Chest
Original ResearchCritical CarePseudomonas aeruginosa-Catecholamine Inotrope Interactions: A Contributory Factor in the Development of Ventilator-Associated Pneumonia?
Section snippets
Strains, Growth Induction, and Antibiotic Sensitivity Assays
The P aeruginosa strains used in this study were a clinical isolate from a patient with ventilator-associated pneumonia (Public Health Laboratory, Leicester Royal Infirmary, England) and P aeruginosa reference strain PA14. The serum-SAPI medium used for growth assays was prepared as described previously.8, 11 L-(-)-norepinephrine bitartrate, epinephrine bitartrate, and dopamine hydrochloride were obtained from Sigma. Vasopressin (20 units/mL, 600 units/mg) and phenylephrine (10 mg/mL) were
Inotropes Increase P aeruginosa Growth and Pyoverdine Synthesis
Previous analyses of P aeruginosa-catecholamine interactions used norepinephrine levels of 50 μM and higher.7, 8, 11 However, in the current study, we found that incubation of an inoculum of < 102 CFU/mL of P aeruginosa strains clinical isolate and PA14 in serum-SAPI for 18 h with 5 μM concentrations of the inotropes norepinephrine and dopamine (drug levels that have been reported in the blood of patients medicated with inotrope19, 20) resulted in up to 50-fold increases in bacterial numbers
Discussion
Ventilator-associated pneumonia, a hospital-acquired infection, remains a major cause of morbidity and death, despite intensive research.1, 2, 3, 4, 5, 6 P aeruginosa, a pathogen that rarely causes pneumonia outside of intensive care, is responsible for a high proportion of these infections.1, 2, 3, 4, 5, 6 In this study, we presented evidence that levels of catecholamine inotropes that are within the ranges reported in the plasma of inotrope-supplemented patients19, 20 can greatly increase
Conclusions
In conclusion, this study suggests that administration of inotropes to patients in the ICU, particularly if high doses are given systemically or via direct local application, may be an unappreciated risk factor in the development of ventilator-associated pneumonia by P aeruginosa. Further investigations are therefore needed to determine whether the higher circulating catecholamines of the ventilated patient,19, 20 combined with the presence of administered inotropes and naturally occurring
Acknowledgments
Author contributions: Dr O'Callaghan is the guarantor of the manuscript and takes responsibility for the integrity of the data and accuracy of the data analysis.
Dr Freestone: conceived and designed the study, the carrying out of many of the experiments, analysis of the data, and writing and revision of the manuscript.
Dr Hirst: contributed to parts of the study design, carrying out of some of the experiments, analysis of the data, and writing of some of the manuscript.
Dr Sandrini: contributed to
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Funding/Support: Drs Freestone, Sandrini, and O'Callaghan are funded by the SPARKS Children's Charity (www.sparks.org.uk), England [Grant 09 LCS 01].
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