Pneumocystis jirovecii pneumonia

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

Pneumocystis jirovecii is an opportunistic fungus with a distinctive alveolar syndrome. In untreated HIV, PJP often evolves over days to weeks with fever, non-productive cough and progressive exertional dyspnoea at low CD4 counts. In non-HIV immune suppression it can progress faster, with a lower organism burden, more intense inflammation and abrupt respiratory failure. The different biology affects diagnostic yield and the strength of evidence for adjunctive corticosteroids.

Gas-exchange impairment may be more severe than auscultation or the first radiograph suggests. Exercise desaturation can be an early clue, while established disease causes diffuse alveolar injury and a widened alveolar-arterial oxygen gradient. CT ground-glass opacities, sometimes with cysts or pneumothorax, are supportive but overlap with viral pneumonitis, drug toxicity, oedema, diffuse alveolar haemorrhage and other fungi.

Diagnosis usually combines risk, physiology, imaging and organism detection. PCR on induced sputum or BAL is sensitive but cannot always separate colonisation from disease; quantitative burden, microscopy, beta-D-glucan and pre-test probability help. Bronchoscopy may be dangerous in a profoundly hypoxaemic patient, so do not withhold treatment while arranging an unsafe procedure. Co-trimoxazole remains the treatment standard. Duration is usually 21 days in HIV-associated PJP; non-HIV pathways may use 14 to 21 days depending on severity and host, so use current specialty guidance.

Key points

Think of PJP with subacute dry cough, fever, exertional breathlessness, disproportionate hypoxaemia and bilateral ground-glass change in a person with impaired T-cell immunity.
Risk includes untreated or advanced HIV, prolonged corticosteroids, haematological malignancy, transplantation and selected biologic or cytotoxic therapies; a normal total white count does not reassure.
Chest radiography can be normal early. Thin-section CT usually shows diffuse or patchy bilateral ground glass but is not pathogen-specific.
Measure arterial blood gases on room air when safe, or document inspired oxygen carefully, because PaO2 and the alveolar-arterial gradient determine severity and the HIV corticosteroid decision.
Induced sputum or BAL PCR and microscopy provide microbiological support; PCR is very sensitive and may detect colonisation, so interpret organism burden with the syndrome.
High-dose co-trimoxazole, calculated by the trimethoprim component, is first-line treatment; monitor potassium, renal function, blood count and rash closely.
In HIV-associated moderate-to-severe PJP, start adjunctive corticosteroid early when PaO2 is below 9.3 kPa or the alveolar-arterial gradient is at least 4.7 kPa; non-HIV evidence is less certain.
Evaluate the cause of immune suppression, offer HIV testing with consent when status is unknown, and plan ART or secondary prophylaxis with the appropriate specialist team.

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

Advanced HIV immune suppression

Loss of effective cellular immunity permits Pneumocystis proliferation, particularly when HIV is undiagnosed, untreated or preventive therapy is absent.

Corticosteroid exposure

Sustained systemic corticosteroids impair T-cell and macrophage function and are a major risk outside HIV, especially with additional immune treatments.

Cancer and transplantation

Haematological malignancy, solid-organ or stem-cell transplantation and associated immunosuppression create high-risk host states, and several contributors may coexist in the same patient.

Other immune-modifying therapy

Biological and cytotoxic treatments for autoimmune or malignant disease can confer risk according to regimen, cumulative immune effect and local prophylaxis policy.

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

1
Alveolar organism proliferation
In impaired cellular immunity, Pneumocystis adheres to alveolar epithelium and multiplies within air spaces, which links the underlying lesion to the observed respiratory dysfunction.
2
Foamy alveolar exudate
Organisms, proteins and cellular debris accumulate diffusely, interfering with surfactant and ventilation, with effects that increase as the pathological process progresses.
3
Interstitial inflammation
Host immune responses thicken the alveolar-capillary interface, with the inflammatory pattern differing between HIV and non-HIV hosts.
4
Severe oxygen-transfer failure
Diffuse ventilation-perfusion mismatch and diffusion limitation cause exertional then resting hypoxaemia, often disproportionate to early auscultatory findings.

