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- Title
Activity of colistin alone or in combination with rifampicin or meropenem in a carbapenem-resistant bioluminescent Pseudomonas aeruginosa intraperitoneal murine infection model.
- Authors
Yun Cai; Deqing Yang; Jin Wang; Rui Wang; Cai, Yun; Yang, Deqing; Wang, Jin; Wang, Rui
- Abstract
<bold>Background: </bold>Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections represent a major therapeutic problem and combination therapy may be the chemotherapeutic option.<bold>Methods: </bold>Bioluminescent CRPA was developed through sequential subcultures in subinhibitory concentrations of meropenem from an engineered strain of bioluminescent PA Xen5. Then CRPA was injected intraperitoneally to establish an intraperitoneal murine infection model. Treatments of colistin alone or combined with rifampicin or meropenem were started 1 h after infection. In vivo bioluminescence imaging was applied dynamically at 0 h, and 2 and 5 h after treatment. Ex vivo bacterial counts from liver, kidney, spleen, lung and blood samples were also determined 5 h after treatment.<bold>Results: </bold>In vivo imaging showed that both low- and high-dose colistin combined with rifampicin resulted in a significant decrease in bioluminescence signals compared with monotherapy of colistin or rifampicin alone, whereas colistin and meropenem combination therapy did not show a greater bactericidal effect compared with monotherapy. Ex vivo bacterial count results also confirmed that combination of both low- and high-dose colistin with rifampicin resulted in significantly reduced colony counts from five kinds of tissue samples. However, only combination of high-dose colistin + meropenem resulted in reduced colony counts merely in lung and blood samples.<bold>Conclusions: </bold>Compared with single drugs, colistin and rifampicin combination therapy could exert synergistic effects, which might provide a better alternative when treating CRPA infections in clinical practice. Combination of colistin and meropenem should be considered with caution because it barely shows any synergism in the present in vivo model.
- Subjects
COLISTIN; RIFAMPIN; MEROPENEM; CARBAPENEMS; PSEUDOMONAS aeruginosa infections; THERAPEUTICS; ANIMAL experimentation; ANTIBIOTICS; BACTERIAL growth; BIOLOGICAL models; COMBINATION drug therapy; COMPARATIVE studies; DRUG resistance in microorganisms; DRUG synergism; LUMINESCENCE spectroscopy; RESEARCH methodology; MEDICAL cooperation; MICE; MICROBIOLOGICAL techniques; PSEUDOMONAS; PSEUDOMONAS diseases; RESEARCH; STAINS &; staining (Microscopy); EVALUATION research; TREATMENT effectiveness; INTRA-abdominal infections
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2018, Vol 73, Issue 2, p456
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkx399