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Diagnosis and management of community-acquired pneumonia 

Diagnosis and management of community-acquired pneumonia
Chapter:
Diagnosis and management of community-acquired pneumonia
Author(s):

Antoni Torres

and Adamantia Liapikou

DOI:
10.1093/med/9780199600830.003.0116
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date: 05 December 2020

Key points

  • The microbial pattern of the severe community-acquired pneumonia (SCAP) has changed, with Streptococcus. pneumoniae still the leading pathogen, but a decrease in atypical pathogens, especially Legionella, and an increase in viral and polymicrobial pneumonias.

  • At least two blood samples should be drawn for culture and urinary antigen tests for Legionella pneumophila and S. pneumoniae performed. For intubated patients, an endotracheal aspirate and bronchoscopic samples should be obtained. Polymerase chain reaction (PCR) techniques in respiratory samples and in blood is a promising new method for the detection of viruses and atypical pathogens.

  • New variables, such as hypoglycaemia and thrombocytosis, and a biomarker-procalcitonin will be useful for predicting ICU admission in patients with CAP.

  • Combination treatment offers an advantage over monotherapy by expanding the antimicrobial coverage and improving survival among critically-ill patients with bacteraemic pneumococcal illness. The recommended antibiotic regimen in depends of the presence of Pseudomonas aeruginosa infection.

  • In unresponsive patients, careful re-evaluation of treatment, particularly the initial choice of antibacterials, and further extensive and invasive diagnostic efforts are warranted.

Introduction

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, and the most common infectious cause of death in the developed world [1]‌. In general, the mortality of patients with CAP who require admission to the intensive care unit (ICU) increases to 20–50%. Nearly all patients who die as a consequence of severe CAP develop severe sepsis or septic shock. Approximately 50% of CAP admissions to Spanish ICUs are associated with septic shock.

Aetiology

The spectrum of causal pathogens in severe pneumonia is broader than that in non-severe cases. S. pneumoniae is still the leading pathogen, followed by H. influenzae, S. aureus, L. pneumophila, Enterobacteriaceae, especially Escherichia coli, Klebsiella species, and P. aeruginosa [2]‌. Bacteraemia is more common than CAP and up to 20% of severe CAP episodes are caused by polymicrobial infection.

Viruses are the most common aetiological agents after S. pneumoniae. Easily transmissible viruses such as influenza, metapneumovirus (hMPV), respiratory syncytial virus (RSV) and adenovirus are most common.

In 2009, a new H1N1 strain of influenza A virus emerged, causing a pandemic. Rapidly progressive viral pneumonia, affecting mainly young, obese patients represented the primary cause of ICU admission with mortality ranging from 17.3% to 46% among different sites [3]‌.

In patients admitted in the ICU the most common aetiologies were S. pneumoniae (62%), atypical pathogens (14%) and polymicrobial aetiologies (11%). The most frequent polymicrobial pattern was S. pneumoniae and viral infection, particularly influenza virus [4]‌.

There is a classical correlation of influenza virus infection and pneumonia due to S. aureus and S. pneumoniae.

The microbial pattern of the severe CAP has changed over the years, with the decrease of atypical pathogens, especially Legionella and the increase of viral pneumonia [5]‌. This may be due to improvement in diagnostic tools, such as PCR techniques. A large number of micro-organisms other than S. pneumoniae must be considered, especially Pseudomonas aeruginosa, and CA—MRSA.

  • The risk factors for Pseudomonas pneumonia [6]‌ include:

  • Recent hospitalization.

  • Frequent (>4 courses per year) or recent administration of antibiotics (last 3 months).

  • Severe disease (FEV1 < 30%) and oral steroid use (>10 mg of prednisolone daily in the last 2 weeks).

Accordingly, the risk factors for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), an emerging problem, are participating in contact sport, living in crowded or unsanitary conditions, intravenous drug abuse, and male homosexuality.

Diagnosis

Clinical presentation

Severe CAP is characterized as an acute febrile illness with severe respiratory failure (PO2/FiO2 < 250) requiring invasive or non-invasive ventilation. The patient with sepsis or septic shock from CAP presents with mental confusion, hypotension with the need for vasopressors, tachypnoea, tachycardia, or organ dysfunction as renal failure.

Often the severity reflects a progressive pneumonia with complicated pleural effusion or empyema, or metastatic infection as pericarditis, endocarditis.

