Immunocompromised Patients. Infections, Diagnostics and Nosocomial Transmission

Abstract: The aim of the work presented in this thesis was to improve the management of infections in immunocompromised patients by studying aspects of diagnostics, epidemiology and nosocomial transmission. Infection and rejection are common complications in lung-transplant patients, and early diagnosis and treatment are important for a positive outcome. In a study of lung-transplant patients it was found that heparin-binding protein, IL-1 and IL-8 in bronchoalveolar lavage fluid (BALF) could be useful biomarkers for the detection of pulmonary infection. These biomarkers also seemed to discriminate between infection and rejection.Haematology patients with severely impaired immunity are at high risk of developing invasive fungal disease (IFD), and early diagnosis remains a challenge to clinicians. In a study of 135 severely immunosuppressed haematology patients it was found that both (1-3)- -D-Glucan (BG) and galactomannan showed high diagnostic performance for exclusion of disease, but poor performance in early detection of IFD when used as screening markers. BG was shown to be the most useful tool for the diagnosis of IFD later in the course of infection. For optimal diagnostic performance, the use of the BG test should include quantification of BG above the maximum limit of detection of the assay and graphical evaluation of the dynamic pattern of BG. The diagnostic usefulness of bis(methyl)gliotoxin and the D-arabinitol/L-arabinitol ratio in urine appeared to be questionable in this cohort. It was also found that elevated levels of triglycerides could be a source of false-positive BG findings. The study further highlights the importance of assessment by a qualified radiologist in the diagnosis of IFD. Lung-transplant patients have a high risk of microbial colonisation of the lung, and lung infections. To evaluate positive microbial findings in BALF, and to implement appropriate prophylaxis and treatment of infections, it is important to know the microbial panorama. A study was carried out on all lung-transplant patients in Sweden over a two-year period, and BALF samples from 85% of the patients had microbiologic finding(s), but the frequency of multidrug-resistant bacteria was low. The microbiological agents found in BALF from patients with and without lung infection were similar, providing further evidence that microbial results should be evaluated together with clinical symptoms and macroscopic appearance and in the assessment of lung infection in lung-transplant patients. The final study was carried out during a prolonged nosocomial outbreak of a metallo-β-lactamase-producing Pseudomonas aeruginosa strain, affecting immunosuppressed patients. This was found to be associated with hospital sink drains, and a method of decontamination using acetic acid was proposed.