Bacterial resistance to antibiotics
Many mechanisms of antibiotic resistance in bacteria have been investigated. In different strains of bacteria, resistance to an antibiotic may be due to one or more different mechanisms
Mechanism of antibiotic resistance in bacteria
Many mechanisms of antibiotic resistance in bacteria have been investigated. In different strains of bacteria, resistance to an antibiotic may be due to one or more different mechanisms.
Increases enzymatic destruction of drugs
This is the usual plasmid-mediated resistance mechanism. A good example is the enzyme beta-lactamase that causes resistance to beta-lactam antibiotics. Penicillinase-producing bacteria are resistant to penicillins, cephalosporins-producing bacteria are resistant to cephalosporins, and aminoglycosides are inactivated by phosphorylase, adenylate, and acetylase enzymes. Chloramphenicol is inactivated by acetylase.
Drug receptor changes
This is an important mechanism. Ribosomal drug-specific protein modifications confer resistance to antibiotics such as resistance to aminoglycosides, erythromycin, and resistance to rifampin on the basis of one amino acid per subunit change. the beta of the DNA-dependent RNA polymerase alters the binding of rifampin to this enzyme. The resistance of sulfonamides and trimethoprim is also similar due to the modification of the enzyme molecule, so sulphonamides are not accepted into the reaction to synthesize folic acid.
Reduced permeability in plasma membranes
This property is due to the loss or alteration of the transport system in the plasma membrane. This resistance is seen in antibiotics such as beta-lactamins, chloramphenicol, quinolones, tetracyclines, and trimethoprim. In addition, the normal osmotic barrier of the plasma membrane is also responsible for the natural resistance of many drugs.
Increases the formation of an enzyme
This mechanism may be related to the increased production of inhibitory enzymes as seen in some bacteria carrying resistant plasmids or to the formation of a new enzyme with a stronger affinity for a substrate. different from the drug as in the case of resistance to sulfonamides.
Origin of drug resistance
Antibiotic resistance in bacteria is mainly due to the formation of resistance genes in chromosomes or in plasmids, but in some special physiological states, bacteria become resistant to antibiotics. Bacteria that are dormant, that is, do not multiply, may not be as susceptible to the drug as tuberculosis. The atrophy form of some bacterial cells (L-form) will not be affected by wall-forming inhibitors such as penicillin.
Drug resistance due to chromosomal mutations
A bacterial population may contain strains that are less susceptible to a drug. The presence of such an antibiotic only selectively allows less susceptible strains to survive. Thus, the role of the drug is only as a selective factor, not a role in causing drug resistance mutations. Once a resistant bacterial strain is present, the strain can transmit this resistance to other bacteria by various mechanisms: adaptation, transformation, mating.
Resistance via plasmids
The plasmid is a small self-replicating DNA molecule present in the cytoplasm of many bacteria. This small DNA molecule often carries resistance genes, so it is called an R plasmid. Bacterial plasmids often also carry genes that allow them to attach to mucosal surfaces, produce toxins, and invade; these drug-resistant plasmids can be passed between bacteria, causing the rapid spread of infection. resistance.
Mechanisms for the transmission of drug resistance
As noted above, once mutations carrying drug resistance genes are present in chromosomes or in plasmids, these strains can rapidly spread resistance to other bacteria by three mechanisms of genetic material exchange. after:
Transduction by bacteriophage.
Means of the rapid spread of drug resistance:
Plasmid: in addition to resistance genes, plasmids also carry genes that promote gene exchange between bacteria.
Due to transposons: these are genes that have the ability to move. Transposons carrying antibiotic resistance genes can jump from plasmid to plasmid or from plasmid to chromosome. Some drug-resistant transposons found in Gram-negative bacteria also carry genes that promote transmission.
Because these integrons are vectors that can carry antibiotic resistance genes, integrons can insert into certain locations on chromosomes.
Determination of the susceptibility of bacteria to antibiotics
Currently, many bacteria resistant to antibiotics have caused many serious infections, which has led to the need for national and international monitoring programs for bacterial resistance. A Survey of the epidemiology of bacterial resistance helps clinicians to select appropriate antibiotics to treat infections. Determine bacterial susceptibility to antibiotics using reliable and consistent laboratory methods for comparable data. Bacterial susceptibility testing in the laboratory, also known as antibiogram, can be performed by dilution or by diffusion on a solid medium. When performing antibiotics, bacteria need to be cultured pure, most bacteria that cause disease in humans when isolated need 16-18 hours to grow. If the specimen contains only one type of bacteria, it will take another 16-18 hours to make the antibiotic, so the earliest antibiogram result will take 36-48 hours, in the case of a lot of bacteria, or many bacteria. Slow-growing bacteria need a longer time. For some bacteria whose antibiotic properties are stable and clear, it is not necessary to do an antibiogram such as diphtheria bacteria, hemolytic streptococci. The antibiotic resistance of bacteria is epidemiological, so the results of antibiotic resistance of pathogenic bacteria can vary from hospital to hospital and from region to region, even within the same region. A hospital's bacterial sensitivity also changes daily. Therefore, the bacteriological laboratory in the hospital needs to do the antibiogram to select the appropriate antibiotic for the treatment of infection.
Combination of antibiotics
The combination of antibiotics to treat infections has the following objectives:
Reduce the possibility of the emergence of resistant bacterial strains. For bacteria that are resistant to mutations, it is necessary to combine antibiotics to reduce the frequency of double mutations, for example, the mutation of streptomycin-resistant tuberculosis is 10-7, the rifamycin-resistant mutation is 10-9, then the probability of mutations variable resistance to both drugs is 10-7x10-9 = 10-16. This is the reason why it is important to combine antibiotics to treat TB.
Treatment of mixed infections: An antibiotic with a spectrum of action against a certain group of bacteria. In infections caused by many types of bacteria, such as pneumonia, peritonitis... are often caused by both aerobic and anaerobic bacteria. A combination of antibiotics will kill both types of bacteria.
To increase the ability to kill bacteria: For example, the combination of sulfamethoxazole and trimethoprim increases the ability to kill many bacteria compared to when using either drug alone. This purpose is used in the treatment of infections caused by Pseudomonas aeruginosa, often a combination of carbenicillin and gentamicin...