Review
Usefulness of aetiological tests for guiding antibiotic therapy in community-acquired pneumonia

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Abstract

The goal with antibiotic therapy in community-acquired pneumonia (CAP) is to cure the patient, ideally without causing side effects and without contributing to the further development of antibiotic resistance. Although patients with severe CAP should be treated with broad-spectrum antibiotics, patients with non-severe CAP should preferably receive pathogen-directed therapy. Rapid aetiological tests, such as sputum Gram stain and urinary antigen tests, are useful for targeting initial pathogen-directed therapy. Non-rapid tests, such as cultures, can subsequently support a switch from initial broad-spectrum therapy to narrow-spectrum therapy and direct therapy changes in case of treatment failure. As conventional diagnostic methods often fail to identify the aetiology of CAP, PCR (polymerase chain reaction) tests for respiratory pathogens have become useful and should be further developed. Based on the test specificities, aetiological tests may provide diagnoses with varying reliability, i.e. definite aetiologies (e.g., blood culture and Legionella urinary antigen test), probable aetiologies (e.g., sputum culture and PCR for Mycoplasma pneumoniae), or possible aetiologies (e.g., culture of nasopharyngeal secretions and PCR for Streptococcus pneumoniae). A definite or probable aetiology can often be used to target antibiotic therapy.

Introduction

Community-acquired pneumonia (CAP) is a common and sometimes severe disease with an annual incidence of about 1% [1] and a mortality rate of 0–30% [2]. Thus, selection of antibiotic therapy in CAP is important for the emergence of antibiotic resistance in society and for the outcome in the patients [3]. Ideally, antibiotic therapy should be directed against the pathogen that is causing the pneumonia. However, as the aetiology is often not known at presentation, patients must initially receive empirical antibiotic treatment.

This review will focus on how aetiological tests can be used to guide antibiotic therapy in adult patients with CAP.

Section snippets

Empirical antibiotic treatment in community-acquired pneumonia

In patients with severe CAP, under-use of antibiotics and use of narrow-spectrum antibiotics can be associated with a risk of death [3]. Thus, international guidelines [4], [5], [6], [7], [8], [9] recommend treatment with broad-spectrum antibiotics for severe CAP, as defined by the CURB-65 (confusion, urea, respiratory rate and blood pressure – aged 65 or more) score or Pneumonia Severity Index rules. As CAP due to multiple pathogens can occur [10], [11], patients with severe CAP should be

Prediction of aetiology based on clinical, laboratory, radiological and epidemiological factors

Although single clinical, laboratory and radiological features cannot reliably predict CAP aetiology [11], [21], by combining a number of features the possibility of making a correct prediction increases. Acute onset of illness, pleuritic chest pain, high leukocyte count, and lobar chest X-ray infiltrates are associated with pneumococcal aetiology, while young age, gradual onset of illness, and non-productive cough have been associated with mycoplasmal aetiology [22], [23], [24]. With a

The role of aetiological testing for antimicrobial therapy in CAP

A major role of aetiological testing in CAP is to enable the use of pathogen-directed therapy, and thus reduce the use of broad-spectrum antibiotics. As it is recommended that the antibiotic therapy should be started within 4 h of hospital admission [4], [8], rapid tests with a shorter analysis time can be used to influence the choice of first-line antibiotic therapy. Sputum Gram strain, urinary antigen tests, and real-time PCR for respiratory pathogens are examples of such rapid tests. Less

Definite, probable and possible aetiological diagnoses

When an aetiological test is positive, it is important to question the reliability of the result. Depending on the test specificities, positive results of different tests can be categorised to represent definite, probable or possible CAP aetiologies [27]. Based on a classification by Marston et al. [27], a new categorisation of bacterial aetiologies, which includes additional and newer tests, is presented in Table 1. Tests with high specificities can provide definitive bacterial aetiologies and

Blood culture

Although blood culture has a low sensitivity for the confirmation of CAP aetiology [29], it has a high specificity, and a positive result provides a definite diagnosis. As bacteraemia in CAP is associated with significant mortality [2], blood cultures should always be obtained from hospitalised CAP patients, in order to identify bacteraemia and thus enable optimal pathogen-directed therapy. Meehan et al. [30] found collection of blood culture within 24 h from hospital arrival to be associated

Experience of first-line antibiotic therapy guided by rapid tests

The usefulness of sputum Gram stain and S. pneumoniae urinary antigen test for selecting first-line antibiotic treatment has been discussed in Sections 6.6 Sputum Gram stain, 6.7 Pneumococcal urinary antigen. In a prospective randomised study, van der Eerden et al. [12] compared pathogen-directed therapy with empiric broad-spectrum antibiotic therapy in 303 patients with CAP of different severities. Pathogen-directed therapy was based on the clinical presentation (n = 72), or on the results of

Experience of antibiotic therapy guided by non-rapid aetiological testing

Among CAP patients with an identified aetiological agent, therapy changes were carried out according to these findings in 12% in a study by Lidman et al. [13] and in 32% in a study by Ewig et al. [78]. In a study of patients with severe CAP [79], the results of microbiological investigations led to a change in therapy in 42% of cases. The commonest change was simplification of the treatment.

Economic considerations of diagnostic testing

The main argument against aetiological testing is cost. However, among hospitalised CAP patients, traditional aetiological testing contributes only to a small proportion of the total cost [80]. The largest cost in the management of CAP is the in-patient cost [81]. If the CAP aetiology is known in the early course of disease, optimal therapy with a low risk of adverse events can be given, and the hospital stay can probably be short. In addition, if the aetiology is known, it is possible that the

Recommendations by international guidelines

International guidelines recommend increased efforts to identify the causative organism in severe CAP [4], [5], [6], [7], [8] (Table 2), although therapy should not be delayed if there is difficulty in obtaining adequate samples [5]. As the patient is improving, the initial broad-spectrum therapy can be de-escalated or narrowed, according to the results of the diagnostic tests [4], [5], [8]. However, it is recommended that the therapy should not be narrowed until concerns regarding mixed

Conclusion

In order to cure CAP patients without causing unnecessary side effects and without contributing to the development of antibiotic resistance, antibiotic therapy should be carefully selected. Although patients with severe CAP should be treated with broad-spectrum antibiotics, patients with non-severe CAP should preferably receive pathogen-directed therapy. While rapid aetiological tests may be useful for targeting initial pathogen-directed therapy, non-rapid tests may support switch from broad-

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