Antibiotic Therapy Quiz

Antimicrobial Therapy

• Antimicrobial: Drugs that are toxic to invading organisms but not to mammalian cells.
• Criteria for selecting Antimicrobial agent:
  • Identification of the microorganism
  • Susceptibility of the microorganism to a particular agent
  • Empiric Therapy: Some patients require immediate administration of drugs before bacterial identification and susceptibility testing. Factors include:
    • Site of infection
    • Patient factors
    • Safety of the agent
    • Cost of therapy

Special Considerations When Using Antimicrobial Drugs

• Do not use antimicrobial drugs for mild infections.
• Should be used only for individuals at risk of severe infection.
• Use topical or local antimicrobials when possible to reserve systemic drugs for serious disease.
• Use should be based on a definitive diagnosis.
• Don't use broad-spectrum antibiotics if a specific antibiotic is effective.
• Administer drugs in full therapeutic doses.
• Be careful about antibiotic withdrawal times in animals destined for human consumption and dairy cows.

Identification of the Infecting Organism

• Gram staining and direct microscopic visualization: Provides rapid assessment of the pathogen. Used to identify the presence and morphology of organisms in body fluids that are normally sterile.
• Culture the organism: To get a conclusive diagnosis and determine susceptibility. Obtain a sample for culture prior to starting treatment.
  • Definitive identification may require further laboratory techniques such as detection of microbial antigens, DNA, or RNA.
  • Detection of host immune response.
• Visualization of pathogens is done in different ways. One way is through microscopic observation.

Determining Antimicrobial Susceptibility

• A practical approach to measuring the minimal inhibitory concentration (MIC).
• Minimal Inhibitory Concentration (MIC): The lowest antimicrobial concentration that prevents visible growth of an organism after 24 hours of incubation. Estimated using sensitivity disks. Some pathogens have predictable susceptibility to specific antibiotics.

Bacteriostatic versus Bactericidal Drugs

• Bacteriostatic drugs: Arrest growth and replication of bacteria, allowing the immune system to eliminate the pathogen. If the drug is discontinued before the immune system clears all the organisms, the cycle of infection may reoccur.
• Bactericidal drugs: Kill bacteria. The drug of choice for seriously ill and immunocompromised patients.

Chemotherapeutic Spectrum

• Narrow-spectrum antibiotics: Chemotherapeutic agents acting only on a single or limited group of microorganisms.
• Extended-spectrum antibiotics: Antibiotics modified to be effective against gram-positive organisms and also against a significant number of gram-negative bacteria.
• Broad-spectrum antibiotics: Drugs that affect a wide variety of microbial species.

Time vs. Concentration Determinant Killing

• Concentration-dependent killing: The higher the drug concentration relative to the pathogen MIC, the greater the rate and extent of antimicrobial activity. Aminoglycosides are administered as a once-a-day bolus infusion to achieve high peak levels.
• Time-dependent killing: Clinical efficacy determined by the duration that blood concentrations of a drug remain above the MIC. Continuous (24 hours) infusions can be used instead of intermittent dosing to achieve prolonged time above the MIC for better bacteria killing.

Effect of the Site of Infection on Therapy

• Adequate antibiotic levels must reach the site of infection. Structures like the blood-brain barrier may limit drug diffusion.
• Lipid solubility of the drug may affect penetration into the CNS. Some drugs, like chloramphenicol, have high solubility and more readily enter.
• Molecular weight of the drug affects its ability to cross the blood-brain barrier. Lower molecular weight drugs tend to cross more easily.
• Protein binding of the drug can restrict its entry into the CSF.

Patient Factors

• Immune system: Host defense system eliminates invading organisms. High doses or longer courses may be necessary in cases of malnutrition, autoimmune diseases, pregnancy, or immunosuppressive drugs.
• Renal dysfunction: Poor kidney function may cause accumulation of certain antibiotics. Creatinine levels are used as an index of renal function.
• Hepatic dysfunction: Antibiotics eliminated by the liver (e.g., erythromycin) need careful dosing in patients with liver dysfunction.
• Age: Renal or hepatic elimination processes are often poor in newborns and elderly patients.
• Pregnancy and lactation: Many antibiotics cross the placental barrier or enter the nursing infant's milk.

