1-Introduction to Antimicrobials pdf2.pdf

Pharmacology III INTRODUCTION TO ANTIMICROBIAL AGENTS Dr. Lina Tamimi Definitions Chemotherapy: is the use of chemical agents (either synthetic or natural) to : destroy disease producing microorganisms (i.e bacteria, fungus and viruses, protozoa, and helminthes) or : exert toxic...

Pharmacology III INTRODUCTION TO ANTIMICROBIAL AGENTS Dr. Lina Tamimi Definitions Chemotherapy: is the use of chemical agents (either synthetic or natural) to : destroy disease producing microorganisms (i.e bacteria, fungus and viruses, protozoa, and helminthes) or : exert toxic effects on malignant or cancerous cells.  Antimicrobials: are chemical agents (synthetic/natural) used to treat bacterial, fungal and viral infections. Antimicrobial drug exhibits selective toxicity. i.e. The remarkably powerful and specific activity of antimicrobial drugs is due to their selectivity for targets that are either unique to prokaryote and fungal microorganisms or much more important in these organisms than in humans. Antibacterial … : Inhibits growth of bacteria.  Anticancer agents: Drugs or chemicals used to manage neoplastic diseases. Antiprotozoals: are drugs used to treat malaria, amoebiasis, gardiasis, trichomoniasis, toxoplasmosis, pneumocystis carinii pneumonia, trypanosomiasis and leshmaniasis. Anthelmintics: are drugs used in the treatment of intestinal and tissue worms.  Antibiotics: are substances produced by various species of microorganisms (bacteria, fungi, actinomycetes) that suppress the growth of other microorganisms. It is a drug used to treat bacterial infections. Antibiotics have no effect on viral infections. Originally, an antibiotic was a substance produced by one microorganism that selectively inhibits the growth of another.  Definitions Bactericidal versus bacteriostatic action: Bactericidal Antibiotics: Antibiotics work by killing the bacteria and their actions is irreversible. Bacteriostatic Antibiotics: Antibiotics inhibit growth or reproduction of bacteria, whose actions is reversible. ▪ Bacteriostatic versus 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 immune system attacks, immobilizes, and eliminates the pathogen. If the drug is removed before the immune system has scavenged the organisms???? ✓ Bactericidal drugs kill bacteria at drug serum levels achievable in the patient. Because of their more aggressive antimicrobial action, bactericidal agents are often the drugs of choice in seriously ill and immunocompromised patients  Effects of bactericidal and bacteriostatic drugs on the growth of bacteria in vitro. Copyright © 2015 Wolters Kluwer All Rights Reserved Minimal Inhibitory Concentration „ MIC: Lowest concentration of antibiotic that prevents visible growth. Minimum bactericidal concentration :Lowest concentration that kills 99.9% of bacteria Spectrum of antibiotics  A. Narrow-spectrum antibiotics ✓ Chemotherapeutic agents acting only on a single or a limited group of microorganisms are said to have a narrow spectrum. For example, isoniazid is active only against Mycobacterium tuberculosis (Figure 37.7B). B. Extended-spectrum antibiotics ✓ Extended spectrum is the term applied to antibiotics that are modified to be effective against gram-positive organisms and also against a significant number of gram-negative bacteria. For example, ampicillin is considered to have an extended spectrum because it acts against gram-positive and some gram-negative bacteria (Figure 37.7C). C. Broad-spectrum antibiotics ✓ Drugs such as tetracycline, fluoroquinolones and carbapenems affect a wide variety of microbial species and are referred to as broad-spectrum antibiotics (Figure 37.7D). Principles of Antimicrobial Therapy 15  Figure 37.7 A. Color-coded representation of medically important microorganisms. B. Isoniazid C. Ampicillin D. Tetracycline Copyright © 2015 Wolters Kluwer All Rights Reserved Resistance!!  Antibiotic resistance The major problem threatening the continued success of antimicrobial drugs is the development of resistant organisms. Much attention has been focused on eliminating the misuse of antibiotics to slow the tide of resistance. Antibiotics are misused in a variety of ways, including : 1. Use in patients who are unlikely to have bacterial infections, 2. Use over unnecessarily prolonged periods, 3. Use of multiple agents or broad-spectrum agents when not needed.  Infections caused by antibiotic-resistant pathogens are associated with increased costs, morbidity, and mortality. In the face of continuing development of resistance, considerable effort will be required to maintain the effectiveness of these drug groups.  