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

Classic HIV-associated presentation

Two or more weeks of fever, dry cough, progressive exertional breathlessness, weight loss and oral candidiasis or another clue to advanced HIV. Resting observations can initially be deceptively mild.

Non-HIV fulminant presentationRed flag

A patient receiving corticosteroids, chemotherapy, transplant immunosuppression or a T-cell-active biologic develops rapidly increasing oxygen needs and bilateral ground glass over days.

Severe gas-exchange impairmentRed flag

Cyanosis, respiratory fatigue, PaO2 below 9.3 kPa or a markedly widened alveolar-arterial gradient indicates significant disease. Early critical-care involvement is appropriate if oxygen needs rise.

Cysts and air leakRed flag

Pneumatoceles can complicate PJP and predispose to spontaneous pneumothorax. Sudden pleuritic pain, unilateral loss of breath sounds or acute desaturation requires immediate assessment.

Important mimics or co-infections

COVID-19, CMV, bacterial pneumonia, TB, pulmonary oedema, drug pneumonitis, lymphoma and diffuse alveolar haemorrhage may coexist or resemble PJP; focal lobar consolidation should broaden the search.

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
Arterial blood gas and alveolar-arterial gradientFirst step
Why
Grade hypoxaemia and establish whether HIV-associated disease meets the corticosteroid threshold; record FiO2 and, where safe, obtain the reference sample breathing room air.
Interpretation and limitations
PaO2 below 9.3 kPa or A-a gradient at least 4.7 kPa identifies moderate-to-severe HIV-associated PJP in common UK guidance. Trends matter when oxygen delivery changes.
02
Thin-section CT chest
Why
Detect ground-glass change when radiography is normal and identify cysts, pneumothorax or an alternative diagnosis.
Interpretation and limitations
Diffuse bilateral ground glass is supportive but nonspecific. Predominant pleural effusion, large nodes or dense focal consolidation should prompt investigation for alternatives or co-infection.
03
Induced sputum PJP PCR and microscopy
Why
Obtain a less invasive respiratory sample for molecular detection and organism visualisation where local expertise exists.
Interpretation and limitations
A positive high-burden result with a compatible syndrome supports disease; a low-level PCR result may be colonisation. Negative sensitivity is lower than BAL, especially outside HIV.
04
Bronchoscopy with BAL
Why
Provide higher-yield PCR, immunofluorescence or microscopy and samples for concurrent bacterial, mycobacterial, viral and fungal causes.
Interpretation and limitations
BAL can clarify competing diagnoses, but the procedure may precipitate respiratory failure. Treat empirically and defer if risk outweighs decision value.
05
Serum beta-D-glucan
Why
Use as a supportive fungal cell-wall marker when available, particularly if respiratory sampling is delayed.
Interpretation and limitations
A low value can lower probability, while a high value supports but does not prove PJP; other fungi, haemodialysis products and some exposures cause false positives.
06
Immune and safety baseline
Why
Offer HIV antigen-antibody testing with consent, review CD4 and viral load if positive, identify immunosuppressants, and check FBC, renal and liver profile, potassium, G6PD where primaquine is considered, and pregnancy status where relevant.
Interpretation and limitations
The host diagnosis determines ART, duration, prophylaxis and co-infection search; baseline organ function determines drug choice and monitoring intensity.

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

Viral pneumonitis

COVID-19, cytomegalovirus and other viral infections produce similar bilateral ground-glass change; respiratory molecular testing and host context discriminate.

Bacterial pneumonia

Focal consolidation, purulent sputum and bacterial cultures favour ordinary infection, though coinfection is possible, with targeted examination and testing used to resolve the uncertainty.

Drug-induced pneumonitis

The same immune treatments that create risk can cause inflammatory toxicity; medicine timing and targeted respiratory sampling are critical.

Cardiogenic pulmonary oedema

Volume overload and cardiac dysfunction in renal or cancer care can mimic diffuse pneumonitis but have supporting haemodynamic features.

Pulmonary lymphoma or malignancy

Tumour infiltration may cause diffuse interstitial change and systemic symptoms; tissue may be needed when infection tests are non-diagnostic.

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

01TreatSuspected PJP with respiratory compromiseFirst stepCompatible immune risk, CT pattern and hypoxaemia, with results pending.

1Stabilise using controlled oxygen to an individual target, obtain ABG and early critical-care review if oxygen needs or work of breathing rise; assess immediately for pneumothorax.
2Send induced sputum or BAL only when safe and collect tests for competing infections, but start co-trimoxazole promptly when clinical probability is high.
3Calculate the regimen by trimethoprim weight, adjust for renal function and obesity according to the local protocol, and divide the daily dose as specified.
4AlternativeEscalationReview physiology, microbiology and toxicity daily; failure to improve should trigger an alternative-diagnosis and treatment-exposure review, not automatic dose escalation.

02SteroidAdjunctive corticosteroid in HIV-associated PJPConfirmed or strongly suspected HIV-associated PJP with PaO2 below 9.3 kPa or A-a gradient at least 4.7 kPa.

1Start corticosteroid as early as possible, ideally within 72 hours of anti-Pneumocystis therapy, using the current BHIVA or local taper.
2Monitor glucose, mental state, blood pressure, fluid balance, secondary infection and gastrointestinal risk.
3Do not extrapolate the HIV mortality benefit automatically to non-HIV PJP; seek the responsible specialty and infection advice for an individual decision.
4If criteria are not met, continue close gas-exchange monitoring because deterioration can change the indication.

03RecoverHIV treatment and recurrence preventionPJP occurs in a person with newly diagnosed or uncontrolled HIV.

1Involve the HIV team promptly, screen for co-infections and interactions, and plan antiretroviral therapy usually within two weeks of starting PJP treatment if clinically feasible.
2Watch for immune reconstitution inflammatory syndrome while avoiding unnecessary ART delay; coordinate regimen selection with renal, hepatic and interaction issues.
3Start secondary prophylaxis after acute therapy and continue until immune recovery criteria in current BHIVA guidance are met.
4Address adherence, vaccination, smoking, safeguarding and confidential partner or public-health support through the appropriate consent-based services.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

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

Co-trimoxazole

Treatment uses 15 to 20 mg/kg/day of the trimethoprim component with 75 to 100 mg/kg/day sulfamethoxazole, divided into 3 or 4 doses intravenously or orally; adjust for renal function and follow the host-specific local duration, commonly 21 days in HIV.

Rash including severe cutaneous reactions, marrow suppression, hyperkalaemia, renal dysfunction, hepatitis and interactions such as methotrexate or warfarin. Monitor closely; do not underdose by confusing combined-tablet mass with trimethoprim mass.

Reduces mortality and respiratory deterioration in hypoxaemic HIV-associated PJP meeting gas-exchange thresholds.

Prednisolone or intravenous methylprednisolone

Use the current BHIVA or local staged regimen for moderate-to-severe HIV-associated PJP, started within 72 hours; intravenous methylprednisolone is often given at 75% of the prednisolone dose when oral therapy is unsuitable.

Evidence is not equivalent in non-HIV disease. Hyperglycaemia, delirium, fluid effects and additional infection risk require surveillance; exclude or treat important co-infections.

Alternative anti-Pneumocystis therapy for intolerance, contraindication or failure after expert review.

Intravenous pentamidine

Specialist weight-based once-daily regimen per current BNF or local protocol, generally reserved for severe disease when co-trimoxazole cannot be used.

Hypotension, dysglycaemia, pancreatitis, nephrotoxicity, electrolyte disturbance, cytopenia and QT prolongation. Requires intensive biochemical and ECG monitoring.

Alternative regimen for selected moderate-to-severe disease when co-trimoxazole is unsuitable.

Clindamycin plus primaquine

Specialist oral or intravenous clindamycin plus oral primaquine according to current local or BHIVA guidance; confirm normal G6PD activity before primaquine.

Primaquine can cause haemolysis and methaemoglobinaemia, particularly in G6PD deficiency. Clindamycin has substantial diarrhoea and C. difficile risk.

Alternative when co-trimoxazole is not tolerated and gas-exchange impairment is mild.

Atovaquone

Current BNF or local oral regimen taken with food to improve absorption, for selected mild disease.

Less appropriate for severe disease; variable absorption, gastrointestinal effects, rash and interactions. Treatment failure should prompt exposure and diagnosis review.

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

Acute respiratory failure

Progressive diffuse gas-exchange loss may require high-level oxygen or ventilation, with potentially abrupt deterioration in non-HIV immune suppression.

Pneumothorax

Cystic or subpleural lung injury can rupture, producing recurrent or bilateral pleural air and difficult ventilatory management.

Immune reconstitution inflammation

Recovering immunity after HIV treatment can transiently worsen pulmonary inflammation despite microbiological response, adding morbidity beyond the initial pulmonary disorder.

Treatment toxicity

Antimicrobial therapy can cause rash, cytopenias, renal injury, electrolyte disturbance and important drug interactions, creating an additional need for recognition and targeted treatment.

Recurrence

Persistent immune suppression without effective prevention leaves substantial risk of another episode after apparent recovery, particularly when baseline cardiopulmonary reserve is limited.

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

Measure respiratory rate, work of breathing, oxygen saturation and oxygen requirement frequently; repeat ABG when physiology changes and escalate early for ventilatory support.
Check FBC, urea, creatinine, potassium and liver tests at baseline and repeatedly during high-dose co-trimoxazole, with more frequent review in renal impairment.
Inspect skin and mucosa for evolving drug rash and stop or escalate urgently for blistering, mucosal involvement or systemic hypersensitivity.
Monitor glucose and mental state during corticosteroids, and actively search for bacterial, TB, CMV or fungal co-infection if fever or deterioration persists.
Review respiratory PCR or microscopy quantitatively with microbiology; do not let a low-level positive result close the differential.
For HIV, track ART initiation, interactions, CD4 or viral load recovery and prophylaxis adherence through the specialist service.
After discharge, document completion date, recurrence-prevention plan and urgent return advice for breathlessness, fever or pleuritic pain.

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

Calculate the right component

Co-trimoxazole treatment is prescribed by milligrams of trimethoprim per kilogram per day. Confusing this with the combined tablet weight causes serious dosing error.

Non-HIV PJP can be faster

Lower organism burden may reduce microscopy yield, while a brisk inflammatory response causes rapid respiratory failure. A negative non-invasive sample deserves careful interpretation.

Normal radiography is not exclusion

Exertional desaturation and CT ground glass may precede a visible chest-radiograph abnormality in a high-risk patient.

Pneumothorax changes the tempo

Cyst formation makes sudden air leak possible. Acute pleuritic deterioration demands immediate bedside examination and imaging, not attribution to expected PJP progression.

Diagnosis should reveal the host problem

New PJP may be the first presentation of HIV or an unrecognised cumulative corticosteroid risk. Treating the pneumonia without addressing immunity invites recurrence.

11Common pitfallsFrequent interpretation and management errors.

01
Reassuring oneself with a normal early chest radiograph despite exertional desaturation and major immune risk.
02
Waiting for bronchoscopy before treating a severely hypoxaemic, high-probability patient.
03
Interpreting any positive PCR as disease without considering burden, host and CT.
04
Using the HIV corticosteroid threshold as an automatic mandate in non-HIV PJP.
05
Failing to monitor hyperkalaemia, marrow suppression and renal function on treatment-dose co-trimoxazole.
06
Discharging without ART coordination or a secondary prophylaxis plan when HIV is the cause.