Elevated C-reactive protein increases diagnostic accuracy of algorithm-defined stroke-associated pneumonia in afebrile patients.

BACKGROUND AND AIM: Pyrexia-dependent clinical algorithms may under or overdiagnose stroke-associated pneumonia. This study investigates whether inclusion of elevated C-reactive protein as a criterion improves diagnosis. METHODS: The contribution of C-reactive protein ≥30 mg/l as an additional criterion to a Centers for Disease Control and Prevention-based algorithm incorporating pyrexia with chest signs and leukocytosis and/or chest infiltrates to diagnose stroke-associated pneumonia was assessed in 1088 acute stroke patients from 37 UK stroke units. The sensitivity, specificity, and positive predictive value of different approaches were assessed using adjudicated stroke-associated pneumonia as the reference standard. RESULTS: Adding elevated C-reactive protein to all algorithm criteria did not increase diagnostic accuracy compared with the algorithm alone against adjudicated stroke-associated pneumonia (sensitivity 0.74 (95% CI 0.65-0.81) versus 0.72 (95% CI 0.64-0.80), specificity 0.97 (95% CI 0.96-0.98) for both; kappa 0.70 (95% CI 0.63-0.77) for both). In afebrile patients (n = 965), elevated C-reactive protein with chest and laboratory findings had sensitivity of 0.84 (95% CI 0.67-0.93), specificity of 0.99 (95% CI 0.98-1.00), and kappa 0.80 (95% CI 0.70-0.90). The modified algorithm of pyrexia or elevated C-reactive protein and chest signs with infiltrates or leukocytosis had sensitivity of 0.94 (95% CI 0.87-0.97), specificity of 0.96 (95% CI 0.94-0.97), and kappa of 0.88 (95% CI 0.84-0.93) against adjudicated stroke-associated pneumonia. CONCLUSIONS: An algorithm consisting of pyrexia or C-reactive protein ≥30 mg/l, positive chest signs, leukocytosis, and/or chest infiltrates has high accuracy and can be used to standardize stroke-associated pneumonia diagnosis in clinical or research settings. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN37118456.

Association between nasogastric tubes, pneumonia, and clinical outcomes in acute stroke patients.

OBJECTIVE: To investigate whether nasogastric tubes (NGTs) increase poststroke pneumonia (PSP), mortality, or poor outcomes in nil-by-mouth acute stroke patients. METHODS: This study analyzed prespecified outcomes of PSP at 14 days and mortality and function measured by the modified Rankin Scale at 90 days in 1,217 nil-by-mouth stroke patients at ≤48 hours of symptom onset in a multicenter randomized controlled trial of preventive antibiotics between April 21, 2008, and May 17, 2014. Generalized mixed models adjusted for age, comorbidities, stroke type and severity, and quality of care were used. No patients were lost to follow-up at 14 days, and 36 (3%) were lost at 90 days. RESULTS: Patients with NGT (298 of 1,217 [24.4%]) had more severe strokes (median NIH Stroke Scale score 17 vs 14, p = 0.0001) and impaired consciousness (39% vs 28%, p = 0.001). NGT did not increase PSP (43 of 298 [14.4%] vs 80 of 790 [10.1%], adjusted odds ratio [OR] 1.26 [95% confidence interval (CI) 0.78-2.03], p = 0.35) or 14- and 90-day mortality (33 of 298 [11.1%] vs 78 of 790 [9.9%], adjusted OR 1.10 [95% CI 0.67-1.78], p = 0.71; and 79 of 298 [26.5%] vs 152 of 790 [19.2%], adjusted OR 0.95 [95% CI 0.67-1.33], p = 0.75, respectively). Ninety-day modified Rankin Scale score distribution was comparable between groups (adjusted OR 1.14 [95% CI 0.87-1.56], p = 0.08). PSP independently increased 90-day mortality (40 of 123 [32.5%] vs 191 of 965 [19.8%], adjusted OR 1.71 [95% CI 1.11-2.65], p = 0.015) and was not prevented by antibiotics in patients with NGT (adjusted OR 1.1 [95% CI 0.89-1.54], p = 0.16). CONCLUSIONS: Early NGT does not increase PSP incidence, mortality, or poor functional outcomes and can be used safely in acute stroke patients.

