Antimicrobial Chemotherapies:
Assignment:
Please be sure to appropriately reference the sources used Enzymes are significant in the mode of action of antibiotics (as targets) and in the resistance of bacteria to the action of antibiotics (as inactivating agents). In resistant cells there may be differences in enzymes compared with sensitive cells or the expression of enzymes may be different, These differences may be due to chromosomal changes (mutations; transposons) or to genes on plasmids.
Q1.
(a) Use the mechanisms of resistance to beta-lactams discussed in GG p.1479 (12“ Ed – online text via the library) to explain
i) The beta-Iactam resistance shown by S. aureus M908
ii) The beta-Iactam resistance shown by S. aureus CP11
(b) How is the resistance shown by newly-emerging resistant gram-negative organisms carrying the NDM-1 gene different to those discussed in 1 (a)?
(c) Examine the data collected for the aminoglycoside activities against strains CP10 and CP11. DISCUSS the possible mechanism for the SmR in these strains from the options set out in Goodman and Gilman. (Be concise and make it clear how you use the data in reaching your conclusion. You are asked for one choice and the reason for that choice instead of the others).
Q2. Describe the contribution of B-lactamases to the indirect pathogenicity of some bacteria.
See Maddocks,JL. Indirect pathogenicity. Journal of Antimicrobial Chemotherapy 1980; 6: 307-309. Also an Addendum at page 807 in this volume. and
Brook: The concept of indirect pathogenicity by B-Iactamase production, especially in ear, nose and throat infection. Journal of Antimicrobial Chemotherapy 1989; 24 Suppl. B: 63-72.
[These are the significant early papers on this concept. A more recent review is available online from the library. Clin. Microbiol. Infect. 2004 Sep; 10(9): 777-84.]
Q3.
(a) For most infections, monotherapy is preferred to combination therapy but in some circumstances, combination therapy is warranted. Care must be taken when combining antimicrobials because although there are advantages-there may also be disadvantages. Use the results of the checkerboard titration of Ne/sserla gonorrhoea and Proteus mirabilis obtained during session 11 to prepare a clearly labelled isobologram.
(b) Refer to GG p1103 to explain your isobologram results.
Q4. A consideration of the concept of antibiotic stewardship was first introduced into the Antibiotic Guidelines in version 14 (p.7). Describe how the role of an “antibiotic pharmacist” contributes to antibiotic stewardship.
[Q4 will not be in textbooks and will need to be searched on-line. Use at least two references]