Current & Advanced Treatments for Sexually Transmitted Bacterial Infections Flashcards
one of the most common sexually transmitted infections (STIs)
chlamydia
what species of bacteria are linked to chlamydia that mainly infect humans
chlamydiae -
chlamydia trachomatis
chlamydia pneumonia
symptoms of chlamydia (4)
(can have no symptoms)
pain when urinating
unusual discharge from vagina, penis, rectum
in females, pain in abdomen, bleeding after sex, bleeding between periods
in males, pain and swelling in testicles
causes of chlamydia (2)
unprotected vaginal, anal, oral sex
infected semen or vaginal fluid getting into eye
complications of chlamydia in females (2)
infection can spread to womb, ovaries, fallopian tubes
increased risks of cervical cancer
what condition can chlamydia cause in females if left untreated
pelvic inflammatory disease (PID)
symptoms of pelvic inflammatory disease (PID) (3)
infertility
increased risk of ectopic pregnancy
if untreated during pregnancy, can cause premature labour
complications of chlamydia in males (2)
can cause epididymitis
can cause epididymo-orchitis
(both can affect fertility)
what are the first line treatments of chlamydia (2)
azithromycin
doxycycline
what is the dose/ duration of azithromycin
single dose
what is the dose/ duration of doxycycline
7 day course
between azithromycin and doxycycline, which is prescribed first?
initially azithromycin and then doxycycline if needed, but due to resistance other way around since 2019
what is azithromycin classed as
macrolide antibiotic
what is azithromycin a derivitave of
semi synthetic derivative of erythromycin
what is epididymitis
inflammation of epididymis
what is epididymo-orchitis
inflammation of epididymis and testicles
is azithromycin delivered at a high or low concentration
high concentration
how is azithromycin administered
intramuscular injection at site of infection
why is azithromycin administered as an intramuscular injection at site of infection
to ensure tissue concentration is high but plasma concentration is low - highest bioavaliability
what other infections are azithromycin used for
respiratory, urogenital, dermal and other bacterial infections
mechanism of action of azithromycin
binds at polypeptide exit tunnel of 50S subunit of bacterial ribosome
inhibits mRNA translation thus
inhibits bacterial protein synthesis
is azithromycin bacteriostatic or bacteriocidal
bacteriostatic
what is meant by bacteriostatic
stops bacteria from reproducing, but doesn’t kill them
what are the two mechanisms of azithromycin resistance
alteration of ribosomal components via methylation aka changes antibiotic target and prevents antibiotic binding to it
upregulation of drug efflux pump activity, therefore decreasing intra-bacterial accumulation aka pushing drug out
one mechanism of azithromycin resistance is alteration of ______ components via methylation
ribosomal
one mechanism of azithromycin resistance is alteration of ribosomal components via ____
methylation
one mechanism of azithromycin resistance is ____ drug efflux pump activity, therefore decreasing intra-bacterial accumulation
increased
one mechanism of azithromycin resistance is increased drug efflux pump activity, therefore ______ intra-bacterial accumulation
decreasing
one mechanism of azithromycin resistance is increased drug efflux pump activity, therefore decreasing _________ _____
intrabacterial accumulation
in azithromycin resistance, what efflux pump contributes
Mef transporter
doxycycline’s mechanism of action is ____ to azithromycin
similar
what is doxycycline’s mechanism of action
inhibits protein production by binding the 30S subunit (same as azithromycin but different subunit)
is doxycycline bacteriostatic or bacterocidal
bacteriostatic
what are the two mechanisms of doxycycline resistance
increased expression of efflux pumps
increased expression of ribosomal protection proteins e.g. via methylating ribosomal subunits
how are we infected by chlamydia
chlamydia bind to receptors on membrane
undergo endocytosis
internalise and replicate
burst from cell and infect new cells
what is the interaction between chlamydia and receptor binding
chlamydia binds to platelet derived growth factor receptor-β (PDGFR-β), a RTK
(new preventative medications working towards temporarily inhibiting cells from making PDGFR-β to prevent interaction with chlamydia and spread of infection)
what is growth factor receptor-β (PDGFR-β)
a RTK - receptor tyrosine kinase
new medications working towards temporarily inhibiting cells from making PDGFR-β to prevent spread of infection. what method does this use
gene therapy
what does gene therapy in treating chlamydia rely on
small interfering RNA (siRNA)
what does siRNA do
promote recruitment of RISC
what does recruitment of RISC from siRNA cause
degradation of mRNA preventing protein synthesis
aka cells will not produce PDGFR-β and chlamydia cannot bind to these receptors, cannot enter cell
how can the uptake of siRNA be facilitated
using nanoparticles
inc bioavailability, inc sustained drug release, enhances barrier penetration
