Cephalosporin Antibiotics

Cephalosporins are the most frequently prescribed class of antibiotics. They are structurally and pharmacologically related to the penicillins. Like the penicillins, cephalosporins have a beta-lactam ring structure that interferes with synthesis of the bacterial cell wall and so are bactericidal (which means that they kill bacteria).

Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu. The first agent cephalothin (cefalotin) was launched by Eli Lilly in 1964.

Cephalosporins are derived from cephalosporin C which is an acid-stable molecule with antibacterial activity and is produced from Cephalosporium acremonium.

Mode of action

Cephalosporins are bactericidal agents and have the same mode of action as other beta-lactam antibiotics (such as penicillins). All bacterial cells have a cell wall that protects them. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls, which causes the walls to break down and eventually the bacteria die.

Side Effects

Cephalosporins generally cause few side effects. Common side effects involve mainly the digestive system: mild stomach cramps or upset, nausea, vomiting, and diarrhea. These side effects are usually mild and go away over time. Cephalosporins can sometimes cause overgrowth of fungus normally present in the body. This overgrowth can cause mild side effects such as a sore tongue, sores inside the mouth, or vaginal yeast infections.

More serious but infrequent reactions that can sometimes occur with cephalosporins include: black, tarry stools; chest pain; fever; painful or difficult urination; allergic reactions; serious colitis. Serious colitis is a rare side effect that includes severe watery diarrhea (sometimes containing blood or mucus), severe stomach cramps, fever, and weakness or faintness.

Because the cephalosporins are structurally similar to the penicillins, some patients allergic to penicillins may be allergic to a cephalosporin antibiotic. The incidence of cross-sensitivity is approximately 5–10%.

Indications

Cephalosporins are indicated for the treatment of bacterial infections caused by susceptible organisms. First generation cephalosporins are predominantly active against gram-positive bacteria, and successive generations have increased activity against gram-negative bacteria (often with reduced activity against gram-positive organisms).

Bacteria are classified in several ways. One of the way is by their color after a particular chemical stain (gram stain) is applied. Some bacteria stain blue and are called gram-positive, others stain pink and are called gram-negative. Gram-negative bacteria have a unique outer membrane that prevents many drugs from penetrating them, making gram-negative bacteria generally more resistant to antibiotics than are gram-positive bacteria. Gram-negative bacteria are able to become resistant to antibiotics, gram-positive bacteria are usually slow to develop such resistance.

Cephalosporins are used to treat a wide variety of bacterial infections, such as respiratory tract infections (pneumonia, strep throat, tonsillitis, bronchitis), skin infections and urinary tract infections. They are sometimes given with other antibiotics. Cephalosporins are also commonly used for surgical prophylaxis - prevention of bacterial infection before, during, and after surgery.

Classification of Cephalosporins

Cephalosporins are grouped into "generations" based on their spectrum of antimicrobial activity. The first cephalosporins were designated first generation while later, more extended spectrum cephalosporins were classified as second generation cephalosporins. Each newer generation of cephalosporins has significantly greater gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against gram-positive organisms. Fourth generation cephalosporins, however, have true broad spectrum activity.

The newer agents have much longer half-lives resulting in the decrease of dosing frequency.

First generation

First generation cephalosporins are moderate spectrum agents. They are effective alternatives for treating staphylococcal and streptococcal infections and therefore are alternatives for skin and soft-tissue infections, as well as for streptococcal pharyngitis.

The first generation cephalosporins are:

·         Cefadroxil

·         Cephalexin

·         Cephaloridine

·         Cephalothin

·         Cephapirin

·         Cefazolin

·         Cephradine

Cefazolin is the most commonly used first generation cephalosporin. The other first generation cephalosporins have similar efficacy to Cephalexin, but must be dosed more often, and are therefore not as commonly prescribed.

Second generation

The second generation cephalosporins have a greater gram-negative spectrum while retaining some activity against gram-positive bacteria. They are also more resistant to beta-lactamase. They are useful agents for treating upper and lower respiratory tract infections, sinusitis and otitis media. These agents are also active against E. coli, Klebsiella and Proteus, which makes them potential alternatives for treating urinary tract infections caused by these organisms. Cefoxitin is a second generation cephalosporin with anaerobic activity, and although seldom used as a therapeutic agent, it may be useful for prophylaxis in gastrointestinal surgery.

The second generation cephalosporins are:

·         Cefaclor

·         Cefoxitin

·         Cefprozil

·         Cefuroxime

Third generation

Third generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms. Some members of this group (particularly those available in an oral formulation) have decreased activity against gram-positive organisms. The parenteral third generation cephalosporins (ceftriaxone and cefotaxime) have excellent activity against most strains of Streptococcus pneumoniae, including the vast majority of those with intermediate and high level resistance to penicillin. These agents also have activity against N. gonorrhoeae. Ceftazidime has useful antipseudomonal activity.

The third generation cephalosporins are:

·         Cefdinir

·         Cefixime

·         Cefpodoxime

·         Ceftibuten

·         Ceftriaxone

·         Cefotaxime

Fourth generation

Fourth generation cephalosporins are extended spectrum agents with similar activity against gram-positive organisms as first generation cephalosporins. They also have a greater resistance to beta-lactamases than the third generation cephalosporins. Many can cross blood brain barrier and are effective in meningitis.

Cefepime has broad gram-negative coverage with somewhat enhanced activity against pseudomonas but slightly lesser activity against pneumococci. Cefpirome is more active against pneumococci and has somewhat lesser activity against pseudomonas. Cefepime and cefpirome are highly active against nosocomial pathogens such as Enterobacter and Acinetobacter and their use should therefore be restricted to the setting of nosocomial sepsis².

The fourth generation cephalosporins are:

·         Cefepime

·         Cefluprenam

·         Cefozopran

·         Cefpirome

·         Cefquinome