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A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus
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| Zeitschriftentitel: | Clinical Infectious Diseases |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , , , , , |
| In: | Clinical Infectious Diseases, 68, 2019, 5, S. 738-747 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Oxford University Press (OUP)
|
| Schlagwörter: |
| author_facet |
Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone |
|---|---|
| author |
Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone |
| spellingShingle |
Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone Clinical Infectious Diseases A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus Infectious Diseases Microbiology (medical) |
| author_sort |
newton, paul n |
| spelling |
Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone 1058-4838 1537-6591 Oxford University Press (OUP) Infectious Diseases Microbiology (medical) http://dx.doi.org/10.1093/cid/ciy563 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P &lt; .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration</jats:title> <jats:p>ISRCTN47812566.</jats:p> </jats:sec> A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus Clinical Infectious Diseases |
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| title |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_unstemmed |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_full |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_fullStr |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_full_unstemmed |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_short |
A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_sort |
a prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus |
| topic |
Infectious Diseases Microbiology (medical) |
| url |
http://dx.doi.org/10.1093/cid/ciy563 |
| publishDate |
2019 |
| physical |
738-747 |
| description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P &lt; .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Clinical Trial Registration</jats:title>
<jats:p>ISRCTN47812566.</jats:p>
</jats:sec> |
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| author | Newton, Paul N, Keolouangkhot, Valy, Lee, Sue J, Choumlivong, Khamla, Sisouphone, Siho, Choumlivong, Khamloune, Vongsouvath, Manivanh, Mayxay, Mayfong, Chansamouth, Vilada, Davong, Viengmon, Phommasone, Koukeo, Sirisouk, Joy, Blacksell, Stuart D, Nawtaisong, Pruksa, Moore, Catrin E, Castonguay-Vanier, Josée, Dittrich, Sabine, Rattanavong, Sayaphet, Chang, Ko, Darasavath, Chirapha, Rattanavong, Oudayvone, Paris, Daniel H, Phetsouvanh, Rattanaphone |
| author_facet | Newton, Paul N, Keolouangkhot, Valy, Lee, Sue J, Choumlivong, Khamla, Sisouphone, Siho, Choumlivong, Khamloune, Vongsouvath, Manivanh, Mayxay, Mayfong, Chansamouth, Vilada, Davong, Viengmon, Phommasone, Koukeo, Sirisouk, Joy, Blacksell, Stuart D, Nawtaisong, Pruksa, Moore, Catrin E, Castonguay-Vanier, Josée, Dittrich, Sabine, Rattanavong, Sayaphet, Chang, Ko, Darasavath, Chirapha, Rattanavong, Oudayvone, Paris, Daniel H, Phetsouvanh, Rattanaphone, Newton, Paul N, Keolouangkhot, Valy, Lee, Sue J, Choumlivong, Khamla, Sisouphone, Siho, Choumlivong, Khamloune, Vongsouvath, Manivanh, Mayxay, Mayfong, Chansamouth, Vilada, Davong, Viengmon, Phommasone, Koukeo, Sirisouk, Joy, Blacksell, Stuart D, Nawtaisong, Pruksa, Moore, Catrin E, Castonguay-Vanier, Josée, Dittrich, Sabine, Rattanavong, Sayaphet, Chang, Ko, Darasavath, Chirapha, Rattanavong, Oudayvone, Paris, Daniel H, Phetsouvanh, Rattanaphone |
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| description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P &lt; .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration</jats:title> <jats:p>ISRCTN47812566.</jats:p> </jats:sec> |
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| spelling | Newton, Paul N Keolouangkhot, Valy Lee, Sue J Choumlivong, Khamla Sisouphone, Siho Choumlivong, Khamloune Vongsouvath, Manivanh Mayxay, Mayfong Chansamouth, Vilada Davong, Viengmon Phommasone, Koukeo Sirisouk, Joy Blacksell, Stuart D Nawtaisong, Pruksa Moore, Catrin E Castonguay-Vanier, Josée Dittrich, Sabine Rattanavong, Sayaphet Chang, Ko Darasavath, Chirapha Rattanavong, Oudayvone Paris, Daniel H Phetsouvanh, Rattanaphone 1058-4838 1537-6591 Oxford University Press (OUP) Infectious Diseases Microbiology (medical) http://dx.doi.org/10.1093/cid/ciy563 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Murine typhus, or infection with Rickettsia typhi, is a global but neglected disease without randomized clinical trials to guide antibiotic therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A prospective, open, randomized trial was conducted in nonpregnant, consenting inpatient adults with rapid diagnostic test evidence of uncomplicated murine typhus at 2 hospitals in Vientiane, Laos. Patients were randomized to 7 days (D7) or 3 days (D3) of oral doxycycline or 3 days of oral azithromycin (A3). Primary outcome measures were fever clearance time and frequencies of treatment failure and relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Between 2004 and 2009, the study enrolled 216 patients (72 per arm); 158 (73.2%) had serology/polymerase chain reaction (PCR)–confirmed murine typhus, and 52 (24.1%) were R. typhi PCR positive. The risk of treatment failure was greater for regimen A3 (22.5%; 16 of 71 patients) than for D3 (4.2%; 3 of 71) or D7 (1.4%; 1 of 71) (P &lt; .001). Among R. typhi PCR–positive patients, the area under the time-temperature curve and the fever clearance time were significantly higher for A3 than for D3 (1.8- and 1.9-fold higher, respectively; P = .005) and D7 (1.5- and 1.6-fold higher; P = .02). No patients returned with PCR-confirmed R. typhi relapse.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>In Lao adults, azithromycin is inferior to doxycycline as oral therapy for uncomplicated murine typhus. For doxycycline, 3- and 7-day regimens have similar efficacy. Azithromycin use in murine typhus should be reconsidered. Investigation of genomic and phenotypic markers of R. typhi azithromycin resistance is needed.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration</jats:title> <jats:p>ISRCTN47812566.</jats:p> </jats:sec> A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus Clinical Infectious Diseases |
| spellingShingle | Newton, Paul N, Keolouangkhot, Valy, Lee, Sue J, Choumlivong, Khamla, Sisouphone, Siho, Choumlivong, Khamloune, Vongsouvath, Manivanh, Mayxay, Mayfong, Chansamouth, Vilada, Davong, Viengmon, Phommasone, Koukeo, Sirisouk, Joy, Blacksell, Stuart D, Nawtaisong, Pruksa, Moore, Catrin E, Castonguay-Vanier, Josée, Dittrich, Sabine, Rattanavong, Sayaphet, Chang, Ko, Darasavath, Chirapha, Rattanavong, Oudayvone, Paris, Daniel H, Phetsouvanh, Rattanaphone, Clinical Infectious Diseases, A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus, Infectious Diseases, Microbiology (medical) |
| title | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_full | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_fullStr | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_full_unstemmed | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_short | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| title_sort | a prospective, open-label, randomized trial of doxycycline versus azithromycin for the treatment of uncomplicated murine typhus |
| title_unstemmed | A Prospective, Open-label, Randomized Trial of Doxycycline Versus Azithromycin for the Treatment of Uncomplicated Murine Typhus |
| topic | Infectious Diseases, Microbiology (medical) |
| url | http://dx.doi.org/10.1093/cid/ciy563 |