Cephalosporins – Infectious Diseases – MSD Manual Professional
Cephalosporins are one of the most widely prescribed classes of medications in the world. Chances are that you have encountered these antibiotics even if you are unfamiliar with the name. For example, among other things, Keflex (cefalexin) is used to treat skin infections. Additionally, Rocephin (ceftriaxone) is used to treat pneumonia.There are five generations of cephalosporins.
What Are Cephalosporins?
Cephalosporins were first discovered in sewer water off the coast of Sardinia in 1945. By 1964, the first cephalosporin was prescribed.Cephalosporins are structurally similar to other antibiotics. Like penicillins, cephalosporins have a beta-lactam ring attached to a dihyrdothiazole ring. Hanging off this dihyrdothiazole ring are various side chains, the composition of which makes for different cephalosporins with different pharmacology and antimicrobial activity.Cephalosporins have three different mechanisms of action:
- Binding to specific penicillin-binding proteins.
- Inhibition of cell wall synthesis.
- Activation of autolytic (self-destructive) enzymes in the bacterial cell wall
Cephalosporins are divided into five generations. However, different cephalosporins in the same generation are sometimes chemically unrelated and have different spectra of activity (think cephamycins).A generalization taught to many health care professionals is that with subsequent generations of cephalosporins, gram-positive coverage decreases while gram-negative coverage increases. One to 3 percent of all people are allergic to cephalosporins. In reality, however, this number is probably higher because people with penicillin allergies are often not prescribed cephalosporins.
First-generation cephalosporins come in oral and intravenous forms. They are active against Viridans streptococci, group A hemolytic streptococci, Staphylococcus aureus, E. coli, Klebsiella and Proteus bacteria. Like all other cephalosporins, first-generation cephalosporins don’t work on enterococci.
- Cephalexin (Keflex)
- Cefazolin (intravenous and intramuscular)
In general, first-generation cephalosporins can be used to fight skin and other soft-tissue infections, respiratory tract infections, and urinary tract infections. Intravenous first-generation cephalosporins can be used as prophylaxis after clean surgical procedures. Of particular note, the prevalence of MRSA has diminished the efficacy of first-generation cephalosporins as a means of prophylaxis and treatment.
In general, second-generation cephalosporins are more active against gram-negative organisms, making them more useful in many clinical situations.For example, second-generation cephalosporins are active against strains of Proteus and Klebsiella. Second-generation cephalosporins also combat H. influenza—a cause of pneumonia, sepsis, and meningitis. Nevertheless, first-generation cephalosporins are generally still better at treating gram-positive infections.
- Cefoxitin (cephamycin)
- Cefotetan (cephamycin)
- Cefuroxime (oral and intravenous)
Second-generation cephalosporins treat the following:
- Otitis media (ear infection)
- Mixed anaerobic infections including peritonitis and diverticulitis
- Prophylaxis after colorectal surgery
Second-generation cephalosporins have no activity against Pseudomonas aeruginosa.
A major advantage of third- and fourth-generation antibiotics is significantly expanded coverage against gram-negative bacteria. Furthermore, the third-generation cephalosporin ceftazidime is active against Pseudomonas aeruginosa, a bacteria that can cause skin infections in people with normal immune systems (think after exposure to an under-chlorinated hot tub or pool) as well as pneumonia, blood infections and so forth in those with weakened immune systems (think post-surgical and hospitalized patients).There are several third-generation cephalosporins. Discussing them all would be outside the scope of this article. Let’s instead focus on ceftriaxone (Rocephin) which has numerous uses including:
- Lower respiratory tract infections
- Skin and soft tissue infections
- Uncomplicated gonorrhea
- Urinary tract infections
- Otitis media
- Pelvic inflammatory disease
- Surgical prophylaxis
- Bacteria septicemia (blood infection)
- Bone infections
- Joint infections
- Intra-abdominal infections
Cefepime is the only available (FDA-approved) fourth-generation cephalosporin. Like the third-generation cephalosporin ceftazidime, cefepime is active against Pseudomonas aeruginosa. Furthermore, cefepime is more active against Enterobacter and Citrobacterr bacteria. Finally, cefepime has gram-positive coverage comparable with ceftriaxone.
Here are some clinical uses for cefepime:
- Moderate to severe pneumonia
- Severe urinary tract infection
- Skin and soft tissue infections
- Complicated intra-abdominal infections
In 2010, the FDA approved Ceftaroline (Teflaro), the only fifth- or advanced-generation cephalosporin. Like cefepime, ceftaroline is a potent antibiotic that should be reserved for serious infection. Specifically, it’s active against multidrug-resistant infections like MRSA (methicillin-resistant S. aureus) and VRSA (vancomycin-resistant S. aureus). This drug is also injectable and prescribed to fight community-acquired pneumonia and serious skin and soft tissue infections. Fortunately, ceftaroline is safe and hs little ability to induce resistance.As you can now appreciate, cephalosporins are a remarkably diverse class of antibiotics with broad coverage. However, as with most antibiotics, antibiotic resistance is a concern for many clinicians, epidemiologists, public health officials, patients and so forth.Bacterial resistance is partially due to physicians overprescription; nevertheless, we, as patients, can also help combat the development of resistance. For example, you shouldn’t always expect or demand that your prescriber gives you antibiotics to treat an infection which may very well be viral in nature. (Antibiotics are ineffective against viruses.) Furthermore, when prescribed antibiotics, it’s imperative that you finish the entire course even if you “feel better.”