Drug resistant strains refer to the corresponding strainsantibioticStrains producing tolerance.With the widespread use of antibiotics, drug-resistant strains have become a common cause of clinical infectionPathogen。Especially the infection of drug-resistant strains in hospitals has greatly increased the mortality, and its treatment has become a clinical problem.
Drug resistant strains refer to those strains that have resistance to corresponding antibiotics after long-term antibiotic selection.BacterialDrug resistanceIt refers to the effect of bacteria on drugsusceptibilityReduction or even disappearance, resulting in reduced or even ineffective efficacy of drugs against drug-resistant bacteria.The emergence of drug-resistant strains has increased the difficulty of curing infectious diseases, and forced humans to find new ways to fight microbial infection.
In recent years, due to the rapid development of clinical treatment methods and the extensive and unreasonable use of antibiotics, the negative effects arenosocomial infectionWith the increase of the rate and drug-resistant strains, drug-resistant strains have become more common pathogens causing clinical infections.BacteriaDrug resistanceThe continuous increase of HIV/AIDS leads to the failure of clinical treatment, recurrence of infection, and increased risk of death.
There is a serious phenomenon of irrational use of antibiotics in China, which not only causes a great waste of antibiotics and the continuous spread of drug-resistant strains, but also brings serious economic burden to patients by prolonging treatment time.The rational use of antibiotics in clinical practice can reduce the cost of treatment, shorten the course of disease, improve the cure rate, and reduce the spread of drug-resistant strains in the region.[1]
Reports from all over ChinaMethicillin resistant Staphylococcus aureus(MRSA) infection rate ranged from 20% to 80%.MRSA is a common hospital infection with strong pathogenicity and poor therapeutic effect.Patients in intensive care units, patients undergoing invasive examinations, and burn patients are susceptible to MRSA infection, and most of them are multi drug resistant (resistant to more than three different types of antibiotics).All kinds of β - lactam antibiotics can inhibitBacterial cell wallMucin（Peptidoglycan）Synthase activity, thus hindering the synthesis of cell wall, causing the expansion and lysis of bacterial cell wall defects.Penicillin binding proteinPenicillin binding protin (PBPS) is a kind of transpeptidase. The synthesis of bacterial cell wall requires mucopeptide (also called peptidoglycan, glycopeptide, and cytosol). PBPS is not only mucopeptide, but also a special protein located on the bacterial plasma membrane, which can covalently bind with the isotope labeled penicillin G. Therefore, these target sites are called PBPS.MRSAcell surfaceThere are four kinds of PBPS, and a new PBP is generated between the original PBP2 and PBP3. Its molecular weight is 7800, and it is named PBP2a (only on the surface of MRSA). PBP2a has very low affinity with β - lactam antibiotics.PBP2a, which is not bound, continues to complete the synthesis of bacterial cell wall, enabling bacteria to survive and resist drug.[2]The first choice for treatment of MRSA septicemia isLinezolidone。
Streptococcus pneumoniae is a common pathogen of community acquired meningitis, otitis media and bacteremia. Penicillin has been the treatment for many yearsStreptococcus pneumoniae infectionHowever, since the penicillin resistant Streptococcus pneumoniae was reported in the 1970s, its isolation rate has increased significantly worldwide, especially in some European countries, some regions of the United States, and some countries and regions in Southeast Asia. The isolation rate of PRSP has reached 40% - 50%.Increase of PRSP separation rate andβ - lactam antibioticsascephalosporinAnd non beta lactam antibiotics such asMacrolidesIt has a lot to do with the massive use of antibiotics and some unreasonable treatment schemes, such ascefatriaxoneIt has a strong antibacterial effect on PRSP, but if treated with a single dose, the blood drug concentration after treatment is higher than that of anti sensitive Streptococcus pneumoniae but lower than that of anti resistant Streptococcus pneumoniaerespiratory tract infectionResults The separation rate of PRSP was significantly higher than that of the control groupAmoxicillin/Clavulanic acidThe separation rate of PRSP after 10 days of treatment.To treat PRSP infection, it is very important to formulate a reasonable treatment plan.
3. Vancomycin resistant enterococci (VRE)
Due to the large use of glycopeptide drugs in animal husbandry, many animals produce VRE.Glycopeptides are widely used in clinicvancomycinThe treatment of gram-positive bacterial infection further increases the proportion of VRE infection.Moderately resistant to vancomycin or other glycopeptide drugs in recent yearsStaphylococcus aureus(vancomycin or other glycoptide intermediately resistant Stap enterococcus aureus, VISA/GISA) and vancomycin dependent enterococci,The infection caused by VDE) is increasing, and clinical treatment is more difficult. Although the minimum inhibitory concentration (MIC) can be determined through in vitro tests to select effective drugs, it is particularly important to strengthen the monitoring of drug-resistant strains, strictly implement infection control and reasonably use drugs.
