RCP 110 chapter 14 - Antimicrobial Therapy Principles

Principles of Antimicrobial Therapy

• Gram stain is the simplest and most common staining method
• Bacteria stain differently based on the structural components of their cell wall
• Gram-positive bacteria stain purple
• Gram-negative bacteria stain pink
• Acid-fast stain (AFB), 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, liver and kidney function, stomach pH, and pregnancy
• It is important to consider if a drug could harm the fetus during pregnancy

Pharmacodynamics

• Pharmacodynamics studies the optimal effect of a drug based on its concentration and the in vitro minimum inhibitory concentration (MIC) against an organism
• Pharmacodynamics are measured in-vitro by time-kill studies
• The types of effects are: concentration-dependent, time-dependent (concentration independent), and postantibiotic effect (PAE)

Antimicrobial Combinations

• It involves using two or more classes of antimicrobials
• May be necessary to cover a broad spectrum of organisms initially
• The regimen can be narrowed once the organism is identified
• Some infections are polymicrobial
• Drugs can have synergistic or antagonistic effects when combined

Monitoring Response to Therapy

• Monitoring involves assessing laboratory parameters and clinical signs
• Important things include checking for fever, WBC count, culture results, symptom resolution, drug toxicity, and treatment failure

Antibiotics - β-Lactams

• Penicillins, Cephalosporins, Carbapenems, and Monobactams are β-Lactams

Penicillin

• It inhibits cell wall synthesis, killing the bacteria
• Penicillin activates the endogenous autolytic system in bacteria and can act synergistically with aminoglycosides
• The adverse reactions and precautions include hypersensitivity (most common), hematological reactions, gastrointestinal disturbances, and CNS toxicity

Cephalosporins

• It inhibits bacterial cell wall synthesis and is bactericidal
• Adverse reactions include hypersensitivity in 1-3% of patients and minor gastrointestinal complaints
• Hypoprothrombinemia can occur in those with the MTT side chain, leading to flushing, nausea, thirst, palpitations, chest pain, vertigo, and in some cases, death

Carbapenems

• Mechanism of action is similar to other β-lactams
• Carbapenems inhibit cell wall synthesis and are bactericidal
• They are clinically useful against Pseudomonas aeruginosa (except ertapenem), gram-negative bacilli, most anaerobes, MSSA and Streptococcus species
• Adverse reactions include low incidence of adverse reactions and seizures in patients with decreased renal function

Monobactams (Aztreonam)

• Mechanism of action is similar to other β-lactams
• Monobactams are bactericidal
• The clinical uses include gram-negative aerobic bacilli
• Adverse reactions and precautions show it is well tolerated, with rare occurrences of rash or anaphylaxis

Aminoglycosides

• Examples include Gentamicin, Tobramycin, Netilmicin, and Amikacin
• Aminoglycosides inhibit RNA translation, destabilize the cell wall, and are bactericidal
• Clinically, it treats Nosocomial gram-negative infections (VAP)
• Adverse reactions include nephrotoxicity, ototoxicity, and rare neuromuscular blockade with rapid high-dose use

Clindamycin

• It inhibits protein synthesis and is bacteriostatic
• Clindamycin is active against gram-positive and anaerobic bacteria
• It has fairly significant activity against MRSA
• Adverse reactions and precautions include nausea, vomiting, and diarrhea

Vancomycin

• It prevents the formation of a rigid cell wall
• Vancomycin is bactericidal against gram-positive organisms but bacteriostatic against enterococci
• It is clinically useful against Methicillin-resistant S. aureus (MRSA) and an oral formulation is used to treat C. difficile
• Adverse reactions and precautions include Red man syndrome, ototoxicity, and nephrotoxicity

Antimycobacterials

• It is used against Mycobacterium tuberculosis
• One medication is Isoniazid (INH), which inhibits cell wall synthesis and is bactericidal
• Adverse reactions and precautions for INH include hepatotoxicity, neurotoxicity, nausea, loss of appetite, and abdominal pain

Antimycobacterials (Cont.)

• Rifampin and Rifabutin inhibit RNA polymerase
• They are bactericidal against actively dividing bacteria
• Adverse reactions and precautions include hepatotoxicity, rare instances of fever, chills, nausea, and vomiting
• Rifampin may cause bodily fluids to turn an orange color

Antifungals

• The number of fungal infections are increasing dramatically
• Polyenes (amphotericin B and nystatin) increase the permeability of the cell membrane
• They are clinically useful against Aspergillosis, blastomycosis, histoplasmosis, coccidioidomycosis, and cryptococcosis
• Adverse reactions and precautions include flushing, fever, chills (infusion related), and renal impairment

Antifungals (Cont.) - Azoles

• Azoles reduce ergosterol production and have a fungistatic effect
• They are clinically useful against Candidiasis (fluconazole)
• Adverse reactions and precautions include anorexia, nausea, and vomiting

Antifungals (Cont.) - Echinocandins

• Echinocandins inhibit fungal cell wall synthesis, and can be fungicidal or fungistatic depending on the isolate
• It is clinically useful against Candida and Aspergillus
• Adverse reactions and precautions include fever, rash, flushing, and thrombophlebitis

Antifungals (Cont.) - Flucytosine

• Flucytosine inhibits fungal RNA formation and has a fungistatic effect
• It is clinically useful against Candida, Cryptococcus, and Aspergillus
• Adverse reactions and precautions include bone marrow suppression

Antiviral Agents

• Acyclovir and Valacyclovir terminate viral replication
• It is clinically useful against the Herpesvirus family, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and Varicella-zoster virus (VZV)
• Adverse reactions and precautions include neuropathy and burning/irritation if used topically

Respiratory Care Assessment of Antibiotic Therapy

• Before treatment, assess the effectiveness of drug therapy based on indications
• During treatment and short term, consider susceptibility testing and patient assessment
• Long term, monitor response to therapy and consider combination of agents
• General contraindications state antibiotics should not be used unless a specific pathogen is known or suspected