Lipopeptides and Lipoglycopeptides

Lipopeptides and lipoglycopeptides are classes of antibiotics that have activity against gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview and that act on the bacterial cell wall. Lipopeptides (daptomycin) disrupt the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane by creating an ion-conducting channel and causing potassium efflux and membrane depolarization. The subsequent processes lead to inhibited protein synthesis and eventual bacterial cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death. Lipoglycopeptides have a dual action of inhibiting bacterial cell-wall synthesis by binding peptidoglycan precursors and causing cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane depolarization. Telavancin, dalbavancin, and oritavancin belong to this group of drugs. All these medications are administered IV, as they have poor oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption. The lipopeptides and lipoglycopeptides are excreted unchanged in the urine. Dosage adjustments are generally needed in cases of reduced renal function. Both classes of antibiotics are used as alternative agents for gram-positive infections (bacteremia, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and soft tissue infections). Telavancin is also effective against hospital-acquired and ventilator-associated pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Chemistry and Pharmacodynamics

Lipopeptides

  • Daptomycin: only member of its class
  • Structure: 
    • 13 amino acids, with 10 forming an ester-linked amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids ring
    • With a terminal L-tryptophan bonded to decanoic acid
Chemical structure of daptomycin

Chemical structure of daptomycin

Image: “Daptomycin Ball et al.” by Fvasconcellos. License: Public Domain

Mechanism of action of lipopeptides

  • Bactericidal (concentration-dependent killing): 
    • Lipophilic tail binds to bacterial membranes (calcium-dependent) → creates a hole or channel in the membrane, causing potassium ions to leak out
    • Rapid depolarization → loss of membrane potential Membrane potential The membrane potential is the difference in electric charge between the interior and the exterior of a cell. All living cells maintain a potential difference across the membrane thanks to the insulating properties of their plasma membranes (PMs) and the selective transport of ions across this membrane by transporters. Membrane Potential → inhibition of proteins, RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure and DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure synthesis
    • Processes initiated lead to cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death.
  • Activity only against gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
Mechanism of action daptomycin

Mechanism of action:
Daptomycin binds to the bacterial cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane, and holes are created in the membrane by altering the shape of the membrane. Potassium ion leaks out of the membrane, and rapid depolarization occurs. There is loss of ion gradient, which eventually leads to inhibition of protein synthesis, effectively resulting in cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death.
DAP: daptomycin

Image: “Multifunctional pharmaceutical effects of the antibiotic daptomycin” by Yang Ye et al. License: CC BY 4.0, cropped by Lecturio.

Lipoglycopeptides

  • Semisynthetic derivatives of glycopeptides Glycopeptides The glycopeptide antibiotics (GPAs) vancomycin and teicoplanin are inhibitors of bacterial cell wall synthesis and considered the last resort treatment of severe infections due to gram-positive bacteria such as Staphylococcus aureus, Enterococcus spp., and Clostridiodes difficile. Glycopeptides (e.g., vancomycin)
  • Contains lipophilic side chains (that vary depending on the compound) attached to the glycopeptide, prolonging the half-life
  • Activity against gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview
  • Includes: 
    • Telavancin: derivative of vancomycin
    • Dalbavancin: teicoplanin-like molecule
    • Oritavancin

Mechanism of action of lipoglycopeptides

  • Lipoglycopeptides are bactericidal, demonstrating concentration-dependent killing.
  • Dual actions:
    • Have increased binding to the D-alanyl-D-alanine terminus of cell-wall peptidoglycan precursors (similar to glycopeptides Glycopeptides The glycopeptide antibiotics (GPAs) vancomycin and teicoplanin are inhibitors of bacterial cell wall synthesis and considered the last resort treatment of severe infections due to gram-positive bacteria such as Staphylococcus aureus, Enterococcus spp., and Clostridiodes difficile. Glycopeptides, but with improved potency):
      • Block peptidoglycan polymerization 
      • Inhibit cell-wall synthesis
    • Cause direct disruption of the bacterial cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane, causing depolarization, increased permeability and cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death (similar to lipopeptides)
  • Oritavancin also inhibits RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure synthesis.

