Antibiotics: Tetracyclines and Nitroimidazoles

Other Tetracyclines

• Modified tetracyclines with an expanded spectrum
• Poor absorption (omadacycline - moderate)
• Very high distribution - low plasma concentrations
• Long half-life
• Primarily hepatic elimination
• Covers many Gram-negative rods (GNR) and Gram-positive cocci (GPC)
• Includes vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)
• Good anaerobic coverage
• Does not cover Pseudomonas or Proteus species.
• Significant nausea and vomiting (N/V) with tigecycline (~30%)
• Uses: Skin and soft tissue infections (SSTIs), intra-abdominal infections

Nitroimidazoles

• Mechanism of action (MOA): Interacts with DNA, leading to loss in DNA structure and strand breakage
• Bactericidal
• Excellent bioavailability
• High tissue penetration
• Spectrum: Anaerobes and protozoa
• Adverse effects: Gastrointestinal (GI) - nausea, vomiting, diarrhea (N/V/D), Central nervous system (CNS) - dizziness, neuropathy, seizures
• Uses: Anaerobic infections, Clostridium difficile colitis, some parasitic infections

Oxalidinones

• Mechanism of action: Binds to 23S rRNA of 50S subunit, preventing protein synthesis by blocking formation of 70S initiation complex
• Bacteriostatic
• Highly bioavailable
• Elimination:
  • Linezolid - dual hepatic metabolism (not via CYP450) and renal elimination
  • Tedizolid - hepatic elimination
• Linezolid is a weak, reversible inhibitor of monoamine oxidase
• Caution using antidepressants when taking linezolid
• Gram-positive aerobes: Staphylococci (including MRSA), streptococci (including penicillin-resistant strains), enterococci (including VRE)
• Adverse effects:
  • Possibility of serotonin syndrome with some drugs
  • Bone marrow suppression, particularly thrombocytopenia
• Main uses: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections
• Resistance due to altered target site

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline are modified tetracyclines with a broader spectrum of activity than traditional tetracyclines
• Poor absorption, except for omadacycline which has moderate absorption
• Exhibit high tissue distribution but low plasma concentrations
• Have a long half-life, primarily eliminated through the liver
• Effective against many Gram-negative rods and Gram-positive cocci, including resistant strains like vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)
• Provide good anaerobic coverage, but lack activity against Pseudomonas and Proteus species
• Tigecycline commonly causes nausea and vomiting (~30%)
• Clinically used to treat skin and soft tissue infections (SSTIs) and intra-abdominal infections

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazole antibiotics
• They disrupt DNA structure and lead to strand breakage, resulting in bacterial cell death (bactericidal)
• Readily absorbed (high bioavailability) and distribute well into tissues
• Active against anaerobic bacteria and protozoa
• Common adverse effects include nausea, vomiting, diarrhea, dizziness, neuropathy, and seizures
• Used to treat anaerobic infections, Clostridium difficile colitis, and certain parasitic infections

Oxalidinones

• Linezolid and Tedizolid are oxalidinone antibiotics
• Bind to the 23S rRNA of the 50S ribosomal subunit, preventing protein synthesis by blocking the formation of the 70S initiation complex (bacteriostatic)
• Both have high bioavailability
• Elimination:
  • Linezolid is eliminated through both liver metabolism (independent of CYP450 system) and renal excretion
  • Tedizolid is primarily eliminated by the liver
• Linezolid is a weak, reversible inhibitor of monoamine oxidase, an enzyme responsible for breaking down neurotransmitters
• Exercise caution when using linezolid with antidepressants due to potential serotonin syndrome
• Effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE)
• Adverse effects can include bone marrow suppression, particularly thrombocytopenia
• Primarily used to treat methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections
• Resistance primarily arises from alterations in the drug target site

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline: Modified tetracyclines with a broader spectrum of activity.
• Poor absorption: Except for omadacycline, which has moderate absorption.
• High distribution: Leads to low plasma concentrations but excellent tissue penetration.
• Long half-life: Allows for infrequent dosing.
• Hepatic elimination: Primary route of elimination.
• Gram-negative rod (GNR) and Gram-positive cocci (GPC) coverage: Includes vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• Good anaerobic coverage
• No coverage for Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting (~30%)
• Uses: Primarily for skin and soft tissue infections (SSTIs), and intra-abdominal infections.

