ReviewUsefulness of aetiological tests for guiding antibiotic therapy in community-acquired pneumonia
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-
References (82)
- et al.
Impact of initial discordant treatment with beta-lactam antibiotics on clinical outcomes in adults with pneumococcal pneumonia: a systematic review
Mayo Clin Proc
(2006) - et al.
Comparative clinical and laboratory features of Legionella with pneumococcal and mycoplasma pneumonias
Br J Dis Chest
(1987) - et al.
Can Legionnaires disease be diagnosed by clinical criteria? A critical review
Chest
(2001) - et al.
The value and complications of percutaneous transthoracic lung aspiration for the etiologic diagnosis of community-acquired pneumonia
Chest
(1999) - et al.
Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients
Lancet
(2002) Commentary to ‘Community-acquired pneumonia due to Escherichia coli’ by Marrie TJ et al.
Clin Microbiol Infect
(1998)- et al.
Intra and inter technologist variability in the quality assessment of respiratory tract specimens
Diagn Microbiol Infect Dis
(2000) - et al.
Diagnostic fiberoptic bronchoscopy and protected brush culture in patients with community-acquired pneumonia
Chest
(1990) - et al.
New developments in the diagnosis of bloodstream infections
Lancet Infect Dis
(2004) - et al.
Performance of six influenza rapid tests in detecting human influenza in clinical specimens
J Clin Virol
(2007)
Influenza: historical aspects of epidemics and pandemics
Infect Dis Clin North Am
Laboratory diagnosis of Mycoplasma pneumoniae infection
Clin Microbiol Infect
Microbiological testing and outcome of patients with severe community-acquired pneumonia
Chest
Cost analyses of community-acquired pneumonia from the hospital perspective
Chest
Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland
Am J Epidemiol
Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis
JAMA
Use of broad-spectrum antimicrobials for the treatment of pneumonia in seriously ill patients: maximizing clinical outcomes and minimizing selection of resistant organisms
Clin Infect Dis
Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults
Clin Infect Dis
Canadian guidelines for the initial management of community-acquired pneumonia: an evidence-based update by the Canadian Infectious Diseases Society and the Canadian Thoracic Society
Clin Infect Dis
Guidelines for the management of adult lower respiratory tract infections
Eur Respir J
Swedish guidelines for the management of community-acquired pneumonia in immunocompetent adults
Scand J Infect Dis
Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumonia
Neth J Med
Multiple pathogens in adult patients admitted with community-acquired pneumonia: a one year prospective study of 346 consecutive patients
Thorax
Etiology of community-acquired pneumonia: impact of age, comorbidity, and severity
Am J Respir Crit Care Med
Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study
Thorax
Limited value of routine microbiological diagnostics in patients hospitalized for community-acquired pneumonia
Scand J Infect Dis
A European study on the relationship between antimicrobial use and antimicrobial resistance
Emerg Infect Dis
“Collateral damage” from cephalosporin or quinolone antibiotic therapy
Clin Infect Dis
Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter?
Clin Infect Dis
An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome
Clin Infect Dis
Effectiveness of beta lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis
BMJ
Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials
Arch Intern Med
New and emerging etiologies for community-acquired pneumonia with implications for therapy: a prospective multicenter study of 359 cases
Medicine (Baltimore)
Rapid aetiological diagnosis of pneumonia based on routine laboratory features
Scand J Infect Dis
Prediction of microbial aetiology at admission to hospital for pneumonia from the presenting clinical features: British Thoracic Society Pneumonia Research Subcommittee
Thorax
Usefulness of the Streptococcus pneumoniae urinary antigen test in the treatment of community-acquired pneumonia
Clin Infect Dis
Incidence of community-acquired pneumonia requiring hospitalisation. Results of a population-based active surveillance study in Ohio
Arch Intern Med
Etiologic diagnosis of adult bacterial pneumonia by culture and PCR applied to respiratory tract samples
J Clin Microbiol
Quality of care, process, and outcomes in elderly patients with pneumonia
JAMA
Nonresolving pneumonia and mimics of pneumonia
Med Clin North Am
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2014, New England Journal of MedicineCitation Excerpt :The generalizability of this method to patients without AIDS in developed countries remains to be determined. Scoring systems may predict the severity of disease and help determine whether a patient with CAP requires hospitalization or admission to an intensive care unit (ICU).46,47 Validated instruments include the Pneumonia Severity Index (PSI) (Tables S1 and S2 in the Supplementary Appendix, available with the full text of this article at NEJM.org),48 the CURB-65 score (a measure of confusion, blood urea nitrogen, respiratory rate, and blood pressure in a patient ≥65 years of age),49 and the guidelines of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS).14,50