibiotics

• An antibiotic residue is the presence of a chemical or its metabolites in animal tissue or food products• Residue is not usually degraded

by cooking/ pasteurization– Antibiotic residues can cause

allergic reactions in people or can produce resistant bacteria that can be transferred to people who consume these products

– Withdrawal times for antibiotics are aimed at eliminating antibiotic residues in food-producing animals

Considerations when using antibiotics

• The FDA approves all drugs marketed for use in animals in the United States

• The FDA also establishes tolerances for drug residues to insure food safety

• The FDA also establishes withdrawal times and withholding periods– Times after drug treatment when milk and eggs are not to

be used for food, and also when animals are not to be slaughtered for their meat

– FARAD: Food Animal Residue Avoidance Databank

Classes of Antibiotics

• Cell wall agents

• Protein synthesis agents

• Antimetabolites

• Nucleic acid agents

• Miscellaneous agents

Cell Wall Agents

• Penicillins (mold)Penicillins (mold)– Have beta-lactambeta-lactam

structure that interferes with bacterial cell wall synthesis

– Identified by the –cillin ending in the drug name

– Spectrum of activity depends on the type of penicillin

Cell Wall Agents

• Natural PenicillinsNatural Penicillins

– Penicillin G and V are narrow-spectrum gram-positive antibiotics (Staphylococcus sp. & Streptococcous sp.)

• Penicillin G is given parenterally (inactivated by stomach acid)

– Only sodium or potassium salt of Pen-G can be admin. IV, IM: peak levels 20 mins

– Refrigerated: 14 days

– Procaine & Benzathine (suspensions): increase duration

– PPG: 24 hr. duration

– Benzathine PG: 5 days

– SE: Anorexia, V/D (orally), hypersensitivity

Cell Wall Agents

• Natural Penicillin (cont …)

• Penicillin V is given orally

– Give PCN on empty stomach (except amoxicillin)

– Penicillin V potassium: preferred better absorbed in GI and stable in stomach acid

– Broader-spectrum penicillins are semi-synthetic

• Slowly excreted from kidneys

• Examples include amoxicillin, ampicillin,

carbenicillin, ticarcillin, and methicillin

Cell Wall Agents

• Beta-lactamase resistant penicillins • More resistant to beta-lactamase / penicillinase(an enzyme produced by

some bacteria that destroys the beta-lactam structure of penicillin)• Examples include methicillin, oxacillin, dicloxacillin, cloxacillin,

and floxacillin

– Potentiated penicillins are chemically combined with another drug to enhance the effects of both

• An example is a drug containing amoxicillin and clavulanic acid amoxicillin and clavulanic acid (which binds to beta-lactamase to prevent the beta-lactam ring from being destroyed)

• E.g. Clavamox and Augmentin

Table 14-2

Cell Wall Agents

• Cephalosporins (fungus derivative)Cephalosporins (fungus derivative)– Are semi-synthetic, broad-spectrum

• Have the beta-lactam ring (like penicillins)

• Can be identified by the ceph- or cef- prefix in the drug name

• Tx: Respiratory, skeletal, genitourinary, skin, soft tissue

• Peri-operatively

• SE: v/d (give w/food), phlebitis, myositis, nephrotoxic

– Are classified into four generationsfour generations• In general, as the number of the generation increases, the spectrum

of activity broadens (but becomes less effective against gram-positive bacteria)

Cell Wall Agents

1st generation• Greatest cidal/static gram – and some against gram +

• Can be inactivated by beta-lactamase

• No blood-brain barrier

– 2nd generation• Broader spectrum of activity gram – compared to 1st

• No BBB

– 3rd gen.• Better gram –

• Resistant to some beta-lactamase

– 4th gen. • Like 3rd and Pseudomonas aeruginosa and Enterobacteriaceae

• More active against gram + than 3rd

Cefpodoxime: DailyCefovecin: 14 days Cefpodoxime: DailyCefovecin: 14 days

• Convenia® (cefovecin sodium)Convenia® (cefovecin sodium)– First antibiotic that provides an assured course of

treatment by providing up to 14 days of treatment in a single injection, eliminating missed doses associated with daily oral antibiotic administration

– Labeled specifically for secondary superficial pyoderma, abscesses, and wounds (S. intermedius, S. canis ) in dogs and abscesses and wounds (P. multocida) in cats.

– Must be reconstituted, refrigerated, and used within 28 days of reconstitution

– Second dose may be necessary in 14 days.

Cell Wall Agents

• BacitracinBacitracin – Disrupts the bacterial cell wall via polypeptide chain– Effective against gram-positive bacteria– Used topically (skin, mucous membranes, eyes) and as a

feed additive– SE: Nephrotoxic

• VancomycinVancomycin– Bacteriocidal; effective against many gram-positive

bacteria; used for resistant infections (to penicillin/cephalo.)

