What Are the Beta Lactam Antibiotics?

-lactams antibiotics (-lactams) refer to a large class of antibiotics with a -lactam ring in the chemical structure, including the most commonly used penicillins and cephalosporins in clinical practice, as well as newly developed cephalomycins and thiomycetes Other atypical -lactam antibiotics such as hormones and monocyclic -lactams. Such antibiotics have the advantages of strong bactericidal activity, low toxicity, wide indications and good clinical efficacy. The chemical structure of this class of drugs, especially the side chain changes, has formed many antibiotics with different antibacterial spectrum and antibacterial effects, as well as various clinical pharmacological properties.

-lactams antibiotics (-lactams) refer to a large class of antibiotics with a -lactam ring in the chemical structure, including the most commonly used penicillins and cephalosporins in clinical practice, as well as newly developed cephalomycins and thiomycetes Other atypical -lactam antibiotics such as hormones and monocyclic -lactams. Such antibiotics have the advantages of strong bactericidal activity, low toxicity, wide indications and good clinical efficacy. The chemical structure of this class of drugs, especially the side chain changes, has formed many antibiotics with different antibacterial spectrum and antibacterial effects, as well as various clinical pharmacological properties.

Chinese name

beta-lactam antibiotics

Foreign name

-lactams

Types of

antibiotic

Mechanism

Mucosin synthase

Including

Penicillin and its derivatives

Features

Strong bactericidal activity, low toxicity, wide indications, etc.

Introduction to -lactam antibiotics

Beta-lactam antibiotics are a wide variety of antibiotics, including penicillin and its derivatives, cephalosporins, monoamide rings, carbapenems, and penicillin enzymes. Agent. -lactam antibiotics (-lactams) refer to a large class of antibiotics with a -lactam ring in the chemical structure. Basically all antibiotics that include a -lactam nucleus in their molecular structure belong to -lactams Antibiotics, which are the most widely used classes of existing antibiotics, including the most commonly used penicillins and cephalosporins in the clinic, and newly developed cephalomycins, thiomycins, monocyclic -lactams and other Atypical -lactam antibiotics. Such antibiotics have the advantages of strong bactericidal activity, low toxicity, wide indications and good clinical efficacy. The chemical structure of this class of drugs, especially the side chain changes, has formed many antibiotics with different antibacterial spectrum and antibacterial effects, as well as various clinical pharmacological properties.

Mechanism of -lactam antibiotics

The mechanisms of action of various -lactam antibiotics are similar. They can inhibit cell wall mucin synthetase, penicillin binding proteins (PBPs), thereby hindering cell wall mucin synthesis and causing bacterial cell wall defects. Body swelling and lysis. In addition, for fine

Enzymatic functions of E. coli PBPs

The lethal effect of the bacteria should also trigger the autolysin activity of the bacteria, and mutant strains lacking the autolysin show resistance. Animals have no cell wall and are not affected by -lactam drugs. Therefore, this class of drugs has a selective bactericidal effect on bacteria and has low toxicity to the host. In the past ten years, it has been confirmed that the special protein PBPs on the bacterial cytoplasmic membrane is the target of -lactam drugs. The functions of PBPs and their binding to antibiotics are summarized in Figure 38-1. The number, molecular weight, and sensitivity of -lactam antibiotics on the cell membranes of various bacteria are different, but bacteria with similar taxonomy have similar types of PBPs and physiological functions. For example, Escherichia coli has 7 types of PBPs, PBP1A, and PBP1B, which are related to prolonged bacteria. Penicillin, ampicillin, and ceftiofen have a high affinity for PBP1A and PBP1B, which can inhibit the growth and reproduction of bacteria, and dissolve and die. Relevant to the shape, mecillin, clavulanic acid, and thiomycin (imipenem) can selectively bind to it, so that the bacteria form large round cells, stable to osmotic pressure, and can continue to lyse and die after several generations. PBP3 has the same function as PBP1A, but with a small amount. It is related to the formation of septa and bacterial division. Most penicillin or cephalosporin antibiotics mainly combine with PBP1 and / or PBP3 to form filaments and spheroids, which can deform bacteria Atrophy, gradually dissolving to death. PBP1,2,3 are necessary for the survival, growth and reproduction of bacteria. PBP4,5,6 are related to carboxypeptidase activity, which is not important for the survival and reproduction of bacteria. When antibiotics are combined with it, it has no effect on bacteria.

Factors affecting -lactam antibiotics

Factors affecting the antibacterial effect of -lactams

The structure of Gram-positive bacteria is very different from that of negative bacteria. Different side chains connected to the mother nucleus can affect the lipophilicity or hydrophilicity of various -lactam drugs. Effective drugs must be able to enter the target PBPs on the cell membrane. The main factors affecting the antibacterial effect are:

Difficulty of the drug to penetrate the cell wall of Gram-positive bacteria or the outer membrane of negative lipoproteins (that is, the first way to penetrate the barrier);

Stability to -lactamase (secondary enzyme hydrolysis barrier);

Affinity to PBPs with antibacterial targets.

