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antibacterial drugs. By Dechang Zhang Department of Pharmacology, School of Basic Medicine, Peking Union Medical College. Principles of antimicrobial use.
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antibacterial drugs By Dechang Zhang Department of Pharmacology, School of Basic Medicine, Peking Union Medical College
12 Factors to consider when selecting antimicrobial agents for therapy in patients1. Is an antimicrobial agent necessary? 2. Identification of the pathogen 3. Empiric versus directed therapy 4. Susceptibility of infecting microorganism
12 Factors to consider when selecting antimicrobial agents for therapy in patients5. Need for bactericidal versus bacteriostatic agent 6. Pharmacokinetic and pharmacodynamic factors 7. Anatomical site of infection 8. Cost 9. Toxicity
12 Factors to consider when selecting antimicrobial agents for therapy in patients10. Host factors Allergy history Age Renal function Hepatic function Pregnancy status Genetic or metabolic abnormalities Host defenses function
12 Factors to consider when selecting antimicrobial agents for therapy in patients11. Need for combination therapy 12. Antibiotic resistance concerns
• viral infections that do not respond to antibiotics • noninfectious processes mimicking a bacterial infection • culture isolation of an organism that is colonizing an anatomical site and not causing an infection
In general, the clinician should resist temptation to begin antimicrobial therapy unless there is a reasonable probability that a bacterial infection is present.
When the downside risk of withholding therapy is great, such as with bacterial meningitis or in clinically unstable patients, therapy should be started without delay even when the presence of a bacterial infection is uncertain.
Another indication for antimicrobials is prophylactic therapy, which is intended to prevent illness in someone at risk of infection.
2.Identification of the pathogen
Characterization of the organism is central to selection of the proper drug.
Presence and morphologic features of microoganisms in body fluids that are normally sterile.
Culture the infective organism to arrive at a conclusive diagnosis and to determine the susceptibility of antimicrobial agents.
The acutely ill patient with infections of unknown origina neutropenic patienta patient with severe headache, a rigid neck, and sensitivity to bright lights(meeningitis)
Therapy is initiated after specimens for laboratory analysis have been obtained but before the results of the culture are available.
The choice of drug in the absence of susceptibility data the site of infection the patient's history
Broad-spectrum therapy may be needed initially for serious infections when the identity of the organism is unknown or the site makes a polymicrobialinfection likely.
A gram-positive coccus in the spinal fluidA newborn infant most likely to be Group B Streptococcus. sensitive to penicillin G. A forty-year old patient most likely to be S. pneumoniae. frequently resistant to penicillin G, sensitive to a third-generation cephalosporin or vancomycin.
Bacteristatic drugs arrest the growth and replication of bacteria at serum levels achievable in the patient, thus limiting the spread of infection while the body’s immune system attachs, immoblilizes, and eliminates the pathogens.
Bactericidal drugs kill bacteria at drug serum levels achievable in the patient. They are more aggressive compare with bicteriostatic antimicrobial drugs .
A given agent may show bactericidal actions under certain conditions but bacteriostatic actions under others, depending on the concentration of drug and the target bacteria.
A bacteriostatic agent often is adequate in uncomplicated infections because the host defenses will help eradicate the microorganism.
Bactericidal agents are required for management of infections in areas "protected" from host immune responses, such as endocarditic vegetations and cerebrospinal fluid (CSF).
5. Determination of antimicrobial susceptibility of infective organisms
In the laboratory, susceptibility is most often measured using a disk diffusion test
In the Stokes controlled sensitivity test, a control organism is inoculated on part of a plate and the test organism is plated on the remainder. Disks are placed at the interface and the zones of inhibition are compared.
The use of a sensitive control shows that the antibiotic is active, so that if the test organism grows up to the disk it may safely be assumed that the test organism is resistant to that drug.
An alternative measure of susceptibility is to determine the Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of a drug.
A series of broths are mixed with serially diluted antibiotic solutions and a standard inoculum is applied. After incubation, the MIC is the first broth in which growth of the organism has been inhibited.
The more resistant an organism is, then the higher will be the MIC.
The MBC is measured by inoculating the broths used for MIC determinations onto drug-free medium. The MBC is the first dilution at which no growth is observed.
Cidal drugs have MBC values that are close to the MIC value for particular organisms. With static agents, the MIC is much lower than the MBC.
The MIC/MBC test of a moderately resistant bacteriostatic drug. Note that once the bacteria are removed from the drug they can grow on drug free medium at most concentrations.
The MIC/MBC test of a moderately resistant bactericidal drug. The bacteria removed from the drug cannot grow on drug free medium. One tube difference is allowed in this test.
Oral peak concentrations :1 to 2 hours may be delayed by food or delayed intestinal transit vary widely in their oral bioavailability
Most life-threatening infections are treated, at least initially, with IV agents.
Parenteral therapy ensures adequate serum levels, and, for many agents, higher drug levels can be achieved when administered IV.
