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Intravenous Antibiotic Administration and Mechanisms of Action

  • Imipenem
      - Competitive antagonist of GABA
      - Dose > 2 g/day leads to neurotoxicity
        - Limits use in conditions such as epilepsy, craniocerebral trauma, meningitis, stroke

  • Meropenem (Meronem)
      - Increased activity against Gram-negative bacteria
      - Less active against staphylococci and streptococci
      - Not inactivated by renal dihydropeptidase-1; can inhibit this enzyme
      - Resistant to β-lactamases
      - Minimal neurotoxicity, infrequent nausea and vomiting
      - Administered via intravenous bolus over 5 minutes

  • Ertapenem (introduced in 2000)
      - Broad-spectrum and long-acting
      - Adverse reactions:
        - Allergic reactions
        - Gastrointestinal dysfunction (nausea, vomiting, abdominal pain, diarrhea)
        - Neurotoxicity (tremor, convulsions, confusion)
          - Thrombocytopenia

Monobactams

  • Aztreonam
      - Represented by a narrow-spectrum antibiotic
      - Effectiveness against Gram-negative aerobic microflora from the Enterobacteriaceae family
        - Includes: E. coli, Enterobacter, Klebsiella, Proteus, Serratia, Morganella, Cytrobacter, Providentia
      - No activity against Gram-positive bacteria or anaerobes
      - Destruction by β-lactamases present in many bacteria

Main Features of Monobactams

  • Strong bactericidal action

  • Narrow antibacterial spectrum (mainly Gram-negative aerobes)

  • Absence of cross-resistance with penicillins and cephalosporins

  • Favorable pharmacokinetics, including blood-brain barrier permeability

  • Primarily eliminated by the kidneys

Pharmacokinetics of Aztreonam

  • Not absorbed from the gastrointestinal tract

  • Administered parenterally (intramuscular and intravenous)

  • Excreted unchanged by the kidneys

  • Half-life (T1/2) approximately 2 hours, extended during renal insufficiency

Clinical Uses

  • Reserved for infections of the urinary tract, respiratory tract, skin, etc. caused by aerobic Gram-negative bacteria

  • Adverse effects: dyspepsia, skin allergies, thrombocytopenia, injection site irritation

  • No observed cross-allergy with other β-lactam antibiotics

Macrolides and Azalids

  • Macrolides are low toxicity antibiotics with a broad spectrum of activity
      - Bacteriostatic (bactericidal at high doses) effects
      - Chemical structure based on a macrocyclic lactone ring connected to various sugars

Classification of Macrolides

  1. Fourteen-membered lactone ring:
       - Natural: erythromycin, oleandomycin
       - Semisynthetic: roxithromycin, clarithromycin, dirithromycin, fluritromycin, telithromycin

  2. Fifteen-membered lactone ring (Azalids):
       - Semisynthetic: azithromycin

  3. Sixteen-membered lactone ring:
       - Natural: midecamycin, spiramycin, josamycin
       - Semisynthetic: midecamycin acetate

Main Properties of Macrolides

  • Stable in the acidic stomach environment (except erythromycin)

  • Well absorbed from the gastrointestinal tract

  • Good tissue distribution

  • Accumulate in macrophages and polymorphonuclear cells

  • Excreted mainly through bile

  • Low toxicity

  • Wide antimicrobial activity

  • Bacteriostatic action, bactericidal at high concentrations

Pharmacokinetics

  • Rapid gastrointestinal absorption but incomplete

  • Food interferes with absorption of erythromycin, spiramycin, roxithromycin, azithromycin

  • Distribution in tissues/fluids but limited blood-brain barrier penetration

  • Half-lives vary: longer in azithromycin (up to 95 hours), shorter in erythromycin and josamycin (1.5 hours)

Mechanism of Action

  • Inhibition of protein biosynthesis in bacterial cells at the 50S ribosomal subunit

  • Bacteriostatic at therapeutic concentrations, bactericidal at high concentrations

Clinical Uses

  • Broad spectrum including Gram-positive cocci, intracellular pathogens (mycoplasmas, chlamydia, rickettsia, legionella)

  • Often used when penicillin is intolerable or ineffective

  • Azithromycin exhibits efficacy against E. coli, Helicobacter pylori, and others

Adverse Effects

  • Common dyspeptic disorders

  • Rare allergic reactions

  • Many inhibit cytochrome P-450 which elevates concentrations of liver-metabolized drugs

Lincosamides

  • Components: Natural lincomycin; semisynthetic clindamycin

  • Spectrum: Narrow, mainly Gram-positive cocci, some anaerobes

  • Mechanism of Action: Inhibition of protein synthesis (bacteriostatic)

Pharmacokinetics

  • Poor gastrointestinal absorption for lincomycin (20-30%), clindamycin well absorbed (90%)

  • Distributed in various tissues, with high concentrations in bones and joints

  • Metabolized in the liver, excreted mainly through the gastrointestinal tract

  • Half-life: 2-6 hours

Uses

  • Reserve antibiotics for bone, joint, respiratory, skin, and soft tissue infections

  • Alternative treatment for protozoa infections (toxoplasmosis, malaria)

Adverse Effects

  • Common dyspeptic reactions (nausea, vomiting, diarrhea)

  • Rare allergy and risk of pseudomembranous colitis

Tetracyclines

  • Broad-spectrum antibiotics with bacteriostatic effects

  • Structure: Four condensed six-membered rings

  • Classification: Natural (Tetracycline, Oxytetracycline), Semisynthetic (Doxycycline, Metacycline), Combined (Oletetrine, Erycycline)

Pharmacokinetics

  • Poorly soluble in water, well absorbed in the gastrointestinal tract

  • Food can interfere with absorption, especially dairy products

  • High concentrations in bile and tissue storage

  • Tetracyclines have slow resistance development

Mechanism of Action

  • Inhibition of microbial protein synthesis by binding to the 30S ribosomal subunit

Use and Therapeutic Considerations

  • Used as reserve antibiotics for sensitive pathogens; effective in 5-7 days

  • Reserved for dangerous infections (e.g., plague, anthrax, syphilis, rickettsiosis)

  • Doxycycline preferred for its bioavailability

Aminoglycosides

  • Characterized by presence of aminosugars

  • Broad-spectrum but poor penetration through the bacterial cell wall

  • Classification: 1st generation (Streptomycin, Neomycin), 2nd generation (Gentamycin), 3rd generation (Amikacin)

Characteristics and Mechanism

  • Not absorbed orally; administered parenterally

  • Bactericidal mechanism, leading to disruption of protein synthesis

  • Effective against aerobic Gram-negative bacteria, some Gram-positive cocci

Pharmacokinetics

  • Secreted in urine

  • Do not penetrate blood-brain barrier

Clinical Uses

  • Used in systemic infections from aerobic Gram-negative bacteria; frequently combined with β-lactam antibiotics

  • Important examples include treatment of tuberculosis, sepsis, and resistant strains

Adverse Effects

  • High toxicity: nephrotoxicity and ototoxicity

  • Caution in renal insufficiency and myasthenia

Glycopeptides

  • Includes Vancomycin and Teicoplanin

  • Used for multidrug-resistant bacterial infections, particularly staphylococci

Mechanism of Action

  • Inhibit bacterial cell wall synthesis leading to bactericidal properties

  • Bacteriostatic against enterococci and some streptococci

Pharmacokinetics

  • Poor oral absorption; administered intravenously

  • Not metabolized, excretion via kidneys; dosing adjusted in renal insufficiency

Uses

  • Effective against MRSA and other resistant Gram-positive infections

Adverse Effects

  • Common: red man syndrome, hypotension, headache, skin reactions

Polymyxins

  • Cyclic polypeptides with narrow spectrum and high toxicity

Mechanism of Action

  • Disrupts microbial cell membrane leading to bactericidal effects

Pharmacokinetics

  • Not absorbed in the gastrointestinal tract; topical and oral uses available

Adverse Effects

  • Nephrotoxicity and neurotoxicity

  • Caution in patients with renal insufficiency

Miscellaneous Antibiotics

  • Fusidic Acid
      - Narrow spectrum, primarily against staphylococci
      - Inhibits protein synthesis
      - Good tissue penetration; used in staphylococcal infections

  • Chloramphenicol
      - Broad-spectrum, used for resistant infections but has serious side effects
      - Mechanism involves inhibition of protein synthesis

  • Phosphomycin Trometamol (Monural)
      - Bactericidal against Gram-negative bacteria
      - Used for urinary tract infections

  • Spectinomycin
      - Effectiveness against N. gonorrhoeae; narrow spectrum
      - Bacteriostatic effects; used intramuscularly
       

Note:

  • Keep in mind that the pharmacological properties, mechanisms of action, and adverse effects can vary widely among antibiotics - understanding each group's characteristics is critical for effective treatment.

