PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP): study protocol for a randomised controlled trial.

BACKGROUND: Differentiating infection from inflammation in acute pancreatitis is difficult, leading to overuse of antibiotics. Procalcitonin (PCT) measurement is a means of distinguishing infection from inflammation as levels rise rapidly in response to a pro-inflammatory stimulus of bacterial origin and normally fall after successful treatment. Algorithms based on PCT measurement can differentiate bacterial sepsis from a systemic inflammatory response. The PROCalcitonin-based algorithm for antibiotic use in Acute Pancreatitis (PROCAP) trial tests the hypothesis that a PCT-based algorithm to guide initiation, continuation and discontinuation of antibiotics will lead to reduced antibiotic use in patients with acute pancreatitis and without an adverse effect on outcome. METHODS: This is a single-centre, randomised, controlled, single-blind, two-arm pragmatic clinical and cost-effectiveness trial. Patients with a clinical diagnosis of acute pancreatitis will be allocated on a 1:1 basis to intervention or standard care. Intervention will involve the use of a PCT-based algorithm to guide antibiotic use. The primary outcome measure will be the binary outcome of antibiotic use during index admission. Secondary outcome measures include: safety non-inferiority endpoint all-cause mortality; days of antibiotic use; clinical infections; new isolates of multiresistant bacteria; duration of inpatient stay; episode-related mortality and cause; quality of life (EuroQol EQ-5D); and cost analysis. A 20% absolute change in antibiotic use would be a clinically important difference. A study with 80% power and 5% significance (two-sided) would require 97 patients in each arm (194 patients in total): the study will aim to recruit 200 patients. Analysis will follow intention-to-treat principles. DISCUSSION: When complete, PROCAP will be the largest randomised trial of the use of a PCT algorithm to guide initiation, continuation and cessation of antibiotics in acute pancreatitis. PROCAP is the only randomised trial to date to compare standard care of acute pancreatitis as defined by the International Association of Pancreatology/American Pancreatic Association guidelines to patients having standard care but with all antibiotic prescribing decisions based on PCT measurement. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number, ISRCTN50584992. Registered on 7 February 2018.

Correction: Cardiac implantable electronic device (CIED) infections are expensive and associated with prolonged hospitalisation: UK Retrospective Observational Study.

[This corrects the article DOI: 10.1371/journal.pone.0206611.].

Cardiac implantable electronic device (CIED) infections are expensive and associated with prolonged hospitalisation: UK Retrospective Observational Study.

BACKGROUND: There are limited reports outlining the financial cost of treating cardiac implantable electronic device (CIED) infection outside the United States. This study aimed to determine the average treatment cost of CIED infection in a large UK tertiary referral centre and compared costs of different treatment pathways that are recognised in the management of CIED infection (early versus delayed re-implantation). METHODS: We retrospectively analysed cost and length of stay (LOS) data for consecutive patients undergoing infected CIED extraction with cardiac resynchronization therapy (CRT-D [with defibrillator], CRT-P [with pacemaker]), implantable cardioverter-defibrillators (ICDs) and permanent pacemakers (PPMs). RESULTS: Between January 2013 and March 2015, complete data was available for 84 patients (18 [21.4%] CRT-D, 24 [28.6%] ICDs and 42 [50.0%] PPMs). When all cases were considered the cost of infection ranged from £5,139 (PPM) to £24,318 (CRT-D). Considering different treatment strategies; 41 (48.8%) underwent CIED extraction and re-implantation during the same admission (early re-implant strategy (ER). 43 (51.2%) underwent extraction, but were then discharged home to be re-admitted for day-case re-implantation (delayed re-implant strategy (DR)). Median LOS was significantly shorter in DR compared to ER (5.0 vs. 18.0 days, p<0.001). The total cost of CIED infection episode was similar for both treatment strategies (median £14,241.48 vs. £14,741.70 including wearable defibrillator (Lifevest) and outpatient antibiotics costs, ER vs. DR; p = 0.491). CONCLUSION: CIED infections are expensive and associated with significant health-economic burden. When all device types were considered, a DR strategy is associated with reduced LOS without an increased cost penalty.

Early diagnosis of cardiac implantable electronic device generator pocket infection using ¹8F-FDG-PET/CT.

AIMS: To examine the utility of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the early diagnosis of cardiac implantable electronic device (CIED) generator pocket infection. METHODS AND RESULTS: A total of 86 patients with CIEDs were evaluated with (18)F-FDG PET/CT imaging: 46 with suspected generator pocket infection and 40 without any history of infection. (18)F-FDG activity in the region of the generator pocket was expressed as a semi-quantitative ratio (SQR)-defined as the maximum count rate around the CIED divided by the mean count rate between normal right and left lung parenchyma. All patients underwent standard clinical management, independent of the PET/CT result. Patients with suspected generator pocket infection that required CIED extraction (n = 32) had significantly higher (18)F-FDG activity compared with those that did not (n = 14), and compared with controls (n = 40) [SQR: 4.80 (3.18-7.05) vs. 1.40 (0.88-1.73) vs. 1.10 (0.98-1.40), respectively; P < 0.001]. On receiver operator characteristic analysis, SQR had a high diagnostic accuracy (area under curve = 0.98) for the early identification of patients with confirmed infection (i.e. those ultimately needing extraction)-with an optimal SQR cut-off value of >2.0 (sensitivity = 97%; specificity = 98%). CONCLUSION: This study highlights the potential benefits of evaluating patients with suspected CIED generator pocket infection using (18)F-FDG PET/CT. In this study, (18)F-FDG PET/CT had a high diagnostic accuracy in the early diagnosis of CIED generator pocket infection, even where initial clinical signs were underwhelming.

Brucella melitensis sternal osteomyelitis following median sternotomy.

Human brucellosis, a zoonotic infection, may present with a range of symptoms but is rarely described as a cause of surgical site infections. We present the first reported case of Brucella melitensis causing sternal osteomyelitis of a midline sternotomy for a coronary artery bypass graft. The operation was performed in a non-endemic country but the patient had travelled to Syria immediately before surgery, where the infection was assumed to have been acquired. The infection resolved following treatment with doxycycline, rifampicin and gentamicin. We review the literature for surgical site infections related to Brucella species and discuss the infection control implications. Human brucellosis has the potential to cause surgical site infections and it should be in the differential diagnosis of any patient with a relevant exposure history presenting with a febrile illness and musculoskeletal findings.

False-negative rate of gram-stain microscopy for diagnosis of septic arthritis: suggestions for improvement.

We quantify the false-negative diagnostic rate of septic arthritis using Gram-stain microscopy of synovial fluid and compare this to values reported in the peer-reviewed literature. We propose a method of improving the diagnostic value of Gram-stain microscopy using Lithium Heparin containers that prevent synovial fluid coagulation. Retrospective study of the Manchester Royal Infirmary microbiology database of patients undergoing synovial fluid Gram-stain and culture between December 2003 and March 2012 was undertaken. The initial cohort of 1896 synovial fluid analyses for suspected septic arthritis was reduced to 143 after exclusion criteria were applied. Analysis of our Gram-stain microscopy yielded 111 false-negative results from a cohort size of 143 positive synovial fluid cultures, giving a false-negative rate of 78%. We report a false-negative rate of Gram-stain microscopy for septic arthritis of 78%. Clinicians should therefore avoid the investigation until a statistically significant data set confirms its efficacy. The investigation's value could be improved by using Lithium Heparin containers to collect homogenous synovial fluid samples. Ongoing research aims to establish how much this could reduce the false-negative rate.