Cephalosporins are a general term for cephalosporins. Cephalosporins (Cephalosporins) are a class of antibiotics obtained by the semi-synthetic modification of their side chains, using natural cephalosporin C obtained from the culture of Cephalosporium as raw material. About 30 species commonly used are classified into one, two, three and four generations according to the order of their inventions and their different antibacterial properties.

In the antibiotic market, cephalosporin antibiotics occupy a larger share, and its related intermediates also show considerable market potential.

The most widely sold varieties of cephalosporin antibiotics are ceftriaxone, cefazolin sodium, cefotaxime, ceftriaxone, cefoperazone, and cefuroxime (ester). The corresponding intermediates include 7-ACA, 7- ADCA, GCLE, citraconic acid, AE-active ester, triazine ring, tetrazolium acetic acid, formamidine, HO-EPCP, methoxyamine hydrochloride, furanamine salt (SIMA), isocyanate chlorosulfate, and the like.

Related classification first generation:

Cephalothin Sodium Cefalexin Cefadroxine Cefazolin Cefradine

Cephathiazin Cefaclor Cephalosporin Cephalosporins Cephalosporins Cephalosporins Acetonitrile

Cefepillin Ceftezine

The second generation:

Cefuroxime sodium cefuroxime axetil cefurantol cefuroxime sodium cefaclor cefotene cefmetazole cefoxitin cefaclor cephalexin

Third Generation:

Cefotaxime Sodium Cefoperazone Ceftazidime Ceftriaxone Ceftizoxime Cefmenoxime Cephalosporin Cefantran Cefixime Cephalosporin Cefetadenium Ceftazidime Cefodiac Ceftriaxime Cefdinir Cephalosporins Cephalosporin Oxycephemium cephalosporin Cefminox Cefprozil

Fourth Generation:

Cefepime Cefpirome Ceftriaxone [1]

1. Fellow cephalosporins

The first generation cephalosporins began to be marketed in the early 60s. In terms of antibacterial properties, the first generation of cephalosporin-sensitive bacteria are mainly β-hemolytic streptococci and other streptococci, including Streptococcus pneumoniae (but Enterococcus resistant), Staphylococcus (including enzyme-producing strains), Haemophilus influenzae, E. coli, Klebsiella, Proteus mirabilis, Salmonella, Shigella and the like. Different varieties of cephalosporins may have their own antibacterial properties, such as ceftiophene better antibacterial effect against Gram-positive bacteria, and cefazolin has certain effects on certain Gram-negative bacteria. However, the first-generation cephalosporins have weaker resistance to gram-negative bacteria, and therefore Gram-negative bacteria are more resistant to antibiotics of this generation.

The first-generation cephalosporins were ineffective against sputum-positive proteus, Citrobacter, aerobacter, Pseudomonas, Serratia, Bacteroides, and Streptococcus faecalis (except cefotaxime).

Commonly used antibiotics in this generation are cefazolin, cephalexin, cefradine, cefadroxil, and cefaclor. In addition to cefazolin, which can only be used for injection, other can be used for oral administration, also known as oral cephalosporins. Ceftiophene, ceftazidime, cefuralin, cephalosporin, cefepillin, etc. have been used sparingly or not.

2. Second generation cephalosporins

The second-generation cephalosporins have similar or lower antibacterial efficacy against gram-positive bacteria than the first generation, and they are superior to gram-negative bacteria in terms of:

(l) Strong anti-enzyme performance Some gram-negative bacteria (such as E. coli, Proteus mirabilis, etc.) are resistant to the first generation of cephalosporins. Second-generation cephalosporins are often effective against these resistant strains.

(2) Antibacterial spectrum The antibacterial spectrum of the second-generation cephalosporins has been expanded compared to the first generation. It has antibacterial effects on Neisseria, some Proteus-proteus, some Citrobacter, and some Enterobacter species. .

The second-generation cephalosporins are not effective against Pseudomonas (Pseudomonas aeruginosa), Acinetobacter, Serratia, Streptococcus faecalis, and the like.

The main varieties of second-generation cephalosporins used clinically include cephalosporin, cefuroxime and cefotiam.

3. Three generations of cephalosporins

The third-generation cephalosporins are generally lower in antibacterial efficacy against Gram-positive bacteria than the first generation (similar to some individual varieties), and are more effective against Gram-negative bacteria than the second-generation cephalosporins.

(1) Antibacterial spectrum expansion The antibacterial spectrum of the third generation cephalosporins has been expanded compared to the second generation. It is effective against Pseudomonas aeruginosa, Serratia, Acinetobacter, Peptococcus, and some Bacteroides fragilis (different Antibacterial efficacy of different types of drugs is not the same). For Streptococcus faecalis, Clostridium difficile and other invalid.

(2) Some gram-negative strains resistant to the first-generation or second-generation cephalosporins, the third-generation cephalosporins are often effective.

4. Four generations of cephalosporins

The third-generation cephalosporins have weaker effects on gram-positive bacteria and cannot be used to control S. aureus infections. In recent years, some new species such as Cefpirome have been discovered, which not only have the antibacterial properties of the third generation cephalosporins but also have an antibacterial effect on staphylococci and are called the fourth generation cephalosporins.

The division of the first to fourth generations applies not only to cephalosporins but also to some other β-lactam antibiotics.

5. Cephamycins

Cephamycins, a nucleus with a cephalosporin, and a trans methoxy group at the 7-position C atom, a cephamycin produced by S. lactamdurans (Cephamy- Cin C) Prepared by semi-synthetic modification of side chains. The main varieties are cefoxitin, cefmetazole, cefotetan and so on. Similar to cephalosporins, are discussed in this section.

