Editors

PekkaHonkanen

Pneumonia

Essentials

This article deals with pneumonia in adults. A separate article is available on pneumonia in children Pneumonia in Children.
Pneumonia should be considered as a possible diagnosis in a patient who presents with an acute illness with principal symptoms of cough, fever, deteriorating general condition and, particularly in the elderly, confusion and worsening of an underlying disease.
The signs and symptoms are very similar in pneumonia and acute bronchitis but are usually more severe in pneumonia. The two conditions are different degrees of severity of the same disease process.
The diagnosis of pneumonia is based on a chest x-ray.
Pneumonia should initially be assumed to be a bacterial disease, and any treatment prescribed must be effective against pneumococcal infection.
- In outpatient care, amoxicillin is the first choice antimicrobial drug (for patients with penicillin allergy doxycycline, for patients with severe symptoms either moxifloxacin or levofloxacin).
- In hospital care, the first choice is intravenous cefuroxime or penicillin G (for patients with penicillin allergy moxifloxacin or levofloxacin).
- As extensive use of fluoroquinolones involves the risk of problem microbes becoming more common, there must be clear proof of penicillin allergy.
A repeat x-ray should not be taken sooner than 6-8 weeks after recovery. No repeat x-ray is needed if the patient is below 50 years of age, non-smoking, and the response to treatment is good. A repeat x-ray must always be taken if the clinical symptoms have not improved within 1-2 weeks.

Aetiology

The most common causative pathogen of community-acquired pneumonia is Streptococcus pneumoniae, followed by Mycoplasma pneumoniae, Chlamydophila pneumoniae and Haemophilus influenzae.
It is not possible to identify the causative organism on the basis of clinical presentation.
In 30-35% of patients, a viral infection can be detected by a nucleic acid detection test. In these cases, the disease is usually a mixed infection.
The microbial aetiology depends essentially on whether the patient contracted the infection in or out of hospital and whether predisposing aetiological factors are present, e.g. possibility of aspiration, chronic pulmonary disease, immunosuppressive therapy or surgery.

Symptoms and findings

Common signs and symptoms of an acute lower respiratory tract infection include
- cough
- purulent sputum
- fever (often higher than 38.0°C; may be absent in an elderly patient)
- dyspnoea
- wheezing
- chest pain.
Pneumonia should be suspected if, in addition to the above symptoms
- the illness has affected the patient's general health
- the symptoms have emerged rapidly
- the symptoms of respiratory tract infection have worsened again
- the patient has additional risk factors (age, underlying medical conditions).
In the elderly, confusion, abdominal symptoms, overall poor health or worsening of an underlying disease may be the most prominent symptoms. Fever is absent in up to every third patient over 65 years with pneumonia.
Auscultation usually reveals fine crackles or crepitations, but the auscultation findings may also be normal (in one in three patients).

Diagnosis

Pneumonia is likely and antimicrobial treatment should be started if clinical findings are clear (CRP > 100 mg/l, oxygen saturation ≤96%, respiration rate ≥16/min).

Chest x-ray

A definite pneumonia diagnosis is based on chest x-ray. Whenever pneumonia is suspected a chest x-ray is indicated, provided that the investigation is feasible and within reasonable reach. Suggestive evidence regarding some other, possible lung disease is obtained at the same time.
Lack of infiltrates does not exclude pneumonia if the clinical picture and laboratory findings suggest it.

Laboratory tests

A plasma CRP concentration of > 100 mg/l strongly suggests pneumonia. If the plasma CRP concentration is < 20 mg/l and the patient has no symptoms or findings consistent with pneumonia, pneumonia is unlikely Crp Concentration in the Diagnostics of Lower Respiratory Infections.
- Remember: pneumococcal pneumonia may develop very rapidly and the CRP concentration may not yet be increased in the very early stages of the disease. If symptoms have continued for less than 24 hours, CRP concentrations are not a reliable indicator.
If the patient's general condition is poor, plasma potassium, sodium and creatinine, as well as oxygen saturation (or arterial blood gas analysis if the test is available) should be checked.
When pneumonia is suspected in an elderly person, an ECG as well as urine bacterial culture and particle counting are often needed for differential diagnosis.

Other tests

No aetiological tests are needed in outpatient care.
Blood cultures should be done twice for patients admitted to an in-patient ward. Taking a blood culture must not cause a delay in starting the antimicrobial treatment.
The following investigations can be performed at discretion in order to assess the aetiology.
- Pneumococcal urinary antigen; a positive result is quite reliable
- Mycoplasma pneumoniae and Chlamydophila pneumoniae, or even other respiratory bacteria, can be diagnosed by PCR method from a sample obtained from the respiratory tract. In Finland, the diagnosis of these infections has mainly been based on antibody assays.
- Rapid tests for detecting influenza viruses are useful in the early phase of an influenza epidemic before influenza has become more common in the region.
  - Viral aetiology is more reliably determined by PCR methods that allow the detection of as many as 16 different viruses in a sample (respiratory virus antigen detection).
- Legionella urinary antigen test (only detects the Legionella pneumophila serogroup 1 that is most commonly responsible for the disease)

Differential diagnosis

Diseases to be considered in the differential diagnosis of pneumonia are presented in table T1.

