Nonbacterial community – acquired pneumonia

Nonbacterial community – acquired pneumonia

Pneumonia caused by viruses, fungi and the atypical organisms that do not look like pus on a film, how each one shows, and why the antibiotic that works for pneumococcus often does not.

Viral pneumonia, from infection to diffuse alveolar damage

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A film in three scenes on a white page. A cluster of alveoli round a small airway, the respiratory bronchiole, which comes in from the upper left, is cut open towards the viewer, so the thin pink walls between the alveoli show in section, like a sponge cut through. First, small sea-green virus particles come down the airway; the pink cells lining the alveoli, nearest the airway first, swell and darken, set more particles free beside them, and disappear, while the walls begin to redden. Second, the walls between the alveoli grow thick and deeper pink, and small blue-grey lymphocytes gather inside them, while the air spaces stay empty. Third, a pale green membrane forms on the inside of the alveoli, lining them, and some alveoli fill with pale teal fluid.

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The virus kills the lining

Scenes

About this film

Many viruses that reach the alveoli, influenza among them, kill the cells lining them, and the body's response, mostly lymphocytes in the walls rather than neutrophils in the air spaces, thickens the walls between the alveoli: an interstitial pneumonia, which is why the chest film shows diffuse hazy shadows rather than one solid lobe. In severe cases the dead lining is replaced by hyaline membranes and the alveoli flood: diffuse alveolar damage, the typical pathology of the acute respiratory distress syndrome.

Simplified: not to scale: cells and virus particles drawn far larger than life, and far fewer; the cells and particles drawn only on the cut face, as a section through lung shows them, with the capillaries in the walls shown only by the walls' colour; the lining cells, lymphocytes and virus particles drawn as dots of their colours, and the two kinds of lining cell drawn as one; one cluster of alveoli going all the way to diffuse alveolar damage, which only the most severe viral pneumonias reach; many stay in the airways or stop at interstitial inflammation; days squeezed into seconds.

1 source
  1. Corrin B, Nicholson AG. Pathology of the Lungs, 3rd edition. Churchill Livingstone, 2011. Chapter 5, Infectious diseases: viral infections.
Contents6 sections

At a glance

  1. "Nonbacterial" pneumonia is mostly viral, with fungi in the immunocompromised and in some regions. The syllabus pairs it with the atypical pneumonias (Mycoplasma, Chlamydia, Legionella, Coxiella), which are bacteria but behave differently, so they are covered here.
  2. Mycoplasma and Chlamydia pneumonia start gradually with headache, malaise and a dry cough, with few chest signs, a patchy or bilateral film and an often normal white count; Legionella is abrupt and severe. The pattern is a teaching aid, not a test. β-lactams are useless against these organisms; macrolides, doxycycline and fluoroquinolones work.
  3. Mycoplasma comes in waves every few years in schoolchildren and young adults and can cause haemolysis, rashes and neurological problems. Legionella is waterborne and severe, with hyponatraemia and gut symptoms; the urinary antigen finds it.
  4. Influenza, SARS-CoV-2 and RSV are the important viruses. They can cause a primary viral pneumonia or open the way to a bacterial one, and Staph. aureus after influenza is the dangerous example.
  5. Treat influenza with oseltamivir as early as possible. In COVID-19, give oxygen and dexamethasone when oxygen is needed. Most viral pneumonias need only support.

Definition and overview

Nonbacterial community-acquired pneumonia means pneumonia acquired outside hospital that is not due to the usual pyogenic bacteria. Strictly, it is viral (and in some places fungal or, rarely, parasitic). The syllabus puts it next to the bacterial form, and in teaching it is bundled with the atypical pneumonias, organisms that do not cause the lobar, pus-filled picture of pneumococcus and that do not respond to penicillins. Several of these are bacteria. This topic covers both groups, so that every cause of community-acquired pneumonia that is not typical bacterial pneumonia is in one place.