Nitroimidazoles

• Metronidazole, Tinidazole: Treat bacterial and parasitic infections.
• Mechanism of action: Interacts with DNA, disrupting its structure and leading to strand breakage.
• Bactericidal: Kills bacteria.
• Excellent bioavailability: Absorbed well by the body.
• High tissue penetration: Reaches various tissues effectively.
• Spectrum: Primarily active against anaerobes and protozoa.
• Adverse effects: Can cause gastrointestinal distress (N/V/D), central nervous system (CNS) effects like dizziness, neuropathy, and seizures.
• Uses: Treat anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxazolidinones

• Linezolid, Tedizolid: Treat bacterial infections, particularly those resistant to other antibiotics.
• Mechanism of action: Binds to the 23S rRNA of the 50S subunit, preventing protein synthesis by blocking the formation of the 70S initiation complex.
• Bacteriostatic: Stops the growth of bacteria but doesn't necessarily kill them.
• Highly bioavailable: Reaches therapeutic levels after oral administration.
• Elimination:
  • Linezolid: Eliminated through hepatic metabolism (not via CYP450) and renal elimination
  • Tedizolid: Eliminated through hepatic metabolism.
• Linezolid: Weak, reversible inhibitor of monoamine oxidase, an enzyme involved in the breakdown of neurotransmitters. May cause interactions with antidepressants.
• Gram-positive aerobes: Effective against staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Adverse effects: May cause serotonin syndrome when used with certain drugs, and bone marrow suppression, especially thrombocytopenia.
• Uses: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance: Develops due to alterations in the bacterial target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline are modified tetracyclines with a broader spectrum of activity.
• They are poorly absorbed, except for omadacycline, which has moderate absorption.
• These drugs have very high distribution, leading to low plasma concentrations.
• They have a long half-life and are primarily eliminated by the liver.
• They cover many Gram-negative rods (GNR) and Gram-positive cocci (GPC), including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They have good anaerobic coverage but do not cover Pseudomonas or Proteus species.
• Tigecycline has a significant side effect of nausea and vomiting (~30%).
• These drugs are used for skin and soft tissue infections (SSTIs) and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles that interact with DNA, leading to DNA damage and strand breakage.
• They are bactericidal and have excellent bioavailability.
• They have high tissue penetration, reaching therapeutic levels in various tissues.
• Their spectrum covers anaerobes and protozoa.
• Common side effects include gastrointestinal (GI) upset (nausea, vomiting, diarrhea) and central nervous system (CNS) effects like dizziness, neuropathy, and seizures.
• They are used for anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinones that bind to the 23S rRNA of the 50S subunit, blocking protein synthesis and preventing the formation of the 70S initiation complex.
• They are bacteriostatic antibiotics.
• Both have good oral bioavailability.
• Linezolid is eliminated through both hepatic metabolism and renal elimination. Its hepatic metabolism is independent of CYP450 enzymes. Tedizolid is eliminated primarily through the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase, potentially causing interactions with certain antidepressants.
• Their spectrum covers Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Both drugs can cause bone marrow suppression, particularly thrombocytopenia, and there is a risk of serotonin syndrome when used with certain medications.
• They are primarily used for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE).
• Resistance can develop due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline: Modified tetracyclines with expanded spectrum, poor absorption (except moderate for omadacycline), high distribution, long half-life, hepatic elimination.
• Cover: Gram-negative rods, Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• Also covers anaerobic bacteria.
• Do not cover Pseudomonas or Proteus species.
• Adverse effects: tigecycline - significant nausea and vomiting (~30%).
• Uses: Skin and soft tissue infections (SSTIs), intra-abdominal infections.

Nitroimidazoles

• Metronidazole, Tinidazole.
• Mechanism of action: Interacts with DNA, leading to loss in DNA structure and strand breakage.
• Bactericidal.
• Excellent bioavailability and high tissue penetration.
• Spectrum: Anaerobes and protozoa.
• Adverse effects: Gastrointestinal (GI) - nausea, vomiting, diarrhea (N/V/D), Central nervous system (CNS) - dizziness, neuropathy, seizures.
• Uses: Anaerobic infections, Clostridium difficile colitis, some parasitic infections.

