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      CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions

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          Abstract

          The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD) is controversial and a biomarker identifying patients who benefit from antibiotics is mandatory. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription.

          Patients hospitalised with acute exacerbations of COPD were randomised to receive antibiotics based either on the GOLD strategy or according to the CRP strategy (CRP ≥50 mg·L −1).

          In total, 101 patients were randomised to the CRP group and 119 to the GOLD group. Fewer patients in the CRP group were treated with antibiotics compared to the GOLD group (31.7% versus 46.2%, p=0.028; adjusted odds ratio (OR) 0.178, 95% CI 0.077–0.411, p=0.029). The 30-day treatment failure rate was nearly equal (44.5% in the CRP group versus 45.5% in the GOLD-group, p=0.881; adjusted OR 1.146, 95% CI 0.649–1.187, p=0.630), as was the time to next exacerbation (32 days in the CRP group versus 28 days in the GOLD group, p=0.713; adjusted hazard ratio 0.878, 95% CI 0.649–1.187, p=0.398). Length of stay was similar in both groups (7 days in the CRP group versus 6 days in the GOLD group, p=0.206). On day-30, no difference in symptom score, quality of life or serious adverse events was detected.

          Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found. Further research is needed for the generalisability of these findings.

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          Is Open Access

          Procalcitonin to guide antibiotic administration in COPD exacerbations: a meta-analysis

          Challenges in the differentiation of the aetiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to significant overuse of antibiotics. Serum procalcitonin, released in response to bacterial infections, but not viral infections, could possibly identify AECOPD requiring antibiotics. In this meta-analysis we assessed the clinical effectiveness of procalcitonin-based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD. Based on a prospectively registered protocol, we reviewed the literature and selected randomised or quasi-randomised trials comparing procalcitonin-based protocols to initiate or discontinue antibiotics versus standard care in AECOPD. We followed Cochrane and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidance to assess risk of bias, quality of evidence and to perform meta-analyses. We included eight trials evaluating 1062 patients with AECOPD. Procalcitonin-based protocols decreased antibiotic prescription (relative risk (RR) 0.56, 95% CI 0.43–0.73) and total antibiotic exposure (mean difference (MD) −3.83, 95% CI (−4.32–−3.35)), without affecting clinical outcomes such as rate of treatment failure (RR 0.81, 0.62–1.06), length of hospitalisation (MD −0.76, −1.95–0.43), exacerbation recurrence rate (RR 0.96, 0.69–1.35) or mortality (RR 0.99, 0.58–1.69). However, the quality of the available evidence is low to moderate, because of methodological limitations and small overall study population. Procalcitonin-based protocols appear to be clinically effective; however, confirmatory trials with rigorous methodology are required. Current evidence suggests that serum procalcitonin could safely halve antibiotic administration in COPD exacerbations http://ow.ly/c693304JkYB
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            Procalcitonin vs C-reactive protein as predictive markers of response to antibiotic therapy in acute exacerbations of COPD.

            Rational prescription of antibiotics in acute exacerbations of COPD (AECOPD) requires predictive markers. We aimed to analyze whether markers of systemic inflammation can predict response to antibiotics in AECOPD. We used data from 243 exacerbations out of 205 patients from a placebo-controlled trial on doxycycline in addition to systemic corticosteroids for AECOPD. Clinical and microbiologic response, serum C-reactive protein (CRP) level (cutoffs 5 and 50 mg/L), and serum procalcitonin level (PCT) (cutoffs 0.1 and 0.25 μg) were assessed. Potential bacterial pathogens were identified in the majority of exacerbations (58%). We found a modest positive correlation between PCT and CRP (r = 0.46, P 50 mg/L, respectively. Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics. CRP might be a more valuable marker in these patients.
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              Management and prevention of exacerbations of COPD.

              Patients with chronic obstructive pulmonary disease (COPD) are prone to acute respiratory exacerbations, which can develop suddenly or subacutely over the course of several days. Exacerbations have a detrimental effect on patients' health status and increase the burden on the healthcare system. Initial treatment is unsuccessful in 24-27% of patients, who have a relapse or a second exacerbation within 30 days of the initial event. No obvious benefit has been seen in recent clinical trials of anti-tumour necrosis factor therapy, anti-leukotriene therapy, intensive chest physiotherapy, or early inpatient pulmonary rehabilitation for treatment of exacerbations. By contrast, clinical trials of prevention rather than acute treatment have shown promising results. Long acting β agonist (LABA) or long acting anti-muscarinic (LAMA) bronchodilators and inhaled corticosteroid-LABA combinations prevent exacerbations in patients at risk, with relative risk reductions averaging 14-27% for each of these drugs relative to placebo. Triple therapy with inhaled corticosteroid-LABA plus LAMA may provide additional benefit, although study results to date are heterogeneous and more studies are needed. Pneumonia is an important complication of treatment with inhaled corticosteroid-LABA products, and the risk of pneumonia seems to be doubled in patients with COPD who use fluticasone. The addition of azithromycin to usual COPD therapy prevents exacerbations, although it may prolong the Q-T interval and increase the risk of death from cardiovascular disease in patients prone to arrhythmia. New potential drugs--including mitogen activated protein kinase inhibitors, phosphodiesterase 3 inhibitors, and monoclonal antibodies to the interleukin 1 receptor--offer additional hope for treatments that may prevent exacerbations in the future.
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                Author and article information

                Journal
                European Respiratory Journal
                Eur Respir J
                European Respiratory Society (ERS)
                0903-1936
                1399-3003
                May 23 2019
                May 2019
                May 2019
                March 17 2019
                : 53
                : 5
                : 1802014
                Article
                10.1183/13993003.02014-2018
                30880285
                1863b438-1a93-4cfb-b9a1-1876a314e904
                © 2019

                https://www.ersjournals.com/user-licence

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