Introduction: Pseudomonas aeruginosa is one of the main pathogens causing infection in intensive care units (ICUs) and usually presents antimicrobial resistance. Methods: Data were obtained from ICUs between 2010 and 2013. Results: P. aeruginosa had a prevalence of 14.5% of which 48.7% were multidrug resistant. We observed increasing resistance to carbapenems and polymyxin B and growing consumption of aminoglycosides, meropenem, ceftazidime, and polymyxin B. The regression impact between resistance and consumption was significant with respect to amikacin, imipenem, meropenem, and polymyxin B. Conclusions: Monitoring antimicrobial consumption and resistant microorganisms should be reinforced to combat antimicrobial-and multidrug resistance.
Fosfomycin disodium is a potential therapeutic option to manage difficult-to-treat infections, especially when combined with other antimicrobials. In this study, we evaluated the activity of fosfomycin in combination with meropenem or polymyxin B against contemporaneous KPC-2-producing K. pneumoniae clinical isolates (KPC-KPN). Synergistic activity was assessed by checkerboard (CKA) and time–kill (TKA) assays. TKA was performed using serum peak and trough concentrations. The activity of these combinations was also assessed in the Galleria mellonella model. Biofilm disruption was assessed by the microtiter plate technique. CKA resulted in an 8- to 2048-fold decrease in meropenem MIC, restoring meropenem activity for 82.4% of the isolates when combined with fosfomycin. For the fosfomycin + polymyxin B combination, a 2- to 128-fold reduction in polymyxin B MIC was achieved, restoring polymyxin B activity for 47% of the isolates. TKA resulted in the synergism of fosfomycin + meropenem (3.0–6.7 log10 CFU/mL decrease) and fosfomycin + polymyxin B (6.0–6.2 log10 CFU/mL decrease) at peak concentrations. All larvae treated with fosfomycin + meropenem survived. Larvae survival rate was higher with fosfomycin monotherapy (95%) than that observed for fosfomycin + polymyxin B (75%) (p-value < 0.0001). Finally, a higher biofilm disruption was observed under exposure to fosfomycin + polymyxin B (2.4–3.4-fold reduction). In summary, we observed a synergistic effect of fosfomycin + meropenem and fosfomycin + polymyxin B combinations, in vitro and in vivo, against KPC-KPN, as well as biofilm disruption.
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