Penicillins

Chemistry

Penicillins are members of the beta-lactam family of drugs and consist of:

• A beta-lactam ring: a 4-membered ring containing 2 carbons (α and β carbons), a nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle, and a carbonyl group (a carbon double-bonded to oxygen)
  • The beta-lactam group in the compound is responsible for antibacterial activity.
  • Can be hydrolyzed (i.e., broken down) by beta-lactamases, which are produced by certain resistant 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
  • If the beta-lactam ring is broken, the drug loses its antibacterial properties.
  • All beta-lactams contain a beta-lactam ring.
• Thiazolidine ring: a 5-membered ring containing both sulfur and nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle
• Side chain: 
  • Bound to the α-carbon in the beta-lactam ring
  • Differentiates penicillins from each other
  • Responsible for their unique 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 and spectra of activity
  • Certain structures can sterically inhibit the hydrolysis Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water. Proteins and Peptides of the beta-lactam ring by beta-lactamases. 
  • Certain compounds can be more readily taken up by gram-negative bacteria gram-negative bacteria Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Bacteriology than others.

Mechanism of Action and Resistance

All beta-lactams, including penicillins, exert their effects by inhibiting bacterial cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic synthesis Synthesis Polymerase Chain Reaction (PCR).

Background: understanding Understanding Decision-making Capacity and Legal Competence cell walls

• Bacterial cell walls contain peptidoglycan chains (large, thick layers in gram-positive organisms and relatively smaller/thinner layers in gram-negative organisms).
• Peptidoglycan chains are composed of:
  • A sugar backbone with 2 alternating sugars: 
    • N-acetylmuramic acid (NAM) 
    • N-acetylglucosamine acid (NAG)
  • Short peptide side chains branching off the NAM sugars
• The short peptides form crosslinked bridges between adjacent peptidoglycan chains and create a fishnet structure:
  • Crosslinked bridges are necessary for the peptidoglycan (and thus cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic) structure.
  • Penicillin-binding 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 (PBPs) are 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 that create these crosslinked bridges. 

Mechanism of action

All beta-lactams work by irreversibly inhibiting PBPs → beta-lactam antibiotics inhibit cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic synthesis Synthesis Polymerase Chain Reaction (PCR)

Bactericidal activity

Beta-lactams, including penicillins, exert a bactericidal (rather than a bacteriostatic Bacteriostatic Sulfonamides and Trimethoprim) effect. 

• Bacterial cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic is necessary for its survival → if lacking, 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 is initiated
• When 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 attempt to replicate, they shed their cell walls.
• In the presence of penicillins, however, 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 are unable to form a new cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic.
• 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 are unable to effectively divide, and the remaining cell autocatalyzes and dies.

Mechanisms 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

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 use 3 primary mechanisms to resist penicillins:

• Beta-lactamase 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 (penicillins are inactivated): 
  • Beta-lactamase is an enzyme that cleaves the beta-lactam ring and inactivates the antibiotic.
  • In the case of penicillin Penicillin Rheumatic Fever 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, the 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 are often called penicillinases.
  • Can be produced by both gram-positive and gram-negative organisms
  • Usually secreted
  • May be secreted only in the presence of a beta-lactam antibiotic
  • Most common type 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
  • Most gram-negative bacilli Bacilli Shigella possess a beta-lactamase gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.
• PBP-mediated 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 (↓ penicillin Penicillin Rheumatic Fever binding to PBPs): 
  • Mutations in PBPs → ↓ affinity of penicillins to PBPs 
  • Despite the mutations, the PBPs are still able to produce a cell wall Cell wall The outermost layer of a cell in most plants; bacteria; fungi; and algae. The cell wall is usually a rigid structure that lies external to the cell membrane, and provides a protective barrier against physical or chemical agents. Cell Types: Eukaryotic versus Prokaryotic.
• Porin-mediated 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 (↓ penicillin Penicillin Rheumatic Fever uptake): 
  • Penicillins enter 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 through channels Channels The Cell: Cell Membrane called porins in the cell walls.
  • 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 can ↓ production of porins → ↓ antibiotic levels within the cell → antibiotic 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
  • Common mechanism 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 in Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas

Penicillinase-resistant medications

• Some drugs can help overcome penicillinase by acting as penicillinase inhibitors.
• Penicillinase-resistant medications are often combined with penicillinase-sensitive penicillins to enhance activity.
• Penicillinase inhibitors include:
  • Clavulanic acid Clavulanic Acid A beta-lactam antibiotic produced by the actinobacterium streptomyces clavuligerus. It is a suicide inhibitor of bacterial beta-lactamase enzymes. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with other beta-lactam antibiotics it prevents antibiotic inactivation by microbial lactamase. Cephalosporins 
  • Sulbactam Sulbactam A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. Cephalosporins
  • Tazobactam Tazobactam A penicillanic acid and sulfone derivative and potent beta-lactamase inhibitor that enhances the activity of other anti-bacterial agents against beta-lactamase producing bacteria. Cephalosporins

Classification

Penicillins can be classified as natural penicillins, antistaphylococcal penicillins, and broad-spectrum Broad-Spectrum Fluoroquinolones penicillins. Penicillins can also be classified as penicillinase-sensitive or penicillinase-resistant compounds.

Penicillinase-sensitive penicillins

• Natural penicillins (chemicals that are naturally produced):
  • Penicillin Penicillin Rheumatic Fever G
  • Penicillin Penicillin Rheumatic Fever V
• Broad-spectrum Broad-Spectrum Fluoroquinolones penicillins (much better activity against gram-negative bacilli Bacilli Shigella):
  • 2nd generation (aminopenicillins):
    • Ampicillin (IV/oral)
    • Amoxicillin (oral)
  • 3rd-generation drugs (carbenicillin and ticarcillin) are not available in the U.S.
  • 4th generation (also known as antipseudomonal penicillins):
    • Piperacillin
    • Mezlocillin

Penicillinase-resistant penicillins

Penicillinase-resistant penicillins have a large R group next to the beta-lactam ring, which prevents the degradation of drugs by penicillinase. Penicillinase-resistant penicillins are effective against methicillin-susceptible staphylococci; thus, they are commonly referred to as antistaphylococcal penicillins.

• Dicloxacillin
• Cloxacillin
• Oxacillin
• Nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS)
• Methicillin (rarely used due to 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 and the risk of interstitial nephritis)

Penicillin-penicillinase inhibitor combinations

• Ampicillin-sulbactam (Unasyn)
• Amoxicillin-clavulanate (Augmentin)
• Piperacillin-tazobactam Piperacillin-Tazobactam Multidrug-resistant Organisms and Nosocomial Infections (Zosyn)

Pharmacokinetics

Distribution

• All penicillins are distributed in:
  • Pleural cavity Pleural cavity Paired but separate cavity within the thoracic cavity. It consists of the space between the parietal and visceral pleura and normally contains a capillary layer of serous fluid that lubricates the pleural surfaces. Pleura: Anatomy/ lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
  • Pericardial fluid Pericardial fluid Watery fluid produced in the serous and visceral pericardium surrounding the surface of the heart. Heart: Anatomy
  • Peritoneal fluid/ ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
  • Synovial fluid
  • Urine
  • 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 (especially mezlocillin)
• Poor penetration Penetration X-rays across 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 (exception: during 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 in meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis)

Protein binding

• Varies based on the drug
• Penicillinase-resistant penicillins ( nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS), oxacillin, cloxacillin): > 90% is protein bound.
• Penicillin Penicillin Rheumatic Fever V: > 80% is protein bound.
• Amoxicillin, ampicillin, and piperacillin: 15%–20% is protein bound.

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

• Relatively short for all penicillins (generally < 1 hour)
• Parenteral agents are typically administered every 4 hours.
• Exception: Piperacillin has a longer 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 when administered at higher doses.

Metabolism

• Penicillinase-resistant penicillins ( nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS), oxacillin, cloxacillin) undergo hepatic metabolism.
• Most others are not extensively metabolized.

