CHAPTER 28: ANTIMICROBIAL THERAPY Flashcards
Selective Toxicity
antimicrobial drugs ability to kill invading microorganism “WITHOUT” cells of the host
Factors when selecting antimicrobial agent
- microorg identity
- microorg susceptibility to a particular agent
- site of infecton
- patient factors
- safety of the agent
- cost of therapy
- Identifying Infectious Organism
- lab analysis (gram stain) to identify susceptibility and pick correct therapy
Identifying Infectious Organism: Empiric therapy
- therapy initiated before knowing the microorg
- timing is critical
- drug selected based on association of microorg in a given clinical setting and PTs history
BROAD SPECTRUM CHOSEN FIRST
- Determination of Antimicrobial Susceptibility
- bacteriostatic vs bactericidal
bacteriostatic drugs: stop growth and replication at drug levels achievable in PT
bactericidal drugs: KILL within 18-24 hrs of incubation
- Determination of Antimicrobial Susceptibility
- MIC vs MBC
MIC: minimum inhibitory conc
- lowest antimicrobial conc that presents visible growth of org after 24 hrs incubation
MBC: minimum bacteridical conc
- lowest conc of antimicrobial agent that results in 99.9% decline in colony count after overnight incubation
- Site of Infection
- natural barrier to drug delivery (prostate, placenta, CNS, vitreous eye humor)
limiting factors for BBB penetration
- lipid solubility
- size of drug
- protein binding of drug
- susceptibility to transporters or efflux pumps
PT Factors
- immune system: alcoholism, diabetes, HIV infec, autoimmune disease, pregnancy
- renal dysfunc: check creatinine levels
- hepatic dysfunc: impact drug metab
- poor perfusion: drug doesn’t reach infected areas
- age: newborn/young/elderly PT
- pregnancy/lactation: cross placenta and found in milk
- multdrug resistant org
- Safety of the Agent
- least and most toxic?
- toxicity
least toxic: penicillin
most toxic: chloramphenicol (for life-threatening infections)
3 properties that influence dosing
- concentration dep killing: significant inc in rate of bacterial killing as conc of antibiotic inc
- time dep killing: clinical efficacy dep on percentage of time blood conc of a drug remains above MIC
- post-antibiotic effect (PAE): suppression of microbial growth that occurs after antibiotic level fall BELOW the MIC
chemotherapeutic spectra: 3 types of antibiotic spectrums
narrow spectrum: act on single/limited group of microorg
extended-spectrum: act against gram pos and gram neg microorg
broad spectrum: act on wide variety of microbial species
drug resistance: 2 types
- how are bacteria considered resistant
resistant to antibiotic if MAX level of antibiotic that can be tolerated by the host does NOT halt growth
- DNA can undergo spontaneous mutation
- natural/intrinsic resistance
- acquired resistance
Natural/Intrinsic Resistance
- antimicrobial drugs act on specific enzyme system or bio process
- many microorg not affected by these drugs bc they LACK that particular system
Acquired Resistance
microbial species responsive to a particular drug may develop more virulent or resistant strains
- strains can become resistant to more than 1 antibiotic
