What Are 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. 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 (see figure); in addition, its 6-position hydroxyethyl group The side chains are in the trans 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.

Chinese name: Carbapenem antibiotics
Types of: antibiotic

Mechanism: Mucosin synthase
Commonly used drugs: Imipenem, Meropenem, Ertapenem, etc.
Features: -lactamase resistance, broad spectrum, strong antibacterial activity

Carbapenems

The domestically marketed varieties are imipenem, meropenem, panipenem, urtapenem, biapenem, and donipenem.

[ Development time to market and development company ]

1 Imipenem cilastatin sodium (trade name: Taineng) was successfully developed by Merck Company in 1979.

2 Panipenem Betametholone (Kempinin) is a variety developed by Sankyo Co., Ltd., which was launched in March 1994. Listed in China in 2002.

3 Meropenem was developed by Sumitomo Pharmaceuticals in Japan and I-CI Pharmaceuticals in the United Kingdom. It was launched in Italy in 1994. Entering the Chinese market in 1999, it is a Class B drug for national medical insurance.

4 Ertapenem is a new type of long-acting penicillin for injection developed by Merck Company, USA, trade name: Yiwanzhi. Entered the Chinese market in 2005.

5 Biapenem is a new carbapenem antibiotic developed by Wyeth-lederle laboratory. It was launched in Japan in November 2002. In 2008, Xiansheng Pharmaceutical was listed in China for the first time under the trade name: Anxin. It is a Class B drug for national medical insurance.

Characteristics of Carbapenems

Carbapenem antibacterial activity

Imipenem, meropenem, and panipenem have strong antibacterial activity against most Gram-positive, negative aerobic bacteria, anaerobic bacteria, and multidrug-resistant bacteria, but methicillin-resistant Staphylococcus and fecal intestines Cocci, Stenotrophomonas maltophilia, etc. are resistant to this product. At a concentration of 8mg? L-1, imipenem can inhibit more than 90% of the main pathogenic bacteria. Meropenem's effect on staphylococci and enterococci is 2-4 times weaker than that of imipenem, and it is also resistant to methicillin-resistant staphylococcus and enterococcus faecium; but the antibacterial activity against enterobacteriaceae is imipenem 2-16 times the antibacterial activity against Pseudomonas aeruginosa is 2-4 times that of imipenem. Panipenem's antibacterial activity against G + bacteria is similar or slightly stronger than that of imipenem, and its antibacterial activity against Enterobacteriaceae is similar to that of imipenem, and its antibacterial activity against Pseudomonas aeruginosa is inferior to that of imipenem. south.

Carbapenem stability

Carbapenems are highly stable to plasmid-mediated extended-spectrum -lactamases (ESBLs), chromosomes, and plasmid-mediated cephalosporinases (AmpC enzymes). However, it can be hydrolyzed and inactivated by metal -lactamase, causing carbapenem antibiotic resistance.

Carbapenem- binding protein

PBP is a special protein molecule on the bacterial cell membrane, and it is also the target of -lactam antibiotics. Carbapenems are tightly bound to PBP and show strong bactericidal activity. Imipenem binds to PBP, especially PBP2, which has a strong affinity, hinders the synthesis of cell walls, can quickly swell and dissolve bacteria, and its effects are rarely affected by the amount of inoculated bacteria and pH value (5.5-8.5). Meropenem quickly penetrated to the target site, mainly binding tightly to PBP2 and PBP3. The affinity of Panipenem to PBP of P. aeruginosa was PBP2, PBP1A, PBP3, PBP1B, PBP4 in that order.

The relationship between carbapenems and endotoxin

Antibiotics can induce endotoxin production. Many antibiotics are endotoxin inducers. Fast-acting antibiotics are the strongest endotoxin inducers. -lactam antibiotics are related to the point of action of PBPS. Imipenem acts on PBP2. Only a small amount of endotoxin was induced, while meropenem and panipenem acted on PBP2 and PBP3, and the level of induced endotoxin release was higher than that of imipenem. Increased endotoxin levels in the blood circulation are associated with worsening hemodynamic parameters. Although the body has the ability to clear endotoxins, for some severely infected patients, due consideration should be given to the treatment options.

