CEPHALOSPORINS

-broad-spectrum semisynthetic beta-lactam antibiotics similar in structure and actions to the penicillins.
These drugs are bactericidal and are often resistant to beta-lactamases.

First to Fifth Generations

The cephalosporins can be grouped into five “generations” based on the order of their introduction to
clinical use. In general, as we progress from first-generation agents to fifth-generation agents, there is (1)
increasing activity against gram-negative bacteria and anaerobes, (2) increasing resistance to destruction
by beta-lactamases, and (3) increasing ability to reach the cerebrospinal fluid (CSF).

First Generation: highly active against staphylococci and nonenterococcal streptococci + gram-negative
bacteria P.mirabilis, E.coli, K. pneumoniae

cefazolin, cephradine, cefadroxil, cephalexin

Second Generation: Previously mentioned + H. influenza, Enterobacter aerogenes, Neisseria

cefoxitin, cefuroxime, cefotetan, loracarbef, cefaclor, cefprozil

Third Generation: relatively weak against gram-positive but more potent against gram-negative bacilli +
Serratia macecens; Can reach clinically effective concentrations in the CSF

cefotaxime, ceftizoxime, ceftriaxone, ceftazidime, cefpodoxime, ceftibuten, cefdinir

Fourth Generation: Active against gram-negative and gram-positive organisms including cephalosporin-
resistant staphylococci and P. auruginosa

cefepime, cefditoren

Fifth Generation: same spectrum as 3rd gen + methicillin-resistant S. aureus (MRSA)

ceftaroline

Mechanism of Action

Cephalosporins interfere with peptidoglycan cell wall synthesis by binding to penicillin-binding proteins
(PBPs) and thereby activating autolysins (enzymes that cleave bonds in the cell wall). The resulting weak
cell wall causes increase in osmotic pressure within the cell, thus the cell swells and bursts.

Contraindications

Avoid the use of cephalosporins in patients with known allergies to cephalosporins or penicillins because
cross-sensitivity is common.

Use with caution in patients 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 lactating patients 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.
Adverse Effects

GI tract: N&V, diarrhea, anorexia, abdominal pain, and flatulence, pseudomembranous colitis

CNS: headache, dizziness, lethargy, paresthesia

CV: phlebitis, thrombophlebitis

Other: hypersensitivity reactions (maculopapular rash, bronchospasms, anaphylaxis, urticarial,

hypotension, DOB) superinfection

Interactions

Ethanol (Alcohol): Acute alcohol intolerance after drinking alcoholic beverages within 72 hr of taking
cefotetan caused by accumulation of acetaldehyde metabolite of ethanol. Symptoms include stomach
cramps, N&V, diaphoresis, pruritus, headache, and hypotension

Antacids, Iron: Decreases absorption of certain oral cephalosporins.

Probenecid: decreases renal excretion thus increasing cephalosporin levels.

Oral Contraceptives (OC): Enhances OC metabolism. Alternative birth control methods should be used at
least 1 month during and after taking cephalosporins.

Live-virus vaccines: may decrease effectiveness of live-virus vaccines. Concurrent use is not
recommended.

Aminoglycosides: may increase risk of nephrotoxicity. Avoid using together.

Warfarin: May enhance anticoagulant effect (inhibits prothrombin levels). Monitor therapy.

Nursing Considerations:

Culture sensitivity test to evaluate causative organism and appropriate sensitivity to the antibiotic used.