Immunosuppression changes everything about respiratory infection risk. The RCGP curriculum expects you, as a GP, to recognise how a weakened immune system alters the pattern and severity of respiratory infections, and to spot opportunistic infections and evolving sepsis early. “Immunosuppression affecting the respiratory system” and lower respiratory tract infections are explicitly flagged as priority AKT topics, so you can expect questions that test both your clinical reasoning and your guideline knowledge.

In everyday primary care you will regularly see causes of immunosuppression such as:

• Systemic steroids

• Cancer chemotherapy and post-transplant immunosuppressants

• Biologics for rheumatological disease

• Poorly controlled DM, CKD, HIV, malnutrition

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These states:

• ↑ Risk of reactivation of latent infections (e.g. TB)

• ↑ Risk of unusual pathogens (fungal, parasitic, opportunistic)

• ↑ Severity of “routine” infections (common viral/bacterial LRTIs)

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Understanding which pathogens to think about, what to test for, when to escalate, and how to prevent deterioration into sepsis is high-yield for the AKT and directly impacts patient safety in real GP work.

Major Causes of Immunosuppression – Primary Care

Category	Simple working definition in primary care	Why it matters for respiratory infections (think: “What should I worry about?”)
Systemic corticosteroids	Prednisone ≥10 mg OD for ≥3 months or ≥20 mg OD for ≥4–5 weeks (oral or equivalent IV); repeated high-dose bursts.	↑ Risk of severe CAP, PCP, Strongyloides hyperinfection, TB reactivation; blunted fever/signs → lower threshold for CXR, antibiotics, admission & PCP prophylaxis.
HIV infection / AIDS	Known HIV, especially CD4 <200 cells/mm³ (or untreated / poorly controlled); consider undiagnosed HIV in high-risk patients with recurrent / atypical chest infections.	↑ Risk of TB (pulmonary & extrapulmonary), PCP, atypical / severe CAP, cryptococcal disease; often atypical CXR / presentations → think HIV test, TB screen, PCP prophylaxis.
Biologic & targeted therapies	Anti-TNF, rituximab, JAK inhibitors, anti-IL agents etc.; often used for rheumatological / IBD / dermatology indications.	Impaired B-cell / T-cell function → recurrent chest infections, opportunistic pneumonias (e.g. PCP), TB reactivation; check TB/HIV screen done? PCP prophylaxis? Lower threshold to refer.
Triple immunosuppression / transplant regimens	Typical post-transplant combo: calcineurin inhibitor + antiproliferative + steroid; also some severe autoimmune disease regimens.	Very high risk of PCP, CMV pneumonitis, invasive fungal disease, severe CAP → any fever + resp symptoms = same-day hospital referral; do not manage as routine CAP in the community.
Cancer, chemotherapy, haematological disease	Active chemo, haematologic malignancy (e.g. leukaemia, lymphoma), neutropenia (neutrophils <1.0; especially <0.5).	↑ Risk of severe sepsis, invasive fungal infections (aspergillus), atypical/absent signs; fever + cough in neutropenic patient = medical emergency → immediate hospital.
Conventional DMARDs (csDMARDs)	Methotrexate, azathioprine, leflunomide etc. as monotherapy (without high-dose steroids or biologic).	Mild–moderate ↑ infection risk; lower than steroids alone. Still consider TB, PCP if combined with steroids/biologics; in AKT, steroids are the bigger respiratory risk signal.
Chronic systemic diseases (risk amplifiers)	Poorly controlled diabetes, CKD/ESRF, chronic lung disease, active cancer, significant CVD, frailty, malnutrition.	↑ Risk of severe / recurrent CAP, worse outcomes, higher sepsis risk. Not “classic opportunistic” infections but lower threshold for admission, early antibiotics, vaccinations (flu, pneumococcal, COVID).
Primary / congenital immunodeficiency	Known diagnoses (e.g. common variable immunodeficiency, IgA deficiency); often flagged in hospital letters.	Recurrent bacterial & atypical respiratory infections; many on immunoglobulin replacement or prophylactic antibiotics → closely follow specialist plans, refer early if unwell.