According to these factors, there are roughly 6 types of -lactams currently used clinically on Gram-positive and negative bacteria.

Class I is penicillin and oral penicillin V, which can easily penetrate the mucopeptide layer of the gram-positive bacteria, but they cannot penetrate the outer membrane of the glycoprotein phospholipids of the gram-negative bacteria, so they are narrow-spectrum effective only for gram-positive bacteria.

Type includes ampicillin, carbenicillin, acylurea penicillin, imipenem, and some cephalosporins. It can moderately penetrate the mucosin layer of the gram-positive bacteria and penetrate the outer membrane of gram-negative bacteria. Passive is very good, so it is a broad-spectrum antibacterial drug.

Type is penicillin and other penicillins that are easily destroyed by gram-positive bacteria's extracellular -lactamase, penicillinase, and often show obvious resistance to enzyme-producing bacteria.

Class isoxazole penicillins, cephalosporins 1, 2 and imipenem are stable to penicillinase and effective to Gram-positive enzyme-producing bacteria, but to the structure of PBPs changed by chromosomal mutations, which can make the drug The affinity with PBPs decreases or disappears, and is therefore ineffective.

Type includes ureide penicillins (aloxicillin and meloxicillin, etc.), carbenicillin, and cephalosporins first and second generation. When a small amount of -lactamase in the extracellular space is present, it has antibacterial effect. A large number of enzymes When present, it is destroyed and invalid.

Type VI including third-generation cephalosporins, aztreonam, imipenem, etc. are very stable to -lactamase, and even if a large number of -lactamase is present, it is effective for PBPs that have been changed due to chromosomal mutations. It is not effective, and the addition of aminoglycoside antibiotics is still ineffective.

-lactam antibiotic resistance mechanism

The resistance mechanism of bacteria to -lactam antibiotics can be summarized as:

Bacteria produce -lactamase (penicillinase, cephalosporinase, etc.) to hydrolyze and inactivate susceptible antibiotics;

The broad-spectrum penicillin and second- and third-generation cephalosporins that are stable against -lactamase produced by gram-negative bacteria are not caused by the hydrolysis of antibiotics by -lactamase, but by the antibiotics and a large number of -lactamase binds quickly and firmly, making it stay in the extracellular space, so it cannot enter the target site (PBPs) for antibacterial effect. The non-hydrolytic mechanism of such -lactamase is also called "trapping mechanism";

The decrease of affinity of PBPs target protein and antibiotics, the increase of PBPs or the generation of new PBPs can make antibiotics lose their antibacterial effect. For example, MRSA (methicillin resistant Staphylococcus aureus) has multiple drug resistance, and its mechanism is the result of changes in PBPs. High resistance is due to a new type of PBP2 '(ie, PBP2a) between the original PBP2 and PBP3. Moderate resistance is caused by increased production of PBPs or decreased affinity with methicillin, etc .;

The permeability of the cell wall or outer membrane of the bacteria changes, so that antibiotics cannot or rarely enter the bacteria to reach the target site. The outer membrane of Gram-negative bacteria is the first barrier to limit the penetration of -lactam antibiotics into the bacteria.

In recent years, studies have confirmed that antibiotics penetrate the outer membrane into non-specific channels and specific channels. The outer membrane of E. coli K-12 has a hydrophilic non-specific porin as a trimer structure and has two porosins, namely OmpF and OmpC, whose synthesis is regulated by the OmpB3 gene. OmpF has a diameter of 1 nm, and many important -lactam antibiotics diffuse into the bacteria through this channel. The mutant strains of Salmonella typhimurium OmpF and OmpC deficient mutants are 10 times less permeable to ceftazidime than wild strains, and are therefore resistant. Escherichia coli mutants containing only a small amount of OmpF and OmpC had a doubled penetration of ceftizolin and ceftiophene compared to wild strains, and their MICs were significantly higher and resistant. Pseudomonas aeruginosa resistance to -lactam antibiotics has been proven to be caused by a defect in the outer membrane non-specific channel protein OprF. The specific channel of the gram-negative outer membrane, in the imipenem-resistant mutant of Pseudomonas aeruginosa, has been proven to be due to the loss of an outer membrane of a protein with a molecular weight of 45 to 46 kD, OprD. If this OprD is recombined in the outer membrane protein liposome of the mutant strain with defective OprD, the permeability of imipenem can be increased by more than 5 times, and its MIC is correspondingly reduced, so the drug resistance of bacteria is eliminated.

Due to the lack of autolysozyme, bacteria have resistance to antibiotics, that is, antibiotics have normal bacteriostatic effects, but they have poor bactericidal effects.

-lactam antibiotics penicillins

Basic structure of -lactam antibiotics

Penicillin G is the earliest antibiotic used in clinical practice. Because of its advantages such as strong bactericidal power, low toxicity, low price, convenient use, etc., it is still the drug of choice for treating various infections caused by sensitive bacteria. However, penicillin has disadvantages such as intolerance to acid, penicillinase, narrow antibacterial spectrum, and easy to cause allergic reactions, and is limited in clinical application. Since 1959, people have used penicillin's mother nucleus 6-amino penicillic acid (6-APA) to carry out chemical transformation and connect different side chains to synthesize hundreds of "semi-synthetic penicillins". Chemical structure and pharmacological properties of commonly used penicillin.

