McKenna's Pharmacology for Nursing, 2e

101

C H A P T E R 9  Antibiotics

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).

Calculations

BOX 9.4

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

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,