1. PHL 424 Antimicrobials 1 st Lecture By Abdelkader Ashour, Ph.D. Phone: 4677212Email: aeashour@ksu.edu.sa

2. Antimicrobials, Overview  Antimicrobial agents are among the most commonly used and misused of all drugs  The most common consequence of the widespread use of antimicrobial agents has been the emergence of antibiotic-resistant pathogens, fueling an ever-increasing need for new drugs  However, the pace of antimicrobial drug development has slowed dramatically, with only a small number of new agents, few of which are novel, being introduced into clinical practice each year  Reducing inappropriate antibiotic use is thought to be the best way to control resistance  Although awareness of the consequences of antibiotic misuse is increasing, overprescribing remains widespread, driven largely by patient demand, time pressure on clinicians, and diagnostic uncertainty  If the gains in the treatment of infectious diseases are to be preserved, clinicians must be wiser and more selective in the use of antimicrobial agents

3. Antibiotics, Overview  Definition In the strictest sense, antibiotics are antibacterial substances produced by various species of microorganisms (bacteria, fungi and actinomycetes) that suppress the growth of other microorganisms  Common usage often extends the term antibiotics to include synthetic antimicrobial agents, such as sulfonamides and quinolones  The first antibiotic to be discovered was penicillin, a natural product of Penicillium mold. Innumerable microbial products have been investigated since then  Semi-synthetic antibiotics: chemically modified natural antibiotics  Why modified? They are modified in an attempt to: enhance the beneficial effects minimize the undesirable effects increase solubility increase stability improve pharmacokinetics (i.e., wider distribution and longer half-life)

4. Antibiotics, Terminology  Synergism vs. antagonism  Drug synergism occurs when drugs can interact in ways that enhance or magnify one or more effects, or side effects, of those drugs. For example,  - lactams and aminoglycosides  The opposite of synergy is antagonism, the phenomenon where two agents in combination have an overall effect that is less than that predicted from their individual effects. For example, chloramphenicol (generally bacteriostatic) antagonizes the actions of penicillins (bactericidal)  Bacteriostatic vs. bactericidal drugs  Bacteriostatic agents inhibit bacterial cell replication but require the host's immune factors to clear the infection, whereas bactericidal agents kill the bacteria If host immunity is suppressed or the infection is in an area of poor immunologic surveillance (e.g., CSF), bacteriostatic agents may not be as effective as bactericidal agents  Minimal inhibitory concentration (MIC)  The lowest concentration of antibiotic that inhibits bacterial growth

5. Basis of Choice of the Proper Antibiotic  However, in the critically ill patient in whom there is some chance that a bacterial infection may be a contributing factor, it is prudent to administer antibiotics effective against the most likely pathogens  The decision to prescribe an antibiotic is based upon proof or strong suspicion that the patient has a bacterial infection  Probable viral infectious or noninfectious processes should not be treated with antibiotics  Whenever possible the antibiotic selection should be based upon the isolation of a pathogen (followed by cultivation and identification and the susceptibility to antibiotics)  But most patients who require antibiotic therapy present with an acute problem that mandates initial empiric therapy

6.  Empiric Therapy  the specific antibiotic chosen is based upon: 1.knowledge of the pathogens likely to cause a specific infection and its susceptibility to a particular antibiotic 2.the ability of the pathogen to inactivate the antibiotic 3.spectrum of activity of the antibiotic 4.safety of the antibiotic and its most common side effects 5.site of infection 6.patient’s history 7.cost of the therapy, compared to agents of equal safety and efficacy  If more than one antibiotic is active against the likely pathogens at the site of infection, the specific agent should be chosen on the basis of relative toxicity, convenience of administration and cost Basis of Choice of the Proper Antibiotic

7. Classification of Antibiotics by Mechanism of Action Inhibition of cell-wall synthesis Vancomycin Penicillins Cephalosporins Aztreonam Imipenem Inhibition of nucleic acid synthesis Rifampin Quinolones Metronidazole Inhibition of protein synthesis Aminoglycosides Spectinomycin Tetracyclines Chloramphenicol Erythromycin Clindamycin Inhibition of folate synthesis Sulfonamides Trimethoprim