Combinations of Antimicrobial Drugs

• It is advisable to use a single agent specific to the infecting organism. This reduces the possibility of superinfections, the emergence of resistant organisms, and minimizes toxicity.
• Certain drug combinations (e.g., beta-lactams and aminoglycosides) show synergism (combination is more effective than either drug alone).
• Combined therapy may cause interference with each other's actions. Co-administration of an agent that causes bacteriostasis may interfere with a second agent killing multiplying bacteria

Drug Resistance

• Bacteria are resistant to an antibiotic if the maximum level of the antibiotic does not halt growth or kill the bacteria.

• Mechanisms of Resistance:

  • Alteration of the antibiotic's binding site through mutation (e.g., alterations in penicillin-binding proteins).
  • Decreased accumulation (decreased uptake or increased efflux).

• Enzymatic inactivation: Destruction or inactivation of the antimicrobial agent (e.g., inactivation of penicillin by β-lactamases).

Some Mechanisms of Resistance to Antibiotics

• Different drugs have different mechanisms of resistance that can be grouped together for study.

Prophylactic Use of Antibiotics

• Used for prevention, not treatment, of infections. Restricted to situations where benefits outweigh risks (e.g., bacterial resistance).

Complications of Antibiotic Therapy

• Hypersensitivity: Penicillin can cause hypersensitivity reactions ranging from a mild urticaria (hives) to a life-threatening anaphylactic shock..
• Direct toxicity: Certain antibiotics can cause toxicity by affecting cellular processes. Aminoglycosides can cause ototoxicity (damaging auditory hair cells)..
• Superinfections: Broad-spectrum antimicrobials or combinations can disrupt normal microbial flora leading to overgrowth of opportunistic organisms in respiratory, oral, intestinal, and genitourinary tracts..

Classification of Antimicrobial Drugs

• Based on chemical structure (e.g., beta-lactams, aminoglycosides).
• Based on mechanism of action (e.g., cell wall synthesis inhibitors, protein synthesis inhibitors).

Antibiotics' Mechanisms of Action

• Diagram showing different mechanisms of antimicrobial action. Cell wall synthesis, folate synthesis, nucleic acid synthesis, cell membrane, and protein synthesis are categorized. The different types and subtypes of antibiotics are categorized accordingly.

Cell Wall Inhibitors

• Selectively inhibit the transpeptidase enzyme involved in cross-linking peptidoglycan, the final step in cell wall biosynthesis. This requires actively proliferating microorganisms.
• Important members include beta-lactam antibiotics (contain beta-lactam ring), vancomycin, carbapenems, bacitracin, and polymyxins.

Penicillins

• General structure: Different members of this family differ from one another in the R group.
• Mechanism of action: Inhibits transpeptidase, an enzyme involved in cross-linking peptidoglycans. This leads to cell lysis and is considered bactericidal. Effective against rapidly growing organisms synthesizing peptidoglycan cell wall.
• Natural penicillins: Penicillin G (procaine benzylpenicillin) is used for infections caused by Gram-positive and non-penicillinase-producing pathogens. Penicillin V is used for long-term oral therapy in dogs, cats, and horses.
• Penicillinase-resistant penicillins: Methicillin, oxacillin, and cloxacillin are used for severe staphylococcal infections caused by beta-lactamase-producing organisms.
• Broad-spectrum penicillins: Aminopenicillins (ampicillin, amoxicillin), carboxypenicillins (carbenicillin, ticarcillin), and piperacillin. Mechanisms and uses vary among these.
• Potentiated penicillins (beta-lactamases inhibitors): Clavulanic acid, sulbactam, augmentin are used to limit bacteria resistance..

