Cephalosporin

 ( Acetaldehyde Dehydrogenase Inhibitors ) 

disulfiram-like reaction with ethanol. These include latamoxef (moxalactam), cefmenoxime, cefoperazone, cefamandole, cefmetazole, and cefotetan. This is thought to be due to the methylthiotetrazole side-chain of these cephalosporins, which blocks the enzyme vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde dehydrogenase (causing alcohol intolerance).

Stork CM (2025). 9780071437639, McGraw-Hill. ISBN 9780071437639

Thus, consumption of alcohol after taking these cephalosporin orally or intravenously is contraindicated, and in severe cases can lead to death. The methylthiodioxotriazine sidechain found in ceftriaxone has a similar effect. Cephalosporins without these structural elements are believed to be safe with alcohol.

---

Mechanism of action Cephalosporins are bactericidal and, like other β-lactam antibiotics, disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan.

---

Resistance Resistance to cephalosporin antibiotics can involve either reduced affinity of existing PBP components or the acquisition of a supplementary β-lactam-insensitive PBP. Compared to other β-lactam antibiotics (such as penicillins), they are less susceptible to β-lactamases. Currently, some Citrobacter freundii, Enterobacter cloacae, Neisseria gonorrhoeae, and Escherichia coli strains are resistant to cephalosporins. Some Morganella morganii, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Serratia marcescens and Klebsiella pneumoniae strains have also developed resistance to cephalosporins to varying degrees.

---

Classification The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-spectrum cephalosporins were classified as second-generation cephalosporins. Each newer generation 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 classification of cephalosporins into "generations" is commonly practised, although the exact categorization is often imprecise. For example, the fourth generation of cephalosporins is not recognized as such in Japan. In Japan, cefaclor is classed as a first-generation cephalosporin, though in the United States it is a second-generation one; and cefbuperazone, cefminox, and cefotetan are classed as second-generation cephalosporins.

---

First generation Cefalotin, cefazolin, cefalexin, cefapirin, cefradine, and cefadroxil are among the drugs belonging to this group.

---

Second generation Cefoxitin, cefuroxime, cefaclor, cefprozil, and cefmetazole are classed as second-generation cephems.

---

Third generation Ceftazidime, ceftriaxone, and cefotaxime are classed as third-generation cephalosporins. Flomoxef and latamoxef are in a new, related class called .

(1990). 9783642756191 ISBN 9783642756191

---

Fourth generation Drugs included in this group are cefepime and cefpirome.

---

Further generations Some state that cephalosporins can be divided into five or even six generations, although the usefulness of this organization system is of limited clinical relevance.

---

Naming Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking countries. This continues to be the preferred spelling in the United States, Australia, and New Zealand, while European countries (including the United Kingdom) have adopted the International Nonproprietary Names, which are always spelled "cef-". Newer first-generation cephalosporins and all cephalosporins of later generations are spelled "cef-", even in the United States.

---

Activity There exist bacteria which cannot be treated with cephalosporins of generations first through fourth:

• Listeria
• Atypicals (including Mycoplasma and Chlamydia)
• MRSA
• Enterococci

Fifth-generation cephalosporins (e.g. ceftaroline) are effective against MRSA, Listeria spp., and Enterococcus faecalis.

---

Overview table

(#) = noncephalosporins similar to generation #				H, medicine; V, veterinary; W, withdrawn; P, Pseudomonas; MR, methicillin-resistant Staphylococcus aureus; An, anaerobe
1		Gram-positive: Activity against penicillinase-producing, methicillin-susceptible Staphylococcus and Streptococcus (though they are not the drugs of choice for such infections). No activity against methicillin-resistant staphylococci or Enterococcus. Gram-negative: Activity against Proteus mirabilis, some Escherichia coli, and Klebsiella pneumoniae ("PEcK"), but have no activity against Bacteroides fragilis, Pseudomonas, Acinetobacter, Enterobacter, indole-positive Proteus, or Serratia.
2		Gram-positive: Less than first-generation. Gram-negative: Greater than first-generation: HEN Haemophilus influenzae, Enterobacter aerogenes and some Neisseria + the PEcK described above.
(2)	An	sometimes grouped with second-generation cephalosporins
	An
	An
	The carbacephem analog of cefaclor
3		Gram-positive: Some members of this group (in particular, those available in an oral formulation, and those with antipseudomonal activity) have decreased activity against gram-positive organisms. Activity against staphylococci and streptococci is less with the third-generation compounds than with the first- and second-generation compounds. (2025). 9780195125283, Oxford University Press. ISBN 9780195125283 Gram-negative: Third-generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms. They may be particularly useful in treating hospital-acquired infections, although increasing levels of extended-spectrum beta-lactamases are reducing the clinical utility of this class of antibiotics. They are also able to penetrate the central nervous system, making them useful against meningitis caused by pneumococci, meningococci, H. influenzae, and susceptible E. coli, Klebsiella, and penicillin-resistant N. gonorrhoeae. Since August 2012, the third-generation cephalosporin, ceftriaxone, is the only recommended treatment for gonorrhea in the United States (in addition to azithromycin or doxycycline for concurrent Chlamydia treatment). Cefixime is no longer recommended as a first-line treatment due to evidence of decreasing susceptibility.
	P
	P
(3)	Latamoxef	An oxacephem sometimes grouped with third-generation cephalosporins
4	P	Gram-positive: They are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation cephalosporins. Gram-negative: Fourth-generation cephalosporins are that can penetrate the outer membrane of Gram-negative bacteria. (2009). 9780781778152, Lippincott Williams & Wilkins. . ISBN 9780781778152 They also have a greater resistance to β-lactamases than the third-generation cephalosporins. Many can cross the blood–brain barrier and are effective in meningitis. They are also used against Pseudomonas aeruginosa. Cefiderocol has been called a fourth-generation cephalosporin by only one source as of November 2019.
	V
An oxacephem sometimes grouped with fourth-generation cephalosporins
5	MR	Ceftobiprole has been described as "fifth-generation" cephalosporin, though acceptance for this terminology is not universal. Ceftobiprole has anti-pseudomonal activity and appears to be less susceptible to development of resistance. Ceftaroline has also been described as "fifth-generation" cephalosporin, but does not have the activity against Pseudomonas aeruginosa or vancomycin-resistant enterococci that ceftobiprole has. Ceftolozane is an option for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. It is combined with the beta-lactamase inhibitor tazobactam, as multi-drug resistant bacterial infections will generally show resistance to all β-lactam antibiotics unless this enzyme is inhibited.
	MR
	These cephems have progressed far enough to be named, but have not been assigned to a particular generation. Nitrocefin is a chromogenic cephalosporin substrate, and is used for detection of β-lactamases.

---

History Cephalosporin compounds were first isolated from cultures of Acremonium strictum from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.

(1998). 9781482229738, CRC Press. ISBN 9781482229738

He noticed these cultures produced substances that were effective against Salmonella typhi, the cause of typhoid fever, which had β-lactamase. Guy Newton and Edward Abraham at the Sir William Dunn School of Pathology at the University of Oxford isolated cephalosporin C. The cephalosporin nucleus, 7-aminocephalosporanic acid (7-ACA), was derived from cephalosporin C and proved to be analogous to the penicillin nucleus 6-aminopenicillanic acid (6-APA), but it was not sufficiently potent for clinical use. Modification of the 7-ACA side chains resulted in the development of useful antibiotic agents, and the first agent, cefalotin (cephalothin), was launched by Eli Lilly and Company in 1964.

---

External links

• Cephalosporins