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«INFLAMMATORY PROTEINS, GENETIC VARIATION, AND ENVIRONMENTAL INFLUENCES ON HEALTH CARE ASSOCIATED INFECTION DEVELOPMENT IN SEPSIS A Dissertation ...»

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Severity of illness contributes to risk of HAI development. Based on the multivariate model, every one point increase in APACHE II score there is a 3.4% increase in the risk of developing HAI. APACHE II scores range from 0 to 71 with a higher scores associated with a worse outcome.38 The APACHE II has been correlated with baseline inflammatory response but not HAI development.12 Patients with a higher severity of illness require a higher level of care. These patients are potentially exposed to a higher risk due to the presence of more invasive devices and also have a higher exposure to multiple hospital personnel and equipment needed to provide their care. For each additional invasive device there was a 9.1% reduced risk in the development of HAI. This does not make intuitive sense. It is likely that the format of the invasive device score used in the model is problematic and additional models will be explored using only the number of invasive devices present at the time of HAI, rather than the cumulative score. Table 4-6 provides the cumulative invasive device score at the time of HAI (52.8 ± 26.7) and Table 4-8 provides the cumulative invasive device score at ICU discharge (23.9 ± 23.0) for those who did not develop HAI. More investigation is needed to fully assess these findings.

We found that early antibiotic use prior to ICU stay reduces risk of HAI in patients with sepsis. The importance of early antibiotic use has been incorporated into several guidelines. The surviving sepsis campaign recommends antibiotics within the first hour for septic shock.26 The IDSA recommends antibiotic administration in the ER prior to ICU admission for patients with CAP.55 In this study, we examined whether patients received antibiotics before transfer to the ICU. The early administration of antibiotics reduces morality associated with sepsis and may, according to Zubert, be a “surrogate marker for quality of care in the broader sense”. 129 While early antibiotic use is important, appropriately deescalating therapy based on culture sensitivities is also important.130 The presence of IL6 rs1800795 CC compared to GG and GC compared to GG had a higher risk in the univariate mode, and the risk increased in the multivariate model when controlling for other variables. The final model included only variables that were significant (p 0.05). The higher risk associated with rs1800795 genotypes CG and CC is consistent with higher risk associated with the C allele noted in the literature. The rs1800795 C Allele has also been found to be associated with late blood stream infections in African American infants,128 and has been shown to be more prevalent in coronary artery patients developing myocardial infarction compared to coronary artery patients with stable and unstable angina.131 More analysis is needed to fully explore the relationships of these variables.

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Study strengths are summarized below:

1. This study occurred in a teaching hospital where the attending physicians and medical team rotate monthly; however, the MICU team include a PharmD who is present for daily rounds with the team in the morning and afternoon on Monday through Friday. This provides consistency in patient management in regards to the appropriate use, selection, and dosing of antibiotics in the ICU. This PharmD reviewed cultures and antibiotics with me to determine appropriate antibiotics based on current guidelines.

2. This study occurred in one facility, limiting the biases that could occur at multiple sites by multiple data collectors.

3. The inclusion of biomarkers and use in a multivariate model strengthens conclusions about risk factors associated with development of HAI.

–  –  –

Study limitations are summarized below:

1. A potential limitation of this study was the heterogeneous sample. Some patients were not as sick as others and were discharged from the ICU prior to three days.

Since development of HAI has been strongly associated with length of stay, this is a limitation that was accounted for by using Cox regression modeling.

2. Limiting this study to a single site with primarily older male veterans limits generalizability of findings.

3. It was a major assumption that baseline systemic inflammation would be prolonged. Measuring only baseline cytokine levels is a limitation.

4. The usage of corticosteroid therapy may impact the degree and duration of systemic inflammation; thus, potentially limiting the possible impact of systemic inflammation on the development of HAI in participants receiving corticosteroids.

5. The use of corticosteroids may limit fever among participants experiencing HAI, and may result in failure to detect HAI when they occur. It is recommended clinical practice in our ICU to use sepsis surveillance, and thus a high degree of suspicion when steroids are used.

6. There may be other predisposing factors for development of HAI that were not measured.

7. The investigator is a novice bench researcher, and although efforts were made to accurately follow protocols, it is possible that errors could have influenced results.

8. Endpoint genotyping of rs1800896 required manual calls in seven samples.





9. Interleukin 6 was selected as a proinflammatory cytokine; however, it does have some anti-inflammatory properties.

Implications

This study provides important insights into risk factors that contribute to the development of HAI in patients presenting to the ICU with sepsis. These findings may impact nursing and other critical care clinician practice first by helping to identify patients at risk, then implementing stricter targeted infection control practices in efforts to prevent development of HAIs (in addition to current standard and recommended practices). JACHO patient safety goals include prevention of HAI.

Since the completion of this study, new processes are in place in the facility where this study occurred. These including daily surveillance of central line sites and implementation of a UTI bundle to reduce UTI. The findings of this study reveal a need to further investigate the cause of Candida in this population and to follow-up on the incidence of Candida in this unit. The use of antibiotic timing and duration should be reviewed. A high percentage (9 of 11, 81.8%) of the Candida infections occurred during corticosteroids use, indicating a need to assure appropriate sepsis surveillance is followed in patients receiving corticosteroids. Specific nursing measures would include a review of standard IV care practices such as tubing changes, site rotation for peripheral lines, duration of central lines, routine site evaluation and care, hub care, cleaning of IV equipment, cleaning of transducer holders, and no re-use of disposable pressure bags.

This may include changing the catheter hub after blood draws when flushing cannot completely clear the hub as well as protocol driven hub care.

Cleaning the environment closest to the patient needs to be considered. The side rails, call light, bed controls, and equipment in use in the room are typically only cleaned when they become soiled. These items could be wiped down with sanitary wipes daily when other areas of the room are cleaned. Cleaning of other environmental areas would include routine cleaning of medication carts, including the front of medication drawers, keyboard, scanner, and the work surface. Routine cleaning of the sink handles and light switches should also be evaluated.

Conclusions

This study provides evidence of a genetic risk for development of HAI. Despite best evidenced based practices some patients will develop HAI. Strict aseptic technique is essential to preventing infection. In addition to eliminating invasive devices as quickly as possible, patients with a high severity of illness may need to be isolated to lower their risk. Early administration of antibiotics not only provides prompt treatment for the initial infection but also lowers risk for subsequent infections.

LIST OF REFERENCES

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2. Ylipalosaari P, Ala-Kokko TI, Laurila J, Ohtonen P, Syrjala H. Intensive care acquired infection is an independent risk factor for hospital mortality: a prospective cohort study. Critical Care 2006;10:R66.

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17. Wurfel MM, Gordon AC, Holden TD, et al. Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. American Journal of Respiratory and Critical Care Medicine 2008.

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Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical Care Medicine 2001;29:1303-10.

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