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PHM Antibiotics

Infectious Disease

Definitions

  • Pathogen: An organism that can cause disease.

  • Resistance: The ability of pathogens to resist the effects of medication that once successfully treated them.

  • Pharmacodynamics: The study of the effects of drugs and their mechanisms of action.

  • Drug: Any substance that causes a change in an organism's physiology or biology when introduced.

  • Toxicity: The degree to which a substance can harm humans or animals.

  • Pharmacokinetics: The study of how drugs move through the body, including absorption, distribution, metabolism, and excretion.

  • Immune Response: The body's defensive reaction to invasion by foreign substances such as pathogens.

  • Infection: The invasion and multiplication of pathogenic microorganisms in a host organism.

  • Patient: An individual receiving medical care or treatment.

Common Bacterial Infections

Outpatient Bacterial Infections

  • Strep throat: Caused by Streptococcus bacteria, presenting with sore throat and fever.

  • Sinusitis: Inflammation of the sinuses, often occurring after a cold.

  • Acute otitis media: A middle ear infection common in children.

  • Community-acquired pneumonia: A lung infection contracted outside of a hospital setting.

  • Skin/soft tissue infections: Infections involving the skin and underlying tissues.

  • Urinary tract infections (UTI)/Cystitis: Infections in the urinary system, often marked by painful urination.

  • Chlamydia/Gonorrhea: Common sexually transmitted infections caused by bacteria.

Inpatient Bacterial Infections

  • Sepsis: A systemic, life-threatening response to infection, often leading to organ failure.

  • Pneumonia: A lung infection that occurs while the patient is hospitalized.

  • Pyelonephritis: A kidney infection, impacting renal function.

  • Cellulitis: A diffuse skin infection characterized by redness and swelling.

  • Clostridium difficile: An anaerobic bacteria that can cause severe colitis and is known for its resistance to various antibiotics.

Mechanism of Action

Antibiotic Classes Based on Mechanism

  • Cell wall synthesis inhibitors: Includes Penicillins and Cephalosporins which interfere with bacterial cell wall formation.

  • Protein synthesis inhibitors: Includes Tetracyclines and Macrolides, which inhibit bacterial protein manufacturing.

  • RNA or DNA synthesis inhibitors: Includes Rifampin and Fluoroquinolones, targeting the genetic material of bacteria.

  • Antimetabolites: Includes Sulfonamides that disrupt metabolic processes in bacteria.

Guidelines for Antibiotic Use

  • Indication: Use antibiotics only for approved indications.

  • Spectrum: Favor the narrowest spectrum agent suitable for the infection.

  • Dosage: Administer the proper dosage as per guidelines.

  • Duration: Use the shortest effective duration of therapy to reduce resistance.

Antibiotic Selection Criteria

Key Considerations

  • Effectiveness against the pathogen: Efficacy of the antibiotic against the specific bacteria causing infection.

  • Site of infection: Determining if the antibiotic can reach the infected area effectively.

  • Host defenses: Consideration of bactericidal versus bacteriostatic actions.

  • Allergy status: Any known allergies the patient has to antibiotics must be taken into account.

  • Patient variables: Consideration of age, pregnancy status, and any concurrent illnesses when selecting antibiotics.

Pathogen Classification

Gram-Positive Pathogens

  • Staphylococcus species:

    • Staph aureus: Known for its virulence and resistance to antibiotics.

    • Staph epidermidis: Typically a coagulase-negative staphylococcus found on skin.

  • Streptococcus species:

    • Group A Strep: Often causes throat infections and skin conditions.

    • Group B Strep: Can cause severe infections in newborns.

    • Strep pneumoniae: A major cause of community-acquired pneumonia.

  • Enterococcus:

    • Enterococcus faecalis: Known for its resistance to multiple antibiotics.

Gram-Negative Pathogens

  • Escherichia coli: Common cause of UTIs.

  • Klebsiella: Known for causing pneumonia and bloodstream infections.

  • Pseudomonas: Found in various infections, particularly in immunocompromised patients.

  • Proteus: Another common UTI-causing bacterium.

  • Neisseria meningitides: Responsible for meningitis.

  • Neisseria gonorrhoeae: Causes gonorrhea.

