Pneumocystis jirovecii pneumonia

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

P. jirovecii is adapted to humans and occupies alveoli. Inadequate cell-mediated immunity allows organisms and foamy proteinaceous material to fill gas-exchange surfaces while interstitial inflammation thickens the alveolar-capillary barrier. Diffusion impairment first appears during exertion, explaining profound desaturation despite modest auscultatory signs.

Risk assessment must quantify immune suppression rather than simply ask whether the patient is immunocompromised. Record HIV status and CD4 count, systemic corticosteroid dose and duration, cytotoxic or biologic treatment, transplantation, lymphocyte-depleting therapy, previous PJP and whether prophylaxis was prescribed and taken. Concomitant CMV, bacterial infection, tuberculosis and pulmonary malignancy remain possible.

The diagnostic trade-off differs by host. People with untreated HIV generally carry a higher organism burden, making induced sputum useful; non-HIV patients may have low burden and severe inflammation, often requiring BAL. Treatment should start after high-yield samples are secured when safe, but respiratory instability should not wait for bronchoscopy.

Key points

Pneumocystis jirovecii pneumonia is an opportunistic fungal pneumonia associated with advanced HIV, prolonged corticosteroids, haematological malignancy, transplantation and selected immune-modulating therapies.
HIV-associated disease often evolves over weeks with dry cough, fever and exertional breathlessness; non-HIV disease may progress rapidly with more severe hypoxaemia and fewer organisms.
First-line imaging is chest radiography followed by CT when suspicion persists; bilateral diffuse ground-glass opacity is typical but not specific.
Preferred microbiological confirmation is Pneumocystis PCR or microscopy from induced sputum or bronchoalveolar lavage; a highly sensitive PCR must be interpreted against fungal burden and clinical probability because colonisation occurs.
Serum 1,3-beta-D-glucan is a useful supportive test and a low result can reduce probability, but it is not species specific and cannot establish PJP alone.
First-line treatment is co-trimoxazole delivering trimethoprim 15 to 20 mg/kg/day plus sulfamethoxazole 75 to 100 mg/kg/day in three or four divided doses.
Treat HIV-associated PJP for 21 days; non-HIV duration is commonly 14 to 21 days and should be individualised with infection specialists.
Use adjunctive prednisolone for moderate-to-severe HIV-associated disease: 40 mg twice daily on days 1 to 5, 40 mg once daily on days 6 to 10, then 20 mg once daily on days 11 to 21.

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

Advanced HIV

Risk rises markedly with CD4 depletion, especially below 200 cells per microlitre, uncontrolled viraemia and absent or interrupted prophylaxis.

Iatrogenic immune suppression

Prolonged systemic corticosteroids, transplantation, haematological malignancy, cytotoxic treatment and lymphocyte-targeting biologics impair cellular defence against Pneumocystis.

Previous disease

A prior PJP episode predicts recurrence while immune suppression persists and creates a strong indication for secondary prophylaxis.

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

1
Alveolar proliferation
Organisms attach to type I pneumocytes and accumulate with proteinaceous debris throughout alveoli when T-cell and macrophage control fails.
2
Diffusion impairment
Foamy alveolar material and interstitial inflammation widen the gas-exchange barrier, producing early exertional and later resting hypoxaemia.
3
Inflammatory lung injury
Host neutrophilic inflammation contributes substantially to respiratory failure, especially after treatment begins and in non-HIV immune suppression.
4
Cyst formation
Fragile subpleural cysts or pneumatoceles can rupture, causing pneumothorax or pneumomediastinum during active or recovering disease.

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

Subacute HIV presentationRed flag

Progressive exertional dyspnoea, dry cough, fever, fatigue and weight loss develop over days to weeks, with initially subtle examination findings.

Rapid non-HIV presentationRed flag

Fever, severe hypoxaemia and diffuse pneumonitis may evolve over only a few days during corticosteroid, transplant or haematology treatment.

Exertional desaturationRed flag

Oxygen saturation can be near normal at rest but fall markedly with minimal exertion because impaired diffusion precedes resting respiratory failure.

Sparse chest signs

Fine inspiratory crackles may occur, but auscultation can be surprisingly quiet despite extensive CT disease and major oxygen impairment.

Extrapulmonary clue

Oral candidiasis, wasting, lymphadenopathy or another opportunistic illness may reveal previously undiagnosed advanced HIV or broader immune failure.

Red flags requiring action

Resting hypoxaemia, rapid oxygen escalation, marked exertional desaturation, severe tachypnoea or respiratory fatigue requires urgent critical-care assessment.
Room-air arterial oxygen below 9.3 kPa or an alveolar-arterial gradient above 4.7 kPa in HIV-associated PJP supports early adjunctive corticosteroid treatment.
A pneumothorax, pneumomediastinum or cystic lung lesions can cause sudden pleuritic pain and decompensation and require immediate imaging and respiratory care.
A normal early chest radiograph does not exclude PJP; persistent compatible symptoms in a high-risk host require CT and organism-directed sampling.
Failure to improve after four to eight days raises wrong diagnosis, co-infection, drug toxicity, poor absorption, immune reconstitution or a complication rather than automatic resistance.
New PJP should prompt urgent HIV testing with consent and review of corticosteroid, transplant, chemotherapy or immune-modulator exposure.

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
Immediate oxygen assessmentFirst step
Why
Grade severity and determine need for corticosteroid and critical-care escalation.
Interpretation and limitations
Record resting and exertional saturation and obtain a room-air arterial blood gas when safe. Calculate the alveolar-arterial gradient; oxygen therapy can obscure the validated threshold.
02
First-line chest imagingFirst line
Why
Identify diffuse pneumonitis and complications while evaluating alternative diagnoses.
Interpretation and limitations
Chest radiography may be normal early. Thin-section CT commonly shows bilateral ground-glass opacity, sometimes with cysts or upper-lobe predominance after aerosolised prophylaxis.
03
Respiratory Pneumocystis PCR
Why
Detect organism DNA from induced sputum or bronchoalveolar lavage with high analytical sensitivity.
Interpretation and limitations
A negative good-quality BAL PCR makes PJP unlikely. A low-level positive can represent colonisation, so integrate cycle threshold, microscopy, beta-D-glucan and syndrome.
04
Microscopy or immunofluorescence
Why
Demonstrate Pneumocystis cysts or trophic forms and support a definite organism diagnosis.
Interpretation and limitations
Sensitivity depends on organism burden and specimen quality and is lower in non-HIV disease; negative microscopy does not exclude PJP.
05
Serum 1,3-beta-D-glucan
Why
Provide a sensitive supportive fungal marker when PJP is suspected.
Interpretation and limitations
PJP often produces a high value, but Candida and other fungi also raise it and some medical products cause false positivity; interpret serially and locally.
06
Host and co-infection screen
Why
Identify the immune defect and simultaneous causes of diffuse lung disease.
Interpretation and limitations
Offer HIV antigen-antibody testing, CD4 and viral load if positive, FBC and lymphocytes, cultures, viral PCR and targeted TB or CMV testing according to risk.

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

Bacterial pneumonia

More acute fever, focal consolidation and purulent sputum support bacterial infection, but co-infection is common in immunocompromised patients.

Viral pneumonitis

Influenza, SARS-CoV-2, CMV and other viruses cause bilateral ground glass and hypoxaemia; molecular testing and host context distinguish them.

Pulmonary tuberculosis

Cough, fever, weight loss and HIV overlap; sputum molecular testing and culture remain necessary, particularly with upper-lobe or nodal disease.

Drug pneumonitis

Immune therapy, methotrexate and other medicines can cause diffuse inflammatory lung disease, diagnosed only after infection has been carefully excluded.

Pulmonary oedema

Orthopnoea, volume overload, cardiac findings and septal or pleural fluid patterns suggest oedema, although both processes can coexist.

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

01STABILISEAssess suspected PJP immediatelyFirst stepAn immunocompromised patient develops progressive dry cough, fever, dyspnoea or unexplained oxygen impairment.

1EscalationUse ABCDE, measure resting and exertional oxygen saturation, obtain a room-air arterial blood gas where safe, and involve critical care for escalating oxygen or fatigue.
2Obtain chest radiography and urgent thin-section CT when the film is normal or non-diagnostic but clinical suspicion remains high.
3Send induced sputum or BAL for Pneumocystis PCR and microscopy plus bacterial, mycobacterial, viral and fungal studies appropriate to the host.
4Start treatment after sampling when possible, but do not delay for bronchoscopy in a patient whose respiratory physiology is deteriorating.

02FIRST-LINEGive weight-based co-trimoxazoleFirst linePJP is confirmed or strongly suspected and treatment cannot safely await final molecular results.

1Calculate dosing from the trimethoprim component: 15 to 20 mg/kg/day trimethoprim with 75 to 100 mg/kg/day sulfamethoxazole, divided every six to eight hours.
2Use intravenous treatment for severe hypoxaemia, vomiting or unreliable absorption; switch to oral treatment once stable and absorbing without reducing the total daily dose inadvertently.
3Treat HIV-associated disease for 21 days; agree a 14- to 21-day course for non-HIV disease from severity, response and immune context.
4Monitor FBC, creatinine, potassium, sodium, liver tests, rash and interactions closely and distinguish trimethoprim-related creatinine rise from true renal injury.

03STEROIDAdd corticosteroid for supported hypoxaemiaHIV-associated PJP has room-air PaO2 below 9.3 kPa or an alveolar-arterial oxygen gradient above 4.7 kPa.

1Start adjunctive corticosteroid as early as possible and within 72 hours of anti-Pneumocystis therapy.
2Give prednisolone 40 mg orally twice daily on days 1 to 5, 40 mg once daily on days 6 to 10, then 20 mg once daily on days 11 to 21.
3Use an equivalent intravenous methylprednisolone dose, commonly 75% of the prednisolone dose, if oral absorption is unreliable.
4For non-HIV PJP, evidence is less certain; use corticosteroid only after respiratory, infection and underlying-specialty review of severity and competing infection.

04ALTERNATIVEManage major co-trimoxazole intoleranceFirst lineAlternativeSevere allergy, life-threatening toxicity or inability to continue first-line treatment is established.

1For moderate-to-severe disease, choose intravenous pentamidine or clindamycin plus primaquine with infection and pharmacy oversight; check G6PD activity before primaquine.
2AlternativeFor mild disease, atovaquone is an oral alternative but requires administration with fatty food and is not suitable for severe hypoxaemia or unreliable absorption.
3Do not label transient fever or a manageable rash as absolute failure without assessing severity; supervised continuation or desensitisation can be valuable in selected HIV care.
4Continue the full required duration using active therapy and monitor regimen-specific glucose, renal, electrolyte, haematological and haemolysis risks.

05PREVENTStart and stop prophylaxis safelyHIV, transplantation, prolonged corticosteroid or another treatment creates a recognised PJP risk, or a treated episode requires secondary prophylaxis.

1PreferredUse co-trimoxazole 960 mg orally once daily as a common preferred regimen, with local alternatives such as 960 mg three times weekly where the specialist protocol permits.
2In HIV, start according to current CD4, viral-load and clinical criteria and continue after an episode until durable immune recovery on antiretroviral therapy is documented.
3In non-HIV care, coordinate prophylaxis with the prescribing haematology, transplant, rheumatology or oncology service because risk depends on combined immunosuppression and duration.
4Check FBC, renal function, potassium, allergy and interactions, educate about rash and fever, and document who will review prophylaxis when immune treatment changes.

Key medicines and prescribing safety6 treatments · regimens, roles and cautions

First-line treatment for mild, moderate and severe PJP when tolerated.

Co-trimoxazole treatment

Give trimethoprim 15 to 20 mg/kg/day plus sulfamethoxazole 75 to 100 mg/kg/day orally or intravenously in three or four divided doses.

Adjust for renal impairment and monitor potassium, sodium, creatinine, FBC, liver, rash and interactions with methotrexate, warfarin, ACE inhibitors or potassium-sparing drugs.

Reduces respiratory deterioration and mortality in HIV-associated moderate-to-severe PJP when started within 72 hours.

Prednisolone adjunct

Use prednisolone 40 mg by mouth twice daily for days 1–5, followed by 40 mg once daily for days 6–10 and 20 mg once daily for days 11–21.

Use only with the supported oxygen threshold; monitor glucose, mental state, gastrointestinal and co-infection risk, and seek specialist advice in non-HIV disease.

Alternative for moderate-to-severe PJP when co-trimoxazole cannot be continued.

Clindamycin plus primaquine

Use clindamycin 600 mg orally or intravenously every six hours or 900 mg intravenously every eight hours plus primaquine base 30 mg orally once daily under specialist protocol.

Confirm G6PD status before primaquine and monitor haemolysis and methaemoglobinaemia; watch for C. difficile diarrhoea with clindamycin.

Alternative treatment for moderate-to-severe disease when co-trimoxazole is contraindicated.

Intravenous pentamidine

Give 4 mg/kg intravenously once daily, reducing to 3 mg/kg if toxicity develops, under infection-specialist and pharmacy supervision.

Monitor glucose for hypo- and hyperglycaemia, renal function, potassium, magnesium, calcium, blood pressure, QT interval and pancreatitis.

Oral alternative for mild disease and an option for prophylaxis using its separate specialist regimen.

Atovaquone

Give 750 mg orally twice daily with food containing fat for mild PJP when absorption is reliable.

Variable absorption and gastrointestinal intolerance limit use; do not rely on it for severe hypoxaemia, vomiting or inability to eat.

Primary or secondary prevention during a defined period of cellular immune deficiency.

Co-trimoxazole prophylaxis

A common preferred adult regimen is 960 mg orally once daily; 960 mg three times weekly is an accepted alternative in selected protocols.

Review blood count, renal function, potassium, interacting medicines and severe sulfonamide allergy; the responsible specialty must define start and stop criteria.

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

Respiratory failure

Progressive diffusion failure and inflammatory injury can require high-flow oxygen, non-invasive support or invasive mechanical ventilation.

Pneumothorax

Subpleural cyst rupture causes sudden pleuritic pain and hypoxaemia and may be bilateral or difficult to manage.

Treatment toxicity

High-dose co-trimoxazole causes rash, hyperkalaemia, renal dysfunction, hepatitis and marrow suppression that may force a regimen change.

Immune reconstitution

Pulmonary symptoms can worsen after antiretroviral recovery, requiring exclusion of treatment failure and co-infection before diagnosing inflammatory rebound.

Recurrent PJP

Disease can recur when immune suppression persists, prophylaxis is omitted, adherence fails or prophylaxis is stopped prematurely.

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

Record oxygen saturation, respiratory rate and work of breathing frequently; repeat arterial gases when oxygen need or clinical effort changes.
Expect possible early respiratory worsening from inflammation, but investigate a new pneumothorax, fluid overload, bacterial co-infection, pulmonary embolism or treatment toxicity.
Check FBC, creatinine, urea, electrolytes and liver tests at baseline and repeatedly during high-dose co-trimoxazole; hyperkalaemia and cytopenias are common limiting toxicities.
Assess response over four to eight days rather than after only 24 hours, unless physiology deteriorates and demands immediate diagnostic or critical-care reassessment.
For newly diagnosed HIV, coordinate antiretroviral initiation with the HIV team, generally within two weeks of PJP treatment while managing interaction and immune-reconstitution risk.
Before discharge, establish prophylaxis, oxygen recovery, HIV or immune-disease follow-up, medication monitoring and a clear plan for recurrent breathlessness.

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

LDH is non-specific

Lactate dehydrogenase often rises with lung injury but cannot confirm PJP and performs particularly poorly as a rule-out test in non-HIV disease.

PCR detects colonisation

A low organism burden can yield a positive PCR without pneumonia, making sample type, cycle threshold, CT and beta-D-glucan important.

Non-HIV disease is abrupt

Patients without HIV often carry fewer organisms but develop more intense inflammation and faster respiratory failure, reducing induced-sputum sensitivity.

Creatinine can mislead

Trimethoprim inhibits tubular creatinine secretion and may raise measured creatinine without a matching fall in filtration, although true renal injury also occurs.

Prophylaxis has dual benefit

Co-trimoxazole also prevents toxoplasmosis and some bacterial infections in advanced HIV, strengthening its value when safely tolerated.

11Common pitfallsFrequent interpretation and management errors.

01
Do not exclude PJP because the initial chest radiograph or resting saturation is normal; assess exertion and obtain CT when risk remains high.
02
Do not interpret any positive respiratory PCR as active pneumonia without considering organism burden, imaging and beta-D-glucan.
03
Do not prescribe a fixed number of co-trimoxazole tablets without calculating the daily trimethoprim dose from actual body weight and renal function.
04
Do not delay adjunctive corticosteroid beyond 72 hours when HIV-associated disease meets the arterial oxygen threshold.
05
Do not apply the HIV corticosteroid evidence automatically to every non-HIV patient; competing infections and uncertain benefit require specialist judgement.
06
Do not discharge after treatment without secondary prophylaxis and a defined immune-recovery stop plan.