ICU · Infectious Diseases
Pneumocystis jirovecii pneumonia (PCP) in the ICU
Also known as Pneumocystis pneumonia (PCP) · PJP pneumonia · Pneumocystis carinii (former name)
PCP is an opportunistic fungal pneumonia affecting immunocompromised patients (HIV with CD4 <200, transplant, chemotherapy, prolonged steroids). Presents with progressive dyspnoea, dry cough, fever, bilateral interstitial infiltrates on CXR, hypoxia (often disproportionate to CXR findings). Diagnosis: induced sputum or BAL with immunofluorescence/PCR for Pneumocystis. Elevated beta-D-glucan (non-specific). Treatment: co-trimoxazole (trimethoprim-sulfamethoxazole) high-dose (15-20 mg/kg/day trimethoprim component) IV for 21 days. Add corticosteroids if PaO2 <70 mmHg or A-a gradient 35 (reduces mortality — prevents inflammatory response from organism lysis). Prophylaxis: co-trimoxazole for CD4 <200 or high-dose steroids.
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Background and taxonomy
Pneumocystis jirovecii is an extracellular, obligate fungal pathogen of the human lung (renamed from P. carinii in 2001 — carinii now refers only to the rat species). Unusual features that shape clinical management:[4]
- Cannot be cultured on artificial media (diagnosis relies on microscopy/PCR of respiratory specimens).
- Exists in two forms in the lung: the trophic form (adherent to type I pneumocytes, the predominant form) and the cyst (contains up to 8 intracystic bodies, the form seen on silver stain).
- Cell wall contains beta-D-glucan (basis for the serum biomarker) and cholesterol — but NOT ergosterol, which is why echinocandins do NOT work (they inhibit beta-1,3-glucan synthase but the cyst wall, not the trophozoite, is the target).
- Host defence is cell-mediated (CD4 T-cells + alveolar macrophages) — hence neutropenia per se is NOT the key risk; lymphocyte depletion is. This explains why PCP is the classic AIDS-defining illness and why prophylaxis is CD4-driven.[4]
Transmission is thought to occur via airborne person-to-person spread and possibly reactivation of latent childhood-acquired infection. Asymptomatic colonisation occurs; symptomatic disease reflects failed cell-mediated clearance.[2]
Epidemiology and risk groups
HIV / AIDS
CD4 < 200
- CLASSIC AIDS-defining opportunistic infection — CD4 <200 cells/microL
- Risk proportional to CD4 nadir: ~80% lifetime risk in untreated AIDS before ART era
- Often the first presentation of HIV (index diagnosis) — always offer HIV testing
- On ART but immune reconstitution delayed: still at risk if CD4 <200 (immune non-responder)
- IRIS (immune reconstitution inflammatory syndrome) can mimic/precipitate PCP early after ART
Transplant
Solid organ / HSCT
- Solid organ transplant: peak incidence 2-6 months post-transplant (peak immunosuppression)
- Renal transplant historically highest load; lung/heart-lung recipients highest per-patient risk
- Haematopoietic stem cell transplant: risk peaks during engraftment and with graft-vs-host disease
- Most centres use universal co-trimoxazole prophylaxis for 6-12 months (longer for lung)
- Breakthrough PCP on prophylaxis: question adherence, species resistance, drug interactions
Steroids & biologics
Iatrogenic
- Prednisolone >20 mg/day (or equivalent) for >4 weeks — classic "steroid taper" risk (often flares as dose is weaned)
- Other immunosuppressants: cyclophosphamide, azathioprine, mycophenolate, methotrexate, calcineurin inhibitors
- Anti-TNF biologics (infliximab, adalimumab, etanercept) — significant PCP risk, often warrant prophylaxis
- Rituximab (B-cell depletion) and alemtuzumab — prolonged risk
- Idiopathic CD4 lymphocytopenia — rare but classic
Other / congenital
Less common
- Primary immunodeficiencies: hyper-IgM syndrome (CD40L deficiency), severe combined immunodeficiency
- Malnutrition / severe undernutrition (developing-world infants — "epidemic" PCP in nurseries)
- Advanced malignancy — especially haematological (lymphoma, CLL)
- Solid tumours on prolonged chemotherapy or fludarabine/cladribine (purine analogues cause prolonged lymphopenia)
- Previously immunocompetent: increasingly recognised in critically ill ICU patients (relative immunoparesis)
Pathophysiology
Inhaled organisms reach the alveoli and proliferate attached to type I pneumocytes. The host response (not the organism itself) produces most of the pathology:[1]
- Alveolar filling with a foamy, eosinophilic, honeycomb exudate (organisms + surfactant + cell debris) — the histological hallmark on H&E.
