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C-Reactive Protein (CRP) and Pro-calcitonin (PCT) Point of Care Testing - J Bolodeoku MBBS MSc MBA DPhil (Oxon) FRCPath

In the United Kingdom, about 79% of the prescribing of antibiotics occurs in community and respiratory tract infections account for about 60% of the diagnosis. With many of these respiratory tract infections, the condition is self-limiting or caused by viruses, and therefore do not warrant the use of antibiotics1. A diagnostic test that could differentiate between a viral and bacterial infection respiratory tract infection could help inform or guide the healthcare professional as to whether the patient requires antibiotics or not. It can be difficult to predict pneumonia in patients with respiratory tract infections based on their symptoms alone: absence of a runny nose, breathlessness, crackles, diminished breath sounds on auscultation, tachycardia and fever2. CRP is an acute-phase protein produced by the liver following infection or injury. There is usually only a very small amount detectable within the blood and a viral infection would generally give rise to a modest increase in the blood, peaking about day 2 and 4. CRP levels correlate with the degree of severity of the infection3. Measuring CRP in patients presenting with a suspected respiratory tract infections can help differentiate between viral and self-limiting infections from more serious bacterial infections that need antibiotics. Therefore, complementing the history, clinical signs and symptoms and measuring the CRP would improve the probability of predicting pneumonia.

There are several studies conducted with CRP point of care testing in adults to guide antibiotic prescribing in respiratory tract infections which we would evaluate. In a general practice study conducted in the Netherlands assessing the effect of general practitioner testing using CRP and training in communication skills on antibiotic use in lower respiratory tract infections, the general practitioners in the CRP test group prescribed antibiotics to 31% of patients compared with 53% in the group of general practitioners who did not test the CRP. The general practitioners trained in the enhanced communication skills prescribed antibiotics to 27% of the patients compared with 54% in the no training group. In this study, 227 patients were allocated to point of care testing, the range determined was <8 to 225 mg/L. Overall, 69% of the patients had CRP levels of less than 2 mg/L, 24% had CRP levels of 20 – 99 mg/L and only 7% had greater than 100 mg/L4. In the United Kingdom, another study of 99 patients presenting with symptoms of respiratory tract infections in a GP surgery between July 2014 and May 2015. CRP levels of 0 - 5, 6 - 13, 31 – 100, > 100 ng/mL, were observed in 48 (48%), 35 (35%), 13 (13%) and 3 (3%) patients, respectively5. Recently, the Scottish Microbial Prescribing Group (SAPG) developed a proposal to evaluate the feasibility of using CRP testing in GP Practices and unscheduled care settings (e.g. out-of-hours service). The objective was primarily to evaluate the qualitative aspect of the implementation, but within the methodological limitations of a pragmatic feasibility study to also assess the perceived impact on antibiotic prescribing behaviour. Ten GP Practices were recruited from four health board areas through direct invitation by SAPG members. The test methodology used the following test result ranges (recommended by NICE) to inform treatment options: Low CRP (<20mg/L) rules out need for antibiotic Intermediate; (CRP 20 – 100mg/L) use clinical judgement to decide need for antibiotics; High CRP (>100mg/L) rules in need for antibiotics. Details of each consultation were collected to provide information on patient demographics, test results and prescribing decisions. CRP test results were documented for 231 patients (94%) with the remaining tests having problems with instrument error messages. For the majority of patients (72%), the CRP test result was <20mg/L and in 74% of cases GPs perceived that the CRP test results did have an influence on prescribing decisions. The outcome of using the test was that no prescription for antibiotics was issued in 64% of cases and a delayed prescription was issued in 14%. About 22% of patients were prescribed antibiotics6.

The current NHS treatment pathway for the management of a suspected respiratory tract infection provides the decision to prescribe antibiotics is based on medical history, clinical examination and assessment of risk. The NICE guidelines on the diagnosis and management of pneumonia in adults recommends that point of care CRP testing should be considered for people with symptoms of lower respiratory tract infection if a diagnosis is on clear after clinical assessment, and that antibiotic should be prescribed based on the results. Immediate antibiotic treatment should be offered if the CRP level is more than 100mg/L and delayed prescription should be considered at the levels between 20 and 100 mg/L. It is not recommended for CRP levels less than 20 mg/L7. Currently, CRP levels can be measured using a number of point of care devices. NICE is aware of the following CE marked devices that all quantify CRP levels in the blood: Afinion AS 100 (Alere), AQT90 Flex (Radiometer Medical ApS), iCHROMA (Boditech Med), NycoCard Reader II (Alere), Smart analyser (Eurolyser Diagnostica), Quik Read Go (Orion Diagnostics) and has published innovation briefings on the QuikRead Go (Orion Diagnostics)8 and Afinion (Alere)9.

