Pseudomonas aeruginosa and risk of death and exacerbations in patients with chronic obstructive pulmonary disease: an observational cohort study of 22 053 patients.

OBJECTIVES: The role of Pseudomonas aeruginosa in the long-term prognosis of chronic obstructive pulmonary disease (COPD) is unknown. The purpose of this study was to determine whether P. aeruginosa is associated with increased risk of exacerbations or death in patients with COPD. METHODS: This is a multiregional epidemiological study based on complete data on COPD outpatients between 1 January 2010 and 31 October 2017 and corresponding microbiology and national register data. Time-dependent Cox proportional hazards models and propensity matching was used to estimate hospitalization-demanding exacerbations and death after 2 years, separately and in combination. RESULTS: A total of 22 053 COPD outpatients were followed for a median of 1082 days (interquartile-range: 427-1862). P. aeruginosa was present in 905 (4.1%) patients. During 730 days of follow-up, P. aeruginosa strongly and independently predicted an increased risk of hospitalization for exacerbation or all-cause death (HR 2.8, 95%CI 2.2-3.6; p <0.0001) and all-cause death (HR 2.7, 95%CI 2.3-3.4; p <0.0001) in analyses adjusted for known and suspected confounders. The signal remained unchanged in unadjusted analyses as well as propensity-matched subgroup analyses. Among patients 'ever colonized' with P. aeruginosa, the incidence of hospital-demanding exacerbations doubled after the time of the first colonization. CONCLUSIONS: COPD patients in whom P. aeruginosa can be cultured from the airways had a markedly increased risk of exacerbations and death. It is still not clear whether this risk can be reduced by offering patients targeted antipseudomonal antibiotics. A randomized trial is currently recruiting patients to clarify this (ClinicalTrials.gov: NCT03262142).

Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial.

BACKGROUND: Accumulation of fluids is frequent in intensive care unit (ICU) patients with acute kidney injury and may be associated with increased mortality and decreased renal recovery. We present the results of a pilot trial assessing the feasibility of forced fluid removal in ICU patients with acute kidney injury and fluid accumulation of more than 10% ideal bodyweight. METHODS: The FFAKI-trial was a pilot trial of forced fluid removal vs standard care in adult ICU patients with moderate to high risk acute kidney injury and 10% fluid accumulation. Fluid removal was done with furosemide and/or continuous renal replacement therapy aiming at net negative fluid balance > 1 mL/kg ideal body weight/hour until cumulative fluid balance calculated from ICU admission reached less than 1000 mL. RESULTS: After 20 months, we stopped the trial prematurely due to a low inclusion rate with 23 (2%) included patients out of the 1144 screened. Despite the reduced sample size, we observed a marked reduction in cumulative fluid balance 5 days after randomisation (mean difference -5814 mL, 95% CI -2063 to -9565, P = .003) with forced fluid removal compared to standard care. While the trial was underpowered for clinical endpoints, no point estimates suggested harm from forced fluid removal. CONCLUSIONS: Forced fluid removal aiming at 1 mL/kg ideal body weight/hour may be an effective treatment of fluid accumulation in ICU patients with acute kidney injury. A definitive trial using our inclusion criteria seems less feasible based on our inclusion rate of only 2%.

Fluid accumulation during acute kidney injury in the intensive care unit.

INTRODUCTION: Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. METHOD: We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. RESULTS: The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. CONCLUSION: Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery.

Mortality in enterococcal bloodstream infections increases with inappropriate antimicrobial therapy.

Enterococcus species are common in nosocomial bloodstream infections and their incidence is rising. Although well recognized in several serious bacterial infections, the influence of appropriate antimicrobial therapy in enterococcal bacteraemia has not been fully settled. The aim of the study was to determine whether administration of inappropriate antibiotics in enterococcal bacteraemia is an independent risk factor for mortality, among other known and suspected risk factors. We conducted a cohort study of E. faecalis/faecium bacteraemia during a 3-year period at a single tertiary care hospital in Denmark. Patients with growth of non-enterococcus co-pathogens apart from the enterococcal bacteraemia were also included, as were patients with repeated enterococcal bacteraemia. Time to appropriate antimicrobial therapy was counted from the first episode. Appropriate antibiotic therapy was defined as any therapy with documented clinical effect, in vitro activity and a minimum treatment length of 6 days. Multivariate regression models were built to determine the independent risk factors for mortality. We included 196 patients with enterococcal bacteraemia. Appropriate antibiotics for at least 6 days were administered in 146 of these (74%). Thirty-day mortality was 26%. Multivariate logistic regression identified independent predictors of 30-day all-cause mortality: appropriate antimicrobial therapy for ≥ 6 days (odds ratio for mortality 0.33, 0.14-0.79), ICU admission (4.2, 1.7-10), thrombocytopenia (3.9, 1.6-9.3), chronic liver failure (3.3, 1.1-10) and age ≥ 60 years (2.2, 0.99-5.0). Antibiotics not appropriately covering enterococci are frequently administered empirically in suspected bloodstream infections. Inappropriate antibiotic therapy was an independent risk factor for mortality in enterococcal bacteraemia.

Control of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a day-care institution.

This article describes an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in two institutions for multi-handicapped children in Copenhagen. The aim of the study was to determine whether it was possible to eradicate MRSA in a setting with multi-handicapped children and staff where there was a high degree of physical interaction. This was a prospective interventional uncontrolled cohort study that took place from January 2003 to March 2005. All individuals in close contact with the two institutions and/or in close contact with an MRSA-colonized subject from the outbreak were included in the study: 38 children, 60 staff members and 12 close relatives of colonized subjects. Infection control measures included screening all individuals. When MRSA infection or colonization was found, an attempt was made to eradicate MRSA, staff education was undertaken and attempts were made to determine the route of transmission. Eleven individuals were found to be positive for MRSA (10.0%). All isolates were identical by pulsed-field gel electrophoresis and harboured the staphylococcal cassette chromosome mec (SCCmec) type IV. All colonized and infected individuals were associated with a single room in one of the institutions. MRSA was eradicated from all the colonized and infected subjects. This study shows that it is possible to control an MRSA outbreak in institutions for multi-handicapped children where there is a high degree of physical contact.

Relationship between angiotensin-converting enzyme and lysozyme in sarcoidosis.

The relationship between serum angiotensin-converting enzyme (SACE) and serum lysozyme (SLZ) was examined in 48 patients with sarcoidosis. The level of at least one enzyme was elevated in all 41 cases with active sarcoidosis; both enzymes were elevated in 24. SACE and SLZ were positively correlated. The elevation of SLZ or SLZ+SACE was most frequent in patients with pulmonary parenchymal involvement or extrathoracic manifestations. Both enzymes are suitable for disease monitoring, but in most cases the more specific SACE must be preferred as a measure of disease activity, although SLZ seems to be a little more sensitive. Blood for SACE analysis must arrive at the laboratory not later than 3 days after blood collection in order to avoid enzyme inactivation.