First generation cephalosporins, including cefazolin, are active against most gram-positive cocci except for enterococci, oxacillin-resistant staphylococci, and penicillin-resistant pneumococci. They are also active against most strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.
The second generation cephalosporins include two subgroups. One subgroup has activity against Haemophilus influenzae and Moraxella catarrhalis. The other subgroup consists of the cephamycins, which are active against many strains of Bacteroides．
Third generation cephalosporins have less activity against most gram-positive organisms than first generation agents but are highly active against Enterobacteriaceae, Neisseria, and H. influenzae. Ceftazidime and cefoperazone are also active against Pseudomonas aeruginosa.
The fourth generation cefepime has similar activity as the third generation cephalosporins, including against P. aeruginosa, with the addition of greater activity against enteric gram-negative rods that have an inducible chromosomal beta-lactamase.
The fifth generation cephalosporins have activity against oxacillin-resistant staphylococci, penicillin-resistant pneumococci, and enteric gram-negative rods.
Oral cephalosporins are also divided into different generations and their spectra of activity generally mirror those parenteral agents of the corresponding generation. However, oral third generation drugs are less active against enteric gram-negative bacteria than the parenteral third generation cephalosporins. Second and third generation oral cephalosporins have similar indications, namely otitis media, respiratory tract infections, and urinary tract infections.
Many of the available parenteral cephalosporins have short serum half-lives and require frequent administration. All of the cephalosporins except cefoperazone and ceftriaxone require dose modification in the presence of severe renal failure．
All of the cephalosporins achieve therapeutic levels in pleural, pericardial, peritoneal, and synovial fluids, and urine.
First and second generation cephalosporins enter into cerebrospinal fluid poorly.
Third generation cephalosporins achieve more reliable cerebrospinal fluid levels in patients with meningeal irritation.
Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. - PubMed - NCBI
A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. - PubMed - NCBI
Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. - PubMed - NCBI