Bacterial resistance has become a major problem in clinical treatment of infectious diseases, and the irrational use of antibiotics is an im
Bacterial resistance has become a major problem in clinical treatment of infectious diseases, and the irrational use of antibiotics is an important cause of bacterial resistance, if we do not pay attention to this problem, the near future we will be no drugs available. Therefore, the rational use of antibiotics is the common responsibility of each of our clinical medical workers.
Recent advances in antibiotic therapy are based on the pharmacokinetics and pharmacodynamics of drugs. The so-called PK is the pharmacokinetics of antibiotics, refers to the drug absorption, distribution, excretion and other metabolic processes in the body; the so-called PD is the pharmacodynamics of antibiotics, the drug in the body how to play a bactericidal effect.
1 antibiotics PK/PD: according to the PK/PD parameters of antibiotics, antibiotics can be divided into the following two types: 1 concentration dependent: evaluation parameters of such drugs: the peak concentration of drug serum after treatment (Cmax) and the minimum inhibitory concentration (MIC) which is the ratio of Cmax/MIC, 8-10, such as the ratio drugs have the strongest antibacterial activity; the serum after administration of the area under the concentration time curve (AUC) and the minimum inhibitory concentration (MIC) which is the ratio of AUC/MIC (also called AUIC), when the ratio is more than 30 (gram positive cocci), or 125 (Ji Lan negative bacillus) of these drugs have the strongest antibacterial activity. The time dependent: evaluation parameters of such drugs as percentage of serum concentration of MIC was higher than that of bacteria in medication during the period of time (T > MIC), when more than 40% of these drugs have the strongest antibacterial activity. 2 antibacterial drugs on the basis of PK/PD is divided into: the concentration dependence of the concentration on Yu Feng: antibiotic bactericidal effect of pathogens, such as aminoglycosides, fluoroquinolones, ketolides, amphotericin B, the main reference parameters: AUC0-24/MIC (AUIC, Cmax/MIC). The time dependence of antibiotics antibacterial effects with the same bacteria is closely related to the time, such as the majority of beta lactams, lincomycin, oxazolidinone, main parameters: T, MIC.
The time related, but the antibacterial activity lasted for a long time: the antibacterial activity of some drugs are not only related to time, and concentration and post antibiotic effect (PAE), as the main for the time dependent but PAE or longer elimination half-life (T1/2) drugs, such as streptogramin, tetracycline, carbapenem glycopeptide, macrolides and azole antifungal agents, the main parameters: MIC, PAE, T, T1/2, AUC/MIC.
Two, quinolone antibacterial drugs
Antibacterial drug is a very rapid development in recent years, domestic has been widely used in clinical, the drugs have many advantages, but there are also many deficiencies, there are certain tendency of abuse, should be noted: 1 is the typical concentration dependent antibiotics; usually should be the total dose of a drug. A new classification method, 1 quinolones (Table 1):
Table 1 quinolones antibacterial spectrum characteristics and classification
Valid only for G -.
The main effective on G -.
G - G+ of Bacillus and coccus; G+ aureus increased activity based on the second generation
G - G+ aureus, bacillus, anaerobic bacteria; the anaerobic bacteria to increase the activity based on the third generation
For intestinal tract, urinary tract infection, toxic
Can be used for each
Infection by system
Infection by system
We will be the third and fourth generation fluoroquinolone called new quinolones, because of its antibacterial activity to expand the positive cocci, the pharmacokinetic characteristics of long half-life, the increase of AUC, is more typical of concentration dependent antimicrobial agents, more suitable for once daily drug. From the point of view of community respiratory tract infections, the common pathogens due to Streptococcus pneumoniae, Haemophilus influenzae, and atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila, and the third generation and the fourth generation of fluoroquinolone antibacterial spectrum covering these pathogens, and they will call for respiratory quinolone antibacterial drugs.