Cephalosporins

• Mechanism of action: Similar to penicillins, acting as beta-lactam antibiotics with different generations offering varied spectrums of action. They are bactericidal.
• First-generation cephalosporins: Cephalexin, cefadroxil, cephapirin, cephalothin - used as an alternative to penicillins for Gram(+) infections, and some Gram(-).
• Second-generation cephalosporins: Cefaclor, cefoxitin - They have wider antibacterial spectrum than first-generation, covering both Gram(+) and Gram(-) bacteria, including anaerobic coverage.
• Third-generation cephalosporins: Ceftiofur, cefoperazone, cefotaxime, cefixime, cefpodoxime - have broader Gram(-) spectrum and are resistant to bacterial enzymes
• Fourth-generation cephalosporins: Cefepime - Gram(-) including pseudomonas and less active Gram(+).
• Administration and adverse effects: Acid stable can be administered orally, others are parenteral. Cephalosporins are generally safer than penicillins and less likely to cause allergic reactions
• Other considerations such as hypersensitivity, ototoxicity, nephrotoxicity should be considered.

Carbapenems

• Mechanism of action: Similar to other beta-lactam antimicrobial drugs.
• Uses: Treating serious infections, including peritonitis, intestinal spillage, Gram+ and Gram- aerobic and anaerobic bacteria
• Pharmacokinetics: Administered intravenously. Acid hydrolysis and poor absorption, thus not suitable for oral administration.
• Adverse effects: Hypersensitivity, anorexia, vomiting, diarrhea, seizures, and tremors.

Monobactams

• Mechanism of action: Binds to penicillin binding proteins in gram (-) aerobic bacteria and disrupts cell wall synthesis. Stable to most beta-lactamases
• Uses: Strict G(-), no activity G(+), replace aminoglycosides, used against pseudomonas.
• Pharmacokinetics: Similar distribution to penicillin G. Penetrates the CSF, and excreted by the kidneys.
• Adverse effects: Hypersensitivity reactions.

Vancomycin

• Mechanism of action: Blocks bacterial cell wall synthesis by inhibiting polymer release from the cell membrane. Bactericidal for Gram-positive organisms.
• Therapeutic uses: Methicillin-resistant staphylococcal infections of bone and soft tissue. Can be used to treat multidrug-resistant enteric infections.
• Pharmacokinetics: Not absorbed orally, distributed to ECF and transcellular fluids, excreted unchanged by glomerular filtration..
• Adverse effects: Ototoxicity and nephrotoxicity

Bacitracin

• Mechanism of action: Inhibits cell wall synthesis, bactericidal against Gram (+) bacteria and Spirochetes.
• Therapeutic uses: Topical ointments and solutions. Frequently combined with polymixin B and/or neomycin.
• Pharmacokinetics: Not absorbed orally; is nephrotoxic for systemic use.
• Adverse effects: No systemic toxicity with topical or oral administration.

Polymyxin B

• Mechanism of action: Interacts with phospholipids in bacterial cell membranes to cause membrane disruption. Bactericidal towards Gram (-) organisms..
• Therapeutic uses: Topical treatment of Gram (-) infections in the skin, eye, and ear. Can be administered orally to cattle and swine for Gram-(-) enteric infections.
• Pharmacokinetics: Not absorbed orally and it is nephrotoxic for parenteral use.
• Adverse effects: Does not cause systemic toxicity with topical or oral administration..

Protein Synthesis Inhibitors

• Inhibit bacterial protein synthesis by targeting bacterial ribosomes.
• High selectivity ensures minimal adverse effects on mammalian cells.

Tetracyclines

• Mechanism of action: Inhibit protein synthesis by binding to the 30S ribosome subunit, preventing tRNA attachment. Bacteriostatic.
• Spectrum of activity: Broad-spectrum, active against Gram-positive and Gram-negative aerobes and anaerobes.
• Therapeutic uses: Large animal and small animal applications across various infections.
• Pharmacokinetics and administration: Lipid soluble, penetrate CNS, eye, and prostate. Orally or intravenously administered.
• Adverse effects: Tetracyclines are nephrotoxic, except doxycycline and minocycline. Oral use may disrupt ruminal/colonic microflora.

