Treatment of pneumonia in immunocompromised host

Prof. Dr. Volkan Korten

Marmara Univ. School of Medicine

Dept. of Infectious Diseases

Pneumonia in immunocompromised host

• Community acquired

• Nosocomial

• Aspiration

• Reactivation

• Environmental exposure

Pneumonia in immunocompromised host - Etiology

• Conventional bacteria % 37

• Fungi % 14

• Viruses % 15

• Pneumocystis carinii/jirovecii % 8

• Nocardia asteroides % 7

• Mycobacterium tuberculosis % 1

• Mixed infections % 20

Community acquired pneumonia

• Etiology – not changed in imm.comp. host– Focal – segmental infiltrates suggest bacterial

etiology. – Typical - atypical pneumonia

S.pneumoniae, H.influenzae or L.pneumophila etc

• Severely impaired cellular immunity: – CMV, Tbc, MAI

CAP guidelines are valid – according to severity / empiric treatment - similar to pts with underlying diseases

Empiric Ab (antipseudomonal beta-lactams), MRSA ? Legionella ?

Empiric Ab + empiric antifungal

+ PCP ?+ Mycoplasma – legionella ?+ Viral ?

Antipseudomonal beta-lactams• Antipseudomonal cephalosporins

– Cefepime 2 g tid– Ceftazidime ? 2 g tid

• Carbapenems– Imipenem 500 mg qid, 1 g tid– Meropenem 1-2 g tid– Doripenem 0.5-1 g tid

• Beta-lactam/beta-lactamase inhibitors – Piperacilin-tazobactam 4.5 g qid– Cefoperazone-sulbactam 2 g tid

Combinations ? (shock – MDR)- FQ- Aminoglicosides

Risk classification for invasive aspergillosis

Allo BMT + GVHD

Allo BMT ± GVHD

PNL <500/mm3 + Hematological malignancies+ Auto BMT+ Aplastic Anemia+ MDS

SOT, AIDS

High dose steroids

Invasive pulmonary aspergillosis

www.aspergillus.man.ac.uk

Normal lungIPA

IPA occurs in ~7% of acute

leukaemia patients, 10-15% allogeneic

BMT patients

ProbableProbableMycologyClinical features

Host factors + =

MycologyClinical features

Host factors + + = Proven Proven

tissue

Invasive fungal disease - Definitions II

PossiblePossibleClinical features+ =Host

factors

Negativeor

Not done

Clinical features+ =Host

factors

Negativeor

Not done

De Pauw B, Definitions of Invasive Fungal Disease, CID 2008;46:1813-21

Host factors for IA• Recent history of neutropenia (< 500/mm3 for > 10 days)• Allogeneic stem cell transplant• Prolonged use of corticosteroids • T cell immunosuppressants, such as cyclosporine, TNF-

a blockers, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days

• Inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency)

• Microbiological criteria– Culture– Cytology– Galactomannan, Beta-glucan

• Clinical criteriaCT– Halo sign– Air - crescent sign– Cavity in consolidation

Specific pulmonary infiltrates on CT scan

halo signhalo sign

air crescent signair crescent sign cavitycavity

nodulesnodules

IDSA Clinical Practice Guidelines for Aspergillosis 2008

Walsh TJ, et al. Clin Infect Dis 2008;46:327-60

Risk factors for Pneumocystis pneumonia

• HIV infection - CD4 < 200• Non-HIV

– Glucocorticoid use– Other immunosuppressive drugs: Antirejection medications, Purine analogs (eg,

fludarabine), Infliximab – Defects in cell-mediated immunity– Cancer (particularly hematologic malignancy)– HSCT; especially allo– Solid organ transplantation– Treatment for rejection– Treatment for inflammatory conditions (eg, Wegener's granulomatosis)– Severe malnutrition (especially protein malnutrition)– Primary immunodeficiencies (particularly severe combined immunodeficiency)– Prematurity

Anti-inflammation Therapy:Prednisone: needs definitive diagnosis

• Shown to improve survival in patients with paO2 < 70 or Aa gradient >35 mm Hg.

• Decreases the risk of respiratory failure and death by 50%.

• Tapered dose (40 mg BID x 7, 40mg QD x 7, 20 mg QD x 7).

Nocardia

• TMP-SMZ 15 mg/kg/d TMP iv or po – first 4 wks,– 10 mg/kg/d TMP equivalent 5 months / 1 year in

imm. compromised pts.– cranial imaging

• Imipenem 500 mg qid or Ceftriaxone 2 g/d + Amikacin 1 g/d 3-4 wks, followed by TMP-SMZ

• Linezolid 600 mg bid, po

RSV / Influenza

• Ribavirin aerosol or po

• Ribavirin + palivizumab (monoclonal antibody developed against RSV)

• Oseltamivir / zanamivir

Treatment duration

• Community acquired: 7 days after defervescence

• Nosocomial: 14 days after defervescence

• Neutropenic pts: till PNL > 500/mm3 ?