- Interstitial oedema and plasma-cell/lymphocytic infiltrate → thickened alveolar septa → impaired diffusion.
- Type II pneumocyte hyperplasia as type I cells are lost.
- Result: marked diffusion impairment with relatively preserved ventilation → type 1 respiratory failure with a widened A-a gradient. This explains the disproportionate hypoxia relative to a chest film that may look deceptively normal early.[4]
Steroid rationale: when co-trimoxazole kills organisms, the lysis of cysts releases antigen and recruits neutrophils, worsening alveolitis and gas exchange (paradoxical deterioration at days 3-5 of therapy). Corticosteroids blunt this inflammatory response — the only intervention proven to reduce mortality in moderate-severe disease.[2]
Clinical features
Presentation
Insidious onset
- Progressive dyspnoea over days-weeks (insidious — unlike bacterial pneumonia)
- Dry cough (non-productive)
- Low-grade fever
- Hypoxia DISPROPORTIONATE to CXR (may have normal CXR early)
- Tachypnoea, increased work of breathing
- Bilateral crackles on auscultation
- Malaise, weight loss, night sweats (subacute constitutional features)
- Minimal purulent sputum (organisms do not invade — host inflammation scanty)
- Pleuritic pain and haemoptysis are UNCOMMON — think pneumothorax or alternative diagnosis if present
Imaging
Progressive infiltrates
- CXR: bilateral interstitial infiltrates (perihilar, "butterfly" pattern). May be NORMAL early (up to 25% of proven cases).
- CT chest: ground-glass opacities (more sensitive than CXR) — patchy, often central/parahilar, sparing subpleural regions
- Pneumothorax (cystic changes / pneumatoceles in severe PCP — beware, may be bilateral)
- Upper lobe predominance if on pentamidine prophylaxis (aerosolised — does not reach apices)
- Nodules, lymphadenopathy, pleural effusion are atypical — reconsider diagnosis
- Miliary / nodular pattern seen rarely (especially post-transplant)
Differential diagnosis in the immunocompromised patient with pulmonary infiltrates
PCP
Fungal
- Subacute dyspnoea + dry cough + fever, CD4 <200
- Bilateral perihilar ground-glass on CT, normal CXR early
- Elevated beta-D-glucan, LDH often markedly raised
- Diagnosis: BAL with immunofluorescence / PCR / silver stain
CMV pneumonitis
Viral
- Similar host (CD4 <50, transplant) — frequently coexists with PCP
- More systemic: fever, malaise, leucopenia, thrombocytopenia, transaminitis
- CT: ground-glass + nodules + small nodules with halo
- Diagnosis: BAL CMV PCR / shell-vial culture; CMV DNAaemia; intranuclear inclusions on biopsy
- Treat with ganciclovir / valganciclovir
Bacterial pneumonia
Pyogenic
- Acute onset (hours-days), purulent sputum, high fever, localising signs
- Lobar / segmental consolidation on imaging
- Responds to standard empirical antibiotics (e.g. ceftriaxone + azithromycin)
- Encapsulated organisms (S. pneumoniae, H. influenzae) common in HIV (B-cell dysfunction) — consider after splenectomy / functional hyposplenism
Invasive aspergillosis
Mould
- Neutropenia (not lymphopenia) is the key risk — prolonged, profound
- Pleuritic pain, haemoptysis, wedge / nodule with halo or air-crescent sign on CT
- Galactomannan (BAL & serum), beta-D-glucan elevated
- Treat with voriconazole / isavuconazole
TB / NTM
Mycobacterial
- Subacute, weight loss, night sweats — easy to confuse with PCP
- HIV with CD4 <200: TB may be disseminated / miliary, smear-negative, extrapulmonary
- CXR: apical cavitation (classic) OR miliary (immunocompromised)
- Diagnosis: sputum / BAL AFB smear and NAAT (Xpert MTB/RIF). ISOLATE until TB excluded.