-lactam antibiotic penicillin

Penicillin G, also known as benzyl penicillin, is a natural penicillin with a benzyl side chain. Commonly its sodium salt or

penicillin

Potassium salt, whose crystal powder is stable at room temperature, easily soluble in water, and the aqueous solution is unstable at room temperature. After being left at 20 ° C for 24 hours, the antibacterial activity rapidly decreases, and antigenic degradation products can be generated. Therefore, penicillin should be used in clinical use. Before formulating into an aqueous solution.

Antibacterial effect :

Penicillin mainly acts on Gram-positive bacteria, Gram-negative cocci, Haemophilus, and various pathogenic Borrelia.

Penicillin has a strong effect on hemolytic streptococcus, Streptococcus green, Streptococcus pneumoniae, etc., and enterococci are less sensitive. Staphylococcus aureus that does not produce penicillinase and most epistaphylococci are sensitive to penicillin, but Staphylococcus aureus that produces penicillinase is highly resistant to it. Gram-positive bacilli, diphtheria, anthracnose, and gram-positive anaerobic bacilli such as Percobacterium perfringens, Tetanus, Clostridium difficile, Propionibacterium, Eubacteria, and Lactobacillus are all sensitive to penicillin. Meningococci among gram-negative bacteria are highly sensitive to penicillin and are rarely resistant. Penicillin-sensitive gonococci are increasingly rare. Pertussis is sensitive to penicillin. Pathogenic Borrelia, such as Treponema pallidum and Leptospira are highly sensitive to it.

In vivo processes :

Penicillin easily decomposes when exposed to acid, and has poor oral absorption. After intramuscular injection of 1 million units, the absorption is fast and very complete. It reaches the peak plasma concentration in 0.5 hours, about 20 U / ml, and the elimination half-life (t1 / 2) is 1/2 hour. Five million units of penicillin sodium were intravenously dripped within 6 hours, and a blood concentration of 20 to 30 U / ml was obtained after 2 hours. The serum protein binding rate of penicillin was 46% to 58%. Penicillin is mainly distributed in extracellular fluid, lymph fluid, placenta, liver, kidney, lung, striated muscle, middle ear fluid, etc. Penicillin is low in fat solubility and the amount of cells entering it is reduced; the contents of aqueous humor and cerebrospinal fluid are also lower, but the amount of penicillin penetrating into the cerebrospinal fluid and the eyes during inflammation can be slightly increased to reach an effective concentration. Almost all penicillin was excreted in urine in its original form, and about 10% was filtered through the glomerulus. 90% are secreted by the renal tubules. The elimination half-life of penicillin in anuria patients can be extended up to 10 hours. Probenecid can compete with penicillin for renal tubular secretion. When combined with both drugs, it can increase the blood concentration of penicillin and extend its half-life.

In order to prolong the action time of penicillin, the insoluble preparations procaine penicillin and benzathine penicillin (bicillin) can also be used. After intramuscular injection of their aqueous suspension or oil preparation, they are slowly dissolved and absorbed at the injection site. Procaine penicillin can be injected for 400,000 units at a time, which can be maintained for 24 hours. The solubility of benzathine penicillin is very small, and 1.2 million units can be injected at one time, which can be maintained for 15 days. The patient may be used to prevent infection.

Clinical application :

Penicillin is the drug of choice for the treatment of group A and group B hemolytic streptococcal infections, sensitive staphylococcal infections, gas gangrene, syphilis, and rat fever. Pneumococcal infection and meningitis can also be used. When the pathogen is more resistant, vancomycin or rifampicin can be used instead. Penicillin is also the first choice for treating Streptococcus grass endocarditis. It can also be used as the drug of choice for actinomycosis, leptospirosis, syphilis, recurrent fever, etc. and to prevent the occurrence of infective endocarditis. Patients with tetanus and diphtheria should be combined with antitoxin when penicillin is used.

Adverse reactions :

The toxicity of penicillin is very low. In addition to its large amount of potassium salts, it is likely to cause hyperkalemia and intramuscular injection pain. The most common are allergic reactions, including anaphylactic shock, drug eruption, serotype reactions, hemolytic anemia and granulocyte Cell loss and so on. Degradation products such as penicillium thiazole protein, penicillin acid, and penicillin or 6-APA polymer in toxomycin preparations can become allergens. In order to prevent allergic reactions, a detailed medical history should be asked, including medication history, drug allergy history, family history of allergy, and penicillin skin allergy test. When applying penicillin and skin tests, first aid preparations should be made, such as epinephrine, hydrocortisone and other drugs and syringe materials, so that in case of anaphylactic shock, timely treatment can be performed.

