Overview of Antimicro- Waller Flashcards
Top 5 drugs:
Amoxicillin Azithromycin Amoxicillin-clavulanic acid Trimethoprim-sulfamethoxazole Ciprofloxacin
antibiotic Misuse may occur in a variety of ways:
Given when not needed
Continued when no longer necessary
Given at the wrong dose
Broad spectrum agents used for very susceptible bacteria
The wrong antibiotic given to treat infection
inappropriate prescribing
Over 50% of antibiotic prescribing may be inappropriate Most of this inappropriate use is for: Acute respiratory infections Pharyngitis Sinusitis Bronchitis
Antibiotics are a common cause of ADE-related ED visits, accounting for:
7 of top 15 drugs in pediatric patients ADE-ED visits
1 of 5 ADE-related visits to ED in adults
A 37 y/o female with poorly controlled type 1 diabetes and end-stage renal disease, on hemodialysis, presents to the ED with 3-day history of dyspnea, cough with purulent sputum production, and intermittent fever.
She recently completed a course of meropenem for catheter-associated blood-stream infection 2 weeks ago.
Physical and laboratory findings are consistent with pneumonia. She is admitted to the hospital.
Questions to ask yourself about anti-microbial therapyp
Ask yourself whether an antimicrobial agent is warranted:
Is an antimicrobial indicated based on clinical findings? yes
Have appropriate cultures been obtained?
What is the most likely causative organism?-
What must be done to prevent secondary exposure?- not likely to have a 2ndary exposure in this case,
Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?- yes, esp. for pneumonia
A 37 y/o female with a history of end-stage renal disease, on dialysis, is admitted to the hospital with pneumonia. Antibiotics are initiated to cover the most likely pathogen(s).
Types & Goals of Therapy?
Empiric therapy; we suspect common organisms
A 68 y/o male presents for a total hip replacement. Prior to surgery, he is given one dose of cefazolin to prevent development of a surgical wound infection.
Types & Goals of Therapy?
Prophylaxis
A 37 y/o female with a history of end-stage renal disease, on dialysis, is admitted to the hospital with pneumonia. Cultures result with sensitive Pseudomonas, vancomycin (mostly for gram positive) discontinued.
Types & Goals of Therapy?
Definitive therapy
An 8 y/o male presents to the ED with a perforated appendix. Antibiotics are initiated pre-operatively to reduce risk of intra-abdominal abscess & wound infection.
Types & Goals of Therapy?
pre-emptive; this patient already has appendicitis
to prevent abdominal abscess
A 75 y/o male presents for follow-up of prosthetic hip joint infection. He receives continued, low dose antimicrobial therapy as hip prosthesis was unable to be removed.
Types & Goals of Therapy?
Suppressive
Most valuable, time tested method for immediate ID of bacteria =
gram stain
gram positive vs negative
neg- 2 cell membranes, LPS endotoxin
pos- thicker peptidoglycan layer, teichoic acid stabilizes peptidoglycan layer (rigid, provides structural shape)
beta lactamase
an important resistance mechanism against beta lactam antibiotics
Susceptibility Testing
Susceptible
- Likely to inhibit pathogenic microorganism
Intermediate
- May be effective at higher dosage, more frequent administration, or in specific body site
Resistant
- Not effective at inhibiting growth of microorganism
Types of Susceptibility Tests:
Dilution Tests
Disk Diffusion
Gradient Diffusion
Minimum inhibitory concentration (MIC)
lowest concentration of drug required to inhibit growth
Breakpoints established by Clinical and Laboratory Standards Institute (CLSI)
Antibacterial Spectrum
Narrow-spectrum
- Act on a single or a limited group of microorganisms
Extended-spectrum
- Active against gram-positive bacteria but also against significant number of gram-negative bacteria
Broad-spectrum
- Act on a wide variety of bacterial species, including both gram-positive and gram-negative
Bacteriostatic vs. Bactericidal
Bacteriostatic: arrests growth and replication of bacteria (limits spread of infection)
Bactericidal: kills bacterial
- Concentration-dependent killing: rate and extent of killing increase with increasing drug concentrations
- Time-dependent killing: activity continues as long as serum concentration above minimum bactericidal concentration
This concept is relative
Certain drugs are –cidal against specific bacteria while –static against others
Drug-drug enhancement or synergism
Gentamicin – ineffective against enterococci in the absence of a cell-wall inhibitor
Combining penicillin with gentamicin leads to bactericidal activity
Antimicrobial Classification
Antimicrobials classified based on:
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure
Sites of Antibacterial Action
Cell wall synthesis Cell membrane synthesis Protein synthesis Nucleic acid metabolism Function of topoisomerases Folate synthesis
β-Lactams- MOA, list, resistance
cell wall inhibitors
Penicillins
Cephalosporins
Monobactam
Carbapenems
Time-dependent; structural analogs of D-Ala-D-Ala; covalently bind penicillin-binding proteins (PBPs), inhibit the last transpeptidation step in cell wall synthesis
Structural difference in PBPs
Decreased PBP affinity
Inability for drug to reach site of action (i.e. gram-negative organisms)
Active efflux pumps
Drug destruction/inactivation by B-lactamases
β-Lactamase Inhibitors
Amoxicillin + clavulanic acid,
ticarcillin + clavulanic acid,
ampicillin + sulbactam,
piperacillin + tazobactam
MOA: prevent destruction of B-lactam antibiotics
Fluoroquinolone Mechanism of Action
Concentration-dependent, targets bacterial DNA gyrase & topoisomerase IV. Prevents relaxation of positive supercoils
Inhibitors of Protein Synthesis- areas of action
Formation of initiation complex
Amino-acid incorporation
Formation of peptide bond
Translocation
Aminoglycosides MOA
blocks initiation of protein synthesis
blocks further translation and elicits premature termination
incorporation of incorrect amino acid
Bind 30S subunit
Tetracyclines MOA
Bind 30S subunit
