Amikacin and cefoperazone/sulbactam alone or in combination against carbapenem-resistant Pseudomonas aeruginosa

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become a major therapeutic problem worldwide. Combination therapy may be an alternative chemotherapeutic option.

Bioluminescent CRPA Xen5-D9 was developed in the present study. Minimum inhibitory concentration of amikacin (AMK) or cefoperazone/sulbactam (SCF) against CRPA Xen5-D9 was determined by microdilution method. CRPA Xen5-D9 was intraperitoneally injected to establish a mouse model of intraperitoneal infection. In vivo bioluminescence imaging was applied at 2 and 5 h after treatment to dynamically evaluate bactericidal effects of AMK alone or in combination with SCF. After 5 h of treatment, ex vivo bacterial colony counts from liver, kidney, spleen, lung, and blood were also determined.

CRPA Xen5-D9 was AMK sensitive and SCF intermediate. In vivo imaging showed that AMK alone significantly decreased bioluminescent signals compared with the control, while signals from the SCF-alone group barely changed. Moreover, the AMK-SCF combination did not show greater bactericidal effect compared with AMK alone. Results of ex vivo bacterial counts confirmed that AMK alone significantly decreased the colony counts from different tissues. Although SCF also decreased the colony counts in liver, kidney, spleen, and lung compared with the control, the counts were still higher than those of the AMK-alone group. In addition, AMK-SCF combination resulted in significantly lower numbers of colony-forming units in blood compared with individual antibiotics.

AMK-SCF combination did not show better bactericidal effect on AMK-sensitive CRPA-caused infections compared with AMK alone. Although further studies are needed, these results suggest that this combination does not seem to be indicated for treatment of CRPA-caused infections.