Combined application of antibacterial drugs
I. The results of the combination of drugs: irrelevant, cumulative, synergistic, antagonistic
Second, the mechanism of action of antibacterial drugs.
(1) reproductive phase bactericides: such as penicillins, cephalosporins
(2) quiescent bactericides: such as aminoglycosides, polymyxins
(3) fast-acting bactericidal agents: such as tetracyclines, chloramphenicol, macrolides, etc.
(4) Slow-acting antibacterial agents: such as sulfonamides, cycloserine, etc. Xu Xinbao, Department of Hepatobiliary Surgery, Air Force General Hospital
Third, the general rule of combined application of the above antibacterial drugs.
Reproductive period bactericides + resting period bactericides = synergistic effect
Fast-acting bacteriostatic agents + reproductive period bactericides = reduced the possibility of action (if the reproductive period bacteriostatic dose is large enough, there is no antagonism)
Fast-acting inhibition + stationary fungicide = cumulative or synergistic effect
Slow-acting bactericides + reproductive fungicides = the possibility of cumulative effects
IV. Successful synergism.
Sulforaphane + TMP (sulforaphane inhibits bacterial dihydrofolate synthase; TMP inhibits dihydrofolate reductase)
Methicillin + β-lactams (methicillin acts on penicillin-binding protein 2 – becomes large and round; β-lactams act on penicillin-binding protein 3 – becomes filamentous)
β-lactams + aminoglycosides (β-lactams act on the cell wall, making it easier for aminoglycosides to pass through the damaged cell wall to the target site)
Amphotericin B + flucytosine, rifampin, tetracycline (amphotericin B damages fungal cell membranes and facilitates penetration of other drugs into cells, and amphotericin B can be used in reduced doses to avoid adverse effects)
Polymyxin + tetracycline, cotrimoxazole (polymyxin damages the fungal cell membrane and facilitates the infiltration of other drugs into the cells, and polymyxin can be used in reduced doses to avoid adverse reactions)
V. Combined anti-infective drugs should have the following conditions.
1, the combination of the two antibacterial drugs at least one of the pathogenic microorganisms have considerable antibacterial activity, and the other should not be highly resistant to the pathogenic bacteria
2, the pathogenic bacteria to the two drugs without cross-resistance, in vitro experiments are synergistic or cumulative effect
3, the pharmacokinetic properties of the two are similar, absorption, distribution, metabolism, excretion and other laws are basically the same
4. For serious infections of unknown etiology, two anti-infective drugs with synergistic antibacterial effects should be used with a broad anti-infective spectrum and estimated to cover the possible pathogenic bacteria.
Sixth, the combination of drug indications.
1|, serious infections of unknown etiology: if the probability of Gram-positive coccus infection is estimated to be high, larger doses of penicillin or cloxacillin + aminoglycosides can be used; if the probability of Gram-negative bacteria infection is estimated to be high, aminoglycosides + piperacillin or 2nd or 3rd generation cephalosporins can be used
2, a single anti-infective drugs can not control the serious infection: for example, infective endocarditis, immunodeficient or granulocytopenia in a variety of serious infections, a single antibacterial drugs often can not effectively control the infection, it is appropriate to apply a combination of bactericidal agents. Endocarditis caused by enterococci and Streptococcus griseus can be used with ampicillin or penicillin + gentamicin, or ceftazidime, cefoperazone + aminoglycosides
3, a single anti-infective drugs can not effectively control the mixed infection: thoracic, abdominal severe trauma or intestinal perforation caused by peritonitis is a serious mixed bacterial infection. There are many kinds of pathogenic bacteria, including aerobic or parthenogenic bacteria (such as Escherichia coli, Bacillus aerogenes, Aspergillus, Pseudomonas aeruginosa, Enterococcus, etc.) and anaerobic bacteria (such as Bacteroides fragilis, Streptococcus pepticus, etc.). Piperacillin or 2nd and 3rd generation cephalosporins + aminoglycosides or metronidazole, clindamycin, chloramphenicol, etc. can be used.
4, a single drug prone to drug-resistant strains of infection: tuberculosis, chronic urinary tract infections, chronic osteomyelitis, etc.
5, in order to reduce the toxic side effects of drugs.
6, other cases: such as the treatment of bacterial meningitis, in the application of larger doses of ampicillin or penicillin at the same time, the joint application of sulfonamides or chloramphenicol and other drugs that can easily penetrate into the cerebrospinal fluid to go, can improve the efficacy. For example, when treating chronic osteomyelitis of Staphylococcus aureus, in addition to the application of β-lactam antibiotics, it is appropriate to add clindamycin, fusidic acid sodium, phosphomycin, quinolones and other drugs that can easily enter the bone tissue.