Antimicrobial Therapy Principles PDF

Principles of Antimicrobial Therapy Antimicrobial drugs Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity; that is, they have the ability to injure or kill an invading microorganism without harming the cells of the host. SELECTION OF ANTIMICROBIAL...

Principles of Antimicrobial Therapy Antimicrobial drugs Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity; that is, they have the ability to injure or kill an invading microorganism without harming the cells of the host. SELECTION OF ANTIMICROBIAL AGENTS Selection of the most appropriate antimicrobial agent requires knowing 1. The organism’s identity 2. The organism’s susceptibility to a particular agent 3. The site of the infection 4. Patient factors 5. The safety of the agent 6. The cost of therapy 1. Identification of the infecting organism Characterizing the organism is central to selection of the proper drug. A rapid assessment of the nature of the pathogen can sometimes be made on the basis of the Gram stain, which is particularly useful in identifying the presence and morphologic features of microorganisms in body fluids that are normally sterile (blood, serum, cerebrospinal fluid [CSF], pleural fluid, synovial fluid, peritoneal fluid, and urine). Empiric therapy prior to identification of the organism Ideally, the antimicrobial agent used to treat an infection is selected after the organism has been identified and its drug susceptibility established. 2. Determining antimicrobial susceptibility of infective organisms After a pathogen is cultured, its susceptibility to specific antibiotics serves as a guide in choosing antimicrobial therapy. Bacteriostatic vs. bactericidal drugs: Bacteriostatic drugs arrest the growth and replication of bacteria at serum (or urine) levels achievable in the patient, thus limiting the spread of infection until the body’s immune system attacks, immobilizes, and eliminates the pathogen. Bactericidal drugs kill bacteria at drug serum levels achievable in the patient. 3. Effect of the site of infection on therapy: Adequate levels of an antibiotic must reach the site of infection for the invading microorganisms to be effectively eradicated. 4. Patient factors In selecting an antibiotic, attention must be paid to the condition of the patient. For example, the status of the patient’s immune system, kidneys, liver, circulation, and age must be considered. In women, pregnancy or breast-feeding also affects selection of the antimicrobial agent. 5. Safety of the agent Many of the antibiotics, such as the penicillins, are among the least toxic of all drugs. Other antimicrobial agents (for example, chloramphenicol) are reserved for life-threatening infections because of the drug’s potential for serious toxicity to the patient. 6. Cost of therapy Often several drugs may show similar efficacy in treating an infection, but vary widely in cost. ROUTE OF ADMINISTRATION v The oral route of administration is chosen for infections that are mild and is favorable for treatment on an outpatient basis. v In patients requiring a course of intravenous therapy initially, the switch to oral agents should occur as soon as possible. v However, some antibiotics, such as vancomycin, the aminoglycosides, and amphotericin B, are so poorly absorbed from the gastrointestinal tract that adequate serum levels cannot be obtained by oral administration. v Parenteral administration is used for drugs that are poorly absorbed from the gastrointestinal tract and for treatment of patients with serious infections. CHEMOTHERAPEUTIC SPECTRA 1. Narrow-spectrum antibiotics Chemotherapeutic agents acting only on a single or a limited group of microorganisms are said to have a narrow spectrum. 2. Extended-spectrum antibiotics Extended spectrum is the term applied to antibiotics that are effective against gram- positive organisms and also against a significant number of gram-negative bacteria 3. Broad-spectrum antibiotics Drugs such as tetracycline and chloramphenicol affect a wide variety of microbial species and are referred to as broad-spectrum antibiotics. DRUG RESISTANCE v Bacteria are said to be resistant to an antibiotic if the maximal level of that antibiotic that can be tolerated by the host does not halt their growth. v Some organisms are inherently resistant to an antibiotic. v However, microbial species that are normally responsive to a particular drug may develop more virulent or resistant strains through spontaneous mutation or acquired resistance and selection. v Some of these strains may even become resistant to more than one antibiotic. PROPHYLACTIC ANTIBIOTICS Certain clinical situations require the use of antibiotics for the prevention rather than the treatment of infections. COMPLICATIONS OF ANTIBIOTIC THERAPY a) Hypersensitivity b) Direct toxicity c) Superinfections: Drug therapy, particularly with broad-spectrum antimicrobials or combinations of agents, can lead to alterations of the normal microbial flora of the upper respiratory, intestinal, and genitourinary tracts, permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria.