Antibiotics II

AMINOGLYCOSIDES
"Mean" GNATS canNOT kill anaerobes.

"Mean" = aminoglycosides. Bacteriocidal. Block formation of initiation complex, causing misreading of mRNA. Require oxygen for uptake, so ineffective against anaerobes.
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin.
Nephrotoxicity (esp with cephalosporins), Otoxicity (esp with furosemide, ethacrynic acid, and cisplatin: "lisp"), Teratogenic. Most toxic antibiotic in common use -- must monitor blood levels.
Use: severe gram negative infections, synergistic with beta-lactam antibiotics. Neomycin for bowel surgery. Good for enterococcal endocarditis. Good for Pseudomonas.

MACROLIDES
Erythromycin, Azithromycin, Clarithromycin.
Mechanism: Inhibit protein synthesis by binding 23S rRNA of 50S subunit (large bacterial subunit). Bacteriostatic. Cross-resistance since all drugs bind at same site.
Clinical use: URIs, pneumonias, STIs. GPC (esp strep if patient allergic to penicillin), Campylobacter, Helicobacter, atypical pneumonial agents (Mycoplasma, Legionella, Chlamydia; latter two since achieves high intracellular concentration).
Toxicity: Erythromycin prolongs QT interval (not good idea to use orally anymore). Telithromycin has severe liver toxicity. Oral bioavailability of azithromycin and clarithromycin is better, so lower dose and not as GI toxic as erythromycin, which causes GI discomfort (most common cause of noncompliance). Cholestatic jaundice. Eosinophilia, skin rashes. Inhibits P450, so increases serum concentration of theophyllines and oral anticoagulants. Exception:

Azithromycin has no P450 interactions, is the macrolide of choice. Mostly metabolized by liver. Since gets into cells so well, large volume of distribution, long half life. Typical uses: strep throat, pertussis and meningoccus carraige, chlamydia and chanchroid, shigella in kids.

Clarithromycin. Similar side effects to erythromycin (P450 etc) but better absorbed. For atypical Mycobacterium infection (Mycobacterium avium) and H pylori.

CLINDAMYCIN
Mechanism: Blocks peptide bond formation at 50S ribosome subunit. Bacteriostatic. (As opposed to Cephalosporin; Similar to Chloramphenicol). Cross-resistance with macrolides. Resistance has discouraged use.
Clinical use: Anaerobes above the diaphragm (Bacteroides fragilis, Clostridium perfringens).
Pharm: Prodrug. Liver-excreted.
Toxicity: Can cause pseudomembranous colitis from C. difficiles overgrowth. Fever, diarrhea.

TETRACYCLINES
Tetracycline, doxycycline, minocycline, democlocyline.
Mechanism: Binds 30S, blocks tRNA binding. Bacteriostatic. Limited CNS penetration. Don't give with milk, antacids, iron or anything with divalent cations because it inhibits absorption in gut. Doxycycline is fecally eliminated can be used in patients with renal failure. Demeclocycline -- acts as a Diuretic, blocks ADH receptors, used in SIADH.

VACUUM THe BedRoom
Vibrio cholera
Acne
Chlamydia
Ureaplasma Urealyticum
Mycoplasma pneumoniae
Tularemia
H. pylori
Borrelia burgdorferi (Lyme disease)
Rickettsia

Toxicity: GI distress, discoloration of teeth, inhibition of bone growth in children, photosensitivity --> rash. Contraindicated in children. Crosses placenta, contraindicated in pregnancy.

Tigecycline: new tetracycline that is not effluxed by drug pump, common way to be resistant to doxycycline and minocycline.

None of the tetracyclines used for Pseudomonas, Proteus, Acinetobacter, MRSA.

LINEZOLID
For Gram+ (esp Vancomycin-resistant enterococcus, and also MRSA/all kinds of Staph) and mycobacterium.
Well absorbed orally, large volume of distribution, long half life (b.i.d). Basically a Vanc alternative that can be given orally. Still use Vanc only though for C. difficiles colitis.
Toxicity: Serotonin syndrome (linezolid is mild MAO inhibitor); mitochondrial toxin (peripheral neuropathy, pancreatitis, pancytopenia, etc.)

SYNERCID
Designed to use for VRE and MRSA. Difficult to use: IV, drug interactions, muscle problems. Usually would go with Vanc for MRSA and Linezolid for VRE.