Non Resolving Pneumonia

Includes cases of presumed pneumonia that progress slowly or fail to achieve complete resolution inspite of what is thought to be appropriate treatment

Causes for slow or incomplete resolution of pneumonia :

i) Misdiagnosis or presence of resistant pathogen

ii) Host factor iii) Development of complications iv) Non infectious etiologies that mimic as infectious pneumonia.

Normal versus delayed resolutionNormal resolution- subjective

improvement within 3-5 days of treatment

Tachycardia, hypotension-2 daysFever,tachypnea,arterial

oxygenation: 3 daysCough & fatigue:14 days or longer.

Slow resolution : persistence of radiological abnormalities for >1 month in clinically improved host.

Factors affecting rate of resolution :

i) Comorbidities: slow reolution of pneumonia

ii) Age : < 50 yrs- resolution by 4 wks.

iii) Severe pneumonia – 10wks mild to moderate- 3-4 wksiv) Infectious agents : resolution

more rapid with Mycoplasma pneumoniae, Steptococcus pneumoniae , Chlamydophilia,Moraxella catarrhalis.

Influence of specific bacterial pathogens:

Streptococcus pneumoniae: responsible for most cases of non resolving pneumonia of infective origin

risk factors for delayed resolution- severe presentation,multilobular disease,infection with drug resistant organisms

Radiographic improvement is much slowerRisk factors for delayed radiologic

resolution: persistant fever & leucocytosis > 6days,chronic copd,advanced age alcoholism

Radiologic clearance : 1-5 months.

Legionella infection-risk factors : alcoholism, smoking, age>65 yrs, immunosuppresion(glucocorticoid use) CKD.

Radiographic deterioration despite treatment is common

Resolution is slow-begins after 2-3 wks. ½ of pts show residual abnormalities upto 10wks. Resolution takes upto 6-12 months.

Pts experience generalised weakness & fatigue for months. Abnormalities in pulmonary function tests may be seen as long as upto 2 yrs.

Residual fibrosis : 25% pts

Mycoplasma pneumoniae : common cause of RTI.Rarely causes severe pneumonia.

Resolution is rapid. Significant clinical improvement occurs within first 2wks.

Radiographic deterioration after treatment is rare (< 25% cases)

Avg. duration of radiological abnormalities 2-4 wks.

Radiological abnormalitis is unusual.

Chamydophilia pneumoniae : relatively mild disease.

30-50% of young adults have serological evidence of prior infection.

Prompt resolution occurs in young individuals.

Radiological deterioration is uncommom

Clearing occurs in < 3months.

Haemophilus influenzae : common cause of pneumonia in smokers, elderly & in pts with COPD.

Vaccination against H.influenzae b have reduced incidence of infection.

Resolution is slow with need for prolonged hospitalization.

Only 50%pts return to their previous level of function by 6 wks.

Misdiagnosis of nonbacterial pathogens:Alternative pathogens in addition to

bacteria causing pneumonia should be considered in pts who fail to respond to treatment.

Important pathogens in this caterory :

Mycobacteria(M.tuberculosis, atypical mycobacteria)

Fungi Nocardia

Actinomyces

Tuberculosis : it is of significant concern in elderly , h/o I.V drug use & other risk factors for AIDS

Clinical presentation is atypical, especially in elderly & diabetic , who commonly have radiographic findings in middle or lower lung zones.

Diagnosis is difficult as sputum in not always available & culture results take weeks after collection of specimen.

PCR is approved for smear positive cases.

Fungi : oppurtunistic & endemic fungi cam mimic bacterial pneumonia.

Aspergillus is important pathogen in non resolving pneumonia presenting as chronic necrotising or invasive aspergillosis.

Invasive aspergillosis occurs in neutropenic pts on multiple antibiotics. Increasingly recognised in pts with chronic lung disease on corticosteroids

Endemic fungi like histoplasmosis, coccidioidomycosis,blastomycosis,cryptococcosis should be considered in endemic areas.

Nocardia & Actinomyces : although these are higher order bacteria, clinical presentation is consistent with fungal etiology.

Nocardia infection presents commonly on chest x-ray as localised alveolar infiltrats that are homogeneous non segmental & cavitary.

Actinomyces has similar appearance, but may invade chest wall.

Resistant bacterial pathogens:Presence of resistant pathogen is

important consideration in pneumonia not responding to antibiotic therapy.

Streptococcus pneumoniae- organism of most concern.

Others : multidrug resistant haemophilus influenzae, pseudomonas aureginosa,mrsa.

Suspicion of penicillin resistant S.pneumoniae should be high in :

childern <5yrsPrior treatment with beta

lactams(within 6 months)Previous pneumonia within past

yearHospitalization within past

3months.Nosocomial infection

Host factors :Variety of host factors may be

responsible for delayed resolution of pneumonia that includes :

Alcoholism Older age Co morbid disease ( diabetes,

COPD) Disorders of immune functions

(AIDS , deficient humoral immunity)

Acquired immunodeficiency syndrome

Pneumocystis jirovecii pneumonia

is an important consideration in pts with AIDS.

It is important to consider underlying HIV infection in pts with non resolving or progressive pneumonia

Primary humoral immune deficiencies: it is important to identify primary humoral immune deficiency as an underlying cause for pneumonia because of effect of treatment with IVIG on resolution of pneumonia.

Most common organisms in these pts are Streptococcus pneumoniea & Haemophilus influenzae

Development of complications from initial pneumonia: Sequestered foci of infection may prevent adequate amount of antibiotic from reaching site of infection. These include:

Empyema: rare complication of CAP. seen in young drug users. Most common pathogen cultured was

Streptococcus milleri.Evaluation is by CT or UltrasoundThoracentesis should be done in pts

with non resolving pneumonia showing any significant amount of pleural fluid

Lung abscess : predisposing factors – alcoholism, seizures,poor oral

hygeine,previous aspiration.Chest radiography demonstrates air-

liquid levels.CT is more sensitive.Most pts respond to conservative

treatment & prolonged course of antibiotic.

Poor prognosis is seen in – age related(pediatric or elderly),large cavity size,prolonged duration of symptoms proir to therapy,lower lobe location,multiple abscess,associated with malignancy.

Non infectious etiologies:Variety of non infectious etiologies of

pulmonary infiltrates can mimic pneumonia. These include :

i)Neoplastic disorders : these may be associated with nonresolving pneumonia either by compromise of airway lumen & secondary post obstructive pneumonia or mimic infiltrative process.

Bronchogenic carcinoma & Carcinoid tumour are common causes of endobronchial obstruction.

Bronchioloalveolarcell carcinoma & lymphoma mimic alveolar infiltrates

. ii)Inflammatory disorders : Numerous inflammatory disorders can mimic & be misdiagnosed as pneumonia

iii)Systemic vasculitis or connective tissue disorders cause fever, dyspnea & pulmonary infiltrates & can be misdiagnosed as pneumonia.

iv)Eosinophilic pneumonia -characterised by accumulation of eosinophils in alveolar spaces. Acute form has rapid onset of fever,non productive cough,dypnoea & pleuritic chest pain

v) Acute interstitial pneumonia.vi) Pulmonary alveolar proteinosisvii) Sarcoidosisviii) Pulmonary embolismix) Hydrostatic pulmonary oedemaxi) Drug induced pneumonia :

Amiodarone toxicity mimic of non resolving pneumonia.

Other drugs include Methotrexate, bleomycin, nitrofurantoin etc.

Further evaluation :

Imaging studies : Chest CT (high resolution)

Broncoscopy

Lung biopsy