Chloramphenicol

• Mechanism of action: Binds to bacterial 50S ribosome unit inhibiting peptide formation. Bacteriostatic and broad-spectrum, active against most anaerobic bacteria.
• Therapeutic uses: Local and systemic infections in dogs, cats, horses, and birds.
• Pharmacokinetics: Rapidly absorbed from the Gl tract and widely distributed to all tissues including the CNS. Metabolized by the liver.
• Adverse effects: Aplastic anemia is often fatal and related to its use in food producing animals.

Macrolides

• Mechanism of action: Bacteriostatic, inhibit bacterial protein synthesis by binding to the 50S ribosome to prevent amino acid translocation to the growing peptide chain. Active against Gram-positive aerobes, anaerobes, Mycoplasma.
• Therapeutic uses: Primarily used in respiratory infections caused by certain pathogens and mycoplasma.
• Pharmacokinetics: Absorbed orally if protected. Widely distributed to all tissues except the CNS.
• Adverse effects: Erythromycin can cause abdominal pain and diarrhea. Tilmicosin can cause cardiovascular toxicity in species where it is not usually applied (ex. cattle, rather than pigs).

Lincosamides

• Mechanism of action: Bind to bacterial 50S ribosome to inhibit protein synthesis. Bacteriostatic. Avoid combined use with Chloramphenicol because they use same binding site.
• Therapeutic uses: Treat various infections, such as swine dysentery, staphylococcal, streptococcal, and mycoplasmal infections, and periodontal disease, osteomyelitis, dermatitis, and deep soft tissue infections. Treatment of toxoplasmosis in dogs and cats and neosporosis in dogs.
• Pharmacokinetics: Can be administered either orally or by injection. Oral bioavailability varies (usually 50-90% for administered medicine)
• Adverse effects: May produce severe diarrhea due to altered Gl flora.

Aminoglycosides

• Mechanism of action: Bind to 30S ribosomal fragment inhibiting protein synthesis rate.
• Therapeutic uses: Enteric, skin, ear, and eye infections, skin respiratory tract, urinary tract, and septicemia, used for all species.
• Pharmacokinetics: Not absorbed from GI tract because of high polarity. Accumulate in renal cortex, leading to toxicity. Excreted unchanged in urine by glomerular filtration..
• Administration: IM or SC for systemic infections--oral for enteric issues. High dose once daily used to limit adverse effects like renal and cochlear toxicity.
• Resistance: Inactivation by bacterial enzymes. Amikacin is more resistant to degradation than other aminoglycosides..
• Adverse effects: Relatively more toxic than other classes of antimicrobials--uses should be made carefully with caution for animals with decreased renal function and not be used with other ototoxic/nephrotoxic drugs. Ototoxicity and nephrotoxicity are major risks.

Aminocyclitols

• Mechanism of action: Bind to the 30S ribosome and inhibit protein synthesis.
• Therapeutic uses: Treatment of enteric and respiratory infections, especially colibacillosis..
• Pharmacokinetics: Less than 10% is absorbed orally; effectively distributed to ECF. Excreted essentially unchanged and unaffected by kidney function or dysfunction.
• Adverse effects: Significant toxicity is not observed.

Tiamulin

• Mechanism of action: Binds to the 50S bacterial ribosome and inhibits protein synthesis.. Active against Gram(+) cocci, Mycoplasma, spirochetes, and some Gram(-) pathogens such as Haemophilus spp..
• Therapeutic uses: Treatment of Haemophilus pneumonia and swine dysentery
• Pharmacokinetics: Absorbed orally, widely distributed, and metabolized by the liver. Elimination of metabolites occurs in feces (70%) and urine (30%).
• Adverse effects: Dermatitis with erythema and pruritus may be observed if pigs are overcrowded due to the irritant metabolites in the urine.

