Characteristics and selection of various antibacterial drugs

Characteristics and selection of various antibacterial drugs

Characteristics and selection of various antibacterial drugs.Antibacterial treatment is one of the most commonly used clinical treatments. However, in the face of a wide variety of antibacterial drugs with different indications, mechanisms of action and side effects, it is not easy to familiarize themselves with their characteristics and choose them reasonably.

Anti-infective drugs: drugs used to treat infections caused by various pathogens (bacteria, fungi, chlamydia, mycoplasma, viruses, rickettsiae, spirochetes, protozoa, worms, etc.). The concept is slightly broader than antimicrobial drugs. The latter generally does not include anti-worm drugs.

• Antibacterial drugs (antibacterial drugs): refer to drugs that kill and inhibit bacteria. Including antibiotics and other synthetic or semi-synthetic chemical drugs.
• Antibiotics: are substances produced by microorganisms, such as bacteria, fungi, actinomycetes, etc., that have inhibitory or killing effects on pathogens or tumor cells.

Classification and characteristics of antibacterial drugs. According to the efficacy, it can be divided into the following 4 categories:

• Category I: Fungicides during the reproduction period: such as penicillins, cephalosporins
• Category II: Static fungicide: such as aminoglycosides, polymyxins
• Class III: Fast-acting bacteriostatic drugs: such as tetracyclines, chloramphenicols and macrolides
• Category IV: Slow-acting antibacterial drugs: such as sulfonamides

The combined effects of the above 4 types of drugs are:

• I+II = synergy (enhancement);
• I+III = antagonism (possible);
• II+III = synergy (enhancement or addition);
• I+IV = synergy

According to the structure, antibacterial drugs can be divided into the following categories, some of which also contain multiple subcategories or subcategories:

01. β-lactams

These drugs all contain β-lactam rings; they can inhibit bacterial cell wall synthesis and activate bacterial autolysing enzymes. It can be divided into penicillins, cephalosporins, atypical β-lactams and β-lactamase inhibitors (Table 1). Because it has antibacterial effect on Gram-positive (G+), Gram-negative (G-) bacteria and some anaerobic bacteria, and has strong antibacterial activity, low toxicity and wide indications, it is more commonly used in clinical practice.

Attention should be paid when using β-lactam drugs:

• ① It is necessary to inquire about the related allergy history in detail, and do a skin test first, and those who are allergic to related drugs are prohibited;
• ② Penicillin potassium salt cannot be injected intravenously quickly;
• ③ Cefoperazone and Laoxycephalosporin can cause hypothrombinemia or bleeding; Cefoperazone, Cefmetazole, Cefminol, Laoxycephalosporin can cause alcohol withdrawal-like reactions, which should be prevented;
• ④ In recent years, the resistance rate of non-fermenting bacteria, especially Acinetobacter bacteria, to carbapenem drugs has increased rapidly, and some carbapenem resistance has also appeared in Enterobacteriaceae bacteria, which has seriously affected its clinical efficacy. Therefore, such drugs should not be used for mild infections, let alone preventive drugs.

02. Aminoglycosides

Acts on the 70S and 30S subunits of bacterial ribosomes, inhibits protein synthesis and destroys the integrity of bacterial cell membranes. It is a quiescent, concentration-dependent bactericide. It is still an important drug for the treatment of serious infections of aerobic G-bacteria. Commonly used ones include: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, etimicin, sisomycin, ribomycin, and isipramide Star, dalmicin, asmicin, dibekacin and neomycin.

The common feature is a broad antibacterial spectrum, stronger anti-G-bacillus activity than penicillins and first-generation cephalosporin drugs; good antibacterial effect on Staphylococcus bacteria; can be combined with β-lactams and vancomycins Synergistic effect, etc.; no anti-anaerobe activity; poor effect on streptococci; ear and kidney toxicity.