2, select the PK/PD parameters of quinolone antibacterial drugs. In order to achieve the ideal antibacterial effect: AUIC: G- > 100-125 G+ bacteria bacteria should be, should be > 30; Cmax/MIC > 8-10 should, in order to reduce the resistance should be: Cmax/MIC > 8-10. The AUIC is a key parameter of the PK/PD concentration dependent effect of antibiotics, the most is mainly used for the evaluation of fluoroquinolone. The quinolone antibacterial drugs: AUIC < 125, the bacterial clearance rate < 30%; AUIC > 125, the bacterial clearance rate of 80%; the critical value of AUIC > 125; therefore, the G + cocci, immunocompromised patients: AUIC = 30; patients with G coli and immune damage is greater than or equal to 100 (125): AUIC. The key parameters of the PK/PD Cmax/MIC is also a concentration dependent effect of antibiotics, aminoglycoside antibiotics commonly used in the evaluation of curative effect: Cmax/MIC8 ~ 12, the clinical efficiency of 90%; critical value: Cmax/MIC10 ~ 12. 3, how to choose the quinolones? The moxifloxacin, levofloxacin, ciprofloxacin? If considering the possibility of gram positive cocci, four generation such as "moxifloxacin"; if we consider the possibility of gram negative bacteria in the two generation, such as ciprofloxacin; if it is difficult to determine the possibility of what kind of bacteria, can choose levofloxacin". The disadvantages of quinolones antibacterial spectrum is relatively narrow, relatively low blood concentration, bacterial resistance, adverse reactions, drug interaction. At present already delisting of quinolone drugs (see Table 2):
Table 2 quinolones for adverse drug reactions of delisting
Adverse drug reaction
Hemolysis, allergy, liver and kidney function damage of Ya Pei
Grepafloxacin (Otsuka) Q-T prolongation and torsades de pointes (stop into Chinese)
Liver function impairment (restricted to use in specific cases) in the United States
(Japanese) photosensitive reaction of sparfloxacin, shock, prolonged Q-T (restricted)
Lomefloxacin (Q-T, Japan) photosensitive extension
Klisha's star toxicity and hypoglycemia reaction (discontinued)
Enoxacin theophylline metabolism (P450 enzyme)
Gatifloxacin (Shi Guibao) glucose metabolism disorder (effect on islet)
The common adverse reactions and drug interactions: general side effects: gastrointestinal reaction, rash, central nervous system; side effects: light toxicity, pefloxacin, S Pasha Singh; articular cartilage toxicity; liver toxicity; cardiac toxicity; drug interactions: interactions such as theophylline, non steroidal anti-inflammatory drugs; other.
4, quinolone usage: quinolones as is typical of the concentration dependence of drug delivery methods, so usually once daily dosing, such as levofloxacin, according to severity, can be used 0.3/ times, 0.5/ times, 0.75/ times, but 1 times daily dosing, either oral or intravenous administration. Moxifloxacin also is such, 0.4/ time, 1 times daily dosing, either oral or intravenous administration. However, the exception of ciprofloxacin, due to its early development of the drug, eliminating the short half-life, still need to be divided into two groups, the usual dose of 0.2/ times, 8 ~ 12 hours 1 times, severe patients can be 0.4/ times, 8 ~ 12 hours. 5, the unreasonable application of quinolones: for patients with central nervous system infection and has a history of epilepsy patients; for children, pregnant and lactating women; as the first-line anti TB drugs; it is not good in the effect of a quinolone, replace another quinolones; with aminophylline and caffeine and 5. Oral anticoagulants (Hua Faling) and application (traditional quinolones); and the aluminum salt and magnesium salt acid inhibitors and non steroidal anti-inflammatory agents in combination.
