PRINCIPLES OF ANTIMICROBIAL THERAPY

ANTIMICROBIAL THERAPY TAKES ADVANTAGE OF BIOCHEMICAL DIFFERENCES BETWEEN MICRO ORGANISMS AND HUMANS. SELECTIVE TOXICITY RELATIVE RATHER THAN ABSOLUTE.

PRINCIPLES OF ANTIMICROBIAL THERAPY SELECTION OF ANTIMICROBIAL AGENT Identity of organism & its sensitivity Site of infection Safety of agent Patient factors Cost of therapy

Identity of organism Obtain sample prior to starting therapy Microsopic examination Gram stain Culture media sensitivity

Site of infection The blood brain barrier Choose drugs which are more lipid soluble Low degree of protein binding Low molecular weight

Safety of the agent Penicillins are among the least toxic of the antibiotics Drugs such as chloramphenicol are reserved for severe resistant cases

Patient factors All conditions which can ,< immune function have to be looked for Alcoholism, DM, malnutrition, advanced age, HIV. Renal function– drugs which are nephrotoxic are to be avoided Pregnancy Lactation Drugs like tetracyclines, aminoglycosides are to be avoided. Age new born –avoid chloramphenicol , infants-- tetracycline

Emperic therapy prior to organism identification Acutely ill patient Identification & sensitivity of organism Selection of drug -- Status of the patient- renal, hepatic. Pregnancy & lactation, age -

-Bacteriostatic -Bactericidal Spectrum Narrow spectrum-- Isoniazid Extended spectrum-- ampicillin Broad spectrum– tetracycline, chloramphenicol

Minimum inhibitory concentration (MIC) LOWEST concentration of the antibiotic which inhibits growth To provide effective antimicrobial therapy the antibiotic concentration should be more than MIC

Minimum bactericidal concentration Lowest concentration of antimicrobial agent that results in a 99.999 percent decline in colony count.

Combination of drugs used in Mixed infections Unknown origin Resistant organisms Better to use bacteriostatic with bacteriostatic, or bactericidal with bactericidal!

Synergism between the actions of two or more drugs. Two bactericidal agents: Use a penicillin and an aminoglycoside. The increase in cell-wall permeability caused by the penicillin allows for easier access of the aminoglycoside. To delay development of resistance. For the treatment of "mixed" infections.

Drug resistance Mainly by Mutations of DNA DNA transfer of drug resistance Modification of target sites Decreased accumulation Enzymic inactivation

Complications of antibiotic therapy Hypersensitivity--- penicillin-urticaria, anaph shok Direct toxicity---- aminoglycoside Super infections SUPERINFECTIONS: Oral, GU, and GI superinfections can occur with use of antibiotics. GI infections are most common. Intestinal Candidiasis: Fungal overgrowth of the Candida secondary to giving an oral antibiotic and depleting intestinal flora. Add an antifungal drug to treat it.

Staphylococcal Enterocolitis: Life-threatening infection with Staph Aureus as a result of antibiotics. To treat it: Stop the original antibiotic therapy. Start therapy with vancomycin or some other appropriate agent to fight Staph Aureus. Pseudomembranous Colitis: Life-threatening infection of Clostridium Difficile secondary to antibiotic therapy. Start therapy with vancomycin and/or metronidazole

Prophylactic antibiotics

prevention of streptococcal infections in patients with history of RHD Prevention of TB in close relatives of patient Prior to surgical procedures Prevent transmission of hiv from mother to fetus.