  • Haemophilus influenzae: Known for respiratory infections.

  • Moraxella catarrhalis: Often associated with respiratory tract infections.

Atypical Respiratory Pathogens

  • Mycoplasma pneumoniae: Lacks a cell wall, making it resistant to many antibiotics.

  • Chlamydia pneumoniae: Requires host cells for reproduction.

  • Legionella pneumophila: Can cause severe pneumonia and has a unique cell membrane structure.

Anaerobic Pathogens

  • Bacteroides fragilis: Common in polymicrobial infections.

  • Clostridium difficile: Causes antibiotic-associated diarrhea.

  • Clostridium botulinum: Produces botulinum toxin.

  • Clostridium tetani: Causes tetanus, resulting from toxin production.

Antimicrobial Resistance

Overview

  • Antimicrobial Resistance: Bacteria have developed mechanisms to resist antibiotics, leading to treatment failures.

  • Selection of Resistance: Resistance can develop during treatment; hence the importance of selecting the appropriate drug, dose, and duration.

  • Trend: Increasing resistance rates across the nation coupled with a decrease in new antibiotic development.

  • IDSA Initiatives: Infectious Diseases Society of America highlights the public health crisis of antibiotic resistance.

Antibiotic Classification

Groups Based on Chemical Structure

  • Beta-lactams: Include Penicillins, Cephalosporins, Carbapenems, Monobactams.

  • Glycopeptides: Effective against Gram-positive bacteria.

  • Fluoroquinolones: Broad-spectrum agents that inhibit DNA replication.

  • Macrolides: Target ribosomal functions to inhibit protein synthesis.

  • Tetracyclines: Broad-spectrum antibiotics that also inhibit protein synthesis.

  • Miscellaneous Agents: Other agents that have unique mechanisms of action.

Beta-Lactam Antibiotics

Characteristics

  • Mechanism of Action (MOA): All beta-lactams share the same MOA, targeting bacterial cell wall synthesis.

  • Killing Pattern: Exhibit time-dependent killing, whereby the susceptibility of bacteria is influenced by the time the drug concentration remains above the minimum inhibitory concentration (MIC).

  • Therapeutic Range: They have a wide therapeutic range; however, very high doses can lead to seizures.

  • Adverse Reactions: Can cause hypersensitivity and allergic reactions in patients.

Hypersensitivity Reactions to Beta-Lactams

Prevalence

  • Commonality: Most commonly reported drug allergy, with about 10% of patients reporting a penicillin allergy.

  • Hospitalized Patients: Approximately 50% of allergic reactions in hospitalized patients are due to beta-lactams.

  • Difference from Side Effects: Allergic reactions differ from common side effects such as gastrointestinal disturbances and headaches.

  • Cross-Sensitivity: Variable cross-sensitivity exists among different beta-lactams; the severity of reactions can range from mild rash to anaphylaxis.

Hypersensitivity Types

Type 1

  • Mechanism: IgE-mediated allergic reactions.

  • Population Impact: Affects about 1% of the population.

  • Timing: Reactions occur within 1 hour of exposure.

  • Symptoms: Symptoms include urticaria (hives), laryngeal edema, bronchospasm, and hypotension.

Type 2

  • Mechanism: Non-IgE mediated reactions, involving IgG or IgM antibodies.

  • Population Impact: Affects approximately 10% of the population.

  • Timing: Reactions may occur hours to days after exposure.

  • Symptoms: Primarily manifests as maculopapular rashes located on the legs, buttocks, and trunk.

Type 3

  • Symptoms: Characterized by drug fever, can mimic fever from bacterial infection.

Type 4

  • Rarity: Very rare with beta-lactams.

  • Examples of Response: Contact dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Clinical Approach to Reactions

  • Drug fever or rash: Cross-reactivity with other beta-lactams is about 3-5%.

  • Hives (immediate) or anaphylaxis: Higher risk for serious cross-reactivity leads to the recommendation of not administering other beta-lactam antibiotics, except for aztreonam which is usually considered safe due to its unique structure.