Intravenous Antibiotic Administration and Mechanisms of Action - Imipenem

 - Competitive antagonist of GABA

 - Dose > 2 g/day leads to neurotoxicity

 - Limits use in conditions such as epilepsy, craniocerebral trauma, meningitis, stroke - Meropenem (Meronem)

  • Increased activity against Gram-negative bacteria

  • Less active against staphylococci and streptococci

  • Not inactivated by renal dihydropeptidase-1; can inhibit this enzyme

  • Resistant to β-lactamases

  • Minimal neurotoxicity, infrequent nausea and vomiting

  • Administered via intravenous bolus over 5 minutes - Ertapenem (introduced in 2000)

  • Broad-spectrum and long-acting

    • Adverse reactions:

       - Allergic reactions

       - Gastrointestinal dysfunction (nausea, vomiting, abdominal pain, diarrhea)

       - Neurotoxicity (tremor, convulsions, confusion)

       - Thrombocytopenia

Classifications

  1. Carbapenems:

    • Imipenem

    • Meropenem

    • Ertapenem

Monobactams - Aztreonam

 - Represented by a narrow-spectrum antibiotic

 - Effectiveness against Gram-negative aerobic microflora from the Enterobacteriaceae family

 - Includes: E. coli, Enterobacter, Klebsiella, Proteus, Serratia, Morganella, Cytrobacter, Providentia

 - No activity against Gram-positive bacteria or anaerobes

 - Destruction by β-lactamases present in many bacteria

Main Features of Monobactams

  • Strong bactericidal action

  • Narrow antibacterial spectrum (mainly Gram-negative aerobes)

  • Absence of cross-resistance with penicillins and cephalosporins

  • Favorable pharmacokinetics, including blood-brain barrier permeability

  • Primarily eliminated by the kidneys

Pharmacokinetics of Aztreonam

  • Not absorbed from the gastrointestinal tract

  • Administered parenterally (intramuscular and intravenous)

  • Excreted unchanged by the kidneys

  • Half-life (T1/2) approximately 2 hours, extended during renal insufficiency

Clinical Uses

  • Reserved for infections of the urinary tract, respiratory tract, skin, etc. caused by aerobic Gram-negative bacteria

  • Adverse effects: dyspepsia, skin allergies, thrombocytopenia, injection site irritation

  • No observed cross-allergy with other β-lactam antibiotics

Macrolides and Azalids

  • Macrolides are low toxicity antibiotics with a broad spectrum of activity

     - Bacteriostatic (bactericidal at high doses) effects

     - Chemical structure based on a macrocyclic lactone ring connected to various sugars

Classification of Macrolides

  1. Fourteen-membered lactone ring:

    • Natural: erythromycin, oleandomycin

    • Semisynthetic: roxithromycin, clarithromycin, dirithromycin, fluritromycin, telithromycin

  2. Fifteen-membered lactone ring (Azalids):

    • Semisynthetic: azithromycin

  3. Sixteen-membered lactone ring:

    • Natural: midecamycin, spiramycin, josamycin

    • Semisynthetic: midecamycin acetate

Main Properties of Macrolides

  • Stable in the acidic stomach environment (except erythromycin)

  • Well absorbed from the gastrointestinal tract

  • Good tissue distribution

  • Accumulate in macrophages and polymorphonuclear cells

  • Excreted mainly through bile

  • Low toxicity

  • Wide antimicrobial activity

  • Bacteriostatic action, bactericidal at high concentrations

Pharmacokinetics

  • Rapid gastrointestinal absorption but incomplete

  • Food interferes with absorption of erythromycin, spiramycin, roxithromycin, azithromycin

  • Distribution in tissues/fluids but limited blood-brain barrier penetration

  • Half-lives vary: longer in azithromycin (up to 95 hours), shorter in erythromycin and josamycin (1.5 hours)

Mechanism of Action

  • Inhibition of protein biosynthesis in bacterial cells at the 50S ribosomal subunit

  • Bacteriostatic at therapeutic concentrations, bactericidal at high concentrations

Clinical Uses

  • Broad spectrum including Gram-positive cocci, intracellular pathogens (mycoplasmas, chlamydia, rickettsia, legionella)

  • Often used when penicillin is intolerable or ineffective

  • Azithromycin exhibits efficacy against E. coli, Helicobacter pylori, and others

Adverse Effects

  • Common dyspeptic disorders

  • Rare allergic reactions

  • Many inhibit cytochrome P-450 which elevates concentrations of liver-metabolized drugs

