1, the choice of antibiotics in respiratory infections
1.1 Upper respiratory tract infection
Upper respiratory tract infection is a collective term, including the common cold, acute sinusitis, tonsillopharyngitis, laryngitis, pharyngitis. More than 90% of the pathogens are viruses, such as rhinovirus, adenovirus, influenza virus and parainfluenza virus. Bacteria only account for about 10%. Most of these patients have a low blood count and a short duration of illness (usually 1 week). Treatment is based on rest, fluid intake and symptomatic treatment without the use of antibiotics. Antibiotics may be used if the symptoms do not improve for 7-10 days, if there is fever, 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 cephalosporins and macrolides are also available. The general course of antibiotics is 5-7 days, with rheumatism, glomerulonephritis 10-14 days. If there are serious septic complications, the course of antibiotics can be extended according to the condition.
1.2 Lower respiratory tract infection
It 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) predominate in out-of-hospital acquired lower respiratory tract infections, followed by Gram-negative bacilli (most commonly Klebsiella pneumoniae). About 60% of nosocomial acquired infections are Gram-negative bacilli, the most common of which are Pseudomonas aeruginosa. Out-of-hospital lower respiratory tract infections used to be treated with penicillin as the first choice, but in recent years there has been a major change in bacterial resistance. For example, the resistance rate of pneumococci to benzocillin and ampicillin is 50%, and the resistance rate to erythromycin and clindamycin is 50%-70%. The resistance rate of Staphylococcus aureus and Staphylococcus epidermidis to penicillin is more than 97%, and the resistance rate to erythromycin and clindamycin is about 70%, and vancomycin-resistant staphylococci have 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 obtain the desired efficacy. In-hospital lower respiratory tract infection treatment is preferred to ampicillin, hydroxyampicillin or second-generation cephalosporins. Metronidazole or clindamycin may be added for combined anaerobic infections. According to the relationship between blood concentration and effect, the antibacterial effect increases with the increase of blood concentration, and the total effective time can be increased by splitting the dose. β-lactam antibiotics are recommended to be split. 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 common antibiotics for the respiratory system:
1.2.1 Quinolone antibiotics
It is an important drug for the treatment of lower respiratory tract infection in recent years. It is characterized by high tissue concentration and low minimum bacterial inhibitory concentration. The concentration of this drug is 2 times higher in bronchial mucosa than in blood, 2 to 3 times higher in alveolar epithelium than in blood, and 9 to 15 times higher in alveolar macrophages than in blood.
1.2.2 β-lactam antibiotics
They are most widely used in the treatment of respiratory tract infections. They mainly include penicillins, cephalosporins and atypical β-lactam antibiotics. β-lactam antibiotics in combination with β-lactamase inhibitors (rods, 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
Most commonly used in the treatment of out-of-hospital bacterial respiratory tract infections, they have strong antibacterial activity against Gram-positive cocci (Streptococcus pneumoniae, Staphylococcus aureus), antibacterial activity against Gram-negative bacilli (such as Haemophilus influenzae) and various anaerobic bacteria other than Clostridium difficile, and have positive efficacy against atypical pneumonia (Mycoplasma, Chlamydia, Legionella). 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
It has powerful antibacterial activity against Gram-negative bacilli, and its main adverse reactions 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, and the speed is slow, and the local medication can maintain a good concentration.
2, digestive system infections and the application of antibiotics
2.1 Biliary infection
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, with a high mortality rate (11.8%). Under normal conditions, bile is sterile. The anatomical and physiological characteristics of the biliary and intestinal tracts determine the route of infection of the biliary system as an upstream infection of the intestine or an 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 Aspergillus, and often a mixture of more than two kinds of infection. The anaerobic bacteria infection rate 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, etc. Bile culture and drug tests are of great guidance. Before the results of drug sensitivity test are obtained, drugs with strong antibacterial or bactericidal power, high concentration in bile and low adverse effects should be selected.
2.1.1 Penicillins
Penicillin G is not highly concentrated in 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, while the biliary concentration is higher than the serum concentration.
2.1.2 Cephalosporins
The first generation cephalosporins are mainly effective against Gram-positive cocci, so they are available for enterococcal infections. Second generation cephalosporins are effective for some Gram-negative bacilli and Gram-positive cocci. The biliary concentration of cefuroxime, cefadroxil and cefoperazole sodium (Pioneer) is higher than the serum concentration and can be used for biliary infections, but it is not effective for Pseudomonas aeruginosa. The third generation cephalosporins have strong bactericidal ability for Gram-negative bacilli and Pseudomonas aeruginosa, and low nephrotoxicity, but not as good as the first and second generations for Gram-positive cocci.
2.1.3 Quinolones
It has bactericidal activity for most Gram-positive cocci and Gram-negative bacilli, and can reach effective concentration in bile, which is more suitable for patients with mixed biliary tract infection, but has certain toxicity to central nervous system, liver, kidney and bone.
