antimicrobials- Flashcards
Chemical substances produced by microorganisms with the capacity to inhibit
(bacteriostatic) or kill (bactericidal) other microorganisms.
antibiotics/antimicrobials
produce amphotericin B
streptomyces nodosus
produce Nystatin
Streptomyces noursei
produce Chloramphenicol
Streptomyces venezuelae
produce Bacitracin
Bacillus subtilis
produce Polymyxin
Bacillus polymyxa
produce Cephalosporins
Cephalosporium
produce Gentamicin
Micromonospora purpurea
produce Penicillin
Penicillium notatum
produce Erythromycin
Streptomyces erythraeus
produce Neomycin
Streptomyces fradiae
effective against a limited number of pathogens.
narrow spectrum
example of narrow-spectrum
Bacitracin, clindamycin, erythromycin, gentamicin, penicillin and
Vancomycin
destroy different kinds of organisms.
broad spectrum
example of broad spectrum
Ampicillin, cephalosporins, chloramphenicol, ciprofloxacin, rifampicin,
trimethoprim and tetracycline.
drugs produced by bacteria or fungi.
natural drugs such as Erythromycin, amphotericin B, vancomycin, tetracycline, penicillin
modified drugs with added chemical groups.
semi-synthetic drugs such as Ampicillin, carbenicillin and methicillin.
a chemically-produced drugs
synthetic drugs such as Sulfonamides, trimethoprim, ciprofloxacin, isoniazid.
inhibit the bacterial growth but generally they do not kill the microorganisms.
Bacteriostatic agents such as Chloramphenicol, erythromycin, clindamycin
usually kill or destroy organisms and are used for the treatment of life-threatening infections.
bactericidal agents such as:
Aminoglycosides ( gentamicin,amikacin & streptomycin)
β-lactams ( ceftriaxone, imepenem, penicillin & cefotaxime)
Glycopeptides ( isoniazid, quinolones, bacitracin and metronidazole)
Characteristics of Antimicrobial agents
- Must be in an active form.
- Must able to achieve concentration at the site of infection that is higher than the
pathogen’s MIC to be effective. - Must have “selective toxicity”.
are genetic elements that are capable of integrating genes(cassettes) by an integrin
encoded site-specific recombinase.
integrons
lowest concentration of a drug that can still
inhibit bacterial growth.
Minimal-inhibitory concentration (MIC)
the lowest concentration of a drug that can kill bacteria.
Minimal lethal concentration
are enzymes (transpeptidase or transglycolase) that mediate
peptidoglycan cross-linking with reduced affinity for B-lactam antibiotics.
Penicillin-binding proteins
the ratio of the toxic dose to the therapeutic dose and as such, the higher the
therapeutic index, the more effective the chemotherapeutic agent.
therapeutic index
DNA elements that encode transposition and excision functions and which are also
able to carry antibiotic resistance genes among plasmids and chromosomes
transposons
most selective antibiotics with a high therapeutic index. Inhibits the transpeptidase enzymes in which cell growth stops and the death of the cells occurs.
cell wall inhibitors
inhibits the synthesis of peptidoglycan precursors
bacitracin
inhibits transpeptidation
β-lactams
acts on growing cells & can either be a bactericidal or bacteriostatic agent
isoniazid
inhibits the translocation and elongation of peptidoglycan.
vancomycin
binds with a 30S subunit that result in the misreading
of mRNA and 50S subunit that results in the inhibition of peptidyl transferase and peptide
chain elongation.
protein synthesis inhibitors such as
Tetracycline, aminoglycosides (30S)
Erythromycin,chloramphenicol & clindamycin ( 50S)
Linezolid – blocks the initial step in protein synthesis.
nucleic acid inhibitors
rifampicin, quinolones, metronidazole
inhibits RNA polymerase
Rifampicin
interferes with DNA gyrase and topoisomerase IV and highly effective for enteric bacteria.
Quinolones
disrupts DNA and is effective against anaerobic bacteria.
Metronidazole
cell membrane inhibitors
Polymyxin B and E – Gram- negative bacteria (P.aeuruginosa) also used as a topical
antibiotic.
Essential metabolite inhibitors
SMZ, Dapsone, Trimethoprin
inhibits folic acid and metabolism and has a higher
therapeutic index.
Sulfamethoxazole (SMZ)
interferes with folic acid synthesis
Dapsone
blocks the tetrahydrofale synthesis
Trimethoprim
Result of both the use and overuse of antimicrobial agents and may arise within antibiotic-producing microorganism (autotoxicity)
Antibiotic Resistance
2 types of A.R
Intrinsic Resistance and Acquired Resistance
Result of the biochemical make up of wild type of organism.
Depends on the hydrophobic or hydrophilic nature of the antibiotic and on the
impermeability of the cell wall to the antibiotic
Passed vertically into new cell.
Intrinsic Resistance
All Gram-negative bacteria mediate this type of resistance through the inactivation of
penicillin
intrinsic resistance
enzymes that chemically inactivate β-lactam drugs by disrupting β-lactam ring component of the molecule.
B-lactamases
clinically important B-lactamases
Class A enzymes - plasmids found
Class C enzymes - chromosomally localed and inducible by exposure to β-lactams.
structurally similar with the β-lactam antibiotics and functions as
a substrate, thus reducing their harmful effects on the β-lactam antibiotics.
Β-lactamase Inhibitors
Present only on a certain isolates that are different from the parental strains and usually expressed as a modification of target sites or enzymatic modification of antibiotics.
Acquired Resistance
ex. of Acquired Resistance
Chromosomal mutations (transformation and recombination)