Diseases to be considered in the differential diagnosis of pneumonia

Common
Acute bronchitis Acute Bronchitis
Exacerbation of COPD Chronic Obstructive Pulmonary Disease (COPD)
Heart failure Acute Heart Failure and Pulmonary Oedema
Old changes seen in the chest x-ray and erroneously interpreted as a fresh infection (important to compare images taken at different times)
More rare
Tumour Lung Cancers
Pulmonary tuberculosis Diagnosing Tuberculosis
Allergic alveolitis Allergic Alveolitis
Eosinophilic pneumonia Eosinophilic Pneumonia
Drug reaction
Sarcoidosis Sarcoidosis
Atelectasis
Pulmonary infarction
Respirator-induced lung damage
Cryptogenic organizing pneumonia
Pulmonary fibrosis Idiopathic Pulmonary Fibrosis Asbestos-Related Diseases Silicosis
Vasculitis Vasculitides
Radiation pneumonitis Management of Adverse Effects of Radiotherapy

Antimicrobial treatment Empiric Antibiotic Coverage of Atypical Pathogens for Community Acquired Pneumonia in Hospitalized Adults

The choice of antimicrobial treatment in community-acquired pneumonia is presented in tables T2 and T3.

Antimicrobial drugs for community-acquired pneumonia in outpatient care. Adapted from: Acute lower respiratory tract infection in adults, Finnish Current Care Guideline 2015.

Drug	Dose	Notes
First-line drug
Amoxicillin	750 mg - 1 g 3 times daily	Not effective against Chlamydophila pneumoniae or Mycoplasma. Combine with a macrolide or with doxycycline if indicated ¹⁾ .
Second-line drugs (first-line drugs for patients with penicillin allergy).
Doxycycline	100 mg twice daily	When cover for Chlamydophila pneumoniae and Mycoplasma is wanted. Not as sole medication in severe pneumonia
Moxifloxacin	400 mg once daily	Also to be considered if the patient has been treated with other antimicrobial drugs during the past 3 months (excluding treatment for an urinary tract infection) or has travelled abroad or has a severe underlying disease. These drugs increase drug resistance in a number of bacterial species.
Levofloxacin	500 mg (1-)2 times daily or 750 mg once daily

¹⁾Amoxicillin can be combined with a macrolide or with doxycycline. The patient has to be sufficiently informed to ensure that he/she takes both drugs concurrently.

The choice of initial intravenous antimicrobial treatment for community-acquired pneumonia in a hospitalized patient. Source: Acute lower respiratory tract infection in adults, Finnish Current Care Guideline 2015.

Drug	Dose	Notes
First-line drugs
Cefuroxime¹⁾	1.5 g 3-4 times daily intravenously	Effective in many other severe infectionsbesides pneumonia Oral administration is not effective enough.
Penicillin G (benzylpenicillin)¹⁾	2 million IU 6 times daily or 2.5-5 million IU 4 times daily intravenously	For a young fit patient with lobar pneumonia and no underlying diseases Cefuroxime can be replaced with penicillin G as soon as pneumococcal aetiology has been confirmed.
Second-line drugs
Moxifloxacin	400 mg once daily intravenously or orally	Change over to oral administration as soon as possible
Levofloxacin	500 mg twice daily or 750 mg once daily intravenously or orally	Change over to oral administration as soon as possible

¹⁾ May be given in combination with an oral macrolide or doxycycline in order to cover Chlamydophila pneumoniae and Mycoplasma

Any treatment prescribed must be effective against pneumococcal infection. Other causative agents must be considered if there are clinical or epidemiological reasons to suspect their presence. Pneumococcal infection cannot be definitely excluded even during epidemics clearly caused by Mycoplasma or Chlamydophila pneumoniae.

The first dose of oral medication should be given in the doctor's office already.

If the patient's condition does not improve with the first-line drug within 2-4 days, antimicrobial medication that is effective against Chlamydophila pneumoniae and Mycoplasma should be added to the regimen.

Parenteral antimicrobials are indicated for patients whose general condition has deteriorated or who have a concomitant disease that affects the immune system. After intravenous medication, drugs that are used for the treatment of pneumonia at home should be used.

Aspiration pneumonia is treated on a hospital ward with the same principles as community-acquired pneumonia. If treatment response is poor and there is a strong suspicion of aspiration, metronidazole may be combined to the antimicrobial treatment.

Cefalexin is not recommended as first-line treatment in uncomplicated pneumonia because its spectrum is too broad and its efficacy against pneumococci is inferior to that of amoxicillin. It can, however, be considered in a patient with penicillin allergy for further antimicrobial treatment after intravenous administration at a minimum dose of 750 mg 3 times daily.
Ciprofloxacin is not suitable in community-acquired pneumonia as it is not sufficiently effective against pneumococci.
Levofloxacin and moxifloxacin are also effective against pneumococci. However, they should be reserved for patients with reliably, through careful history taking, confirmed penicillin allergy and for use should the resistance of pneumococci against penicillin increase.
- Widespread use of these drugs would also jeopardise the treatment of urinary tract infections and infections caused by Gram-negative bacteria.
As 10-15% of pneumococci are resistant to the macrolides, use of macrolides alone is not recommended. Country/region-specific differences may exist in the level of resistance to antimicrobials.

