tetracyclines, chloramphenicol, aminoglycosides

tetracycline mechanism of resistance

(Resistant organisms Contain active efflux system TC's cannot enter cells) Resistance is transmitted by plasmids Genes for TC, CAP & AMG linked together Plasmids transmit resistance to all three antibiotics (multiple drug resistance)

Prophylaxis for Traveler's diarrhea (Doxycycline)

Alternative agents for Traveler's diarrhea : ciprofloxacin & Norfloxacin (Fluoroquinolones)

adverse effects of tetracyclines

Damage of teeth, bone, nails Children < 8 years old Contraindicated in pregnancy Bone deformity, growth inhibition of fetus Suprainfection (or superinfection) caused due to use of broad spectrum antibiotics C. defficile toxin induced diarrhea Supra infection is treated with oral vancomycin (remember) or metronidazole

chloramphenicol (bacteriostatic)

First synthetic antibiotic Limited practical uses Other new effective drugs available Not recommended for use outside of a hospital (Cause pancytopenia: deficiency of all cell elements of the blood (aplastic anemia) -very rare) Death

tetracycilne chemistry

Formation of chelate complexes with Mg+2, Ca+2 & Al+3 can cause yellowish stain on teeth due to intense yellow color of these drugs, therefore it is not recommended with food or laxative

chloramphenicol adverse reaction

Gray Baby Syndrome Baby (premature, newborns) - ash gray color Symptoms of gray baby syndrome vomiting, poor feeding, vasomotor collapse, irregular respiration, death Cause of gray baby syndrome deficiency of hepatic conjugating enzyme glucuronyl transferase to metabolize chloramphenicol

aminoglycoside adverse effects

Hearing loss to fetus or newborn (given during pregnancy) Vestibular function progressive loss of vestibular organ of the ear vertigo & loss of balance VERY SERIOUS OTOTOXICITY Renal (nephrotoxic) due to: Increase serum creatinine level Reduced clearance of creatinine AMG accumulation in renal insufficiency dose adjustment necessary Neuromuscular blockade Potentiation by other drugs Ototoxicity: ethacrynic acid & furosemide Nephrotoxicity: ethacrynic acid, furosemide, cisplatin, polymixin

chloramphenicol adverse reaction

Hemolytic anemia (Could be life threatening) Low red blood cell counts G-6P-D deficient patients (Afro Americans),same as sulfonamides

chlormphenicol metabolism

Inactivated by hepatic conjugation to glucuronic acid

tetracycline (bacteriostatic)

Increased resistance of many organisms to the drugs Cause Suprainfection: use oral vancomycin or metronidazole to treat suprainfection Very toxic compared to Penicillins/Cephalosporins

aminoglycoside mechanism of action

Inhibit bacterial protein synthesis & Bactericidal Breakup of polysomes into monosomes Incapable of protein synthesis

chloramphenicol mechanism of action

Inhibitor of bacterial protein synthesis Binds to 50 S ribosome similar to erythromycin, clindamycin, other macrolides interfere with each other's action if given concurrently Inhibits peptidyl transferase

chloramphenicol therapeutic uses

It is very toxic. So use is restricted to life-threatening infection in which there is no alternatives (such as meningitis) It is used as possible drug of second choice only due to its toxic side effects

gentamycin use

Mainly employed for severe infections, often immunocompromised patient with bugs resistant to other antibiotics Active against Staph, coliforms, pseudomonas, proteus, Enterobacter, Klebsiella, Serratia, & other gram (-) rods

tetracycline drug of second choice for

Mycoplasma pneumonia (it is DOC also; erythromycin, a macrolide is often DOC for non-pregnant and pregnant persons)

chloramphenicol mechanism of resistance

Only bacteria produce the enzyme chloramphenicol acetyl transferase (CAT) Acetylates chloramphenicol inactive

aminoglycoside mechanism of resistance

Plasmid dependent resistance Production of adenylating, phosphorylating, acetylating enzymes to destroy drugs

tetracycline mechanism of action

Protein synthesis inhibitor Binds to 30S subunit of bacterial ribosome Blocks the binding of aminoacyl t-RNA Inhibits the addition of new amino acids to the growing peptide chain (Sensitive bacteria have TC uptake system only and thus concentrate TC's Mammalian cells & resistant bacteria have both TC uptake & efflux systems) Cannot concentrate TC's Bacteriostatic agents

clinical use of aminoglycosides

Used in combination with b-lactams, synergistic, extends spectrum to gram (+) Pseudomonas aeruginosa In combination with antipseudomonal penicillin, piperacillin or ticarcillin Enterococcal endocarditis (use PenG +aminoglycoside) c

aminoglycosides (bactericidal)

Very toxic. Reserved for serious infections Effective against aerobic gram negative bacteria only Nephrotoxic Ototoxic auditory damage (hearing loss) vestibular damage (imbalance) Given with a penicillin or a cephalosporin to produce synergistic effect. Very rarely used alone because aminoglycoside is very toxic.

(gentamicin, tobramycin, amikacin) use and adverse effect

broadest spectrum, most widely used aminoglycosides no allergy, vestibular dysfunction, hearing loss

netilmicin use and adverse effect

less ototoxic than than other, similar to amikacin (preferred prolong use)

neomycin use and adverse effect

limited topical use most toxic highest amount of hearing loss curare-like block

streptomycin use and adverse effect

oldest and best studied, used only in treatment of endocarditis caused by enterococci and viridans group and for TB interferes with vestibular function

streptomycin clinical use

second line drug for TB

common aminoglycosides

streptomycin, (gentamicin, tobramycin, amikacin), neomycin, netilmicin

clinical uses for tetracyclines

very broad spectrum drug of choice for Rickettsia, chlamydia, vibrio cholera, plague, Lyme disease, gastric and duodenal ulcer disease caused by H.pylori, and protozoa (amoebae with iodoquinol) Gastric and duodenal ulcer disease (PUD) caused by H.pylori: Preferred treatment is (proton pump inhibitor + amoxicillin + clarithomycin)