Point-of-Care C-Reactive Protein Testing and Antibiotic Prescribing for Respiratory Tract Infections: A Randomized Controlled Trial

Jochen W. L. Cals; Marjolein J. C. Schot; Sanne A. M. de Jong; Geert-Jan Dinant; Rogier M. Hopstaken

doi:10.1370/afm.1090

Published eLetters

If you would like to comment on this article, click on Submit a Response to This article, below. We welcome your input.

Submit a Response to This Article

Compose eLetter

Title *

Author Information

Contributors
First Name and Middle Initial * First or given name, e.g. 'Peter'. Last Name * Your last, or family, name, e.g. 'MacMoody'. Email Address * Your email address, e.g. higgs-boson@gmail.com Occupation * Your role and/or occupation, e.g. 'Orthopedic Surgeon'. Affiliation * Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.

Statement of Competing Interests

Competing interests? *

Yes

Please describe the competing interests

CAPTCHA

This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

What code is in the image? *

Enter the characters shown in the image.

Vertical Tabs

Jump to comment:

C-reactive protein testing leads to a reduction in antibiotic use in patients with respiratory tract infections
Lars Bjerrum

Published on: 13 April 2010
Clinical practice guidelines will not foster evidence-based decision-making but relationship-centered interventions may
France Legare

Published on: 12 April 2010
Value of C-reactive protein in elderly and immunocompromised patients unclear
Wim Opstelten

Published on: 25 March 2010
Further details about nature of patient advice needed
Tom Fahey

Published on: 22 March 2010
CRP, Respiratory Tract Infections, Antibiotics, Individuals and Families
Henry Bloom, MD,CCFP, ABFP

Published on: 17 March 2010

Published on: (13 April 2010)
Page navigation anchor for C-reactive protein testing leads to a reduction in antibiotic use in patients with respiratory tract infections
C-reactive protein testing leads to a reduction in antibiotic use in patients with respiratory tract infections
Lars Bjerrum, Denmark
Other Contributors:
We read with high interest the well written paper by Cals et al. about the effect of CRP-testing in reducing antibiotic prescribing in patients with sinusitis and lower respiratory tract infections (RTI)(1) However, we find some issues that merit to be discussed more in depth. Most of the patients included were classified with the diagnosis sinusitis. The diagnostic criteria were based on a history of rhinorrhea and blo...
Show More

We read with high interest the well written paper by Cals et al. about the effect of CRP-testing in reducing antibiotic prescribing in patients with sinusitis and lower respiratory tract infections (RTI)(1) However, we find some issues that merit to be discussed more in depth. Most of the patients included were classified with the diagnosis sinusitis. The diagnostic criteria were based on a history of rhinorrhea and blocked nose plus at least one more of the following symptoms: purulent rhinorrhea, unilateral facial pain, headache, teeth pain, pain when chewing, maxillary/frontal pain when bending over, or worsening of symptoms after initial improvement. According to the paper, the duration of symptoms should have been less than 4 weeks, but there was no lower limit for duration. According to Table 1 half of patients had symptoms for less than 7 days (CRP group) and 8 days (control group). Since patients with symptom duration of less than 1 week are more likely to have common cold than sinusitis it would be interesting to see if the effect of CRP testing was the same after exclusion of patients with assumed common cold, i.e. those with a shorter duration of symptoms.
The authors advised not to prescribe antibiotics when CRP test results were less than 20 mg/L, to give immediate antibiotics when CRP test results were greater than 100 mg/L, and to consider a delayed prescription when CRP levels were between 20 and 99 mg/L. The cutoff points were considered as a recommendation used in combination with the clinical findings from medical history and physical examination when deciding on management. It is, however, surprising that the authors used same cutoff point for all type of RTIs (both upper and lower RTIs). Hansen et al (2) examined CRP values in patients with sinusitis and found that a CRP level of 11-49 was strongly associated (OR 8.9) with a positive culture for Streptococcus pneumoniae or Haemophilus influenzae and cutoff points of 10-25 have been proposed in patients with clinical symptoms and signs of sinusitis(2,3). For lower RTIs, however, much higher cutoff points (>100 mg/L) have been proposed for treating with antibiotics (4,5). We would like to know why did the authors use the same cutoff point (100 mg/L) for all patients with RTIs.
Among patients allocated to “the intermediate” risk group there was a substantial difference in antibiotic treatment rate between the two groups. In the CRP group 22.7% received antibiotics compared to 72.4% in the control group. This striking difference is even more curious when only 40% of the Dutch population find the delayed prescription an acceptable strategy (1). It is not clear why knowing the result of a CRP value between 20 and 99 mg/L can influence patients not to fill an antibiotic prescription. However, other factors than the information about CRP may have played a role. Therefore, it would be relevant to know if both groups were informed alike (except the information about the value of CRP).
Another important issue addressed by Cals et al in this paper is that we are running the risk of encouraging medicalization among patients undertaking this rapid test since more patients in the CRP-assisted group did reconsult in the next month than patients assigned to the control group and the former were also more likely to reconsult for a similar condition in the future.
References
1. Cals JW, Schot MJ, de Jong SA, Dinant GJ, Hopstaken RM. Point-of- care C-reactive protein testing and antibiotic prescribing for respiratory tract infections: a randomized cntrolled trial. Ann Fam Med. 2010;8(2): 124-133.
2. Hansen JG, Hojbjerg T, Rosborg J. Symptoms and signs in culture- proven acute maxillary sinusitis in a general practice population. APMIS. 2009; 117(10):724-729.
3. Young J, Bucher H, Tschudi P, Periat P, Hugenschmidt C, Welge- Lussen A. The clinical diagnosis of acute bacterial rhinosinusitis in general practice and its therapeutic consequences. J Clin Epidemiol. 2003; 56(4):377-384.
4. Falk G, Fahey T. C-reactive protein and community-acquired pneumonia in ambulatory care: systematic review of diagnostic accuracy studies. Fam Pract. 2009; 26(1):10-21.
5. Almirall J, Bolibar I, Toran P, et al. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest. 2004; 125(4):1335-1342.
Competing interests: None declared
Show Less

