C H A P T E R 9
Antibiotics
101
First-generation cephalosporins are largely effective
against the same gram-positive bacteria that are affected
by penicillin G, as well as the gram-negative bacteria
Proteus mirabilis
,
E. coli
and
Klebsiella pneumoniae
(use the letters
PEcK
as a mnemonic device to remember
which bacteria are susceptible to the first-generation
cephalosporins). First-generation drugs include cephazo-
lin (
Kefzol
) and cephalexin (
Cilex
,
Keflex
,
Rancef
).
Second-generation cephalosporins are effective
against the previously mentioned strains, as well as
Haemophilus influenzae
,
Enterobacter aerogenes
and
Neisseria
species (remember
HENPeCK
). Second-gen-
eration drugs are less effective against gram-positive
bacteria. These include cefaclor (
Ceclor
), cefoxitin and
cefuroxime (
Zinnat
).
Third-generation cephalosporins, which are effec-
tive against all of the previously mentioned strains, are
relatively weak against gram-positive bacteria but are
more potent against the gram-negative bacilli, as well
as against
Serratia marcescens
(remember
HENPeCKS
).
Third-generation drugs include cefotaxime, ceftazidime
(
Fortum
) and ceftriaxone (
Rocephin
).
Fourth-generation cephalosporins are in develop-
ment. The first drug of this group, cefepime (
Maxipime
),
is active against gram-negative and gram-positive organ-
isms, including cephalosporin-resistant staphylococci
and
P. aeruginosa.
Fifth-generation cephalosporins are also in devel-
opment and appear to be less susceptible to resistance.
The first drug of this group, ceftaroline (
Zinforo
) is
active against gram-positive and gram-negative organ-
isms, including Methicillin-resistant
Staphlococcus
aureus
(MRSA) and penicillin resistant
Streptococcus
pneumoniae
.
Therapeutic actions and indications
The cephalosporins are both bactericidal and bacterio-
static, depending on the dose used and the specific drug
involved. In susceptible species, these agents basically
interfere with the cell wall-building ability of bacteria
when they divide; that is, they prevent the bacteria
from biosynthesising the framework of their cell walls.
The bacteria with weakened cell walls swell and burst
as a result of the osmotic pressure within the cell (see
Figure 9.1).
Cephalosporins are indicated for the treatment of
infections caused by susceptible bacteria. See Table 9.3
for usual indications for each of these agents. Selection
of an antibiotic from this class depends on the sen-
sitivity of the involved organism, the route of choice
and sometimes the cost involved. It is important to
reserve cephalosporins for appropriate situations
because cephalosporin-resistant bacteria are appearing
in increasing numbers. Before therapy begins, perform
a culture and sensitivity test to evaluate the causative
organism and appropriate sensitivity to the antibiotic
being used.
Pharmacokinetics
The following cephalosporins are well absorbed from
the GI tract: the first-generation drug cephalexin; the
second-generation drugs cefaclor and cefuroxime; the
third-generation drug cefotaxime; and the fourth-
generation drug cefepime. The others are absorbed
well after IM injection or IV administration. (Box 9.4
provides calculation practice using cefaclor.)
The cephalosporins are primarily metabolised in the
liver and excreted in the urine. These drugs cross the
placenta and enter breast milk (see contraindications
and cautions).
You are caring for a 20-kg child with a severe case
of tonsillitis. An order is written for cefaclor (Ceclor)
20 mg/kg/day q 8 hours for 10 days.The drug comes in
an oral suspension 125 mg/5 mL. What amount should
you administer at each dose?
The order is for 20 mg/kg, so 20 mg/kg
×
20 = 400 mg
per day.
stock required
stock strength
×
volume
1
400
125
×
5
1
=
2000
125
= 16 mL/day
therefore, each dose = 16/3 = 5.3 mL per dose
Calculations
BOX 9.4
Contraindications and cautions
Avoid the use of cephalosporins in people with known
allergies to cephalosporins or penicillins
because
cross-sensitivity is common.
Use with caution in people
with hepatic or renal impairment
because these drugs
are toxic to the kidneys and could interfere with the
metabolism and excretion of the drug.
In addition,
use with caution in pregnant or breastfeeding women
because potential effects on the fetus and infant are not
known; use only if the benefits clearly outweigh the
potential risk of toxicity to the fetus or infant.
Reserve cephalosporins for appropriate situations
because cephalosporin-resistant bacteria are appearing
in increasing numbers. Before therapy begins, perform
a culture and sensitivity test to evaluate the causative
organism and appropriate sensitivity to the antibiotic
being used.
Adverse effects
The most common adverse effects of the cephalo-
sporins involve the GI tract and include nausea,
