Cephalosporins are bactericidal beta-lactam antibiotics. They inhibit enzymes in the cell wall of susceptible bacteria, disrupting cell wall synthesis. There are 5 generations of cephalosporins.
(See also Overview of Antibacterial Drugs.)
Pharmacokinetics
Cephalosporins penetrate well into most body fluids and the extracellular fluid of most tissues, especially when inflammation (which enhances diffusion) is present. However, the only cephalosporins that reach cerebrospinal fluid levels high enough to treat meningitis are
All cephalosporins penetrate poorly into intracellular fluid and the vitreous humor.
Indications for Cephalosporins
Cephalosporins are bactericidal for most of the following:
Gram-positive bacteria
Cephalosporins are classified in generations (see table Some Clinical Uses of 3rd- and 4th-Generation CephalosporinsStaphylococcus aureus. Cephalosporins have the following limitations:
Lack of activity against enterococci
Lack of activity against anaerobic gram-negative bacilli
First-generation cephalosporins
These drugs have excellent activity against
Gram-positive cocci
Oral 1st-generation cephalosporins are commonly used for uncomplicated skin and soft-tissue infections, which are usually due to staphylococci and streptococci.
endocarditis due to methicillin-sensitive S. aureus and for prophylaxis before cardiothoracic, orthopedic, abdominal, and pelvic surgery.
Second-generation cephalosporins and cephamycins
Second-generation cephalosporins are active against
Gram-positive cocci
Certain gram-negative bacilli
Cephamycins are drugs that were originally produced by Streptomyces but are now synthetic. They are typically classed with 2nd-generation cephalosporins. Cephamycins are more active against anaerobes, such as
Bacteroides species, including Bacteroides fragilis
These drugs may be slightly less active against gram-positive cocci than 1st-generation cephalosporins. Second-generation cephalosporins and cephamycins are often used for polymicrobial infections that include gram-negative bacilli and gram-positive cocci. Because cephamycins are active against Bacteroides species, they can be used when anaerobes are suspected (eg, in intra-abdominal sepsis, decubitus ulcers, or diabetic foot infections). However, in some medical centers, these bacilli are no longer reliably susceptible to cephamycins.
Third-generation cephalosporins
These drugs are active against
Haemophilus influenzae and some Enterobacterales (formerly Enterobacteriaceae; eg, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis) that do not produce AmpC beta-lactamase or extended-spectrum beta-lactamase (ESBL)
S. aureus and, if used for skin and soft-tissue infections, should be restricted to uncomplicated infections due to streptococci.
Pseudomonas aeruginosa, whereas the rest of the class is not. Both are also active against StreptococcusKlebsiella pneumoniae carbapenemase (KPC).
These cephalosporins have many clinical uses, as does the 4th-generation cephalosporin (see table Some Clinical Uses of 3rd- and 4th-Generation Cephalosporins).
Fourth-generation cephalosporins
Gram-negative bacilli (enhanced activity), including P. aeruginosaEnterobacter species
Fifth-generation cephalosporins
Methicillin-resistant S. aureus (MRSA)
Penicillin-resistant streptococci
Enterococcus faecalis
Their activity against other gram-positive cocci and gram-negative bacilli is similar to that of 3rd-generation cephalosporins. The 5th-generation cephalosporins are not active against Pseudomonas species.
Contraindications to Cephalosporins
Cephalosporins are contraindicated in patients with a history of major hypersensitivity to other cephalosporins. Cross-reactivity with penicillins and other classes of beta-lactams including other cephalosporins is less common than previously thought, especially among patients who have had mild (nonanaphylactic) reactions to penicillins. About 2% of penicillin-allergic patients have cross-reactivity with cephalosporins (1, 23, 4, 5).
is contraindicated as follows:
Contraindications references
1. Shenoy ES, Macy E, Rowe T, Blumenthal KG: Evaluation and management of penicillin allergy: A review. JAMA 321(2):188–199, 2019. doi: 10.1001/jama.2018.19283
2. Campagna JD, Bond MC, Schabelman E, Hayes BD: The use of cephalosporins in penicillin-allergic patients: A literature review. J Emerg Med 42(5):612–620, 2012. doi: 10.1016/j.jemermed.2011.05.035
3. Chaudhry SB, Veve MP, Wagner JL: Cephalosporins: A focus on side chains and β-lactam cross-reactivity. Pharmacy (Basel) 7(3):103, 2019. doi: 10.3390/pharmacy7030103
4. Collins CD, Scheidel C, Anam K, et al: Impact of an antibiotic side chain-based cross-reactivity chart combined with enhanced allergy assessment processes for surgical prophylaxis antimicrobials in patients with beta-lactam allergies. Clin Infect Dis pii:ciaa232, 2020. doi: 10.1093/cid/ciaa232
5. DePestel DD, Benninger MS, Danziger L, et al: Cephalosporin use in treatment of patients with penicillin allergies. J Am Pharm Assoc (2003) 48(4):530–540, 2008. doi: 10.1331/JAPhA.2008.07006
Use During Pregnancy and Breastfeeding
Cephalosporins are widely considered to be safe for use during pregnancy. No studies have shown risk to human fetuses, but rigorous prospective studies have not been done.
Cephalosporins can enter breast milk and may alter bowel microbiota of the infant. Thus, use during breastfeeding is often discouraged.
Adverse Effects of Cephalosporins
Significant potential adverse effects of cephalosporins include
Hypersensitivity reactions (most common)
Clostridioides (formerly Clostridium) difficile–induced diarrhea (pseudomembranous colitis)
Positive Coombs test (although hemolytic anemia is very uncommon)
Hypersensitivity reactions are the most common systemic adverse effects; rash is common, but immediate IgE-mediated urticaria and anaphylaxis are rare.
Cross-sensitivity between cephalosporins and penicillins is uncommon; cephalosporins can be given cautiously to patients with a history of delayed hypersensitivity to penicillin if necessary. Pain at the IM injection site and thrombophlebitis after IV use may occur.