Mechanism of Carbapenems

Mode of action: Carbapenem antibiotics all inhibit the mucosin synthase enzymes, namely penicillin-binding proteins (PBPs), thereby hindering the synthesis of mucosin in the cell wall, causing the bacterial cell wall to be defective, and causing the bacterial cytoplasm to penetrate due to the expansion of the bacterial cell. Changes in pressure and lysis of cells kill bacteria. Mammals have no cell wall and are not affected by such drugs, so 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 cytoplasmic membrane of the bacterium is the target of this drug. For example, the combination of imipenem and PBP, especially the strong affinity of PBP2, hinders the synthesis of the cell wall and makes the bacteria quickly. Swelling, lysis, and its effect is rarely affected by the amount of inoculated bacteria (PH 5.5 ~ 8.5). Meropenem can quickly penetrate into Enterobacteriaceae and Pseudomonas aeruginosa targets, and is mainly tightly bound to PBP2 and PBP3. Panipenem targets PBP1 and PBP3 on Staphylococcus aureus and PBP2 on E. coli, P. aeruginosa, and Pseudomonas aeruginosa.

Pharmacological properties of carbapenems

Antibacterial active carbapenem antibiotics are by far the broadest antibacterial spectrum and a very strong class of antibiotics. They are highly stable against a variety of -lactamase enzymes and can still exert excellent antibacterial effects against cephalosporin-resistant bacteria. Bacteria do not have cross-resistance to this class of drugs, so they have strong antibacterial activity against Gram-positive, negative, and anaerobic bacteria.

Panipenem's antibacterial activity against gram-positive bacteria is similar or slightly stronger than imipenem, while meropenem is less effective against gram-positive bacteria; meropenem has the strongest anti-negative bacteria activity, and its anti-negative bacteria have The activity is 2-16 times that of imipenem; the activity against Pseudomonas aeruginosa is also the strongest with meropenem, which is 4 times that of imipenem. The antibacterial activity of meropenem and other drugs was determined by the agar double dilution method for 412 clinically isolated pathogenic bacteria. The results show that meropenem has a stronger antibacterial activity against a variety of gram-negative bacteria, stronger than imipenem, cefepime, ceftazidime, ciprofloxacin, netilfloxacin; against Escherichia coli, gram The MIC90 of the genus Rabbiella, Enterobacter aerogenes, Shigella, Salmonella, Lemongrass, Proteus, Serratia is 0.08 0.25ug / ml, which is 1 of the imipenem MIC90. / 4 1/16; antibacterial activity against Enterobacter cloacae and Acinetobacter is equivalent to imipenem, MIC90 is 0.25 0.5ug / ml; MIC90 is 0.125ug / ml, which is sub- 1/16 of amipenem MIC90 is 1/4 of cefepime MIC90. The effect on gram-positive bacteria is worse than imipenem, but it is better than other 4 antibiotics.

Carbapenem resistance and its production mechanism

The emergence of new antibacterial drugs is always accompanied by the development of bacterial resistance. Although the resistance of the bacteria to carbapenems was quite low at the beginning of use, the sensitivity to common pathogenic bacteria was quite high. Like other -lactams, enes have emerged as resistant strains after clinical application. Imipenem has been used clinically for many years. The strains resistant to imipenem are Xanthomonas, Enterococcus faecalis, and methicillin-resistant Staphylococcus. Pseudomonas aeruginosa resistant to imipenem is still sensitive to meropenem.

At present, the main clinical pathogenic bacteria are rarely resistant to carbapenems. The resistance mechanisms are: 1. Penicillin binding protein declines, mainly found in methicillin-resistant Staphylococcus and some enterococci; 2. Type -lactamase hydrolyzes the weak activity of carbapenems and the bacteria's decreased permeability to carbapenems results in drug resistance, mainly found in some Enterobacteriaceae and Pseudomonas aeruginosa; 3. Zinc -lactamase hydrolyzes carbapenems. Most of these strains are clinically rare pathogenic bacteria.

