Biomarker guided antibiotic stewardship in community acquired pneumonia: A randomized controlled trial

Background In community-acquired pneumonia (CAP), the role of biomarkers to shorten duration of antibiotic treatment has not been firmly established. We assessed the effectiveness of active feedback of treatment algorithms based on procalcitonin (PCT) and C-reactive protein (CRP), compared to standard care, on the duration of antibiotic treatment in patients hospitalized with community-acquired pneumonia (CAP) in non-ICU wards. Methods and findings We performed a randomised, open label, parallel group, multi-centre trial in 3 Dutch teaching hospitals. Treatment was guided by a PCT algorithm, CRP algorithm or standard care. Participants were recruited by a member of the study team and randomised at day 2–3 of admission in a 1:1:1 ratio. Treatment was discontinued upon predefined thresholds of biomarkers that were assessed on admission, day 4 and days 5–7 if indicated. The primary outcome was total days on antibiotic treatment until day 30. In total 468 participants were included in this study. The median days on antibiotics (IQR) was 7 (IQR 7–10) in the control group, 4 (IQR 3–7) in the CRP group (rate ratio (RR) of 0.70, 95% CI 0.61–0.82 compared to standard care; p <0.001), and 5.5 (IQR 3–9) in the PCT group (RR of 0.78, 95% CI 0.68–0.89 compared to standard care; p <0.001). New antibiotics within the first 30 days were prescribed to 24, 23 and 35 patients in standard care, CRP and PCT groups, respectively. The hazard ratio for a new prescription in patients in the PCT group compared to standard care 1.63 (CI 0.97–2.75; p = 0.06). No difference in time to clinical stability or length of stay was found. Conclusions A strategy of feedback of CRP-guided and PCT-guided treatment algorithms reduced the number of days on antibiotic in the first 30 days after hospital admission in non-ICU wards for CAP. The study was not powered to determine safety of shortening duration of antibiotic treatment. (NCT01964495)

Dynamic networks and behavior: separating selection from influence.

A current problem in the analysis of behavioral dynamics, given a simultaneously evolving social network, is the difficulty of separating effects of partner selection from effects of social influence. In this paper we present a recently developed family of statistical models that enables researchers to separate the two effects in a statistically adequate manner. To illustrate our method we make use of a three-wave panel measured in the years 1995-1997 at a school in the West of Scotland. We are able to assess the strength of selection and influence mechanisms associated with friendship networks of substance-using adolescents

