Antimicrobial Therapy: Key Terms and Principles

Key Terms

• Antagonism occurs when one antibiotic interferes with the activity of another, resulting in less effectiveness than if each drug were administered individually.
• Antibiotics are substances derived from microorganisms that can either inhibit or kill other microorganisms.
• Antimicrobials are natural or synthetic compounds capable of inhibiting or killing microorganisms.
• Synergy is when the combined effect of two antimicrobials is greater than their individual effects.

Principles of Antimicrobial Therapy

• Gram staining is a simple and common method for identifying pathogens, where bacteria stain differently based on their cell wall's structural components, which affects their susceptibility to antimicrobials.
• Gram-positive bacteria stain purple.
• Gram-negative bacteria stain pink.
• An acid-fast stain (AFB) is a technique to identify bacteria resistant to decolorization by acid-alcohol.
• ELISA (Enzyme-Linked Immunosorbent Assay) and latex agglutination techniques are also used.
• Antimicrobial therapy effectiveness depends on host factors, antimicrobial susceptibility/resistance, and pharmacodynamics.

Host Factors

• Host factors include impaired immune function, age (related to liver, kidney function, and stomach pH), and pregnancy due to potential harm to the fetus.

Pharmacodynamics

• Pharmacodynamics studies the optimal drug effect based on its concentration in vitro (MIC) against an organism.
• Measured by time-kill studies, including concentration-dependent, time-dependent (concentration independent), and post-antibiotic effects (PAE).
• Using multiple antimicrobials may be needed to cover a broad spectrum of organisms initially.

Monitoring and Regimens

• After identification, the regimen may be narrowed.
• Drugs can work together (synergistic) or against each other (antagonistic).
• Monitoring therapy involves lab tests and clinical assessment of fever, WBC count, culture results, symptom resolution, and drug toxicity.

Penicillin

• Works by inhibiting cell wall synthesis in bacteria.
• It is Bactericidal.
• Effective against gram-positive bacteria and anaerobes.
• Penicillin activates an autolytic system in bacteria and can be synergistic with aminoglycosides.
• Common adverse reaction is hypersensitivity.

Cephalosporins

• Inhibits bacterial cell wall synthesis.
• It is bactericidal.
• Adverse reactions include hypersensitivity and minor gastrointestinal issues.
• Flushing can occur which is the redding of the skin.
• Hypoprothrombinemia can occur (those with MTT side chain.
• Death

Carbapenems

• Can induce seizures.

Carbapenems Action and Uses

• Action is similar to other Beta-lactams.
• Inhibits cell wall synthesis.
• Bactericidal.
• Used for Pseudomonas A. (except ertapenem), gram-negative bacilli, most anaerobes, gram-positive organisms, MSSA, and streptococcus species.
• Low incidence of adverse reactions, but can cause seizures in patients with decreased renal function.

Monobactams (Aztreonam) Action and Uses

• Similar to Beta-lactams.
• Bactericidal.
• Used for gram-negative aerobic bacilli.
• Generally well-tolerated.
• Rare side effects include rash and anaphylaxis.

Aminoglycosides

• Includes Gentamicin, Tobramycin, Netilmicin, and Amikacin.
• Inhibits RNA translation, destabilizes cell wall, and is bactericidal.
• Treats nosocomial gram-negative infections (VAP).
• Side effects include nephrotoxicity and ototoxicity.
• Rare: Neuromuscular blockade with rapid high-dose use.

Clindamycin

• Inhibits protein synthesis in bacteria.
• Bacteriostatic.
• Active against gram-positive and anaerobic bacteria.
• Offers activity against MRSA.
• Side effects include nausea, vomiting, and diarrhea.

Vancomycin

• Prevents formation of the rigid cell wall in bacteria.
• Bactericidal against gram-positive organisms.
• Bacteriostatic against enterococci.
• Treats Methicillin-resistant S. Aureus (MRSA) and C. Difficile (oral formulation).
• Side effects include red man syndrome, ototoxicity, and nephrotoxicity.
• Commonly used for resistant pathogens.

Tuberculosis (TB)

• Airborne infection caused by Mycobacterium tuberculosis that affects the lungs and spreads.
• Antimycobacterials are used against tuberculosis, like Isoniazid (INH).
• Side effects include hepatotoxicity, neurotoxicity, nausea, loss of appetite, and abdominal pain.

Rifampin and Rifabutin

• Inhibits RNA polymerase.
• Bactericidal against actively dividing bacteria.
• Side effects include hepatotoxicity.
• Rare side effects include fever, chills, nausea, and vomiting.
• Bodily fluids may turn an orange color.

Antifungals

• The number of fungal infections is sharply increasing.
• Polyenes (amphotericin B and nystatin) are antifungals.
• Increases permeability of cell membrane.
• Treats Aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis, and cryptococcosis.
• Side effects include flushing, fever, chills (infusion-related), and renal impairment.

Azoles

• Reduces ergosterol production, resulting in a fungistatic effect.
• Treats Candidiasis (fluconazole).
• Side effects include anorexia, nausea, and vomiting.

Echinocandins

• Inhibits fungal cell wall synthesis and can be fungicidal or fungistatic.
• Treats Candida and Aspergillus.
• Side effects include fever, rash, flushing, and thrombophlebitis.

Flucytosine

• Inhibits fungal RNA formation and is fungistatic.
• Treats Candida, Cryptococcus, and Aspergillus.
• Side effects include bone marrow suppression.

Antiviral Agents

• Acyclovir and Valacyclovir.
• Terminates viral replication.
• Treats Herpesvirus family, Cytomegalovirus (CMV), Varicella-zoster virus (VZV), and Epstein-Barr virus (EBV).
• Side effects include neuropathy, burning, and irritation (topical use).

Respiratory Care Assessment of Antibiotic Therapy

• Before treatment, assess the effectiveness of drug therapy.
• During treatment, consider susceptibility testing and patient assessment.
• Monitor therapy response and consider combined agents long term.
• Do not use unless a specific pathogen is known or suspected.

Antimicrobial Agents

• The Gram stain is the most simple preparation.
• Gram-positive stains purple, and gram-negative stains pink.
• Structural components of the cell wall affect a bacteria's susceptibility to antimicrobials.
• Bacteriostatic drugs inhibit growth, while bactericidal drugs kill bacteria, virucidal drugs kill viruses, and fungicidal drugs kill fungi.
• MRSA and VRE are examples of resistant bacterial pathogens.

Mechanisms of Resistance

• Include enzyme production, alteration of cell walls, upregulation of efflux pumps, and alteration of the site of antimicrobial action.
• Penicillins inhibit cell wall synthesis by preventing cross-linking of peptidoglycans.
• TB treatment involves multiple drugs for 6-12 months due to resistance.
• Drugs are categorized as first or second-line.
• Outcome depends on host factors, susceptibility/resistance, and pharmacodynamics.
• Vancomycin treats gram-positive bacteria.
• Antivirals mimic nucleosides and inhibit DNA synthesis.
• Aminoglycosides (tobramycin) can be inhaled to treat Pseudomonas aeruginosa in cystic fibrosis patients.