1. Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients B J Philips, J Redman, A Brennan, D Wood, R Holliman, D Baines, E H Baker Thorax 2005;60:761–764. doi: 10.1136/thx.2004.035766

2. Background Critically ill patients : ↑susceptibility to nosocomial infections including resistant organisms such as MRSA → ↑ Mortality, morbidity, and hospital costs On one ICU, ↓mortality by control of blood glucose to normal limits (4.4–6.1 mmol/l) through reduction in episodes of sepsis but unknown mechanisms Glucose is not normally detectable in airway secretions but appears : blood glucose > 6.7–9.7 mmol/l. Hypothesise : the presence of glucose in airway secretions in critically ill patients predisposes to respiratory infection

3. Methods Study design association between glucose in airways secretions and colonisation of the airways by pathogenic bacteria observational cross sectional study newly admitted patients to ICU who require ventilatory support Subjects 98 critically ill patients requiring intubation more than 48 hours and ventilation Excluded expected to die within 24 hours previous ICU admission during this hospital admission

4. Glucose measured arterial blood : glucose analyse (ABL2000, Radiometer) bronchial aspirates : glucose oxidase stick & bronchial aspirate filtrate : positive for glucose after one positive result at any time Bronchial aspirates were analysed twice weekly for microbiological analysis whenever an infection was suspected Severity of illness measured using the sequential organ failure assessment (SOFA) system At discharge from the ICU and after 6 months Statistics using SPSS Version 12.0

5. Results

7. <

8. Relative risk 2.4 Relative risk 2.1 7 29/51 10/36 44/51 21/36

9. < < < No difference in ICU outcome dependent on detection of glucose or MRSA

10. Conclusion The results imply a relationship between the presence of glucose in the airway and a risk of colonisation or infection with pathogenic bacteria including MRSA

11. DISCUSSION In most cases, the detection of glucose in bronchial aspirates preceded the development of MRSA → →glucose may be cause,promotion of MRSA growth presence of MRSA - association with infiltrates on the chest radiograph, increased levels of C reactive protein, and prolonged ICU stay Mechanisms ? → → may be both bacterial and host factors

12. bacterial factors Bacteria use glucose during growth : S aureus Glucose in standard microbiological growth media > 10 mmol/l Glucose in the bronchial aspirates of our patients : mean 3.5 mmol/l Glucose affect the virulence of bacteria E. coli : adheres to the uroepithelial cells of diabetic patients more S aureus : glucose ↓ expression of the agr gene (regulation of virulence gene expression) S aureus : glucose is required for biofilm formation (protect bacteria ) host factors glucose in the airway interfere with local immune processes Influenza A : glucose causing impaired function of surfactant protein D →replicate more rapidly in the lungs of diabetic mice ↓ respiratory burst of alveolar macrophages but ↑ alveolar macrophage phagocytosis in vitro ↑unopsonised phagocytosis of P. aeruginosa in presence of glucose

13. Yeasts ↑from patients without glucose ↑more common in patients without pathogenic bacteria (p=0.025) absence of competing organisms use of antibiotics probably This study not designed to profile glucose in airway over time Further investigation is required hyperglycaemia causes glucose in airway secretions However, glucose in bronchial aspirates with normal or low blood glucose concentrations – possible explanations ? Glucose may be entering the airway via leaky inflamed lung tissue at the point of testing, missed an episode of hyperglycaemia glucose is readily cleared from the airway impaired glucose clearance in critically ill patients

14. Nosocomial infections by resistant organisms →serious problem for critical care medicine Strategies : hand washing and patient isolation… but little is understood about the susceptibility for acquiring organisms such as MRSA Glucose in airway secretions secondary to hyperglycaemia may be such a risk factor. It remains to be seen whether the risk of acquiring MRSA can be reduced by the control of blood glucose