Achieve Mastery of Medical Concepts

Study for medical school and boards with Lecturio

Macrolides and Ketolides

Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis Synthesis Polymerase Chain Reaction (PCR) by binding to the 50S ribosomal subunit and blocking transpeptidation Transpeptidation Lincosamides. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Common macrolides are erythromycin, clarithromycin, and azithromycin. Side effects include GI upset, QT prolongation, and hepatotoxicity Hepatotoxicity Acetaminophen. Resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing mechanisms include ribosomal methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids or mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations, inactivation of the drug through enzyme production, or removal of the drug through efflux pumps Efflux Pumps Lincosamides.

Last updated: Aug 18, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Chemistry and Pharmacodynamics

Chemical structure

  • Macrolides: characterized by a macrocyclic lactone ring Lactone Ring Polyenes
    • Ring contains 14‒16 atoms
    • 1 or more sugars are attached via glycosidic bonds
    • Erythromycin is the prototype drug of the class.
  • Ketolides (e.g., telithromycin): similar structure to macrolides 
    • 14-atom ring
    • 1 of the sugars is substituted with a keto group
    • Derived from erythromycin

Mechanism of action

  • Inhibits bacterial protein synthesis Synthesis Polymerase Chain Reaction (PCR) by binding reversibly to the 50S ribosomal subunit   
  • Limits bacterial growth → bacteriostatic Bacteriostatic Sulfonamides and Trimethoprim
  • Additional effects:
    • Antiinflammatory effect by ↓ interleukins Interleukins Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins and tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor-alpha
    • Erythromycin is a motilin Motilin A peptide of about 22-amino acids isolated from the duodenum. At low ph it inhibits gastric motor activity, whereas at high ph it has a stimulating effect. Gastrointestinal Secretions receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonist at duodenal enterochromaffin cells → has prokinetic properties
The site of action for macrolides

The site of action for macrolides on the 50S ribosomal subunit
tRNA tRNA The small RNA molecules, 73-80 nucleotides long, that function during translation (translation, genetic) to align amino acids at the ribosomes in a sequence determined by the mRNA (RNA, messenger). There are about 30 different transfer rnas. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl trnas (RNA, transfer, amino Acyl), each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure: transfer RNA Transfer RNA The small RNA molecules, 73-80 nucleotides long, that function during translation to align amino acids at the ribosomes in a sequence determined by the mRNA (messenger RNA). There are about 30 different transfer RNAs. Each recognizes a specific codon set on the mRNA through its own anticodon and as aminoacyl tRNAs, each carries a specific amino acid to the ribosome to add to the elongating peptide chains. RNA Types and Structure
mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure: messenger RNA Messenger RNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure

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

Pharmacokinetics

Table: 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 of macrolides and ketolides
Macrolides Ketolides
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 Erythromycin:
  • Destroyed by stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acid → requires enteric coating
  • Relatively poor 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
  • Food interferes with 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
Azithromycin and clarithromycin:
  • Stable in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy
  • Better 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
Rapid 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
Distribution
  • Lipophilic
  • Widely distributed in body fluids and tissues
  • Uptake by macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation:
    • Most notable in azithromycin
    • Contributes to a long half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics
  • Cross the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity
  • Do not cross the blood-brain barrier Blood-brain barrier Specialized non-fenestrated tightly-joined endothelial cells with tight junctions that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. Systemic and Special Circulations
  • Widely distributed in tissues
  • 70% protein bound ( albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests)
Metabolism
Excretion
  • Hepatic ( bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy → feces):
    • Azithromycin
    • Erythromycin
  • Renal: clarithromycin
  • Renal
  • Feces