Lymphoma / malignancy
Non-infective
- HIV patients have high burden of NHL — pulmonary involvement can mimic PCP
- Persistent infiltrates not responding to antibiotics, LDH very high
- Diagnosis: biopsy (cytology / histology of BAL or transbronchial)
Diagnosis
PCP diagnostic approach
Risk factors
Immunocompromised: HIV with CD4 <200 (most common), solid organ transplant, haematological malignancy, chemotherapy, prolonged corticosteroids (>20 mg prednisolone >3-4 weeks), TNF inhibitors, primary immunodeficiency.
Bedside: arterial blood gas
Calculate A-a gradient on room air if possible (or correct for FiO2). PaO2 <70 mmHg or A-a gradient >35 mmHg defines moderate-severe disease and TRIGGERS STEROID therapy. Hypoxia with relatively normal CXR is a clue. Also send LDH (often markedly elevated, mirrors disease severity; falls with response).
Beta-D-glucan
Non-specific marker of fungal cell wall component. Elevated in PCP (Pneumocystis has beta-D-glucan in cyst wall). Also elevated in: Candida, Aspergillus, other fungi. NOT elevated in bacterial or viral infections. Also FALSE POSITIVE with IVIG, albumin, gauze/cellulose dialysis membranes, certain antibiotics. Useful as a screening test — negative beta-D-glucan makes PCP unlikely (high negative predictive value).
Induced sputum
Less invasive first-line test. Nebulised 3% hypertonic saline (15-20 min) → induced sputum → send for immunofluorescence (DFA) / PCR / silver stain. Sensitivity ~50-90% (highest in HIV, where organism burden is high; lower in non-HIV). Requires a cooperative patient and trained staff. Dental hygiene first to reduce oral contamination.
BAL (bronchoalveolar lavage)
Gold standard. Send: immunofluorescence (direct fluorescent antibody — detects organisms), PCR (molecular — highest sensitivity/specificity; quantitative PCR useful — high burden suggests true disease), Grocott methenamine silver stain or Toluidine blue O (histological — detects cysts). BAL also rules out other causes (bacterial, viral, mycobacterial, fungal). Yield enhanced by BAL from the most affected lobe and by transbronchial biopsy. In the hypoxic patient, NIV-assisted bronchoscopy reduces peri-procedure deterioration.
Do NOT delay therapy for the test
In moderate-severe disease, start empiric co-trimoxazole (+ steroids if indicated) immediately and perform bronchoscopy within 24 h. Diagnostic yield of BAL remains high for 48-72 h after starting therapy.
Treatment
PCP treatment protocol
Co-trimoxazole (trimethoprim-sulfamethoxazole) FIRST-LINE
High dose: 15-20 mg/kg/day trimethoprim component (usually 4 tablets QID of 160/800 mg, or IV equivalent — 2 ampoules IV QID for a 70 kg adult). Duration: 21 days. Mechanism: sequential inhibition of folate synthesis (TMP inhibits dihydrofolate reductase, SMX inhibits dihydropteroate synthetase — synergistic). Side effects: rash (including SJS), fever, nausea, hepatitis, hyperkalaemia (TMP blocks distal tubular ENaC — amiloride-like), crystalluria, marrow suppression (especially with high doses — monitor FBC). Switch to oral once tolerating and improving.