The groups differ in how they are caught and treated, but the illness that results shares much: a respiratory illness that is often preceded by a viral-type prodrome, a dry cough, patchy or diffuse shadows rather than a single dense lobe, and little to find on the chest.

Etiology and pathophysiology

GroupOrganismWhere it comes from
Atypical bacteriaMycoplasma pneumoniaeperson to person by droplets, in families, schools, barracks; epidemics every 3 to 5 years
Chlamydia pneumoniaeperson to person, mild, common in young adults
Chlamydia psittacipsittacosis, from parrots, pigeons and poultry, by dried droppings
Coxiella burnetiiQ fever, from sheep, goats and cattle, by dust and aerosol of birth products
Legionella pneumophilaLegionnaires' disease, from water: showers, hot tubs, cooling towers; not from person to person
Virusesinfluenza A and Bseasonal epidemics; A also causes pandemics
SARS-CoV-2since 2019; pandemic, now endemic
respiratory syncytial virus (RSV), human metapneumovirus, parainfluenza, rhinovirus, adenoviruswinter epidemics; children and older adults
varicella-zoster viruschickenpox in adults, pregnancy, smokers
FungiHistoplasma, Coccidioides, Blastomycesendemic mycoses, from soil and bird or bat droppings in certain regions

Modern PCR testing shows that viruses are found in a large proportion of adults admitted with pneumonia. In a large American study, rhinovirus (9 per cent) and influenza (6 per cent) were found more often than S. pneumoniae (5 per cent), and no pathogen was found in more than six patients in ten.

Atypical bacteria

Mycoplasma pneumoniae is the smallest free-living bacterium and has no cell wall. It attaches to the respiratory epithelium by an adhesin, damages the cilia, and the damage and the host's immune response produce the illness; this explains why the lung picture is worse than the bacterial burden would suggest, and why immune phenomena (cold agglutinins, rashes, neurological and cardiac effects) are common. Legionella is a Gram-negative bacillus that survives in warm water and in amoebae. It is inhaled in aerosol and multiplies inside alveolar macrophages, where β-lactams do not reach it, and it causes a severe pneumonia with multisystem effects on the liver, kidney, brain and gut. Chlamydia and Coxiella are obligate intracellular organisms, and for the same reason out of the reach of penicillins.

Viruses

A respiratory virus infects the epithelium of the airway or alveolus. Many, such as influenza and adenovirus, kill the cell directly, while others, such as RSV and measles, make it proliferate, and the immune response then adds injury. In primary viral pneumonia the virus itself reaches the alveoli: the walls become inflamed and oedematous with a mononuclear infiltrate, and in the worst cases a diffuse alveolar damage like that of the acute respiratory distress syndrome (ARDS) follows. In secondary bacterial pneumonia the virus has stripped the cilia and impaired the macrophages, so that S. pneumoniae, Staph. aureus and H. influenzae invade. Influenza A can change its surface proteins in two ways:

  • antigenic drift, small point mutations that cause the yearly epidemics; and
  • antigenic shift, a reassortment of gene segments between human and animal (avian or swine) viruses, which produces a new subtype that few people are immune to and which can cause a pandemic.

SARS-CoV-2 enters cells through the ACE2 receptor. In some patients the lung injury is followed by a dysregulated inflammatory response, microvascular thrombosis and a prolonged ARDS.

Alveolar and interstitial pneumonia
Two round fields of lung under the microscope, side by side, each a pink sponge of thin walls round many small air spaces, with small red capillaries cut across in the walls. In the first, the typical bacterial pneumonia: the walls are thin, but every air space is filled with a pale rose fluid, and in it sit many small pale blue neutrophils, each with a nucleus in three lobes, and here and there a red cell. In the second, a viral pneumonia: the walls are clearly thicker, small pale blue lymphocytes, almost all nucleus, sit inside them, and the air spaces between them are empty white.

Point at a name or a part to light it.

Typical bacterial pneumonia fills the air spaces: protein-rich fluid with neutrophils and red cells takes the place of air, and the lung becomes solid. Viruses, and Mycoplasma, inflame the walls instead: oedema and lymphocytes thicken the walls between the alveoli while the air spaces stay largely clear of pus, so the chest film shows patchy or diffuse shadows rather than one dense lobe, and there may be little to find on examining the chest.

Simplified: not to scale: the cells drawn larger than life against the alveoli, and fewer; the exudate drawn as a pale fluid without its fibrin, and the walls without the cells that line them; each pattern drawn pure, though they often mix: a viral pneumonia can fill the air spaces when severe, a bacterial one can follow it, interstitial pneumonias may hold some oedema fluid and macrophages in their air spaces, and not every 'atypical' organism gives this pattern: Legionella and psittacosis fill the air spaces; one field standing for each kind of pneumonia, which in the lung is patchy.

1 source
  1. Corrin B, Nicholson AG. Pathology of the Lungs, 3rd edition. Churchill Livingstone, 2011. Chapter 5, Infectious diseases: lobar pneumonia, viral infections and mycoplasmal pneumonia.

Clinical features

Mycoplasma and the other atypical organisms

Mycoplasma starts slowly after an incubation of two to three weeks, with malaise, headache and sore throat, and then a dry, irritating cough that can last for weeks. The patient is often well enough to be at work ("walking pneumonia"). There are few chest signs and the film looks worse than the patient. Extrapulmonary features include:

  • rashes: erythema multiforme and erythema nodosum, and rarely Stevens–Johnson syndrome;
  • cold agglutinin haemolytic anaemia;
  • myocarditis and pericarditis;
  • neurological problems: meningoencephalitis, Guillain–Barré syndrome and cerebellar ataxia; and
  • arthralgia and myalgia.

Legionella has an incubation of 2 to 10 days, sometimes up to two weeks. The illness is abrupt and often severe: high fever, dry cough, headache, confusion, and diarrhoea or abdominal pain, with a relative bradycardia. The laboratory pointers are lymphopenia, hyponatraemia, hypoalbuminaemia and raised liver enzymes; creatine kinase, creatinine and CRP are often raised too. The film shows rapidly spreading consolidation, often more than one lobe, and respiratory failure and renal failure are common. Ask about travel, hotels, cruise ships, spas, and a recent change in water plumbing.

Chlamydia pneumoniae gives a mild illness, often with hoarseness and sore throat, and a prolonged cough. Psittacosis (C. psittaci) follows contact with birds and begins with a flu-like illness, severe headache, high fever and a dry cough, with splenomegaly and a relative bradycardia, and sometimes hepatitis. Q fever presents after 2 to 4 weeks as a fever with a headache and myalgia, and then pneumonia or hepatitis; chronic Q fever, many months later, causes culture-negative endocarditis.

Viral pneumonia

Influenza starts abruptly with fever, shivering, muscle aches and severe headache, a sore throat and a dry cough; the cough can last weeks, and tiredness and low mood can last months. Pneumonia can be:

  • primary viral, with breathlessness within days, bilateral shadowing and hypoxaemia, which can progress to ARDS, especially in pregnancy, obesity, heart and lung disease, and the pandemic 2009 H1N1 virus; or
  • secondary bacterial, with a second fever after an apparent recovery, a productive cough, and focal consolidation. Staph. aureus is rarer but the most severe (mortality up to 20 per cent, and over half in Panton–Valentine leucocidin-positive necrotising pneumonia).

COVID-19 ranges from a minor illness to bilateral pneumonia. Fever, cough, loss of smell and taste and breathlessness are typical, and some patients become very hypoxic while remaining comfortable ("silent hypoxaemia"). CT shows bilateral peripheral ground-glass opacities. Thromboembolism is common in severe disease.

RSV and human metapneumovirus cause bronchiolitis in infants and, in older adults and the immunocompromised, an influenza-like illness that can end in pneumonia and a flare of COPD or heart failure. Adenovirus can cause a pneumonia that is clinically like that of Mycoplasma, and a severe one in the immunocompromised and in military recruits. Varicella pneumonia appears a few days after the rash in adults, especially pregnant women, smokers and the immunosuppressed, and can be fatal. Rarer causes include the Middle East respiratory syndrome coronavirus (MERS), avian influenza viruses such as H5N1, and hantavirus (the cardiopulmonary syndrome occurs in the Americas, so a travel history is the clue).

Fungal pneumonia

Endemic mycoses cause a self-limiting influenza-like or atypical pneumonia in healthy people who live in or travel to the region: histoplasmosis (the Ohio and Mississippi valleys, Latin America, parts of Africa and Asia, and caves with bats or birds), coccidioidomycosis ("valley fever", the American Southwest, northern Mexico and parts of Central and South America) and blastomycosis. Mild histoplasmosis or coccidioidomycosis in a healthy person often settles without treatment, but a heavy exposure, or an immunocompromised patient, gives an acute severe pneumonia or a disseminated infection; blastomycosis is treated even when mild. In a European patient, ask about travel. Fungal pneumonia in the immunocompromised (Pneumocystis, Aspergillus) is covered in hospital-acquired pneumonia.

Diagnosis and management

Diagnosis

The routine tests of CAP apply: chest X-ray, blood tests, oxygen saturation and CURB65 or CRB65. Clues pointing toward a non-typical cause are a gradual onset, a dry cough, extrapulmonary features, a normal white count (in Legionella, a low lymphocyte count and a low sodium instead), an epidemic, and the exposure history. Specific tests:

CauseTest
Influenza, SARS-CoV-2, RSV and other respiratory virusesmultiplex PCR of a nose and throat swab (or a lower respiratory sample)
Legionellaurinary antigen (detects L. pneumophila serogroup 1 only); PCR or culture of a lower respiratory sample, on special charcoal yeast agar
MycoplasmaPCR of a throat swab or sputum; serology (IgM, or a four-fold rise in IgG); cold agglutinins; blood count and Coombs test if anaemic
Chlamydia species, Coxiellaserology and PCR
Endemic mycosesurinary or serum antigen, serology, culture, and histology

Routine microbiological tests are unnecessary in low-severity CAP, but a legionella urinary antigen is considered in moderate or high-severity disease when there are risk factors, and hospital inpatients have viral swabs, which also help infection control. A low procalcitonin supports a viral cause but does not exclude a bacterial one.

Treatment

  • Atypical bacteria. Because these organisms have no wall or live inside cells, the antibiotic must enter cells and block protein synthesis or DNA replication. The choices are a macrolide (clarithromycin, azithromycin), doxycycline or a fluoroquinolone (levofloxacin, moxifloxacin). For Legionella, a fluoroquinolone or azithromycin, for 7 to 10 days (longer if immunocompromised); for Mycoplasma, a macrolide or doxycycline, and doxycycline or a fluoroquinolone if a macrolide fails or resistance is likely (macrolide resistance is common in East Asia and still uncommon in Europe); for psittacosis and Q fever, doxycycline. The usual 5-day course, the combination with amoxicillin in moderate disease, and the alternatives are in the treatment of pneumonias.
  • Influenza. Oseltamivir 75 mg twice daily for five days, started as soon as possible in outpatients at risk (the benefit is greatest in the first 48 hours) and in hospital patients whatever the length of illness; longer courses are considered in the severely ill or immunocompromised. Baloxavir, a single dose, is licensed for uncomplicated influenza in outpatients; it added nothing to a neuraminidase inhibitor in hospital patients and is not recommended routinely for them. Corticosteroids are not recommended in influenza pneumonia, unlike COVID-19. Add antibiotics when a bacterial infection is likely (a second fever, focal consolidation), covering S. pneumoniae and Staph. aureus. Isolate hospital patients. Contacts at risk can be given oseltamivir.
  • COVID-19. Oxygen, and dexamethasone 6 mg daily for up to ten days in patients who need oxygen, with an IL-6 inhibitor (tocilizumab) or baricitinib in patients with progressing hypoxia and inflammation, and thromboprophylaxis. In outpatients at high risk who do not need oxygen, nirmatrelvir with ritonavir (started within 5 days of the first symptoms, for 5 days, after checking for interactions with other drugs) or remdesivir (3 days); remdesivir is also used for 5 to 10 days in pneumonia that needs oxygen.
  • RSV, hMPV, adenovirus. Support: oxygen, fluids, and ventilation when needed. Ribavirin is used in selected severe RSV disease in the immunocompromised, and cidofovir for severe adenovirus disease in them.
  • Varicella pneumonia. Intravenous aciclovir.
  • Endemic mycoses. Mild histoplasmosis or coccidioidomycosis in a healthy person is often watched; blastomycosis is treated, with itraconazole for 6 to 12 months; severe or disseminated disease of any of the three starts with liposomal amphotericin B, then itraconazole.