In penicillin treatment of syphilis or leptospirosis, symptoms may worsen, known as Herxheimer reaction or contradiction in treatment. This reaction generally occurs 6 to 8 hours after penicillin begins treatment and disappears within 12 to 24 hours. For general discomfort, chills, fever, sore throat, dyspnea, rapid heartbeat, etc. At the same time, there may be aggravation of the disease, and even life-threatening. This response may be the result of an immune complex formed by the Treponema antigen with the corresponding antibody, or it may be related to the release of non-endotoxin pyrogens by Treponema pallidum.

Medication Note :

Peripheral neuritis can occur locally by intramuscular injection, and intrathecal injection and systemic high-dose application can cause penicillin brain pain. Severe infection should be administered by intravenous drip. Large-dose intravenous injection should monitor serum ion concentration to prevent hypernatremia and hyperkalemia.

-lactam antibiotics semi-synthetic penicillin

1. Acid-resistant penicillin and phenoxypenicillin include penicillin V and phenoxyethyl penicillin. The antibacterial spectrum is the same as that of penicillin, and the antibacterial activity is not as good as that of penicillin. It is resistant to acids and oral absorption, but it is not resistant to enzymes and should not be used for severe infections.

2. The chemical structure of enzyme-resistant penicillin is characterized by the steric hindrance of the acyl side chain (R1), which protects the -lactam ring from enzymatic hydrolysis. It is mainly used for penicillin-resistant Staphylococcus aureus infection.

The isoxazole penicillin side chain is phenyl isoxazole, which is resistant to acids, enzymes, and can be taken orally. Commonly used are: oxacillin (neo penicillin ), cloxacillin, dicloxacillin and flucloxacillin.

Antibacterial effect : The antibacterial spectrum of this class of drugs and their effects on drug-resistant Staphylococcus aureus are basically similar. They have the best effect on Streptococcus A. and pneumococcus, but they are not as effective as penicillin. Xilin is the strongest, followed by flucloxacillin, clozacillin, and oxacillin, which have no significant effect on gram-negative enterobacteria or enterococci.

In vivo process : The gastrointestinal tract absorbs well, and food residues will affect its absorption. Therefore, the drug should be taken on an empty stomach one hour before a meal. The blood concentration reaches a peak in about 1 to 1.5 hours, and the effective concentration can be maintained for 2 to 3 hours. Among the drugs, oxacillin was the worst, followed by clozacillin, and diclocillin was the best. Plasma protein binding rates were high (more than 95%). It is mainly excreted from the urine as a prototype and is slower than penicillin.

Adverse reactions : gastrointestinal reactions, individual rash or urticaria.

Clinical application : used for various infections of drug-resistant Staphylococcus aureus, or chronic infections that require long-term medication. For severe Staphylococcus aureus infection, injection should be given.

3. Broad-spectrum penicillin tincture has bactericidal effect on Gram-positive and negative bacteria. It is also acid-resistant and can be taken orally, but not enzyme-resistant.

Amp Ampicillin is less effective than penicillin on penicillin-sensitive Staphylococcus aureus, but it has better effect on enterococci than penicillin. It has a strong effect on gram-negative bacteria, similar to or slightly stronger than chloramphenicol and tetracycline, but not as good as gentamicin and polymyxin, and ineffective against Pseudomonas aeruginosa.

In vivo process: peak plasma concentration is reached 2 hours after oral administration and excretion by the kidney, probenecid can delay its excretion. Effective antibacterial concentrations can be achieved in body fluids, and cerebrospinal fluid concentrations are higher during meningitis.

Clinical application: It is mainly used for typhoid fever, paratyphoid fever, gram-negative bacillus sepsis, pulmonary, urinary tract, and biliary tract infections. In severe cases, it should be combined with aminoglycoside antibiotics.

Adverse reactions: slight gastrointestinal reactions.

Amoxicillin is parahydroxyampicillin. Its antibacterial spectrum and antibacterial activity are similar to ampicillin, but it has a stronger bactericidal effect on pneumococci and proteus than ampicillin. It is well absorbed through the gastrointestinal tract, and the blood concentration is about 2.5 times that of oral ampicillin. Amoxicillin is more effective than ampicillin in the treatment of lower respiratory infections, especially caused by pneumococci.

(3) Pivampicillin is a diester of ampicillin, which is better absorbed by mouth than ampicillin, and can be quickly hydrolyzed to ampicillin to exert antibacterial effect. Normal people take 250mg orally, and their blood and urine concentrations are 3 and 2 times higher than equivalent doses of ampicillin, respectively.

4.Anti-Pseudomonas aeruginosa broad-spectrum penicillin

Carb Carbenicillin has similar antibacterial spectrum to ampicillin. It is characterized by a strong effect on Pseudomonas aeruginosa and Proteus. Poor oral absorption requires injection and prolonged action when renal function is impaired. It is mainly used for various infections caused by Pseudomonas aeruginosa and E. coli. Bacteria are prone to drug resistance when used alone, often combined with gentamicin, but cannot be mixed for intravenous injection. Low toxicity, occasionally cause granulocyte deficiency and bleeding.