Excretion

• Most are excreted primarily in the urine:
  • Most are excreted unchanged.
  • Ampicillin and piperacillin require dose adjustments in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with renal insufficiency.
• Some are excreted primarily in the 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, including:
  • Penicillinase-resistant penicillins ( nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS), oxacillin, and cloxacillin)
  • Mezlocillin

Indications

Adverse Effects and Contraindications

Adverse effects

The most common effects are related to allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions.

• IgE-mediated allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions:
  • Present with:
    • Pruritis
    • Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)
    • Angioedema Angioedema Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Angioedema
    • 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
    • Anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction
  • Symptoms typically appear within 4 hours of administration (often within minutes).
• Serum sickness Serum sickness Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses. Type III Hypersensitivity Reaction:
  • A late allergic reaction due to circulating immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency
  • Characterized by:
    • 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
    • Urticaria Urticaria Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation. Urticaria (Hives)
    • Adenopathy
    • Arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Glomerulonephritis (occasionally)
• Dermatologic reactions:
  • Morbilliform Morbilliform Erythema Infectiosum rash Rash Rocky Mountain Spotted Fever: a maculopapular Maculopapular Dermatologic Examination eruption due to a hypersensitivity reaction
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion multiforme: target lesions developing with acute onset
  • Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome: a desquamating 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 condition involving mucosal surfaces
• Neurologic reactions:
  • Encephalopathy Encephalopathy Hyper-IgM Syndrome
  • Penicillin Penicillin Rheumatic Fever neurotoxicity: 
    • Decreased level of consciousness (e.g., somnolence, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma)
    • Generalized hyperreflexia
    • Myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination
    • 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
• GI and hepatic reactions:
  • 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 (especially with ampicillin and amoxicillin)
  • Clostridioides difficile colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis 
  • Suppression Suppression Defense Mechanisms of gut flora leading to vitamin K deficiency Vitamin K Deficiency A nutritional condition produced by a deficiency of vitamin K in the diet, characterized by an increased tendency to hemorrhage (hemorrhagic disorders). Such bleeding episodes may be particularly severe in newborn infants. Fat-soluble Vitamins and their Deficiencies
  • Hypersensitivity hepatitis (especially with oxacillin and nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS))
• Renal reactions:
  • Glomerulonephritis (occurring in association with allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions)
  • Allergic interstitial nephritis (especially with nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS) and methicillin)
  • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury (associated with the concomitant use of piperacillin-tazobactam Piperacillin-Tazobactam Multidrug-resistant Organisms and Nosocomial Infections and vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides)
• Hematologic reactions:
  • Neutropenia Neutropenia Neutrophils are an important component of the immune system and play a significant role in the eradication of infections. Low numbers of circulating neutrophils, referred to as neutropenia, predispose the body to recurrent infections or sepsis, though patients can also be asymptomatic. Neutropenia due to immune-mediated destruction of polymorphonuclear (PMN) leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology
  • Hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia
  • Immune thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, especially with ticarcillin
  • Suppression Suppression Defense Mechanisms of gut flora → vitamin K deficiency Vitamin K Deficiency A nutritional condition produced by a deficiency of vitamin K in the diet, characterized by an increased tendency to hemorrhage (hemorrhagic disorders). Such bleeding episodes may be particularly severe in newborn infants. Fat-soluble Vitamins and their Deficiencies → coagulopathy

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 reactions
• Serious 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 reactions (e.g., Stevens-Johnson syndrome Stevens-Johnson syndrome Stevens-Johnson syndrome (SJS) is a cutaneous, immune-mediated hypersensitivity reaction that is commonly triggered by medications, including antiepileptics and antibiotics. The condition runs on a spectrum with toxic epidermal necrolysis (TEN) based on the amount of body surface area (BSA) involved. Stevens-Johnson Syndrome)

Comparison of Antibiotic Coverage and Classification

Comparison based on mechanisms of action

Antibiotics can be classified in several ways. One way is to classify them based on their mechanism of action:

Comparison based on 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. The table below outlines the antibiotics that are active 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, including gram-positive cocci Cocci Bacteriology, gram-negative bacilli Bacilli Shigella, and anaerobes Anaerobes Lincosamides.