Other treatment Intra-Pleural Fibrinolytic Therapy in Parapneumonic Effusions and Empyema, Chest Physiotherapy for Pneumonia in Adults

Assess the need for oxygen therapy (pulse oximetry, blood gas analysis) in inpatients.
Treat any dehydration.
Avoid unnecessary antipyretic and antitussive medication.
Treat underlying diseases (heart failure, diabetes).

Indications for hospital treatment

Choice of the place of treatment is principally based on the assessed severity of the pneumonia and the facilities available to carry out the planned treatment.
- Successful outcome of home care depends on the home circumstances and the availability of help with daily activities if the patient's performance capacity is impaired.
In pneumonia with rapid onset (symptoms developing within a few hours), the patient should always be quickly referred to hospital because of suspected pneumococcal disease.
- In patients aged 50 years or less, respiratory rate ≥ 20/min and oxygen saturation ≤ 92% are suggestive of severe disease.
- Moreover, a CRP concentration of more than 100 mg/l may be a sign of severe or quickly progressing pneumonia.
A severe pneumonia should be suspected and the need for hospital treatment considered if the patient has
- any of the following signs of severe pneumonia:
  - confusion or reduced level of consciousness
  - respiratory rate 20/min or higher
  - systolic blood pressure below 90 mmHg
  - pulse rate over 105/min
  - body temperature < 36°C or > 38.5°C
  - blood leucocyte count < 3 × 10⁹ /l or > 15 × 10⁹ /l.
- severe underlying disease (severe pulmonary disease, cancer, hepatic, renal or cardiac failure, cerebrovascular disorder or immunosuppression [prednisone dose 10 mg/day or more] or other immunodeficiency)
- extensive changes in several pulmonary lobes or in both lungs
- poor general condition without the findings described above.
Hospitalisation may be indicated in pneumonia with mild symptoms if the patient presents with any of the following:
- vomiting which prevents the intake of medication
- dyspnoea and other complications
- problems with differential diagnosis
- severe primary disease
- immunosuppression
- unsatisfactory home situation.

Follow-up

It is difficult to predict the course of pneumonia. Regardless of the chosen treatment, follow-up must be arranged for all patients, as well as the possibility of seeking examination and treatment again if recovery does not proceed as expected.
In inpatients, intravenous administration is changed to oral medication as soon as the patient is haemodynamically stable, there are clinical signs of recovery and the patient is able to swallow medication Early Switch and Early Discharge Strategies in Patients with Community-Acquired Pneumonia.
Antimicrobial treatment should continue for 5 to 7 days, at least. Treatment can usually be discontinued after 10 days. Medication must not be withdrawn before the patient has had 2-3 days without fever.
Treatment response is evaluated after 2-3 days. The evaluation is based on the clinical picture. CRP concentration starts to decrease only after 3-4 days.
If there is no response to antimicrobial treatment, the following questions should be dealt with:
- are there signs of a complication; or does the patient possibly have some other disease resembling pneumonia;
- does the treatment cover Chlamydia pneumoniae and Mycoplasma?
Consider any complications in hospitalised or very ill patients (pleural effusion Pleural Effusions and Thoracentesis, empyema, pulmonary abscess). Do not hesitate to consult a specialist.
A repeat x-ray is indicated in patients over 50 and smokers but no sooner than 6-8 weeks from the end of treatment because any changes in the chest x-ray disappear slowly. A repeat x-ray is always indicated no later than after 2 weeks if the symptoms have not improved significantly by that time.
Recovery often takes a long time, and sick leave must be extended accordingly.

Prevention Vitamin C for Pneumonia

Risk groups must receive influenza vaccination.
Pneumococcal conjugate vaccine prevents severe pneumococcal diseases and pneumonia. It is recommended for all persons who have previously had community-acquired pneumonia requiring hospitalization and for persons who are at great risk of acquiring a severe pneumococcal infection or a complication associated with such an infection.
- These include e.g. patients who have
  - chronic cardiac or pulmonary disease
  - diabetes
  - liver failure
  - removed or non-functioning spleen
  - HIV infection or other immunodeficiency
  - undergone organ or tissue transplantation
  - permanent systemic glucocorticoid or other immunosuppressive medication
  - age at least 65 years
  - permanent place in a care institution.
- The vaccine is administered in one dose. No revaccinations are required.
Smoking cessation Smoking Cessation
Hand hygiene

References

NICE Guidance. Pneumonia in adults: diagnosis and management.Clinical guideline [CG191]. Published date: December 2014. Last updated: September 2019 http://www.nice.org.uk/guidance/cg191.
Metlay JP, Waterer GW, Long AC ym. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200(7):e45-e67. [PubMed] http://www.atsjournals.org/doi/full/10.1164/rccm.201908-1581ST

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