Competing Interests: None declared.
Published on: (12 April 2010)
Page navigation anchor for Clinical practice guidelines will not foster evidence-based decision-making but relationship-centered interventions may
Clinical practice guidelines will not foster evidence-based decision-making but relationship-centered interventions may
France Legare, Quebec City, Canada
Other Contributors:
We congratulate Dr Cals and colleagues for this study. In line with the literature about the failure to translate evidence into clinical practice,(1) participating family physicians (FPs) in the experimental group were not more likely than FPs in the control group to comply with guidelines indicating when to prescribe antibiotics based on (CRP) point of- care results. For example, in the experimental group, based on the...
Show More

We congratulate Dr Cals and colleagues for this study. In line with the literature about the failure to translate evidence into clinical practice,(1) participating family physicians (FPs) in the experimental group were not more likely than FPs in the control group to comply with guidelines indicating when to prescribe antibiotics based on (CRP) point of- care results. For example, in the experimental group, based on the CRP point of- care results, out of the 129 patients, 73 should not have received a prescription for antibiotics (56 did not), 45 should have received a delayed prescription (22 did) and only 11 should have received a prescription for immediate antibiotics (51 did). These results suggest that FPs may be immune to guidelines when the consultation with the patient is factored in. Interestingly, data shows that in the experimental group, a larger proportion of patients who had received a delayed prescription decided against filling out the prescription than in the control group. This suggests that the active component of the intervention may be understood to occur during the consultation or immediately after. This is in line with the core value of family medicine namely that is it relationship-centered.(2) FPs and their patients may have influenced each others during the consultation while deciding about antibiotics.(3) This in turn may have mediated the impact of the intervention that was planned by the investigators.(4) Moreover, similar to the impact of patient decision aids,(5) the intervention had most of its impact on “uncertain” patients (those who left with a delayed prescription). Therefore, we agree with the authors that it may be the combination of both the FP and the patient sharing the decision that may have contributed to the outcome. We would like to suggest the investigators consider using a General Linear Mixed Model (GLMM) like the GLIMMIX procedure in SAS. One of the advantages of using the GLIMMIX procedure would be to minimise the sources of error by using the Log as the link function instead of the Logit. Given that the observed 95% confidence intervals for the relative risks almost include 1.0, we can not exclude that using the GLMMIX procedure may yield different results. In summary, Dr Cals and his colleagues study emphasises the importance of the consultation when translating evidence into clinical practice. Let’s hope that more health services researchers will value a relationship-centered approach when translating evidence into family medicine practice.
References
1. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients' care. Lancet. 2003; 362: 1225-30.
2. Stange KC, Miller WL, McWhinney I. Developing the knowledge base of family practice. Fam Med. 2001; 33: 286-97.
3. LeBlanc A, Kenny DA, O'Connor AM, Legare F. Decisional conflict in patients and their physicians: a dyadic approach to shared decision making. Med Decis Making. 2009; 29: 61-8.
4. Street RL, Jr., Makoul G, Arora NK, Epstein RM. How does communication heal? Pathways linking clinician-patient communication to health outcomes. Patient Educ Couns. 2009; 74: 295-301.
5. O'Connor AM, Bennett CL, Stacey D, Barry M, Col NF, Eden KB, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev. 2009; CD001431.
Competing interests: None declared
Show Less