Sulbenicillin has similar antibacterial spectrum and strong antibacterial activity. Oral ineffective, the drug concentration in bile is three times the blood concentration, especially in urine, mainly used to treat genitourinary and respiratory infections. Side effects are gastrointestinal reactions with occasional rashes and fever.

(3 ) The antibacterial spectrum of ticarcillin is similar to that of carbenicillin, and its activity against Pseudomonas aeruginosa is 2 to 4 times stronger. The activity of Gram-positive cocci is less than that of penicillin, and it is not absorbed orally. It reaches the peak blood concentration 0.5 to 1.0 hour after intramuscular injection. It is widely distributed, with high drug concentration in bile, and most of it is excreted by the kidney. It is mainly used for various infections caused by Pseudomonas aeruginosa.

Fur Furbenicillin is 6-10 times stronger than Carbenicillin and has a strong antibacterial effect on Staphylococcus aureus, Streptococcus, and Shigella. Side effects are the same as carbenicillin.

Allocicillin (azlocillin) has an antibacterial spectrum similar to that of carbenicillin. Its antibacterial activity is similar to that of piperacillin and stronger than that of carbenicillin. It has a strong effect on most enterobacteriaceae and enterococci and Pseudomonas aeruginosa. It also works well against Carbenicillin and Gentamicin-resistant Pseudomonas aeruginosa. It is mainly used to treat infections caused by Pseudomonas aeruginosa, E. coli, and other enterobacteriaceae.

Rac Piperacillin has a broad antibacterial spectrum similar to that of carbenicillin, but has a strong antibacterial effect and has certain effects on various anaerobic bacteria. Combined with aminoglycosides, it has a synergistic effect on Pseudomonas aeruginosa and certain B. fragile and Enterobacteriaceae bacteria. Except for S. aureus producing penicillinase, it is very sensitive to other Gram-negative cocci and anthracis. There are fewer adverse reactions, which can be administered intramuscularly and intravenously. It has been widely used in clinical practice.

-lactam antibiotics cephalosporins

Basic structure of -lactam antibiotics

Cephalosporin antibiotics are semi-synthetic antibiotics made from the parent nucleus of 7-aminocephalosporanic acid (7-ACA) with different side chains.

Cephalosporins quickly grab the market

This class of antibiotics has the advantages of broad antibacterial spectrum, strong bactericidal activity, stability to gastric acid and -lactamase, less allergic reactions, and only partial cross-allergy with penicillin. According to its antibacterial effect and clinical application, it can be divided into four generations of cephalosporins.

Classification characteristics of -lactam antibiotics

First-generation cephalosporins such as cephalexin, cefradine, cefazolin, etc.

The antibacterial effect on Gram-positive bacteria (including S. aureus that is sensitive or resistant to penicillin) is stronger than that of the second and third generations, and the effect on Gram-negative bacteria is poor;

Stable to penicillinase, but can still be destroyed by -lactamase of gram-negative bacteria;

It is toxic to the kidneys.

Second-generation cephalosporins such as cefuroxime, cefmendo, cefaclor, etc.

The effect on Gram-positive bacteria is similar to or slightly worse than that of the first-generation cephalosporins, and the effect on most Gram-negative bacteria is significantly enhanced. Some of them are highly effective against anaerobic bacteria, but are not effective against Pseudomonas aeruginosa;

relatively stable to a variety of -lactamase;

The toxicity to the kidney is lower than that of the first generation.

Third-generation cephalosporins such as cefotaxime, ceftazidime, ceftriaxone, cefoperazone, ceftizoxime, etc.

It has considerable antibacterial activity against Gram-positive bacteria, but it is not as good as the first and second-generation cephalosporins, and it has a strong effect on Gram-negative bacteria including Enterobacter spp.

The plasma t1 / 2 is longer, the body is widely distributed, the tissue penetration is strong, and a certain amount of penetration into the cerebrospinal fluid;

High stability to -lactamase;

Basically non-toxic to kidneys.

Fourth-generation cephalosporins such as cefepime, cefpirome, etc.

1. Compared with the third-generation cephalosporins, the affinity with -lactamase is reduced, the stability to AmpC enzyme is higher, and the bacterial cell membrane is more penetrating.

2. A broader antibacterial spectrum, methicillin-sensitive staphylococci and certain class I enzyme-negative bacilli such as Enterobacter spp., Froudis citrate bacillus, Serratia spp., Demonized Morgan spp. Both have strong antibacterial effects.

3. The activity against Pseudomonas aeruginosa is similar to or slightly worse than ceftazidime, and it also has good antibacterial activity against anaerobic bacteria.

4. The blood half-life is prolonged, and there is no nephrotoxicity.

Antibacterial mechanism of -lactam antibiotics

Antibacterial spectrum is wide, most gram-positive bacteria are sensitive to it, but enterococci are often resistant; most gram-negative bacteria are extremely sensitive, except for individual cephalosporins, Pseudomonas aeruginosa and anaerobic bacteria are often resistant. There is a synergistic antibacterial effect between this class of drugs and penicillin and aminoglycoside antibiotics.

Cephalosporins are bactericidal drugs. Their antibacterial mechanism is similar to that of penicillins. They can also bind to different penicillin-binding proteins (PBPs) on the cell wall.

