Point-of-care tests to inform antibiotic prescribing

 

 

by Alastair Hay, Professor of Primary Care, Centre for Academic Primary Care, University of Bristol

This article was first published in the BMJ.

The tests have potential but more evidence is needed. 

Given the global concerns(1) about antibiotic resistance, antimicrobial stewardship is essential to preserve the future effectiveness(2) of antibiotics. Healthcare practitioners must balance public and patient health, ensuring that only patients who need antibiotics receive them, and that they receive an antibiotic to which their infection is susceptible, at the optimum time, dose, and duration. Whether to prescribe an antibiotic is a key issue for clinicians treating respiratory infections in the community.

Point-of-care tests provide results in time to inform treatment. For respiratory infections, the tests can identify the presence of a microbe(3-5) or measure markers of a host’s response to a microbe, such as C reactive protein or procalcitonin, in finger prick quantities of blood.

The only point-of-care tests currently recommended in the UK are urine dipstick for suspected urinary tract infections by Public Health England(6) and C reactive protein for suspected pneumonia by the National Institute for Health and Care Excellence(7). Although dipstick, C reactive protein, and procalcitonin point-of-care tests are widely used internationally, the use of C reactive protein and procalcitonin remains rare in UK primary care.

Existing evidence shows that C reactive protein point-of-care tests are highly effective, with absolute risk reductions in antibiotic prescribing of 15% to 22% in patients with acute uncomplicated lower respiratory tract infection (number needed to test to prevent one antibiotic prescription (NNT) of 6.6. to 4.5 (8,9) and 20% (NNT 5) in patients with exacerbation of chronic pulmonary obstructive disease.(10) Existing evidence for procalcitonin is mixed(11-13), and no studies of procalcitonin in acute uncomplicated lower respiratory tract infection have been previously conducted in primary care.

Two novel, high quality randomised trials strengthen this evidence. The first, by Boere and colleagues, shows C reactive protein tests to be effective in Dutch nursing home residents with acute lower respiratory tract infections (diagnosis at doctor’s discretion)(14). The tests were
associated with an absolute risk reduction of 28.8% (NNT 3.5) in antibiotic prescribing. The second paper, by Lhopitallier and colleagues, shows procalcitonin tests to be effective in adults presenting to Swiss primary care with clinical pneumonia—defined as acute onset
cough and at least one of patient reported fever for four or more days; patient reported shortness of breath; elevated respiratory rate; or abnormal focal lung sounds on auscultation(15). Testing was associated with an unadjusted absolute risk reduction of 30.5% (NNT 3.3; cluster adjusted 26%, NNT 3.8).

Neither trial reached the prespecified sample size, but both observed effects large enough to leave little doubt. The Swiss trial also reported a reduction in the use of chest radiography(15). Both trials were rigorously conducted and independent of test manufacturers (though it should be noted that point-of-care tests were provided at no cost).

Both studies chose to randomise clusters (general practices, nursing homes) rather than individual patients. Randomising clusters minimises contamination and maximises opportunities to estimate real world effects, but the price is post-randomisation bias: in the Dutch study, for example, the intervention group comprised double the number of participants recruited to the control group, and intervention participants appeared to be less unwell. Nevertheless, the lower antibiotic prescribing rates were robust to adjustments for variations in clinician and resident baseline characteristics.

Other study characteristics should be considered when interpreting these findings. Firstly, the timing of the point-of-care tests: in the nursing home study, clinicians decided if residents had a lower respiratory tract infection before doing a test.(14) Similarly in the Swiss study, general practitioners screened patients for eligible infections before testing.(15) These results would likely change if testing preceded clinical assessment.

Secondly, cost. In the UK, machines for C reactive protein typically cost more than £1000 ($1383; €1172) plus £5 per test for primary care practices wanting to provide this service. Few do. Although NICE considers C reactive protein to be cost effective for lower respiratory tract infections(7), its models have not taken account of antimicrobial resistance costs(16), nor the potential to medicalise self-limiting illness (whereby patients attend for testing when developing similar future illnesses)(17). Less information is available for procalcitonin point-of-care tests. One study used £11 per test, but it was not clear whether this was the cost of the machine or the test, or both.(18)

Thirdly, many will assume that point-of-care tests are accurate—both for sensitivity (low risk of missed infections) and specificity (minimising unnecessary antibiotic use). However, while they appear diagnostically helpful for patients with severe infections admitted to hospital,(19) C reactive protein and procalcitonin have been shown to add little or no diagnostic value over symptoms and signs in patients with mild infections.(20,21) Their mechanism of action may be the low prevalence of abnormal results: 5.9% of patients in one arm of the Swiss study had an increased procalcitonin level,(15) thereby favouring a decision to not prescribe antibiotics more than nine times out of 10. Other studies have observed similar rates of elevated C reactive protein,(8-10) leading to the hypothesis(22) that point-of-care tests could be principally acting as behaviour change tools by modifying patient expectations.

Finally, larger studies with longer periods of follow-up are necessary to detect uncommon safety events and to determine whether using point-of-care tests has unintended consequences, such as medicalising self-limiting illnesses.(17)

In conclusion, high quality trials suggest that point-of-care tests can be useful tools for antimicrobial stewardship in a growing range of patients and settings, but more evidence is needed to establish how they work, evaluate cost effectiveness, and confirm safety. In the meantime, clinicians should not be distracted from the information already available to them: by taking a good history and, when appropriate, performing a careful examination.

