1, the choice of antibiotics in respiratory infections
1.1 Upper respiratory tract infection Upper respiratory tract infection is a generic term, including the common cold, acute sinusitis, tonsillopharyngitis, laryngitis, pharyngitis. More than 90% of the pathogens are viruses, commonly rhinovirus, adenovirus, influenza virus, parainfluenza virus, etc.. Bacteria only account for about 10%. Most of these patients are clinically not high blood count, and the duration of the disease is short (usually 1 week). Treatment is based on rest, fluid intake and symptomatic treatment without the use of antibiotics. Antibiotics may be used if symptoms do not improve in 7-10 days, if there is fever and elevated white blood cells, or if septic or non-septic complications (rheumatism, glomerulonephritis) occur. The first choice of antibiotics is penicillin (penicillin G, amoxicillin), and the first and second generation of cephalosporins and macrolides are also available. The general course of antibiotics is 5 to 7 days, with rheumatism, glomerulonephritis 10 to 14 days. If there are serious septic complications, the course of antibiotics can be extended according to the condition.
1.2 Lower respiratory tract infection is the most common infectious disease. It includes acute and chronic bronchitis, pulmonary infections, etc. The pathogens are bacteria (common Gram-positive cocci, such as Streptococcus pneumoniae, Staphylococcus aureus; Gram-negative bacilli, such as Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Escherichia coli, Aspergillus; anaerobic bacilli, such as Corynebacterium, Clostridium difficile, etc.), viruses, fungi, protozoa, Mycoplasma, Chlamydia, etc. The rate of bacterial infection is 80% in adults and 70% in children. The rate of fungal infections is significantly higher in immunosuppressed states, in old age, and in cases of heavy use of hormones and antibiotics. It is now accepted that Gram-positive cocci (mainly pneumococci) and Gram-negative bacilli (most commonly Klebsiella pneumoniae) predominate in out-of-hospital acquired lower respiratory tract infections. About 60% of hospital-acquired infections are Gram-negative bacilli, the most common of which is Pseudomonas aeruginosa. In the past, penicillin was the first choice for the treatment of out-of-hospital lower respiratory tract infections, but in recent years, the resistance of bacteria has changed significantly. For example, the resistance rate of pneumococci to benzocillin and ampicillin reached 50%, and the resistance rate to erythromycin and clindamycin reached 50%-70%. The resistance rate of Staphylococcus aureus and Staphylococcus epidermidis to penicillin is over 97%, to erythromycin and clindamycin is about 70%, and vancomycin-resistant staphylococci have also been reported abroad. However, the resistance rate to cotrimoxazole and quinolones is low, especially the new generation of quinolones. Therefore, the combination of cotrimoxazole and quinolones can often achieve the desired effect. Ampicillin, hydroxyampicillin or second-generation cephalosporins are preferred for the treatment of nosocomial lower respiratory tract infections. In combination with anaerobic infections, metronidazole or clindamycin can be added. The total effective time can be increased by splitting the dose. β-lactam antibiotics are recommended for splitting the dose. For mild and moderate infections can be given orally, for serious lower respiratory tract infections or combined with other diseases, intravenous administration is recommended, and the combination of antibiotics can be used, generally the second combination can achieve satisfactory results.
The following is a brief description of the role and mechanism of several commonly used antibiotics for the respiratory system:
1.2.1 Quinolone antibiotics are important drugs in the treatment of lower respiratory tract infections in recent years. It is characterized by high tissue concentration and low minimum bacterial inhibitory concentration. The concentration of this drug in bronchial mucosa is 2 times higher than that in blood, in alveolar epithelium is 2-3 times higher than that in blood, and in alveolar macrophages is 9-15 times higher than that in blood.
1.2.2 β-lactam antibiotics are most widely used in the treatment of respiratory tract infections. They mainly include penicillins, cephalosporins and atypical β-lactam antibiotics. β-lactam antibiotics combined with β-lactamase inhibitors (rotenone, sulbactam) can significantly increase antibacterial activity and reduce the emergence of drug-resistant strains. Tylenol, Temetin and Maspine have potent bactericidal activity against Gram-positive cocci, Gram-negative bacilli and anaerobic bacilli.
1.2.3 Macrolide antibiotics are most commonly used in the treatment of out-of-hospital bacterial respiratory infections, and have powerful antibacterial activity against Gram-positive cocci (Streptococcus pneumoniae, Staphylococcus aureus), and against Gram-negative bacilli (such as Haemophilus influenzae) and various anaerobic bacteria other than Clostridium difficile. Its new generation drugs (such as roxithromycin, azithromycin, clarithromycin) are stable to gastric acid, with high bioavailability, high tissue cell concentration and blood concentration, long-lasting maintenance, and few adverse reactions.
1.2.4 Aminoglycoside antibiotics have strong antibacterial activity against Gram-negative bacilli, and their main adverse effects are ototoxicity and nephrotoxicity. Adverse reactions are closely related to blood concentration. These antibiotics have a long antibiotic follow-up effect. This phenomenon is concentration- and time-dependent, so a short, high-dose, once-daily regimen is advocated. These drugs enter the cells through cellular uptake, the speed is slow, and the local drug can maintain a good concentration.
2.Digestive system infection and the application of antibiotics
2.1 Biliary infections Biliary infections are acute and chronic inflammatory lesions of the entire biliary system, mostly secondary to stones and tumors, and inflammation promotes the formation and increase of stones and has a high mortality rate (11.8%). Under normal conditions, bile is sterile. Due to the anatomical and physiological characteristics of the biliary tract and intestine, the route of infection of the biliary system is either upstream infection of the intestine or infection of the portal and lymphatic systems. Most of the bacteria infecting the biliary system flow directly from the intestine to the bile duct through the sphincter of Oddi, so the pathogenic bacteria are basically the same as the intestinal flora, mainly Escherichia coli, followed by Pseudomonas, Enterococcus and Proteus, and are often a mixture of two or more kinds of infections. The infection rate of anaerobic bacteria is about 51% higher than other parts. The selection of antibiotics should take into account the pathogenic species, bacterial resistance, antibiotic spectrum and its concentration in the bile, and the bile culture and drug test are important guidelines. Before getting the results of drug sensitivity test, we should choose the drugs with strong antibacterial or bactericidal power, high concentration in bile and low adverse effects.
2.1.1 Penicillin Penicillin G is not highly concentrated in the bile and is generally ineffective against biliary infections. The concentration of hydroxybenzyl penicillin and carboxybenzyl penicillin in bile is lower than the blood concentration, and the effect is not satisfactory. In contrast, oxypiperazine penicillin has powerful bactericidal activity against biliary pathogenic bacteria, and at the same time, the biliary concentration is higher than the serum concentration. Extracted from: 医學教 育网www.med66.com
2.1.2 Cephalosporins The first generation cephalosporins are mainly effective against Gram-positive cocci, so they can be used in enterococcal infections. The second generation cephalosporins are effective for some Gram-negative bacilli and Gram-positive cocci, and the biliary concentration of cefuroxime, cefadroxil and cefoperazole sodium (Pioneer) is higher than the serum concentration, so they can be used for biliary infection, but they are not effective for Pseudomonas aeruginosa. The third generation cephalosporins have strong bactericidal ability against Gram-negative bacilli and Pseudomonas aeruginosa and low nephrotoxicity, but are not as effective as the first and second generations against Gram-positive cocci.
2.1.3 Quinolones have bactericidal activity against most Gram-positive cocci and Gram-negative bacilli, and can reach effective concentration in bile, which is suitable for patients with mixed biliary tract infections, but have certain toxicity to the central nervous system, liver, kidney and bone.
2.1.4 Aminoglycoside antibiotics have a strong bactericidal effect on Gram-negative bacilli, but their clinical application is somewhat limited due to ototoxicity and nephrotoxicity. Enterococci resistant to vancomycin and aminoglycosides are sensitive to Linezol2id and Oritarancin, which are newly developed azolidinones.
2.1.5 Metronidazole has strong antibacterial activity against common anaerobic bacteria, and the concentration in bile is greater than the serum concentration, so it is often used in the treatment of biliary infections, and has better efficacy when combined with other drugs. The commonly used combination of metronidazole plus oxypiperazine penicillin, or second or third generation cephalosporins (except ceftazidime and cefmetaxel), or quinolones, can obtain good results.
2.1.6 Macrolide antibiotics have some antibacterial activity against gram-positive cocci, and the concentration in bile is greater than the serum concentration, but there is a certain degree of hepatotoxicity, so the liver function is impaired, so use with caution. Antibiotics for biliary infections are usually administered intravenously and can be stopped 3-4 days after the body temperature is normal and the symptoms have subsided. For serious infections of unknown etiology, which require prolonged medication, bacterial resistance may easily develop, and the combination of medication should be adopted.
2.2 Abdominal infections 2.2.1 Cirrhosis with abdominal infections Patients with cirrhosis have low immunity and are prone to bacterial abdominal infections, and abdominal infections are directly related to morbidity and mortality. Infectious bacteria are mostly Escherichia coli and Klebsiella pneumoniae. The ideal antibiotic is a third-generation cephalosporin. Quinolones are commonly used to treat abdominal infections because of their broad antibacterial spectrum and strong antibacterial activity. However, foreign data reported a 50% resistance rate to E. coli. After the occurrence of abdominal infection, the patient’s condition deteriorates rapidly, so it is emphasized that early, adequate and combined application of antibiotics, the dose should be high in the first few days, and we cannot wait for the results of bacterial culture, and adjust the medication according to the treatment response and culture results, and the medication time is not less than two weeks.