Opportunistic Respiratory Infections – Quick Primary Care Grid

Infection	Who to suspect (in 1 line)	Key GP action / exam-style hook
PCP	HIV with CD4 <200, high-dose / prolonged steroids, chemo, transplant, haematological malignancy, anti-TNF	Subacute dry cough + exertional dyspnoea + hypoxia out of proportion to chest signs → urgent CXR + same-day admission; check if on PCP prophylaxis (TMP-SMX).
Invasive pulmonary aspergillosis	Prolonged neutropenia, haematologic malignancy, stem-cell/solid organ transplant, high-dose steroids, IL-6 inhibitors	Neutropenic patient with persistent fever ± pleuritic chest pain / haemoptysis despite antibiotics → suspect IPA → urgent hospital referral (CT + galactomannan).
Strongyloides hyperinfection	Steroids/biologics or transplant plus residence/travel in tropical/subtropical regions; HTLV-1	“Asthma” or wheeze not responding to steroids, ± abdo pain/diarrhoea or sepsis → think Strongyloides → same-day referral, request stool/sputum; consider pre-steroid screening in at-risk patients.
Paragonimiasis	Raw/undercooked freshwater crab/crayfish in endemic areas (Asia/Africa/Latin America)	Chronic cough, chest pain, haemoptysis, weight loss mimicking TB/cancer in someone with relevant food/travel history → CXR + sputum/stool ova & parasite testing + refer.
Tuberculosis	HIV, biologics, steroids, CKD, DM, low BMI, substance use, high-prevalence country, close contacts	Cough >3 weeks, weight loss, night sweats, haemoptysis, non-resolving pneumonia → send CXR + sputum, arrange TB service referral; screen high-risk patients before biologics.
Legionella	Age ≥50, smoker, chronic lung disease, immunosuppression, recent travel / hot-tub / hospital water exposure	Pneumonia + GI symptoms, confusion, hyponatraemia = red flag for Legionella → request urinary antigen, urgent referral if hypoxic or systemically unwell.
Viral bronchiolitis (RSV)	Infants (esp. preterm, CHD/CLD, neuromuscular disease, immunodeficiency) with winter LRTI	Cough, tachypnoea, ↑ work of breathing, poor feeding, apnoea → assess SpO₂, admit if SpO₂ <92 %, apnoea, or poor feeding; remember nirsevimab / maternal RSV vaccine for prevention.
Pertussis	Unvaccinated / waning immunity; any age with prolonged cough; more severe in infants/immunocompromised	Paroxysmal cough, whoop, post-tussive vomiting or “100-day cough” → give macrolide early, notify public health, arrange Tdap and post-exposure prophylaxis for high-risk contacts.
CAP in immunocompromised host	Any of the major immunosuppressive categories above	Use CURB-65/CRB-65 but lower threshold to admit. Start appropriate empiric ABx promptly, check vaccination status, think atypicals (Legionella, Mycoplasma) and opportunists (PCP, fungi) if poor response to first-line therapy.

Sepsis in Immunocompromised Patients

Why this matters in primary care

Immunocompromised patients can become severely septic with very few signs. Fever and “classic” sepsis features may be blunted or absent, but deterioration is often rapid and more deadly. You need a lower threshold to think “sepsis?” and to arrange urgent hospital transfer.

What sepsis does to the immune system -briefly

On top of the patient’s baseline immunosuppression, sepsis itself causes immunoparalysis:

• Shift towards anti-inflammatory cytokines (e.g. IL-10, IL-4)

• Apoptosis of key immune cells (lymphocytes, dendritic cells)

• ↓ HLA-DR expression on monocytes → weaker antigen presentation

• ↑ Immune checkpoint signalling (e.g. PD-1)

• Expansion of regulatory T cells and myeloid-derived suppressor cells

👉 Result: higher risk of secondary infections, organ failure, and late sepsis death.

How presentation differs in immunocompromised patients

Typical features may be muted or missing:

• Fever may be absent

  • Especially with neutropenia or high-dose steroids

• Minimal chest / focal signs despite major pulmonary infection

• Fast progression

  • Can move from “mildly off” to shock in hours

• Higher mortality than non-immunocompromised patients.

GP priorities – sepsis in the immunocompromised

Think: “Is this sepsis until proven otherwise?” in any immunocompromised patient with suspected infection.