Clinical application of carbapenems

Carbapenem antibiotics are mainly used in the following three types of patients:

1. Severe infections include fever patients with nosocomial acquired pneumonia, sepsis, peritonitis, and neutropenia. Before the pathogen is identified, in order to cover the possible pathogens as much as possible, it is often used as the drug of choice for empirical treatment. After the pathogen is identified, it can continue to be used. Can be "step down treatment".

2. Treatment of multidrug-resistant bacteria infections, such as infections with ESBLs-producing strains, AmpC-enzyme-producing strains, or both ESBLs- and AmpC-enzyme-producing strains.

3 Peritonitis, pneumonia, and sepsis caused by bacteria with unsatisfactory curative effects of the third and fourth generations of cephalosporins and composite preparations.

Imipenem (IMP) is a brand name Taineng, composed of imipenem-cilastatin (1: 1), and has a curative effect of more than 95% on septicemia, urinary tract infections and gynecological infections caused by sensitive bacteria. , The effect on soft tissue, bone joints and intra-abdominal infection is more than 90%, the effect on lower respiratory tract infection is 85%, and the bacterial clearance rate is 76% -92%. Pregnant women should be weighed carefully after weighing the pros and cons. This product is not suitable for the treatment of meningitis and cannot be combined with acyclovir. Taineng dosage is 0.5 g or 1.0 g every 6-12 for adults and 12.5 mg / kg for children. The dosage should not be too fast. When the dosage is 500 mg or more, the infusion time should be more than 30-60min.

Meropenem (MEP) is a trade name of Meiping. Meropenem has a satisfactory effect on sepsis, pulmonary infections including pulmonary cystic fibrosis and infection, abdominal infections, and meningitis. The dosage of meropenem is 0.5-1g for adults, and it is given intravenously every 6-8h, and 10-20mg / kg for children every 6-8h. When treating meningitis, it is recommended to take 2g each time, once every 8h, in order to reach a sufficient concentration in the cerebrospinal fluid.

Panipenem (PAPM), trade name Kebenin, is composed of Panipenem-Betamirone (1: 1), and is suitable for sepsis, osteomyelitis, lung infections, empyema caused by sensitive bacteria , Biliary infection, abdominal infection, meningitis, etc. The clinical effectiveness and bacteriological effect are over 80%. Kebenin is administered at a dose of 0.5g (based on panipenem), bid, the highest daily dose is 2g intravenously, 10-20 mg / kg for children, and 2-4 intravenously daily.

Carbapenem Indications

Carbapenems have a broad antibacterial spectrum and strong antibacterial activity, and have a good effect on respiratory infections, sepsis, urinary system infections, reproductive system infections, and biliary tract infections, abdominal cavity infections, and skin and soft tissue infections.

1. Severe infections caused by aerobic gram-negative bacilli with multiple drug resistance but sensitive to this class of drugs, including Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Citric acid bacteria, Serratia marcescens, etc. Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter and other bacteria caused by sepsis, lower respiratory tract infections, pyelonephritis and complex urinary tract infections, abdominal infections, pelvic infections, etc .; used by Pseudomonas aeruginosa During infection, it should be noted that some strains may develop resistance during the course of treatment.

2. Severe patients with mixed infection of anaerobic and aerobic bacteria such as B. fragile.

3. Empirical treatment of severe infections in immunodeficiency patients whose pathogens have not been identified.

Imipenem / cilastatin may cause serious central nervous system adverse reactions such as epilepsy, myoclonus, and disturbance of consciousness, so it is not suitable for treating central nervous system infection. In addition to the above indications, meropenem and panipenem-betametholone can also be used in patients with bacterial meningitis over 3 months.