– Useful in treatment of Staphylococcus aureus & Clostridium difficile (humans)

– SE: Nephro/Oto toxicity, pain IV injection

Cell Membrane Agents

• Polymyxin B (plasma membrane, polypeptide)Polymyxin B (plasma membrane, polypeptide)– Works by attacking the cell

membrane of bacteria (remember that animal cells have cell membranes too)

– Is a narrow-spectrum, gram - antibiotic• Not absorbed when taken orally or applied topically• Used as an ointment or wet dressing

– Often combined with neomycin and bacitracin = triple ABX ointment

Protein Synthesis Agents• Aminoglycosides (Aminoglycosides (StreptomycesStreptomyces microbes) microbes)

– Interfere with the production of protein in bacterial cells– Are a specialized group of antibiotics with a broad spectrum of

activity, used for gram-negative bacteria (septicemia, ocular, otic)

– Are not absorbed well from the GI tract, so are given parenterally

– May be recognized by –micin or –mycin ending in drug name (but are not the only group to use these suffixes)

– Side effects are nephrotoxicity and ototoxicity– Examples include gentamicin, neomycin, amikacin, tobramycin,

and dihydrostreptomycin– NOT approved for use in food-producing animals.– Vancomycin & Erythromycin ARE NOT

aminoglycosides

Protein Synthesis Agents• TetracyclinesTetracyclines

– Are a group of bacteriostatic antibiotics with a broad spectrum of activity, including rickettsial agents (Mycoplasma, Chlamydia)

• Treats Lyme disease, Ehrlichia, Hemobartonella, leptospirosis, – Can bind to calcium (affecting muscle contraction) and be deposited

in growing bones and teeth (yellow), or bind components of antacids and other mineral-containing compounds

– Are recognized by –cycline ending in drug name– Short acting water soluble: tetracycline, oxytetracycline,

chlortetracycline, – Long acting lipid soluble: doxycycline, and minocycline– Oral and parenteral forms– Don’t give to young, pregnant or with dairy products, antacids, kaolin,

pectin, bismuth– SE: ORAL: v/d, renal damage; PARENTERALLY: anaphylaxis,

hypotension, shock

Protein Synthesis Agents

• ChloramphenicolChloramphenicol– Is a broad-spectrum antibiotic that penetrates tissues and

fluids well (including the eyes and CNS)– Has toxic side effects (bone marrow depression) that

extremely limit use: Aplastic anemia– Use caution when handling this product (gloves)– Chloramphenicol is the only drug in this category– Also available in ophthalmic solution– Used for RMSF (among other conditions)– Banned from use in food-producing animals.– Not considered a first-line drug (cause of toxic

SE)

Protein Synthesis Agents

• Florfenicol (Nuflor®)Florfenicol (Nuflor®)– Is a synthetic, broad-spectrum antibiotic– Injectable solution– Used to treat bovine respiratory disease and foot

rot.– SE: include local tissue reaction (possible loss of

tissue at slaughter), inappetence, decreased water consumption, and diarrhea

– Florfenicol is the only drug in this category

Protein Synthesis Agents

• MacrolidesMacrolides– Interfere with the production of protein in bacterial

cells– Are broad-spectrum antibiotics that have a large

molecular structure– Used to treat penicillin-resistant infections or in

animals that have allergic reactions to penicillins– May cause stomach upset in animals

• Erythromycin (oral or ointment)• Tylosin (used mainly in livestock - can cause fatal diarrhea

in horses)• Tilmicosin (used to treat bovine respiratory disease – single

injection – 3 days)

Protein Synthesis Agents

• LincosamidesLincosamides– Interfere with the production of protein in bacterial

cells

– Are narrow-spectrum, gram-positive antibiotics

– Side effects include GI problems• Veterinarians typically use erythromycin instead.

– Examples include clindamycin, pirlimycin, and lincosamide

Antimetabolites

• SulfonamidesSulfonamides– Are broad-spectrum antibiotics that inhibit the synthesis of folic

acid (needed for the growth of many bacteria)– Some are designed to stay in the GI tract (enteric forms); some

are absorbed by the GI tract and penetrate tissues (systemic forms)

– Side effects include crystalluria, KCS (dry eye), and skin rashes– Precipitate in kidneys of animals that are dehydrated or have

acidic urine; Adequate water intake = very important!– Bactericidal when potentiated with trimethoprim or ormetoprim– Examples include sulfadiazine/trimethoprim, sulfadimethoxine,

and sulfadimethoxine/ormetoprim

Miscellaneous Agents

• NitrofuransNitrofurans– Are broad-spectrum antibiotics that include furazolidone,

nitrofurazone, and nitrofurantoin– Used to treat wounds (topically) and urinary tract

infections– Filtered unchanged through kidneys– Carcinogenic residues in animal tissues

• NitroimiazolesNitroimiazoles– Have antibacterial and antiprotozoal activity; work by

disrupting DNA and nucleic acid synthesis– An example is metronidazole, which is considered by some

the drug of choice for canine diarrhea

Nucleic Acid Agents

• FluoroquinolonesFluoroquinolones– Are antibiotics with fluorine bound to the quinolone base,

which increases the drug’s potency, spectrum of activity, and absorption

– Are broad-spectrum antibiotics (gram + and gram -)– Can be recognized by –floxacin ending in drug name– Side effects include development of bubble-like cartilage bubble-like cartilage

lesions in growing dogslesions in growing dogs, and crystalluria– Quinolone-induced blindness in cats.– Indiscriminate use may result in bacterial resistance.– Examples include enrofloxacin, ciprofloxacin, orbifloxacin,

difloxacin, marbofloxacin, and sarafloxacin

• Metronidazole (Flagyl®) Metronidazole (Flagyl®) is drug of choice for canine diarrhea– Used to treat Giardia and

Trichomonas infections

– Also used for amoebiasis and anaerobic bacteria

– Oral or intravascular administration

– No approved veterinary form of metronidazole (used off-label)

– Do not use in pregnant animals

– Can cause neurologic signs (especially when given IV)

Miscellaneous Agents

• RifampinRifampin– Disrupts RNA synthesis

– Is broad-spectrum; used in conjunction with other antibiotics (usually erythromycin)

– May impart a reddish color to urine, tears, sweat, and saliva.

• Refer to Table 14-2 in your textbook for a review of antibiotics used in veterinary practice