Macrolide resistance in two
organisms: a view from the lab
KAITLIN TAGG
Macrolide resistance in two
organisms: a view from the lab
KAITLIN TAGG
A view from the lab
Treponema pallidum
T. pallidum
Mycoplasma genitalium
M. genitalium
Azithromycin exposure
T. pallidum
M. genitalium
Azithromycin exposure
Alternative
treatment
First-line
treatment
RESISTANCE!
T. pallidum
M. genitalium
Global prevalence of resistance?
M. genitalium
 40% Denmark, UK
 20% Melbourne
Global prevalence of resistance?
T. pallidum
 0-1% Taiwan, Madagascar
 60-90% UK, USA, China
The road to resistance
Binds to 50S ribosomal
subunit
Blocks peptide tunnel
Arrests protein synthesis
The road to resistance
Point mutation
Structural change
Macrolides cannot bind
Resistance mutations
Resistance mutations
Detection?
T. pallidum
M. genitalium
Resistance mutations
23S rRNA gene amplification
T. pallidum
M. genitalium
Resistance mutations
23S rRNA gene amplification
Restriction digestion
T. pallidum
M. genitalium
Resistance mutations
23S rRNA gene amplification
Sequencing
T. pallidum
M. genitalium
Resistance mutations
Prevalence?
T. pallidum
M. genitalium
Syphilis story
• 353 T. pallidum samples (2004-2011)
• Detects A2058G mutation
• 84.4% resistance
T. pallidum
Moving on to M. genitalium
• 143 M. genitalium samples (2007-2011)
• Detects 2058/2059 mutations
• 43% resistance
M. genitalium
Moving on to M. genitalium
M. genitalium
More about M. genitalium
 Reports of fluoroquinolone resistance mutations
 Genes - parC and gyrA
 Moxifloxacin – second-line
M. genitalium
More about M. genitalium
 PCR amplification and sequencing
 parC and gyrA mutations – 15%
M. genitalium
Laboratory detection?
85%
T. pallidum
43%
M. genitalium
Laboratory detection?
 Global resistance surveillance
 Insight into selection pressures
 Inform appropriate treatment
T. pallidum
M. genitalium
Laboratory detection?
T. pallidum
Laboratory detection?
M. genitalium
To sum it all up…
85%
43%
PCR and digestion
PCR and sequencing
1 step RT-PCR
1 step RT-PCR
Turn-around time?
Cost?
Benefit to patient?
T. pallidum
M. genitalium
Acknowledgments
Lyn Gilbert
Neisha Jeoffreys
Phill Read
T. pallidum
Debbie Couldwell
M. genitalium