ICU · infectious-diseases

Pneumonia in the Immunocompromised Patient — Comprehensive ICU Management

Also known as Pneumonia in the immunocompromised host · Opportunistic pneumonia · Pulmonary infiltrates in the cancer patient · Pneumonia in transplant recipients · Pneumonia in haematological malignancy · Invasive pulmonary aspergillosis · Pneumocystis jirovecii pneumonia · CMV pneumonitis

Pneumonia in the immunocompromised host (non-HIV) — haematological malignancy, stem-cell/solid-organ transplant, prolonged steroids, cytotoxic chemotherapy, biologics. The pathogen spectrum is dictated by the SPECIFIC IMMUNE DEFECT: (1) NEUTROPENIA (post-chemo, <0.5 x 10^9/L) - Pseudomonas aeruginosa, other gram-negative bacilli, invasive pulmonary aspergillosis, Candida, mucositis-related viridans streptococci; (2) T-CELL DEFECT (transplant calcineurin inhibitors, fludarabine, alemtuzumab) - Pneumocystis jirovecii (PCP), CMV, Legionella, Nocardia, Cryptococcus, mycobacteria; (3) B-CELL / HUMORAL DEFECT (CLL, myeloma, post-rituximab) - encapsulated bacteria — Streptococcus pneumoniae, Haemophilus influenzae; (4) PROLONGED STEROIDS (20 mg/day prednisone 4 weeks) - PCP, Nocardia, Aspergillus. The intensivist's task: (1) classify the immune defect, (2) get a diagnostic BAL EARLY (galactomannan for Aspergillus, (1-3)-beta-D-glucan for PCP/fungal, CMV PCR, respiratory virus panel, bacterial + fungal + mycobacterial culture), (3) start BROAD EMPIRIC THERAPY — anti-pseudomonal beta-lactam + empiric antifungal (caspofungin for Candida, voriconazole for suspected mould) + ganciclovir if CMV likely + co-trimoxazole if PCP possible + reduce immunosuppression, (4) prefer NIV over intubation (lower VAP/mortality), (5) prophylaxis — co-trimoxazole (PCP), posaconazole (Aspergillus), valganciclovir (CMV). Mortality 20-50% — far higher than immunocompetent CAP. Early appropriate (pathogen-directed) therapy is the single biggest modifiable determinant of survival.

high6 referencesUpdated 2 July 2026

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The PATHOGEN SPECTRUM follows the IMMUNE DEFECT — neutropenia -> Pseudomonas/Aspergillus; T-cell defect -> PCP/CMV/Nocardia; B-cell defect -> S. pneumoniae/H. influenzae; steroids -> PCP/Nocardia/Aspergillus. Classify the defect BEFORE choosing empiric therapyGet a diagnostic BAL EARLY — do not sit on empiric therapy. Send the full panel: bacterial/fungal/mycobacterial culture, galactomannan (Aspergillus), (1-3)-beta-D-glucan (PCP/fungal), CMV PCR, respiratory virus panel, Nocardia, PCP PCR/immunofluorescenceInvasive pulmonary aspergillosis in neutropenia — voriconazole FIRST-LINE, check BAL galactomannan (OD index >=1.0) and CT HALO SIGN (nodule with ground-glass halo = angioinvasion)CMV pneumonitis 1-4 months post-transplant or during rejection treatment — ganciclovir 5 mg/kg IV BD; diagnose on BAL CMV PCR + cytopathic effect (owl's-eye inclusions)Prefer NIV over intubation for hypoxaemic respiratory failure — immunocompromised patients who are intubated have high VAP and mortality; early NIV reduces bothReduce immunosuppression if possible (balance against graft rejection / GVHD) — the 'net state of immunosuppression' must come down for any antimicrobial to work

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Cinematic ICU scene of immunocompromised pneumonia: transplant/chemo patient on oxygen, CT concept of infiltrates, clinical-blue, no faces — FigureImmune defect dictates pathogens — early CT and BAL before or with broad layered antimicrobials.