Carbapenem Drug Interactions

Cilastatin combined with imipenem 1: 1 can prevent imipenem metabolism in the kidney and eliminate nephrotoxicity. Betametholone can be used in combination with panipenem in a ratio of 1: 1, which can competitively inhibit panipenem's secretion to the renal tubules, thereby reducing its concentration in the renal cortex and reducing panipenem. Nephrotoxicity. Meropenem is 4 times more stable than renal dehydropeptidase I and diapenem, and does not need to be used in combination with betametholone or the enzyme inhibitor cilastatin.

Carbapenems metabolism and excretion

The marketed carbapenem antibiotics are all water-soluble drugs. A single dose of 0.5g or 1g can achieve good distribution in the body, such as sputum, lung tissue, bile, gallbladder, intestinal and abdominal cavity, but the concentration in the cerebrospinal fluid It is 8% to 16% of the blood concentration. Its clearance rate in cerebrospinal fluid (t1 / 2 is 7.4h) is significantly lower than that in blood (t1 / 2 is 1.0h). The half-life is about 1 hour, and the urine recovery rate is about 60% to 75%. It is mainly excreted from the kidney; therefore, those with impaired kidney function may accumulate in the body and the half-life is prolonged. Therefore, patients with impaired renal function should reduce their creatinine clearance accordingly. dose.

Half-life and renal function: The half-life of imipenem, panipenem, and melopenem is about 1 hour, and the urine recovery rate is about 60-75%, which are mainly excreted from the kidney. Accumulation in the body and prolonged half-life. Therefore, patients with impaired renal function should reduce the dose according to the creatinine clearance rate. The drug can be cleared during dialysis. Therefore, it should be supplemented according to the renal function after dialysis.

Panipenem has good stability to renal dehydropeptidase . Biamipenem is good, but it is still mostly hydrolyzed in the body and excreted by the kidneys.

Carbapenem adverse reactions

Adverse reactions to carbapenem antibiotics are mainly gastrointestinal reactions such as nausea, vomiting, abdominal pain, diarrhea, and eosinophilia, leukocytopenia, neutropenia, and granulocytopenia in hematology. Tolerated. When overdose is used, neurological toxicity may occur, such as headache, tinnitus, temporary loss of hearing, muscle spasms, nervous disorders, epilepsy, etc., especially those with renal insufficiency associated with epilepsy; therefore, once tremor, muscle spasm or epilepsy occurs, it should be Reduce or discontinue immediately. At the same time, carbapenem antibiotics can cause allergic reactions such as rash, itching, fever, and shock; therefore, be cautious for those with allergies.

Imipenem (Taineng) mainly includes gastrointestinal reactions such as nausea, vomiting, diarrhea, allergic reactions such as rash, itching, fever, phlebitis, leukopenia, eosinophilia, platelet increase or decrease, and serum transaminase increase , Central nervous system symptoms, can have seizures for those with epilepsy-inducing factors. Meropenem (Meping) is mainly rash, pruritus, phlebitis, allergic reactions, headache, thrombocytosis, increased eosinophils, elevated serum transaminase, AKP, LDH, etc., occasional seizures (0.05%), but Much lower than imipenem, impaired renal function, disturbance of consciousness, central nervous system symptoms, etc. until the incidence of serious adverse reactions is less (generally less than 0.1%). Panipenem (kebenin) is mainly for gastrointestinal reactions such as nausea, vomiting, diarrhea, rash, drug rash, fever, itching, etc. to allergic reactions.

The incidence of anaphylactic shock is low, but attention should be given. People who are allergic to penicillins, cephalosporins, and other -lactams may have cross-allergies to carbapenem antibiotics. Therefore, those who have experienced severe systemic allergic reactions to the above drugs should be banned from this group of drugs.

Carbapenems are contraindicated

It is contraindicated in patients who are allergic to this class of drugs and their compatible ingredients.

Carbapenems considerations

1. This class of drugs should not be used for the treatment of mild infections, let alone as preventive drugs.

2. Severe central nervous system reactions caused by this class of drugs mostly occur in patients with central nervous system diseases such as previous epilepsy history and patients with impaired renal function. Therefore, patients with original central nervous system diseases such as epilepsy should avoid using this class. drug. Patients with central nervous system infection have indications for serious adverse reactions such as convulsions when using meropenem or panipenem.