Competing Interests: None declared.
Published on: (25 March 2010)
Page navigation anchor for Value of C-reactive protein in elderly and immunocompromised patients unclear
Value of C-reactive protein in elderly and immunocompromised patients unclear
Wim Opstelten, Netherlands
Other Contributors:
Editor,
With respect to the interesting study of Cals et al.(1), we would like to make the following comment.
The identification of patients who need antibiotic treatment for LRTI is in particular difficult in elderly (> 65 years, especially those with chronic pulmonary disease) and immunocompromised patients. In these patients, signs and symptoms of LRTI may be less clear and the immune response (i...
Show More

Editor,
With respect to the interesting study of Cals et al.(1), we would like to make the following comment.
The identification of patients who need antibiotic treatment for LRTI is in particular difficult in elderly (> 65 years, especially those with chronic pulmonary disease) and immunocompromised patients. In these patients, signs and symptoms of LRTI may be less clear and the immune response (including the production of C-reactive protein) delayed or decreased.(2) As the mean age in Cals’ RCT was about 45 years and the percentage of included elderly patients was not mentioned, a sensitivity analysis by age may be inappropriate to extrapolate the results of the study to this age group. Moreover, the definition of the exclusion criterion ‘immunocompromised’ was not defined. Therefore, it is unclear whether their result are also valid in e.g. patients with rheumatic arthritis, COPD, or those who are on a low dosage of corticosteroids.
References
1. Cals JW, Schot MJ, Dinant GJ, Hopstaken RM. Point-of-care C- reactive protein testing and antibiotic prescribing for respiratory tract infections: a randomized controlled trial. Ann Fam Med 2010;8:124-33.
2. McElhaney JE, Meneilly GS, Lechelt KE, Blackley RC. Split-virus influenza vaccines: do they provide adequate immunity in the elderly? J Gerontol 1994;49:M37-43.
Wim Opstelten, MD, PhD
Roeland Geijer, MD, PhD
Dutch College of General Practitioners
Competing interests: None declared
Show Less

Competing Interests: None declared.
Published on: (22 March 2010)
Page navigation anchor for Further details about nature of patient advice needed
Further details about nature of patient advice needed
Tom Fahey, Dublin, Ireland
Other Contributors:
Editor,
We read with interest Cals et al’s randomized controlled trial (RCT) on the assistive value of point of care CRP testing in reducing antibiotic prescribing for patients presenting with respiratory tract infections.[1] Potentially inappropriate antibiotic prescribing for these infections may result in increased antibiotic resistance, inflated costs, and increased side effects.[2]
We would seek a...
Show More

Editor,
We read with interest Cals et al’s randomized controlled trial (RCT) on the assistive value of point of care CRP testing in reducing antibiotic prescribing for patients presenting with respiratory tract infections.[1] Potentially inappropriate antibiotic prescribing for these infections may result in increased antibiotic resistance, inflated costs, and increased side effects.[2]
We would seek additional clarification about the nature of the intervention in terms of recommended decision making in relation to CRP levels for both arms of the RCT. The open design of the RCT is to facilitate physician decision making regarding antibiotic prescribing utilising CRP levels as a diagnostic test alongside findings from the clinical assessment of each individual patient. Similar proportions of patients in the two arms of the RCT were recommended to take immediate, delayed or no antibiotics, suggesting that the incremental value of knowing the CRP reading did not alter physician’s prescribing advice. However, a lower proportion of patients’ in the CRP assisted arm of the RCT filled their delayed prescriptions (22.7% compared to 72.4% in intervention group).
The implications of these findings are that the value of knowing CRP levels does not alter physician management strategies in terms of advice given to patients about taking antibiotics. Indeed, this is consistent with our own systematic review that CRP testing is of limited use in ‘ruling out’ community acquired pneumonia in a community settings.[3] It seems the value of knowing CRP level enables reassurance in an “intermediate” risk group (CRP reading between 20 to 99mg/L) but we are unsure whether the value of CPR and its clinical meaning was conveyed to the intervention arm patients when advice was given in relation to a delayed script. Awareness of CRP level may also influence illness perception in terms of subsequent patient diary reporting and re- consultation rates. Lastly, a systematic review regarding rates of delayed prescriptions being filled in acute respiratory infections concludes that 32% of patients fill these prescriptions.[4] The findings that 72% of patients in the control group filled their prescription in this RCT is not consistent with previous delayed prescribing findings.
We would appreciate further clarification from the authors on these issues.
Yours sincerely,
Emma Wallace (Clinical Research Fellow)
Tom Fahey (Professor) HRB Centre for Primary Care Research, RCSI Medical School, Dublin 2
References
1. Cals JWL, Schot MJC, de Jong SA et al. Point-of-Care C-Reactive Protein testing and Antibiotic Prescribing for Respiratory Tract Infections: A Randomized Controlled Trial. Ann Fam Med 2010;8:124-133.
2. Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD000245. DOI: 10.1002/14651858.CD000245.pub2.
3. Falk G, Fahey T. C-reactive protein and community-acquired pneumonia in ambulatory care: systematic review of diagnostic accuracy studies. Family Practice 2009;26:10-21.
4. Spurling GKP, Del Mar C, Dooley L, Foxlee R. Delayed antibiotics for respiratory infections. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004417. DOI: 10.1002/14651858.CD004417.pub3.
Competing interests: None declared
Show Less