Inflammatory markers, such as CRP or white blood cells lack specificity for bacterial infections and therefore has led to the investigation of other more specific markers for bacterial infections such as procalcitonin (PCT). PCT is more specific about infections and may also help to distinguish between bacterial infections from viral illnesses, it is seen to increase within 6 to 12 hours. PCT also corresponds with bacterial load and the severity of infection. In addition, it has some prognostic indications in predicting fatal outcome in patients with community-acquired pneumonia. A meta-analysis was performed to evaluate the accuracy of determination of pro-calcitonin (PCT) and CRP levels for the diagnosis of bacterial infection. PCT levels were more sensitive and more specific than CRP levels for differentiating bacteria from non-infective causes of information10. The use of the combination of CRP and PCT in a ‘both positive’ test format, a higher specificity (86%) and higher positive predictive value (PPV) of 90%11. There are several bench top PCT assay methods available but there are is only one point of care device that measures both CRP and PCT, the i-CHROMA (Boditech Med). The was good correlation between POCT system i-CHROMA SMART and traditional laboratory method DxC for CRP and PCT12. The future would probably require a POCT system that is able to measure both CRP and PCT to improve the sensitivity of antibiotic prescription for upper respiratory infection.

References

  1. NICE. Respiratory tract infections - antibiotic prescribing. Prescribing of antibiotics for self limiting respiratory tract infections in adults and children in primary care. NICE clinical guideline 69 www.nice.org.uk/guidance/cg69/evidence/cg69-respiratory-tract-infections-full-guideline3 2008
  2. Hopstaken R, Muris J, Knottnerus J, Kester A, Rinkens P, Dinant G. Contributions of symptoms, signs, erythrocyte sedimentation rate and C-reactive protein to a diagnosis of pneumonia in acute lower respiratory tract infection. Br J Gen Pract 2003; 53 (490): 358 – 364
  3. Melbye H, Hvidsten D, Holm A, Nordbo SA, Brox J. The course of C-reactive protein response in untreated upper respiratory tract infection. Br J Gen Pract 2004; 54 (506): 653 – 658
  4. Cals JWL, Butler CC, Hopstaken RM, Hood K, Dinant G-J. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. BMJ 2009; 338: b1374
  5. Penney O C-reactive protein point of care testing reduces diagnostic uncertainty and unnecessary antibiotic prescribing for respiratory tract infections in general practice. Poster No 003 presented at the RCGP Annual Meeting, Glasgow, 1-3 October 2015
  6. SAPG Executive summary report on Evaluation of CRP testing in primary care. http://www.scottishmedicines.org.uk/files/sapg1/Executive_summary_Evaluation_of_CRP_testing_in_primary_care_July_2016.pdf
  7. NICE (December 2014). Pneumonia- Diagnosis and management of community- and hospital-acquired pneumonia in adults
  8. QuikRead go for C-reactive protein testing in primary care/Advice/NICE http://www.nice.org.uk/advice/mib78 September 2016
  9. Alere Afinion CRP for C-reactive protein testing in primary care/Advice/NICE http://www.nice.org.uk/advice/mib81 September 2016
  10. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and c-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2014; 39: 206 – 217
  11. Li H-X, Liu Z-M, Zhao S-J, Zhang D, Wang S-J, Wang Y-S. Measuring both procalcitonin and C-reactive protein for a diagnosis of sepsis in critically ill patients. J Int Med Res 2014 42 (4) 1050 – 1059
  12. Rim JH, Ahn H-J, Yoon KK, Kim HR, Kim Y-A, Lim HS, Yoo JY. Performance evaluation of the ichroma SMART analyzer in measuring c-reactive protein and procalcitonin levels. Lab Med Online 2016 6 (1) 19 -24

Content provided by J Bolodeoku MBBS, MSc, MBA, DPhil (Oxon), FRCPath
Independent Pharmaceutical Physician and Chemical Pathologist, JB Consulting MDP Limited, UK & Honorary Consultant Physician, North Hampshire Hospital, Basingstoke
JB Consulting (MDP) Limited, Cherwell Innovation Centre, 77 Heyford Park, Upper Heyford, Oxfordshire, OX25 5HD, United Kingdom

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