Pharmaceutical Microbiology Lecture 8 (Mahmoud) PDF

Pharmaceutical microbiology Dr. Reem Sharaby 01116178465 Lecture 8 (Mahmoud) Major adverse effects (Sulfonamides) Hypersensitivity reactions (3%), such as rashes, Stevens-Johnson syndrome (a severe defoliating rash with prominent mucous membrane involvement), vasculitis, se...

Pharmaceutical microbiology Dr. Reem Sharaby 01116178465 Lecture 8 (Mahmoud) Major adverse effects (Sulfonamides) Hypersensitivity reactions (3%), such as rashes, Stevens-Johnson syndrome (a severe defoliating rash with prominent mucous membrane involvement), vasculitis, serum sickness, drug fever, anaphylaxis. Crystalluria, oliguria, and anuria Hematologic reactions, such as agranulocytosis (an acute condition involving a severe and dangerous leukopenia). Thrombocytopenia and in patients with G6PD deficiency (favism) (contraindicated in those patient), hemolytic anemia. Kernicterus in neonates (contraindicated Antibacterial agents combinations A combination of two or more antibacterial agents may be needed for the following reasons: 1- Treatment of mixed infections when not all organisms are susceptible to the same antibiotic. E.g. peritonitis, leg ulcers in diabetic patients (mixture of aerobes, anaerobes, G+ve and G-ve organisms). 2- To achieve adequate cover of the range of possible pathogens before full diagnosis is reached (empiric treatment). 3- Prevention or delay of the development of bacterial resistance. E.g. Treatment of prosthetic valve endocarditis due to coagulase-negative Staphylococci with combinations of rifampin plus vancomycin and TB combined therapy (quadrable therapy). 4- To achieve synergism. E.g. β-lactam + aminoglycoside (often gentamicin), sulfamethoxazole-trimethoprim (the mixture becomes bactericidal) 5- To reduce toxicity or side effects through dose reduction in combination therapy. E.g. Triple sulphonamide combination. DR REEM SHARABY Horus University 01116178465 6- Other reasons apply to certain antibiotics like macrolides, which are able to attenuate severe inflammation, or clindamycin, which is able to inhibit bacterial toxin production. Ex. β-lactam–β-lactamase inhibitor drug. This combination will increase the spectrum of β-lactam antibiotic to cover Gram- negative anaerobes. E.g. amoxicillin/clavulanic acid, ampicillin/sulbactam, piperacillin/tazobactam. Combinations of antibacterial agents may result in 1-Autonomous or indifferent: The result with two drugs is equal to the result with the most effective drug by itself. 2-Additive: assumes that the result observed with more than one drug should be the sum of the separate effects of the drugs being tested if those drugs do not interact with one another (1+1=2). E.g. combination of some B-lactam antibiotics together. 3-Antagonistic: is a negative interaction between two drugs; the combined effect of their combination is significantly less than the sum of the respective effect when tested separately (1+1 toxic plasma concentration. Cross-resistance: a single mechanism of resistance confers resistance to multiple antimicrobial agents Multidrug resistance (MDR): non-susceptibility to at least one agent in three or more antimicrobial categories (i.e. different resistance mechanisms). Extensive drug resistance (XDR): non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) DR REEM SHARABY Horus University 01116178465  Pandrug resistance (PDR): non-susceptibility to all agents in all antimicrobial categories. Mechanisms of resistance 1-Slow or prevent entry of drug into the cell. E.g. resistance to aminoglycosides and beta-lactam antibiotics. 2- Pump antimicrobial drug out of the cell before it can act. E.g. resistance to quinolones. 3- Production of enzyme that destroys or deactivates drug. E.g. Beta-lactamases that inactivate beta-lactam antibiotics, resistance to aminoglycosides 4- Alter target of drug so it binds less effectively. E.g. resistance to aminoglycosides, macrolides, tetracyclines and vancomycin (D-alanyl-D-alanine to D- alanyl-D Lactate). 5- Over production of the target that the antibacterial agent works on. E.g. resistance to sulfonamides. 6- Alter their metabolic pathways to avoid their inhibition by the antibacterial agent. E.g. resistance to sulfonamides DR REEM SHARABY Horus University 01116178465 DR REEM SHARABY Horus University 01116178465