Pharmacokinetics

Lipopeptides: daptomycin

  • Absorption and distribution:
    • Poor oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, and toxic to the muscle (cannot give IM) → only administered IV 
    • Serum half-life: 8–9 hours
    • Highly protein-bound, with different organ pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics:
      • Good skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and soft tissue penetration
      • Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Daptomycin is excreted unchanged in the urine, so it is an option for complicated urinary tract infections Urinary tract infections Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Urinary Tract Infections.
      • Respiratory tract: Daptomycin is inactivated by pulmonary surfactant, so it is not useful for pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia.
      • CNS: poor penetration of CSF even with inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
  • Metabolism and excretion:
    • Excreted renally as an active drug 
    • Dose adjustments needed for creatinine clearance < 30 mL/min

Lipoglycopeptides

  • Telavancin: 
    • Absorption and distribution:
      • Not absorbed orally
      • Highly protein-bound
      • Serum half-life: 7–8 hours
      • Adequate concentration in skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and soft tissues and lung tissue (thus, used in pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and soft tissue infections)
    • Metabolism and excretion:
      • Minimal metabolism
      • Primarily excreted in the urine
      • Dose adjustment needed for creatinine clearance < 50 mL/min
  • Dalbavancin:
    • Absorption and distribution:
      • Not absorbed orally
      • Highly protein-bound
      • Long half-life (allowing 1- or 2-dose regimen)
      • Good penetration of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones tissues, but poor CSF penetration
    • Metabolism and excretion:
      • Eliminated unchanged in the urine
      • Dose adjustment needed for creatinine clearance < 30 mL/min
  • Oritavancin:
    • Absorption and distribution:
      • Not absorbed orally
      • Highly protein-bound
      • Long half-life (allowing single dose as treatment)
    • Metabolism and excretion:
      • No hepatic metabolism
      • Excreted slowly in the urine 
      • No dose adjustment for mild to moderate renal impairment

Indications

Lipopeptides and lipoglycopeptides are agents active against gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview.

Lipopeptides: daptomycin (IV)

  • Treatment of gram-positive infections in which there is intolerance to standard therapy or antibiotic resistance is present:
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus bacteremia (bloodstream infections):
      • Includes MRSA
      • Includes right-sided endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis 
    • Complicated skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and soft tissue infections (SSTIs):
      • Approved for vancomycin-sensitive Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus (VSE)
      • Likely with activity against vancomycin-resistant Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus (VRE), but studies are insufficient for FDA approval.
  • Important note: not for pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia because lung surfactant inactivates the drug

Lipoglycopeptides

  • Telavancin (IV):
    • Alternative agent for complicated SSTIs due to gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, including MRSA and VSE
    • Hospital-acquired and ventilator-associated pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Dalbavancin (IV): acute bacterial skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin structure infections (ABSSSI) due to gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, including MRSA and VSE
  • Oritavancin (IV):
    • ABSSSI:
      • Gram-positive pathogens, including MRSA and VSE
      • In vitro activity against VRE but no trial data
    • An alternative agent, used for individuals who cannot receive 1st-line agents

Adverse Effects and Contraindications

Lipopeptides: daptomycin

  • Adverse effects include (but not limited to):
    • Myopathy/ rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis:
      • Monitor for muscle pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain/weakness.
      • CK monitoring
      • More frequent monitoring important in those with renal dysfunction and/or taking statins Statins Statins are competitive inhibitors of HMG-CoA reductase in the liver. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis. Inhibition results in lowered intrahepatocytic cholesterol formation, resulting in up-regulation of LDL receptors and, ultimately, lowering levels of serum LDL and triglycerides. Statins
    • Eosinophilic pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia:
      • Occurs 2–4 weeks after initiation of therapy
      • Presents as new-onset fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and infiltrate on chest X-ray
    • Anaphylactic hypersensitivity reactions
    • Peripheral neuropathy
    • Can falsely ↑ prothrombin time and INR
  • Contraindication: hypersensitivity to daptomycin or its components