Educational classification of immune defects: neutropenia, T-cell, humoral, with typical pulmonary pathogens, clinical-blue — FigureNeutropenia → Pseudomonas/moulds; T-cell → PCP/CMV/Nocardia; humoral → encapsulated bacteria.

Management algorithm for immunocompromised pneumonia: cultures, CT, BAL, empiric layers, de-escalation — FigureDo not guess one bug — cover by defect, obtain lower-airway samples early, de-escalate on results.

Overview

The one-paragraph exam answer

Pneumonia in the immunocompromised host is fundamentally different from CAP in the immunocompetent: the pathogen spectrum is dictated by the SPECIFIC IMMUNE DEFECT, not by community epidemiology. (1) Neutropenia (post-cytotoxic chemo, <0.5 x 10^9/L, nadir day 7-14) -> Pseudomonas aeruginosa and other gram-negative bacilli, invasive pulmonary aspergillosis, Candida, and mucositis-related viridans streptococci. (2) T-cell defect (calcineurin inhibitors post-transplant, fludarabine, alemtuzumab, purine analogues) -> PCP, CMV, Legionella, Nocardia, Cryptococcus, mycobacteria. (3) B-cell / humoral defect (CLL, multiple myeloma, post-rituximab) -> encapsulated bacteria — S. pneumoniae, H. influenzae. (4) Prolonged steroids (>20 mg/day prednisone >4 weeks) -> PCP, Nocardia, Aspergillus.[2] Two non-negotiable rules: get a diagnostic BAL EARLY and send the full panel (bacterial/fungal/mycobacterial culture, galactomannan for Aspergillus, (1-3)-beta-D-glucan for PCP/fungal, CMV PCR, respiratory virus panel, Nocardia, PCP PCR); and start BROAD EMPIRIC THERAPY while awaiting results — anti-pseudomonal beta-lactam (piperacillin-tazobactam/cefepime/meropenem) + empiric antifungal (caspofungin for Candida, voriconazole for suspected mould) + ganciclovir if CMV likely + co-trimoxazole if PCP possible, with immunosuppression reduced. Prefer NIV over intubation (lower VAP and mortality in hypoxaemic immunocompromised patients). Mortality 20-50% — the single biggest modifiable determinant of survival is early appropriate (pathogen-directed) therapy, which requires an early invasive diagnostic.[2][5][6]

The cardinal principle is that the immune defect predicts the pathogen, and the pathogen predicts the therapy. A neutropenic leukaemia patient 10 days post-induction with a cavitating lung lesion has invasive aspergillosis until proven otherwise; a renal transplant recipient 3 months post-operatively on tacrolimus with diffuse ground-glass infiltrates and hypoxaemia out of proportion to the CXR has PCP or CMV until proven otherwise. Unlike CAP — where a syndromic "cover typicals + atypicals" approach is adequate — immunocompromised pneumonia demands a structured, defect-specific differential and an early invasive diagnostic (bronchoalveolar lavage), because the consequences of treating the wrong pathogen for 48-72 hours are fatal, and because half of these patients have an organism (fungal, viral, opportunistic) that no routine empiric antibiotic will reach.[2]

The immune-defect framework — pathogens follow the defect

[5]

Diagnostic approach — image, sample, send the full panel

Early chest imaging and an invasive diagnostic (BAL) are the two highest-yield manoeuvres. Do not manage immunocompromised pneumonia "empirically only" — the diagnosis is almost never made on clinical grounds alone, and empiric therapy that misses a mould or a virus is fatal.[5]