The effect of cephamycins on Gram-positive bacteria was significantly lower than that of the first-generation cephalosporins, and their effects on gram-negative bacteria were excellent. The gram-negative bacterial β-lactamases of this class have strong performance. The antibacterial spectrum of cefoxitin is similar to that of the second-generation cephalosporins, and the others are similar to the third-generation cephalosporins. This class of drugs has a strong effect on anaerobes such as V. faba.

6. Oxycephalosporins

The structure of Oxacephems is similar to that of cephalosporins. The S atoms in the mother nucleus are replaced by O atoms, and there is also a trans methoxy group at the 7-position C, such as cephalosporin, whose properties are similar to those of cephalosporins. This type of drug has a stronger effect on anaerobes.

Development History

The cephalosporin compound was first introduced in 1948 by the Italian scientist Giuseppe Brotzu from the ceforium in the drains of Sardinia. He found that these cephalosporins secreted substances that could effectively counteract the typhoid-producing Salmonella typhi. Oxford University has succeeded in extracting cephalosporin C that is stable to beta-lactamase but has not been sufficiently effective for clinical use. The core of the cephalosporin is 7-aminocepsporic acid (abbreviated 7-ACA) which is derived from cephalosporin C and has been shown to be similar to the core of penicillin (ie 6-aminopenicillanic acid, 6-APA). . The modification of the side chain of 7-ACA resulted in some very useful antibiotics. The first cefalotine was issued by Eli Lilly in 1964.

main feature

Cephalosporins can be distributed in various parts of the body, so that infection occurs in various tissues and organs, as long as the pathogen is sensitive to cephalosporins can use it. It is a bactericidal agent. When the concentration is high enough, the bacteria can be killed, unlike those antibacterial agents such as tetracycline, erythromycin, and chloramphenicol, and they generally act as inhibitors of bacterial growth at a conventional dose. Therefore, cephalosporins can be used to compare critical infections.

Advantage 1: The antibacterial spectrum of cephalosporin is relatively wide, and cephalosporin has good antibacterial effect on some Gram-positive bacteria or Gram-negative bacteria. (Bacteria are stained with gram stains. The bacteria stained with purple are positive bacteria, and stained with erythrocytes are negative bacteria). That means for various clinical departments such as internal medicine, surgery, obstetrics and gynecology, and skin Most of the common pathogenic bacteria in the family, cephalosporins often have a certain degree of antibacterial activity, so it is widely used in clinical practice.

Advantage 2: Bacteria can produce resistance to certain antibacterial drugs if they produce some enzymes that destroy certain antibacterial drugs. For example, bacteria are resistant to penicillin, and cephalosporins are most stable to bacteria produced by bacteria. Can replace penicillin to kill bacteria. The cephalosporins are also relatively common in oral administration. This is because there are many varieties of oral into the stomach, the body's stomach acid is difficult to destroy it, the efficacy is relatively stable.

Advantage 3: Compared with penicillin, the incidence of penicillin allergy is relatively high, especially penicillin can cause anaphylactic shock and fatal. The molecular structure of cephalosporins is similar to that of penicillin, which also produces an allergic reaction. However, the incidence of allergic reactions is lower than that of penicillin, and the incidence of anaphylactic shock is even lower.

Due to the above characteristics, it is decided that cephalosporins have a high practical value in clinical practice. [2]

Principle of use

There are several principles to follow for cephalosporins:

Principle One

Can not be abused

Since cephalosporins have so many advantages, they are favored by sick families and doctors. Once a patient is infected and has a fever, cephalosporin is immediately used no matter what kind of infection it is. Especially the third-generation cephalosporins, which are produced in large quantities in our country, are quite cheap, so abuse has been common in the past. In the recent five years, many strains of E.coli, K. pneumoniae and other bacteria that have been difficult to treat in the third generation of cephalosporins have emerged. The extended-spectrum β-lactamase produced by these bacteria can destroy cephalosporin resistance. The proportion of bacteria resistant to 3rd-generation cephalosporins in Shanghai, such as E. coli and K. pneumoniae, has accounted for 10%-40%. A large amount of cephalosporins are abused. As a result, the good antibacterial effects of these drugs have been greatly weakened. The infection caused by these resistant bacteria is clinically difficult to handle.

Principle two

Orally administered orally, intravenous drip

Many patients now actively seek medical advice for intravenous cephalosporins in order to seek recovery sooner. This is wrong. Whether or not to use cephalosporins in the end, do not intravenously, follow the doctor's decision. In the application of cephalosporin when there is a light choice, the infection is relatively light to choose oral, all generations of cephalosporins have oral preparations. The infection is heavier and intravenous administration is optional. Intravenous infusions are usually used with minimal bolus injections. Why is this? This is because, as mentioned above, cephalosporins can also cause adverse reactions. If a patient has a serious allergic reaction or other serious adverse reactions, if a bolus is used, the drug has rapidly entered the bloodstream and the doctor cannot terminate it. medicine. With drip infusion, even if the drip is fast, the patient can immediately slow down the drip rate if he has an adverse reaction, and can even immediately stop the administration. Allow doctors to fight for the rescue.

Principle III

Cannot be mixed with other drugs

In principle, antibacterial drugs and any other drugs cannot be freely mixed together, even if they are all antibacterials. For example, if a patient intravenously injects both cephalosporin and gentamicin antibiotics, it is not possible to place the two drugs in one bottle at the same time. Because of the different physicochemical characteristics of various antibacterial drugs, they are added together and they are visually inspected. The color does not change, and there may not be precipitates. However, in fact, they may have already interacted with each other, reducing their respective antibacterial effects. , It will even produce new compounds that will harm the human body. Therefore, the use of antibiotics must require separate administration. Never place two drugs in one container at the same time. [