Lipoglycopeptides

  • Telavancin:
    • Adverse effects include (but not limited to):
      • Renal dysfunction or nephrotoxicity, foamy urine
      • Rapid infusion can cause vancomycin flushing syndrome (VFS; previously known as red man syndrome), which consists of flushing, erythema, itching, and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension from histamine release, as with vancomycin
      • QT prolongation
      • Embryofetal toxicity (need to verify pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care)
      • Taste disturbance (metallic), nausea, vomiting
      • May interfere with coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies
    • Contraindications:
      • Hypersensitivity to telavancin or its components
      • Concomitant use of unfractionated heparin
  • Dalbavancin:
    •  Adverse effects include (but not limited to):
      • GI intolerance (nausea, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
      • Transaminitis
      • Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
      • Hypotension
    • Contraindication: hypersensitivity to dalbavancin or its components
  • Oritavancin:
    • Adverse effects include (but not limited to):
      • Nausea, vomiting
      • Infusion-related reactions
      • May interfere with coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies
    • Contraindications:
      • Hypersensitivity to oritavancin or its components
      • Concomitant use of unfractionated heparin (≤ 5 days after oritavancin administration)

Comparison of Antibiotics

The following antibiotics are agents with activity against gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview. All act on the bacterial cell wall through varying mechanisms.

Table: Comparison of antibiotics
Class of antibiotics Mechanism of action Drugs
Lipopeptides Disruption of the bacterial cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane by generating an ion-conducting channel, depolarizing the membrane, and leading to cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death Daptomycin
Glycopeptides Inhibition of cell wall synthesis by binding to the D-alanyl-D-alanine terminus of cell wall peptidoglycan (PG) precursors
  • Vancomycin
  • Teicoplanin
Lipoglycopeptides Dual action of inhibition of cell wall synthesis and depolarization of the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane
  • Telavancin
  • Dalbavancin
  • Oritavancin

Comparison of Antibiotic Coverage

Different antibiotics have varying degrees of activity against different bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview. The table below outlines the antibiotics with activity against 3 important classes of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview: gram-positive cocci, gram-negative bacilli, and anaerobes.

Antibiotic sensitivity chart

Antibiotic sensitivity:
Chart comparing the microbial coverage of different antibiotics for gram-positive cocci, gram-negative bacilli, and anaerobes.

Image by Lecturio. License: CC BY-NC-SA 4.0

References

  1. Abbott, I., Cairns, K. (2021). Daptomycin: an overview. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/daptomycin-an-overview
  2. Binda, E., Marinelli, F., Marcone, G.L. (2014). Old and new glycopeptide antibiotics: action and resistance. Antibiotics 3:572–594. https://doi.org/10.3390/antibiotics3040572
  3. Dalbavancin: drug information. (2021). UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/dalbavancin-drug-information
  4. Daptomycin: drug information. (2021). UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/daptomycin-drug-information
  5. Damodaran, S.E., Madhan, S. (2011). Telavancin: a novel lipoglycopeptide antibiotic. Journal of Pharmacology & Pharmacotherapeutics 2(2):135–137. https://doi.org/10.4103/0976-500X.81918
  6. MacDougall, C. (2017). Protein synthesis inhibitors and miscellaneous antibacterial agents. Chapter 59 of Brunton L.L., Hilal-Dandan, R., Knollmann, B.C. (Eds.), Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13th ed. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2189&sectionid=172485211
  7. Murray, B., Miller, W. (2021). Treatment of enterococcal infections. UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/treatment-of-enterococcal-infections
  8. Oritavancin: Drug information. (2021). UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/oritavancin-drug-information
  9. Patel, S., Saw S. (2021). Daptomycin. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK470407/
  10. Riedel, S., et al. (Eds.). (2019). Antimicrobial chemotherapy. Chapter 28 of Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2629&sectionid=217773038
  11. Rosenthal, S., et al. (2018). Oritavancin (Orbactiv): a new-generation lipoglycopeptide for the treatment of acute bacterial skin and skin structure infections. P T 43:143–179. https://pubmed.ncbi.nlm.nih.gov/29491695/
  12. Telavancin: drug information. (2021). UpToDate. Retrieved July 18, 2021, from https://www.uptodate.com/contents/telavancin-drug-information

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