Fluoroquinolones

• Mechanism of action: Inhibit bacterial DNA gyrase, controls DNA supercoiling. Bactericidal
• Therapeutic uses: Treatment for various infections, including those affecting the dermal, respiratory, and urinary tracts, are effective against G- and some G+ bacteria. Different types of infections such as bovine respiratory infections and in dogs and cats.
• Administration: Orally or parenterally in all species, but it is important to pay attention to different modes of administration for each subtype.
• Resistance: Reduced intracellular concentration due to decreased porin channels and efflux pumps. Growth of mutants in which fluoroquinolones do not bind to DNA gyrase.
• Adverse effects: Erosion of articular cartilage in young dogs and foals and seizures in dogs on phenobarbital for epilepsy.

Metronidazole

• Mechanism of action: Reduced by anaerobic bacteria and protozoa, producing cytotoxic metabolite that disrupts DNA synthesis and RNA synthesis, bacteriocidal toward obligate anaerobes
• Therapeutic uses: Treating anaerobic pathogens, especially brain abscesses, pelvic and genitourinary tract and respiratory tract infections in dogs, cats, and horses. Protozoal infections in dogs and cats.
• Adverse effects: High or prolonged dosage may cause neurotoxicity (signs like nystagmus, ataxia, and seizures)..
• Safety Considerations: Banned for food-producing animals due to potential carcinogenic effects.

Rifampin

• Mechanism of Action: Inhibits bacterial RNA polymerase and blocks RNA synthesis. Bactericidal for mycobacteria and Gram(+) pathogens.
• Therapeutic Uses: Combined with other drugs (e.g., erythromycin) to treat Rhodococcus equi in foals. Used to treat fungal infections like aspergillosis or histoplasmosis in dogs and cats.
• Pharmacokinetics: Absorbed orally and rapidly distributed to cells and tissue; commonly administered in foals, dogs, and cats.
• Adverse Effects: Hepatotoxicity may occur in animals with preexisting liver disease. Produce red-orange colored urine, sweat, and saliva.

Nitrofurans

• Mechanism of Action: Bacteria reduce nitrofurans to form reactive intermediates, causing DNA fragmentation and inhibiting mRNA translation. Broad-spectrum and bacteriostatic.
• Therapeutic Uses: Orally to treat lower urinary tract infections in dogs and cats and topically as ointments. Used as a powder for wound dressings in all species..
• Pharmacokinetics: Absorbed orally and rapidly excreted by glomerular filtration..
• Adverse Effects: Not used in food-producing animals due to potential carcinogenic effects.

Novobiocin

• Mechanism of Action: Blocks bacterial DNA gyrase, which inhibits supercoiling of bacterial DNA. Bacteriostatic for Gram-positive cocci..
• Therapeutic Uses: Used for wound treatment and treatment of mastitis, especially in Staphylococcus infections.
• Pharmacokinetics: Absorbed orally; poor tissue penetration..
• Administration: Intrammammary infusion with procaine penicillin to limit resistance.
• Adverse Effects: Does not produce systemic toxicity

Sulfonamides

• Mechanism of action: Competitive inhibitors of bacterial dihydropteroate synthetase, an enzyme involved in folate synthesis. This inhibits the synthesis of purines (a DNA precursor) and pyrimidines for cell growth, effectively stopping bacteria from replicating.
• Therapeutic uses: Various infections including respiratory, enteric, and urinary tract infections. Used as ophthalmic preparations and to treat colitis and inflammatory bowel disease.
• Pharmacokinetics: Well absorbed orally and widely distributed to tissues.. Metabolized via acetylation and glucuronide conjugation with elimination by glomerular filtration.
• Preparations: combinations of sulfonamides with trimethoprim or ormetoprim-- these offer a broader spectrum of action and reduced rate of resistance.
• Adverse effects: Precipitation in the urine (crystalluria) in neutral or acid urine can occur if large doses or dehydration occur.. Can cause keratoconjunctivitis and hemopoietic disturbances (anemia and thrombocytopenia).

Test your knowledge on the potential disadvantages and complications of antibiotic therapy. Explore how bacteria develop resistance to antibiotics and learn about mechanisms that bacteria use to reduce antibiotic accumulation in their cells. This quiz covers important concepts in microbiology and pharmacology.