Resistance-guided antimicrobial therapy using doxycyclinemoxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection

efficacy and tolerability

Duygu Durukan, Tim Read, Gerald Laurence Murray, Michelle Doyle, Eric P.F. Chow, Lenka A. Vodstrcil, Christopher K. Fairley, Ivette Aguirre, Elisa Mokany, litty Y tan, Marcus Y Chen, Catriona S. Bradshaw

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background
Macrolide-resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions and quinolone-resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5g-azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance.

Methods
Patients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded.

Results
A total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4% (95% CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0%(88.1-94.6). De novo macrolide-resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n=186) yielded a pooled cure of 95.7% (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22% of macrolide-resistant cases at baseline.

Conclusion
These findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.
Original languageEnglish
Number of pages24
JournalClinical Infectious Diseases
DOIs
Publication statusAccepted/In press - 20 Oct 2019

Cite this

@article{5af428da61b5411ba90ae5c5e04d47ee,
title = "Resistance-guided antimicrobial therapy using doxycyclinemoxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability",
abstract = "BackgroundMacrolide-resistance in Mycoplasma genitalium (MG) exceeds 50{\%} in many regions and quinolone-resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5g-azithromycin cured 92{\%} and 95{\%} of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance.MethodsPatients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded.ResultsA total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4{\%} (95{\%} CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0{\%}(88.1-94.6). De novo macrolide-resistance was detected in 4.6{\%} of cases. Combining doxycycline-azithromycin data with our prior RGT study (n=186) yielded a pooled cure of 95.7{\%} (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22{\%} of macrolide-resistant cases at baseline.ConclusionThese findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.",
author = "Duygu Durukan and Tim Read and Murray, {Gerald Laurence} and Michelle Doyle and Chow, {Eric P.F.} and Vodstrcil, {Lenka A.} and Fairley, {Christopher K.} and Ivette Aguirre and Elisa Mokany and tan, {litty Y} and Chen, {Marcus Y} and Bradshaw, {Catriona S.}",
year = "2019",
month = "10",
day = "20",
doi = "10.1093/cid/ciz1031",
language = "English",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",

}

Resistance-guided antimicrobial therapy using doxycyclinemoxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection : efficacy and tolerability. / Durukan, Duygu; Read, Tim; Murray, Gerald Laurence; Doyle, Michelle ; Chow, Eric P.F.; Vodstrcil, Lenka A.; Fairley, Christopher K.; Aguirre, Ivette ; Mokany, Elisa; tan, litty Y; Chen, Marcus Y; Bradshaw, Catriona S.

In: Clinical Infectious Diseases, 20.10.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Resistance-guided antimicrobial therapy using doxycyclinemoxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection

T2 - efficacy and tolerability

AU - Durukan, Duygu

AU - Read, Tim

AU - Murray, Gerald Laurence

AU - Doyle, Michelle

AU - Chow, Eric P.F.

AU - Vodstrcil, Lenka A.

AU - Fairley, Christopher K.

AU - Aguirre, Ivette

AU - Mokany, Elisa

AU - tan, litty Y

AU - Chen, Marcus Y

AU - Bradshaw, Catriona S.

PY - 2019/10/20

Y1 - 2019/10/20

N2 - BackgroundMacrolide-resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions and quinolone-resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5g-azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance.MethodsPatients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded.ResultsA total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4% (95% CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0%(88.1-94.6). De novo macrolide-resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n=186) yielded a pooled cure of 95.7% (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22% of macrolide-resistant cases at baseline.ConclusionThese findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.

AB - BackgroundMacrolide-resistance in Mycoplasma genitalium (MG) exceeds 50% in many regions and quinolone-resistance is increasing. We recently reported that resistance-guided therapy (RGT) using doxycycline followed by sitafloxacin or 2.5g-azithromycin cured 92% and 95% of macrolide-resistant and macrolide-susceptible infections, respectively. We now present the data on RGT using doxycycline-moxifloxacin, the regimen recommended in international guidelines, and extend the data on the efficacy of doxyxycline-2.5g azithromycin and subsequent de novo macrolide-resistance.MethodsPatients attending Melbourne Sexual Health Centre between 2017-2018 with STI-related syndromes were treated with doxycycline for 7 days and recalled if positive for MG. Macrolide-susceptible cases then received 2.5g azithromycin (1g, then 500mg daily for 3 days) and resistant cases received moxifloxacin (400 mg daily, 7 days). Test of cure (TOC) was recommended 14-28 days post-completion of antimicrobials. Adherence and adverse effects were recorded.ResultsA total of 383 patients (81 females/106 heterosexual males/196 men-who-have-sex-with-men) were included. Microbial cure following doxycycline-azithromycin was 95.4% (95% CI 89.7-98.0) and doxycycline-moxifloxacin was 92.0%(88.1-94.6). De novo macrolide-resistance was detected in 4.6% of cases. Combining doxycycline-azithromycin data with our prior RGT study (n=186) yielded a pooled cure of 95.7% (91.6-97.8). ParC mutations implicated in moxifloxacin failure were present in 15-22% of macrolide-resistant cases at baseline.ConclusionThese findings support the inclusion of moxifloxacin in resistance-guided strategies and extend the evidence for use of 2.5g azithromycin, and presumptive use of doxycycline. These data provide an evidence-base for current UK, Australian and European guidelines for the treatment of MG, an STI which is increasingly challenging to cure.

U2 - 10.1093/cid/ciz1031

DO - 10.1093/cid/ciz1031

M3 - Article

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

ER -