1.In-vitro activity of β-lactams/trimethoprim-sulfamethoxazole combinations against different strains of Burkholderia pseudomallei
Mohamad, N.I. ; Harun, A. ; Hasan, H. ; Deris, Z.Z.
Tropical Biomedicine 2022;39(No.1):11-16
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.