Indications

Antimicrobial coverage

  • Gram positive Gram positive Bacteria which retain the crystal violet stain when treated by gram’s method. Nocardia/Nocardiosis:
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
    • 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
  • Gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis:
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae and H. ducreyi
    • Moraxella catarrhalis Moraxella catarrhalis Gram-negative aerobic cocci of low virulence that colonize the nasopharynx and occasionally cause meningitis; bacteremia; empyema; pericarditis; and pneumonia. Moraxella
    • Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella
    • Yersinia enterocolitica Yersinia enterocolitica A species of the genus yersinia, isolated from both man and animal. It is a frequent cause of bacterial gastroenteritis in children. Yersinia spp./Yersiniosis
    • Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella
    • Campylobacter Campylobacter Campylobacter (“curved bacteria”) is a genus of thermophilic, S-shaped, gram-negative bacilli. There are many species of Campylobacter, with C. jejuni and C. coli most commonly implicated in human disease. Campylobacter jejuni
    • Vibrio Vibrio Vibrio is a genus of comma-shaped, gram-negative bacilli. It is halophilic, acid labile, and commonly isolated on thiosulfate-citrate-bile-sucrose (TCBS) agar. There are 3 clinically relevant species: Vibrio cholerae (V. cholerae), Vibrio vulnificus (V. vulnificus), and Vibrio parahaemolyticus (V. parahaemolyticus). Vibrio cholerae
    • Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria
    • Helicobacter pylori Helicobacter pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter
    • Bordetella Bordetella Bordetella is a genus of obligate aerobic, Gram-negative coccobacilli. They are highly fastidious and difficult to isolate. The most important pathologic species is Bordetella pertussis (B. pertussis), which is commonly isolated on Bordet-Gengou agar. Bordetella pertussis Pertussis Pertussis, or whooping cough, is a potentially life-threatening highly contagious bacterial infection of the respiratory tract caused by Bordetella pertussis. The disease has 3 clinical stages, the second and third of which are characterized by an intense paroxysmal cough, an inspiratory whoop, and post-tussive vomiting. Pertussis (Whooping Cough)
  • Atypical
    • Mycoplasma Mycoplasma Mycoplasma is a species of pleomorphic bacteria that lack a cell wall, which makes them difficult to target with conventional antibiotics and causes them to not gram stain well. Mycoplasma bacteria commonly target the respiratory and urogenital epithelium. Mycoplasma pneumoniae (M. pneumoniae), the causative agent of atypical or “walking” pneumonia. Mycoplasma pneumoniae
    • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia pneumoniae
    • Legionella Legionella Legionella is a facultative intracellular, gram-negative bacilli. Legionella does not grow on common culture media because it requires certain supplementation (cysteine and iron). Legionella pneumophila (L. pneumophila) accounts for the majority of human infections. Legionella/Legionellosis pneumophila
    • Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema pallidum
    • Babesia Babesia Babesiosis is an infection caused by a protozoa belonging to the genus, Babesia. The most common Babesia seen in the United States is B. microti, which is transmitted by the Ixodes tick. The protozoa thrive and replicate within host erythrocytes. Lysis of erythrocytes and the body’s immune response result in clinical symptoms. Babesia/Babesiosis microti
    • Ureaplasma
  • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium avium complex (MAC)

Types of infection

  • Respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Community-acquired 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
    • MAC prophylaxis Prophylaxis Cephalosporins and treatment
    • Legionnaire disease
    • Pertussis Pertussis Pertussis, or whooping cough, is a potentially life-threatening highly contagious bacterial infection of the respiratory tract caused by Bordetella pertussis. The disease has 3 clinical stages, the second and third of which are characterized by an intense paroxysmal cough, an inspiratory whoop, and post-tussive vomiting. Pertussis (Whooping Cough)
    • Streptococcal pharyngitis Streptococcal Pharyngitis Rheumatic Fever
  • Sexually transmitted infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Gonorrhea Gonorrhea Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Gonorrhea
    • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia
    • Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid
  • H. pylori H. pylori A spiral bacterium active as a human gastric pathogen. It is a gram-negative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the micro-organism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. Helicobacter infection (clarithromycin is part of triple therapy)
  • 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. Skin: Structure and Functions and soft tissue Soft Tissue Soft Tissue Abscess infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (acne)
    • Acne

Other indications

  • Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) and cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis exacerbations (anti-inflammatory effect)
  • Gastroparesis Gastroparesis Chronic delayed gastric emptying. Gastroparesis may be caused by motor dysfunction or paralysis of stomach muscles or may be associated with other systemic diseases such as diabetes mellitus. Malabsorption and Maldigestion (erythromycin, promotility effect)

Ketolide indications

  • Similar antimicrobial activity as macrolides
  • Telithromycin was discontinued in the United States (previously only indicated for community-acquired 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).

Adverse Effects and Contraindications

Macrolides

  • Adverse effects:
    • GI upset (especially with erythromycin)
    • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
    • Hepatotoxicity Hepatotoxicity Acetaminophen
      • Abnormal liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
      • Hepatitis
      • Cholestatic jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
      • Hepatic necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
      • Hepatic failure Hepatic failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis
    • QT prolongation
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation: history of hepatic impairment or cholestatic jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Warnings:
    • Altered cardiac conduction (especially those with QT prolongation and electrolyte abnormalities) 
    • Hepatotoxicity Hepatotoxicity Acetaminophen 
    • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis exacerbation
    • Clarithromycin: potential ↑ mortality Mortality All deaths reported in a given population. Measures of Health Status in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with coronary artery Coronary Artery Truncus Arteriosus disease  
  • Drug interactions (particularly with erythromycin and clarithromycin due to CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) inhibition):
    • Warfarin Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. Anticoagulants: ↑ INR
    • Simvastatin Simvastatin A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase, which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic ldl receptors, it increases breakdown of ldl cholesterol. Statins, lovastatin Lovastatin A fungal metabolite isolated from cultures of aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme a reductase, which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. Statins: ↑ risk of myalgia Myalgia Painful sensation in the muscles. Ion Channel Myopathy and/or rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis
    • Midazolam Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at ph less than 4 and lipid-soluble at physiological pH. Benzodiazepines: somnolence
    • Theophylline Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3. Asthma Drugs: seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • ↑ Serum concentrations of:
      • Tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants 
      • Cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants
      • Ergot alkaloids Ergot alkaloids Alkaloids originally isolated from the ergot fungus claviceps purpurea (hypocreaceae). They include compounds that are structurally related to ergoline (ergolines) and ergotamine (ergotamines). Many of the ergot alkaloids act as alpha-adrenergic antagonists. Triptans and Ergot Alkaloids 
      • Colchicine Colchicine A major alkaloid from colchicum autumnale l. And found also in other colchicum species. Its primary therapeutic use is in the treatment of gout. Gout Drugs

Ketolides

  • Adverse effects:
    • GI upset
    • Visual disturbance
    • Hepatotoxicity Hepatotoxicity Acetaminophen
    • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Hypersensitivity to macrolide antibiotics
    • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
    • Hepatitis or jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Warnings:
    • Hepatotoxicity Hepatotoxicity Acetaminophen
    • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis exacerbation
    • QT prolongation

Mechanism of Resistance

There are 3 methods of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to macrolides:

  • Ribosomal methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids or mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • Prevents macrolide binding
    • Can be either plasmid mediated or chromosomal
  • Production of drug-inactivating enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
    • Esterases
    • Kinases 
  • Production of active ATP-dependent efflux proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis
    • Transport the drug outside the cell
    • Ketolides are not affected by this resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing mechanism → allows for their use in some macrolide-resistant strains

