Results
The 21 most relevant studies included systematic reviews of randomised controlled trials, cluster randomised controlled trials, and observational and economic evaluations as shown in online supplementary table 1.
The most comprehensive evidence of the value of CRP POCT in patients presenting with symptoms of RTI in primary care in reducing antimicrobial prescribing is reported in a systematic review (Cochrane Review) that concluded ‘Performing a point-of-care CRP test in ambulatory care accompanied by clinical guidance on interpretation reduces the immediate antibiotic prescribing in both adults and children’.38 Nineteen studies used CRP POCT and included 11 RCTs and 8 non-randomised studies reporting on 16 064 patients in total. The Forest plots from this study show highly significant difference towards CRP POCT for antibiotic prescribing at index consultation for all patients, RCTs; all patients, non-randomised studies, RCTs; adults only, if cut-off guidance applied; and RCTs, children only, if cut-off guidance applied.
There was no available evidence to suggest an effect on other patient outcomes or healthcare processes. This is a pivotal publication and included studies until March 2017.
A systematic review of studies reporting reduction of antibiotic prescriptions for ARTIs in primary care found that communication skills training and POCT were the most effective interventions and that trials with initially lower prescription rates were less likely to be successful.39 A narrative review of what factors affect antibiotic prescribing for ARTIs in primary care concluded that widespread adoption of successful strategies in primary care is imperative.40
A cluster randomised to usual care, internet-based training on CRP POCT, internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. Internet-based training in enhanced communication skills remained effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing. However, due to a less intensive follow-up there was very poor take-up of booklets and POCT in the second phase of the study.41
Using CRP POCT in LRTI a multicentre, open-label, randomised, controlled trial in participants aged at least 1 year with a documented fever or a chief complaint of fever resulted in a modest but significant reduction in antibiotic prescribing, with patients with high CRP being more likely to be prescribed an antibiotic, and no evidence of a difference in clinical outcomes.42
A thematic analysis of data from preintervention and postintervention patients and healthcare workers found widespread positive attitudes towards CRP POCT among patients and healthcare workers. Patients’ views were influenced by an understanding of CRP POCT as a comprehensive blood test that provides specific diagnosis that corresponds to notions of good care. Healthcare workers use the test to support their negotiations with patients and to legitimise ethical decisions in an increasingly restrictive antibiotic policy environment.43
In an audit-based study aimed at assessing GPs’ reliance on patient history, examination findings and the influence of the utilisation of POCTs in antibiotic prescribing for sore throat and LRTI, a negative POCT result was negatively associated with antibiotic prescribing and GPs using POCTs attached less weight to clinical criteria.44
In a small feasibility study, patients who would have received antibiotics for RTI were referred by a GP practice to a local pharmacy for CRP POCT. Patients who had a CRP of less than 100 were given a leaflet and told to visit the GP if symptoms did not resolve within 3 weeks. Sixty-three per cent of patients had a CRP value of <5 mg/L and were deemed to have self-limiting illness and not requiring an antibiotic. Ten per cent of the patients had a CRP over 100 mg/L and were recommended to receive an antibiotic. Most CRP tests took an additional 5–10 min from the initial consultation with the GP to the patient’s total consultation time. Almost all patients found the test useful and would recommend it as it provided reassurance that the symptoms were not serious.45
In another pilot study to investigate CRP POCT in a community pharmacy patients accessed the scheme by either referral from GPs, pharmacy staff or self-referral. This study showed high degrees of patient satisfaction with concurrent reduction in unnecessary antibiotic prescribing by 86%.46
In a prospective observational study, Dutch GPs were surveyed about specific antibiotic prescribing following Dutch College of General Practitioners (DCGP) guidance on the use of CRP POCT. The largest variation in prescribing occurred in patients who presented with CRP values between 20 mg/L and 100 mg/L. Most GPs followed the DCGP guidelines and used low CRP values as a negative indicator not to prescribe an antibiotic.47
Paediatrics
In a study to assess whether use of POC CRP by the GP reduces antibiotic prescriptions, children with suspected non-serious LRTI were included and randomised to either use of POC CRP or usual care. Antibiotic prescription rates were measured and compared between groups using generalising estimating equations. The study did not reach the required number of patients and while a small reduction of antibiotics was found, statistical significance was not reached.48
In another study in children with non-severe acute infections, CRP POCT did not influence antibiotic prescribing concluding that systematic CRP POCT without guidance is not an effective strategy to reduce antibiotic prescribing for non-severe acute infections in children in primary care. Eliciting parental concern and providing a safety net without POC CRP testing conversely increased antibiotic prescribing. GPs possibly need more training in handling parental concern without inappropriately prescribing antibiotics.49
In a qualitative study, Dutch GPs' perceptions of the addition of point-of-care CRP testing to the diagnostic process in children with suspected LRTI differed from their perceptions of this in adults. GPs noted that they used POCT CRP in adults for diagnostic certainty, and as a tool to communicate a non-prescription decision. GPs indicated they seldom used POCT CRP in children to convince parents that antibiotics were not necessary. Themes identified included: patient characteristics; vulnerability of the child; clinical presentation; availability of evidence; the impact of the procedure; and use of point-of-care CRP testing as a communication tool.50
These studies are at variance with findings that CRP POCT in children is feasible in primary care and is likely to be acceptable.38 51 However, it will not reduce antibiotic prescribing and hospital referrals until GPs accept its diagnostic value in children.52
Chronic obstructive pulmonary disease
A multicentre, open-label, randomised, controlled trial involving patients with a diagnosis of COPD CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.53
Health economics
Using a decision-analytical model to estimate the cost-effectiveness of testing, compared with standard care, in adults presenting in primary care with symptoms of ARTI, POC CRP testing as implemented in routine practice was less cost-effective than when adhering to clinical guidelines.54 A budget impact model calculated that CRP POCT was more expensive than usual care.55 However, in both studies there were no estimates of the implications for antibiotic resistance nor for Clostridium difficile infection.
Barriers and facilitators to CRP POCT adoption
A qualitative study explored the views of general practice staff on the use of CRP POCT for the management of lower RTIs in England who felt the test could help general practice staff improve patient care and education if incorporated into routine care, but this would need enthusiasts with dedicated POCT instruments or smaller, cheaper, more portable instruments.56
A mathematical model for designing networks of CRP POCT could optimise the cost and travel distance for patients to access testing across a given region.57
A mixed-methods UK study with CRP POCT confirmed costs and funding as important barriers in addition to physical and operational constraints and cited training and the value of a local champion as enablers.58
In a US study to ascertain which POCTs would be most beneficial to add to clinical practice, incorporating CRP POCT with clinical guidelines was felt to strengthen the utility of this test, when there is diagnostic uncertainty.59 A qualitative study highlighted reimbursement and incentivisation, quality control and training, laboratory services, practitioner attitudes and experiences, effects on clinic flow and workload, use in pharmacy and gaps in evidence as barriers to implementation.60 In a South African study, clinicians saw POCTs as potentially useful for positively addressing both clinical and social drivers of the overprescribing of broad-spectrum antibiotics.61
Governmental reviews
The use of CRP POCT may reduce unnecessary antibiotic prescribing (which carries a risk of adverse effects and the development of antibiotic resistance), but seems unlikely in the absence of a funded implementation programme.4
HTA assessments in EU and Ireland have confirmed the value of CRP POCT in helping to reduce antibiotic prescribing in primary care that might address the AMR crisis.62