Principles of Antimicrobial Therapy Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture 1 September 17, 2011

Chemotherapy The chemical treatment of infection Of course, treatment of cancer has also been included In fact, the word ‘chemotherapy’ is increasingly restricted nowadays to the treatment of cancer In a series of lectures, we will discuss about chemotherapeutic drugs Infestation refers to the state of being invaded or overrun by parasites. or other pests

What is Antimicrobial Drugs? Substances that kill or inhibit the growth of microorganisms Example: bacteria, virus, fungi, protozoa Antimicrobial drugs either kill microbes or prevent the growth of microbes Disinfectants are antimicrobial substances used on non-living objects

Few Terminology Antibacterial Drugs used to treat infections caused by bacteria Classified as either Gram-positive or Gram-negative depending on whether or not stain with Gram's stain The cell wall of Gram-positive organisms is a relatively simple structure. Whereas, the cell wall of Gram-negative organisms is much more complex Difficulty in penetrating this complex outer layer is probably the reason why some antibiotics are less active against Gram-negative than Gram-positive bacteria Method is named after the Danish bacteriologist Hans Christian Gram A method of differentiating bacterial species into two large groups (Gram-positive and Gram-negative). It is based on the chemical and physical properties of their cell walls. Primarily, it detects peptidoglycan, which is present in a thick layer in Gram positive bacteria. A Gram positive results in a purple/blue color while a Gram negative results in a pink/red color

Few Terminology, continued…… Antiviral Drugs used to treat infections caused by virus Viruses are small (usually in the range 20-30 nm) infective agents Incapable of reproduction outside their host cells The free-living virus particle is termed as virion, and consists of either RNA or DNA

Few Terminology, continued…… Antifungal Drugs used to treat infections caused by fungi Infectious diseases caused by fungi are called mycoses, and they are often chronic in nature Infections are superficial and only involve the skin Some fungi may penetrate the skin, causing subcutaneous infections

Few Terminology, continued…… Bacteriostatic Drugs that inhibit the growth of bacteria Bactericidal Drugs that kill the bacteria A bactericidal antibiotic kills the bacteria, usually either interferes with the formation of the bacterium's cell wall or its cell contents. A bacteriostatic stops bacteria from multiplying

What is Antibiotic? Definition Selective toxicity Drugs obtained from some microorganisms which are effective against other organisms in small doses Selective toxicity Able to kill or stop growth of microorganisms but have no effect in host cells Choice of antibiotic Requires clinical judgment and detailed knowledge of pharmacological and microbiological factors

Diagnosis of Infection This is usually made on history and clinical examination supported by appropriate investigations, e.g. chest X-ray, bacteriological culture The site and severity of infection are important

Patient Factors Age, sex Weight and height Pregnant, lactating Immune status, renal function, hepatic function and concurrent medication that may cause drug interaction

Drug Factors Antimicrobial spectrum Pharmacokinetics, i.e. availability at the site of action Adverse effects Drug interaction Convenience Cost

MIC and MBC Minimal inhibitory concentration (MIC): Below this concentration microbial growth is not prevented Minimal bactericidal concentration (MBC): Minimum bactericidal concentration of an antibiotic that kills 99.9% of the bacteria

Effectiveness of Antibiotic Microbial Resistance Microbes are said to be resistance to an antibiotic if their growth is not prevented by the maximal level of the antibiotic that can be tolerated by the host Effectiveness of Antibiotic Must reach its target in an active form Bind to the target Interfere with its function

Mechanisms of Bacterial Resistance Drug does not reach its target Restriction of entry of the drugs into the microbe by altered permeability Drug is not active Inactivation of the drug either by disruption of its chemical structure or by addition of a modifying group Modification of the bacterial targets May take an enzyme with reduced affinity for an inhibitor or an altered organelle with reduced drug binding property

Drug Combinations Most infections can be treated with single agent However, there are 4 main situations in which more than one antimicrobial drug is prescribed concurrently To achieve broad antimicrobial activity in critically ill patients with an undefined infection, e.g., aminoglycoside plus penicillin to treat septicemia To treat mixed bacterial infections (e.g., following perforation of bowel) where no single agent is effective To prevent emergence of resistance, e.g., treating tuberculosis To achieve an additive or synergistic effect, e.g., co-trimoxazole in the treatment of pneumocystic carinii pneumonia Septicemia is the presence of bacteria in the blood

Antimicrobial Spectrum Narrow Spectrum Antibiotic acting on a single or limited group of microorganism, e.g., isoniazide Extended Spectrum Antibiotics that are effective against Gram +ve and also against some Gram –ve organisms, e.g., amoxycillin Broad Spectrum Antibiotics acting against a wide variety of microorganisms, e.g., tetracycline

Classification of Antibiotic Cell wall synthesis inhibitor Penicillin, cephalosporine Protein synthesis inhibitor aminoglycoside Anti-metabolites sulfonamide Inhibitors of nucleic acid metabolism rifampicin