C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Butler, Christopher Collett; Gillespie, David; White, Patrick; Bates, Janine; Lowe, Rachel; Thomas-Jones, Emma; Wootton, Mandy; Hood, Kerenza; Phillips, Rhiannon; Melbye, Hasse; Llor, Carl; Cals, Jochen; Naik, Gurudutt; Kirby, Nigel; Gal, Micaela; Riga, Evgenia; Francis, Nick

doi:10.1056/nejmoa1803185

Cited by 193 publications

(168 citation statements)

References 42 publications

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“…Importantly, in the subset with a final diagnosis of “acute bronchitis” there was a significant reduction in the procalcitonin group. Further, a recent randomized trial in 653 patients with chronic obstructive pulmonary disease found that use of CRP safely reduced antibiotic use . Another validated clinical rule used CRP in conjunction with signs and symptoms and was able to identify patients with LRTI likely to have an uncomplicated course without antibiotics …”

Section: Discussionmentioning

confidence: 99%

“…Further, a recent randomized trial in 653 patients with chronic obstructive pulmonary disease found that use of CRP safely reduced antibiotic use. 37 Another validated clinical rule used CRP in conjunction with signs and symptoms and was able to identify patients with LRTI likely to have an uncomplicated course without antibiotics. 28,33 We would argue that these biomarkers are most likely to be helpful for supporting clinical decisions about antibiotics in the outpatient setting, where chest radiography may not be readily available and where better antibiotic stewardship is needed.…”

Section: Discussionmentioning

confidence: 99%

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Accuracy of Biomarkers for the Diagnosis of Adult Community‐acquired Pneumonia: A Meta‐analysis

Ebell

Bentivegna

Cai

et al. 2020

Academic Emergency Medicine

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Background Biomarkers such as C‐reactive protein (CRP) and procalcitonin may help distinguish community‐acquired pneumonia (CAP) from other causes of lower respiratory tract infection. Methods We performed a systematic review of the literature to identify prospective studies evaluating the accuracy of a biomarker in patients with acute cough or suspected CAP. We performed parallel abstraction of data regarding study inclusion, characteristics, quality, and test accuracy. Study quality was evaluated using QUADAS‐2. Bivariate meta‐analysis was performed using the mada package in R, and summary receiver operating characteristic (ROC) curves were created. Results Fourteen studies met our inclusion and exclusion criteria; three were at low risk of bias and four at moderate risk of bias, largely due to failure to prespecify diagnostic thresholds. Considering all studies regardless of the cutoff used, CRP was most accurate (area under the ROC curve = 0.802), followed by leukocytosis (0.777) and procalcitonin (0.771). Lipopolysaccharide‐binding protein and fibrinogen are promising, but were only studied in a single report. For CRP and procalcitonin, the positive and negative likelihood ratios (LR+ and LR–, respectively) varied inversely based on the cutoff. For CRP, LR+ and LR− were 2.08 and 0.32 for a cutoff of 20 mg/L, 3.64 and 0.36 for a cutoff of 50 mg/L, and 5.89 and 0.47 for a cutoff of 100 mg/L. For procalcitonin, LR+ and LR− were 2.50 and 0.39 for a cutoff of 0.10 µg/L, 5.43 and 0.62 for a cutoff of 0.25 µg/L, and 8.25 and 0.76 for a cutoff of 0.50 µg/L. The combination of CRP >49.5 mg/L and procalcitonin >0.1 µg/L had LR+ of 2.24 and LR− of 0.44. Conclusions The best evidence supports CRP as the preferred biomarker for diagnosis of outpatient CAP given its accuracy, low cost, and point‐of‐care availability.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accuracy of Biomarkers for the Diagnosis of Adult Community‐acquired Pneumonia: A Meta‐analysis

