In-vitro activity of β-lactams/trimethoprim-sulfamethoxazole combinations against different strains of Burkholderia pseudomallei
https://doi.org/10.47665/tb.39.1.004
- Author:
Mohamad, N.I.
1
;
Harun, A.
2
;
Hasan, H.
2
;
Deris, Z.Z.
2
Author Information
1. Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia&School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
2. Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia&Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
- Publication Type:Journal Article
- Keywords:
Melioidosis;
Burkholderia pseudomallei;
β-lactam antibiotics;
trimethoprimsulfamethoxazole;
drug combination
- From:Tropical Biomedicine
2022;39(No.1):11-16
- CountryMalaysia
- Language:English
-
Abstract:
Trimethoprim-sulfamethoxazole is an active agent against Burkholderia pseudomallei and is
being used in intensive and maintenance phases of melioidosis therapy. In this study, we
evaluated the bactericidal activities of β-lactams (imipenem, ceftazidime and amoxicillinclavulanate) alone and in combinations with trimethoprim-sulfamethoxazole against
B. pseudomallei. Four clinical strains of B. pseudomallei were selected based on different
genotypes that are frequently found in Malaysia. The minimum inhibitory concentrations of
trimethoprim-sulfamethoxazole, ceftazidime, imipenem and amoxicillin-clavulanate were
determined using microdilution broth method. The bactericidal activities and synergy effects
of β-lactams and/or trimethoprim-sulfamethoxazole were evaluated by checkerboard and
static time-kill analyses at 1×MIC concentration of each antibiotic. Using checkerboard
method, the β-lactam/trimethoprim-sulfamethoxazole combinations exhibited ΣFIC of
0.75-4.00. In time-kill analysis, ceftazidime/trimethoprim-sulfamethoxazole combination
demonstrated synergy against three strains (less 2.25-2.41 log10CFU/mL compared to the
most active antibiotic monotherapy) whereas imipenem/trimethoprim-sulfamethoxazole
combination regimen showed synergy against one strain (less 3.32 log10CFU/mL). No
antagonist effect or major re-growth was observed in all combination regimens, whereas 11
out of 12 of β-lactam monotherapy regimens were associated with re-growth of bacteria.
However, all β-lactam monotherapy regimens exhibited rapid and stronger killing activities
against BUPS/07/14, in the initial 12 hours compared to β-lactam/ trimethoprimsulfamethoxazole combination regimens. The combination of β-lactams with trimethoprimsulfamethoxazole demonstrated better killing effect at 24 hours compared to monotherapy
and no major bacterial regrowth was observed. Nevertheless, delay in killing activities of
β-lactam/trimethoprim-sulfamethoxazole combination regimens against BUPS/07/14 need
further examination because this phenomenon can lead to treatment failure in some
patients.
- Full text:8.2022my1307.pdf
