Investigating Infections and Antibiotics

Question 1

Describe the choice of antibiotics to be tested on a bacterial infection using lab results- ie how are the lab results recorded?

Give a semi quantitative method of testing

Answer 1

Results are usually recorded as:
Resistant: high likelihood of treatment failure
Susceptible: high likelihood of treatment success
Moderately sensitive: uncertain effect. Higher drug conc may treat infection

a semi quantitative method of antibiotic testing= disc diffusion, zone of inhibition. EUCAST breakpoints which quantify ZOI

Question 2

What is the MIC? (min inhibitory conc)
what does it determine, what does it depend on?

Answer 2

The exact conc of antibiotic needed to inhibit growth
Often needed bc disc diffusion isn’t reliable for e.g. N.meningitidis and penicillin, cefotaxime, ciprofloxacin.
MIC determines treatment, or investigates activity of new antimicrobials.
Depends on age, weight, renal/liver function and infection severity

Question 3

Someone presents with diarrhoea and give a stool sample. Which staining and lab techniques would be the most helpful?

Answer 3

Direct Gram stain of stools gives too much information bc feces already stores millions of bacteria
Staining and observing the sample would be useful- mucho erythrocytes/WBCs indicates infection bc they shouldn’t be there

Question 4

How can we detect certain bacteria from a sample?

Answer 4

• Select for or indicate TARGET organisms
• Often target single organisms
• Suppress commensals
• Differentiate
• Use salts, chemicals, sugars, indicators, antibiotics to achieve desired effect
  Examples of media: MacConkey agar, Campy-blood agar etc

Question 5

Explain the value of blood agar and MacConkey’s agar in bacterial identification

Answer 5

MacConkey agar containing bile salts and lactose indicator cultured overnight at 37oC in air.
A selective and differentiating agar that only grows gram-negative
Campy-blood agar: selective for Camplyobacter jejuni from fecal or rectal swabs
incubated overnight at 42oC in anaerobic jar, microaerophilic

Both types reduce the growth of normal flora

Question 6

Explain the investigation of urine, including a type of agar which is used and the colour results
What is the relationship between bacterial numbers in a urine specimen and urinary tract infections?

Answer 6

Individuals w a UTI typically have greater number of bacteria (>10^5) in their urine
Ecoli commensal can turn pathogenic in UTI

Question 7

Describe identification of staph in the lab to see if it is commensal or not (staph aureus)

Answer 7

Staph. aureus produces coagulase enzyme – most other Staphs do not. These can be used as lab identification tests
Staph aureus is coagulase positive and staph epidermis is coagulase negative.

Question 8

Why should we consider the therapeutic margin when giving antibiotics? Why musnt we give very large doses?

Answer 8

Therapeutic Margin: effects of the MIC versus toxic effect
This can be narrow for toxic drugs: aminoglycosides, vancomycin (ototoxic, nephrotoxic)

Large doses, esp broad spectrum kill flora–>Antibiotic associated Colitis: (clindamycin, broad-spectrum lactams, fluoroquinolones)

Pseudomembranous colitis/C.diff colitis:C.dif can disturb the main part of the flora, leading to: Ulcerations – inflammation, severe diarrhoea. Serious hospital cross-infection risks

Question 9

Antibiotics have selective toxicity due to differences between host and pathogen. (hence cannot target viruses (intracellular), fungi and parasites)

Compare bactericidal and bacteriostatic antibiotics

Answer 9

Question 10

Describe the mechanism of action of penicillin

Answer 10

Certain bacteria eg staphA coss link peptidoglycan chains using penicillin binding protein (transpeptidases)
Penicillin stops action of penicillin binding protein.
Cell wall inhibition–> kills the bacterium
beta lactam= the active site of the antibiotic

Question 11

Give the other ways in which bacteria can be inhibited by antibiotics

Answer 11

Antibiotics like Trimethoprim inhibit dihydrofolate reductase which inhibits bacterial folate production
Note: avoid trimethoprim in first two trimesters, bc it can cause folate deficiency which is essential for fetal neuro development

PS inhibitors either bind to 30s (streptomycin, tet) or 50s (chloramphenicol, eryth)

Question 12

What does this graph show?
Explain the 2 types of antibiotics in terms of their pharmacodynamic properties

Answer 12

Antibiotic conc will rise above mic and then fall as that drug is eliminated until its next dose.
Conc above the MIC line is what you want for efficacy
Time-dependent antibiotics: more effective when maintained at a certain conc over an extended time
Conc-dependent: work best by reaching a v high conc for a short period and then rapidly decrease, eg glycosides. Compared to time dependent, this reduces side effects of prolonged drug exposure.

Question 13

Draw a table showing the stages of antibiotic therapy

Answer 13

Question 14

When can we get failure of antibiotic therapy?
Drug, host, bacteria and lab

Answer 14

.

Question 15

When would we use combination therapy?

Answer 15

BEFORE an organism identified in life-threatening infections e.g. endocarditis, septicaemia
Polymicrobial infections eg abscess, GI perforation, anaerobes and aerobes
Synergy: e.g. penicillin and gentamicin. Co-trimoxazole (sulphonamides + trimethoprim)
Less toxic doses of an individual drug is possible
Reduce resistance e.g. Tuberculosis

Question 16

Describe the basic penicillins: what are they active against, are they broad or narrow spec, how are they administered?

Answer 16

Basic penicillins: benzylpenicillin(PenG), penicillin V
Active against strep, pneumococci, meningococci, treponemes. Narrow range. Most strains of Staph A are resistant.

Pen G: not acid stable so can be given i/v or i/m. Good for some G-ves and G+ves

Pen V/phenoxymethlypenicillin: given orally (more acid stable than penG).
Less active for G-ves, but same activity for G+ves as PenG

Question 17

Complete this table

Answer 17