Legionella, Mycoplasma and other atypical pneumonia

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The term atypical describes microbiology better than bedside appearance. Legionella can be lobar and fulminant, Mycoplasma can cause extrapulmonary immune phenomena, and psittacosis or Q fever may look like influenza before pneumonia is recognised. Exposure, severity and the test window should drive decisions.

Testing should preserve public-health value. A urinary antigen result cannot identify every Legionella, whereas respiratory culture can support environmental linkage and PCR broadens species detection. Psittacosis and Q fever often need reference-laboratory molecular or serological interpretation, so the laboratory must hear the exposure story before specimens are processed.

Treatment begins as severity-matched CAP because an organism is rarely known at the first dose. Once evidence returns, unnecessary beta-lactam or duplicate intracellular cover can stop. Confirmed severe disease, immune suppression, endocarditis or neurological complications require organism-specific specialist duration rather than an automatic five-day rule.

Key points

The clinically useful group includes Legionella species, Mycoplasma pneumoniae, Chlamydia psittaci and Coxiella burnetii, but ordinary bacteria and respiratory viruses can produce the same radiological pattern.
Translate exposure into a dated hypothesis: water aerosols, hotels, spas or healthcare plumbing for Legionella; birds and dried droppings for psittacosis; ruminants and birth products for Q fever; close-contact outbreaks for Mycoplasma.
Diarrhoea, confusion, hyponatraemia or liver and renal abnormalities increase suspicion for Legionella but cannot confirm it or justify excluding competing emergencies.
Legionella urinary antigen is rapid yet principally detects L pneumophila serogroup 1; obtain lower-respiratory PCR and culture in severe, antigen-negative high-probability or epidemiologically important disease.
A beta-lactam alone has no reliable activity for these intracellular or cell-wall-deficient pathogens; add or select an intracellular-active agent when probability and severity warrant it.
Use current CAP guidance for the empirical phase, then revise agent and duration with microbiology once the organism, host, pregnancy status and complications are known.
Fluoroquinolones are restricted because disabling and potentially irreversible adverse effects occur; use them only when common recommended alternatives are inappropriate and document the reason.
Legionnaires' disease requires urgent public-health notification in England, while suspected zoonotic clusters or occupational hazards should be discussed promptly even when the individual disease is not routinely notifiable.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Legionella water aerosol

Legionella multiplies within engineered water-system biofilms and amoebae; inhaled contaminated droplets can seed lung, particularly in older, smoking, immunosuppressed or chronically ill adults.

Mycoplasma close contact

M pneumoniae spreads between people in households, schools and other close settings and lacks the peptidoglycan target required for beta-lactam activity.

Bird and ruminant reservoirs

C psittaci is acquired from infected birds or dried excreta, while C burnetii can disperse in aerosols from livestock and birth products.

Host severity modifiers

Age, immune suppression, pregnancy, cardiopulmonary disease and delayed active therapy shape progression more reliably than whether the initial cough sounds 'typical'.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Lower-airway inoculation
Droplets or environmental aerosols deposit organisms in distal airways, where they attach to respiratory cells or enter susceptible host cells.
2
Protected microbial niche
Intracellular residence or absence of a conventional cell wall limits beta-lactam effect and makes adequate intracellular drug exposure important.
3
Alveolar immune injury
Cellular infection and host inflammation produce interstitial and alveolar exudate, reducing ventilation and impairing oxygen transfer without a unique radiographic signature.
4
Extrapulmonary inflammation
Direct dissemination and immune-mediated effects can disturb sodium, liver, kidney, blood cells, myocardium, skin or nervous tissue according to the organism.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Water-associated LegionellaRed flag

Severe pneumonia follows hotel, spa, cooling, healthcare or domestic water-aerosol exposure and may include gastrointestinal symptoms, confusion, low sodium or organ injury.

Mycoplasma outbreak syndrome

A gradually progressive cough and fever occurs among close contacts, sometimes with rash, mucositis, haemolysis, cardiac or neurological features despite modest chest examination findings.

Bird-associated psittacosisRed flag

High fever, headache and pneumonia after aviary, poultry, pigeon or veterinary exposure can progress to respiratory failure, hepatitis, myocarditis or encephalopathy.

Ruminant-associated Q fever

Fever with hepatitis or pneumonia after sheep, cattle, goats or birth products raises acute Q fever; valvular or vascular disease increases concern about persistent focal infection.

