c. These agents are widely distributed to most body tissues and fluids with
maximum concentrations in the liver and kidneys. Penetration of the CSF is
accomplished only by moxalactam that penetrates with or without inflamed meninges.
Therapeutic blood levels are reached in bone with the use of cephradine, cefamandole,
and cefazolin. Cefazolin levels are even higher in inflamed bone tissue.
d. Metabolism does occur with some agents, but their metabolic byproducts
show less antibacterial activity. The kidneys through glomerular filtration and tibular
secretion excrete all of the cephalosporins.
e. Because of the many products available, it is best to check the appropriate
literature for dosage information. Depending on the agent's characteristics and route of
administration, the dose may vary from 500mg to 12g per day.
f. First generation agents.
(1) The prototype of first generation cephalosporins is cephalothin (Keflin).
These agents are effective against gram-positive and a large number of gram negative
organisms. Gram-positive bacteria include Group A strep pyrogenes, beta-lactamase
producing and non-producing staph aureus, clostridium perfringens, and many other
streptococcal infections. Examples of gram-negative include N. gonorrhea, Salmonella,
most Shigella and Proteus, 75 percent of E. coli, 50 percent of H. influenzae, and all
strains of Klesbiella.
(2) Hypersensitivity is the most common adverse reaction of these agents,
especially in patients with demonstrated immediate allergic reaction to penicillin. A rash
may develop after several days of therapy and may or may not be accompanied by
fever or eosinophilia. High doses of first generation agents will cause a positive
Coombs' reaction, but hemolysis seldom occurs. High doses may also cause
nephrotoxicity, especially in elderly patients. Administering these agents intravenously
can cause thrombophlebitis, and IM injections are painful.
(3) With first generation cephalosporin therapy, all patients should be
monitored for superinfection, and elderly patients should have their renal functions
The first generation cephalosporin preparations are:
Cephradine (Velosef, Anspor).