3. Renal insufficiency should be reduced according to the degree of renal dysfunction when applying this class of drugs.

Carbapenems for the elderly

Elderly patients should reduce the dosage according to the degree of renal dysfunction when applying this class of drugs.

The latest research results of carbapenems

The development of new carbapenem antibiotics is mainly carried out in the following aspects: First, the development of a highly effective renal dehydropeptidase (DHP-1) inhibitor in combination with an effective active drug to prevent the drug from being degraded by DHP-1 Nephrotoxicity; the second is to structurally modify imipenem to stabilize DHP-1 and eliminate the use of enzyme inhibitors alone; the third is to enhance the activity against Pseudomonas aeruginosa; the fourth is to develop oral varieties, For example, GV 118819 developed by the British Glaxo Corporation is an ester-type prodrug, which is well absorbed orally, and is quickly hydrolyzed into the original drug in the body to exert antibacterial effects. There are six main types of drugs that have been marketed or under development.

Meropenem

Meropenem was developed by Japan's Sumitomo Pharmaceutical Company and British ICI Pharmaceutical Company. It was first listed in Italy in 1994 and entered the Chinese market in 1999 under the brand name "Meiping". It was developed earlier in the country. Zhejiang Hisun Pharmaceutical Co., Ltd. obtained the approval of Meropenem API and powder injection in 1998 with the trade name "Hisense Mete". Subsequently, Shenzhen Haibin Pharmaceutical Co., Ltd. obtained the approval of Meropenem API and powder injections under the trade name "Beneng" in 2001. Meropenem is currently the most widely approved variety in China.

Meropenem is the second generation of carbapenem antibiotics and the first carbapenem antibiotic to be used alone. It penetrates bacterial cell walls, is stable to most -lactamase enzymes, and has a high affinity for penicillin-binding protein (PBPS). Therefore, meropenem has a broad spectrum of antibacterial activity against aerobic and anaerobic bacteria.

Imipenem

Imipenem was developed by Merck & Co. (known domestically: Merck) in 1979, and it was also the first carbapenem antibiotic created by it. Imipenem cilastatin sodium preparation was first marketed in Germany in 1985 and approved for marketing in the United States on November 26, 1985. Imipenem compound patents are no longer binding in all countries in the world, but there are protections for their substances, methods and other patents and the protection period is long.

Imipenem and Cilastatin Sodium, Imipenem and Cilastatin Sodium, are carbapenem (Peinan) compound antibiotics, whose main ingredients are imipenem and cilastatin sodium. Imipenem is the latest type of -lactam antibiotic imithiomycin and a fluorenyl derivative. It has a broad antibacterial spectrum, and it is effective against Gram-negative and positive bacteria, aerobic bacteria and anaerobic bacteria. Good antibacterial activity. Cilastatin sodium is a specific enzyme inhibitor that can block the metabolism of imipenem in the kidney, thereby increasing the concentration of imipenem in the urinary tract.

Imipenem and cilastatin sodium are mainly used for lower respiratory tract infections, intra-abdominal infections, gynecological infections, urogenital infections, skin and soft tissue infections, bone and joint infections, sepsis, and endocarditis caused by sensitive bacteria. It can also be used to prevent infection before surgery and to prevent infection after surgery. The main adverse reactions of imipenem and cilastatin sodium are the more common symptoms of allergic reactions such as rash, pruritus, and fever, as well as gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

Panipenan

Panipenem / Betamilon, alias: Kebeining. It is a carbapenem (also known as Penan) antibiotic. Antibacterial activity against methicillin-sensitive Staphylococcus, Streptococcus pneumoniae, Streptococcus and Enterococcus faecalis is similar or slightly stronger than imipenem. Methicillin-resistant Staphylococcus and Enterococcus faecium are resistant to this product. It has outstanding effects on Acinetobacter and good effects on anaerobic bacteria such as B. fragile and Clostridium difficile. For severe infections caused by sensitive bacteria: sepsis, infective endocarditis, lower respiratory infections, abdominal infections, urinary tract infections, bacterial meningitis, skin and soft tissue indications, and gynecological infections.

