أ. م . د. وحدة اليوزبكيHead of Department of Pharmacology- College of Medicine- University of Mosul-2014
Antimicrobial (Antibiotics) 1
ObjectivesAt end of this lecture, the students will be able to: 1- Differentiate between the meaning of antimicrobial & antibiotic. 2- List the principles of antimicrobial therapy. 3- Enumerate the general complications of antibiotics. 4- Enumerate the classes of antibiotics. 5- State introduction to Penicillin. 6- Discuss adverse reactions of Penicillin. - At a level accepted to the quality assurance standards for the College of Medicine/ University of Mosul.
Antimicrobial therapy
Definition: Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity (the ability to kill the invading microorganism (MO) without harming the cells of the host), this is because of the biochemical differences that exist between MO and human beings.Principles of Antimicrobial Therapy
Selection of the most appropriate antimicrobial agent requires knowledge of: (A) The organism's identity and its sensitivity to a particular agent. (B) The site of the infection. (C) Patient factors. (D) The safety of the agent. (E) The cost of therapy.
A: Determination of antimicrobial susceptibility to the infective organisms
1- Bacteriostatic Versus Bactericidal Drugs 2. Minimum inhibitory concentration. 3. Minimum bactericidal concentration.Bacteriostatic versus Bactericidal drugs
- Bacteriostatic 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 attacks, immobilizes & eliminates the pathogens. - Bactericidal agent: kills bacteria and the total number of viable organisms decreases.2. Minimum inhibitory concentration MIC: is the lowest concentration of antibiotic which inhibits growth of bacteria when kept overnight incubation (in vitro culture). - The clinically obtainable antibiotic concentration in body fluids should be greater than the MIC, to provide effective antimicrobial therapy. 3. Minimum bactericidal concentration MBC: is the lowest concentration of antibiotic that kills the bacteria under investigation.
B.Effect of the site of infection on therapy
1. Blood-Brain Barrier (BBB) - Treatment of CNS infections, such as meningitis, depends on the ability of a drug to penetrate into the CSF. - The BBB ordinarily excludes many antibiotics. However, inflammation facilitates penetration and of many (but not all) antibiotics to enter the CSF. - The penetration and concentration of an antibacterial agent in the CSF is particularly influenced by: a. Lipid solubility of the drug b. Molecular weight of the drug c. Protein binding of the drug
2. Prostate: a- Prostatic epithelium b- Acidic (pH 6.4) of prostatic fluid Trimethoprim is effective in prostitis ,(because it is a basic antimicrobic with good lipid solubility) Penicillin G, not effective in prostitis (because it is acidic and poorly lipid soluble).
C- Patient Factors
1. Immune system: 2. Renal dysfunction: 3. Hepatic dysfunction: 4. Poor perfusion: 5. Age: 6. Pregnancy: 7. Lactation:Chemotherapeutic Spectra of the Antibiotics
- The chemotherapeutic spectrum of a particular drug refers to the species of organisms affected by that drug. 3 Types: 1- Narrow spectrum: - Chemotherapeutic agents acting only on a single or a limited group of MO. eg. Isoniazidis (INH) active only against Mycobacterium.2- Extended spectrum
- This term applied to antibiotics that are effective against gram-positive MO and also against a significant number of gram-negative bacteria. Eg. Ampicillin.
3- Broad spectrum
- Antibiotics that affect a wide variety of microbial species. eg. Tetracycline & Chloramphenicol Note: - Administration of broad spectrum antibiotics can drastically alter the nature of the normal bacterial flora and can precipitate a superinfection or an organism (such as Candida) whose growth is normally kept in check by the presence of other microorganisms.Combinations of Antimicrobial Drugs
A. Advantages of drug combinationCertain combinations of antibiotics, such as B-lactams and glycosides, show synergism, (that is, the combination is more effective than either of the drugs used separately). Note:- Because synergism among antimicrobial agents is rare, multiple drugs 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, co administration of an agent that causes bacteriostasis plus a second agent that is bactericidal may result in the first drug interfering with the action of the second drug and so decrease its efficacy.Empiric therapy prior to organism identification
Empiric therapy: Immediate administration of drug(s) covering infections by both gram-positive and gram-negative microorganisms prior (before) to organism identification.
Empiric therapy Indications
1. The acutely ill patient. 2. Selecting a drug: The choice of drug in the absence of sensitivity data is influenced by: a- Site of infection: 1. Blood-brain barrier. 2. Prostate. b- Patient history: whether the infection was hospital or community acquired, whether the patient is immunocompromised, as well as the patient's travel record, age, Renal dysfunction.Notes: 1- Therapy is initiated after specimens for laboratory analysis have been obtained but before the results of the culture are available. 2- Broad-spectrum antimicrobial therapy may be needed initially for serious infections when the identification of the MO is unknown or the site of infection makes the polymicrobial infection is more likely.
Complications of Antibiotic Therapy
A. Hypersensitivity eg. Penicillins B. Direct toxicity eg. Aminoglycosides can cause ototoxicity C. Superinfections Broad-spectrum antibiotic eg. TetracyclineClassification of the Antimicrobials
Antimicrobials (Antibiotics)
I- Inhibition of cell wall synthesis Betalactams: Penicillin CephalosporinPenicillin
Penicillin was discovered 1st by Alexander Felming in 1929 who demonstrates inhibition of bacterial growth with penicillin moulds. Benzyl penicillin in 1942, is produced by growing one of the penicillin moulds in deep tank. In 1957, the penicillin nucleus (6-amino penicillanic acid) was then synthesized and it became possible to make semisynthetic penicillin.Adverse reactions of Pencillin
1- Hypersensitivity: The most important. Approximately 5% of patients have some kind of reactions, ranging from maculopapular rash to angioedema (marked swelling of lips, tongue, periorbital area) and anaphylaxis. 2- GIT: a- Diarrhea: caused by a disruption of the normal balance of intestinal microorganisms. It is a common problem. b- Pseudomembranous colitis (Clostridium difficile diarrhea ).Notes: Ampicillin & Amoxicillin are the commonest antibiotic associated with diarrhea, although is related to the frequency of their use rather to their innate risk of causing the disease. (This is probably highest for cephalosporin). 3- Nephritis: All penicillins, but particularly methicillin, have the potential to cause acute interstitial nephritis.
4- Neurotoxicity: The penicillins are irritating to neuronal tissue and can provoke seizures if injected intrathecally or with very high blood levels. 5- Platelet dysfunction: with the antipseudomonal penicillin (carbenicillin and ticarcillin) and, to some extent, with penicillin G. 6- Cation toxicity: Toxicities may be caused by the large quantities of sodium or potassium that accompany the penicillin.