Oxalidinones

• Linezolid, Tedizolid.
• Mechanism of action: Binds to 23S rRNA of 50S subunit, preventing protein synthesis by blocking formation of 70S initiation complex.
• Bacteriostatic.
• Highly bioavailable.
• Elimination: Linezolid - dual hepatic metabolism (not via CYP450) and renal elimination, Tedizolid - hepatic elimination.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase, use caution with antidepressants.
• Gram-positive aerobes: Staphylococci (including MRSA), streptococci (including penicillin-resistant strains), enterococci (including VRE).
• Adverse effects: Possibility of serotonin syndrome with some drugs.
• Bone marrow suppression, particularly thrombocytopenia.
• Main uses: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance due to altered target site.

Other Tetracyclines

• Tigecycline, Eravacycline, and Omadacycline are modified tetracyclines with a broad spectrum of activity.
• These drugs have poor absorption, except for omadacycline, which has moderate absorption.
• They are highly distributed throughout the body, resulting in low plasma concentrations.
• They have a long half-life, allowing for once-daily dosing.
• They are primarily eliminated by the liver.
• They are effective against many Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They also have good anaerobic coverage.
• However, they do not cover Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting, occurring in approximately 30% of patients.
• These drugs are used to treat skin and soft tissue infections (SSTIs) and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles that interact with DNA, leading to its degradation and strand breakage.
• They exhibit bactericidal activity.
• They have excellent bioavailability and penetrate tissues well.
• Their spectrum of activity includes anaerobes and protozoa.
• Common adverse effects include nausea, vomiting, diarrhea, dizziness, neuropathy, and seizures.
• They are used to treat anaerobic infections, Clostridium difficile colitis, and certain parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinones that bind to the 23S rRNA of the 50S ribosomal subunit, inhibiting protein synthesis by blocking the formation of the 70S initiation complex.
• Their action is bacteriostatic.
• They have high bioavailability.
• Linezolid undergoes dual hepatic metabolism (independent of CYP450) and renal elimination, while Tedizolid is eliminated primarily by the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase, which can be relevant when considering the use of antidepressants.
• They are effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Potential adverse effects include serotonin syndrome in combination with certain drugs and bone marrow suppression, particularly thrombocytopenia.
• Their main use is for treating methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance to these drugs develops due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, and Omadacycline are modified tetracyclines with an expanded spectrum of activity.
• They have poor absorption, except for omadacycline which has moderate absorption.
• They have a very high distribution, leading to low plasma concentrations, but with a long half-life.
• They are primarily eliminated by the liver.
• These drugs cover many Gram-negative rods (GNR) and Gram-positive cocci (GPC), including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They also have good anaerobic coverage, but do not cover Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting (~30%).
• They are used for skin and soft tissue infections (SSTIs) and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles.
• Their mechanism of action involves interacting with DNA, leading to loss of DNA structure and strand breakage.
• They are bactericidal.
• They have excellent bioavailability and high tissue penetration.
• Their spectrum of activity includes anaerobes and protozoa.
• Common adverse effects include gastrointestinal (GI) issues (nausea, vomiting, diarrhea), and central nervous system (CNS) effects (dizziness, neuropathy, seizures).
• They are used against anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinones.
• Their mechanism of action involves binding to 23S rRNA of the 50S subunit, preventing protein synthesis by blocking the formation of the 70S initiation complex.
• They are bacteriostatic.
• They are highly bioavailable.
• Linezolid is eliminated by both hepatic metabolism (not via CYP450) and renal excretion, while Tedizolid is primarily eliminated by the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase.
• They cover Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Adverse effects include the possibility of serotonin syndrome with some drugs, and bone marrow suppression, particularly thrombocytopenia.
• Their main uses are for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance to these drugs develops due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline are modified tetracyclines with an expanded spectrum.
• They have poor absorption, except for omadacycline which has moderate absorption.
• They have very high distribution and low plasma concentrations.
• These drugs have a long half-life and are primarily eliminated by the liver.
• They have a good coverage of Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus.
• They also provide good anaerobic coverage.
• They do not cover Pseudomonas or Proteus species.
• These drugs can cause side effects, with tigecycline specifically causing significant nausea and vomiting in approximately 30% of patients.
• They are commonly used for skin and soft tissue infections, and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles that disrupt DNA structure and lead to strand breakage.
• They are bactericidal and have excellent bioavailability.
• These medications penetrate tissues well and are active against anaerobes and protozoa.
• Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea, as well as central nervous system effects such as dizziness, neuropathy, and seizures.
• They are used for anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinones that work by inhibiting protein synthesis.
• They bind to the 23S rRNA of the 50S subunit of ribosomes and prevent the formation of the 70S initiation complex.
• They are bacteriostatic and have high bioavailability.
• Linezolid is eliminated through both hepatic metabolism (not through CYP450) and renal elimination.
• Tedizolid is eliminated solely through the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase.
• They are active against Gram-positive aerobes like staphylococci, including MRSA, streptococci, including penicillin-resistant strains, and enterococci, including VRE.
• Potential side effects include serotonin syndrome if combined with certain drugs, bone marrow suppression, particularly thrombocytopenia, and resistance due to altered target sites.
• They are primarily used for infections caused by Methicillin-resistant Staphylococcus aureus or Vancomycin-resistant Enterococci.
• Be cautious when using antidepressants with linezolid.