Community-acquired pneumonia : monitoring and modulation of the host response

De krachtige ontstekingsremmers corticosteroïden geven geen verbeterd herstel bij patiënten die buiten het ziekenhuis een longontsteking oplopen, blijkt uit het onderzoek van Dominic Snijders. In zijn proefschrift brengt Snijders de afweerreactie, die optreedt bij een buiten het ziekenhuis verworven longontsteking, nauwgezet in kaart. Hij zoomt verder in op de activiteit van het stollingsysteem en op de gewijzigde samenstelling van het bloed, zogenaamde hematologische veranderingen. In een gerandomiseerd onderzoek onder 213 patiënten met een buiten het ziekenhuis verworven longontsteking geeft de behandeling met corticosteroïden naast antibiotica geen beter klinisch herstel, zo stelt Snijders vast. Wel kan toediening van corticosteroïden extra medicamenteuze behandeling noodzakelijk maken. Ook onderzocht Snijders hematologische veranderingen bij patiënten met een buiten het ziekenhuis verworven longontsteking. D-dimeren, afbraakproducten van stollingsactivatie, blijken niet geschikt als prognostische markers. Noch als zelfstandige marker, noch in combinatie met het vaak gebruikte CURB-65 risicomodel leiden zij tot een betere risico-inschatting. Snijders stelt vast dat hematologische veranderingen tijdens een longontsteking berusten op een verminderde inbouw van ijzer in rode bloedcellen. Dit lijkt in belangrijke mate gereguleerd te worden door het eiwit hepcidine. De inzichten uit dit proefschrift bieden aanknopingspunten voor verder onderzoek naar de werking en behandeling van buiten het ziekenhuis opgelopen longontstekingen In this thesis several possible intervention strategies are explored for improving outcome in hospitalised patients with community-acquired pneumonia (CAP). COPD as co-morbidity in patients with CAP. In patients with CAP seyeral co-morbidities can increase mortality. COPD is one co-morbidity often present in patients with CAP of which it is uncertain whether it increases the mortality risk. Several studies found a higher mortality in patients with both CAP and COPD. In Chapter 1 data is presented which demonstrates the influence of COPD on patients with CAP. One of the most striking findings of this study is the reclassification of COPD as co-morbidity by using pulmonary function testing (PFT). Almost 70 % of included patients had one or more co-morbidities. COPD was found as a co-morbidity in 36.3 % of the patients. The diagnosis was confirmed by PFT according to the GOLD guidelines. However in nearly 20 % of the patients no PFT were available due to lost to follow or death. By means of pre-admission PFT COPD was identified in 6 patients. Of the 95 (36.3%) patients with COPD according to chart review, medical history or information pre-admission, only in 66 (69.5%) patients the diagnosis was confirmed with PFT during follow up. While 29 patients were reclassified as having no COPD, in 29 other patients without diagnosis of COPD prior to admission, the diagnosis was made during follolw up by means of PFT. Approximately one third ofthe patients were reclassified according to their COPD status. Mortality in this study was slightly, although not significantly lower in the non-COPD group (8 [8.4 %]patients) than in the COPD group (20 [12.0%] patients, P=0.37). Patients with COPD did have more severe CAP than non-COPD patients according to the PSI. The CURB-65 score did not differ between the two groups. The reasons for the higher PSI classes were a higher age and higher number of males, next to a higher blood rate at admission. Role of corticosteroids in the treatment of patients hospitalised with CAP. The use of corticosteroids as an adjunctive treatment in patients with CAP is not a new concept. The first studies using prednisolone in patients with pneumococcal pneumonia date from the 1950'S. In some recent publications it has been shown that patients with severe CAP might be benefit by corticosteroids. In Chapter 2 a randomised clinical trail is presented. In this trial 1. 13 patients hospitalised with CAP were randomised between antibiotic therapy according to current guidelines in combination with prednisolone (od -10 mg for 7 days) and antibiotic therapy according to current guidelines with placebo. Patients in the prednisolone group did have a higher level of C-reactive protein (CRP) at admission, but ol'erall the groups were balanced. The priman endpoint was clinical cure at day 7. In the prednisolone group 84 (80.8%) patients had a clinical cure at day 7 while in the placebo group 93 (B5.3 %) patients had a clinical cure at day 7 (P=0.3B). The secondary endpoint clinical cure at day 30 was reached in 93/109 (85.3 %) in the prednisolone group and 84/109 (77.1 %) of the subjects receiYing placebo (p=o.oB). Patients on prednisolone had a faster defeveresence and faster decline in serum CRP levels compared to patients who had placebo. There was also no differences in length ofstay (LOS) and time to clinical stability (TTCS). Sub-analysis of patients with severe pneumonia did not show differences in clinical outcome. Late failure (>72 hours after admittance) was more common in the prednisolone group (20 (19.2%)) than in placebo-treated patients (10 [6-4%], p=o.O-l).

The influence of COPD on mortality and severity scoring in community-acquired pneumonia

Background: Chronic obstructive lung disease (COPD) is a frequent co-morbidity in patients hospitalised with community-acquired pneumonia (CAP). In recent retrospective studies, higher mortality in patients with CAP and COPD was found. Objectives: The aim of the study was to determine the 30-day mortality and to evaluate the differences in CAP severity scoring in hospitalised patients with COPD. Methods: A subanalysis of a randomized clinical trial was performed. Results: A total of 262 patients with CAP were included. Ninety-five (36.3%) patients had COPD. A total of 28 (10.7%) patients died within 30 days. No differences between patients with and without COPD in 30-day mortality were observed [8 (8.4%) vs. 20 (12.0%), p = 0.37]. In the Pneumonia Severity Index (PSI), significant differences in age, gender and heart rate between patients with and without COPD were observed. Patients with COPD were stratified in higher PSI classes. In the CURB-65 score, age ≥65 years was significantly higher in patients with COPD [72 (75.8%) vs. 88 (52.7%), p = <0.01]. In a multivariate analysis, only the need for intensive care unit admission and high serum glucose were predictors of mortality [OR 32.50 (95% CI 6.87-153.75), p < 0.01; OR 7.34 (95% CI 1.19-45.4), p = 0.03]. Conclusions: Mortality was not increased in patients with COPD hospitalised with CAP. Severity scores are influenced by age and gender. Further studies evaluating CAP in patients with COPD are needed to explain these findings

Disseminated Mycobacterium chelonae infection in a patient with T-cell lymphoma

AbstractInfections with rapidly growing mycobacteria are rare and most often seen in immunocompromised patients. We herein present the case of a 69-year-old man with a T-cell lymphoma treated by chemotherapy and mogamulizumab with a 6-month history of febrile episodes and subcutaneous nodules in both arms and arthritis of metacarpophalangeal joints. Blood cultures and DNA sequencing results demonstrated the growth of Mycobacterium chelonae. The patient was successfully treated with clarithromycin, moxifloxacin, and tobramycin, but died shortly after due to lymphoma progression