|Year : 2009 | Volume
| Issue : 1 | Page : 88-89
In vitro interactions between cotrimoxazole and doxycycline in Burkholderia pseudomallei : How important is this combination in maintenance therapy of melioidosis?
S Saraya1, C Soontornpas2, B Chindavijak3, P Mootsikapun4
1 Department of Microbiology, Mahidol University, Sri-Ayudhaya Rd, Rajadhevi, Bangkok 10 400, Thailand
2 Department of Pharmacy Practices, Faculty of Pharmaceutical Sciences, Khon Kaen University, Friendship Highway, Khon Kaen 40 002, Thailand
3 Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-Ayudhaya Rd, Rajadhevi, Bangkok 10 400, Thailand
4 Department of Medicine, Faculty of Medicine, Mahidol University, Sri-Ayudhaya Rd, Rajadhevi, Bangkok 10 400, Thailand
|Date of Submission||26-Mar-2008|
|Date of Acceptance||06-May-2008|
Department of Pharmacy Practices, Faculty of Pharmaceutical Sciences, Khon Kaen University, Friendship Highway, Khon Kaen 40 002
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Saraya S, Soontornpas C, Chindavijak B, Mootsikapun P. In vitro interactions between cotrimoxazole and doxycycline in Burkholderia pseudomallei : How important is this combination in maintenance therapy of melioidosis?. Indian J Med Microbiol 2009;27:88-9
|How to cite this URL:|
Saraya S, Soontornpas C, Chindavijak B, Mootsikapun P. In vitro interactions between cotrimoxazole and doxycycline in Burkholderia pseudomallei : How important is this combination in maintenance therapy of melioidosis?. Indian J Med Microbiol [serial online] 2009 [cited 2017 Apr 24];27:88-9. Available from: http://www.ijmm.org/text.asp?2009/27/1/88/45188
Melioidosis is a serious community-acquired infection endemic in Southeast Asia and northern Australia, and is particularly prevalent in northeast Thailand. The treatment of septicaemic melioidosis is problematic having not only a 40% fatality rate but also a 23% relapse rate after the completion of antibiotic therapy. , In Thailand, current treatment recommendations include administration of intravenous ceftazidime or a carbapenem for 10-14 days followed by cotrimoxazole plus doxycycline for 12-20 weeks.  As an in vitro study indicated that either trimethoprim (TMP) or sulfamethoxazole (SXT) antagonized the antibacterial activity of doxycycline,  we still do not know the rationale of cotrimoxazole plus doxycycline for treating melioidosis. The present study was undertaken to assess the antibacterial activity of doxycycline, cotrimoxazole and their combination on Burkholderia pseudomallei , the causative microorganism of melioidosis. Ten strains of B. pseudomallei, isolated from patients with confirmed melioidosis infection at the Srinagarind Hospital, Khon Kaen, Thailand, were used in this study. All isolates had same cotrimoxazole susceptibility, with minimum inhibitory concentrations (MICs) of 2/38 mg/mL (TMP/SXT) determined by a broth microdilution method follow the guidelines of the NCCLS.  For doxycycline susceptibility, MICs ranged between 0.5 and 2 mg/mL. Experiments were conducted using a method modified from the time-kill study described by Smith et al .  A bacterial suspension was prepared from an overnight broth culture in 30-mL culture bottles containing 10 mL pre-warmed cation-adjusted Mueller-Hinton broth with the required concentration of antimicrobial (4 x MIC) to give an initial bacterial inoculum of ca. 5 x 10 5 CFU/mL. All culture bottles were incubated for up to 24 h at 37oC on a 150 rpm shaking waterbath. Viable counts were carried out after 0, 2, 4, 6, 8, 12 and 24 h of incubation. All experiments were repeated three times and carried out within biosafety level 3 containment. The change in log 10 colony count at each sampling time point from the starting inoculum was calculated and then the time-kill curve was constructed. A bactericidal effect was defined as a > 3 log 10 reduction in CFU/mL compared with the initial test inoculum within 24 h.
All strains exposed to cotrimoxazole showed the maximum bactericidal activity at 24 h, with a mean + SD of 2.5384 + 1.1103 log 10 reduction, but only two of 10 strains showed a bactericidal effect. Experiments performed with doxycycline showed negligible changes and implied a bacteriostatic effect. All strains exposed to cotrimoxazole plus doxycycline showed a mean + SD of 1.4214 + 0.4738 log 10 reduction, which is less than cotrimoxazole alone, and implied an antagonistic effect of doxycycline to cotrimoxazole as shown in [Figure 1]. The present study suggested that cotrimoxazole monotherapy is better than doxycycline monotherapy or cotrimoxazole plus doxycycline for eradication therapy of melioidosis. Our finding supported an unacceptable relapse rate of doxycycline monotherapy for maintenance phase therapy.  The results of the present time-kill experiments should be integrated and confirmed in clinical trials in patients infected with B. pseudomallei.
| ~ Acknowledgements|| |
This study was supported by a grant from the Faculty of Pharmacy, Mahidol University, Thailand.
| ~ References|| |
|1.||Chaowagul W, Chierakul W, Simpsom AJ, Short JM, Stepniewska K, Maharjan B, et al . Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. Antimicrob Agent Chemother 2005;49:4020-5. |
|2.||Chaowagul W, Simpson AJ, Suputtamongkol Y, Smith MD, Angus BJ, White NJ. A comparison of chloramphenical, trimethoprim-sulfamethoxazole, and doxycycline with doxycycline alone as maintenance therapy for melioidosis. Clin Infect Dis 1999;29:375-80. |
|3.||Dance DA, Wuthiekanun V, Chaowagul W, White NJ. Interactions in vitro between agents used to treat melioidosis. J Antimicrob Chemother 1989;24:311-6. |
|4.||National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 6 th ed. Approved standard M7-A6, Wayne: NCCLS; 2003. |
|5.||Smith MD, Wuthiekanun V, Walsh AL, White NJ. Susceptibility of Pseudomonas pseudomallei to some newer β -lactam antibiotics and antibiotic combinations using time-kill studies. J Antimicrob Chemother 1994;33:145-9. |