Other Tetracyclines

• Tigecycline, Eravacycline, and Omadacycline are modified tetracyclines with an expanded spectrum of activity.
• They have poor absorption, except for omadacycline which has moderate absorption.
• These drugs have very high distribution with low plasma concentrations, a long half-life, and are primarily eliminated by the liver.
• They cover a wide range of Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), and have good anaerobic coverage.
• They do not cover Pseudomonas or Proteus species.
• Significant nausea and vomiting (N/V) are significant side effects with tigecycline.
• They are primarily used for skin and soft tissue infections (SSTIs) and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles that disrupt DNA structure and strand breakage, leading to cell death.
• They are bactericidal, have excellent bioavailability, and penetrate tissues well.
• They are effective against anaerobes and protozoa.
• Common adverse effects include gastrointestinal upset (N/V/D) and central nervous system (CNS) side effects like dizziness, neuropathy, and seizures.
• Nitroimidazoles are used to treat anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinones that bind to the 23S rRNA of the 50S subunit of bacterial ribosomes, blocking protein synthesis.
• These drugs are bacteriostatic and have high bioavailability.
• Linezolid is eliminated through both hepatic metabolism and renal excretion, while Tedizolid is only eliminated by the liver.
• Important to note that Linezolid is a weak, reversible inhibitor of monoamine oxidase, which can impact the metabolism of certain antidepressants.
• Oxalidinones are effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Potential side effects include serotonin syndrome when used with certain medications, bone marrow suppression, particularly thrombocytopenia.
• Oxalidinones are primarily used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE).
• Resistance to these drugs often arises due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, and Omadacycline are modified tetracyclines with expanded antibiotic spectrums
• Omadacycline has moderate absorption, while the others are poorly absorbed.
• High distribution - low plasma concentrations
• Long half-life
• Primarily eliminated by the liver
• Coverage:
  • Gram-negative rods (GNR)
  • Gram-positive cocci (GPC) including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA)
  • Good anaerobic coverage
• Does not cover Pseudomonas or Proteus species.
• Significant adverse effects (AEs) for tigecycline: nausea and vomiting (~30%)
• Typical uses: skin and soft tissue infections (SSTIs), intra-abdominal infections

Nitroimidazoles

• Metronidazole and Tinidazole - mechanism of action (MOA) involves interaction with DNA leading to loss of structure and strand breakage
• Bactericidal
• Excellent bioavailability
• High tissue penetration
• Spectrum: anaerobes and protozoa
• Adverse effects:
  • Gastrointestinal (GI) - nausea, vomiting, diarrhea (N/V/D)
  • Central nervous system (CNS) - dizziness, neuropathy, seizures
• Common uses: anaerobic infections, Clostridium difficile colitis, some parasitic infections

Oxalidinones

• Linezolid and Tedizolid - mechanism of action (MOA) involves binding to the 23S rRNA of the 50S subunit, preventing protein synthesis by blocking formation of the 70S initiation complex
• Bacteriostatic
• Highly bioavailable
• Elimination:
  • Linezolid - dual hepatic metabolism (not via CYP450) and renal elimination
  • Tedizolid - hepatic elimination
• Linezolid is a weak, reversible inhibitor of monoamine oxidase
• Be cautious of using antidepressants when taking linezolid.
• Coverage:
  • Gram-positive aerobes - staphylococci (including MRSA), streptococci (including penicillin-resistant strains), enterococci (including VRE)
• Adverse effects:
  • Possibility of serotonin syndrome with some drugs
  • Bone marrow suppression, particularly thrombocytopenia
• Main uses: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections
• Resistance often occurs due to altered target receptor sites

