Abstract
Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies. In the present study, 19 antibiotics in combinations were tested against an MDRSP isolate. In vitro susceptibility studies including minimum inhibitory concentration (MIC), minimal bactericidal concentrations (MBC) and disk agar diffusion (DAD), tolerance to resistant antibiotics, checkerboard assay, time-kill curve, hemolytic assay, and autolysis assay were performed on the test strain to study its in vitro susceptibility to combination therapy. From the checkerboard assay and time-kill curve, it was observed that a combination of levofloxacin (MIC, 16 µg/mL) and ceftriaxone (MIC, 2 µg/mL), at sub-MIC concentration was synergistic and most effective against the MDRSP isolate (penicillin MIC, > 64 µg/mL). Hemolytic activities also increased significantly with combination therapy compared to monotherapy (p < 0.05). Moreover, the hemolytic activity of levofloxacin in combination with ceftriaxone was better than ciprofloxacin plus ceftriaxone or cefepime. The autolysis rate was also found to increase rapidly within one hour of exposure to levofloxacin plus ceftriaxone, and this was found to be significantly different from the other combinations at the fifth and sixth hour post incubation (p < 0.05). This data suggests that this combination is bactericidal in vitro, and requires further studies in in vivo models for treatment against MDRSP infections.
Highlights
Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies
Determination of minimum inhibitory concentration (MIC), minimal bactericidal concentrations (MBC) and disk agar diffusion (DAD) for different antibiotics tested against S. pneumoniae
Median MIC values for different antibiotics against the test isolates AMRISP-1 and ATCC-49619 were determined in triplicate according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution technique
Summary
Preference for combination therapy to treat infection due to multidrug-resistant S. pneumoniae (MDRSP) has not been well elucidated in previous studies. Treatment with a single antibiotic such as a betalactam or third-generation cephalosporin or a fluoroquinolone was considered to be effective previously [5], but with the emergence of multidrugresistant S. pneumoniae (MDRSP) strains, use of a beta-lactam or macrolide as empirical therapy is of great concern. Combination therapy using antimicrobials with different mechanisms of action has been used to treat infections for decades, with the goal of producing a wider spectrum of action, preventing the emergence of multidrug-resistant (MDR) populations, reducing the dose of a single agent, or achieving a synergistic effect [9]
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