Imaging

High-resolution CT chest is the imaging modality of choice (chest X-ray is normal or non-specific in up to 50% early). Get a CT within hours of admission.
Halo sign — nodule surrounded by ground-glass attenuation = alveolar haemorrhage around an area of angioinvasive mould = invasive pulmonary aspergillosis (classic in neutropenia).[6]
Air-crescent sign — crescent of air rimming a necrotic nodule = late angioinvasive aspergillosis (appears as neutrophils recover).
Reversed halo / atoll — central ground-glass with peripheral consolidation = organising pneumonia; can be PCP or Mucorales.
Diffuse bilateral ground-glass = PCP or CMV (also drug-induced pneumonitis, pulmonary haemorrhage).
Tree-in-bud = endobronchial spread — bacterial bronchopneumonia, Nocardia, mycobacteria.
Multiple nodules ± cavitation = Aspergillus, Nocardia, Cryptococcus, septic emboli, metastatic infection.

Bronchoalveolar lavage — the single most important diagnostic test

BAL is indicated early (within 24-48 h) in any immunocompromised patient with pulmonary infiltrates of unclear aetiology, or who fails to respond to 48-72 h of empiric therapy. It carries a low complication rate (bleeding in thrombocytopenic patients — transfuse platelets to keep >50 before scope) and a diagnostic yield of 40-70%.[2]

Serum biomarkers complement BAL: serum galactomannan (OD index >=0.5, twice) is a useful screen for invasive aspergillosis in neutropenic patients; serum (1-3)-beta-D-glucan is elevated in PCP and deep fungal infection (negative in Cryptococcus/Mucorales); LDH is characteristically very high in PCP; 1,3-beta-D-glucan + procalcitonin help separate fungal/viral from bacterial. Blood cultures (2 sets + line cultures) are still mandatory — bacteraemia with Pseudomonas or Candida changes duration and prognosis.[2]

Management protocol — the first 24 hours

[2]

Empiric therapy by suspected syndrome

The empiric regimen is built by layering agents onto an anti-pseudomonal backbone according to the most likely pathogen(s) implied by the immune defect and imaging. Start broad, then narrow within 48-72 h using BAL results.[6]

Respiratory support — prefer NIV, avoid intubation when possible

[2]

The evidence base (Antonelli 2000, Azoulay trials): in immunocompromised patients with pulmonary infiltrates and hypoxaemia, early NIV lowered the intubation rate and 90-day mortality compared with standard oxygen ± intubation. The message for the exam: reach for the BiPAP mask before the laryngoscope — but recognise NIV failure early (rising respiratory rate, rising PaCO2, falling pH, exhaustion) and intubate without delay.[2]

Prophylaxis — prevent the predictable

Prophylaxis is the single most effective intervention against opportunistic pneumonia and should be audited on every immunocompromised ICU admission (patients are often non-adherent or the prophylaxis was stopped).[1][4]

[1]

SAQ — defect-driven differential in the allogeneic HSCT recipient

SAQ — Defect-driven differential and diagnostic approach in an immunocompromised lung

10 minutes · 10 marks

A 60-year-old man is day +90 after allogeneic haematopoietic stem-cell transplant for AML. He is on tacrolimus and prednisolone 1 mg/kg/day for grade II skin GVHD. Co-trimoxazole was stopped two weeks ago because of neutropenia. He presents with five days of dry cough, exertional dyspnoea and fever (38.9°C). On room air his SpO2 is 88% with an A-a gradient of 50 mmHg; the chest X-ray is subtly hyperinflated and unremarkable. High-resolution CT chest shows diffuse bilateral ground-glass opacification without nodules or cavitation.

[1]

SAQ — CMV pneumonitis in a high-risk solid-organ transplant recipient

SAQ — CMV pneumonitis in a D+/R- kidney transplant recipient

10 minutes · 10 marks

A 35-year-old man is two months after deceased-donor kidney transplant (donor CMV IgG-positive, recipient CMV IgG-negative). His immunosuppression is tacrolimus, mycophenolate mofetil and prednisolone. He was admitted for biopsy-proven acute cellular rejection one week ago and received a methylprednisolone pulse. He now has five days of fever, malaise, progressive dyspnoea, leucopenia (WCC 1.8 ×10^9/L) and thrombocytopenia. CT chest shows diffuse bilateral ground-glass opacities and scattered small nodules. Plasma CMV PCR is 350,000 IU/mL and bronchoalveolar lavage transbronchial biopsy shows cytomegalic cells with characteristic intranuclear owl's-eye inclusions.