Often severe CAP presents with decomposition of an underlying comorbidity such as chronic obstructive pulmonary disorders (COPD), diabetes, congestive heart failure, chronic liver, or renal insufficiency.

Radiographic evaluation

A chest radiograph is required to establish the diagnosis, suggest the aetiological agent, extent, or complications of CAP, prognosis, and to aid in differentiating CAP from other common causes of cough and fever, such as acute bronchitis.

The radiograph of severe CAP consists more often of multilobar infiltrates or a rapid increase in the size of infiltrates>50% during the first day of treatment. Moreover, the chest X-ray may show complications of pneumonia as pleural effusion or abscess formation.

Microbiological diagnosis

Diagnostic efforts to isolate a defined pathogen are necessary, as the results may influence both initial treatment and secondary therapy after initial treatment failure. However, the responsible pathogen is not isolated in up to 50% to 60% of patients with severe CAP [1]‌.

The recommendations of IDSA/ATS for microbiological diagnosis are summarized in Table 116.1.

Table 116.1 Recommendations IDSA/ATS and ERS for microbiological diagnosis of SCAP

1.

Pre-treatment Gram stain and culture of expectorated sputum should be performed only if a good-quality specimen can be obtained and quality performance measures for collection, transport, and processing of samples can be met.

Moderate recommendation; level II evidence.

2.

Patients with severe CAP, should have at least two blood samples drawn for culture, urinary antigen tests for Legionella pneumophila and S. pneumoniae performed, and expectorated sputum samples collected for culture. For intubated patients, an endotracheal aspirate sample should be obtained.

Moderate recommendation; level II evidence.

3.

Diagnostic thoracentesis should be performed in hospitalized patients with CAP when a significant (as judged by the admitting physician) pleural effusion is present.

A3; consistent evidence, level 3.

4.

Bronchoscopic sampling of the lower respiratory tract can be considered in intubated patients and selected non-intubated patients, where gas exchange status allows.

A3; consistent evidence, level 3.

Reproduced from Mandell LA et al., ‘Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults’, Clinical Infectious Diseases, 2007, 44(Suppl. 2), pp. S27–72, by permission of Oxford University Press. Data from Woodhead M et al., 'Guidelines for the management of adult lower respiratory tract infections', Clinical Microbiological Infections, 2011, 17(Suppl. 6), pp. E1–59.

Sputum samples

A culture from a purulent sputum specimen of a bacterial species compatible with the morphotype observed in the Gram stain should be considered for confirmation of the species identification and antibiotic susceptibility testing. The sensitivity of sputum Gram stain was 82% for pneumococcal pneumonia, 76% for staphylococcal pneumonia and 79% for Haemophilus influenzae pneumonia, with specificities ranging from 93 to 96% [7]‌.

In addition to routine cultures, a specific request for culture of respiratory secretions on buffered charcoal yeast extract agar to isolate Legionella species may be useful in areas where Legionella is endemic, as well as in patients with a recent travel history [1]‌. Sputum cultures for Legionella spp. should always be attempted for patients who are Legionella urine antigen positive in order to provide isolates for epidemiological typing and comparison with isolates from putative environmental sources.

During bronchoscopy in severe CAP, bronchoalveolar lavage (BAL) quantitative culture (cut-off 104 cfu) is a sensitive method for aetiological diagnosis (resistant microorganism, polymicrobial, unusual pathogen). In mechanical ventilation a BAL or protected sheath brush (PSB)/BAL have to be taken from the very beginning and may be useful in guiding therapy even performed during antibiotic treatment.

PCR techniques increased the total viral yield five-fold compared with direct fluorescence antibody assay in the respiratory samples of critically-ill patients [8]‌. This rapid tool minimizes the proportion of undiagnosed severe CAP, especially in immunocompromised patients, and guides treatment towards a more specific antibiotic regimen.

Blood cultures

Although the overall yield of blood cultures is probably less than 20% in patients hospitalized for SCAP, the positivity of the results and the likelihood of changes in treatment based on the results, increases with severity.

Immunological methods

The S. pneumoniae urinary antigen test in adults has a sensitivity of 65–100% and a specificity of 94%. This test should also be considered whenever a pleural fluid sample is obtained in the setting of a parapneumonic effusion [6]‌. In the diagnosis of CAP caused by L. pneumophila urinary antigen detection for serotype 1 has a sensitivity of almost 80% and a specificity approaching 100% [1].

Paired serology for infections caused by M. pneumoniae, C. pneumonia, and Legionella sp. is more useful in epidemiological studies than clinical practice.