Three, beta lactam antibiotics generally higher blood drug concentration, wide antibacterial spectrum, strong sterilization, low toxicity, but it should be noted that: the concentrations of drug resistant strains increased; lung tissue often is only one part of the blood concentration, to avoid toxicity under the premise to properly increase the dose; is typical of the time dependence of antibiotics, shall be the total dosage; the attention of allergic reaction. (a) beta lactam antibiotics include penicillins, cephalosporins and atypical beta lactams. 1, penicillins: 1: penicillin G penicillin: narrow spectrum of gram positive cocci; II: penicillin V, penicillin resistant enzyme can be taken orally, Germany; the long-acting preparation: procaine penicillin, penicillin G benzathine penicillin G (Tardocillin). The penicillin resistant enzyme of semi synthetic penicillin resistant Staphylococcus aureus: mainly used for penicillin G infection, but methicillin resistant Staphylococcus aureus (MRSA) is invalid, the methicillin (Xingqing 1); the oxacillin (oxacillin resistant); 3 ethoxynaphthalene (nafcillin); the West benzamine Lin (ClOx); 5 floxacillin (floxacillin); 6 dicioxacillin (soldak). The broad-spectrum semisynthetic penicillin against gram negative bacteria: increase of beta lactamase is not stable, the MRSA is invalid, there are currently four generation products. The first generation: aminopenicillin, broad-spectrum, general aureus, bacillus, Pseudomonas aeruginosa: ampicillin amoxicillin; the invalid. The second generation: carboxyl penicillin, expand to gram negative bacilli, effective to Pseudomonas aeruginosa, but the effect is not strong. Oxacillin. The third generation: Penicillin G, a strong effect on Pseudomonas aeruginosa; anaerobic bacteria, as well as: Rasilin. The fourth generation: amidine penicillin, effective against gram-negative bacilli, the positive cocci; for Pseudomonas aeruginosa: mezlocillin. 2, cephalosporins: cephalosporins is a broad-spectrum semisynthetic antibiotics, the nucleus by cleavage of cephalosporin C obtained 7- aminocephalosporanic acid, has the advantages of strong antibacterial activity, penicillin resistant enzyme, clinical efficacy, low toxicity and allergic reaction of penicillin is less, according to the antibacterial spectrum of beta in enzyme stability and antibacterial activity against gram negative bacilli is different, at present will be divided into four generation cephalosporins. The first generation of gram positive bacteria, slightly better than the second generation, the third generation was significantly stronger than that of gram negative bacilli; difference, ineffective against Enterobacteriaceae; the difference in stability of beta lactamases; have certain toxicity to the kidneys. Such as cephalexin, cefazolin, cefradine etc.. The second generation of gram positive bacteria is slightly worse than the first generation of leather or similar effect of Gram-negative bacteria than the first generation, but not as good as the third generation, ineffective against Pseudomonas aeruginosa; of beta lactamase stable; on renal toxicity. Such as cefamandole, cefotiam, cefuroxime, cefaclor, cefprozil etc.. The third generation of gram positive bacteria is weak, has a strong antibacterial activity against gram negative bacteria, some varieties have strong effect on Pseudomonas aeruginosa; high stability to beta lactamase; kidney nontoxic. Such as cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefmenoxime, cefsulodin, cefodizime, Cefpiramide, cefpimizole, cefdinir (oral) etc.. The fourth generation: compared with the three generation cephalosporin antibiotic spectrum expansion, especially for G+ aureus, blood drug concentration, through the blood brain barrier ability increased; the beta lactamase is highly stable, especially AmpC enzyme; the current clinical recommendations for bacterial meningitis, hospital acquired pneumonia, ventilator-associated pneumonia, septicemia, neutropenia and infection in patients with severe community-acquired pneumonia. Such as cefepime (cefepime), cefpirome, cefozopran. 3, atypical beta lactam antibiotics to cephamycins: antibacterial spectrum similar with the second generation cephalosporin, on the stability of beta lactamase is most strong characteristics of cephalosporin; aerobic and anaerobic bacteria had strong antibacterial activity. Such as cefoxitin, Cefmetazole, cefotetan, cefbuperazone, of Mino. The carbapenems wide antibacterial spectrum, can cover almost all of the common gram positive bacteria, gram negative bacteria (including Enterococcus and Pseudomonas) and anaerobic bacteria, antibacterial activity. The imipenem (imipenem, imipenem): easy to be two kidney peptide enzyme inactivation, so Garcia ulinastatin (renal hydrogen peptidase inhibitor, 1: 1) combined; the meropenem (Mei Ping): to dhp-i stable, without kidney enzyme inhibitors; Pani Phoui Nan (g Ning: double) times betamipron (1: 1), the latter can reduce Pani Phoui Nan accumulation in renal tissue and reduce the renal toxicity; 4 biapenem; 5 doriipenem. The carbapenem: faropenem. The enzyme inhibitor beta and its compound preparation: no or only has weak antibacterial activity; the number of bacteria, beta lactamase has a strong inhibitory effect. Beta lactamase inhibitor: clavulanic acid (acid): only has weak antibacterial activity; Shubatan (cp-45899): no antibacterial activity, enzyme inhibition effect of acid is only 1/2 to 1/4, but it has a special role, single drug on the pan resistant real coli; tazobactam (3 three tazobactam): enzyme inhibition strength better than Shubatan and clavulanic acid. β内酰胺类/酶抑制剂复合制剂：①克拉维酸＋阿莫西林(安美汀)(1∶2～1∶14)②克拉维酸＋替卡西林(特美汀)(1∶30，1∶15)③舒巴坦＋氨苄西林(优立新)(1∶2)④舒巴坦＋头孢哌酮(舒普深)(1∶1)⑤三唑巴坦＋哌拉西林(特治星)(1∶8)⑥舒巴坦＋头孢三嗪(可赛舒)(1∶4)⑦舒巴坦＋阿莫西林(泰霸猛)(1∶2，1∶1)⑧舒巴坦＋哌拉西林(特灭)(1∶2)⑨舒巴坦＋美洛西林(汉光)(1∶4)⑩舒巴坦＋头孢他啶⑾三唑巴坦＋头孢三嗪⑿三唑巴坦＋头孢哌酮(凯舒特)(1∶4)（二）β-内酰胺类抗生素—时间依赖性抗生素的药效学参数1、T＞MIC的临界值：表3。
Table 3 effective T of beta lactam antibiotics MIC
2,%T > MIC maximization: to increase the amount of each dose; increase the number of times a day; to extend the duration of intravenous drip or continuous administration. (three) application of beta lactam antibiotics of time dependent antimicrobial agents, are T > MIC; it must be divided doses, usually 6 ~ 8 hours 1 times, but do not advocate Bid or Tid administration; only a few or light condition can be 12 hours 1 times, such as cefepime; only ceftriaxone and imipenem because it Ecuador has a long half-life, mild patients can be 1 times daily dosing. The method of drug delivery; usually antibiotic intravenous infusion is about half an hour, such as prolonged intravenous administration time to 2-3 hours, can increase the T > MIC, may increase the curative effect, helps to overcome the limitation of bacterial resistance. Some authors propose continuous intravenous administration, can also increase the drugs such as T, MIC, meropenem, give a loading dose, then continuous intravenous infusion, can also increase the curative effect. (four) unreasonable application of beta lactam antibiotics
The third generation cephalosporins as the preferred drug for the treatment of community acquired pneumonia "; when the effects of a drug is not good, replace the similar between drugs; put the cefoperazone containing cephalosporin used methyl tetrazole side chain structure in patients with bleeding tendencies; the cefazolin and aminoglycosides (such as Amikacin) the combined application of the elderly or potential renal insufficiency patients; without attention to the history of penicillin allergy inquiry, allergic 10% between cephalosporins and penicillin cross; 6 time dependence of beta lactam antibiotics 1 times daily dose.