Mechanism of PK/PD-based Combination of Biapenem and Other Antibiotics on Antibacterial Activity of Pseudomonas aeruginosa in Vitro

Abstract

Background: The aim of this study was to utilize a pharmacokinetic/pharmacodynamic (PK/PD) model for evaluating the in vitro antibacterial effectiveness of biapenem when used in combination with amikacin, fosfomycin, and sulbactam against Pseudomonas aeruginosa (PAE). The single drug (combined) inhibitory concentrations of these four antibiotics against eight common bacteria were detected, and PK/PD model was established for evaluation. Methods: Twenty-one strains of PAE were isolated from sputum samples of the patients and the cultures were maintained on Mueller-Hinton (M-H) agar and M-H broth media. The sensitivity of bacteria to these antibacterial drugs was tested using K-B susceptibility disk method both as a single drug sensitivity test or combination therapy sensitivity test. Furthermore, minimum inhibitory concentration (MIC) was determined for each drug as well in combination. Moreover, the PK/PD model was developed by using probability of target attainment (PTA) and cumulative fraction of response (CFR) values. Results: Single drug sensitivity test showed that, out of the total PAE strains, 7 strains (33.33%) were resistant to biapenem, 5 strains (23.81%) were resistant to amikacin, 3 strains (14.29%) were resistant to fosfomycin, and 9 strains (42.86%) were resistant to sulbactam. Furthermore, the combined drug sensitivity test revealed that 3 PAE strains exhibited synergistic effect when biapenem was combined with amikacin, with a synergistic rate of 19.04%, 12 strains showed synergistic effect when biapenem was combined with fosfomycin, with a synergistic rate of 57.14%, and 11 strains showed synergistic effect when biapenem was combined with sulbactam, with a synergistic rate of 52.38%. Moreover, it was found that, except Acinetobacter baumannii, the MIC₅₀, t > MIC₅₀ of all strains exceeded 50%, However, the MIC₉₀, t > MIC₉₀ for PAE, Acinetobacter baumannii, and Serratia was equal to 0%. Conclusions: In summary, the combination of biapenem and sulbactam was recommended for the treatment of multidrug-resistant-induced infections to effectively control infections and improve therapeutic outcomes.