Panipenem is a product developed by Japan's Sankyo Co., Ltd., which was launched in March 1994 and is a product of Japan's First Pharmaceutical Sankyo. The global panipenem / betamilon market was US $ 86 million in 2004 and US $ 73 million in 2005.

The effect of this drug is the same as that of imipenem, and it has a strong antibacterial effect on Gram-positive and negative bacteria, aerobic bacteria and anaerobic bacteria. In order to further improve the safety, this product and the organic ion transport inhibitor betamylron (-benzoylamino propionic acid, betamipron) were synthesized 1: 1 into a compound preparation panipenem / betamylron.

Ertapenem

Ertapenem is a new type of long-acting penicillin for injection developed by Merck Pharmaceuticals in the United States. It has a reliable curative effect on multidrug-resistant Enterobacter but does not cover non-fermentative bacteria and has good pharmacokinetic properties. The trade name is "Yiwanzhi". Merck spokesman Graeme Bell said: "This product is suitable for situations where it is not possible to determine what caused the infection." Compared to imipenem and meropenem, ertapenem focuses on treating community-acquired infections. Ertapenem approved indications are: intra-abdominal infection; community-acquired pneumonia; urinary tract infections with complications; acute reproductive system infections; skin and soft tissue infections with complications.

Ertapenem went public in the United States in 2001, and Merck sold $ 140 million in 2006.

Faropenem

Faropenem sodium was first developed by Japan's Yamanouchi Pharmaceutical Co., Ltd. and was approved for marketing in Japan in 1997. Faropenem sodium is the only penem drug administered orally, which greatly improves oral bioavailability. Compared with other existing similar varieties, faropenem sodium has at least the following advantages: (1) the oral absorption is good, without injection, the patient's compliance is better; (2) the marketed drugs all show different degrees of renal toxicity In the preclinical study of faropenem sodium, dogs were administered continuously for 26 weeks at a dose of 2000 mg / kg without nephrotoxicity. (3) The antibacterial spectrum was further expanded and fewer resistant strains were observed.

Because of the promising outlook for faropenem sodium, domestic manufacturers have joined. In 2006, Shandong Lunan Beite Pharmaceutical Co., Ltd. first obtained the approval of faropenem sodium tablets, trade name: Jundi. So far, 7 manufacturers have obtained approvals for preparations, and 5 manufacturers have obtained approvals for production of raw materials. There are also reviews of faropenem sodium dispersible tablets, injection of ropenem sodium, and faropenem sodium enteric-coated tablets. Faropenem sodium entered the hospital market in China in the third quarter of 2007.

Biapenem

Biapenem is a carbapenem antibiotic for injection developed by Japan Lederle Corporation and American Cyanamide Corporation in 1989. It was launched in Japan in 2002 under the trade name "Omegaei". In 2008, Jiangsu Zhengda Tianqing Pharmaceutical Co., Ltd. and Nanjing Xiansheng Dongyuan Pharmaceutical Co., Ltd. obtained approval for the production of Biapenem APIs and powder injections. Biapenem powder injections of both manufacturers are 0.3g specifications. The trade name of Biapenem of Zhengda Tianqing Pharmaceutical Co., Ltd. is "Tian Ce" and the trade name of Xiansheng Dongyuan Pharmaceutical Co., Ltd. is "Anxin".

Biapenem is a new penem drug that has a broad spectrum of antibacterial activity, can inhibit the synthesis of bacterial cell walls, and can withstand the hydrolysis of a variety of -lactamase enzymes. It is highly bound to penicillin-binding proteins and negative to Gram. Bacteria have good cell penetration, and less bacterial resistance to other -lactam antibiotics. This product has a methyl group at the C 1 position of the molecule, so it is stable to human renal dihydropeptidase-1 (DHP-1) and does not need to be combined with the DHP-1 inhibitor cilastatin.