Comparison of the diagnostic utility of physician-diagnosed with algorithm-defined stroke-associated pneumonia.

OBJECTIVE: Diagnosing stroke-associated pneumonia (SAP) is challenging and may result in inappropriate antibiotic use or confound research outcomes. This study evaluates the diagnostic accuracy of algorithm-defined versus physician-diagnosed SAP in 1088 patients who had dysphagic acute stroke from 37 UK stroke units between 21 April 2008 and 17 May 2014. METHODS: SAP in the first 14 days was diagnosed by a criteria-based algorithm applied to blinded patient data and independently by treating physicians. Patients in whom diagnoses differed were reassigned following blinded adjudication of individual patient records. The sensitivity, specificity, positive predictive value (PPV) and diagnostic OR of algorithmic and physician diagnosis of SAP were assessed using adjudicated SAP as the reference standard. Agreement was assessed using the κ statistic. RESULTS: Physicians diagnosed SAP in 176/1088 (16%) and the algorithm in 123/1088 (11.3%) patients. Diagnosis agreed in 885/1088 (81.3%) patients (κ 0.22 (95% CI 0.14 to 0.29)). On a blinded review, 129/1088 (11.8%) patients were adjudicated as patients with SAP. The algorithm and the physicians had high specificity (97% (95% CI 96% to 98%) and 90% (95% CI 88% to 92%), respectively) but only moderate sensitivity (72% (95% CI 64% to 80%) and 65% (95% CI 56% to 73%), respectively) in diagnosing SAP. The algorithm showed better PPV (76% (95% CI 67% to 83%) vs 48% (95% CI 40% to 55%)), diagnostic OR (80 (95% CI 42 to 136) vs 18 (95% CI 12 to 27)) and agreement (κ 0.70 (95% CI 0.63 to 0.78) vs 0.48 (95% CI 0.41 to 0.54)) than physician diagnosis with adjudicated SAP. CONCLUSIONS: Algorithm-based approaches can standardise SAP diagnosis for clinical practice and research. TRIAL REGISTRATION NUMBER: ISRCTN37118456; Post-results.

Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial.

BACKGROUND: Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in patients with dysphagia after acute stroke. METHODS: We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com, number ISRCTN37118456. FINDINGS: Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 [13%] of 564 patients in antibiotics group vs 52 [10%] of 524 in control group; marginal adjusted odds ratio [OR] 1·21 [95% CI 0·71-2·08], p=0·489, intraclass correlation coefficient [ICC] 0·06 [95% CI 0·02-0·17]. Algorithm-defined post-stroke pneumonia could not be established in 129 (10%) patients because of missing data. Additionally, we noted no differences in physician-diagnosed post-stroke pneumonia between groups (101 [16%] of 615 patients vs 91 [15%] of 602, adjusted OR 1·01 [95% CI 0·61-1·68], p=0·957, ICC 0·08 [95% CI 0·03-0·21]). The most common adverse events were infections unrelated to post-stroke pneumonia (mainly urinary tract infections), which were less frequent in the antibiotics group (22 [4%] of 615 vs 45 [7%] of 602; OR 0·55 [0·32-0·92], p=0·02). Diarrhoea positive for Clostridium difficile occurred in two patients (<1%) in the antibiotics group and four (<1%) in the control group, and meticillin-resistant Staphylococcus aureus colonisation occurred in 11 patients (2%) in the antibiotics group and 14 (2%) in the control group. INTERPRETATION: Antibiotic prophylaxis cannot be recommended for prevention of post-stroke pneumonia in patients with dysphagia after stroke managed in stroke units. FUNDING: UK National Institute for Health Research.