Add CORTICOSTEROIDS if hypoxic
If PaO2 <70 mmHg or A-a gradient >35 mmHg: add prednisolone 40 mg BD x 5 days, then 40 mg daily x 5 days, then 20 mg daily x 11 days (total 21 days). Equally: methylprednisolone 30 mg BD IV x 5d, then 30 mg daily x 5d, then 15 mg daily x 11d. Mechanism: reduces inflammation from organism lysis after starting antibiotics (improves oxygenation, reduces mortality — Cochrane confirms benefit in moderate-severe PCP). Give at the SAME time as the first antibiotic dose — do not wait for deterioration.<Cite id="2" />
NIV preferred over intubation
NIV (CPAP/BiPAP, typically EPAP 5-8, IPAP titrated to ventilation/comfort, FiO2 to SpO2 88-92%) reduces intubation rates and mortality in immunocompromised patients with respiratory failure (avoids VAP — devastating in immunocompromised). Use full face mask, PEEP to recruit, FiO2 to target. If NIV fails (rising RR, falling SpO2, exhaustion, rising CO2) or patient deteriorates: intubate with lung-protective ventilation (6 mL/kg tidal volume, plateau pressure <30, permissive hypercapnia — ARDS protocol).<Cite id="4" />
Alternative agents (sulfa allergy or treatment failure)
Primaquine 30 mg PO daily + clindamycin 600 mg IV Q6H (or 600-900 mg IV Q8H) — best alternative for moderate-severe disease; check G6PD first (primaquine causes haemolysis). Pentamidine isethionate 4 mg/kg IV daily — effective but nephrotoxic, pancreatic toxicity (diabetes / hypoglycaemia from insulin release), QT prolongation, hypotension on infusion. Atovaquone 750 mg PO BD — oral only, for MILD disease; less effective than co-trimoxazole. Dapsone 100 mg PO daily + trimethoprim 5 mg/kg QID — milder side-effect profile, less effective.
Treatment failure — reassess at 5-7 days
If no clinical improvement (or worsening hypoxia) by day 5-7: confirm adherence and adequate dosing, exclude alternative/overlapping diagnosis (CMV co-infection, bacterial superinfection, pneumothorax, IRIS), consider resistant organism (rare), and consider switching therapy. Continue full 21-day course — deterioration at day 3-5 may be the inflammatory response rather than failure. Adding steroids (if not already given) or boosting the steroid dose may help.
Prophylaxis (after treatment, and in at-risk groups)
Co-trimoxazole 1 SS tablet (800/160 mg) daily OR 1 DS tablet 3x weekly. Continue until: CD4 >200 for >3-6 months (HIV on ART), >6 months post-transplant (or indefinitely for some, e.g. lung), immunosuppression reduced below threshold. Alternatives if sulfa-allergic: dapsone 100 mg daily (check G6PD), atovaquone 1500 mg daily, aerosolised pentamidine 300 mg monthly via Respirgard II nebuliser. Breakthrough on aerosolised pentamidine classically = UPPER-lobe disease.
Corticosteroids for moderate-severe PCP (consolidated RCT evidence / NIH-IACT)
RCTs of adjunctive corticosteroids vs placebo in PCP with PaO2 < 70 or A-a gradient > 35
Population: HIV-positive adults with documented PCP and moderate-severe hypoxaemia
Key finding
Adjunctive corticosteroids reduced progression to respiratory failure (~40% → ~10%) and halved mortality in moderate-severe PCP. Benefit greatest if started within 72 h of antibiotics.
Practice change
Give prednisolone 40 mg BD with the first co-trimoxazole dose whenever PaO2 < 70 mmHg or A-a gradient > 35 mmHg. Do not wait for deterioration.
Co-trimoxazole vs pentamidine for PCP (ACTG 108 / Bozzette, NEJM 1995)
RCT, three arms, ~340 patients with mild-to-moderate PCP
Population: HIV-positive adults with first episode of histologically confirmed PCP
Key finding
Co-trimoxazole had the best overall outcome; tolerability was the main differentiator rather than efficacy. Dapsone-TMP equivalent for mild disease.
Practice change
High-dose co-trimoxazole remains first-line for PCP of any severity; switch only for toxicity or failure.