what other role do siPDGFR-β nanoparticles play in already infected cells (chlamydia)
trigger autophagy cascade by upregulating autophagy, including of bacteria
what is autophagy
the regulated mechanism of the cell that removes unnecessary or dysfunctional components
degrades invading pathogen
what bacteria is gonorrhoea caused by
Neisseria gonorrhoeae or gonococcus
how else can gonorrhoea be indirectly spread
can be passed from a mother to her baby during childbirth
symptoms of gonorrhoea (4)
pain when urinating
unusual discharge from vagina, penis, rectum
in females, pain in abdomen, bleeding after sex, bleeding between periods
in males, swelling of foreskin, pain, swelling in testicles
how is gonorrhoea spread
unprotected vaginal, anal, oral sex
first line treatment of gonorrhoea
oral azithromycin and intramuscular ceftraxione
the first line treatment of gonorrhoea is oral azithromycin and intramuscular ceftraxione. how much is administered
single dose of both antibacterial agents
what type of drug is ceftraxione classed as
belongs to the β-lactam family of antibiotics
ceftriaxone mechanism of action (5)
binds to and inhibits transpeptidases
these catalyse cross linking of peptidoglycan polymers which form bacterial cell wall
prevents final linking stage of cell wall synthesis, leading to weakened cell wall with gaps
water can enter bacterial cells
cells swell and lyse due to osmotic pressure within cell - burst
is ceftriaxone bacteriostatic or bactericidal
bactericidal
ceftriaxone mechanism of resistance (2)
mutation of transpeptidases e.g. of target site preventing binding
increased drug efflux pump activity and decreased drug influx pumps
what medication has been developed in response to antibiotic resistant gonorrhoea
zoliflodacin
what does zoliflodacin in the treatment of gonorrhoea target
bacterial type 2 topoisomerases
zoliflodacin mechanism of action (6)
topoisomerase II e.g. DNA gyrase causes double strand break, and then religates the strands back together to relive tension and prevent snaps from supercoiling
supercoiling can cause DNA to break, triggers apoptosis
zoliflodacin stabilises topoisomerase 2 in a conformation - by inhibiting ATP-dependent conformational changes and ATPase activity, preventing it from ligating DNA back together
causing accumulation of double strand DNA breaks
triggers bacterial cell death
is zoliflodacin bacteriostatic or bactericidal
bactericidal
Zoliflodacin shows ____ efficacy for human Topo II enzymes to date
little
ideal as does not affect human cells, just bacterial
what else can zoliflodacin be used for
antibiotic resistant chlamydia as well as gonorrhoea
what bacteria is syphilis caused by
treponema pallidum
symptoms of syphilis (5)
small painless sores or ulcers on penis, vagina, anus, mouth
blotchy red rash that affects palms of hands or soles of feet
small skin growths like warts that can develop in women on vulva or in both men and woman around anus
white patches in mouth
tiredness, headaches, joint pains, fever, swollen glands in neck, groin, armpits
if left untreated, what can syphilis cause
neurosyphilis
what population is neurosyphilis most often found in
in HIV-positive patients as they are immunocompromised
first line treatment of syphilis (3)
doxycycline
erythromycin (works same as azithromycin, but poorer ADME)
benzathin penicillin
how is benzathin penicillin administered
single intramuscular injection
how long is doxycycline and erythromycin recommended for
14 days
zoliflodacin is more effective in treating ___/___ infection than ____
urogenital/rectal
pharyngeal
as poor drug penetration into pharyngeal tissue
chlamydiae trachomitis primarily targets ___ cells
gential epithelial
siRNA is administered ____
topically
PLGA
commonly used polymer for intravaginal nanoparticle formulations, is biodegradeable and naturally degrades into lactic acid and glycolytic acid through hydrolysis in body where can join cellular process or be excreted unchanged
but, hydrophobic, less able to penetrate mucus
new advancements
PLGA
zoliflodacin
siRNA
viral treatments - tenofovir gel
tenofovir gel case study
usually for HIV - viral
CAPRISA 004 trial found 1% tenofovir gel had some broad spectrum antimicrobial ability against bacterial STIs
led to in vitro studies that tenofovir exhibit some activity against bacterial pahtogens like chlamydia trachomitis
not studied enough yet
complications for babies born to mothers infected with syphilis
severe, including death and loss of vision and hearing
clinical shit we gaf about - 3
syphilis - treponemia pallidium (can cause neurosyphilis)
chlamydia (which can lead to PID, epididymis, mo orchitis - all affect fertility)
gonorrhoea
current/ old treatments - 7
syphilis - doxyxyxline, ezithromycin, benzathin penicillin
chlamydia - azithromycin, doxyxyxline
gonorrhoea - oral azithromycin and intramuscular ceftraxione
new treatments - 5
syphilis - tenofovir gel case study
chlamydia - zoliflodacin, Cas9 gene therapy and nanoparticles (like PLGA)
gonorrhoea - zoliflodacin