Bacteria are partially cross-resistant to cephalosporins and penicillins.

Beta-lactam antibiotics in vivo processes

Need more injections. However, cephalexin, cefadroxil, and cefaclor are acid-resistant, have good gastrointestinal absorption, and can be taken orally.

After cephalosporin absorption, it is well distributed, can penetrate into various tissues, and easily penetrate the placenta. High concentrations can be obtained in bursal fluid and pericardial effusion. Cefuroxime and third-generation cephalosporins are mostly distributed in the prostate. Third-generation cephalosporins can also penetrate into the aqueous humor of the eye. The concentration in bile is also higher. Cefoperazone is the highest, followed by ceftriaxone. Cefuroxime, ceftriaxone, cefotaxime, ceftazidime, cefoperazone, etc. can penetrate the blood-brain barrier and reach effective concentrations in the cerebrospinal fluid. The plasma t1 / 2 of most cephalosporins is short (0.5 to 2.0 hours), but the t1 / 2 of ceftriaxone is the longest, which can reach 8 hours.

-lactam antibiotic adverse reactions

Common cases are allergic reactions. Occasionally, anaphylactic shock, asthma, and immediate skin rash are seen. About 5% to 10% of people with penicillin allergies have cross-allergic reactions to cephalosporins; intravenous administration can cause phlebitis; Renal toxicity can occur at high doses of cefotaxime, cefotaxime, and cephalexin, which is related to the damage of proximal tubule cells. Because the sodium content of cephalosporin can reach 2.0-3.5Eq / g, attention should be paid to the occurrence of hypernatremia in a large amount of intravenous injection.

Disulfiram-like reactions can occur in cefmendo, cefoperazone, and the third generation of cephalosporins occasionally have double infections or the proliferation of enterococci, Pseudomonas aeruginosa, and candida. Hypoprothrombinemia may occur at high doses of cefmendo and cefoperazone.

Clinical application of -lactam antibiotics

The first generation of cephalosporins is mainly used for drug-resistant Staphylococcus aureus infections. Cephalotin, cefradine, and cefazolin are commonly used. The latter has the highest intramuscular injection concentration of cephalosporins and is the most widely used variety in the first generation. . Oral cephalosporins are mainly used for mild to moderate respiratory and urinary tract infections.

Second-generation cephalosporins are used to treat pneumonia, biliary tract infections, bacteremia, urinary tract infections, and other tissue and organ infections caused by sensitive bacteria such as Escherichia coli, Klebsiella, Enterobacteriaceae, and indole-positive Proteus. The more commonly used are cefuroxime and cefmendo.

The third-generation cephalosporins can achieve satisfactory results in the treatment of urinary tract infections and severe infections such as life-threatening sepsis, meningitis, and pneumonia. Third-generation cephalosporins are also available for meningococcal pneumonia. Ceftazidime is currently the strongest antibiotic against Pseudomonas aeruginosa in clinical use. In addition, cefoperazone is also available. For enterobacteriaceae ceftriaxone and cefotaxime are similar, cefoperazone is slightly worse. Adult meningitis caused by neonatal meningitis and enterobacteriaceae should be selected from the third generation of cephalosporins.

-lactam antibiotics atypical

Atypical beta-lactam antibiotics

-lactam antibiotics cephalomycins

Cephamycin is a -lactam antibiotic obtained from Streptomyces. There are three types of A-, B-, and C-types. The C-type is the strongest. Broad antibacterial spectrum, strong effect on Gram-negative bacteria, stable to a variety of -lactamase. The chemical structure of cephalosporin is similar to that of cephalosporins, but the cephalosporin has a methoxy group on the carbon at position 7. At present, cefoxitin is widely used. Its antibacterial spectrum and antibacterial activity are the same as those of the second-generation cephalosporins. It has a good effect on anaerobic bacteria, including Bacteroides fragile, and is suitable for aerobic infections such as pelvic infection, gynecological infection and abdominal cavity Mixed infection with anaerobic bacteria.

-lactam antibiotic

Lamoxef is also known as moxalactam. Its chemical structure is oxycephem. Sulfur at position 1 is substituted by oxygen. There is also a methoxy group at the 7-position carbon. It has a broad antibacterial spectrum and antibacterial activity. Similar to oxime, it has a strong effect on Gram-positive and negative bacteria and anaerobic bacteria, especially B. fragile, is extremely stable to -lactamase, and maintains blood drug concentration for a long time.

- beta-lactam antibiotic beta-lactamase inhibitor

1. Clavulanic acid (Clavulanic acid) is a broad spectrum -lactamase inhibitor of oxypenicillin, which has a broad antibacterial spectrum but low antibacterial activity. When combined with a variety of -lactam antibiotics, the antibacterial effect is significantly enhanced. Clinical use of augmentin (amulinin) and timentin (timentin), clavulanic acid and amoxicillin and ticarcillin are compatible preparations.

