Chapter 10: Antimicrobial Treatment Flashcards
Postantibiotic Era
Point in time where the drugs we currently have are no longer effective
Goal of antimicrobial Chemotherapy
administer a drug to an infected person that destroys the infective agent without harming the host’s cells
A drug must be able to…(3)
(1) be easy to administer and able to reach the infectious agent anywhere in the body; (2) be absolutely toxic to the infectious agent and absolutely nontoxic to the host; (3) remain in the body as long as needed and be safely and easily broken down and excreted
Why do bacteria and fungi produce antibiotics in nature?
to inhibit the growth of competing microbes in the same habitat
Genera of bacteria antibiotics are derived from
Streptomyces and Bacillus
Genera of molds antibiotics are derived from
Penicillium and Cephalosporium
3 factors that must be known before beginning antimicrobial therapy
(1) the nature of the microorganism causing the infection; (2) the degree of the microorganism’s susceptibility (or sensitivity) to various drugs; (3) the overall medical condition of the patient
Sources from which specimens can be obtained from the patient (3)
body fluids, sputum, stool
How would you treat a sore throat caused by Streptococcus pyogenes?
Penicillin
The two bacterium responsible for meningitis in children.
Streptococcus pneumoniae (most common) and Neisseria meningitidis
Bacteria that commonly show resistance to drugs (5)
Staphylococcus species, Neisseria gonorrhoeae, Streptococcus pneumoniae, Enterococcus faecalis, and aerobic gram-negative enteric bacilli
When is testing for drug susceptibility unnecessary? (2)
(1) fungal and protozoan infections; (2) If that patient is allergic to certain antibiotics (duh)
Kirby-Bauer Technique
(1) surface of an agar plate is spread with bacteria; (2) small discs containing a prepared amount of antibiotic are placed on the plate; (3) zone of inhibition surrounding the discs is measured and compared with a standard for each drug; (4) antibiogram provides data for drug selection
Tube Dilution Tests
A more sensitive and quantitative test than the Kirby-Bauer Technique that involves diluting antimicrobial solutions serially in tubes of broth; each tube is inoculated with pure culture
Minimum Inhibitory Concentration (MIC)
the smallest concentration (highest dilution) of drug that visibly inhibits growth
Purpose of tube dilution tests
useful in determining the effective dosage and providing a comparative index against other antimicrobials
Factors that contribute to the failure of a drug (3)
(1) the inability of the drug to diffuse into that body compartment (brain, joints, skin); (2) resistant microbes in the infection that didn’t make it into the sample collected for testing; (3) an infection caused by more than one pathogen (mixed), some of which are resistant to the drug
Therapeutic Index
the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective (therapeutic) dose (dose required Vs minimum impact); the smaller the ratio, the greater the potential for drug reactions; the drug with the highest therapeutic index has the widest margin of safety
TI = 1.1
Risky choice on the therapeutic index
TI = 10
Safer choice on the therapeutic index
Factors that a physician must check for in a patient history before prescribing antibiotics (7)
(1) preexisting conditions that might influence the activity of the drug; (2) history of allergy to a certain class of drugs; (3) underlying liver or kidney disease; (4) infants, the elderly, and pregnant women require special precautions; (5) intake of other drugs can result in increased toxicity or failure of one or more drugs; (6) genetic or metabolic abnormalities; (7) site of infection, route of administration, cost
Goal of antimicrobial drugs (5)
(1) DISRUPT; (2) INHIBIT; (3) INTERFERE; (4) DESTROY; (5) SELECTIVELY TOXIC
DISRUPT…
cell processes or structures of bacteria, fungi, or protozoa
INHIBIT…
virus replication
INTERFERE…
with the function of enzymes required to synthesize or assemble macromolecules
DESTROY…
structures already formed in the cell
SELECTIVELY TOXIC…
kill or inhibit the actions or synthesis of molecules in microorganisms but not vertebrate cells
Drugs with excellent selective toxicity…
block the synthesis of the bacterial cell wall (penicillins); human cells lack the chemical peptidoglycan and are therefore unaffected by the drug
Goals of Chemotherapy
identifying structural and metabolic needs of a living cell and removing, disrupting, or interfering with these requirements
Antimicrobial Drug Categories (5)
(1) inhibition of cell wall synthesis; (2) inhibition of nucleic acid structure and function; (3) inhibition of protein synthesis; (4) interference with cell membrane structure and function; (5) inhibition of folic acid (vitamin B) synthesis for several metabolic functions in the body
Primary Sites of Action of Antimicrobial Drugs on Bacterial Cells (5)
(1) Protein synthesis inhibitors on ribosomes; (2) Folic acid synthesis in cytoplasm; (3) DNA/RNA; (4) Cell membrane; (5) Cell wall inhibitors
Broad-Spectrum Drugs
effective against more than one group of bacteria; tetracycline antibiotics
Narrow-Spectrum Drugs
target a specific group; polymyxin
DNase
Helps penetrate biofilms
Why are drugs that are toxic to fungi also toxic to human cells?
Similarities between the two cells means the drug cannot be selectively toxic
Quinine
principal treatment of malaria for hundreds of years
Replacements of Quinine
synthesized quinolones, chloroquine and primaquine
Why are viral infections difficult to treat?
disrupting viral metabolism requires disruption of cellular metabolism
Drug resistance
an adaptive response in which microorganisms begin to tolerate an amount of drug that would normally be inhibitory; due to the genetic versatility and adaptability of microbial populations; can be intrinsic as well as acquired
Microbes become newly resistant to a drug after one of the following occurs…
(1) SPONTANEOUS MUTATIONS in critical chromosomal genes; (2) ACQUISITION OF ENTIRE NEW GENES or sets of genes via horizontal transfer from another species
Resistance (R) Factors
Plasmids containing antibiotic resistance genes; present BEFORE exposed to antibiotics; can transfer through conjugation or transformation
Probiotics
preparations of live microorganisms fed to animals and humans to improve intestinal biota
Prebiotics
nutrients that encourage the growth of beneficial microbes
Fructan
Encourages the growth of Bifidobacterium
Superinfection
microbes that were once small in number overgrow when normal resident biota are destroyed by broad-spectrum antimicrobials
Overgrowth of this bacteria causes yeast infection or oral thrush
Candida albicans
Overgrowth of this bacteria invades the intestinal lining and releases toxins that cause diarrhea, fever, and abdominal pain
Clostridium difficile