Antimicrobial alternatives compared
Co-trimoxazole
First-line
- TMP 15-20 mg/kg/day + SMX 75-100 mg/kg/day, oral or IV, 21 days
- Efficacy: ~90% cure in mild-moderate, ~70% in severe
- Toxicity: rash (10-20%, including SJS), hyperkalaemia, AKI, marrow suppression, hepatitis, crystalluria
- Switch to oral when improving and tolerating PO
- Reduce hyperkalaemia: avoid concurrent K-sparing diuretics / ACEi, monitor U&E
Primaquine + clindamycin
Best second-line
- Primaquine 30 mg PO daily + clindamycin 600 mg IV Q6H (or 300-450 mg PO Q6H), 21 days
- Efficacy comparable to co-trimoxazole in moderate-severe disease
- CHECK G6PD before primaquine — causes haemolysis / methaemoglobinaemia in deficiency
- Toxicity: rash, diarrhoea/C. difficile, haemolysis (G6PD), methaemoglobinaemia
Pentamidine IV
Reserve
- 4 mg/kg IV daily (slow infusion to avoid hypotension), 21 days
- Effective but TOXIC — reserve for co-trimoxazole failure / severe sulfa allergy
- Toxicity: nephrotoxicity (~25%), pancreatic — hyper/hypoglycaemia (insulin release → diabetes), QT prolongation, arrhythmias, transaminitis, marrow suppression
- Monitor U&E, glucose, ECG daily
Atovaquone
Mild only / oral
- 750 mg PO BD with fatty food, 21 days
- Oral only — for MILD disease in patients who cannot tolerate co-trimoxazole
- Less effective than co-trimoxazole; not for ICU / hypoxic patients
- Toxicity: rash, GI upset, transaminitis — generally well tolerated
Dapsone + TMP
Mild alternative
- Dapsone 100 mg PO daily + TMP 5 mg/kg QID, 21 days
- Check G6PD first (haemolysis / methaemoglobinaemia)
- For mild disease or sulfa component intolerance; less effective than co-trimoxazole
Steroid taper regimen for moderate-severe PCP
Prednisolone taper (start with first antibiotic dose)
Days 1-5
Prednisolone 40 mg PO BD (80 mg/day), OR methylprednisolone 30 mg IV BD if NBM. Continue alongside co-trimoxazole.
Days 6-10
Prednisolone 40 mg PO daily (40 mg/day). Reassess oxygenation — most improvement seen in first 5 days.
Days 11-21
Prednisolone 20 mg PO daily (20 mg/day). Total corticosteroid course 21 days, matching the antibiotic course.
Pitfalls
In non-HIV immunocompromised patients (who often have a more inflammatory phenotype), consider a longer/slower taper to avoid rebound. Cover for PJP-mimicking IRIS if starting ART. Co-proxamol of prophylaxis: stress-ulcer (PPI) and PCP prophylaxis should continue. Watch for: hyperglycaemia, candidiasis, neuromyopathy, reactivation of HSV/CMV/strongyloides.
ICU supportive management
Supportive care bundle
Respiratory support
Target SpO2 88-92% (permissive — avoid hyperoxia-induced absorption atelectasis and free-radical injury). Escalate: nasal specs → HFNO → NIV (CPAP/BiPAP) → invasive ventilation. HFNO increasingly used as a bridge; NIV is the preferred modality for hypoxaemic respiratory failure in immunocompromised (reduced intubation and mortality vs standard O2). If intubated: lung-protective ventilation (Vt 6 mL/kg PBW, Pplat <30, driving pressure <15), permissive hypercapnia, consider prone positioning for severe refractory hypoxaemia.
Fluid strategy
Conservative fluid strategy (as in ARDS) — the lung in PCP is exquisitely oedema-sensitive. Avoid liberal crystalloid; use vasopressors early for shock rather than fluid boluses. This is a classic ARDS-pattern lung.
Concurrent antimicrobials
Empirical bacterial cover initially (the diagnosis may not be confirmed) — ceftriaxone + azithromycin or per local CAP pathway until PCP confirmed. Send atypical and viral panels (CMV co-infection common — treat if BAL CMV PCR high). Continue PCP prophylaxis-dose co-trimoxazole after treatment course? — NO: after a full 21-day treatment course, step DOWN to prophylaxis dose.
HIV testing and ART
Offer HIV testing (opt-out) to all PCP patients — PCP may be the index AIDS diagnosis. If newly diagnosed HIV: do NOT start ART immediately — wait ~2 weeks into PCP treatment to reduce IRIS risk (early ART paradoxically worsened outcomes in early studies; modern data favour ART within 2 weeks for CD4 < 50, deferred 1-2 weeks for higher CD4). Involve ID/HIV team.