Donippenan

Donipenem was developed by Japan's Shiono Yoshihide. It was first listed in Japan in September 2005 under the trade name "Finibax". Its injection is approved for the treatment of complex urinary tract infections and respiratory infections.

In the United States, this product is used to treat nosocomial pneumonia, including respirator-associated pneumonia (VAP). The development of this product inhaler has been reported, mainly for the treatment of pulmonary infection in patients with cystic fibrosis. This product has a broad antibacterial spectrum and strong antibacterial activity, and has a strong antibacterial activity against various aerobic and anaerobic G + and G- bacteria. The in vitro activity shows that this product has stronger activity against G + bacteria than meropenem and biapenem, which is equivalent to imipenem, and has higher activity against G- bacteria than imipenem and biapenem, but slightly lower than Meropenem. Mouse infection model experiments show that this product has a good protection against a variety of G + and G- bacteria infections.

Donipenem is stable against most -lactamase enzymes, including penicillinase, cephalosporinase, and extended-spectrum -lactamase (ESBLs). Donipenem is stable to human dehydropeptidase (DHP-1). It is not hydrolyzed by DHP-1 in the body and can be used alone.

Aippenan

No information at home or abroad.

Market share of carbapenems

In the foreign carbapenem drugs market, Bayer has targeted sales of injectable carbapenem drugs and the fourth-generation Cenhem antibiotics to 15% of the Japanese drug market share, and plans to achieve them by 2002 The value is about 71 billion yen. This equates to approximately 10 billion yen in annual sales. Merck's imipenem / cilastatin (Tienam) is the leading product of this class of drugs in the Japanese market, accounting for 30% of the 69.6 billion yen market. Global sales of the drug in 2000 were US $ 605 million, an increase of 5.2% over 1999, and ranked 82nd among the top 200 best-selling drugs in the world.

In the Japanese market, new drugs considered to be Japan's potential "mega-bombs" include: Panipenem (listed in December 1993), with a market share of approximately $ 3.5 billion, developed and produced by Sankyo; BO-2727 (Phase I clinical) , With a market share of about 3.2 billion U.S. dollars, developed and produced by Universal / Merck.

In the domestic carbapenem drugs market, the main clinically used and sold varieties are imipenem / cilastatin, clobenin, and meropenem. Imipenem / cilastatin has been applied for administrative protection in China by Merck.

In 2000, the amount of imipenem / cilastatin used by domestic hospitals accounted for 2.1% of the total amount of anti-infective drugs.

Future development of carbapenems

Although carbapenems are the class of antibiotics with the broadest antibacterial spectrum, their research and development have been slow. Since 1979, foreign scholars developed imipenem / cilastatin and marketed it in 1985. In 1993, panipenem / betametholone (betametholone is an anionic inhibitor and imipenem / Cilastatin combination drug, which prevents the drug from entering the renal tubules to prevent kidney damage), Meropenem was launched in Japan in 1994. From the characteristics and clinical application of these drugs, the good effects of carbapenems have been confirmed clinically.

In December 1998, China approved the production of meropenem and its powder injections. It is believed that the drug will play a greater role in the treatment of infectious diseases. From the perspective of China's clinical use and market development in the future, carbapenems have begun to enter the growth stage. Therefore, with the development of China's antibiotic industry and the currently existing clinically resistant bacteria, this class of drugs is undoubtedly Drugs that are very effective in the clinical treatment of infectious diseases will certainly have broad development space in the future.

The widespread application of antibiotics has increased the resistance of bacteria and brought new challenges to clinical anti-infective treatment. Carbapenem antibiotics have high activity against a wide range of drug-resistant bacteria and have a broad antibacterial spectrum, which has become a powerful weapon against clinically resistant bacteria. With the structure, antibacterial activity and clinical significance of carbapenems In-depth research on the role and the continuous emergence of new carbapenems are expected to become first-line drugs for the treatment of severe infections.