b-Lactam-Antibiotics

Penicillins

spectrum of activity and in potency against

Penicillins are classified mainly according to the

Gram-negative bacilli.34

The first group

cephalosporin cephalexin

different chemical structures of the substituents

harbors the phenylglycine side chain that is also

at position 6 of the b-lactam molecule.

encountered in the aminopenicillins.Cephalexin

Penicillin G is primarily active against Gram

is primarily active

against staphylococci, but

positive pathogens, if no resistance mechanisms

less active against many Gram-negative bacte-

have been acquired.31

ria, because it is hydrolyzed by their b-lactama-

The aminopenicillins ampicillin and amoxi-

ses. The bioavailability of cephalexin is about

cillin feature the amino group, which confers

90%, and the renal excretion is about 90%

stability against amidase, an enzyme produced

either.35 First group cephalosporins should how-

by some Gram-negative bacteria that hydrolyzes

ever not be used for the treatment of UTI, but

the penicillin side chain, and stability against

only for prophylaxis,because of the overall lower

gastric acid. Oral absorption

of ampicillin

is

activities compared with second group cepha-

approximately 50%, whereas

amoxycillin

is

losporins.

absorbed 90%. Urinary excretion of both antibi-

Second

group

cephalosporins

such

as

otics is about 70%. The aminopenicillins ampi-

cefuroxime and cefotiam show an increased

cillin and amoxycillin are active against E. coli

b-lactamase stability. This is mainly due to the

and P. mirabilis, but almost

inactive against

oxime-group in cefuroxime and the thiazole-

other enterobacteria and totally inactive against

amino group

in cefotiam. After intravenous

Pseudomonas spp. The aminopenicillins are not

injection the renal excretion is 90% in cefu-

stable against the b-lactamases frequently found

roxime36 and 70% in cefotiam.37 In contrast to

in S. aureus and many enterobacteria. Com-

cefuroxime, the prodrug

cefuroxime

axetil

is

bination with a b-lactamase-inhibitor such as

resorbed with a total bioavailability of 40% after

clavulanic acid or sulbactam enhances Gram-

rapid hydrolysis to the active parent compound,

negative activity to a certain extent, but not

cefuroxime.38

These

cephalosporins

show

an

against bacteria producing AmpC b-lactamases,

enhanced activity against some Gram-negative

such as Enterobacter spp. or Citrobacter spp.32

uropathogens.

Against

susceptible

Gram-

The acylamino (ureido)-penicillins, such as

negative bacteria, second group cephalosporins

piperacillin, own stronger polar groups on the

are four to eight times more potent than first

amino-group. However, the compound is not

group compounds. There is no activity against

stable against the b-lactamases of S. aureus and

P. vulgaris, Morganella spp., Serratia spp., and

some strains of Enterobacter spp. and Serratia

P. aeruginosa. Cefotiam is more active against E.

spp. Combination of piperacillin with the b-lac-

coli, Klebsiella spp., and P. mirabilis than

tamase inhibitor tazobactam

can counteract

cefuroxime.

some of the b-lactamases increasingly produced

Cephalosporins of the group 3a such as cefo-

by Gram-negative bacteria. Urinary excretion of

taxime and ceftriaxone, and the orally active

both, piperacillin and tazobactam is approxi-

substances cefpodoxime-proxetil and ceftibuten

mately 70%. Piperacillin exhibits activity against

exhibit a

further increased activity against

Pseudomonas spp. and Proteus vulgaris.33

Gram-negative organisms, because the side

chain protects the molecule from cephalos-

Cephalosporins

porinases

by

steric hindrance.39 Cefotaxime

is metabolized in about 30% to desacetyl-

The cephalosporins are classified according to

cefotaxime, which shows inferiorer antimicro-

their primary route of administration (paren-

biological activitiy.40 Ceftriaxone undergoes a

teral vs. oral), and in groups according to their

partial biliar excretion of about 45%.41 The bio-

antibacterial spectrum. For structure activity

availability of cefpodoxime-proxetil is about

relationships, comparable characteristics can be

40%,42 while the bioavailability of ceftibuten is

seen as with penicillins. Substitutions at the side

about 90%.43 The renal excretion rates are about

chain mainly influence activity, whereas modifi-

80%, 55%, 90%, and 90% for cefotaxime, ceftri-

cations in position 3 of the nucleus influence

axone, cefpodoxime, and ceftibuten, respec-

mainly pharmacokinetics. The various groups

tively.40-43 Third group cephalosporins are

of cephalosporins differ from one another in the

approximately ten times more active than the