Case 1  Tunyapon Sasithorn Pharmacology Clinical case

Problem 1  A clinical study evaluating the efficiency of the antibiotic treatment of the meningitis was carried out. One group of patients with pneumococcal meningitis received parenteral penicillin. A second group received penicillin plus tetracycline therapy.

A. How do penicillin and tetracycline differ in their mechanism of action?

Penicillin Mechanism of Action  B- lactam antibiotics work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall.  The B- lactam moiety of penicillin binds to the enzyme (transpeptidase) that links the peptidoglycan molecules in bacteria, and this weakens the cell wall of the bacterium when it multiplies  This causes cell cytolysis or death when the bacterium tries to divide.  The build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases which further digest the bacteria's existing peptidoglycan.

Tetracycline Mechanism of Action  Tetracyclines inhibit bacterial protein synthesis by blocking the attachment of the transfer RNA-amino acid to the ribosome.  They are inhibitors of the codon- anticodon interaction.

Mechanism of Action  Penicillin  Bactericidal  Tetracycline  Bacteriostatic

 Which group had a lower mortality rate ?

Mortality was significantly higher in the penicillin– tetracycline group compared to the single drug penicillin group: Mortality rate Penicillin – tetracycline group  79% ∞one of seven patients survived Penicillin group  30% ∞ nine of 20 patients survived

3.  If there was a difference, what would account for the observation?

 Penicillin group experienced a bactericidal effect which is very important in treating patients with pneumococcal meningitis.  Penicillin – tetracycline – a combination of a cell wall agent, the bactericidal activity of which depends on cell growth (penicillin), with a reversible protein synthesis inhibitor that interferes with cell growth (tetracycline), is a classical example of antibiotic antagonism, resulting in the lower mortality rate of penicillin – tetracycline group. penicillin – tetracycline group.

 Antagonist reaction of Penicillin and tetracycline renders these drugs in combination ineffective.  The mutual antagonist reaction produces an overall bacteriostatic activity which proves ineffective in treating patients with pneumococcal meningitis.

4.  Any other drug combination that you can recommend? On what basis?

Other drug recommendations due to:  Meningitis with penicillin resistant pneumococcus  Other synergistic reaction

Drug combinations  Drugs of first choice Children  Ceftriaxone  Cefotaxime +/- Vancomycin VancomycinAdults  Ceftriaxone  Cefotaxime Others  Rifampin  B lactam antibiotic  Ex: Penicillin, Ampicillin, Piperacillin and Cefuroxime + Gentamicin  Alternative drugs Children  Chloramphenicol  Systematic corticosteroids Adults  Vancomycin + Ceftriaxone  Vancomycin + Cefotaxime

Thank You sir, mam. Come again! :P