Severe pathogen-unknown CAPRed flag

Shock, profound hypoxaemia, multilobar change or organ failure requires prompt broad CAP treatment including credible intracellular pathogens before exposure testing is complete.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Dated environmental and animal exposure recordFirst step
Why
Separate plausible sources and supply actionable information for reference testing or public-health investigation.
Interpretation and limitations
Record accommodation names and dates, specific water systems, bird species and tasks, farm contact and animal-parturition exposure during the organism's incubation window.
02
Legionella urinary antigen
Why
Rapidly identify many cases caused by L pneumophila serogroup 1.
Interpretation and limitations
A positive result supports disease in the right syndrome. A negative result leaves other serogroups and species unresolved and must not stop active treatment in severe high-probability illness.
03
Lower-respiratory Legionella PCR and culture
Why
Broaden detection and retain an isolate for typing and source linkage.
Interpretation and limitations
Send good-quality sputum, tracheal aspirate or another appropriate specimen and alert the laboratory. Culture may remain useful after antibiotics and is particularly important for clusters.
04
Multiplex respiratory molecular testing
Why
Detect Mycoplasma and competing respiratory viruses when the result alters treatment or isolation.
Interpretation and limitations
Panel composition and sensitivity vary. Detection must be matched to symptoms and outbreak context, and a negative upper-airway sample may not settle severe lower-airway disease.
05
Reference serology or molecular tests
Why
Investigate psittacosis and Q fever when exposure and clinical pattern align.
Interpretation and limitations
Diagnostic yield changes with illness timing and paired samples may be needed. Discuss test choice before relying on a single antibody titre or delaying severe-disease treatment.
06
Severity and complication assessment
Why
Identify respiratory failure, haemolysis, hepatitis, myocarditis, renal injury or neurological disease.
Interpretation and limitations
Use oxygenation, chest imaging, FBC and film, electrolytes, renal and liver tests, ECG and further organ-directed tests according to the syndrome; no laboratory constellation is organism-specific.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Pneumococcal or staphylococcal pneumonia

Lobar change, high fever and systemic illness overlap extensively; culture, antigen, molecular testing and treatment response determine whether ordinary bacteria are present.

Influenza or COVID-19

Viral pneumonitis produces similar systemic and bilateral respiratory illness, requiring current respiratory testing when antiviral or isolation decisions differ.

Pulmonary embolism

Pleuritic pain, fever and hypoxaemia can occur without infection; thrombotic probability and vascular imaging answer a separate diagnostic question.

Tuberculosis or inflammatory pneumonitis

A subacute course, cavitation, exposure, drug history or autoimmune features may redirect investigation toward mycobacterial or non-infectious disease.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First assessmentConvert exposure into testable probabilitiesFirst stepPneumonia has epidemiology or extrapulmonary features suggesting an intracellular pathogen.

1Stabilise ABCDE, grade CAP severity and take routine cultures and imaging without postponing time-critical treatment.
2Build a date-and-place exposure timeline and contact microbiology early for respiratory, reference or paired specimens.
3Start the current severity-based CAP regimen with intracellular activity when the probability is clinically material; document pregnancy, QT, renal and interaction constraints.

02Legionella pathwayPreserve both patient and population evidenceWater, travel, healthcare or severe-pneumonia features make Legionella plausible.

1Send urinary antigen and a lower-respiratory sample for PCR and culture; do not use a negative antigen as a rule-out test.
2Continue a specialist-approved macrolide or, when common alternatives are inappropriate, fluoroquinolone regimen matched to severity, renal function and interactions.
3Telephone the England health-protection team within 24 hours for suspected Legionnaires' disease and provide the complete 14-day exposure history for source investigation.

03Zoonotic pathwayLink bird or livestock contact to the laboratoryBird material, livestock or birth-product exposure precedes compatible pneumonia or hepatitis.

1Discuss psittacosis or Q fever molecular and serological sampling with microbiology or the reference service and assess occupational or cluster risk.
2Use an organism-appropriate intracellular-active drug selected with pregnancy, liver, cardiac and interaction factors; severe illness warrants infection-specialist input.
3Evaluate persistent Q fever for valvular or vascular focal infection and investigate severe psittacosis for hepatic, cardiac or neurological complications.

04Result reviewRemove empiricism and define durationOrganism testing and the 48-hour clinical trajectory are available.

1Decide whether the result explains the pneumonia and stop redundant beta-lactam or duplicate intracellular therapy when safe.
2Recheck QTc, electrolytes, renal and hepatic function and interacting medicines before continuing a macrolide or fluoroquinolone.
3Set an organism- and complication-specific end date with microbiology; investigate pleural infection, myocarditis, haemolysis, encephalitis or endocarditis when recovery is atypical.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides intracellular activity in moderate or high-severity empirical CAP and is active against several implicated organisms.

Clarithromycin

For adult CAP give 500 mg orally or intravenously twice daily for 5 days; specialist-confirmed complicated infection may need longer.

