As long-standing clinical problems, catheter-related infections and other chronic biofilm infections are more difficult to treat due to the high antibiotic resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. In this study, we evaluated the antibacterial activities of several common antibiotics alone and their combinations against biofilm-embedded methicillin-resistant staphylococcus aureus (MRSA) infections, both in vitro and in vivo. In brief, fosfomycin, levofloxacin, and rifampin alone or in combination with linezolid were tested in vitro against planktonic and biofilm-embedded MRSA infection in three MRSA stains. The synergistic effects between linezolid and the other three antibiotics were assessed by fractional inhibitory concentration index (FICI) and time-kill curves, where the combination of linezolid plus fosfomycin showed the best synergistic effect in all strains. For further evaluation in vivo, we applied the combination of linezolid and fosfomycin in a catheter-related biofilm rat model and found that viable bacteria counts in biofilm were significantly reduced after treatment (P < 0.05). In summary, we have shown here that the combination of linezolid and fosfomycin treatment had improved therapeutic effects on biofilm-embedded MRSA infection both in vitro and in vivo, which provided important basis for new clinical therapy development.

Introduction:Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods: The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results: The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fl uid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions: Subinhibitory doses of colistin signifi cantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii.

The antimicrobial treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections has become a great challenge for medical staff all over the world. Increasing numbers of MDR A. baumannii infections have been identified and reported, but effective clinical treatments for them are decreasing. The objective of this study was to investigate the in vitro activities of combinations of rifampin (an established antimicrobial) and other antimicrobials, including biapenem, colistin, and tigecycline, against 73 clinical isolates of MDR A. baumannii. In total, 73 clinical isolates of MDR A. baumannii were collected from two A-level general hospitals in Beijing, and the MICs of rifampin, biapenem, colistin, and tigecycline were determined. The checkerboard method was used to determine the fractional inhibitory concentration indices (FICIs), that is, whether the combinations acted synergistically against these isolates. The MIC 50 , MIC 90 , and MIC range of rifampin combined with biapenem, colistin, and tigecycline against the isolates were clearly lower than those for four antimicrobials (rifampin, biapenem, colistin, and tigecycline) that were used alone. Combinations of rifampin with biapenem, colistin, and tigecycline individually demonstrated the following interactions: synergistic interactions (FICI < 0.5) for 31.51%, 34.25%, and 31.51% of the isolates, partially synergistic interactions (0.5 < FICI < 1) for 49.31%, 43.83%, and 47.94% of the isolates, and additive interactions (FICI ‫؍‬ 1) for 19.18%, 21.92%, and 20.55% of the isolates, respectively. There were no indifferent (1 < FICI < 4) or antagonistic (FICI > 4) interactions. Therefore, combinations of rifampin with biapenem, colistin, or tigecycline may be future therapeutic alternatives for the treatment of MDR A. baumannii infections.A cinetobacter baumannii is the most important pathogenic bacterium of the 21st century. Multidrug-resistant (MDR) isolates can be rapidly acquired and disseminated worldwide (1). The development of multidrug, extensive, and complete resistance in A. baumannii and the appearance of pandemic strains have become significant challenges throughout the world, which raises a lot of discussion in the research field. A. baumannii is the most well-known "superbacterium" in China; it can cause acquired pneumonia, blood infections, abdominal infections, central nervous system infections, urinary system infections, and skin and soft tissue infections (2). Moreover, it is a conditioned pathogen of hospital-acquired and respirator-related pneumonia, and it is easily implanted into the skin, conjunctiva, oral cavity, respiratory tract, gastrointestinal tract, and urogenital tract (3). A pandemic of imipenem-resistant A. baumannii outbreaks in hospitals has been reported (4). A recent study suggested that MDR A. baumannii isolates are susceptible to tigecycline and colistin (5). Unfortunately, colistin is not yet available in China. According to reports, a combination of sulbactam (a ␤-benzosultam inhibitor) with another antimicrobial i...

No abstract