VTE prophylaxis, glycaemic control, nutrition, stress-ulcer
Standard ICU bundle: VTE prophylaxis (LMWH — immunocompromised patients are pro-thrombotic), tight-ish glycaemic control (steroids cause hyperglycaemia), early enteral nutrition, stress-ulcer prophylaxis if intubated/coagulopathic. Daily FBC, U&E (hyperkalaemia from co-trimoxazole), LFTs, LDH (falls with response).
Complications
Respiratory failure / ARDS
Most common reason for ICU
- Progressive hypoxaemia → type 1 respiratory failure
- May meet ARDS Berlin criteria (bilateral opacities, non-cardiogenic, PaO2/FiO2 < 300)
- Manage with lung-protective ventilation; consider prone / ECMO in refractory cases
Pneumothorax
Cystic / pneumatocele rupture
- Pneumatoceles form in severe PCP — thin-walled, often upper lobe
- Rupture → pneumothorax (may be bilateral, tension, persistent)
- Avoid high PEEP and high inspiratory pressures; chest drain if symptomatic; surgical pleurodesis for persistent air leak
- Prophylactic chest drain before transport/ventilation if large cysts present
Drug toxicity
Treatment-related
- Co-trimoxazole: rash, SJS, hyperkalaemia, AKI, marrow suppression, hepatitis
- Pentamidine: AKI, pancreatic (hyper/hypoglycaemia), QT, hypotension
- Primaquine: haemolysis (G6PD), methaemoglobinaemia
- Corticosteroids: hyperglycaemia, candidiasis, neuromyopathy, CMV/HSV reactivation
IRIS (immune reconstitution)
After ART
- Paradoxical worsening 1-4 weeks after starting ART in newly diagnosed HIV
- Fever, worsening infiltrates, hypoxia — clinically indistinguishable from untreated PCP
- Diagnose by confirming ART started recently + negative/high PCP burden on repeat BAL
- Treat with corticosteroids; do NOT stop ART unless life-threatening
Relapse / recurrence
Incomplete clearance
- Relapse rate high without secondary prophylaxis (historically up to 60% in 18 months)
- Secondary prophylaxis (co-trimoxazole) until CD4 > 200 for >3-6 months
- Reinfection vs relapse distinguishable by molecular typing (research)
Prophylaxis
Indications
Who needs prophylaxis
- HIV: CD4 <200 cells/microL, OR CD4 <14%, OR history of prior PCP (secondary), OR thrush with CD4 <200
- Transplant: most solid-organ 6-12 months (lifelong for lung); HSCT until 6 months post-engraftment (longer with GVHD)
- Prolonged steroids: prednisolone >20 mg/day for >4 weeks (and other intensive immunosuppression)
- Anti-TNF therapy, rituximab, alemtuzumab, purine analogues (fludarabine, cladribine)
- Primary immunodeficiency (hyper-IgM, SCID)
Regimens
First-line & alternatives
- FIRST-LINE: co-trimoxazole 1 SS (800/160 mg) tablet daily, OR 1 DS (800/160) tablet 3x weekly
- Alternative (sulfa allergy / intolerance): dapsone 100 mg daily (check G6PD); atovaquone 1500 mg daily; aerosolised pentamidine 300 mg monthly
- Dapsone + pyrimethamine + leucovorin if also toxoplasma prophylaxis needed
- Re-challenge / desensitisation often possible for mild sulfa reactions (graded protocol)
When to stop
Discontinuation criteria
- HIV on ART: CD4 >200 cells/microL sustained >3 months (some guidelines >6 months)
- Transplant: per protocol (typically 6-12 months; indefinite for lung)
- Steroids: when tapered below <20 mg/day and underlying disease controlled
- Never stop in the middle of an acute illness — resume promptly post-treatment
Breakthrough PCP
Prophylaxis failure
- Question ADHERENCE first (most common reason)
- Check dosing adequacy and drug interactions
- Aerosolised pentamidine: upper-lobe / extrapulmonary breakthrough (does not reach apices)
- Consider species-level resistance (rare; controversial) and immune status (CD4 still low)
Non-HIV vs HIV PCP — important differences
HIV-positive PCP
High organism burden
- Insidious over weeks; organism burden HIGH (BAL yield high, induced sputum usually sufficient)
- Hypoxia may be profound but inflammatory response relatively muted (high burden, fewer neutrophils)