Real-time PCR (rt-PCR) assay detected S. pneumoniae DNA in 85.3% of patients with positive blood culture findings, whereas blood culture findings were positive in only 50% of the patients with detectable S. pneumoniae DNA [9]‌. This study confirms the superior sensitivity of PCR in blood and the association between a high quantitative bacterial genomic load of S. pneumoniae in blood samples and increased risk of death.

A Finish study [10] proved that sputum is clearly superior to both nasopharyngeal aspirates and throat swabs for reliable detection of M. pneumoniae by PCR.

Definition of severity

Many studies of the epidemiology of patients with CAP have demonstrated the importance of assessing severity of illness and stratifying patients on the basis of their risk of mortality.

The pneumonia severity index (PSI) and CURB-65 have low sensitivity and specificity for predicting ICU admission compared with the predictive power of mortality in patients with CAP [11].

Furthermore, in comparison with PSI, the CURB-65 has been shown to outperform generic sepsis and early warning scores [12].

IDSA/ATS issued guidelines on the management of CAP include specific criteria (Box 116.1) to identify patients for ICU admission [1]‌. Other models specific to severe CAP have been developed.

Reproduced from Mandell LA et al., ‘Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults’, Clinical Infectious Diseases, 2007, 44(Suppl. 2), pp. S27–72, by permission of Oxford University Press.

There is considerable clinical and research interest in the use of novel biomarkers to diagnose and classify CAP. Of the novel biomarkers, most attention has been focused on procalcitonin. Ramirez et al. [13], in a recent study of 685 patients with CAP, assessed biomarkers for the prediction of ICU admission and the IDSA/ATS guidelines minor criteria for severe CAP. Inflammatory biomarkers (C-reactive protein (CRP), tumour necrosis factor-a, procalcitonin and interleukin-6) identified patients needing ICU admission. Patients with severe CAP by minor criteria and low levels of procalcitonin may be safely admitted to wards.

Available simple biomarkers also have prognostic significance. Hypoglycaemia on admission is associated with nearly three-fold greater inpatient mortality, unaffected by the presence of diabetes [14]. Thrombocytosis may also be a risk factor for 30-day mortality. Hypoglycaemia and thrombocytosis are not presently in the list of IDSA/ATS minor criteria for severe CAP, but may need to be considered.

Empirical treatment: algorithms

Recommendations for antibiotic treatment for severe CAP are based on illness severity, frequency of specific pathogens, local microbial resistance patterns, and drug safety profiles.

In patients with CAP and septic shock, delay must not be more than 1 hour after diagnosis [6]‌.

Empirical recommended therapy for severe CAP is listed in Box 116.2.

a Ceftazidime + penicillin G coverage for S. pneumonia.

b Levofloxacin 750 mg/24 hours or 500 mg bd is an alternative.

Reproduced with permission from Woodhead M et al., ‘Guidelines for the management of adult lower respiratory tract infections’, Clinical Microbiology and Infection, 2011, 17(Suppl. 6), pp. E1–59 © 2011 Woodhead et al. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Combination treatment offers an advantage over monotherapy by expanding the antimicrobial coverage and by improving survival among critically-ill patients with bacteraemic pneumococcal illness [15]. The recommended antibiotic regimen consists of a β‎-lactam (preferably intravenously) with a macrolide or with a respiratory fluoroquinilones, especially ciprofloxacin or levofloxacin.

If the patient has risk factors for Pseudomonas infection the combination of an antipseudomonal β‎-lactam with macrolide+ aminoglycoside or an antipseudomonal β‎-lactam with ciprofloxacin is the favourable treatment [6]‌.

The role of glucocorticoids in severe CAP is still controversial with positive [16] and negative [17] studies. Melvis et al. [18] reported dexamethasone added to antibiotic treatment can reduce length of hospital stay, but not mortality in a population of CAP hospitalized patients.

Low molecular heparin should be given in patients with acute respiratory failure [A3, recommendation].

Several studies indicate that non-invasive ventilation (NIV) may also work in patients with pneumonia, particularly in patients with COPD. NIV has been shown to reduce intubation in patients with ARDS in 54% of treated cases [6]‌.