Gram negative bacteria
1. Pseudomonas aeruginosa
Pseudomonas aeruginosaIt is a common pathogenic strain of hospital acquired infection. Because it produces a variety of proteases to cause tissue destruction and spread of infection, it often leads to fatal infection.Its drug resistance rate is high and its mechanism is complex.
Some pathogens can be resistant to a variety of antibiotics or highly resistant, such asAcinetobacter baumanniiandStenotrophomonas maltophilia（stenotrophomonas maltopailia）。Stenotrophomonas maltophilia is a non fermentative bacterium that widely exists in the environmentGram negative bacteriaIt can also live in the respiratory tract and intestinal tract of peopleConditional pathogenIt is easy to be infected in hospitalized patients with serious basic diseases, with high mortality and natural resistance to carbapenems.In recent years, the isolation rate of Stenotrophomonas maltophilia has gradually increased, becoming an important pathogen of hospital infection, which can cause respiratory tract and digestive tract infections,endocarditisandsepticemiaEtc.Old age, serious basic diseases, application of broad-spectrum antibiotics, immunosuppressants and mechanical ventilation are susceptible factors of infection, and their mortality is high.
A class of strains capable of hydrolyzing β - lactamases of broad-spectrum penicillin, third-generation cephalosporins and monocyclic antibiotics, which can break the amide bond of the β - lactam ring and lose its antibacterial activityCephalosporin、Carbapenem antibioticsandenzyme inhibitorsensitive.[2]
Cefclidin is the fourth generation cephalosporin. The product has a wide antibacterial spectrum, and is resistant to most gram-negative bacteria, especiallyEnterobacteriaceae bacteriaIt has a strong antibacterial effectGram positive bacteriaAnd anaerobic bacteria have good antibacterial effect.The most prominent feature is that it has high activity against Pseudomonas aeruginosa and is mediated by chromosomeCephalosporinaseIt is stable, hydrophilic, and has good penetration to bacterial cell membrane. It is one of the most active antimicrobials against Pseudomonas aeruginosa. It is effective against Acinetobacter calcium acetate resistant to other cephalosporins, and against β 2 lactamase producing bacteriaHaemophilus influenzae、Moraxella catarrhalis, Neisseria gonorrhoeae andMeningococciIt also has good antibacterial effect.It is invalid for MRSA, MRSE and enterococcus.
Cefepime
Cefepime(cefepime) is the fourth generation cephalosporin with high water solubility and rapid penetrationGram negative bacteriaThe negatively charged microporous channels in the outer membrane are stable to many broad-spectrum β 2-lactamases, and their action sites are many major penicillin binding proteins (PBPs), thus affecting the synthesis and metabolism of bacterial cell walls.It has strong bactericidal power and broad antibacterial spectrum. Its antibacterial activity against Pseudomonas aeruginosa and other non fermentative bacteria is better than that of ceftazidine. It has high antibacterial activity against streptococcus, but its antibacterial activity against Stenotrophomonas maltophilia, Enterococcus and methicillin-resistant Staphylococcus aureus is poor.
Biapenem
Biapenem is a new carbapenem antibiotic, which is stable to human dehydropeptidase-1. The tetraammonium cation group on its side chain makes it easier to penetrate the cell membrane, thus strengthening its antibacterial activity against Pseudomonas aeruginosa. It is mainly excreted through the urinary tract. Its half-life is 110~118h, and its protein binding rate is low, which can be dialyzed out.This drug can be used for serious infections caused by drug-resistant Pseudomonas aeruginosa.
Glycopeptides
It inhibits the synthesis of peptidoglycan by binding with D2 alanyl 2D2 alanine of bacterial cell wall, thusSuppressor cellThe synthesis of wall is suitable for all kinds of Gram positive bacteria infection.In addition to vancomycin, the following have been approved for listing: (1)Tekoplanin(teicoplanin), the effect of this drug on streptococcus, staphylococcus aureus and streptococcus pneumoniae is better than vancomycin, and vancomycin resistant enterococci are still sensitive to this product.But the curative effect on coagulase negative staphylococcus is not as good asvancomycin, and bacteria are easy to develop resistance to them, and cannot penetrateblood brain barrier。(2) Oritavanin (L Y333328), a semi synthetic glycopeptide drug, is a derivative of natural glycopeptide drug L Y264826.Its mechanism of action may be similar to vancomycin, and may also reduce RNA synthesis. It has a concentration dependent bactericidal effect. It has good effects on MRSA, PRSP, and VRE, and is one of the drugs with the strongest antibacterial activity against VRE.
Remulanin
Ramoplanin is a ester sugar carboxyl peptide, which plays a bactericidal role by acting on the lipid formation stage of cell wall synthesisGram positive bacteriaIt has powerful killing effect.This drug has poor tolerance during intramuscular injection and intravenous drip, and is not suitable for systemic use.It can be used to clear intestinal VRE or for local medication.
