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A Case of Penicillin Drug Allergy

Case Scenario:

A young female, 26 years old primae underwent C/S. Both mother and baby were clinically stable. She was advised postoperative antibiotic injection to prevent infection. Nursing staff administered her Co-amoxiclav injection, immediately the patient complained of severe difficulty in breathing, abdominal pain and nausea. She was sweating and pulse was weak. Drastic fall in B.P and she fainted.

Learning Objectives:

  1. Definition of drug allergy and hypersensitivity.
  2. What is anaphylaxis?
  3. Other forms of pencillin allergy and their prevention
  4. Management of acute anaphylaxis
  5. Difference between acute anaphylaxis and anaphylactoid reactions.
  6. Definition of physiological antagonism. Clinical settings in which physiological antagonist may be preferred over pharmacological antagonist.

Explanation:

Co-Amoxiclav

Co-Amoxiclav is British approved name for combination of Amoxicillin trihydrate and Potassium clavulanate, a β-lactam antibiotic and β-lactamase inhibitor. This combination increases the spectrum and restores efficacy against amoxicillin-resistant bacteria, that produce β-lactamase. Trade names include Augmentin, Clavamax, CLAMP, Amoxiclav.

Amoxicillin works by interfering with the ability of bacteria to form cell walls. The cell walls of bacteria are vital for their survival. It inhibits Transpeptidase enzyme responsible for inducing cross-linkages in the peptidoglycan layer of cell wall. This leads to decrease strength and integrity of the cell wall. Only useful when bacteria are actively dividing and synthesizing cell wall.

Prophylaxis

It is a measure taken for the prevention of a disease or a condition. It is Greek for ‘advance guard’.

The single most important risk factor for postpartrum maternal infections is cesarean section.(Gibbs 1980)

Complications

Fever, wound infection, endometriosis, bacteremia, pelvic abscess, septic shock, necrotizing fasciitis and septic pelvic vein thrombophlebitis and UTIs.

Sources of infection

Genital tract and skin.

Organisms

Polymicrobial: wounds and endometrosis include Escherichia coli, other aerobic gram negative rods, Group B – Streptococcus and other Streptococcus bacteria, Enterococcus faecalis , Staphylococcus aureus and coagulase negative Staphylococci, anaerobes Peptostreptococcus species and Bacteriodes species Gardnorella vaginalis and genital Mycoplasm. (Watts 1991, Robert 1993, Mortoms 1995)

Staphyloccus aureus and coagulase negative arise from contamination of wound with endogenous flora of skin at the time of surgery (Emmon 1981)

Anaphylaxis

Anaphylaxis is a severe allergic reaction that occurs rapidly and causes a life threatening response involving the whole body. This reaction can lead to difficulty breathing and shock, ultimately leading to death. Sensitizing is required, IgE mediated response.

Drug Allergy:

It is the response of the body in which body’s immune system reacts with the drug.

Irritation, hives, skin rashes, itchy skin or eyes, congestion and swelling in the mouth and throat.

Severe symptoms: Difficulty in breathing , blueness of skin, dizziness, fainting, anxiety, confusion rapid pulse, nausea, diarrhea and abdominal problems.

Other drugs: Sulfa drugs, barbiturates, anticonvulsants, insulin and iodine.

Difficulty in breathing, swelling or spasm in the airways, tongue swelling severe, apnea.

Loss of consciousness due to hypotension.

Cardiac arrest

Skin: Most analphylactic reactions involve the skin.

Hives, welts or wheals, hives can cause severe itching.

Generalized erythema, swelling in the face, eyelids, lips, tongue throat, hands and feet,

Breathing:

Swelling of the surrounding tissues narrows the airways. Difficulty breathing, wheezing, chest tightness, coughing, hoarseness, nasal congestion, sneezing.

Cardiovascular:

Blood pressure may drop dangerously low levels. Rapid or irregular heartbeat, Dizziness, faintness loss of consciousness and collapse.

General:

Tingling or sensation of warmth, difficulty swallowing, nausea, vomiting, diarrhea, abdominal cramping, bloating, anxiety, fear, feeling that you are going to die, Confusion

Management:

Since it is a medical emergency, so ABC is applied

Airways:

Check the patency of the airways.

Breathing:

Use mask or nasal tubes. In serious cases intubation and mechanical ventilator. If required tracheostomy.

Circulation:

Epinephrine injection. IV line for fluids and drugs like H1 blockers beta agonists etc.

Medications:

Epinephrine to increase blood pressure by opposing vasodilation by histamine and stimulating heart.

H1-receptor blocker/ antihistamine (diphenylhydramine)

Beta-agonist: Like albuterol to relieve bronchospasm.

H2-blocker: Zantac, Tagamat, Cimetidine, Ranitidine.

Corticosteroid: Prednisone to combat inflammation.