1. Spot it early

• Very low threshold for sepsis suspicion

• Ask: “Is this patient sicker than they look?” (steroids, chemo, neutropenia, transplant, HIV, biologics, advanced CKD/DM)

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2. Use an early warning score

• Calculate NEWS2 (or local equivalent)

• NEWS2 high / rising → treat as time-critical emergency

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3. Act, don’t wait

• Arrange urgent hospital conveyance

  • 999 / blue-light if NEWS2 high or you have gut concern

• Give a clear handover:

  • Type of immunosuppression (e.g. “post-renal transplant on tacrolimus + pred”)

  • Suspected source (respiratory? abdominal? line?)

  • Any recent ABx / hospital admissions

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4. Link to hospital “Sepsis Six”
You won’t usually complete all elements in primary care, but your job is to trigger early sepsis care:

• Recognise sepsis early

• Do not delay transfer for extra tests if the patient is unstable

• Make sure the receiving team know: “Immunocompromised + possible sepsis” → prompts early IV antibiotics and sepsis bundle within 1 hour.

Core antibiotic concept

Core concept	What it means in practice	AKT / GP hook
Start with severity + host	Always ask: How sick? (CURB-65 / NEWS2) + How immunosuppressed? before choosing ABx or disposition.	Immunosuppression itself ↓ threshold for admission and IV therapy.
Outpatients need atypical cover	Mild immunosuppression: macrolide or doxycycline. Comorbid/immunosuppressed but still outpatient: β-lactam + macrolide or respiratory fluoroquinolone.	Stem: immunosuppressed + CAP at home → plain amoxicillin alone is usually not enough; ensure atypical cover.
Fluoroquinolones = powerful but costly	Excellent cover (typicals + atypicals) and lung penetration, but ↑ risk of tendinopathy, QT prolongation, C. diff, resistance.	Use for higher-risk or β-lactam allergy, not routine CAP. AKT trap = “levofloxacin for everyone”.
Inpatient template = β-lactam + macrolide	Non-severe: amox/co-amox/cefuroxime + clarithromycin. Severe/ICU: ceftriaxone/cefotaxime/pip-taz + clarithromycin (or + fluoroquinolone).	Hospital CAP question → default answer is usually β-lactam + macrolide, unless given strong reasons otherwise.
Add MRSA cover when risk present	MRSA risk (recent healthcare, known colonisation, post-flu pneumonia) → add vancomycin or linezolid.	If MRSA risk factors are spelled out, the next step is often “add MRSA cover”, not “change everything”.
Shorter courses are now standard	Low-severity CAP: 5 days. Moderate–high: 5–7 days if stable by day 5. Atypicals (e.g. Legionella): 7–14 days.	Old 10–14 day courses for simple CAP are usually wrong unless atypical, complicated, or slow response.
Clinical stability defines stop/switch	Use objective criteria: temp <37.8 °C 48h, HR <100, RR <24, SBP >90, SpO₂ >90 %, eating, normal mental state.	Day-5 “doing well” stem → answer is often “switch to oral / plan to stop”, not “continue IV for 10 more days”.
Early IV → oral switch when safe	Consider at 24–48 h once clinically stable and tolerating oral meds; delay in severe or complex infections.	Very common next-step question: improve on IV → switch to oral + discharge planning, not prolong IV.
Immunocompromised ≠ automatic 14 days	Start with 5–7 days CAP framework; extend only if slow response, complications, or unusual pathogen.	Even if immunosuppressed, good response by day 5–7 → it’s usually safe to avoid unnecessarily long courses.
Stewardship still matters	Avoid ABx for clear viral bronchitis; review at 48–72 h; narrow spectrum when cultures return.	Immunosuppression ≠ blanket licence for broad ABx. AKT punishes “just in case” prescribing without indication.

Key principles to internalise

• Suspect opportunistic infections early
  Normal observations, examination and even normal CXR/CT do not exclude serious pathology in an immunosuppressed patient.

• Risk-stratify aggressively
  Use CURB-65 / CRB-65 plus clinical judgement. Immunosuppression itself ↓ your threshold for admission and IV therapy.

• Cast a wide diagnostic net
  Multiple pathogens can coexist. Send appropriate microbiology early (sputum, blood cultures, viral PCR, TB tests) and be ready to rethink if there is poor response to first-line treatment.

• Refer promptly
  Suspected PCP, invasive aspergillosis, TB, severe bacterial pneumonia or sepsis in an immunocompromised patient → same-day hospital assessment and specialist input.

• Prevent proactively
  Use prophylaxis (e.g. PCP, TB where indicated) and vaccination (pneumococcal, influenza, COVID, RSV in selected groups) to ↓ morbidity and mortality.

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