Prevention: yearly influenza vaccination for people at risk, health workers and anyone over 65 (the vaccine is updated every year), and vaccination against COVID-19, pneumococcus and, for older adults and in pregnancy, RSV. For Legionella, control of building water systems (temperature, disinfection) and an investigation of any cluster, since cases are notified to public health.

Epidemiology

Influenza causes seasonal epidemics in winter in temperate countries, with an estimated 3 to 5 million cases of severe illness and 290 000 to 650 000 respiratory deaths a year worldwide. Mycoplasma causes epidemics about every 3 to 5 years, mostly in school-age children and young adults; a large global wave followed the COVID-19 pandemic in 2023 and 2024. Legionnaires' disease is a disease of older, male, smoking or immunosuppressed adults in summer and autumn, and is linked to warm water systems and travel; the case fatality is about 10 per cent. COVID-19 has caused over 7 million recorded deaths since 2020, with the real toll higher. Psittacosis and Q fever are rare in cities and found in people who work with birds, sheep or goats; a large Q fever outbreak in the Netherlands (about 4000 cases) was linked to goat farming. The endemic mycoses are tied to their regions.

Prognosis

Most of these pneumonias are mild and recover without sequelae. Mycoplasma and C. pneumoniae are self-limiting in a few weeks, although the cough can last longer. Severe disease is concentrated in particular groups and organisms:

  • Legionnaires' disease is the most serious of the atypical group, with a case fatality of about one in ten, higher in the immunosuppressed, in those needing intensive care, and if treatment is delayed.
  • Influenza pneumonia is dangerous in older people, pregnant women and those with chronic disease, and secondary Staph. aureus pneumonia has a mortality of 20 per cent or more.
  • COVID-19 pneumonia carried a high mortality before vaccines and dexamethasone, particularly in the elderly and ventilated; lung function and fatigue may remain impaired for months.
  • Varicella pneumonia and severe fungal infection carry a risk of death, especially if the patient is immunosuppressed.
  • Chronic Q fever (endocarditis) needs a year or more of treatment and carries a substantial mortality.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1Why does a β-lactam such as amoxicillin fail against Mycoplasma pneumoniae?

2A man back from a hotel holiday has a high fever, confusion, diarrhoea, a sodium of 123 mmol/L and a rapidly spreading pneumonia. What is the most useful first test?

3When is a neuraminidase inhibitor most useful in influenza?

4A student with a dry cough for a week and patchy shadows on the chest X-ray becomes pale and jaundiced. What is the likely mechanism?

5A young man with influenza improves, then on day 5 has a high fever, haemoptysis and a cavitating pneumonia. Which organism should be covered?

Linked topicsThe concepts this topic shares, and the topics they tie it to.

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Pneumonia

Viruses such as influenza and SARS-CoV-2.