Introduction to cephalosporins

Cephalosporins (Cephalosporins) is Cephalosporium cephalosporium culture medium separated cephalosporin C, the transformation of the side chain and obtained a series of semi-synthetic antibiotics. Its advantages are: broad spectrum of antibacterial, anaerobic bacteria are efficient; caused by allergic reactions than penicillin low; on the acid and a variety of bacteria produced by the β-lactamase more stable; mechanism of action with penicillin, but also inhibition of bacterial cell wall To achieve the purpose of sterilization. Is a breeding period of bactericidal drugs. Because of its adverse reactions and low side effects, is currently developing a class of antibiotics.

The basic classification of cephalosporins

Fourth-generation cephalosporins from third-generation cephalosporins developed from, but with the third-generation cephalosporins and a significant difference between the new generation of cephalosporins. It is structurally characterized by the introduction of C-3 'quaternary ammonium substituents at the C-3 position of the 7-aminocephalosporanic acid (7-ACA) nucleus on the basis of the molecular structure of the third generation cephalosporins; , The above structure changes make it more quickly through the outer membrane of gram-negative bacilli, penicillin-binding protein has a higher affinity for bacterial β-lactamase more stable; from the antibacterial spectrum , Which has a stronger antibacterial activity against Gram-positive cocci. According to the molecular structure C-7 on the side chain can be divided into two different sub-categories: 2-amino-5-thiazole subclass and 5-amino-2-thiazole subclass.

The main characteristics of cephalosporins

1, Antibacterial spectrum is broader

The antibacterial activity of cefpirome and cefepime against Enterobacteriaceae bacteria was stronger than that of ceftazidime and cefotaxime, and the antibacterial activity against cefotaxime was better than that of cefotaxime but slightly lower than that of ceftazidime. But it is worth noting that the fourth-generation cephalosporins on Gram-positive cocci such as Staphylococcus, Streptococcus, especially the penicillin-resistant Streptococcus pneumoniae than the third-generation cephalosporins significantly enhanced bactericidal activity. From the existing data, in the fourth-generation cephalosporins to cefpirome against Gram-positive cocci the strongest antibacterial effect. It should be noted that the fourth-generation cephalosporins are not ideal for anaerobic and methicillin-resistant Staphylococcus aureus (MRSA).

2, The β-lactamase has better stability

Compared with third-generation cephalosporins, the fourth-generation cephalosporins on the Richmond-Sykes classification I by the chromosome-mediated β-lactamase has good stability. Notably, they are also very stable against β-lactamases mediated by the AmpC gene. The AmpC gene is a structural gene coding for β-lactamases in almost all gram-negative bacilli. In some bacteria such as Escherichia coli, the AmpC gene is low in expression, not enough to cause bacterial resistance, but other bacteria such as the gut AmpC gene expression of Enterobacteriaceae, Citrobacter freundii, Serratia marcescens and Pseudomonas aeruginosa can be induced, and various β-lactam antibiotics can induce it, which can cause the enzyme level to be several hundred Thousands of times higher and caused a variety of β-lactam antibiotics cross-resistance, in particular, can cause resistance to third-generation cephalosporins, so it caused by bacterial resistance in clinical treatment is quite Tricky. Since the fourth-generation cephalosporins are stable against AmpC gene-mediated beta-lactamases, the fourth-generation cephalosporins can be tested when gram-negative bacilli are resistant to third-generation cephalosporins. It should be noted that the fourth-generation cephalosporins on TEM-4, SHV-2, SHV-3, SHV-4 and other broad-spectrum enzymes are still unstable, so it is not resistant to all third-generation cephalosporin leather Blue-negative bacteria are effective.

In the pharmacokinetics of the characteristics

And the fourth-generation cephalosporins pharmacokinetic characteristics of roughly the same. Although the fourth-generation cephalosporins short half-life, but serum drug peak concentration. An intravenous injection of 2 grams of cefepime in 4 hours after Pseudomonas aeruginosa, 8 hours after the Staphylococcus aureus, Enterobacteriaceae bacteria, Streptococcus still bactericidal effect. It has been reported that cephalosporins, etc. can effectively through the blood-brain barrier, in the tracheal mucosa, lung tissue drug concentrations were 56% of its plasma concentration, 36%.

Clinical application of cephalosporins

Fourth-generation cephalosporins for the treatment of nosocomial pneumonia is due to the characteristics of pathogens and the fourth-generation cephalosporins antibacterial spectrum and antibacterial activity of the decision. To tracheal intubation patients, for example, early pathogens to Staphylococcus aureus, Haemophilus influenzae-based, while the latter are mostly Enterobacteriaceae bacteria and Pseudomonas aeruginosa, and the fourth-generation cephalosporins can effectively kill These bacteria, so clear pathogens, the choice of fourth-generation cephalosporins as an empirical treatment is desirable. Serious social-acquired pneumonia is the main pathogen Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, these bacteria are the fourth-generation cephalosporins are very sensitive, it was recommended as an empirical The first line of treatment for such infections. Studies have shown that in the treatment of severe social-acquired pneumonia, cefepime and ceftazidime clinical effective rate was 87%, 66%.

In a variety of reasons such as chemotherapy, leukemia caused by the lack of co-infection of granulocytes, ceftazidime has been successfully applied to the experience of anti-infective therapy. However, in recent years Gram-positive bacteria such as Staphylococcus aureus, coagulase-negative Staphylococcus aureus, hemolytic streptococcus infection has an upward trend, ceftazidime for AmpC gene-related β-lactamase and unstable, while the fourth-generation cephalosporium Su-just to overcome the above two deficiencies, it is possible to replace ceftazidime and become the first choice for empirical treatment of drugs. In a multicentre randomized controlled clinical trial of agranulocytosis with co-infection, pathogens were predominantly Staphylococcus epidermidis and Staphylococcus aureus, with cefpirome and ceftazidime achieving clinical efficiencies of 74%, but the bacterial clearance rate , Cephalosporin (89%) was superior to ceftazidime (74%), hospital infection sepsis and the situation is similar.

75% of bacterial meningitis by meningococcus, Haemophilus influenzae, Streptococcus pneumoniae caused after admission may also be secondary to Gram-negative bacilli, Staphylococcus aureus infection. Since the fourth-generation cephalosporins have good bactericidal activity against these bacteria and through the blood-brain barrier, it is expected to be in the treatment of meningitis infection to achieve better results.

In summary, the fourth-generation cephalosporins have the distinction between the first, second and third generation cephalosporin certain characteristics, such as broader antibacterial spectrum, the β-lactamase more stable, high plasma concentration, through Blood-brain barrier. Preliminary clinical results also demonstrate some of the advantages of these drugs. It is expected that these drugs will soon enter the country, whether in the respiratory department and other clinical subjects of the application value, subject to the majority of clinicians objective evaluation.