2. Sulbactam (sulbactam, penicillane sulfone) is a semi-synthetic -lactamase inhibitor, which has a strong and irreversible inhibitory effect on -lactamase produced by Staphylococcus aureus and Gram-negative bacilli. Slightly stronger than clavulanic acid, but it needs to be combined with other -lactam antibiotics, which has obvious antibacterial synergy. Unasyn is a mixture of sulbactam and ampicillin (1: 2) for intramuscular or intravenous injection. Sulperazone is a mixture of sulbactam and cefoperazone (1: 1) for intravenous infusion.

- -lactam antibiotics monocyclic -lactams

Aztreonam is the first monocyclic -lactam antibiotic successfully used in the clinic. It has a strong bactericidal effect on aerobic gram-negative bacteria, and has resistance to enzymes, low toxicity, and no cross-allergy to penicillin. And other advantages, can be used for patients with penicillin allergy and often used as a substitute for aminoglycosides.

-lactam antibiotics carbapenems

Carbapenem antibiotics are atypical -lactam antibiotics with the broadest antibacterial spectrum and the strongest antibacterial activity . Because of their stability to -lactamase and low toxicity, they have become the most important treatment for severe bacterial infections. One of the antibacterial drugs. Thienymycin (thienamycin) has a chemical structure of carbapenems, a thiazole ring has a saturated chain, and the sulfur at position 1 is substituted by carbon. Amipenem (imipenem) has high efficiency, broad antibacterial spectrum, and enzyme resistance. It is easily inactivated by dehydropeptidase in vivo. The combination of this product and the peptidase inhibitor cilasTATin is called tienam, which has good stability and is suitable for intravenous drip infusion.

Carbapenem antibiotics are a new class of -lactam antibiotics modified from the structure of penicillin. They were introduced in the 1980s. Its structure is similar to the penicillin ring of penicillins, except that the sulfur atom on the thiazole ring is replaced by carbon, and there is an unsaturated double bond between C2 and C3. In addition, the 6-hydroxyethyl side chain is inverse Conformation. Studies have shown that it is this special configuration group that makes this compound significantly different from the usual cis conformation of penicillin, has a broad spectrum, strong antibacterial activity , and a high degree of -lactamase activity . stability. Currently, Taineng (imipenem and cilastatin) and meropenem are used.

Preparation and usage

Penicillin G potassium or penicillin G sodium (penicillin G sodium, benzyl penicillin potassium or sodium) is prepared as a solution immediately before use, usually 400-800,000 units / time, intramuscular injection, common infection 2 times / day, severe infection 4 times a day, the total daily amount can be increased if necessary. It can be used as an intravenous infusion in severe infections, but intravenous infusion of potassium salts should be avoided. The potassium content should also be calculated during infusion (39 mg of potassium ion per 600,000 units of penicillin potassium salt), and pay attention to the infusion rate to prevent blood Potassium is too high. When the dosage is large or the patient has renal insufficiency, the sodium salt infusion should be used instead.

Procaine benzylpenicillin (400,000 units / time, once / day), intramuscular injection, can produce quick-acting and long-acting effects.

Benzonthine benzylpenicillin is administered once or twice a month for adults and once a month for children at 600 to 1.2 million units / time by intramuscular injection.

Oxacillin sodium (neoxacin ) is 0.5 to 1.0 g / time for adults, 4 to 6 times / day, and 50 to 100 mg / kg / day for children, divided into 4 to 6 times. It should be taken 1 hour before or 2 hours after a meal to prevent food from interfering with absorption. The dosage for intramuscular injection is the same as oral, intravenous drip, 4-6g / day for adults, 50-100mg / kg / day for children.

Cloxacillin sodium is 250 to 500 mg / time for adults, 2 to 4 times / day; 30 to 60 mg / kg / day for children, to be taken orally 2 to 4 times. Intramuscular injection dose is the same as oral.

Dicloxacillin is 1-3 g / day for adults and 30-50 mg / kg / day for children.

Flucloxacillin for adults 0.125 0.25g / time, 4 times a day or 0.5 1.0g, 3 times a day orally.

Ampicillin for adults: 0.25 1g / time, 4 times / day; children: 20 80mg / kg / day, divided into 4 times. Intramuscular injection dose is the same as oral. Intravenous injection or intravenous drip, 2-6g / day for adults, 50-150mg / kg / day for children.

Amoxycillin (0.3 to 0.6 g / time for adults, 3 to 4 times a day orally, children under 10 years of age, 0.15 g / time for mild cases, 3 times / day, orally).

Pivampicillin has mild to moderate infections, 1.5 to 2.0 g / day in adults, 3 to 4 g / day in severe infections, 40 to 80 mg / kg / day in children, and 3 to 4 doses.

Carbenicillin was injected intramuscularly, 4 g / day for adults, 100 mg / kg / day for children, 4 times. Intravenous injection or intravenous drip is used for Pseudomonas aeruginosa infection, 10 to 20 g / day for adults, and 100 to 400 mg / kg / day for children.

Furbenicillin (furbenicillin) 4 to 8 g / day for adults, 50 to 150 mg / kg / day for children, divided into 4 intravenous injections or intravenous drips.

