Infectious Diseases Flashcards

Question

What are the conventional phenotypic, and the genotypic methods of drug resistance

Answer 1

Conventional – Phenotypic Using solid and liquid media Absolute concentration, resistance ratio and proportion susceptibility testing Time consuming - weeks Genetic tests for mutations in target Rapid, predictive only Needs accurate databases of mutations

Answer 2

PCR in a cartridge which quantitates amount of TB DNA and identified rpoB gene Identifies if it is TB and if there is rpoB mutation resistance to rifampicin There are 5 probes - if one probe fails to bind, it shows there's resistance to RIF within the rpoB gene

Answer 3

High confidence calls INH - katG or inhA SNPs RIF - rpoB SNPs - codons 507-533 Quinolone - gyrA SNPs

Answer 4

Cross resistance No DST (drug susceptibility) data for new SNP's DST and MICs (minimum inhibitory concentration) for drugs unknown Compensatory and secondary mutations

Answer 5

Genome wide mutation screening Public health monitoring - tracking strains

Answer 6

Quick, unbiased, cost effective and can help improve databases However requires bioinformatics, good databases and many studies - not sure if accurate Gives evidence based advice, allowing faster and more effective treatment for better patient outcomes Reduces onwards transmission and chance of further resistance

Answer 7

Other risk factors/comorbidities e.g. HIV, genetic susceptibility to poor response to TB, latent TB etc.

Answer 8

It may be a weak resistance, with a low MIC falling within the therapeutic index Thus you only need to increase the concentration

Answer 9

When the evidence shows the strain is 100% resistant, there is no point wasting resources if you are 100% sure it wont work

Answer 10

By finding out the MIC and prescribing drugs at higher concentrations than the MIC, if safe to do so

Answer 11

Drug side effects Injectables need long central line – risk of infection and venous thrombosis HEPA filtered negative pressure isolation room until culture negative for 6 weeks Unpleasant for patients, expensive and difficult to manage for hospital Poor compliance Longer you wait for testing = drug resistance thus use empirical treatment first False +ve/negative -ve = ineffective treatment +ve = unnecessary side effect

Answer 12

Viral - trichomoniasis This targets mainly women, causing vaginal discharge, preterm birth, increased incidence of HIV, miscarriage and other complication including bacterial vaginosis

Answer 13

Bacterial - syphilis, gonorrhoea, chlamydia, mycoplasma genitalium Syphilis behaviours like a virus which causes a systemic long term illness Gonorrhoea and chlamydia infect primarily the lower tracts They can infect mucosal surfaces e.g. in pharynx, rectum and cause inflammation Can cause blocking of the fallopian tubes, infertility, preterm birth miscarriage Mycoplasma genitalium- recently recognised STD Gonorrhoea and mycoplasma genitalium have developed antimicrobial resistance

Answer 14

It does not tend to cause mortality now Caused severe pelvic inflammatory disease, ectopic pregnancies, infertility Gonorrhoea in eyes of foetus after birth can cause blindness Can cause endocarditis (affecting heart lining) via disseminated gonococcal infection It can increase risk of HIV transmission and acquisition though taking ART can make it safer Antimicrobial resistance needs to be monitored

Answer 15

Samples taken from discharge, gram stained Gram negative intracellular diplococcus - inside neutrophils A lipid membrane inside and outside of the cell wall

Answer 16

Gonorrhoea can be in back of throat, cervix or rectum which cannot be detected easily Thus a antimicrobial culture result needs to come back before a molecular test Treatment given to prevent spread, but it cannot be personalised thus resistance may develop

Answer 17

A UK system to collect samples from STI clinics and microbiology labs These are then tested to see prevalence of resistance and the region form which it came Finds the rates of resistance in England/wales to which drug - determining which drug to avoid

Answer 18

Ciprofloxacin resistance has increased rapidly Ceftriaxone and spectinomycin resistance has so far remained low However in other countries there are so MIC cut off varies between drugs - 1.25 for ceftriaxone And you don’t want more than 5% of population with that resistant strain

Answer 19

Atypical class of bacteria - a mollicute, related to gram positives No cell wall, not susceptible to penicillin Lost ability to synthesise essential amines for survival and become parasitic and dependant on hosts

Answer 20

The genome size is small - 580kb, coding for <500 genes Does not have the genes to synthesise various essential amines

Answer 21

Cervicitis, pelvic inflammatory disease, preterm birth, spontaneous abortion and may cause infertility

Answer 22

Macrolides - bind 50S subunit targeting 23S rRNA Quinolones - bind DNA gyrase and topoisomerase IV Tetracyclines - bind 30S ribosomal subunit

Answer 23

Pus could indicate chlamydia or gonorrhoea, trichomonas, and mycoplasma genitalium

Answer 24

Microscopy - however this cannot inform resistance

Answer 25

PoC testing can help discriminate between the different causes of genital discharge Rapid tests can test within hours Done at microfluidic level which makes it faster

Answer 26

Molecular testing in labs tend to be accurate Sensitivity (true positives, ruling out false results) and specificity Important in STI's as it can cause emotional distress for false results BUT certain populations may not return e.g. live far, not mobile Then you may prioritise speed over sensitivity You may also pretreat them before they come back

Answer 27

Random access platforms They have individuals modules/shelves which runs samples independently within 90mins Realtime PCR Expensive Can test for chlamydia, gonorrhoea, trichomonas and HPV Sample first - samples taken first, then put into geneXpert, wait, consultation and hopefully by the end the result is available

Answer 28

Microfluidic cartridge test - chambers where the sample in inserted and flows through

Answer 29

The DNA is extracted and goes into two different PCR chambers which amplify the targeted genes, there's are them split into two more chambers for detection Can look for multiple different diagnoses - up to 24! Looks for molecular resistance markers

Answer 30

Biology of pathogen Sexual behaviour of patients e.g. partner change Duration of infectiousness

Answer 31

Cell wall alteration - penicillin and cephalosporins Change in porin protein channels preventing antibiotics entering cells Changes in gene control of transporters e.g. efflux pumps which normally pump toxins actively pump out antibiotics Penicillin resistance due to mobile genetic elements - plasmids which can produce beta-lactamase Ribosomal disruptors - macrolides Fluroquinolones can be passed by mutations in topoisomerases Topoisomerases are needed for unwinding of DNA for replication

Answer 32

Fluroquinolones targets topoisomerases II/DNA gyrase A which prevents unwound DNA from twisting Topoisomerase do this by cutting the DNA and reattaching it - thus inhibition = DNA twist = no replication It also targets topoisomerase IV or ParC/E e.g. moxifloxacin This is involved in the circular chromosome

Answer 33

Codon 91 Ser to Phe and codon 95 Asp to = resistance

Answer 34

PCR This can be used to identify those who are susceptible to fluoroquinolones

Answer 35

It can help predict strains accurately It has fast turn around - but it does depend on the platform e.g. NGS Vs long-read