Mythbuster: The 10% cephalosporin-penicillin cross-reactivity risk

The true incidence of an allergy to penicillin in patients believed to have such allergy is <10% (it’s like we have a built in 10-fold safety factor). Cross-reactivity between penicillins and MOST 1st and 2nd generation cephalosporins is negligible. Cross-reactivity between penicillins and ALL 3rd and 4th generation cephalosporins is negligible. If a patient has an allergy to amoxicillin or ampicillin, avoid cefadroxil, cefaclor, cefatrizine, cefprozil, cephalexin, and cephradine.

 Appropriate use of cephalosporins

There are very few indications for the use of cephalosporins as first-line antibiotic treatment. Ceftriaxone is used for the treatment of gonorrhoea, pelvic inflammatory disease and epididymo-orchitis. It is also an alternative to benzylpenicillin in patients with suspected meningitis. Cefaclor may be considered as a second-line treatment for infections such as otitis media, sinusitis, cellulitis, diabetic foot infection and mastitis. Cephalexin is a third-line treatment for urinary tract infection in pregnant women.

 Cephalosporins Can Be Used in Penicillin Allergy

Did you know the literature describing the cross-reactivity between cephalosporins and penicillins is 30-40 years old? It sort of takes the “modern” out of “modern medicine.”

 Penicillin-Cephalosporin Cross-Reactivity Made Easy

The cross-reactivity between cephalosporins and penicillins is significantly lower than the 10% figure many of us learned. In fact, the beta-lactam ring is rarely involved. So, when the warning pops up next time you order ceftriaxone in a penicillin-allergic patient, what should you do?

Cephalosporin Abx in Patients with Penicillin Allergy

The oft quoted 10% “cross-reactivity” rate between penicillins and cephalosporins is inaccurate based on the best available evidence. The true rate is somewhere between 1-3%.

An overview of cephalosporin antibiotics as emerging contaminants: a serious environmental concern

Antibiotics are the emerging pollutants of global concern due to the development of antibiotic resistance. They have been detected worldwide in environmental matrices indicating their ineffective removal from water and wastewater. Cephalosporins make up the largest share of human and animal use antibiotics in most of the countries and account for approximately 50–70% usage.

Antibiotic Resistance & Patient Safety Portal

Antibiotics are prescribed differently across the United States. Reasons for regional variation may include different prescribing behaviors, diagnostic patterns, disease burden, and levels of antibiotic resistance among certain pathogens.

Cephalosporins Pharmacology!

Cephalosporins were discovered in the mid-1940s, first isolated from the fungus Cephalosporium acremonium – a fungus that was found in the sewers of Sardinia. There are now dozens of approved cephalosporins – each of which can be found in one of the five generations that now exist:

Cephalosporins remain empiric therapy for skin infections in pediatric AD

A new study has reaffirmed that, as methicillin‐sensitive Staphylococcus aureus (MSSA) remains the most common skin infection in pediatric atopic dermatitis (AD) patients, first‐generation cephalosporins remain the appropriate empiric therapy.

Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity

The misdiagnosis of β-lactam allergies and misunderstanding of cross-reactivity among β-lactams, including within the cephalosporin class, often leads to use of broader spectrum antibiotics with poor safety and efficacy profiles and represents a serious obstacle for antimicrobial stewardship.

Cephalosporins: A Review

Cephalosporins are beta-lactam antimicrobials that share mechanisms of action and a similar structure with penicillins (Figure). Penicillins and cephalosporins have the same four-member “core” beta-lactam ring, but cephalosporins have an additional atom in the side ring. Modified side chains on either ring alter antimicrobial activity, resistance to beta-lactamases, or pharmacokinetics.

Cephalosporins: How Vital Are They in a Hospitalist’s Toolkit?

Cephalosporins are similar to beta-lactam antibiotics which inhibit the synthesis of the bacterial cell wall, particularly peptidoglycan, the exoskeleton of bacteria that provides structural integrity and shape to bacterial cells and protects them from bursting. Most bacteria possess peptidoglycan polymers, collectively called penicillin-binding proteins (PBPs), which are the target of cephalosporins. The beta-lactam ring of cephalosporins mimics the “D-Ala-D-Ala” moiety of the natural substrate of PBPs. Structural binding of cephalosporins to the active site of PBPs in bacterial cell walls leads to inhibition of their enzymatic activity and synthesis of defective peptidoglycan, resulting in osmotic lysis and subsequent death of the bacterial cells.

Different Generations of Cephalosporin Medication

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.

Giuseppe Brotzu and the discovery of cephalosporins

With the discovery of the fungus and the somewhat rudimentary production of ‘mycetin’, Giuseppe Brotzu gradually realized, from 1943 to 1945, that he had hit upon a therapeutic agent of major importance. He devised plans and projects for research and, in vain, sought the financial support of various institutional bodies. ‘They didn't even answer', he once confessed to me bitterly. And he lost heart.

Honey We Shrunk the Omnicef: 3rd Generation Cephalosporin Stewardship

Why target 3rd Generation cephalosporins (3GC)?

New-Generation Cephalosporins

Since their discovery in the 1950s, cephalosporins have become one of the largest classes of antibiotics. The class is divided into generations or subclasses, which are grouped by chemical properties and subsequent generalized microbiologic spectra.

The Cephalosporins

The cephalosporins are a large group of related β-lactam antimicrobial agents. Favorable attributes of the cephalosporins include low rates of toxicity, relatively broad spectrum of activity, and ease of administration. Various cephalosporins are effective for treatment of many conditions, including pneumonia, skin and soft tissue infections, bacteremia, and meningitis. Differences among the numerous cephalosporin antimicrobial agents are sometimes subtle; however, an understanding of these differences is essential for optimal use of these agents.

The problem with cephalosporins

The cephalosporin antibiotics have become a major part of the antibiotic formulary for hospitals in affluent countries. They are prescribed for a wide variety of infections every day. Their undoubted popularity relies upon lesser allergenic and toxicity risks as well as a broad spectrum of activity. It is the latter feature, however, that encourages the selection of microorganisms that are resistant to these agents. There are long-term implications for the treatment and control of this heterogeneous group of superinfections.