Chemotherapeutic Antibiotics (DONE)

Question 1

Definitions of antibiotics

Answer 1

Substance produced by one micro-organism which inhibits the growth of other micro-organisms Substance produced by a micro-organism or a similar substance (produced wholly or partly by chemical synthesis), which in low concentrations inhibits the growth of other micro-organisms

Question 2

Definition of bacterial resistance to antibiotics

Answer 2

Strain not killed/inhibited by clinical concentration i.e. attained in vivo Strain not killed/inhibited by concentration to which the majority of strains of that organism are susceptible Cells not killed/inhibited by concentration acting upon majority of cells in that culture

Question 3

Micro-organism sources of anitbiotics

Answer 3

Streptomyces spp: streptomycin, tetracyclines Bacillus spp: bacitracin, polymyxin Micromonospora purpurea: gentamicin Pinicillium spp, acremonium spp: penicillins, cephalosporins, griseofulvin Pseudomonas acidophila, gluconobacter spp: monobactam

Question 4

Synthetic sources of antibiotics

Answer 4

Synthetic: sulphonamides, chloramphenicol, fluoroquinolones, dapsone Semi-synthetic- produced by fermentation (micro-organism) and further modified by a chemical process, penicillins and cephaolsporins Future sources: natural plant products, bacteriophages

Question 5

Golden period of discovery

Answer 5

1940s-1960s identification of virtually all current antibiotics with clinical utility Use of empirical screening programmes to identify antibacterial agents by their ability to inhibit bacterial growth Subsequent development of these antibiotics has produced impressive reductions in the burden of disease imposed by bacterial infections The widespread emergence of acquired resistance to antibiotics in bacteria over the last 40 years now constitutes a serious threat to global public health

Question 6

Antimicrobial prescribing- use and misuse

Answer 6

Antibiotics available OTC (Africa and Asia) Patient compliance (long therapy) Responsibility of healthcare professional, particularly pharmacists Better education and awareness of public New responsibilities in prescribing

Question 7

FDA approved recently marketed antibiotics- Linezolid

Answer 7

Mode of action: binds 50s ribosomal sub-unit to block initiation phase of translation Spectrum: Staphylococci (inc. MRSA), enterococci (inc. VRE), streptococcus pneumonia (inc. penicillin resistant strains) Availability: oral and IV PK: high bioavailability Safety: hypertension, lactic acidosis, bone marrow suppression, neuropathy

Question 8

FDA approved recently marketed antibiotics- Daptomycin

Answer 8

Mode of action: binds to cell membranes to produce rapid bactericidal effect Spectrum: Staphylococci (inc. MRSA), enterococci (inc. VRE), streptococcus pneumonia (inc. penicillin resistant strains) Availability: IV PK: t1/2 9 hours, renal excretion Safety: myopathy, elevated creatine phosphokinase

Question 9

FDA approved recently marketed antibiotics- Tigecycline

Answer 9

Mode of action: inhibit 30s ribosomal subunit, evades tet efflux pump and target site inhibition Spectrum: MRSA, some drug resistant coliforms, enterococci (inc. VRE), streptococcus pneumonia (inc. penicillin resistant strains) Availability: IV PK: Cmax 0.6 mg/L, t1/2 27 hours Safety: GI tract intolerance Avoid: pregnancy, lactation and children

Question 10

Bacteria for which treatment is sub-optimal

Answer 10

MRSA C. difficile VRE Penicillin resistant enterococci VISA MDR mycobacterium tuberculosis NDM1 enterobacteria ESBL MDR Acinetobacter spp.

Question 11

Impact of antibiotic resistance in practice

Answer 11

Drive changes in antibiotic prescribing Complicated patient management- significant delays in recovery from illness Increases healthcare costs- prolonged hospital stay, additional procedures, additional drugs Undermine public confidence in health services Increase in medico-legal claims Government targets and league tables

Question 12

Going back to the pre-antibiotic era

Answer 12

Fatal infections become fatal again e.g. meningitis, pneumonia, bacteraemia Post-operative surgical sites infection increase e.g. colectomy rates in >65: 30% Stop of transplantation: e.g. organ transplant Cancer chemotherapy becomes at risk Joint replacement and implant surgery becomes high risk procedures Post-partum and neonatal infections return

Question 13

Options for action

Answer 13

Develop new antibiotics and vaccines Sustain the effectiveness of existing antibiotics Use antibiotics appropriately (antibiotics stewardship) Improve diagnostic precision Reduce healthcare associated infections Reduce the burden of infection