Thread by @DrH_flu

Mandell ch. 26:
Doxycycline acts on 70S ribosomes in mitochondria (in addition to 30S bacterial ribosomes), which gives it activity against protozoa and Plasmodium
1/13
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We all know doxy (and tetra's in general) have awesome spectra of activity, but here's some factoids:

🔹They can be used for all Vibro spp.

🔹Listeria is only intermediately susceptible to doxy with larger inocula

🔹Minocycline has better activity against Acinetobacter
2/13

🔹For Lyme, MICs are actually lower to tetra than doxy

🔹M. hominis is usually susc; M.genitalium usually R to doxy

🔹Mino is best in class for Nocardia

🔹Myco species each vary in susc to each drug. There may be a role for doxy in MDR-TB!
3/13

🔹A recent study was promising for doxy x7 days for reduction of mortality in dengue hemorrhagic fever

🔹Interest in mino for MDR Gm- infections, has succeeded for MDR Acinetobacter, CR-K. pneumo, and Steno
4/13

Tetra is the class representative for MIC testing, but in some cases, doxy or mino might be susc or intermediate when tetra is R, so ask for add'l testing if you might want to use doxy/mino

Most common mech's of resistance are efflux pumps and ribosomal protection proteins
5/13

Tigecycline is derived from mino, with an extra moiety that circumvents the 2 main mech's of resistance (see above) by stronger binding to the ribosomes

It is active against a broad range of resistant aerobic & anaerobic 🦠 but *not* Pseudomonas or some of the SPACE-M 🦠
6/12

Tige is active against Acinetobacter, Steno, and rapidly growing NTM (but not other NTM or TB).

So far I've mostly seen it used for VRE resistant to dapto when linezolid is contraindicated, usually in transplant pts. When has everyone else used it?
7/13

Tigecycline has an FDA boxed warning for increased risk of death based on pooled analysis from 13 trials, but on closer inspection, most of the risk was from the HAP trial, esp VAP pts with bacteremia
8/13

New derivatives of tige: eravacycline (IV) and omadacycline (IV and PO). Similar spectrum to tige, and omadacycline may have the trend toward ⬆️ mortality in the CAP trial
9/13

Chloramphenicol is active against wide range of 🦠 including anaerobes, intracellular, cell wall-less, spirochetes, etc

Exceptions include Pseudomonas, Acinetobacter, and mycobacteria

It is active against most MRSA, VISA/VRSA, and VRE
10/13

It had been shown to be synergistic with colistin against NDM-producing K. pneumo

Oddly, chloramphenicol has better bioavailability by PO than IV (due to hepatic metabolism of IV form, succinate)

PO form available without Rx in many parts of the world
11/13

Chloramphenicol also has almost the best CNS & eye penetration of all abx..
So it is still used (single IM dose) for empiric tx of meningitis in some areas where 3rd gen cephs not available

However, it may fail against resistant H. flu B and PCN-resistant S. pneumo
12/13

Chloramphenicol causes:
1️⃣ Bone marrow suppression due to effects on human 70S ribosome. Dose dependent (serum level >25), reversible

2️⃣ Aplastic anemia, possibly related to toxic metabolites, usually appears after end of tx, extremely rare, irreversible, >50% fatal
13/13