Competing Interests: None declared.
Published on: (17 March 2010)
Page navigation anchor for CRP, Respiratory Tract Infections, Antibiotics, Individuals and Families
CRP, Respiratory Tract Infections, Antibiotics, Individuals and Families
Henry Bloom, MD,CCFP, ABFP, University Heights, OH
In their article, “Point-of-Care C-Reactive Protein{CRP} Testing and Antibiotic Prescribing for Respiratory Tract Infection, a Randomized Controlled Trial,”(1) Cals, et al, appear to show a significant reduction in the use of antibiotics, while getting the same “outcome.” One question, however, is whether the right outcome was looked at. Did others in the family fall ill with the same pathogen more frequently in the CRP...
Show More

In their article, “Point-of-Care C-Reactive Protein{CRP} Testing and Antibiotic Prescribing for Respiratory Tract Infection, a Randomized Controlled Trial,”(1) Cals, et al, appear to show a significant reduction in the use of antibiotics, while getting the same “outcome.” One question, however, is whether the right outcome was looked at. Did others in the family fall ill with the same pathogen more frequently in the CRP group, or in those not treated with antibiotics in either group?
In our own study(2) of 111 episodes of respiratory tract infection, involving 43 families, we used cultures to show what every Family Doctor sees every day, and what any parent can tell you: familial spread of bacterial illness through the family. As well, by exclusion, negative cultures, allowed the inference of viral illness, which we watched as it spread through the family.
The use of the culture in the index patient, enables the doctor to convincingly postpone use of antibiotics, where it seems clinically appropriate (saying that if the culture comes back positive, the doctor will call). As important, for the next member of the family who presents, the doctor can either plausibly postpone antibiotic prescribing, based on the index patient’s negative culture, or be more exact in the choice of antibiotic, based on the sensitivities of the index patient’s positive culture. And our clinical experience would say that this strategy aborts the spread throughout the family of bacterial infections.
What would be ideal would be to repeat Cals, et al’s study, using CRP with and without cultures, looking at familial spread as an outcome. One then would want to look at both the extent of familial spread in each group, and the total numbers of antibiotics given in each group.
1. Cals JWL, Schot MJC, de Jong SAM, et a.. “Point-of Care C-Reactive Protein Testing and Antibiotic Prescribing for Respiratory Tract Infection, a Randomized Controlled Trial.” Ann Fam Med. 2010;8:124- 133.
2. Bloom HR, Zyzanski SJ, Kelly L, et al. Clincial Judgement Predicts Culture Results in Upper Respiratory Infections. J Am Board Fam Pract. 2002; 15:93-100.
Competing interests: None declared
Show Less

Competing Interests: None declared.

Main menu

User menu

Search

Point-of-Care C-Reactive Protein Testing and Antibiotic Prescribing for Respiratory Tract Infections: A Randomized Controlled Trial

Published eLetters

Plain text

Vertical Tabs

Jump to comment:

In this issue

Citation Manager Formats

Related Articles

Cited By...

More in this TOC Section

Similar Articles

Subjects

Content

Info for

Engage

About

Main menu

User menu

Search

Point-of-Care C-Reactive Protein Testing and Antibiotic Prescribing for Respiratory Tract Infections: A Randomized Controlled Trial

Published eLetters

Plain text

Vertical Tabs

Jump to comment:

In this issue

Citation Manager Formats

Jump to section

Related Articles

Cited By...

More in this TOC Section

Similar Articles

Subjects

Content

Info for

Engage

About