Comparison of Medications

Table: Comparison of several classes of bacterial protein synthesis Synthesis Polymerase Chain Reaction (PCR) inhibitor antibiotics
Drug class Mechanism of action Coverage Adverse effects
Amphenicols
  • Gram positives
  • Gram negatives
  • Atypicals
  • GI upset
  • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies
  • Aplastic anemia Aplastic Anemia Aplastic anemia (AA) is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow (in the absence of any abnormal cells) reflecting damage to hematopoietic stem cells. Aplastic anemia can be acquired or inherited, however, most cases of AA are acquired and caused by autoimmune damage to hematopoietic stem cells. Aplastic Anemia
  • Gray baby syndrome Gray Baby Syndrome Chloramphenicol
Lincosamides Lincosamides The lincosamides, lincomycin and clindamycin, are inhibitors of bacterial protein synthesis. Drugs in this class share the same binding site as that of macrolides and amphenicols; however, they differ in chemical structure. Lincosamides target the 50S ribosomal subunit and interfere with transpeptidation. Lincosamides
  • Gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology:
    • MSSA
    • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus
    • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
  • Anaerobes Anaerobes Lincosamides
  • GI upset
  • Allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions
  • Pseudomembranous colitis Pseudomembranous colitis Pseudomembranous colitis is a bacterial disease of the colon caused by Clostridium difficile. Pseudomembranous colitis is characterized by mucosal inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections account for the most commonly diagnosed hospital-acquired diarrheal illnesses. Pseudomembranous Colitis
Macrolides
  • Gram positives
  • Gram negatives
  • Atypicals
  • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium avium complex
  • GI upset
  • QT prolongation
  • Hepatotoxicity Hepatotoxicity Acetaminophen
  • Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis exacerbation
Oxazolidinones Oxazolidinones The oxazolidinones (linezolid and tedizolid) are bacterial protein synthesis inhibitors. Their unique binding site on the 23S ribosomal RNA of the 50S ribosome gives them zero cross-resistance with other antibiotics. Oxazolidinones
  • Bind BIND Hyperbilirubinemia of the Newborn to the 23S rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure of the 50S subunit
  • Prevent initiation complex formation Initiation Complex Formation Oxazolidinones
Gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology:
  • MSSA
  • MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus
  • VRE
  • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
  • Myelosuppression Myelosuppression Oxazolidinones
  • Neuropathy Neuropathy Leprosy
  • Lactic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
  • Serotonin syndrome Serotonin syndrome Serotonin syndrome is a life-threatening condition caused by large increases in serotonergic activity. This condition can be triggered by taking excessive doses of certain serotonergic medications or taking these medications in combination with other drugs that increase their activity. Serotonin Syndrome
rRNA rRNA The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. RNA Types and Structure: ribosomal RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
VRE: 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
Antibiotic sensitivity chart

Antibiotic sensitivity:
Chart comparing the microbial coverage of different antibiotics for gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology, gram-negative bacilli Bacilli Shigella, and anaerobes Anaerobes Lincosamides.

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

References

  1. Bertram G. (2007). Macrolide Antibiotics Comparison: Erythromycin, Clarithromycin, Azithromycin. Basic and Clinical Pharmacology. Retrieved March 5, 2021, from https://www.emedexpert.com/compare/macrolides.shtml.
  2. Tenson T, Lovmar M, Ehrenberg M (2003). The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. Journal of Molecular Biology. 330 (5): 1005–14. https://www.sciencedirect.com/science/article/abs/pii/S0022283603006624?via%3Dihub
  3. Leclercq, R. (2002). Mechanisms of resistance to macrolides and lincosamides: Nature of the resistance elements and their clinical implications. Clinical Infectious Diseases, 34(4):482-492. https://academic.oup.com/cid/article/34/4/482/412492
  4. Werth BJ. (2020). Macrolides. MSD Manual Professional Version. Retrieved June 29, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/macrolides
  5. Patel PH, Hashmi MF. (2021). Macrolides. StatPearls. Retrieved June 29, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK551495/
  6. Graziani, A.L. (2021). Azithromycin and clarithromycin. In Bond, S. (Ed.), UpToDate. Retrieved June 29, 2021, from https://www.uptodate.com/contents/azithromycin-and-clarithromycin
  7. Deck DH, Winston LG. (2012). Tetracyclines, macrolides, clindamycin, chloramphenicol, streptogramins, & oxazolidinones. In Katzung BG, Masters SB, Trevor AJ. (Eds.), Basic & Clinical Pharmacology (12th edition, pp. 809-819). https://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf

USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

¡Hola!

Esta página está disponible en Español.

Details