Definitive adjusted treatment

Table 116.2 lists the recommended antibiotic therapies for the most important pathogens in severe CAP, according to ERS/ESCMID guidelines [6]‌. Panton–Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) or CA-MRSA cause severe pneumonia with rapid lung cavitation and multi-organ failure. The recommended antibiotic treatment for this necrotizing pneumonia includes the combination of intravenous linezolid, clindamycin, and rifampicin [1,6]. Antibiotic resistance among S. pneumoniae is the main concern owing to the dominance of this organism as a cause of severe CAP, and because penicillin and macrolide resistance are frequently linked. The prevalence of S. pneumoniae strains resistant to penicillin dropped to 10% or lower in most reports. In patients with pneumococcal pneumonia resistant (low-level) to penicillin a new formulation of co-amoxiclav acid (2000/125 instead of 875–1000/125), offers the advantage of higher penicillin dosing [19].

Table 116.2 Therapy of specific microorganisms in CAP

Pathogen

Recommended treatment

Highly resistant S. pneumoniae (MIC > 8 mg/dL)

Levofloxacin, moxifloxacin, vancomycin, teicoplanin, linezolid

MSSA

Flucloxacillin, cephalosporin ii, clindamycin, levofloxacin, moxifloxacin

MRSA

Vancomycin, teicoplanin +/– rifampicin linezolid, clindamycin(if sensitive)

Ampicillin-resistant Haemophilus influenzae

Aminopenicillin plus B-lactamase inhibitor levofloxacin, moxifloxacin

Mycoplasma, Chlamidophila pneumoniae

Doxycycline, macrolide, levofloxacin, moxifloxacin

Legionella pn.

Macrolide (azithromycin preferred), levofloxacin, moxifloxacin +/– rifampicin

Coxiella burnetti

Doxycycline, levofloxacin, moxifloxacin

Acinetobacter baumanii

Cefalosporin III + aminoglycoside, ampicilin-sulbactam

Reproduced with permission from Woodhead M et al., 'Guidelines for the management of adult lower respiratory tract infections', Clinical Microbiology and Infection, 2011, 17(Suppl. 6), pp. E1–59 © 2011 Woodhead et al. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

In pneumococci, erythromycin MICs >0.5 mg/L predict clinical failure. The prevalence of resistance in many countries compromises the efficacy of macrolides in the treatment of pneumococcal infection [1,6]. In patients with risk factors for P. aeruginosa, meropenem offers advantages over imipenem because of the option to increase the dose significantly up to 3.2 g. Patients at risk of CAP through P. aeruginosa should always be treated by two antipseudomonal drugs in order to reduce the chance of inadequate treatment.

The emergence of new influenza virus subtypes has rekindled the interest in the clinical course and outcome of patients with influenza-associated pneumonia. The implementation of early (<2 days) antiviral therapy was associated with lower mortality in ventilated patients with 2009 H1N1. Apart from neuraminidase inhibitors such as oseltamivir and zanamivir for pneumonia caused by influenza viruses, antibacterial agents targeting S. pneumoniae and S. aureus are necessary.

Response to treatment

For patients initially admitted to the ICU, the risk of failure to respond to therapy is already high. As many as 40% will experience deterioration even after initial stabilization in the ICU. The inadequate response depends on factors related to initial severity, with the causative organism and host characteristics [1]‌.

Non-responding pneumonia occurring in the first 72 hours of admission is usually due to antimicrobial resistance or an unusually virulent organism or a host defence defect. Non-responsiveness after 72 hours is usually due to a complication (empyema, endocarditis, acute respiratory distress syndrome). The evaluation of non-responding pneumonia depends on the clinical condition.

The percentage of treatment failure in severe CAP is 6–15%.The causes of non-responding pneumonia are classified according to the aetiology as infectious, non-infectious, and of unknown origin.

In hospitalized CAP, infections are responsible for 40% of non-responding CAP. The most frequent micro-organisms found are S. pneumoniae, Legionella, P. aeruginosa and S. aureus. Micro-organisms may show resistance against antibiotics prescribed or may develop resistance during therapy. Unusual micro-organisms requiring specific antibiotic treatment other than that recommended in the guidelines include Mycobacteria, Nocardia spp., anaerobes, fungi, Pneumocystis jirovecii, and others [20]. Non-infectious diseases include neoplasms (especially alveolar cell cancer), pulmonary haemorrhages, bronchiolitis obliterans, and organizing pneumonia, eosinophilic pneumonia, hypersensitivity pneumonitis, and drug-induced lung disease.

