Abstract
The immune systems of most intensive care unit (ICU) patients are impaired due to the sudden onset of severe illness, allowing opportunistic pathogens to emerge and cause infections. In this thesis the role of opportunistic pathogens and the impact of antimicrobial therapy on these pathogens is evaluated.
Because it is impossible
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to distinguish bacterial from viral pneumonia by clinical symptoms alone, performing respiratory virus diagnostics in patients who are admitted to the ICU with a suspected community-acquired pneumonia is important. However, even during the influenza season testing for the presence of any respiratory virus was performed in only 46% of these patients. The incidence of respiratory syncytial virus (RSV) was lower as compared to influenza virus. Moreover, all patients who were positive for RSV recovered, while influenza virus was associated with a crude mortality of 17%.
ICU patients are at an increased risk for virus reactivation. The presence of viruses in the blood may be observed in up to 62% of ICU patients with septic shock. Epstein-Barr virus was most frequently found (48%), followed by herpes simplex virus (26%), human herpesvirus 6 (18%), cytomegalovirus (16%), and varicella zoster virus (1%). Cytomegalovirus reactivation was independently associated with increased ICU mortality despite adjustment for confounding in patients with acute respiratory distress syndrome. The absolute mortality due to cytomegalovirus reactivation was estimated to be 4.4%.
Also bacteria can be opportunistic pathogens, such as Pseudomonas aeruginosa. Antibiotic exposure is an important cause of emerging antibiotic resistance. Carbapenem exposure was associated with the highest increased risk of antibiotic resistance development in Pseudomonas in the lower respiratory tract of ICU patients. Antibiotic-associated resistance acquisition rates were comparable in patients receiving Selective digestive decontamination (SDD) and those not receiving SDD.
In SDD an antifungal component is included to eradicate or prevent Candida colonization in ICU patients. There is some evidence that colonization of the lower respiratory tract by Candida species could promote the development of pneumonia by creating biofilms that are capable of holding other microorganisms. Inhalation therapy with nebulized amphotericin B as part of SDD reduced the duration of Candida colonization of the respiratory tract by approximately three days. However, the incidence rate of ventilator-associated pneumonias was not different between the treatment and control group. Therefore, the clinical significance of Candida in the respiratory tract remains controversial. When amphotericin B was replaced by nystatin in the topical mouth paste and gastro enteral suspension of the SDD regimen, fewer patients acquired intestinal Candida colonization in the intestinal tract.
Although SDD may prevent ICU-acquired infections, some pathogens are not targeted, such as enterococci. Crude differences in mortality were apparent between patients with and those without ICU-acquired enterococcal bacteremia. However, severity of illness, comorbidities and time-dependent bias could largely account for the high case fatality rates that were observed in patients with enterococcal bacteremia. Nonetheless, enterococcal bacteremia remained independently associated with increased case fatality even after taking into account many sources of bias. Yet, the virulence of enterococci seemed comparable to that of coagulase-negative staphylococcal bacteremia.
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