[5]

Clinical pearls

Clinical pearl

The pathogen follows the defect — classify it before prescribing. Neutropenia -> Pseudomonas/Aspergillus; T-cell defect -> PCP/CMV/Nocardia/Legionella/Cryptococcus; B-cell defect -> S. pneumoniae/H. influenzae; steroids -> PCP/Nocardia/Aspergillus. Writing the defect-driven differential explicitly is the single highest-yield exam manoeuvre.[2]
Get a diagnostic BAL EARLY — empiric-only management kills patients. In immunocompromised pneumonia, ~50% of final diagnoses are organisms that no routine empiric regimen covers (a mould, a virus, Nocardia, an atypical mycobacterium). Sitting on broad-spectrum antibiotics without sampling condemns these patients to undirected, escalating, toxic polypharmacy. Bronchoscopy with the full panel within 24-48 h is the standard of care.[2][5]
Send the FULL BAL panel — one scope, many tests. Bacterial + fungal + mycobacterial culture, galactomannan, (1-3)-beta-D-glucan, CMV PCR + cytology, respiratory virus panel, Nocardia (hold plates), PCP PCR/immunofluorescence, cell count and cytology (for haemorrhage / malignancy / drug pneumonitis). Each test answers a different question; a partial panel is a missed diagnosis.[5]
Galactomannan and beta-D-glucan are powerful — but know their limits. BAL galactomannan OD index >=1.0 strongly supports invasive aspergillosis (more sensitive than serum); serum OD >=0.5 twice is a screen. False-positive galactomannan with piperacillin-tazobactam (historically) and in gut-translocation/mucositis. (1-3)-beta-D-glucan is NEGATIVE in Cryptococcus and Mucorales (they lack this cell-wall polymer) — a negative beta-D-glucan in a patient with a sinus/lung mould should raise Mucorales, not reassure you.[6]
Invasive pulmonary aspergillosis — voriconazole first-line, monitor levels and CT. Voriconazole (6 mg/kg IV q12h x2 then 4 mg/kg q12h) improved survival vs amphotericin in the landmark Herbrecht trial. Monitor trough (1-5.5 mg/L) — voriconazole has erratic oral pharmacokinetics and the famous toxicities (visual disturbance, hepatotoxicity, photosensitivity, periostitis). The CT halo sign (nodule + ground-glass halo = angioinvasion) is the radiological signature in neutropenia. Isavuconazole is an alternative (better tolerability, covers Mucorales).[6]
CMV pneumonitis — diagnose on syndrome, not shedding. CMV PCR positivity in BAL or blood is common after transplant; CMV pneumonitis requires the triad of (a) a compatible syndrome (hypoxaemia, diffuse infiltrates, typically 1-4 months post-transplant or during rejection treatment), (b) a rising/high viral load, and (c) cytopathic effect in BAL cells (owl's-eye inclusions). Treat with ganciclovir 5 mg/kg IV q12h (renally dose-adjust) for 14-21 days; add IVIG in severe disease. Resistance (UL97/UL54 mutations) should be suspected with rising load on therapy.[2]
Severe PCP needs steroids within 72 hours — give them. For PCP with PaO2 <70 mmHg or A-a gradient >35, adjunctive corticosteroids (prednisone 40 mg BD x5 days, then 40 mg daily x5, then 20 mg daily to day 21) reduce mortality by preventing inflammatory lung injury at organism lysis. Do not wait for microbiological confirmation if PCP is clinically likely — start co-trimoxazole + steroids immediately.[1][5]
NIV before intubation — but recognise failure early. Immunocompromised patients with pulmonary infiltrates and hypoxaemia given early NIV have lower intubation rates and lower mortality than those intubated upfront. Reach for BiPAP first. BUT: NIV failure (rising PaCO2, falling pH, exhaustion, copious secretions, shock) must trigger prompt intubation — prolonged failed NIV is itself associated with worse outcome.[2]
