Antimicrobial resistance case study Flashcards
what is the global incidence of gonorrhoea?
- around 82 million new cases a year
- 19 cases per 1000 women
- 23 cases per 1000 men
why do men have more gonorrhoea then women?
mainly due to men who have sex with men
where are the most gonorrhoea cases?
africa
what age group is most at risk of gonorrhoea?
adolescents and young adults due to being sexually active with immature organs
what are the common routes of transmission of gonorrhoea?
infects mucosa of the urogenital tract
1. vaginal intercourse
2. oral sex
3. anal sex
4. from mother to baby during childbirth
what are the risk factors for gonorrhoea?
- dangerous sexual contact like unprotected sex with multiple sexual partners
- had or currently have an STI due to co-occurrence or compromised immune system
- under 25 years old due to immature reproductive organs
who are the most at risk groups for gonorrhoea?
- men who have sex with men
- transgender people
- sex workers
- African Americans
what are the stages of gonorrhoea infection?
- adherence to the urogenital epithelium
- competition with resident microbiota for nutrients
- colonisation
- release of virulence factors
- cytokine, chemokine and inflammation activation
- uptake of gonorrhoea into cells
- neutrophil rich purulent facilitates transmission
what is the predominant symptom of gonorrhoea?
purulent - a thick oderless, yellow discharge
how is purulent formed?
- a rapid influx of neutrophils and other fluids during inflammation
- cell damage at the epithelium
- accumulation of dead and dying cells
what are the other symptoms of gonorrhoea?
- itching
- fever
- pelvic or lower abdominal pain
- pain during micturition
- skin rashes
what are some symptoms that indicate complications?
- pelvic pain and fever could indicate pelvic inflammatory disease (PID)(transluminal spread)
- skin rashes and fever could indicate disseminated gonococcal spread (systemic spread)
what causes the pain in PID?
- ascending infection of gonorrhoea
- inflammation and infection in the pelvis
- immune response causes the pain
what are the symptoms of PID?
- lower abdominal pain
- increased vaginal discharge
- irregular menstrual bleeding
- fever
- painful urination
- pelvic organ tenderness
How is a pelvic exam done?
- visual inspection of the external genitalia
- use a speculum to see the vagina and cervix clearly
- may insert fingers and press down on the abdomen
- helps to assess the size, shape and position of the uterus and ovaries
what is the classical presentation of disseminated gonococcal infection?
- Gonorrhoea has spread through the blood to different sites in the body so a variety of symptoms
- septic arthritis
- polyarthralgia
- pustular skin lesions
- bacteremia
- meningitis
what happens in untreated gonorrhoea?
- can lead to PID or disseminated infection
- PID complications like formation of scar tissue, ectopic pregnancy, infertility, long term pain
- untreated disseminated infection can lead to death
what types of samples can be used for gonorrhoea testing?
- urine
- swab of the infected area
- blood and fluid for disseminated infection
what is a nucleic acid amplification test?
Amplification of the genetic material to detect the presence of the bacteria
1. purify the DNA
2. amplify
3. detect
what is a full sexual screening?
- a test that covers all the primary STIs
- Gonorrhoea, chlamydia, syphilis and HIV
- blood test for HIV and syphilis
- swab or urine test for chlamydia and gonorrhoea
what is the standard treatment for gonorrhoea?
a single dose a 500mg of ceftriaxone as an intramuscular injection
what is ceftriaxone?
- a cephalosporin which is a beta-lactam
- bind to the beta lactam core of penicillin binding proteins to prevent the cross linking in bacterial cell walls
how is ceftriaxone different from other antibiotics?
- It has a much longer half-life so it requires less frequent dosage
- very broad spectrum of action so can disrupt both gram negative and gram positive bacteria
- exhibits lower cross reactivity
what factors determine the route of administration for ceftriaxone?
- the severity of infection as life threatening infections may need IV therapy
- if oral therapy cannot be used due to vomiting or inadequate absorption
what are oral cephalosporins used for?
simple easy to treat infections like strep throat
what are IV cephalosporins used for?
more severe infections to ensure it reaches the tissue quickly
what happens if a patient is allergic to cephalosporins?
- reaction to R1 side chains so could be any beta-lactam as well
- Alternatives include macrolides, tetracyclines and fluoroquinolones
what is Ertapenem?
a carbapenem that is effective against a broad spectrum of bacteria
when is ertapenem used to treat gonorrhoea?
if there are concerns about resistance to ceftriaxone
what is ertapenem used to treat?
- severe infection in the skin, lungs, pelvis and urinary tract
- prevent infection in people having surgery
how does ertapenem work?
- it binds and inhibits penicillin binding proteins
- Inhibits cell wall synthesis by interfering with the strengthening and lengthening of the peptidoglycan
- leaves the cell without a cell wall
what is a test of cure swab?
a repeat test after a course of treatment has been carried out to test if the treatment worked and the patient was cured
if treatment was not successful the swabs are investigated for AMR
How is AMR testing carried out?
- collect sample from the infected area
- plate on agar
- disc diffusion or etest strip
- OR use MALDI-ToF to quickly sequence and find resistant strains
- identify in a primary diagnostic lab and then send to secondary lab for confirmation
why do doctors need to report ceftriaxone treatment failure?
to monitor the spread and frequency of resistance
what is the role of public health england in monitoring AMR?
- collecting and disseminating the data about resistance to the relevant authorities
- run AMR surveillance and confirm cases
why are AMR gonorrhoea cases referred to a UK health security agency lab for confirmation?
- high through put testing to confirm AMR cases
- use RT-PCR and MALDI-ToF of PorA and sodC
- ß-lactamase activity tests
- if it is above the alert value then it is investigated further
- data is the available on the gov.uk website
when is gonorrhoea prophylaxis used?
when the mother is at risk or has a gonococcal infection
how do we prevent neonatal gonococcal transmission?
screening and retesting pregnant women in the 3rd trimester
what prophylaxis is used for neonates?
- 0.5% erythromycin ophthalmic ointment
- given <24 hours after birth
- instilled in both eyes
- monitoring for disseminated infection
what N. Meningitidis vaccine are available?
ACWY vaccine:
- good
- causes 90% of UK cases to be MenB
4CMenB vaccine (Bexsero):
- 4 serogroup B antigenic components
- 94% effective
what components make up the Bexsero vaccine?
- Neisserial adhesion protein – NadA
- Outer membrane vesicles containing proteins - OMV
- Neisseria Heparin Binding antigen (NHBA) fused to GNA1030
- Factor H binding protein (fHbp) fused to GNA2091
can we use the bexsero vaccine as a possible gonorrhoea vaccine?
- there is currently no specific vaccine for gonorrhoea
- as bexsero contains the outer membrane vesicles it can provide cross protection
- current trials have shown about 40% efficacy
what new drugs are in clinical trials to treat gonorrhoea?
- Zoliflodacin
- Solithromycin
- Gepotidacin
what is Zoliflodacin?
- An Oral Spiropyrimidinetrione Antibiotic that was developed by AstraZeneca
- Potent antibacterial activity against MDR gonorrhoea
- Inhibits type 2 topoisomerases like bacterial gyrase B
- Zoliflodacin targets distinct binding site that generally haven’t been used as targets before
- Currently in phase 3 global trials
what is a topoisomerase?
Topoisomerases are involved in managing the 3D structures of DNA like supercoils
what is solithromycin?
- an antibiotic normally used for pneumonias
- good against MDR gonorrhoea
- in phase 3 trials
what is Gepotidacin?
- also a topoisomerase inhibitor
- can be used for urogenital gonorrhoea
- Just finished phase 2 trials