References

1 World Health Organization. Global Action Plan on Antimicrobial Resistance, 2015.
https://www.who.int/publications/i/item/9789241509763.

2 NICE. Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use,
2015. https://www.nice.org.uk/guidance/ng15.

3 Biomerieux. BIOFIRE® FILMARRAY® Respiratory 2.1 plus Panel: Biomerieux; 2020
https://www.biomerieux-diagnostics.com/filmarrayr-respiratory-panel. [accessed 02/10/2020].

4 GenMark Dx. Respiratory Pathogen Panels, 2020. [cited 2020 02/10/2020]. https://www.genmarkdx.com/int/solutions/panels/eplex-panels/respiratory-pathogen-panel/.

5 QIAGEN. QIAstat-Dx Respiratory SARS-CoV-2 Panel, 2020. https://qiastat-dx.com/row/wp-content/uploads/sites/3/2020/03/PROM-15948-001_1121481_FLY_QIAstat-Dx-SARS-CoV-2-CEIVD_0320_ROW.pdf [accessed 02/10/2020].

6 PHE. Diagnosis of urinary tract infections. Quick reference tool for primary care for consultation
and local adaptation. Public Health England, 2020. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/927195/UTI_diagnostic_flowchart_NICE-October_2020-FINAL.pdf

7 NICE. Pneumonia: Diagnosis and Management of Community- and Hospital-Acquired Pneumonia
in Adults. National Institute for Health and Care Excellence, 2014.
https://www.nice.org.uk/guidance/cg191

8 Cals JWL, Butler CC, Hopstaken RM, Hood K, Dinant GJ. 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. doi: 10.1136/bmj.b1374 pmid: 19416992

9 Little P, Stuart B, Francis N, etalGRACE consortium. Effects of internet-based training on antibiotic
prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised,
factorial, controlled trial. Lancet 2013;382:1175-82.
doi: 10.1016/S0140-6736(13)60994-0. pmid: 23915885

10 Butler CC, Gillespie D, White P, etal. C-Reactive Protein Testing to Guide Antibiotic Prescribing
for COPD Exacerbations. N Engl J Med 2019;381:111-20.
doi: 10.1056/NEJMoa1803185. pmid: 31291514

11 Briel M, Schuetz P, Mueller B, etal. Procalcitonin-guided antibiotic use vs a standard approach
for acute respiratory tract infections in primary care. Arch Intern Med 2008;168:2000-7, discussion
2007-8. doi: 10.1001/archinte.168.18.2000 pmid: 18852401

12 Schuetz P, Wirz Y, Sager R, etal. Procalcitonin to initiate or discontinue antibiotics in acute
respiratory tract infections. Cochrane Database Syst Rev 2017;10:CD007498.
doi: 10.1002/14651858.CD007498.pub3. pmid: 29025194

13 Huang DT, Yealy DM, Filbin MR, etalProACT Investigators. Procalcitonin-Guided Use of Antibiotics
for Lower Respiratory Tract Infection. N Engl J Med 2018;379:236-49.
doi: 10.1056/NEJMoa1802670. pmid: 29781385

14 Boere TM, van Buul LW, Hopstaken RM, etal. Effect of C reactive protein point-of-care testing
on antibiotic prescribing for lower respiratory tract infections in nursing home residents: cluster
randomised controlled trial. BMJ 2021;374.

15 Lhopitallier L, Kronenberg A, Meuwly J-Y, etal. Procalcitonin and lung ultrasonography point-of-care
testing to determine antibiotic prescription in patients with lower respiratory tract infection in
primary care: pragmatic cluster randomised trial. BMJ 2021;374.

16 Smith R, Coast J. The true cost of antimicrobial resistance. BMJ 2013;346:f1493.
doi: 10.1136/bmj.f1493 pmid: 23479660

17 Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL. Reattendance and
complications in a randomised trial of prescribing strategies for sore throat: the medicalising
effect of prescribing antibiotics. BMJ 1997;315:350-2.
doi: 10.1136/bmj.315.7104.350 pmid: 9270458

18 Bell JM, Shields MD, Agus A, etal. Clinical and Cost-Effectiveness of Procalcitonin Test for
Prodromal Meningococcal Disease-A Meta-Analysis. PLoS One 2015;10:e0128993.
doi: 10.1371/journal.pone.0128993. pmid: 26053385

19 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
2004;39:206-17. doi: 10.1086/421997. pmid: 15307030

20 Le Bel J, Hausfater P, Chenevier-Gobeaux C, etalESCAPED study group. Diagnostic accuracy of
C-reactive protein and procalcitonin in suspected community-acquired pneumonia adults visiting
emergency department and having a systematic thoracic CT scan. Crit Care 2015;19:366.
doi: 10.1186/s13054-015-1083-6. pmid: 26472401

21 van Vugt SF, Broekhuizen BD, Lammens C, etalGRACE consortium. Use of serum C reactive
protein and procalcitonin concentrations in addition to symptoms and signs to predict pneumonia
in patients presenting to primary care with acute cough: diagnostic study. BMJ 2013;346:f2450.
doi: 10.1136/bmj.f2450. pmid: 23633005

22 Thornton HV, Khalid T, Hay AD. Point-of-care testing for respiratory infections during and after
COVID-19. Br J Gen Pract 2020;70:574-5. doi: 10.3399/bjgp20X713561. pmid: 33199292

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