Aminoglycoside

Aminoglycosides mainly act on ribosomes in bacteria, inhibit the synthesis of bacterial proteins, and destroy the integrity of bacterial cell membranes. Aminoglycosides bind to the ribosomal 30S subunit in the cell through the energy-dependent phase II transport system, causing the wrong protein to be inserted into the cell membrane, resulting in changes in cell membrane permeability, intracellular potassium ions, adenine, and nucleosides. Excessive leakage of important substances such as acid causes rapid death of bacteria. The large amount of aminoglycoside molecules entering the cells is an aerobic energy-consuming process, which is inhibited in anoxic environment. At present, the aminoglycosides used in clinical practice can inhibit the synthesis of proteins by prokaryotic cells when the therapeutic concentration (≤25 μg/ml) is reached. Aminoglycosides have a strong killing effect on quiescent bacteria and are a stationary bactericide. 1. Antibacterial spectrum and drug resistance Aminoglycosides have strong antibacterial activity against aerobic Gram-negative bacilli, such as Escherichia coli, Klebsiella, Enterobacter, Proteus, Shigella, and Sharay Genus, Salmonella, etc. It has a poor effect on Gram-negative cocci, such as Alcaligenes, Moraxella, Citrobacter, Acinetobacter, Brucella, and meningococcus. For each group of streptococci (such as group A chain) Cocci, Streptococcus viridans, pneumococci have weak effects, and Enterococcus is most resistant to it. Mycobacterium tuberculosis is sensitive to streptomycin. Aminoglycosides have strong antibacterial activity in alkaline environment, and cations such as Ca2+, Mg2+, Na+, NH4+ and K+ can inhibit their antibacterial activity. 2. Distribution of aminoglycosides in the body is not suitable for intestinal infection; it can be distributed to many important organs in the body after injection, and can be infiltrated into the pleural cavity or peritoneal effusion. This kind of drug is mainly excreted by the kidney, and there is in the urine. Higher concentrations are beneficial for the treatment of urinary tract infections. They are low in bile, have poor efficacy against biliary tract infections, and are not easily permeable to the blood-cerebrospinal fluid barrier and are not suitable for central infections. 3. Indications At present, aminoglycosides are still commonly used in clinical practice in China, mainly for severe systemic infections caused by sensitive aerobic Gram-negative bacilli, including biliary tract infections, bone and joint infections, pneumonia, sepsis, urinary tract infections. , skin and soft tissue infections, etc. However, when dealing with serious infections or sepsis that have not been identified by pathogens, or severe Gram-negative bacilli sepsis, pneumonia, meningitis, or Staphylococcus aureus or Enterococcus infection, this class of drugs is often used in combination with other antibiotics. Aminoglycosides have a poor antibacterial effect on streptococcus. Streptococcus is one of the main bacteria causing upper respiratory tract infections, so treatment with this class of drugs is unreasonable, not only delays treatment, but also increases the incidence of adverse reactions. When treating a serious infection by medication, the first impact should be given regardless of whether the patient's renal function is normal or not, so as to ensure that the effective concentration is quickly reached in the tissue. The dose should be calculated according to the body weight (or standard body weight) + 40% × overweight after fat removal. Since the blood concentration and half-life are often different in different patients, blood concentration should be performed when conditions permit. Monitoring, according to the dose adjustment, to achieve individualized drug delivery. 4. Combination therapy principle Aminoglycosides are often synergistic with penicillins or cephalosporins. The combination of penicillin and streptomycin also has a synergistic effect on Streptococcus viridans. Other combinations that may have synergistic effects: in combination with enzyme-resistant semisynthetic penicillin (such as oxacillin) for S. aureus; in combination with penicillin (or ampicillin) or vancomycin for Enterococcus; and cephalosporin The combination is used for Klebsiella pneumoniae; it is used in combination with penicillin or ampicillin for Listeria; in combination with carbenicillin or piperacillin for Pseudomonas aeruginosa. 【Notes】 1. Aminoglycoside drugs have cross-allergy, allergy is disabled. 2. In combination with penicillin G, it has synergistic antibacterial effect on almost all Streptococcus faecalis and its variants such as Streptococcus mutans and Streptococcus streptococci. When combined with carbenicillin in a sufficient amount, it has synergistic antibacterial effect on certain sensitive strains of Pseudomonas aeruginosa. 3. Combined with alkaline drugs (such as sodium bicarbonate, aminophylline, etc.), the antibacterial effect can be enhanced, but the toxicity is also enhanced accordingly; combined with strong diuretics (such as furosemide, ethenic acid, etc.) It can increase nephrotoxicity; it can increase ototoxicity in combination with other ototoxic drugs (such as erythromycin); it can increase nephrotoxicity in combination with cephalosporins.