- Mortality 10-20% even with treatment; up to 50% if ventilated
- Beta-D-glucan typically very high
- Standard 21-day course; ART deferred 1-2 weeks to avoid IRIS
Non-HIV PCP
Inflammatory phenotype
- More rapid onset (days); organism burden LOWER (BAL yield lower — may need transbronchial biopsy)
- Greater neutrophilic inflammation → often MORE severe course, HIGHER mortality (30-50%) despite lower burden
- More likely to need ICU and ventilation
- Diagnosis often delayed (PCP less suspected) → later presentation
- Beta-D-glucan may be only mildly elevated; LDH useful
- Steroid threshold (PaO2 < 70 / A-a > 35) same; some experts use steroids more liberally
- Reduce immunosuppression if possible (with transplant/oncology teams)
SAQ — Pneumocystis jirovecii pneumonia in HIV
SAQ — Severe Pneumocystis pneumonia in a patient with AIDS
10 minutes · 10 marks
A 36-year-old man is admitted with a 3-week history of progressive dyspnoea, dry cough and low-grade fever. He has lost 8 kg. Examination reveals RR 36, SpO2 84% on room air, bilateral fine crackles. CXR shows diffuse bilateral perihilar interstitial infiltrates (a 'bat-wing' pattern). ABG: PaO2 52 mmHg, A-a gradient 60 mmHg. He is not on any medications and is unaware of his HIV status.
SAQ — Co-trimoxazole-resistant or intolerant PCP
10 minutes · 10 marks
A 45-year-old man with a renal transplant on tacrolimus, mycophenolate and prednisolone 25 mg/day is admitted with severe PCP (PaO2 58 mmHg). He is started on high-dose IV co-trimoxazole but on day 4 develops a generalised maculopapular rash, AKI (creatinine doubled), and worsening hyperkalaemia. Blood cultures are negative.
Clinical pearls
Red flags
Exam practice — viva-style questions
[2]Summary answer (for the oral exam)
"Pneumocystis jirovecii pneumonia (PCP) in an immunocompromised ICU patient presents with insidious dyspnoea, dry cough, fever and hypoxia disproportionate to a chest film that may be normal early — classically in HIV with CD4 under 200, transplant recipients, and patients on prolonged high-dose steroids or anti-TNF biologics. I would confirm the diagnosis with induced sputum or bronchoalveolar lavage sent for immunofluorescence and PCR, supported by an elevated beta-D-glucan and LDH, while NOT delaying therapy in the hypoxic patient. First-line treatment is high-dose co-trimoxazole at 15-20 mg/kg/day of the trimethoprim component for 21 days. I would add corticosteroids — prednisolone 40 mg BD for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days — whenever the PaO2 is under 70 mmHg or the A-a gradient exceeds 35 mmHg, because this blunts the inflammatory response to organism lysis and reduces mortality. I would favour non-invasive ventilation over intubation to avoid ventilator-associated pneumonia in the immunocompromised host, use a conservative fluid strategy and lung-protective settings if intubated, screen and treat for CMV co-infection, and offer HIV testing with ART started roughly two weeks into therapy to balance immune reconstitution against virological control. After recovery I would institute secondary prophylaxis with single-strength co-trimoxazole daily, continuing until the CD4 count has been over 200 for at least three to six months."[2]
References
- [1]Xiao K Pneumocystis jirovecii Pneumonia. The New England journal of medicine, 2026.PMID 41556515
- [2]Ewald H, Raatz H, Boscacci R, et al. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. The Cochrane database of systematic reviews, 2015.PMID 25835432
- [3]Safrin S, Finkelstein DM, Feinberg J, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group. Annals of internal medicine, 1996.PMID 8610948
- [4]Confalonieri M, Calderini E, Terraciano S, et al. Noninvasive ventilation for treating acute respiratory failure in AIDS patients with Pneumocystis carinii pneumonia. Intensive care medicine, 2002.PMID 12209270