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
,
2
;
Harun, A.
1
,
3
;
Hasan, H.
1
,
3
;
Deris, Z.Z.
1
,
3
Author Information
1. Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia&
2. School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia
3. 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