2.2.2 other causes of abdominal infection is often a mixture of a variety of bacterial infections, treatment requires the use of antibiotics effective against a variety of bacteria. Foreign experts recommend a single drug for mild to moderate infections and a combination of drugs for severe infections. If possible, intravenous drugs should be administered intravenously, and it is appropriate to discontinue the drug in three to five days when the blood picture is normal and the body temperature is normal.
3.Urinary tract infections
The incidence of urinary tract infection is second only to the respiratory system, 85% of urinary tract infections are caused by Escherichia coli, followed by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, anaerobic bacilli and staphylococci. Empirical treatment to give cotrimoxazole, norfloxacin and other quinolones after 3 days of treatment, if the condition does not improve, then according to the drug sensitivity results of drug replacement (before the use of drugs should be preceded by urine culture and drug sensitivity test). As far as possible, we should use antibiotics with less nephrotoxicity, fewer adverse reactions, easier to take, and less likely to produce bacterial resistance, and as far as possible, a single drug. If the single drug fails, serious infections, mixed infections or the emergence of drug-resistant strains should be combined with drugs, but generally in duplex. The use of a glycoside plus a semi-synthetic broad-spectrum penicillin or three generations of cephalosporins is often used. Because of the short half-life of these drugs, a daily dose is given in parts to maintain the effective urinary drug concentration and achieve the best therapeutic effect. The course of treatment is generally 2 weeks.
4, central nervous system infection and the application of antibiotics
Central nervous system infection is a very critical clinical condition, the early and correct application of antibiotic treatment is the key to save the patient’s life and reduce the sequelae. The common causative agents of CNS infection are meningococcus, pneumococcus, Listeria monocytogenes and Haemophilus influenzae. For adult patients, attention should be paid to the use of drugs that can easily cross the blood-brain barrier and blood-cerebrospinal fluid barrier in order to play a role in the central nervous system. Erythromycin, lincomycin, and aminoglycosides do not easily reach CNS lesions, while ampicillin, penicillin, sulfonamides, cefotaxime, ceftriaxone, and meropenem are all effective antibiotics for CNS infections. CNS infection is mostly a bacterial infection, so an effective antibiotic can be used. Try to use bactericidal drugs, intravenous administration, and large doses are appropriate. The combination of drugs must be clearly indicated. Central nervous system infection can also be intrathecal administration, but we should pay attention to small doses, low concentrations, slow speed of drug delivery.
5.Orthopedic infectious diseases
Orthopedic infectious diseases mainly include acute and chronic osteomyelitis, septic arthritis and sclerosing osteomyelitis. The causative agents are mainly Pseudomonas, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus haemolyticus and Proteus. In the treatment of bone and joint infections, it is advisable to use drugs that can reach effective concentrations in bone tissue and joint cavities, are less likely to produce resistance and have fewer toxic side effects. Penicillin, lincomycin, clindamycin, fosfomycin, cephalosporins, etc. can easily enter the joint cavity, so they are suitable for use; while erythromycin, chloramphenicol, aminoglycosides, etc. do not easily penetrate into the joint cavity and are relatively more toxic, so they are not suitable for application. Because the causative organism is often Staphylococcus aureus, a drug for Gram-positive cocci and a broad-spectrum antibiotic are usually used. After the return of bacterial culture results should be adjusted in a timely manner, antibiotics should be applied continuously for 3 weeks.
6.Infection of soft tissue of the skin
The soft tissue of the skin is in direct contact with various external pathogens, and the chance of being traumatized is much higher than that of other systems and organs. The pathogenic bacteria are mainly Staphylococcus aureus, Streptococcus haemolyticus and Escherichia coli. In mild cases, oral medication is given, while in moderate and severe cases, systemic medication should be given. Treatment with penicillin and cephalosporins is appropriate. The infection of abdominal cavity and perineum is mainly Gram-negative bacilli, so quinolones, aminoglycosides and metronidazole should be used.
In summary, the bacteria and antibiotic susceptibility of different parts of the infection have different characteristics, before the return of the drug sensitivity test results, clinicians should be based on the patient’s condition, the site of infection empirically selected antibiotics. For each infected patient, the results of the drug sensitivity test should be obtained as much as possible, and individualized treatment should be carried out. This will not only cause economic waste and toxic side effects of antibiotics, but more importantly, it will lead to the increase of drug resistance and drug-resistant bacteria, which will put human beings in a passive position in the long-term war with bacteria.