Tetracyclines (Edelstein lecture) Flashcards
1st generation
Tetracycline (not easily tolerated)
2nd generation
Doxycycline
Minocycline
3rd generation
Tigecycline (overcomes efflux pumps due to glycine residue, bit poorly tolerated because its very large)
Omadacycline
Eravacycline (also has a glycine residue)
Which organisms are INTRINSINCLY RESISTANT to tetracyclines due to EFFLUX PUMPS?
P. aeruginosa
Morganella
Providencia
Proteus
What type of infections for Tetracyclines covers?
Usually broad Sprectrum
Staph (+MRSA)
Strep
E. faecalis
Acinetobacter
B. anthracis
Yersenia pestis
L. monocytogenes
NTM (Mino, Doxy, Omada, Tigecycline)
DOXYCYCLINE (2nd gen): Susceptibility usually NOT performed
Fastidious and intracellular organisms without cells:
Rickettsia
Erlichia/Anaplasma
Mycoplasma
Borrelia burgdorferi
Coxiella burnetii
Franciesella tularensis
Brucella spp.
Plasmodium spp. (may be used as prophylaxis)
C. acnes
Chlamydia
Legionella
How do tetracyclines work?
Bind to the 30S ribosomal subunit and prevent tRNA from binding to the A site for translation to occur
Bacteriostatic
What are the 2 major resistance mechanisms and a rare cause of resistance?
Efflux Pumps
and
Ribosomal protection protein
Rare:
Ribosomal modifications (point mutations in binding sites of tRNA; copy numbers)
What organisms are likely to have high level resistance (higher resistant populations) due to ribosomal modifications and why?
C. acnes (low number of mutated ribosomes required to become resistant, ~2 copies)
H. pylori (1-2 copies)
Mycobacteria (1-2 copies)
S. pneumoniae - 4 copies
E. coli-low level resistance because have more copies (7) multiple copies rescue mutations
Which efflux pumps are present in Gram negative vs positives?
G+ : Tet (K) and Tet (L) pump out 1st generation (high MIC), but not 2nd gen
G- : Tet (A) and Tet (B) pump out 1st and 2nd gen (high MIC), only pump out 3rd gen if the pumps are overexpressed
Pump out of cytoplasm and may be present with decreased porins (decrease entry)
Name some of the ribosomal protection proteins and their mechanism
Tet (M) - bacterial protein that affects binding of tetracycline and ribosome (targets 1st and 2nd gen, BUT NOT 3rd gen because Tigecycline has the glycine group that prevent displacement)
Tet (X) - Ribosomal modifications (point mutations in binding sites of tRNA) “tetracycline destructase” Common in E. coli isolated from pigs in China, due to high administration of tetracyclines
Important factors to consider when testing Tetracycline resistance in the laboratory
Divalent cations are required for the uptake of tetracycline by the bacteria BUT too many cations (Mg) inhibit uptake and too little prevent the uptake
Complex media may give false resistance and old media may also cause false results. E-test most suitable for Tigecycline
Side effects of long exposure to Tetracycline
Teeth discoloration
Photosensativity (easily sunburned)
