Principles of anti microbial therapy

Principles of anti microbial therapy

• 1.
  PRINCIPLES OF ANTI MICROBIALTHERAPY Done By: Rawan ALSulaimani Pharm.D 1
• 2.
  2  Antimicrobial drugsare 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.
• 3.
  SELECTION OF ANTIMICROBIAL AGENTS3 Selection of the most 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.
• 4.
  Identification of theinfecting organism4  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)
• 5.
  Empiric therapy priorto identification of the organism5  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.
• 6.
  The blood-brain barrier(BBB) 6 However, natural barriers to drug delivery are created by the structures of the capillaries of some tissues, such as the prostate, the vitreous body of the eye, and the central nervous system (CNS).  Of particular significance are the capillaries in the brain, which help to create and maintain the blood-brain barrier. This barrier is formed by the single layer of tile-like endothelial cells fused by tight junctions that impede entry from the blood to the brain ….
• 7.
  7
• 8.
  an antibacterial agentin the CSF is particularly influenced by the following:8  1. Lipid solubility of the drug  2. Molecular weight of the drug: A compound with a low molecular weight has an enhanced ability to cross the blood-brain barrier..  3.Protein binding of the drug: A high degree of protein binding of a drug in the serum restricts its entry into the CSF.
• 9.
  Patient factors 9  1.Immune system: Elimination of infecting organisms from the body depends on an intact immune system.  2. Renal dysfunction: Poor kidney function causes accumulation of antibiotics that would be otherwise be eliminated. Dosage adjustment prevents drug accumulation and therefore adverse effects. Serum creatinine levels are frequently used
• 10.
  10  3. Hepaticdysfunction: Antibiotics that are concentrated or eliminated by the liver (for example, erythromycin and tetracycline) are must be used with caution when treating patients with liver dysfunction.  4. Poor perfusion: Decreased circulation to an anatomic area, such as the lower limbs of a diabetic, reduces the amount of antibiotic that reaches that area, making these infections notoriously difficult to treat.  5. Age
• 11.
  11  6. Pregnancy:Many antibiotics cross the placenta. Adverse effects to the fetus are rare, except the for tooth dysplasia and inhibition of bone growth encountered with the tetracyclines.  7. Lactation: Drugs administered to a lactating mother may enter the nursing infant via the breast milk. .
• 12.
  Safety of theagent Many of the antibiotics12  Example such as the penicillins, are among the least toxic of all drugs because they interfere with a site unique to the growth of microorganisms.  Other antimicrobial agents (for example, chloramphenicol) are less microorganism specific and are reserved for life-threatening infections because of the drug’s potential for serious toxicity to the patient.
• 13.
  Cost of therapy 13 Oftenseveral drugs may show similar efficacy in treating an infection, but vary widely in cost.
• 14.
  ROUTE OF ADMINISTRATION 14 The oral route of administration is chosen for infections that are mild and is favorable for treatment on an outpatient basis.  In patients requiring a course of intravenous therapy initially, the switch to oral agents should occur as soon as possible. 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
• 15.
  AGENTS USED INBACTERIAL INFECTIONS15  the clinically useful antibacterial drugs are organized into six families— 1)penicillins, 2)cephalosporins, 3)tetracyclines, 4)aminoglycosides, 5) macrolides, and 6)fluoroquinolones— .
• 16.
  CHEMOTHERAPEUTIC SPECTRA16  A. Narrow-spectrumantibiotics :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 mycobacteria .  B. Extended-spectrum antibiotics : that are 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 .  C. Broad-spectrum antibiotics : such as tetracycline and chloramphenicol affect a wide variety of microbial species and are referred to as broad-spectrum antibiotics . Administration of broad- spectrum antibiotics can alter the nature of the normal bacterial flora and precipitate a superinfection of an organism .
• 17.
  COMBINATIONS OF ANTIMICROBIAL DRUGS 17 A. Advantage of drug combinations Certain combinations of antibiotics, such as β-lactams and aminoglycosides, show synergism; that is, the combination is more effective than either of the drugs used separately. Because such synergism among antimicrobial agents is rare, multiple drugs used in combination are only indicated in special situations—for example, when an infection is of unknown origin.  B. Disadvantages of drug combinations A number of antibiotics act only when organisms are multiplying. Thus, coadministration of an agent that causes bacteriostasis plus a bactericidal may result in the first drug interfering with the action of the second. For example, bacteriostatic tetracycline drugs may interfere with the bactericidal effect of penicillins and cephalosporins
• 18.
  PROPHYLACTIC ANTIBIOTICS 18  Someclinical situation require the use of antibiotics for the prevention rather than the treatment of infections . 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.
• 19.
  19 • Pretreatment mayprevent streptococcal infections in patients with a history of rheumatic heart disease. Patients may require years of treatment. • Pretreating of patients undergoing dental extractions who have implanted prosthetic devices, such as artificial heart valves, prevents seeding of the prosthesis. • Pretreatment may prevent tuberculosis or meningitis among individuals who are in close contact with infected patients. Treatment prior to most surgical procedures can decrease the incidence of infection afterwards. Effective prophylaxis is directed against the most likely organism, not eradication of every potential pathogen. Pretreating with zidovudine protects the fetus in the case of an HIV- infected, pregnant woman.
• 20.
  20 A. Hypersensitivity  Hypersensitivityreactions to antimicrobial drugs or their metabolic products frequently occur. For example, the penicillins, despite their almost absolute selective microbial toxicity, can cause serious hypersensitivity problems, ranging from urticaria (hives) to anaphylactic shock. If a patient has a documented history of Stevens Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) reaction to an antibiotic, it should never be re-challenged, not even for antibiotic desensitization. B.Direct toxicity  High serum levels of certain antibiotics may cause toxicity by directly affecting cellular processes in the host. For example, aminoglycosides can cause ototoxicity . 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.. COMPLICATIONS OF ANTIBIOTIC THERAPY
• 21.
  21 SITES OF ANTIMICROBIAL ACTIONS
• 22.
  22