Reduce the 'net state of immunosuppression'. No antimicrobial regimen will cure an infection in a patient whose immune suppression remains maximal. Where feasible, taper steroids, lower calcineurin-inhibitor targets, and interrupt biologics — always in dialogue with the transplant/haematology team to balance against graft rejection and GVHD. This is Fishman's central concept: infection risk reflects the integrated 'net state' (drug intensity + dose + duration + epidemiological exposure + comorbidity), not the regimen name.[2]
Voriconazole and the calcineurin inhibitors — a dangerous interaction. Azoles (voriconazole, posaconazole, itraconazole) inhibit CYP3A4 and can raise tacrolimus/cyclosporine levels 2-4 fold, causing nephrotoxicity and PRES. Reduce calcineurin-inhibitor dose by 50-75% when starting an azole and re-check troughs within 3-5 days. Co-trimoxazole raises warfarin/DOAC effect; macrolides prolong QTc — review the whole drug chart.[2]
Do not forget non-infectious causes — they mimic infection and BAL can spare you a toxic antimicrobial escalation. Drug-induced pneumonitis (bleomycin, methotrexate, busulfan, checkpoint inhibitors), radiation pneumonitis, pulmonary oedema, diffuse alveolar haemorrhage (vasculitis, thrombocytopenia), graft-versus-host disease of the lung, pulmonary embolism, and leukaemic/lymphomatous infiltrates all produce infiltrates and hypoxaemia. BAL cytology + CT pattern + temporal relationship to drug/radiation/rejection help separate these; continuing to add antibiotics for a deteriorating patient with a non-infectious process is a classic, fatal error.[2]
Mucorales — the mould that breaks the rules. Suspect when a neutropenic/diabetic/iron-overloaded patient deteriorates on voriconazole, has sinus or palatal involvement, a reversed-halo sign, or rapidly progressive infection. Voriconazole does NOT cover Mucorales — switch to high-dose liposomal amphotericin B (5-10 mg/kg/day) and obtain urgent surgical debridement (mucor is angioinvasive and forms thrombi that limit drug penetration). Mortality is 50-80% even with correct therapy.[2]
Respiratory viruses are under-diagnosed and dangerous in the immunocompromised. Influenza, RSV, parainfluenza, adenovirus and metapneumovirus cause severe lower-tract disease with prolonged viral shedding and high rates of bacterial/fungal superinfection in transplant recipients. Send a respiratory virus panel on every BAL — and treat (oseltamivir for influenza even beyond 48 h; ribavirin for RSV in HSCT) and isolate (shedding is prolonged, fuelling nosocomial outbreaks).[3]
Prophylaxis works only if it is taken — audit adherence on admission. PCP, CMV and mould prophylaxis dramatically reduce opportunistic pneumonia, but non-adherence, drug interactions, interruptions during neutropenia/mucositis, and stopped prescriptions are common reasons for 'breakthrough' infection. Reconcile the prophylaxis list on every immunocompromised admission; a patient with PCP in whom co-trimoxazole was stopped weeks earlier is a recurring, preventable tragedy.[1][4]

Red flags

[2] [2]

Prognosis

[3]

The most powerful modifiable prognostic factor is early appropriate, pathogen-directed therapy, which is itself contingent on early invasive diagnosis. Host factors that compound mortality are severe neutropenia of long duration, high-intensity immunosuppression (GVHD, recent T-cell-depleting therapy), mechanical ventilation, multi-organ failure, and the underlying malignancy/transplant status.[1]

Key trials and evidence

ECIL-5 guidelines — Pneumocystis pneumonia in haematological malignancy and HSCT (PMID 27550990 / 27550991)

[2]

IDSA 2016 Aspergillosis guidelines — Patterson TF, et al. (PMID 27365388)

[1]

Maschmeyer & Donnelly — managing lung infiltrates in haematological malignancy (PMID 26729577)

[1]

Examiner densification notes

[1] [3]

References

[1]Cordonnier C, Cesaro S, Maschmeyer G, et al. Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients (ECIL-5). J Antimicrob Chemother, 2016.PMID 27550990
[2]Maschmeyer G, Donnelly JP. How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation. Br J Haematol, 2016.PMID 26729577
[3]Lehners N, Tabatabai J, Prifert C, et al. Long-term shedding of influenza virus, parainfluenza virus, respiratory syncytial virus and nosocomial epidemiology in patients with hematological disorders. PLoS One, 2016.PMID 26866481
[4]Fishman JA. Pneumocystis jiroveci. Semin Respir Crit Care Med, 2020.PMID 32000290
[5]Alanio A, Hauser PM, Lagrou K, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother, 2016.PMID 27550991
[6]Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis, 2016.PMID 27365388

ICU · infectious-diseases

Pneumonia in the Immunocompromised Patient — Comprehensive ICU Management

high6 referencesUpdated 2 July 2026

On this page & tools

Your progress

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Target exams

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Red flags

Your progress

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Target exams

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Red flags

Overview

The one-paragraph exam answer

The immune-defect framework — pathogens follow the defect

[5]

Diagnostic approach — image, sample, send the full panel

Imaging

High-resolution CT chest is the imaging modality of choice (chest X-ray is normal or non-specific in up to 50% early). Get a CT within hours of admission.
Halo sign — nodule surrounded by ground-glass attenuation = alveolar haemorrhage around an area of angioinvasive mould = invasive pulmonary aspergillosis (classic in neutropenia).[6]
Air-crescent sign — crescent of air rimming a necrotic nodule = late angioinvasive aspergillosis (appears as neutrophils recover).
Reversed halo / atoll — central ground-glass with peripheral consolidation = organising pneumonia; can be PCP or Mucorales.
Diffuse bilateral ground-glass = PCP or CMV (also drug-induced pneumonitis, pulmonary haemorrhage).
Tree-in-bud = endobronchial spread — bacterial bronchopneumonia, Nocardia, mycobacteria.
Multiple nodules ± cavitation = Aspergillus, Nocardia, Cryptococcus, septic emboli, metastatic infection.

Bronchoalveolar lavage — the single most important diagnostic test

Management protocol — the first 24 hours

[2]

Empiric therapy by suspected syndrome

Respiratory support — prefer NIV, avoid intubation when possible

[2]

Prophylaxis — prevent the predictable

[1]

SAQ — defect-driven differential in the allogeneic HSCT recipient

SAQ — Defect-driven differential and diagnostic approach in an immunocompromised lung

10 minutes · 10 marks

[1]

SAQ — CMV pneumonitis in a high-risk solid-organ transplant recipient

SAQ — CMV pneumonitis in a D+/R- kidney transplant recipient

10 minutes · 10 marks

[5]

Clinical pearls

Clinical pearl

The pathogen follows the defect — classify it before prescribing. Neutropenia -> Pseudomonas/Aspergillus; T-cell defect -> PCP/CMV/Nocardia/Legionella/Cryptococcus; B-cell defect -> S. pneumoniae/H. influenzae; steroids -> PCP/Nocardia/Aspergillus. Writing the defect-driven differential explicitly is the single highest-yield exam manoeuvre.[2]
Get a diagnostic BAL EARLY — empiric-only management kills patients. In immunocompromised pneumonia, ~50% of final diagnoses are organisms that no routine empiric regimen covers (a mould, a virus, Nocardia, an atypical mycobacterium). Sitting on broad-spectrum antibiotics without sampling condemns these patients to undirected, escalating, toxic polypharmacy. Bronchoscopy with the full panel within 24-48 h is the standard of care.[2][5]
Send the FULL BAL panel — one scope, many tests. Bacterial + fungal + mycobacterial culture, galactomannan, (1-3)-beta-D-glucan, CMV PCR + cytology, respiratory virus panel, Nocardia (hold plates), PCP PCR/immunofluorescence, cell count and cytology (for haemorrhage / malignancy / drug pneumonitis). Each test answers a different question; a partial panel is a missed diagnosis.[5]
Galactomannan and beta-D-glucan are powerful — but know their limits. BAL galactomannan OD index >=1.0 strongly supports invasive aspergillosis (more sensitive than serum); serum OD >=0.5 twice is a screen. False-positive galactomannan with piperacillin-tazobactam (historically) and in gut-translocation/mucositis. (1-3)-beta-D-glucan is NEGATIVE in Cryptococcus and Mucorales (they lack this cell-wall polymer) — a negative beta-D-glucan in a patient with a sinus/lung mould should raise Mucorales, not reassure you.[6]
Invasive pulmonary aspergillosis — voriconazole first-line, monitor levels and CT. Voriconazole (6 mg/kg IV q12h x2 then 4 mg/kg q12h) improved survival vs amphotericin in the landmark Herbrecht trial. Monitor trough (1-5.5 mg/L) — voriconazole has erratic oral pharmacokinetics and the famous toxicities (visual disturbance, hepatotoxicity, photosensitivity, periostitis). The CT halo sign (nodule + ground-glass halo = angioinvasion) is the radiological signature in neutropenia. Isavuconazole is an alternative (better tolerability, covers Mucorales).[6]
CMV pneumonitis — diagnose on syndrome, not shedding. CMV PCR positivity in BAL or blood is common after transplant; CMV pneumonitis requires the triad of (a) a compatible syndrome (hypoxaemia, diffuse infiltrates, typically 1-4 months post-transplant or during rejection treatment), (b) a rising/high viral load, and (c) cytopathic effect in BAL cells (owl's-eye inclusions). Treat with ganciclovir 5 mg/kg IV q12h (renally dose-adjust) for 14-21 days; add IVIG in severe disease. Resistance (UL97/UL54 mutations) should be suspected with rising load on therapy.[2]
Severe PCP needs steroids within 72 hours — give them. For PCP with PaO2 <70 mmHg or A-a gradient >35, adjunctive corticosteroids (prednisone 40 mg BD x5 days, then 40 mg daily x5, then 20 mg daily to day 21) reduce mortality by preventing inflammatory lung injury at organism lysis. Do not wait for microbiological confirmation if PCP is clinically likely — start co-trimoxazole + steroids immediately.[1][5]
NIV before intubation — but recognise failure early. Immunocompromised patients with pulmonary infiltrates and hypoxaemia given early NIV have lower intubation rates and lower mortality than those intubated upfront. Reach for BiPAP first. BUT: NIV failure (rising PaCO2, falling pH, exhaustion, copious secretions, shock) must trigger prompt intubation — prolonged failed NIV is itself associated with worse outcome.[2]
Reduce the 'net state of immunosuppression'. No antimicrobial regimen will cure an infection in a patient whose immune suppression remains maximal. Where feasible, taper steroids, lower calcineurin-inhibitor targets, and interrupt biologics — always in dialogue with the transplant/haematology team to balance against graft rejection and GVHD. This is Fishman's central concept: infection risk reflects the integrated 'net state' (drug intensity + dose + duration + epidemiological exposure + comorbidity), not the regimen name.[2]
Voriconazole and the calcineurin inhibitors — a dangerous interaction. Azoles (voriconazole, posaconazole, itraconazole) inhibit CYP3A4 and can raise tacrolimus/cyclosporine levels 2-4 fold, causing nephrotoxicity and PRES. Reduce calcineurin-inhibitor dose by 50-75% when starting an azole and re-check troughs within 3-5 days. Co-trimoxazole raises warfarin/DOAC effect; macrolides prolong QTc — review the whole drug chart.[2]
Do not forget non-infectious causes — they mimic infection and BAL can spare you a toxic antimicrobial escalation. Drug-induced pneumonitis (bleomycin, methotrexate, busulfan, checkpoint inhibitors), radiation pneumonitis, pulmonary oedema, diffuse alveolar haemorrhage (vasculitis, thrombocytopenia), graft-versus-host disease of the lung, pulmonary embolism, and leukaemic/lymphomatous infiltrates all produce infiltrates and hypoxaemia. BAL cytology + CT pattern + temporal relationship to drug/radiation/rejection help separate these; continuing to add antibiotics for a deteriorating patient with a non-infectious process is a classic, fatal error.[2]
Mucorales — the mould that breaks the rules. Suspect when a neutropenic/diabetic/iron-overloaded patient deteriorates on voriconazole, has sinus or palatal involvement, a reversed-halo sign, or rapidly progressive infection. Voriconazole does NOT cover Mucorales — switch to high-dose liposomal amphotericin B (5-10 mg/kg/day) and obtain urgent surgical debridement (mucor is angioinvasive and forms thrombi that limit drug penetration). Mortality is 50-80% even with correct therapy.[2]
Respiratory viruses are under-diagnosed and dangerous in the immunocompromised. Influenza, RSV, parainfluenza, adenovirus and metapneumovirus cause severe lower-tract disease with prolonged viral shedding and high rates of bacterial/fungal superinfection in transplant recipients. Send a respiratory virus panel on every BAL — and treat (oseltamivir for influenza even beyond 48 h; ribavirin for RSV in HSCT) and isolate (shedding is prolonged, fuelling nosocomial outbreaks).[3]
Prophylaxis works only if it is taken — audit adherence on admission. PCP, CMV and mould prophylaxis dramatically reduce opportunistic pneumonia, but non-adherence, drug interactions, interruptions during neutropenia/mucositis, and stopped prescriptions are common reasons for 'breakthrough' infection. Reconcile the prophylaxis list on every immunocompromised admission; a patient with PCP in whom co-trimoxazole was stopped weeks earlier is a recurring, preventable tragedy.[1][4]