Careful re-evaluation of treatment, particularly the initial choice of antibacterials, and further diagnostic efforts are warranted. New microbiological and imaging studies (CT of the chest) must be performed to rule out other alternative diagnoses. If simpler procedures do not provide a rapid diagnosis, invasive techniques (i.e. bronchoscopy) are recommended in most cases of non-responding pneumonia. Both PSB and BAL sampling should be done during the same procedure.

Changing of the initial empiric antibiotic regimen with a broader spectrum antibacterial coverage is the optimal management.

References

1. Mandell LA, Wunderink RG, Anzueto A, et al. (2007). Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clinical Infectious Diseases, 44(Suppl. 2), S27–72.Find this resource:

2. Falguera M, Carratalà J, Ruiz-Gonzalez A, et al. (2009). Risk factors and outcome of community-acquired pneumonia due to Gram-negative bacilli. Respirology, 14(1), 105–11.Find this resource:

3. Martin-Loeches I, Rodriguez A, Bonastre J, and the H1N1 SEMICYUC Working Group. (2011). Severe pandemic (H1N1)v influenza A infection: report on the first deaths in Spain. Respirology, 16(1), 78–85.Find this resource:

4. Cillóniz C, Ewig S, Ferrer M, et al. (2011). Community-acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis. Critical Care, 15(5), R209.Find this resource:

5. Choi SH, Hong SB, Ko GB, et al. (2012). Viral infection in patients with severe pneumonia requiring intensive care unit admission. American Journal of Respiratory and Critical Care Medicine, 186(4), 325–32.Find this resource:

6. Woodhead M, Blasi F, Ewig S, et al. (2011). Guidelines for the management of adult lower respiratory tract infections. Clinical Microbiological Infections, 17(Suppl. 6), E1–59.Find this resource:

7. Anevlavis S, Petroglou N, Tzavaras A, et al. (2009). A prospective study of the diagnostic utility of Sputum Gram stain in pneumonia. Journal of Infection, 59, 83–9.Find this resource:

8. Aramburo A, van Schaik S, Louie J, et al. (2011). Role of real-time reverse transcription polymerase chain reaction for detection of respiratory viruses in critically ill children with respiratory disease: Is it time for a change in algorithm? Pediatric Critical Care Medicine, 12(4), e160–5.Find this resource:

9. Rello J, Lisboa T, Lujan M, et al. (2009). Severity of pneumococcal pneumonia associated with genomic bacterial load. Chest, 136(3), 832–40.Find this resource:

10. Templeton KE, Scheltinga SA, Graffelman AW, et al. (2003). Comparison and evaluation of real-time PCR, real-time nucleic acid sequence-based amplification, conventional PCR, and serology for diagnosis of Mycoplasma pneumoniae. Journal of Clinical Microbiology, 41(9), 4366–71.Find this resource:

11. Chalmers JD, Mandal P, Singanayagam A, et al. Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis. Intensive Care Medicine, 37(9), 1409–20. [Review.]Find this resource:

12. Barlow G, Nathwani D, and Davey P. (2007). The CURB65 pneumonia severity score outperforms generic sepsis and early warning scores in predicting mortality in community-acquired pneumonia. Thorax, 62, 253–9.Find this resource:

13. Ramírez P, Ferrer M, Martí V, et al. (2011). Inflammatory biomarkers and prediction for intensive care unit admission in severe community-acquired pneumonia. Critical Care Medicine, 39, 2211–17.Find this resource:

14. Gamble JM, Eurich DT, Marrie TJ, and Majumdar SR. Admission hypoglycemia and increased mortality in patients hospitalized with pneumonia. American Journal of Medicine, 123, 556, e11–16.Find this resource:

15. Martínez JA, Horcajada JP, Almela M, et al. (2003). Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clinical Infectious Diseases, 36, 389–95.Find this resource:

16. Confalonieri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. American Journal of Respiratory and Critical Care Medicine, 171(3), 242–8.Find this resource:

17. Snijders D, Daniels JM, de Graaff CS, et al. (2010). Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial. American Journal of Respiratory and Critical Care Medicine, 181, 975–82.Find this resource:

18. Meijvis SC, Hardeman H, Remmelts HH, et al. (2011). Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet, 377(9782), 2023–30.Find this resource:

19. File TM, Garau J, Jacobs MR, et al. (2005). Efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) in adults with community acquired pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant strains. International Journal of Antimicrobial Agents, 25, 110–19.Find this resource:

20. Menendez R and Torres A. (2007). Treatment failure in community-acquired pneumonia. Chest, 132(4), 1348–55.Find this resource: