Antimicrobial Therapy Principles

• Antibiotics can be bactericidal (kills microorganisms) or bacteriostatic (inhibits microorganisms)
• Antimicrobials are natural and synthetic compounds that kill or inhibit microorganisms

Key Terms

• Antagonism: When one antibiotic interferes with another, resulting in less activity than if used individually
• Synergy: When the combined effect of two antimicrobials is greater than their added effect

Principles of Antimicrobial Therapy

• Gram Stain: A simple tool to identify pathogens based on cell wall structural components, which affect susceptibility to antimicrobials
  • Gram stain positive stains purple
  • Gram stain negative stains pink
• Acid-fast stain (AFB): Identifies bacteria resistant to decolorization by acid-alcohol
• Enzyme-linked immunosorbent assay (ELISA) and Latex agglutination are also used
• Antimicrobial therapy depends on host factors, susceptibility/resistance to antimicrobials, and pharmacodynamics

Host Factors

• Include impaired immune function, age, stomach pH, and pregnancy (check for fetal harm)

Pharmacodynamics

• Science to understand the optimal effect of a drug's concentration in vitro (MIC) against an organism
• Measured in vitro by time-kill studies, including concentration dependent effect, time dependent effect, and postantibiotic effect (PAE)
• Using multiple classes of antimicrobials may be needed to cover a broad spectrum of organisms initially

Monitoring and Regimen

• Regimen may be narrowed once the organism is identified
• Certain infections are polymicrobial
• Drugs can be synergistic (works together) or antagonistic (block each other)
• Monitoring involves lab parameters and clinical assessment: fever, WBCs, culture results, symptoms, drug toxicity, and treatment failure

Penicillin

• Mechanism: Inhibits cell wall synthesis
• Bactericidal
• Activates the endogenous autolytic system in bacteria, can act synergistically with aminoglycosides
• Effective against gram-positive bacteria and anaerobes
• Adverse reaction is hypersensitivity

Cephalosporins

• Mechanism: Inhibits bacterial cell wall synthesis
• Bactericidal
• Adverse Reactions: Hypersensitivity, minor gastrointestinal complaints, hypoprothrombinemia, flushing, nausea, thirst, palpitations, chest pains, vertigo, and death in some cases

Carbapenems

• Adverse reaction is seizure

B-lactams

• Mechanism: Similar to other B-lactams, inhibits cell wall synthesis
• Bactericidal
• Clinical Uses: Effective against Pseudomonas A. (except ertapenem), gram negative bacilli, most anaerobes, gram-positive organisms, MSSA, and streptococcus species
• Adverse: Low incidence of adverse reactions, but can cause seizures in patients with decreased renal function

Monobactams (Aztreonam)

• Mechanism: Similar to B-lactams
• Bactericidal
• Clinical Use: Gram negative aerobic bacilli
• Adverse: Well tolerated, but rare reactions include rash and anaphylaxis

Aminoglycosides

• Includes Gentamicin, Tobramycin, Netilmicin, and Amikacin
• Mechanism: Inhibit RNA translation, destabilize cell wall
• Bactericidal
• Clinical Use: Nosocomial gram-negative infections (VAP)
• Adverse: Nephrotoxicity, ototoxicity, and rare neuromuscular blockade with rapid high-dose use

Clindamycin

• Mechanism: Inhibits protein synthesis, Bacteriostatic
• Clinical: Active against gram-positive and anaerobic bacteria, and has activity against MRSA
• Adverse: Nausea, vomiting, and diarrhea

Vancomycin

• Mechanism: Prevents formation of rigid cell wall, Bactericidal against gram-positive organisms, and Bacteriostatic against enterococci
• Clinical: Used for Methicillin-resistant S. Aureus (MRSA), and oral form treats C. Difficile
• Adverse: Red man syndrome (histamine release), ototoxicity, and nephrotoxicity
• Commonly used for resistant pathogens

Tuberculosis

• Spread via airborne caused by Mycobacterium tuberculosis, affecting lungs and other body parts
• Treatment: Antimycobacterials like Isoniazid (INH)
• Adverse: Hepatotoxicity, neurotoxicity, nausea, loss of appetite, and abdominal pain

Rifampin and Rifabutin

• Mechanism: Inhibit RNA polymerase
• Bactericidal against actively dividing bacteria
• Adverse: Hepatotoxicity
• Rare: Fever, chills, nausea, vomiting; turns bodily fluids orange

Antifungals

• The number of fungal infections is increasing dramatically, treat with Polyenes (amphotericin B and nystatin)

Polyenes

• Mechanism is to increase permeability of cell membrane
• Clinical: Used for Aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis, and cryptococcosis
• Adverse: Flushing, fever, chills (infusion related), and renal impairment

Azoles

• Mechanism: Reduce ergosterol production. Fungistatic effect
• Clinical Use: Candidiasis (fluconazole)
• Adverse: Anorexia, nausea, and vomiting

Echinocandins

• Mechanism: Inhibit fungal cell wall synthesis
• Fungicidal or fungistatic depending on isolate
• Clinical Uses: Candida and Aspergillus
• Adverse: Fever, rash, flushing, and thrombophlebitis

Flucytosine

• Mechanism: Inhibits fungal RNA formation
• Fungistatic
• Clinical Use: Candida, Cryptococcus, and Aspergillus
• Adverse: Bone marrow suppression

Antiviral Agents

• Acyclovir and Valacyclovir
  • Mechanism: Terminate viral replication
  • Clinical Uses: Herpesvirus family, Cytomegalovirus (CMV), Varicella-zoster virus (VZV), and Epstein-Barr virus (EBV)
  • Adverse: Neuropathy, burning, and irritation (topical)

Respiratory Care Assessment of Antibiotic Therapy

• Before treatment: Assess effectiveness based on indications
• During (short term): Consider susceptibility testing and patient assessment
• Long term: Monitor response and consider combination of agents
• Contraindications: Should not be used unless a specific pathogen is known or suspected

Gram Stain

• Designates bacteria as gram-positive (purple) or gram-negative (pink)
• Structural components affect antimicrobial susceptibility

Bacteriostatic vs Bactericidal

• Bacteriostatic: Inhibit bacterial growth without killing
• Bactericidal: Kills bacteria
• Virucidal kill viruses and fungicidal kill fungi

Bacterial Resistance

• MRSA and VRE are resistant to many current antimicrobial therapies
• Mechanisms include enzyme production, alteration of cell walls/membranes, efflux pump upregulation, and alteration of the site of antimicrobial action

Penicillin Action

• Inhibits cell wall synthesis by binding enzymes and preventing cross-linking of peptidoglycan

Penicillin Properties

• Bactericidal, exhibit time-dependent killing, and can act synergistically with aminoglycosides

Tuberculosis Treatment

• Requires multiple antibiotic regimens for 6-12 months
• Single-agent regimens are not advised due to high risk of resistance
• Drugs are categorized as first-line or second-line agents based on efficacy and side-effects
• Initial therapy: Isoniazid, pyrazinamide, rifampin, and ethambutol

Host Factors

• Antimicrobial therapy depends on host factors, susceptibility/resistance, and pharmacodynamics
• Vancomycin treats gram-positive bacteria, and is not active against gram-negative bacteria
• Antivirals (excluding antiretrovirals) mimic nucleosides and inhibit DNA synthesis
• Aminoglycosides like tobramycin (TOBI) are used to control Pseudomonas aeruginosa in cystic fibrosis patients via inhalation due to low bronchial concentrations