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline are modified tetracyclines with an expanded spectrum of activity.
• These drugs have poor absorption, except for omadacycline which has moderate absorption.
• They have a high distribution in the body, resulting in low plasma concentrations.
• They have a long half-life and are eliminated primarily through the liver.
• These drugs are effective against many Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They also have good anaerobic coverage, but they do not cover Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting (around 30% of patients).
• These tetracyclines are commonly used to treat skin and soft tissue infections and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are drugs that interact with DNA, leading to its structural damage and strand breakage.
• They are bactericidal and have excellent bioavailability and high tissue penetration.
• Their spectrum of activity includes anaerobic bacteria and protozoa.
• Common adverse effects include gastrointestinal issues (nausea, vomiting, diarrhea) and central nervous system effects (dizziness, neuropathy, seizures).
• Metronidazole and Tinidazole are used for the treatment of anaerobic infections, Clostridium difficile colitis, and certain parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are drugs that bind to 23S rRNA of the 50S subunit, inhibiting protein synthesis by blocking the formation of the 70S initiation complex.
• Their action is bacteriostatic.
• They have high bioavailability and differ in their elimination pathways.
• Linezolid undergoes both hepatic metabolism (not via CYP450) and renal elimination.
• Tedizolid is eliminated primarily through the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase, which should be considered when using antidepressants.
• These drugs are effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Potential adverse effects include serotonin syndrome with some drugs and bone marrow suppression, particularly thrombocytopenia.
• They are primarily used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE).
• Resistance to these drugs can develop due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline: Modified tetracyclines with a broader spectrum of activity.
• Poor absorption: Oral bioavailability is limited, except for omadacycline which has moderate absorption.
• Wide distribution, low plasma concentrations: Drugs distribute widely throughout the tissues and organs, so plasma concentrations might be relatively low.
• Long half-life: Remain active in the body for a prolonged duration.
• Primarily hepatic elimination: Primarily removed from the body via the liver.
• Coverage: Effective against many Gram-negative rods (GNR) and Gram-positive cocci (GPC), including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• Good anaerobic coverage: Effective against bacteria that thrive in the absence of oxygen.
• Does not cover Pseudomonas or Proteus species: These specific bacteria are not susceptible to these drugs.
• Adverse effects: Tigecycline is associated with significant nausea and vomiting (N/V), occurring in approximately 30% of patients.
• Uses: Commonly used to treat skin and soft tissue infections (SSTIs), and intra-abdominal infections.

Nitroimidazoles

• Metronidazole, Tinidazole: Antimicrobial drugs in the nitroimidazole class.
• Mechanism of action (MOA): Interfere with DNA function by causing damage and strand breakage.
• Bactericidal: Kill bacteria directly.
• Excellent bioavailability: Well absorbed by the body after oral administration.
• High tissue penetration: Reach high concentrations in various bodily tissues.
• Spectrum: Effective against anaerobic bacteria and protozoa.
• Adverse effects: May cause gastrointestinal (GI) disturbances like nausea, vomiting, and diarrhea (N/V/D). Can also affect the central nervous system (CNS) leading to dizziness, neuropathy, and seizures.
• Uses: Employed for treating anaerobic infections, Clostridium difficile colitis, and certain parasitic infections.

Oxalidinones

• Linezolid, Tedizolid: Antibiotics belonging to the oxazolidinone class.
• Mechanism of action: Inhibit protein synthesis by binding to a crucial component of the ribosome (23S rRNA) in bacteria.
• Bacteriostatic: Stop bacterial growth but do not directly kill the bacteria.
• Highly bioavailable: Well absorbed after oral administration.
• Elimination: Linezolid is eliminated through a combination of hepatic metabolism (not involving the cytochrome P450 system) and renal excretion. Tedizolid is predominantly eliminated by the liver.
• Inhibition of monoamine oxidase: Linezolid weakly and reversibly inhibits the enzyme monoamine oxidase, which could potentially interact with other medications, especially antidepressants.
• Coverage: Active against gram-positive aerobic bacteria like staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Adverse effects: The potential for serotonin syndrome exists when used in combination with certain other drugs. Bone marrow suppression, particularly thrombocytopenia (low platelet count), can occur.
• Main uses: Treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).
• Resistance: Can develop due to alterations in the bacterial target site, making the drug less effective.