Sulbenicillin (2 to 4 g / day for adults, 8 to 13 g / day for severe cases), divided intramuscular injection, intravenous injection or intravenous drip, 40 to 160 mg / kg / day for children.

Ticarcillin is injected intramuscularly or intravenously at the same dose as carbenicillin or sulfenicillin.

Piperacillin (4 to 8 g / day for adults, 100 to 150 mg / kg / day for children); intravenous injection, 8 to 16 g / day for adults, and 100 to 300 mg / kg / day for children, divided into 4 injections.

Mecillinam (1.6 to 2.4 g / day for adults, 30 to 50 mg / kg / day for children) is given intravenously or intramuscularly in 4 doses.

Cephalotin sodium (cephalosin I) adult 0.5g / time, 4 times / day, intramuscular injection; 2 to 4g daily in severe infection, intravenous injection or intravenous drip.

Cephadidine (cephaloridine) for adults 0.5 ~ 1.0g / time, 2 ~ 3 times / day, intramuscular injection, the daily amount does not exceed 3 to 4 times.

Cefazolin (cefazolin) adult 500mg / time, 2 to 4 times / day, intramuscular or intravenous injection, severe disease or drug-resistant strain, the dose can be increased to 3 ~ 5g / day. The dose for children is 20 to 100 mg / day.

Cefradine (cefradine) for adults 1 to 4 g / day, divided into 4 doses, for severe cases can be injected intravenously, no more than 8 g daily, children 50 to 100 mg / kg / day, divided into 4 divided doses.

Cefadroxil is taken 2 g / day for adults, divided into 2 doses; 30-60 mg / kg / day for children, divided into 2 to 3 doses.

Cefamandole (cefamandole) is 2 to 4 g / day for adults, 50 to 100 mg / kg / day for children, and is injected intramuscularly in 3 to 4 times. Intravenous injection is 8-12 g / day for adults and 100-200 mg / kg / day for children, divided into 2 to 4 times.

Cefuroxime is injected intramuscularly, 2 to 2.5 g / day for adults, 30 to 60 mg / kg / day for children, divided into 3 to 4 times. Intravenous injection, 4.5 to 6 g / day for adults, 50 to 100 mg / kg / day for children, divided into 2 to 4 times.

Cefaclor (cefaclor) for adults 2 to 4 g / day, divided into 4 oral doses.

Cefotaxime intramuscular injection, 2-6g / day for adults, 50-100mg / kg / day for children, 3 to 4 times; intravenous injection, 2-8g / day for adults, 50-150mg / kg / day for children , 2 to 4 times.

Ceftriaxone (ceftriaxone) was injected intramuscularly, 1 g / day, dissolved in 3.5 ml of lidocaine injection, and injected deep. Intravenous infusion, 0.5 ~ 2g / day for adults, once dissolved in normal saline or 5% glucose solution, and finished in 30 minutes.

Ceftazidime: 1.5-6g / day for adults, 50-100mg / kg / day for children, 3 intravenous injections, rapid intravenous drip or intramuscular injection, the latter is usually dissolved in 1% lidocaine 0.5ml, Deep injection.

Cefoperazone (cefoperazone) 2 to 4 g / day for adults, 50 to 150 mg / kg / day for children, 2 to 3 intravenous drips, boluses or intramuscular injections.

Cefoxitin (cefoxitin) 3 to 8 g / day for adults, 3 to 4 times, 45 to 120 mg / kg / day for children, 4 to 6 intravenous drips, or intramuscular injection.

Lamoxef 1 to 2 g / day in adults, divided into two intravenous injections, intravenous drip or intramuscular injection, 4 g / day or higher in severe cases. Children 40 to 80 mg / kg / day, severe cases can be increased to 150 mg / kg / day, divided into 2 to 4 injections.

Adults imipenem 1-2g / day, 4 intravenous injections, should be combined with dehydropeptidase inhibitors, such as Taining.

Aztreonam Adult: 1.5-6g / day, divided into 3 times, intramuscularly, intravenously or intravenously (medicine is added to 100ml physiological saline, and the drip is completed within 30 minutes).

Harmful effects of beta-lactam antibiotics

Beta-lactam antibiotic side effects

Side effects of -lactam antibiotics include: diarrhea, dizziness, rashes, urticaria, overlapping infections (including Candida) (Rossi, 2004). Occasionally -lactam antibiotics can cause fever, vomiting, erythema, skin Inflammation, angioedema, and pseudomembranous enteritis (Rossi, 2004)

Beta-lactam antibiotics and beta-lactamase inhibitors are often painful and inflamed when injected at the same time.

beta-lactam antibiotic allergy

About 10% of patients are allergic to beta-lactam antibiotics. Allergic reactions occur in about 0.01% of patients (Rossi, 2004). About 5-10% of patients are cross-sensitive to penicillin derivatives, cephalosporins, and carbapenem antibiotics. However, different scholars question this conclusion.

Even so, if a patient has shown a hypersensitivity reaction to a beta-lactam antibiotic, care must be taken when using other beta-lactam antibiotics.