Individual clinical symptoms and signs have poor predictive value to differentiate pneumonia from bronchitis.45–48 Emphasis has shifted from differentiating viral from bacterial infections to differentiating those patients who are more likely to benefit from antibiotics from those who are unlikely to benefit.49
Biomarkers and point-of-care tests
Two biomarkers potentially useful in differentiating self-limiting from more serious infections are C-reactive protein (CRP) and procalcitonin. A systematic review of the diagnostic value of CRP testing in LRTIs,50 and a more recent comparison of CRP and procalcitonin testing for LRTI,51 found neither test sufficiently sensitive or specific to differentiate bacterial pneumonia from bronchitis. However, biomarker testing may be helpful in safely reducing antibiotic prescribing for LRTI, mainly through ruling out the need for antibiotic treatment.
Procalcitonin testing has been evaluated in an open randomised controlled trial of 1359 patients with LRTI symptoms (68% diagnosed with community-acquired pneumonia [CAP]) presenting to six EDs in Switzerland where 97.5% were treated as inpatients. Patients randomised to treatment based on procalcitonin monitoring received significantly fewer antibiotics without resulting in differences in clinical outcomes or adverse events.52
Biomarkers need to be available as a point-of-care tests (POCT) to be useful for guiding empirical antibiotic treatment in primary care. CRP is currently available as a POCT that can be done in the surgery in about 4 minutes, and CRP POCTs are widely used in some parts of Europe (but not the UK) to guide antibiotic prescribing decisions. Procalcitonin POCT tests are being developed.
A community-based trial of CRP POCT and communication skills training found that both interventions resulted in independent statistically significant reductions in antibiotic prescribing for LRTI, without adversely affecting recovery or patient satisfaction.53 However, this efficacy study required all patients to be CRP tested and the outcome was antibiotic prescribing in a limited number of consultations.
In everyday practice, GPs will not test all patients, and further studies are needed to determine the effect of providing testing facilities to practices: how often would they use it? Would it have the same impact on antibiotic prescribing?
Qualitative research exploring GPs attitudes to POCTs found enthusiasm for a hypothetical POCT finger-prick blood test that could distinguish viral from bacterial infection.54 GPs emphasised that such a test would be most valuable in ‘selling’ decisions not to prescribe antibiotics to patients. Clinicians were concerned about the limited additional useful information from further tests compared to clinical diagnosis alone, that patients might deteriorate even if the tests correctly identified a viral aetiology, lack of pragmatic research evidence supporting uptake, and felt that the tests would be only ever be useful for a limited number of patients. Additional concerns included time pressures, apparatus maintenance and quality control, cost, and possible objections from patients, especially children.54
In UK primary care, antibiotics are prescribed for over 60% of patients presenting with sore throat.5 Empirical therapy based only on clinical score use results in inappropriate antibiotic prescribing.39,55 Rapid Streptococcal A throat (RSAT) swab POCTs are commonly used in parts of Europe and the US in an attempt to better target antibiotics. The best performing RSAT tests have a sensitivity of over 90% and a specificity of over 95% compared to throat swab cultures.39,56,57 However, the interpretation of a positive GAS result is complicated by asymptomatic carriage. Between 8–52% of children and adolescents are healthy carriers of GAS.58 Carriage is higher in younger children.
A Swiss study of 372 consecutive adults presenting to an ED with a Centor score of 2–4 found that RSAT testing had high sensitivity (91%) and specificity (95%) for detecting GAS compared to culture, and that systematic RSAT testing in this group was more cost- effective than empirical treatment, selective RSAT testing based on symptoms, or systematic culture.39
POCTs can rapidly detect certain viruses. A systematic review of four studies based in EDs concluded that use of rapid viral diagnostic tests for children presenting with acute febrile respiratory illness resulted in a significant reduction in chest X-rays, and a non-statistically significant trend towards reduced use of antibiotics and blood tests.59 Larger trials are required.
Rapid POCTs for influenza A and/or B60 along with tests for respiratory syncitial virus (RSV)61 are widely used in the US. The World Health Organization (WHO) advises rapid influenza POCT use at the beginning of the influenza season or an influenza outbreak to influence clinical decisions and contribute to clinical awareness. The WHO, however, recognises that testing most people during high influenza activity is impractical.62
POCTs for Bordetella pertussis and mycoplasma are in development, but none of these are in routine use in the UK.