Red flags

[2] [2]

Prognosis

[3]

Key trials and evidence

ECIL-5 guidelines — Pneumocystis pneumonia in haematological malignancy and HSCT (PMID 27550990 / 27550991)

[2]

IDSA 2016 Aspergillosis guidelines — Patterson TF, et al. (PMID 27365388)

[1]

Maschmeyer & Donnelly — managing lung infiltrates in haematological malignancy (PMID 26729577)

[1]

Examiner densification notes

[1] [3]

References

[1]Cordonnier C, Cesaro S, Maschmeyer G, et al. Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients (ECIL-5). J Antimicrob Chemother, 2016.PMID 27550990
[2]Maschmeyer G, Donnelly JP. How to manage lung infiltrates in adults suffering from haematological malignancies outside allogeneic haematopoietic stem cell transplantation. Br J Haematol, 2016.PMID 26729577
[3]Lehners N, Tabatabai J, Prifert C, et al. Long-term shedding of influenza virus, parainfluenza virus, respiratory syncytial virus and nosocomial epidemiology in patients with hematological disorders. PLoS One, 2016.PMID 26866481
[4]Fishman JA. Pneumocystis jiroveci. Semin Respir Crit Care Med, 2020.PMID 32000290
[5]Alanio A, Hauser PM, Lagrou K, et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother, 2016.PMID 27550991
[6]Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis, 2016.PMID 27365388