Lincosamides

  • Components: Natural lincomycin; semisynthetic clindamycin

  • Spectrum: Narrow, mainly Gram-positive cocci, some anaerobes

  • Mechanism of Action: Inhibition of protein synthesis (bacteriostatic)

Pharmacokinetics

  • Poor gastrointestinal absorption for lincomycin (20-30%), clindamycin well absorbed (90%)

  • Distributed in various tissues, with high concentrations in bones and joints

  • Metabolized in the liver, excreted mainly through the gastrointestinal tract

  • Half-life: 2-6 hours

Uses

  • Reserve antibiotics for bone, joint, respiratory, skin, and soft tissue infections

  • Alternative treatment for protozoa infections (toxoplasmosis, malaria)

Adverse Effects

  • Common dyspeptic reactions (nausea, vomiting, diarrhea)

  • Rare allergy and risk of pseudomembranous colitis

Tetracyclines

  • Broad-spectrum antibiotics with bacteriostatic effects

  • Structure: Four condensed six-membered rings

  • Classification: Natural (Tetracycline, Oxytetracycline), Semisynthetic (Doxycycline, Metacycline), Combined (Oletetrine, Erycycline)

Pharmacokinetics

  • Poorly soluble in water, well absorbed in the gastrointestinal tract

  • Food can interfere with absorption, especially dairy products

  • High concentrations in bile and tissue storage

  • Tetracyclines have slow resistance development

Mechanism of Action

  • Inhibition of microbial protein synthesis by binding to the 30S ribosomal subunit

Use and Therapeutic Considerations

  • Used as reserve antibiotics for sensitive pathogens; effective in 5-7 days

  • Reserved for dangerous infections (e.g., plague, anthrax, syphilis, rickettsiosis)

  • Doxycycline preferred for its bioavailability

Aminoglycosides

  • Characterized by presence of aminosugars

  • Broad-spectrum but poor penetration through the bacterial cell wall

  • Classification: 1st generation (Streptomycin, Neomycin), 2nd generation (Gentamycin), 3rd generation (Amikacin)

Characteristics and Mechanism

  • Not absorbed orally; administered parenterally

  • Bactericidal mechanism, leading to disruption of protein synthesis

  • Effective against aerobic Gram-negative bacteria, some Gram-positive cocci

Pharmacokinetics

  • Secreted in urine

  • Do not penetrate blood-brain barrier

Clinical Uses

  • Used in systemic infections from aerobic Gram-negative bacteria; frequently combined with β-lactam antibiotics

  • Important examples include treatment of tuberculosis, sepsis, and resistant strains

Adverse Effects

  • High toxicity: nephrotoxicity and ototoxicity

  • Caution in renal insufficiency and myasthenia

Glycopeptides

  • Includes Vancomycin and Teicoplanin

  • Used for multidrug-resistant bacterial infections, particularly staphylococci

Mechanism of Action

  • Inhibit bacterial cell wall synthesis leading to bactericidal properties

  • Bacteriostatic against enterococci and some streptococci

Pharmacokinetics

  • Poor oral absorption; administered intravenously

  • Not metabolized, excretion via kidneys; dosing adjusted in renal insufficiency

Uses

  • Effective against MRSA and other resistant Gram-positive infections

Adverse Effects

  • Common: red man syndrome, hypotension, headache, skin reactions

Polymyxins

  • Cyclic polypeptides with narrow spectrum and high toxicity

Mechanism of Action

  • Disrupts microbial cell membrane leading to bactericidal effects

Pharmacokinetics

  • Not absorbed in the gastrointestinal tract; topical and oral uses available

Adverse Effects

  • Nephrotoxicity and neurotoxicity

  • Caution in patients with renal insufficiency

Miscellaneous Antibiotics

  • Fusidic Acid

     - Narrow spectrum, primarily against staphylococci

     - Inhibits protein synthesis

     - Good tissue penetration; used in staphylococcal infections

  • Chloramphenicol

     - Broad-spectrum, used for resistant infections but has serious side effects

     - Mechanism involves inhibition of protein synthesis

  • Phosphomycin Trometamol (Monural)

     - Bactericidal against Gram-negative bacteria

     - Used for urinary tract infections

  • Spectinomycin

     - Effectiveness against N. gonorrhoeae; narrow spectrum

     - Bacteriostatic effects; used intramuscularly

Note:

  • Keep in mind that the pharmacological properties, mechanisms of action, and adverse effects can vary widely among antibiotics - understanding each group's characteristics is critical for effective treatment.