Other Tetracyclines

• Modifications to tetracyclines yield drugs such as tigecycline, eravacycline, and omadacycline, expanding their antimicrobial spectrum.
• These modified tetracyclines have poor oral absorption (except for omadacycline, which has moderate absorption).
• They exhibit high tissue distribution, resulting in low plasma concentrations.
• They share a long half-life and are primarily eliminated through the liver.
• These drugs effectively target a wide range of Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They exhibit good anaerobic coverage. However, these drugs do not cover infections caused by Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting (approximately 30% of patients).
• These tetracyclines find primary use in treating skin and soft tissue infections (SSTIs) and intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazoles with a unique mechanism of action.
• They interfere with DNA structure and strand breakage, leading to bacterial cell death.
• These drugs are bactericidal and exhibit excellent bioavailability.
• Nitroimidazoles penetrate tissues effectively, proving valuable against anaerobic bacteria and protozoa.
• Common adverse effects include gastrointestinal (GI) disturbances, such as nausea, vomiting, and diarrhea, and central nervous system (CNS) effects, such as dizziness, neuropathy, and seizures.
• They are used for treating anaerobic infections, Clostridium difficile colitis, and selected parasitic infections.

Oxalidinones

• Linezolid and Tedizolid belong to the oxalidinone class of antibiotics.
• They act by binding to the 23S rRNA of the 50S subunit, preventing protein synthesis.
• They are bacteriostatic in action, meaning they inhibit bacterial growth rather than directly killing bacteria.
• Both drugs exhibit high bioavailability.
• Linezolid is eliminated via a dual mechanism: hepatic metabolism (not via CYP450) and renal elimination.
• Tedizolid is primarily eliminated through the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase.
• This interaction necessitates caution when using antidepressants concurrently with linezolid.
• Oxalidinones are effective against a range of gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci, including VRE.
• Common side effects include the possibility of serotonin syndrome when used with some drugs, and bone marrow suppression, especially thrombocytopenia.
• Their primary use is in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE).
• Resistance to these drugs often develops due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, and Omadacycline are modified tetracyclines with broader activity.
• These drugs are poorly absorbed, except for omadacycline, which has moderate absorption.
• Despite poor absorption, they have wide tissue distribution leading to low plasma concentrations.
• They have a long half-life and are primarily eliminated by the liver.
• Offer coverage against a variety of Gram-negative rods (GNR) and Gram-positive cocci (GPC).
• Notably, they are effective against vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• They also provide good anaerobic coverage.
• However, they do not cover Pseudomonas or Proteus species.
• Tigecycline is associated with significant nausea and vomiting, occurring in approximately 30% of patients.
• These drugs are primarily used for skin and soft tissue infections (SSTIs), as well as intra-abdominal infections.

Nitroimidazoles

• Metronidazole and Tinidazole are nitroimidazole antibiotics.
• They disrupt DNA structure and function by interacting with DNA, leading to strand breakage.
• Their action is bactericidal.
• They have excellent bioavailability and high tissue penetration.
• Their spectrum of activity covers anaerobes and protozoa.
• Common adverse effects include gastrointestinal (GI) upset (nausea, vomiting, diarrhea), and central nervous system (CNS) effects like dizziness, neuropathy, and seizures.
• They are used for treating anaerobic infections, Clostridium difficile colitis, and certain parasitic infections.

Oxalidinones

• Linezolid and Tedizolid are oxalidinone antibiotics.
• They inhibit protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit, preventing the formation of the 70S initiation complex.
• Their action is primarily bacteriostatic.
• They are highly bioavailable.
• Linezolid is eliminated through both hepatic metabolism and renal excretion, while Tedizolid is mainly eliminated by the liver.
• Linezolid is a weak inhibitor of monoamine oxidase, requiring cautious use with antidepressants.
• They are effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Potential adverse effects include serotonin syndrome if used in combination with certain medications, and bone marrow suppression, particularly thrombocytopenia.
• They are primarily used to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE).
• Resistance to these drugs can arise from alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline: Modified tetracyclines with a broader range of activity.
• Absorption: Poorly absorbed (omadacycline is moderately absorbed).
• Distribution: Highly distributed, with low plasma concentrations.
• Half-life: Long half-life.
• Elimination: Primarily eliminated by the liver.
• Spectrum of Activity: Covers many Gram-negative rods and Gram-positive cocci, including vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• Anaerobic Coverage: Good coverage against anaerobic bacteria.
• Limitations: Does not cover Pseudomonas or Proteus species.
• Adverse Effects: Tigecycline - significant nausea and vomiting (~30%).
• Uses: Skin and soft tissue infections (SSTIs), intra-abdominal infections.

