Hematology, Oncology & Immunology · Topic 22 of 26

Infections in the Immunocompromised Host

Infectious disease · immunocompromised host

Infections in the Immunocompromised Host

The immune defect predicts the bug: neutropenia breeds bacteria and fungi, T-cell defects breed Pneumocystis and viruses, asplenia breeds encapsulated bacteria.

Key numbers

Neutropenia: bacteria first, fungi when prolongedANC < 500/µL

PJP: TMP-SMX ± prednisonePaO₂ < 70 mmHg

PJP prophylaxis with TMP-SMX for high-risk hostsprednisone > 20 mg × 4 wk

01 · CauseT-cell defects: Pneumocystis, viruses, fungi, intracellular bacteria

Cell-mediated (T-cell) defects — HIV, transplant immunosuppression, high-dose glucocorticoids — predispose to Pneumocystis, herpesviruses (CMV, HSV, VZV), Cryptococcus and other fungi, Toxoplasma, mycobacteria, Listeria and Nocardia.

02 · GivePJP: TMP-SMX ± prednisone

Treat Pneumocystis pneumonia with TMP-SMX (trimethoprim 15–20 mg/kg/day) for 21 days; add prednisone when PaO₂ is < 70 mmHg or the A–a gradient ≥ 35 mmHg on room air, ideally with the first dose.

03 · DoPJP prophylaxis with TMP-SMX for high-risk hosts

Give TMP-SMX Pneumocystis prophylaxis to high-risk hosts without HIV: transplant recipients, hematologic cancers, and prolonged glucocorticoids (prednisone > 20 mg/day for 4 weeks or more, especially with another immunosuppressant).

Causes & risk factors

Why it happens

Neutropenia: bacteria first, fungi when prolonged must knowBelow an ANC of 500/µL the patient's own skin and gut flora cause bacterial infection; prolonged neutropenia (chemotherapy, stem cell transplant), broad-spectrum antibiotics and high-dose steroids add invasive fungal infection.

Asplenia or antibody defect: encapsulated bacteria must knowAsplenia and antibody or early-complement deficiency leave the patient unable to clear encapsulated bacteria — pneumococcus above all — with risk of fulminant bacteremia; terminal complement (C5–C9) deficiency predisposes to recurrent Neisseria infection.

Screen for Strongyloides before steroidsBefore glucocorticoids or transplant in anyone who lived in or traveled to an endemic area, screen for Strongyloides (serology, stool); steroids can trigger hyperinfection with gram-negative bacteremia and meningitis. Treat with ivermectin.

Screen for hepatitis B before rituximabScreen for hepatitis B before rituximab or other potent immunosuppression: reactivation can cause fulminant hepatitis and death. Patients with prior exposure get antiviral prophylaxis (entecavir or lamivudine) and monitoring.

Presentation

What you'll see

Non-HIV PJP: faster, more hypoxemic, deadlierCompared with PJP in HIV, Pneumocystis pneumonia in other immunosuppressed patients progresses faster, causes respiratory failure more often and carries higher mortality — so start empiric treatment early when suspicion is high.

PJP: hypoxemia with bilateral ground-glass opacitiesPJP causes fever, dry cough, dyspnea and hypoxemia, often with exertional desaturation; chest x-ray shows bilateral perihilar infiltrates but is normal in 20–30%, and CT shows ground-glass opacities.

Diagnosis & monitoring

Work-up

Confirm PJP on induced sputum or BALConfirm PJP by staining or PCR of induced sputum or bronchoalveolar lavage; elevated serum β-D-glucan and LDH support but do not prove it. Start treatment before confirmation — cysts persist for weeks.

Do right now

In this order

First moves

Fever may be the only sign of infection

→

PJP: hypoxemia with bilateral ground-glass opacities

→

PJP: TMP-SMX ± prednisonePaO₂ < 70 mmHg

Why each step

Fever may be the only sign of infectionInflammatory signs are blunted — with an ANC below 200/µL there may be no pyuria, infiltrate or pus — so fever alone warrants cultures and prompt empiric antibiotics (see Neutropenic Fever).

PJP: TMP-SMX ± prednisoneTreat Pneumocystis pneumonia with TMP-SMX (trimethoprim 15–20 mg/kg/day) for 21 days; add prednisone when PaO₂ is < 70 mmHg or the A–a gradient ≥ 35 mmHg on room air, ideally with the first dose.

Management

Orders

Sulfa intolerance: dapsone, atovaquone or pentamidineIf TMP-SMX cannot be used: prophylaxis with dapsone (check G6PD first — hemolysis), atovaquone or aerosolized pentamidine; treatment with trimethoprim plus dapsone, clindamycin plus primaquine, atovaquone (mild only) or IV pentamidine.

TMP-SMX also prevents Toxoplasma, Listeria, NocardiaTMP-SMX given for Pneumocystis prophylaxis also protects against Toxoplasma, Listeria, Nocardia and some urinary and GI pathogens — one reason it is preferred over alternatives.

Transplant meningitis: add ampicillin for ListeriaEmpiric therapy for meningitis or encephalitis in a transplant recipient adds ampicillin (Listeria) and high-dose IV acyclovir to vancomycin plus a third- or fourth-generation cephalosporin or carbapenem while CSF results are pending.

Red flags & don'ts

Avoid harm

No live vaccines in significant immunosuppression avoidAvoid live vaccines — MMR, varicella, yellow fever, intranasal influenza, BCG, oral polio — in immunocompromised patients; inactivated vaccines (pneumococcal, meningococcal, hepatitis B, Hib) are recommended although responses may be weaker.

The rules

Know these

In HIV, CD4 count drives PJP prophylaxisIn HIV, prior PJP or a low CD4 count (classically below 200 cells/µL) triggers Pneumocystis prophylaxis, stopped once ART keeps CD4 at 200 or more for 3 months (see HIV in Acute Care).

Pneumocystis pneumonia: HIV or not?

Commonly confused

Who gets prophylaxis	Low CD4 count (see HIV in Acute Care)
Course	Slower progression
First-line drug	TMP-SMX for 21 days
Adjunctive prednisone	PaO₂ < 70 mmHg or A–a gradient ≥ 35

More detail

Reference

Show 7 reference facts

After organ transplant the timeline predicts the pathogen: month 1 surgical and nosocomial infection, months 1–6 opportunistic and reactivated infection (CMV, Pneumocystis, Listeria, Nocardia, Toxoplasma), after 6 months mainly community pathogens.

Nocardia causes cavitary or mass-like lung lesions that spread to brain and skin, sometimes silently — image the brain; treat with two or three active agents for 6–12 months.

Without prophylaxis, PJP occurs in 5–16% of transplant recipients and carries about 30–50% mortality in kidney transplant recipients.

IV pentamidine causes acute kidney injury, hypotension and hypoglycemia; TMP-SMX causes rash, neutropenia, hepatitis and fever, more often in advanced HIV.

Pneumatoceles or cysts in Pneumocystis pneumonia can rupture and cause spontaneous pneumothorax.

Strongyloides eosinophilia may be absent on steroids or chemotherapy, and HTLV-1 coinfection raises hyperinfection risk; advanced HIV alone is not an indication for screening.

CMV is the most common opportunistic infection after transplant; it is prevented by valganciclovir prophylaxis or PCR-guided preemptive therapy, and both ganciclovir and valganciclovir cause myelosuppression and need renal dosing.

Pearl

Name the defect, then the bug: neutrophils guard against bacteria and fungi, T cells against Pneumocystis and viruses, the spleen against encapsulated bacteria.