Check QTc, potassium and magnesium, hepatic function and renal dose requirements. Review strong CYP3A4 interactions; simvastatin or lovastatin and several antiarrhythmics are incompatible, and pregnancy requires an alternative plan where appropriate.

Provides intracellular and respiratory activity, including for selected severe or confirmed Legionella infection under microbiology advice.

Levofloxacin when common alternatives are inappropriate

For high-severity adult CAP, NICE lists 500 mg orally or intravenously twice daily for 5 days, then review.

Use only after documenting why recommended alternatives are inappropriate. Reduce in renal impairment; avoid in pregnancy, previous serious quinolone reaction and concurrent corticosteroid where possible, and counsel about tendon, neuropathy, CNS, QT and aortic or valvular risks.

Active oral option for Mycoplasma and an important treatment component for psittacosis and acute Q fever in suitable adults.

Doxycycline

For uncomplicated adult CAP give 200 mg on day 1 then 100 mg daily to day 5; psittacosis or Q fever requires a specialist-defined regimen and duration.

Avoid in pregnancy unless a specialist judges the benefit to outweigh risk; separate from iron, calcium, magnesium and antacids, take upright with water, and review photosensitivity, oesophagitis and liver disease.

Covers usual extracellular bacteria and credible intracellular pathogens before severe-pneumonia microbiology is established.

Co-amoxiclav plus clarithromycin

For high-severity adult CAP give co-amoxiclav 500/125 mg orally or 1.2 g intravenously three times daily plus clarithromycin 500 mg twice daily for 5 days, then review.

Check beta-lactam allergy, renal and hepatic function, QTc and all interactions. Narrow promptly once an organism is identified; this combination is not routine treatment for mild outpatient illness.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute respiratory failure

Extensive pneumonitis causes shunt, increasing oxygen need and fatigue and occasionally requiring invasive ventilation or extracorporeal support.

Multisystem organ injury

Severe Legionella or zoonotic infection can cause encephalopathy, hepatitis, kidney injury, myocarditis, cytopenia and circulatory shock.

Postinfectious immune disease

Mycoplasma can trigger mucocutaneous, haemolytic, neurological or cardiac immune phenomena that outlast or dominate the pulmonary illness.

Persistent focal Q fever

C burnetii may persist at abnormal valves or vascular prostheses, causing culture-negative endocarditis or vascular infection after the acute syndrome.

Uncontrolled shared exposure

Failure to identify a contaminated water, occupational or animal source can permit additional cases beyond the index patient's illness.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Trend oxygen requirement, respiratory rate, haemodynamics, mental state, sodium and renal and hepatic function in severe or multisystem disease.
Review ECG and electrolyte contributors to QT prolongation before and during macrolide or fluoroquinolone treatment when risk is present.
Track haemoglobin, bilirubin and film when Mycoplasma-associated haemolysis is suspected and use organ-directed monitoring for cardiac or neurological complications.
At 48 hours reconcile urinary antigen, respiratory PCR or culture and reference results; retain appropriate specimens for Legionella typing and cluster work.
Record statutory Legionella notification time, health-protection contact and the complete environmental history rather than only writing 'travel associated'.
For Q fever with valvular or vascular risk, ensure persistent symptoms and follow-up serology are owned by an infection service rather than lost after pneumonia improves.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The label is not the phenotype

No constellation of dry cough, hyponatraemia or extrapulmonary symptoms identifies an organism reliably enough to replace exposure-led microbiology.

Urine answers a narrow question

Legionella urinary antigen is useful because it is fast, not because it detects every pathogenic Legionella; lower-respiratory material preserves the missing breadth.

One exposure can protect others

A precise hotel, spa or healthcare-water history may link cases and lead to environmental control before another person becomes ill.

Fluoroquinolone use needs a reason

Potential efficacy does not erase serious class toxicity or current MHRA restriction; patient factors and suitability of recommended alternatives must be documented.

Persistent Q fever changes the organ

After acute febrile illness, ongoing disease may localise to abnormal valves or vascular material and requires a different diagnostic and prolonged-treatment pathway.

11Common pitfallsFrequent interpretation and management errors.

01
Calling hyponatraemia diagnostic of Legionella.
02
Stopping intracellular-active therapy in severe disease solely because urinary antigen is negative.
03
Sending serology without documenting exposure date or illness day.
04
Using beta-lactam monotherapy when a credible intracellular pathogen materially changes coverage.
05
Prescribing clarithromycin without checking QT, statins, antiarrhythmics and renal or hepatic modifiers.
06
Using a fluoroquinolone without documenting that common recommended agents are inappropriate.
07
Waiting for laboratory confirmation before urgent Legionnaires' disease notification.