Ebell

Bentivegna

Cai

et al. 2020

Academic Emergency Medicine

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“…Despite the critical need for novel biomarkers, very few clinical studies have linked disease outcome (morbidity/mortality) with any reliable biomarkers [116][117][118]. Patient studies have shown correlations between generalized inflammatory markers such as increased white blood cell count [119,120], TNF-α [120,121], IL-6 [121,122], C-reactive protein [123], and IL-8 [120,124], but few show significant correlations with the prediction of exacerbation onset [125,126]. Few biomarkers have been approved for use in clinical trials, with only plasma fibrinogen and soluble receptor for advanced glycation end products (sRAGE) approved by the US Food and Drug Administration (FDA) [127][128][129].…”

Section: Establishment Of Disease and Exacerbation Biomarkersmentioning

confidence: 99%

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

Tanner

Single

2019

J Innate Immun

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Chronic obstructive pulmonary disease (COPD) affects the lives of an ever-growing number of people worldwide. The lack of understanding surrounding the pathophysiology of the disease and its progression has led to COPD becoming the third leading cause of death worldwide. COPD is incurable, with current treatments only addressing associated symptoms and sometimes slowing its progression, thus highlighting the need to develop novel treatments. However, this has been limited by the lack of experimental standardization within the respiratory disease research area. A lack of coherent animal models that accurately represent all aspects of COPD clinical presentation makes the translation of promising in vitro data to human clinical trials exceptionally challenging. Here, we review current knowledge within the COPD research field, with a focus on current COPD animal models. Moreover, we include a set of advantages and disadvantages for the selection of pre-clinical models for the identification of novel COPD treatments.

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“…Studies in the general practice population showed CRP to be the strongest predictor of pneumonia, and that the reliability of the diagnosis improves when CRP is added to the evaluation of clinical signs and symptoms [19,34]. The introduction of CRP POCT in general practice has resulted in a significant and cost-effective reduction in antibiotic prescribing for LRTI in adults as well as in adults with underlying COPD, without negative consequences for clinical recovery [14,[35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial

Boere¹,

Buul²,

Hopstaken

et al. 2020

BMC Health Serv Res

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Background: Antibiotics are over-prescribed for lower respiratory tract infections (LRTI) in nursing home residents due to diagnostic uncertainty. Inappropriate antibiotic use is undesirable both on patient level, considering their exposure to side effects and drug interactions, and on societal level, given the development of antibiotic resistance. C-reactive protein (CRP) point-of-care testing (POCT) may be a promising diagnostic tool to reduce antibiotic prescribing for LRTI in nursing homes. The UPCARE study will evaluate whether the use of CRP POCT for suspected LRTI is (cost-) effective in reducing antibiotic prescribing in the nursing home setting. Methods/design: A cluster randomized controlled trial will be conducted in eleven nursing homes in the Netherlands, with the nursing home as the unit of randomization. Residents with suspected LRTI who reside at a psychogeriatric, somatic, or geriatric rehabilitation ward are eligible for study participation. Nursing homes in the intervention group will provide care as usual with the possibility to use CRP POCT, and the control group will provide care as usual without CRP POCT for residents with (suspected) LRTI. Data will be collected from September 2018 for approximately 1.5 year, using case report forms that are integrated in the electronic patient record system. The primary study outcome is antibiotic prescribing for suspected LRTI at index consultation (yes/no). Discussion: This is the first randomised trial to evaluate the effect of nursing home access to and training in the use of CRP POCT on antibiotic prescribing for LRTI, yielding high-level evidence and contributing to antibiotic stewardship in the nursing home setting. The relatively broad inclusion criteria and the pragmatic study design add to the applicability and generalizability of the study results.

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C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations

Cited by 193 publications

References 42 publications

Accuracy of Biomarkers for the Diagnosis of Adult Community‐acquired Pneumonia: A Meta‐analysis

Accuracy of Biomarkers for the Diagnosis of Adult Community‐acquired Pneumonia: A Meta‐analysis

Animal Models Reflecting Chronic Obstructive Pulmonary Disease and Related Respiratory Disorders: Translating Pre-Clinical Data into Clinical Relevance

Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial

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