Important Facts
Cefoxitin, cefotetan, and cefmetazole are cephamycins. They are grouped with the second-generation cephalosporins because they have similar activity, with one important exception: anaerobes. Cephamycins have activity against many anaerobes in the gastrointestinal (GI) tract, and cefoxitin and cefotetan are often used for surgical prophylaxis in abdominal surgery.
Loracarbef is technically a carbacephem. You should immediately forget this to allow room for more important things.
Cefaclor, cefprozil, and loracarbef are available only orally. Cefuroxime is available in both IV and oral formulations, and the others are IV only.
Like first-generation cephalosporins, second-generation agents do not cross the blood–brain barrier well enough to be useful to treat CNS infections.
What They’re Good For
Upper respiratory tract infections, community-acquired pneumonia, gonorrhea, surgical prophylaxis (cefotetan, cefoxitin, cefuroxime).
Don’t Forget!
The cephamycins have good intrinsic anaerobic activity, but resistance to them is increasing in Bacteroides fragilis group infections. When using them for surgical prophylaxis, limit the duration of antibiotic exposure after surgery. If an infection does develop, use alternative agents such as beta-lactamase inhibitor combinations or another Gram-negative agent with metronidazole.
Third-Generation Cephalosporins
Agents: ceftriaxone, cefotaxime, ceftazidime, cefdinir, cefpodoxime, cefixime, ceftibuten
Third-generation cephalosporins have greater Gram-negative activity than the firstand second-generation drugs. Most of them also have good streptococcal activity, but generally lesser staphylococcal activity than previous generations of cephalosporins. These are broad-spectrum agents that have many different uses.
Mechanism of Action
All beta-lactams inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death.
Spectrum
Good: streptococci (except ceftazidime, which is poor), enteric GNRs,
Pseudomonas (ceftazidime only)
Moderate: MSSA (except ceftazidime, which is poor)
Poor: enterococci, Pseudomonas (except ceftazidime), anaerobes, MRSA
Adverse Effects
Similar to those of other beta-lactams. Third-generation cephalosporins have been shown to be one of the classes of antibiotics with the strongest association with Clostridium difficile–associated diarrhea. Cefpodoxime has the MTT side chain that can inhibit vitamin K production (see section on second-generation cephalosporins for details).
Important Facts
Ceftazidime is the exception to the spectrum of activity rule for thirdgeneration agents. Unlike the others, it is antipseudomonal and lacks clinically useful activity against Gram-positive organisms.
Ceftriaxone, cefotaxime, and ceftazidime cross the blood–brain barrier effectively and are useful for the treatment of CNS infections. However, their differences in activity lead clinicians to use them for different types of infections. Ceftazidime is a poor choice for community-acquired meningitis, in which S. pneumoniae predominates.
Third-generation cephalosporins are notorious for inducing resistance among GNRs. Though they can be useful in nosocomial infections, too much broad-spectrum utilization can result in harder-to-treat organisms.
A one-time dose of ceftriaxone 125 mg intramuscular (IM) has been a drug-of-choice for gonorrhea for many years, but the dose was increased to 250 mg IM due to increasing resistance. Patients treated for gonorrhea should receive azithromycin as well, which adds empiric therapy for chlamydia and may reduce the emergence of ceftriaxone resistance.
Ceftriaxone has the characteristic of having dual modes of elimination via both renal and biliary excretion. It does not need to be adjusted for renal dysfunction, but it does effectively treat UTIs.
Ceftriaxone has two problems that make its use in neonates problematic: it interacts with calcium-containing medications to form crystals that can precipitate in the lungs and kidneys, which has led to fatalities, and it can also lead to biliary sludging with resultant hyperbilirubinemia. Avoid it— cefotaxime is a safer drug for these young patients.
Last ceftriaxone fact: it should be given in higher doses of 2–4 g a day for MSSA infections, particularly invasive infections. Less activity against this organism means higher doses are recommended.
What They’re Good For
Lower respiratory tract infections, pyelonephritis, nosocomial infections (ceftazidime), Lyme disease (ceftriaxone), meningitis, gonorrhea, skin and skin structure infections, febrile neutropenia (ceftazidime).
Don’t Forget!
Ceftriaxone is a once-daily drug for almost all indications except meningitis. Make sure your meningitis patients receive the full 2 g IV q12h dose and also use vancomycin and ampicillin (if indicated). There are a few more indications for the high dose, but meningitis is the most important one.
Fourth-Generation Cephalosporins Agent: cefepime
There is only one fourth-generation cephalosporin, cefepime. Cefepime is the broadest-spectrum cephalosporin, with activity against both Gram-negative organisms, including Pseudomonas, and Gram-positive organisms. One way to remember its spectrum is to think that cefazolin (1st) + ceftazidime (3rd) = cefepime (4th).
Mechanism of Action
All beta-lactams inhibit cross-linking of peptidoglycan in the cell wall, leading to autolysis and cell death.
Spectrum
Good: MSSA, streptococci, Pseudomonas, enteric GNRs
Moderate: Acinetobacter
Poor: enterococci, anaerobes, MRSA
Adverse Effects
Generally, similar to those of other beta-lactams, but cefepime may be associated with more neurotoxicity than other agents.