Point-of-care tests for lower respiratory tract infections

Treating respiratory tract infections is one of the most common reasons for prescribing antibiotics. However, antibacterial therapy is often unnecessary, particularly for viral or other upper respiratory tract infections, and the inappropriate use of antibiotics is closely linked to the emergence of resistance in key respiratory and other pathogens.1,2 Identifying the aetiology of lower respiratory tract infections (LRTIs) has traditionally been slow. Bacterial cultures take at least a day, viral cultures even longer, and, even with aggressive investigation for aetiology, the cause is found only about half the time.3 Thus, treatment of LRTIs is generally empirical, with clinicians reliant on previous aetiology and microbiology studies to guide their choice of therapy, although each of these can be misleading. In Australia, there has been only one published study of the aetiology of community-acquired pneumonia (CAP) — a 1989 study that assessed 106 patients in a single hospital.4 Thus, for the most part, clinicians have depended on international data, which may have uncertain relevance to Australia. Published resistance rates may be misleading. For example, the rate of resistance in consecutive isolates of Streptococcus pneumoniae must be tempered by the knowledge that this organism can be the cause of anywhere between 8% and 75% of episodes of CAP,5 and there has never been a documented microbiological failure when treating pneumococcal pneumonia or bacteraemia with adequate doses of penicillin.6 Although some retrospective studies suggest that combination therapy (such as a β-lactam and a macrolide) may reduce mortality in pneumococcal infections, this is yet to be confirmed in prospective studies.7

One way to help address these issues is to use new, rapid, point-of-care diagnostic techniques. If a general practitioner or emergency physician is quickly able to identify that a respiratory tract infection is of viral origin, then he or she may feel more confident about not prescribing antibiotics and may be able to institute appropriate isolation precautions or even specific antiviral therapy. Early identification that the cause is pneumococcal can allow the clinician to be comfortable treating with a simple, cheap narrow-spectrum β-lactam such as benzylpenicillin or amoxycillin in conjunction with either a macrolide or doxycycline, in line with the recommendations of the Australian antibiotic guidelines.8 Rapid diagnosis of CAP caused by Legionella can facilitate the early institution of appropriate therapy for this potentially fatal disease.9

A summary of rapid point-of-care tests (POCTs) is given in Box 1.

Benefits of POCTs: Obtaining a rapid diagnosis of influenza has several potential benefits. Less money is spent on other investigations, antibiotic use may be reduced, and length of stay in the emergency department and hospital may be shortened.30 As anti-influenza medications have greater efficacy if started within 48 hours of symptom onset, rapid diagnosis allows the more judicious use of these medications, which is especially useful in view of the current scarcity of some of these agents.31 With the current concern about the threat of pandemic influenza from the H5N1 avian strain affecting many parts of the world, the availability of rapid and accurate tests for influenza is particularly desirable. For patients in hospitals or supported accommodation facilities, early diagnosis allows the appropriate use of infection control methods, which can reduce the number of secondary cases within the institution.30,32

Limitations of POCTs: The sensitivity of POCTs for influenza is lower than that of other tests such as the polymerase chain reaction (PCR) or viral culture. Also, POCTs do not give information on the influenza subtype, and it is not yet clear whether all tests will detect H5N1 viruses. As they do not contribute to knowledge of circulating strains, it is important to confirm diagnoses — particularly in the non-epidemic situation — with other, more accurate tests such as PCR. This requires a second sample being obtained from the patient. POCTs generally have a higher sensitivity in children than adults and for nasopharyngeal aspirates (NPAs), which can be more difficult and unpleasant to obtain, rather than throat swabs.13 In addition, the tests are not currently Medicare rebatable when used at the point of care and have a shelf life of about 12–18 months, so cost is certainly an issue. Overall, they are probably more useful at times when the likelihood of influenza is relatively low, such as between epidemics. In times of higher likelihood of influenza illness, empirical antiviral treatment is likely to be more cost-effective.32

POCTs for RSV require a nasopharyngeal swab, NPA or nasal washings. These are intended for use in neonatal or paediatric populations and are less accurate when used in adults.25 The benefits of such tests are the rapid institution of isolation precautions to reduce nosocomial transmission, a possible reduction in antibiotic use, and the option of using specific antiviral therapy such as ribavirin.26,29 The simplest test is the BinaxNOW RSV test (Binax, Scarborough, Me, USA), which is performed in the same way as the BinaxNOW influenza test. Other simple tests for RSV are the SAS RSV test (SA Scientific, San Antonio, Tex, USA), the Clearview RSV test (Unipath Limited, Bedford, UK), and the QuickVue RSV test (Quidel Corporation, San Diego, Calif, USA). Like the POCTs for influenza, sensitivities are moderate but generally over 75%, and specificities are over 90%.25-29

PCR tests can be performed on many types of respiratory specimens and have the advantage of being able to test concurrently for many respiratory viruses with accuracy greater than the POCTs.35 However, they are more expensive, are not fully Medicare rebatable, and take longer to provide a result, mainly because of delays in specimen transport.

Because of the time delay and previous limited usefulness of routine investigations to diagnose LRTIs, there has been a tendency by clinicians to treat these infections empirically with broad-spectrum antibiotics. The increasing emergence of antibiotic-resistant organisms and the limited number of new antibiotics in the development pipeline mean that this approach needs to be re-evaluated. One potential solution is to use rapid POCTs to identify the causative pathogen, such that either no antibacterials are needed (eg, in the case of viral infection) or patients can be safely treated with cheap, narrow-spectrum agents, such as benzylpenicillin or amoxycillin (eg, in the case of pneumococcal pneumonia). Furthermore, the early institution of appropriate infection control or public health measures can be facilitated when influenza, RSV, or Legionella are diagnosed rapidly.

2 QuickVue Influenza A + B test

3 BinaxNOW Streptococcus pneumoniae urinary antigen test showing a positive result on the left and a negative result on the right