Letters to the Editor results. The test is not processed locally, but all meningococcal PCR tests nationwide are processed centrally at the Public Health England (PHE) Meningococcal Reference Unit (MRU) laboratory in Manchester. We undertook a service evaluation project to determine the clinical utility of meningococcal PCR testing in clinical practice and whether or not there was a significant delay in receiving results. We reviewed the last 50 admissions where a blood or CSF sample was sent for meningococcal PCR testing, spanning nearly 2 years (October 2011eApril 2013). Our review showed that in only 2 of these 50 cases did the meningococcal PCR result yield any clinical impact, and these were both cases where the suspicion of meningococcal sepsis was low and a negative result prompted the halting of antibiotic therapy. In both cases the MRU laboratory was phoned by doctors in our paediatric department to retrieve the result. There were 5 positive results from our cohort, and in none of them did the PCR result yield clinical utility, defined as: changed diagnosis, confirmed diagnosis during in-patient stay, changed antibiotic regime, prompted HPA contact, prompted contact prophylaxis. 2 cases had positive blood cultures. The failure of the PCR test to impact on clinical practice was explained from our perspective by a significant delay in receiving results. The mean time from test request to receiving results was over 5 days for both positive and negative results. As a result, 88% of children had actually been discharged before the PCR result was even available to the clinicians. All of the patients who yielded positive results had been discharged on ambulatory antibiotic therapy prior to the PCR result being available, hence not even confirming diagnosis during the acute management. We discussed the results at the regional paediatric meeting where this was felt to be a common experience across our region. We also discussed our results with the MRU laboratory who are currently reviewing their practice to determine why even positive results take this period of time to process and return. Whilst we cannot argue with the public health value of PCR testing for children with probable meningococcal disease, the time required for central processing of samples means the results are rarely available in a clinically useful timeframe. The utility of sending blood for PCR testing in any child with a non-blanching rash might also be challenged. More than a quarter of our patient sample had an admission diagnosis of “viral illness”, bringing into question this current practice, and also highlights the ambiguity of the NICE guidelines for “suspected” meningococcal disease. Meningococcal PCR testing might be best reserved for those cases where the clinical diagnosis is “probable” (i.e. the most likely) to sustain its public health utility, whilst preventing unnecessary diagnostic samples being sent in cases where it is “possible” (i.e. an alternate diagnosis equally or more likely).

References 1. Heinsbroek E, Ladhani S, Gray, Guiver M, Kaczmarski E, Borrow R, et al. Added value of PCR-testing for confirmation of invasive meningococcal disease in England. J Infect 2013; 67:385e90.

607 2. NICE. Bacterial meningitis and meningococcal septicaemia. NICE Guidance; June 2010.

Alasdair Munro* Steve Wadams Paediatric Department, Poole Hospital NHS Foundation Trust, Longfleet Road, Poole BH15 2JB, UK *Corresponding author. Tel.: þ44 7782211999. E-mail address: [email protected] (A. Munro) Accepted 1 February 2014 ª 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2014.02.001

SuPAR in pleural fluid may function as a biological marker for infection in critically ill patients with pleural effusions Dear editor, With interest we have read the studies of Odeh et al.1 and Savva et al.2 on pulmonary biomarkers in critically ill patients. Critically ill patients frequently develop pleural effusions, which is associated with increased morbidity and mortality,3,4 especially in case of infection. Gramstains of pleural fluids have low sensitivity and cultures may take too long for timely initiation of adequate antimicrobial therapy.4 Odeh et al. showed that pleural fluid TNF-a is a good marker for discrimination of infected pleural effusions. The relatively new biological marker soluble urokinase plasminogen activator receptor (suPAR) shows elevated blood levels in severe systemic infection.2,5,6 We hypothesize suPAR levels in pleural fluid to discriminate infectious from non-infectious pleural effusions. Effusions were obtained from 22 intensive care unit (ICU) patients with de novo presentation of pleural effusion (Table 1).7 Using previous reported criteria,3 five pleural effusions were classified as puss, five as infectious exudates, eight as non-infectious exudates and eight as transudate. We determined suPAR levels using a commercially available enzyme-linked immune-assay (suPARnostickit, ViroGates, Copenhagen, Denmark). In patients with positive culture of pleural effusions (i.e., patients with macroscopic puss and patients with pleural fluid that showed bacterial growth), suPAR levels were significantly higher (median, 91 [10e405] ng/mL) compared to patients with non-infectious pleural effusion (13 [0.4e40] ng/mL; P < 0.001) (Fig. 1A). For differentiating between infected and non-infected effusions, the AUC of the ROC curve was 0.94 [95% CI; 0.84e1.04]; P < 0.001 (Fig. 1B). A cut-off value of 9.8 ng/mL yielded a sensitivity of 100% [95% CI; 69e100%] and specificity of

608 Table 1

Letters to the Editor Baseline characteristics.

Age (years) Male sex (n, %) Blood leukocyte count (109/l) PE leukocyte count (109/l) PE LDH (IU/l) PE cholesterol (mmol/l) PE total protein (g/l) PE glucose (mmol/l)

Transudate (n Z 8)

Non-infected exudate (n Z 8)

Infected exudate (n Z 5)

Empyema (n Z 5)

P-value

53  11 4 (50%) 12.3  4.5 0.5 [0.0e1.1] 155 [69e214] Not detectable Not detectable 7.2  1.4

66  14 4 (50%) 12.4  3.1 1.7 [0.0e10.9] 653 [243e3933] 1.26 [0.00e1.95] 0.0 [0.0e36] 6.1  1.7

63  6 2 (40%) 16.0  8.9 2.0 [0.1e10.1] 2197 [570e3787] 0.59 [0.00e1.76] 0.0 [0.0e43] 2.8  2.3

44  6 4 (80%) 15.1  5.5 e e e e e

0.006a 0.603 0.680 0.297 0.001a 0.068 0.280 0.005a

PE Z pleural effusion; LDH Z lactate dehydrogenase. Continuous data are expressed as mean  standard deviation when normally distributed or as median [range] when not normally distributed. Categorical data are expressed as n (%). a Significant (P < 0.05).

Figure 1 Pleural fluid suPAR levels. (A) Median pleural effusion levels of suPAR in patients with culture-positive (i.e., patients with puss, or pleural fluids showing bacterial growth) versus culture-negative pleural effusions. (B) Receiver operating characteristic curve of pleural effusion suPAR levels in patients with infected and non-infected pleural effusions. Differences in suPAR levels were analyzed with the ManneWhitney U test. All analyses were performed with SPSS, version 17.0 and Graphpad Prima, version 5. A P-value

SuPAR in pleural fluid may function as a biological marker for infection in critically ill patients with pleural effusions.

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