2.1.4 Aminoglycoside antibiotics
It has a powerful bactericidal effect on Gram-negative bacilli, but its clinical application is somewhat limited because of ototoxicity and nephrotoxicity. Enterococci resistant to vancomycin and aminoglycosides are sensitive to Linezol2id and Oritarancin, which are newly developed azolidinone antibiotics.
2.1.5 Metronidazole
It has strong antibacterial activity against common anaerobic bacteria, and the concentration in bile is greater than the serum concentration, so it is commonly used in the treatment of biliary infections, and has better efficacy when combined with other drugs. Commonly used combination drug regimen is metronidazole plus oxypiperazine penicillin, or plus second or third generation cephalosporins (except ceftazidime, cefmetaxel), or plus quinolones, all can obtain good results.
2.1.6 Macrolide antibiotics
They have certain antibacterial activity against gram-positive cocci, and the concentration in bile is greater than the serum concentration, but they have certain hepatotoxicity, so they are used with caution in people with impaired liver function. Antibiotics for biliary infections are usually administered intravenously and can be discontinued 3-4 days after the body temperature has normalized and symptoms have subsided. For serious infections of unknown etiology, which require prolonged medication, bacterial resistance is likely to develop and should be used in combination.
2.2 Abdominal infection
2.2.1 Cirrhosis with abdominal infection
Patients with cirrhosis have low immunity and are prone to bacterial abdominal infections, and abdominal infections are directly related to morbidity and mortality. The bacteria of infection are mostly Escherichia coli and Klebsiella pneumoniae. The more desirable antibiotics are third-generation cephalosporins. 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 the early, adequate and combined application of antibiotics is emphasized, and the dose should be high in the first few days, not waiting for the results of bacterial culture, and the medication should be adjusted according to the treatment response and culture results, and the medication should be used for not less than two weeks.
2.2.2 Other causes of abdominal infection
It is often a mixed infection with multiple bacteria, and treatment requires the use of antibiotics that are effective against multiple bacteria. Foreign experts recommend a single drug for mild to moderate infections and a combination of drugs for severe infections. Can be given intravenously as much as possible intravenous administration, and divided administration is generally normal blood picture, body temperature normal 3 to 5 days to stop the drug.
3, urinary tract infections
The incidence of urinary tract infections is second only to the respiratory system, 85% of urinary tract infections are caused by Escherichia coli, followed by Escherichia coli, Pseudomonas aeruginosa, Aspergillus, anaerobic bacteria and staphylococci. Empirical treatment to 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, easy 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. A basal glycoside plus a semi-synthetic broad-spectrum penicillin or a triple cephalosporin is often used. Because of the short half-life of these drugs, 1 day dose is given in parts to maintain the effective urinary drug concentration and achieve the best therapeutic effect. The course of treatment is usually 2 weeks.
4, central nervous system infections and the application of antibiotics
Central nervous system infection is a very critical clinical condition, 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 infections are meningococci, pneumococci, Listeria monocytogenes and Haemophilus influenzae. For adult patients, care should be taken to use drugs that can easily cross the blood-brain barrier and blood-cerebrospinal fluid barrier in order to work 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 infections are mostly infections of one type of bacteria, so one effective antibiotic is sufficient. It is advisable to use bactericidal drugs, intravenous administration, and high doses as much as possible. The combination of drugs must be clearly indicated. The central nervous system infection can also be intrathecal administration, but we should pay attention to small doses, low concentration, slow rate of administration one at a time.
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 not easily resistant to bacteria and have few toxic side effects. Penicillin, lincomycin, clindamycin, phosphomycin, 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 toxic, so they are not suitable for application. Because the causative organism is often Staphylococcus aureus, a drug for Gram-positive cocci and another 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 has a much higher chance of being traumatized than other systems and organs. The pathogenic bacteria are mainly Staphylococcus aureus, Streptococcus haemolyticus and Escherichia coli. In mild cases, oral medication should be given, while in moderate and severe cases, systemic medication should be given. Treatment with penicillin and cephalosporins is appropriate. Infections in the abdominal cavity and perineum are dominated by Gram-negative bacilli, so quinolones, aminoglycosides and metronidazole should be chosen as appropriate.
In summary, the bacteria and antibiotic susceptibility of different sites of infection have different characteristics. Before the return of the drug sensitivity test results, clinicians should select antibiotics empirically according to the patient’s condition and the site of infection. The results of the drug sensitivity test should be obtained for each infected patient as much as possible for individualized treatment. Do not blindly use, abuse, long time high dose or low concentration of antibiotics, otherwise it will not only cause economic waste and toxic side effects of antibiotics, more importantly, it will lead to the increase of drug resistance and drug-resistant bacteria species of pathogenic bacteria, making humans in a passive position in the long-term war with bacteria.