Hypotension persists then Dopamine.

After Epipen or Ana-kit, which contains epinephrine in known concentration for self-administration as IM.

Anaphylactoid Reaction:

An analphylactoid reaction doesn’t need the presence of IgE antibodies for a hypersensitivity reaction to occur. Substances initiating the analphylatoid reactions, such as radiopaque contrast media, non-steroidal anti-inflammatory drugs and aspirin cause a direct breakdown of the mast cell and basophil membranes.

Anaphylactoid Reactions causing substances:

Aspirin, NSAIDs, radiopaque contrast media, fluroscem, Dextran, Thiamn, opiates.

Hypersensitivity:

A state of altered reactivity in which body reacts with an exaggerated immune response to what is perceived as a foreign substance.

Types of reaction Prototypic disorders Immune mechanism Pathologic Lesion
Immediate (type 1) hypersensitivity Anaphylaxis, allergies, bronchial asthma (atopic forms) Production of IgE antibody leads to immediate release of vasoactive amines and other mediators from mast cell, later recruitment of inflammatory cells. Vascular dilation, edema, smooth muscle contraction, mucous production, tissue injury, inflammation.
Antibody-mediated (type-II) hypersensitivity Autoimmune hemolytic anemia ; Good pasture syndrome Production of IgG, IgM leads to their binding to antigen on target cell or tissue leads to phagocytosis or lysis of target cell by activated complement of Fc receptors; recruitment of leukocytes Phagocytosis and lysis of cells; inflammation in some diseases, functional derangements without cell or tissue injury.
Immune complex mediated (type III) hypersensitivity Systemic Lupus Erythmatous; some forms of glomerulnephritis; serum sickness; Arthur reaction Deposition of antigen binding complexes leads to complement activation leading to recruitment of leukocytes by complement products and Fc receptors leads to release of enzymes and other toxic molecules Inflammation, necrotizing vasculitis (fibrinoid necrosis)
Cell-Mediated (type IV) hypersensitivity Contact dermatitis; multiple scelrosis; type I diabetes; rheumatoid arthritis; inflammatory bowel disease; tuberculosis Activated T lymphocytes leads to: 

I)Release of cytokines leading to inflammation and macrophage activation

II)T cell mediated cytotoxicity

Perivascular cellular infiltrates; edema; granuloma formation; cell destruction.

 

Action Mediators
Vasodilation, increased vascular permeability Histamine, PAF, Leukotrienes C4 D4 E4, Neutral proteases that activate complement and kinins, Prostaglandins D2.
Smooth muscle spasm Leukotrienes C4 D4 E4, histamine, Prostaglandins, PAF.
Cellular Infiltration Cytokines, (chemokines, TNF) leukotrienes B4, Eosinophil and neutrophil chemotactic factor.

Events:

  1. Exposure to antigen
  2. Activation of TH2 cells and IgE class switching in B cells.
  3. Production of IgE
  4. Binding of IgE to FcεRI on mast cells
  5. Repeat exposure to antigen
  6. Activation of mast cells, release of mediators

Mediators:

  • Vasoactive amines and lipid mediatiors for immediate hypersensitivity reaction
  • Cytokines for late phase reaction

Two phases of Type I

Immediate: Vasodilation, vascular leakage, smooth muscle spasm.

Late Phase reaction: Leukocyte infiltration, Epithelial damage, Bronchospasm.

To summarize, immediate hypersensitivity is a complex disorders resulting from an IgE-mediated triggering of mast cells and subsequent accumulation of inflammatory cells at sites of antigen deposition. These events are regulated mainly by the induction of TH2 helper T-cells that stimulate production of IgE (which promotes mast cell activation). Cause accumulation of inflammatory cells (particularly eosinophils) and triggers secretion of mucous. The clinical features result from release of mast cell mediators as well as the eosinophil-rich inflammation.

Allergic reactions:

An allergic reaction occurs when the immune system begins to recognize a drug as something “foreign”. Several different symptoms can indicate that a person is allergic to penicillin. These include hives (raised, intensely itchy spots that come and go over hours) angioedema (swelling of the tissue under the skin, commonly around the face), throat tightness, wheezing, coughing, and trouble breathing from asthma-like reactions (narrowing of the airways into the lungs).

A past history of these types of reactions is important because the person might develop a more severe reaction, such as anaphylaxis, if they were to take the antibiotic again. Mild to moderate allergic reactions to penicillins are common, occurring in 1 to 5 percent of people.

Anaphylaxis:

Anaphylaxis is a sudden, potentially life-threatening allergic reaction. Symptoms include those of an allergic reaction, as well as very low blood pressure, difficulty breathing, abdominal pain, swelling of the throat or tongue, and/or diarrhea or vomiting. Fortunately, anaphylaxis is uncommon

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