Figure 37.8 Some mechanisms of resistance to antibiotics Copyright © 2015 Wolters Kluwer All Rights Reserved Prophylactic use of antibiotics ✓ Certain clinical situations, such as dental procedures and surgeries, require the use of antibiotics for the prevention rather than for the treatment of infections (Figure 37.9). ✓ Because the indiscriminate use of antimicrobial agents can result in bacterial resistance and superinfection, prophylactic use is restricted to clinical situations in which the benefits outweigh the potential risks. The duration of prophylaxis should be closely observed to prevent the unnecessary development of antibiotic resistance. Some clinical situations in which prophylactic antibiotics are indicated. Copyright © 2015 Wolters Kluwer All Rights Reserved  COMPLICATIONS OF ANTIBIOTIC THERAPY ✓ Even though antibiotics are selectively toxic to an invading organism, it does not protect the host against adverse effects. For example, the drug may produce an allergic response or may be toxic in ways unrelated to the antimicrobial activity. A. Hypersensitivity B. Direct toxicity C. Superinfections (additional infection occurring during the course of an existing infection, usually caused by opportunistic microorganisms resistant to the antimicrobial agents used in treating the first infection) Principles of Antimicrobial Therapy 23  Antibiotic usage requirements Appropriate antimicrobial therapy for a given infectious disease requires : 1. Selective toxicity 2. The expected activity of the antibiotic(s) against the infecting pathogen(s); 3. The host characteristics. Complementary with host immune system 4. Appropriate diagnosis is crucial. 5. Specimens should be obtained from the suspected site of infection (optimally BEFORE antibiotics are initiated) for microscopy and culture to try and identify the causative pathogen(s)  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. ✓ ✓ ✓ However, some patients require empiric therapy (immediate administration of drug(s) prior to bacterial identification and susceptibility testing). Some laboratory techniques that are useful in the diagnosis of microbial diseases. Copyright © 2015 Wolters Kluwer All Rights Reserved  Selection of antimicrobial agents ▪ 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. ✓ However, in the critically ill patient, such a delay could prove fatal, and immediate empiric therapy is indicated. 1. Timing: ✓ Acutely ill patients with infections of unknown origin—for example, a neutropenic patient or a patient with meningitis—require immediate treatment. ✓ If possible, therapy should be initiated AFTER specimens for laboratory analysis have been obtained but BEFORE the results of the culture and sensitivity are available. 2. Selecting a drug: ✓ Drug choice in the absence of susceptibility data is influenced by the site of infection and the patient’s history. ✓ Broad-spectrum therapy may be indicated initially when the organism is unknown or polymicrobial infections are likely. ✓ The choice of agent(s) may also be guided by known association of particular organisms in a given clinical setting. 3.Determining antimicrobial susceptibility of infective organisms ✓ After a pathogen is cultured, its susceptibility to specific antibiotics serves as a guide in choosing antimicrobial therapy. ✓ The minimum inhibitory and bactericidal concentrations of a drug can be experimentally determined 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 (Figure 37.4) ✓ Infections with multidrug-resistant pathogens need broader antibiotic coverage when initiating empiric therapy. 5. Safety of the agent ✓ Antibiotics such as the penicillins are among the least toxic of all drugs. Other antimicrobial agents have less specificity and are reserved for life- threatening infections. 6.Cost of therapy ✓ Figure 37.5 illustrates the relative cost of commonly used drugs for staphylococcal infections. 29  Figure 37.4 FDA categories of antimicrobials and fetal risk. Copyright © 2015 Wolters Kluwer All Rights Reserved  Figure 37.5 Relative cost of some drugs used for the treatment of Staphylococcus aureus Copyright © 2015 Wolters Kluwer All Rights Reserved Routes of administration ✓ The oral route of administration is appropriate for mild infections that can be treated on an outpatient basis. In addition, economic pressures have prompted the use of oral antibiotic therapy in all but the most serious infectious diseases. ✓ In hospitalized patients requiring intravenous therapy initially, the switch to oral agents should occur as soon as possible. ✓ Parenteral administration is used for : ✓ drugs that are poorly absorbed from the GI tract ✓ for treatment of patients with serious infections, for whom it is necessary to maintain higher serum concentrations of antimicrobial agents. 32  Mechanisms of Action 1. Inhibit cell wall synthesis (penicillin) 2. Anti-metabolites(sulfonamides) 3. Affect nucleic acids (quinolones, rifampin) 4. Act on ribosomes-Reversible (tetracycline, chloramphenicol)-Irreversible (aminoglycosides) 5. Disrupt cell walls (nystatin, polymyxin) Classification of some antimicrobial agents by their sites of action. Copyright © 2015 Wolters Kluwer All Rights Reserved Remember strep sore Summary