Specific indications include:

• ① Moderate to severe G-bacteria infection such as Enterobacteriaceae.
• ② Gentamicin, tobramycin, netilmicin, amikacin, isepamicin, micronomicin, etimicin have strong antibacterial activity against Pseudomonas aeruginosa. It is often used in combination with β-lactams or other antibacterial drugs that have an anti-Pseudomonas aeruginosa effect for moderate to severe Pseudomonas aeruginosa infections. But streptomycin and kanamycin have no effect on Pseudomonas aeruginosa.
• ③ Streptomycin or gentamicin can treat tularemia, plague and brucellosis, and the latter must be used in combination with other antibacterial drugs.
• ④ Combined use for the treatment of severe Staphylococcus, Enterococcus or Acinetobacter baumannii infections (not preferred).
• ⑤ Streptomycin, amikacin and kanamycin can be used in combination chemotherapy for tuberculosis.
• ⑥ Neomycin can only be used for oral preparation before colonic surgery or topical medication; paromomycin can only be used for intestinal cryptosporidiosis.
• ⑦ Renal function should be monitored during medication, and the patient’s hearing, vestibular function, and neuromuscular block symptoms should be closely observed and dealt with promptly; due to the greater toxicity, common respiratory tract infections and simple urinary tract infections that are common in outpatient and emergency departments should not be used for initial cases.

03. Macrolides

Acts on the 50S subunit of the bacterial ribosome to inhibit protein synthesis. It is usually a quick-acting bacteriostatic agent, and is a fungicide for sensitive bacteria at high concentrations. It is also effective for most G+ bacteria, some G- bacteria and some atypical pathogens, such as Legionella, Spirochetes, Mycoplasma pneumoniae, Chlamydia, Rickettsia, Toxoplasma gondii, and atypical Mycobacterium infections.

The first-generation drugs include erythromycin, erythromycin ethylsuccinate, meleumycin, josamycin, acetylspiramycin, midemycin, etc., which are currently less used. The second-generation drugs include roxithromycin, clarithromycin, and azithromycin, which have reduced side effects and increased efficacy. But the resistance of bacteria to these drugs has been increasing. Telithromycin and quinerythromycin are the third generation of these drugs, which have a good effect on the aforementioned drug-resistant bacteria, and have a broader antibacterial spectrum, which has good application prospects.

Specific indications include:

• ① As an alternative medicine for patients with penicillin allergies, it is used to treat ENT infections, mild and moderate pneumonia, scarlet fever and cellulitis caused by sensitive strains of streptococcus;
• ② Treatment of diphtheria and diphtheria carriers, Campylobacter jejuni enteritis, whooping cough, gas gangrene, syphilis, listeriosis;
• ③ It is used to prevent bacterial endocarditis and rheumatic fever in patients with heart disease and rheumatic fever;
• ④ Treatment of respiratory and urogenital infections caused by Legionnaires’ disease, Chlamydia, Mycoplasma, etc.;
• ⑤ The first-generation drugs are mainly used for mild patients with the above-mentioned infections;
• ⑥ Azithromycin, clarithromycin, etc. can still be used for community-acquired respiratory infections caused by Haemophilus influenzae and Moraxella catarrhalis; or combined with other antibacterial drugs for the prevention and treatment of Mycobacterium avium complex infection. Clarithromycin can also be used for combined therapy of Helicobacter pylori.
• ⑦ Combination of erythromycin and clarithromycin with terfenadine is forbidden to avoid adverse cardiac reactions. If the patients with liver function damage are indicated for use, the dose should be appropriately reduced and liver function should be reviewed regularly.

04. Tetracyclines

Including tetracycline, chlortetracycline, oxytetracycline and semi-synthetic doxycycline, metacycline and minocycline. It can act on the 30S subunit of the bacterial ribosome to inhibit bacterial protein synthesis. It has a wide antibacterial spectrum, and has good antibacterial activity against Staphylococcus, Streptococcus, Escherichia coli, Klebsiella, Brucella, Acinetobacter, and Stenotrophomonas maltophilia.

As the first or optional drug, it can be used for the treatment of the following diseases:

• ① Rickettsiosis, such as epidemic typhus, endemic typhus, Rocky Mountain fever, tsutsugamushi, rickettsial pneumonia and Q fever.
• ② Mycoplasma infection, such as mycoplasma pneumonia, urethritis caused by Ureaplasma urealyticum, etc.
• ③ Chlamydia infection, such as Chlamydia pneumonia, psittacosis, lymphogranuloma venereal disease, cervicitis and Chlamydia trachomatis infection.
• ④ Relapsing fever, brucellosis (to be used in combination with aminoglycosides), cholera, tularemia and plague.
• ⑤ Treat tetanus, gas gangrene, yaws, syphilis, gonorrhea and leptospirosis in patients with penicillin allergy.
• ⑥ Acne with significant inflammation.
• ⑦ Minocycline can be used as a combination drug for multi-drug resistant Acinetobacter baumannii infection.

05. Fluoroquinolones

It can act on bacterial DNA gyrase to block DNA replication. Common ones include norfloxacin, ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin and so on. Among them, levofloxacin and moxifloxacin have strong effects on intracellular pathogens or anaerobic bacteria such as G+ cocci, Chlamydia, Mycoplasma, and Legionella.

The main indications include:

• ① Urinary tract and lower respiratory tract infections, prostatitis, non-gonococcal urethritis, and cervicitis caused by G-bacteria such as Klebsiella pneumoniae, Enterobacteriaceae bacteria and Pseudomonas aeruginosa.
• ② Norfloxacin is limited to simple lower urinary tract infections or intestinal infections. But its resistant strains have exceeded 50%.
• ③ Levofloxacin, moxifloxacin, etc. can be used for ENT infections caused by streptococci; lower respiratory tract infections caused by streptococcus pneumoniae, mycoplasma, chlamydia, and sensitive G-bacteria.
• ④ It can be used firstly for adult intestinal infections caused by Salmonella typhi, Shigella, non-typhoid Salmonella, and Vibrio parahaemolyticus.
• ⑤ When treating abdominal cavity, biliary tract and pelvic infections, it should be combined with anti-anaerobic drugs such as metronidazole.
• ⑦ Moxifloxacin can be used as a single agent to treat mild and complicated abdominal infections.
• ⑧ Treatment of MRSA infection. However, MRSA has a high resistance rate to this class of drugs.
• ⑨ Some varieties such as levofloxacin can be used as a second-line combination drug for drug-resistant Mycobacterium tuberculosis and other mycobacteria infection.
• ⑩ This class of drugs is no longer recommended for gonococcal infections, and should be strictly restricted as preventive drugs during perioperative period.

Note: Avoid use for minor patients under 18 years of age. Antacids and drugs containing calcium, aluminum, magnesium and other metal ions can reduce the absorption of this type of drug and should be avoided. Not suitable for patients with epilepsy or other basic diseases of the central nervous system.

06. Lincosamides

Including lincomycin and clindamycin. It can act on the 50S subunit of the bacterial ribosome to inhibit protein synthesis; it can also remove the A protein and fluffy coat on the bacterial surface, making it easy to be swallowed and killed. It has good activity against G+ bacteria and anaerobic bacteria, but Streptococcus pneumoniae is highly resistant to it. Clindamycin is more effective than lincomycin and is used more clinically.

The indications include:

• ① Lower respiratory tract, bloodstream, skin and soft tissue infections, osteomyelitis caused by sensitive anaerobes and aerobic bacteria (streptococcus and Staphylococcus aureus, etc.);
• ② Combined with anti-aerobic G-bacteria drugs to treat obstetrics and gynecology and abdominal infections.
• ③ Attention should be paid to the possibility of antibiotic-related diarrhea and pseudomembranous enteritis. If there is any doubt, the drug should be stopped in time.
• ④ It has a neuromuscular blocking effect, and should be avoided in combination with other neuromuscular blocking agents.

07. Glycylcycline

Currently only tigecycline. Its mechanism of action and antibacterial spectrum are similar to those of tetracyclines, but the current drug resistance rate is low. It has high antibacterial activity against multi-drug resistant Staphylococcus, Enterococcus, Streptococcus, Enterobacteriaceae, and Acinetobacter.

It is also sensitive to coryneform bacteria, lactobacilli, Leuconostoc, anaerobic bacteria, fast-growing mycobacteria, listeria, and mycoplasma. It has antibacterial activity in vitro against Acinetobacter baumannii and Stenotrophomonas maltophilia. But Pseudomonas aeruginosa and Proteus are resistant to it.

At present, the FDA only approved for the treatment of various complicated adult abdominal infections, complicated skin and soft tissue infections, and community-acquired pneumonia caused by the above-mentioned sensitive bacteria. However, it is also used in China for the treatment of severe infections caused by certain specific bacteria, especially multi-drug resistant bacteria. In order to reduce the emergence of drug-resistant bacteria, experts recommend it as the last option and avoid using it alone.

08. Chloramphenicol

Including chloramphenicol and thiamphenicol, which can act on the 50S subunit of the bacterial ribosome and inhibit protein synthesis. It has a broad-spectrum antimicrobial effect, including G+, G- bacteria, anaerobic bacteria, Rickettsia, Spirochetes and Chlamydia, etc.

The use of chloramphenicol is generally reduced due to serious adverse reactions such as high drug resistance of pathogenic bacteria and bone marrow suppression. However, it easily penetrates the blood-brain and blood-eye barriers, and is effective against intracellular pathogens such as Salmonella typhi and Rickettsia. There are still certain indications for its application.

Such as the treatment of ampicillin-resistant Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae meningitis; combined with penicillin for ear-derived brain abscesses. During medication, peripheral blood should be monitored regularly, and long-term medication should be avoided.

Thiamphenicol has bactericidal effect on Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis; it has only bacteriostatic effect on other bacteria. Pseudomonas aeruginosa, Acinetobacter, Enterobacter, Serratia marcescens, Indole-positive Proteus, MRSA and Enterococcus are resistant to it. Its side effects are slightly lower than that of chloramphenicol, and it can also be used for respiratory, urinary, and intestinal infections caused by sensitive bacteria.

09. Rifamycins

Including rifampicin, rifamycin SV, rifapentine and rifabutin. It has a broad antibacterial spectrum and is effective against mycobacteria, G+ bacteria, G- and atypical pathogens.

Indications:

• ① Rifampicin is the main drug for combined chemotherapy for tuberculosis, non-tuberculous mycobacterial infections, and leprosy. Rifapentine can replace rifampicin as one of the combination drugs. Rifabutin can be used for the prevention and treatment of anti-mycobacterial infection in HIV patients.
• ② Rifampicin can also be used as a preventive drug for chronic carriers of Neisseria meningitidis or close contacts of meningitis; however, it should not be used for the treatment of meningitis because the bacteria may quickly become resistant.
• ③ In individual cases, severe infections caused by MRSA and methicillin-resistant coagulase-negative staphylococci (MRCNS) can be treated with vancomycin combined with rifampicin.

10. Glycopeptides

Including vancomycin, norvancomycin, teicoplanin, etc. It can inhibit the synthesis of bacterial cell walls and also has an effect on cytoplasmic RNA, making it difficult to develop drug resistance.

Applies to:

• ① Severe infections caused by drug-resistant G+ bacteria, including MRSA or MRCNS, ampicillin-resistant Enterococcus, and penicillin-resistant Streptococcus pneumoniae; it can also be used for severe G+ bacteria infections in patients allergic to penicillins.
• ② Treat patients with agranulocytosis and highly suspected G+ bacteria infection.
• ③ Vancomycin can still be used for the infection of Flavobacterium meningitidis.
• ④ Oral vancomycin or norvancomycin can be used for C. difficile enteritis that is severely ill or has failed metronidazole treatment.
• ⑤ Vancomycin or norvancomycin is usually not used for preventive medication before surgery. However, in medical units with a high incidence of MRSA infection and/or if the consequences of infection are severe, such as certain brain surgeries, heart surgeries, and total joint replacements, it is also recommended to use its single-dose preventive medication.
• ⑥ Teicoplanin is not used for the treatment of central nervous system infections.
• ⑦ Pay attention to monitor urine routine, renal function and hearing changes during medication. The course of treatment generally does not exceed 14 days.

11. Polymyxins

Commonly used are polymyxin B and E. It has strong effects on aerobic G-bacteria, including Pseudomonas aeruginosa, and has obvious nephrotoxicity. It is mainly used for topical application; but in recent years it has become a candidate for the treatment of multi-drug resistant G-bacteria infections.

The indications for systemic application are:

• ① Severe infections caused by multi-drug-resistant Pseudomonas aeruginosa that have failed other drug treatments; and various infections caused by widely drug-resistant G-bacteria
• ② Topically used for wound infection or spray inhalation to treat respiratory infection.

(source: dxy, reference only)

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