Video Transcription

  • Instructor: James Karboski, PharmD

  • Role: Clinical Professor

Infectious Disease

Definitions

  • Pathogen: An organism that can cause disease, forming a new variable in therapy compared to patient-centric pathophysiologic processes (e.g., high blood pressure, lipid issues). The cause of the problem is external to the patient.

  • Resistance: The ability of pathogens to resist the effects of medication that once successfully treated them. This develops through genetic mutation, driven by antibiotic exposure, where resistant strains multiply rapidly.

  • Pharmacodynamics: The study of the effects of drugs and their mechanisms of action. In infectious disease, this focuses on how well the drug works against the pathogen.

  • Drug: Any substance that causes a change in an organism's physiology or biology when introduced. For infectious diseases, the drug's efficacy is aimed at the pathogen to eliminate it.

  • Toxicity: The degree to which a substance can harm humans or animals. In infectious disease therapy, any effect a drug has on the patient is considered a side effect or toxicity, as the therapy is not aimed at the patient's physiology for efficacy.

  • Pharmacokinetics: The study of how drugs move through the body, including absorption, distribution, metabolism, and excretion. Understanding this is crucial for correct dosing, managing drug interactions, and ensuring the drug reaches the site of infection.

  • Immune Response: The body's defensive reaction to invasion by foreign substances such as pathogens. Often, the immune system can eradicate pathogens before they cause an infection.

  • Infection: The invasion and multiplication of pathogenic microorganisms in a host organism.

  • Patient: An individual receiving medical care or treatment.

Common Bacterial Infections

Outpatient Bacterial Infections

  • Strep throat: Caused by Streptococcus bacteria, presenting with sore throat and fever, often with exudate (white substance) on swollen, red tonsils.

  • Sinusitis: Inflammation and infection of the sinuses, often occurring after a cold, with accumulation of bacteria.

  • Acute otitis media: A middle ear infection common in children. The tympanic membrane appears bulging, inflamed, and less translucent compared to a normal ear drum due to increased pressure from infection.

  • Community-acquired pneumonia: A lung infection contracted outside of a hospital setting, visible as cloudiness or infiltrates on a chest X-ray, indicating inflammatory response.

  • Skin/soft tissue infections: Infections involving the skin and underlying tissues, frequently caused by gram-positive organisms like Staph and Strep that colonize the skin.

  • Urinary tract infections (UTI)/Cystitis: Infections in the urinary system, often in the bladder itself, marked by painful urination (dysuria) and sometimes blood in urine (hematuria). Approximately 85-90% are caused by E. coli. Most common in young, sexually active females due to anatomical factors.

  • Chlamydia/Gonorrhea: Common sexually transmitted infections caused by bacteria.

Inpatient Bacterial Infections

  • Sepsis: A systemic, life-threatening response to infection, often bloodstream-borne, leading to organ failure. Requires aggressive identification and management.

  • Pneumonia: A lung infection that occurs while the patient is hospitalized. Hospital-acquired pneumonias are typically more serious due to potentially more dangerous pathogens.

  • Pyelonephritis: A kidney infection, impacting renal function, which can be a worsening of a bladder infection or standalone. More serious cases require hospitalization and IV antibiotics.

  • Cellulitis: A diffuse, often dangerous, skin infection characterized by redness and swelling that can quickly become a bloodborne septic infection.

  • Clostridioides difficile: An anaerobic bacterium (formerly Clostridium difficile) that can cause severe colitis, known for its resistance to various antibiotics. It can lead to symptomatic and toxic megacolon.

Mechanism of Action

Antibiotic Classes Based on Mechanism

  • Cell wall synthesis inhibitors: These drugs prevent the proper formation or repair of the bacterial cell wall, which is essential for bacterial survival.

    • Includes Penicillins and Cephalosporins.

  • Protein synthesis inhibitors: These agents inhibit the bacteria's ability to produce necessary proteins for biological functions, making continued life incompatible.

    • Includes Tetracyclines and Macrolides.

  • RNA or DNA synthesis inhibitors: These antibiotics target the genetic material of bacteria, preventing successful replication and thus sustaining the bacterial population.

    • Includes Rifampin (used for tuberculosis) and Fluoroquinolones (general-purpose antibiotics).

  • Antimetabolites: These drugs act like