Nitroimidazoles

• Metronidazole, Tinidazole: Antibacterial and antiprotozoal agents.
• Mechanism of Action: Interacts with DNA, leading to DNA damage and strand breakage.
• Bactericidal Activity: Kills bacteria.
• Bioavailability: Excellent bioavailability.
• Tissue Penetration: High tissue penetration.
• Spectrum of Activity: Effective against anaerobes and some protozoa.
• Adverse Effects: Gastrointestinal (GI) - nausea, vomiting, diarrhea. Central nervous system (CNS) - dizziness, neuropathy, seizures.
• Uses: Anaerobic infections, Clostridium difficile colitis, some parasitic infections.

Oxalidinones

• Linezolid, Tedizolid: Synthetic antibacterial agents.
• Mechanism of Action: Binds to 23S rRNA of the 50S ribosomal subunit, blocking protein synthesis by preventing the formation of the 70S initiation complex.
• Bacteriostatic Activity: Inhibits bacterial growth.
• Bioavailability: Highly bioavailable.
• Elimination:
  • Linezolid: Eliminated through dual hepatic metabolism (not via CYP450) and renal elimination.
  • Tedizolid: Eliminated through hepatic metabolism.
• Linezolid and Monoamine Oxidase: Linezolid is a weak, reversible inhibitor of monoamine oxidase.
• Drug Interactions: Use caution when combining linezolid with antidepressants.
• Spectrum of Activity: Effective against Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), enterococci (including VRE).
• Adverse Effects: Possibility of serotonin syndrome with some drugs. Bone marrow suppression, particularly thrombocytopenia.
• Uses: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance Mechanisms: Resistance arises due to alterations in the target site.

Other Tetracyclines

• Tigecycline, Eravacycline, Omadacycline are modified tetracyclines with an expanded spectrum.
• Poor intestinal absorption for most, except for omadacycline which has moderate absorption.
• High distribution throughout the body, with low plasma concentrations.
• Long half-life allows for once daily dosing.
• Primarily eliminated by the liver.
• Covers many Gram-negative rods (GNR) and Gram-positive cocci (GPC).
• Effectively treats vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA).
• Provides good coverage against anaerobic bacteria.
• Does not cover Pseudomonas or Proteus species.
• Adverse effects include significant nausea and vomiting (N/V) for tigecycline (approximately 30%).
• Uses include skin and soft tissue infections (SSTIs), intra-abdominal infections.

Nitroimidazoles

• Metronidazole, Tinidazole, interact with DNA, leading to loss in its structure and strand breakage.
• Bactericidal.
• Excellent bioavailability, easily absorbed from the gastrointestinal tract.
• High tissue penetration, reaching various organs and tissues effectively.
• Spectrum includes anaerobes and protozoa.
• Adverse effects include gastrointestinal (GI) issues such as nausea, vomiting, and diarrhea (N/V/D), as well as central nervous system (CNS) effects like dizziness, neuropathy, and seizures.
• Used against anaerobic infections, Clostridium difficile colitis, and some parasitic infections.

Oxalidinones

• Linezolid, Tedizolid bind to 23S rRNA of the 50S ribosomal subunit, preventing protein synthesis by blocking formation of the 70S initiation complex.
• Bacteriostatic.
• Highly bioavailable.
• Linezolid elimination involves both hepatic metabolism (not via CYP450) and renal elimination.
• Tedizolid is primarily eliminated by the liver.
• Linezolid is a weak, reversible inhibitor of monoamine oxidase.
• Caution required when combining linezolid with other antidepressants due to potential for serotonin syndrome.
• Covers Gram-positive aerobes, including staphylococci (including MRSA), streptococci (including penicillin-resistant strains), and enterococci (including VRE).
• Adverse effects include potential for serotonin syndrome with some medications, bone marrow suppression, particularly thrombocytopenia.
• Main uses are treatment of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infections.
• Resistance develops due to alterations in the target site.

Explore the properties, uses, and mechanisms of antibiotics focusing on tetracyclines and nitroimidazoles. This quiz covers their spectrum of activity, pharmacokinetics, and potential adverse effects. Understand the clinical applications and limitations of these important antimicrobial agents.