details of non resolving pneumonia

1. NON RESOLVING PNEUMONIA
Dr Sayantan saha

2. DEFINITIONS
• Failure to respond to antimicrobial treatment was classified as nonresponding & progressive
pneumonia.
• Nonresponding pneumonia was defined as persisting fever > 38.8 C and/or clinical symptoms (malaise,
cough, expectoration, dyspnea) after at least 72 h of antimicrobial treatment.
• Progressive pneumonia was defined as clinical deterioration in terms of the development of acute
respiratory failure requiring ventilatory support and/or septic shock after at least 72 h of
antimicrobials.
• The expected time course for resolution is controversial. However, conventionally it is taken as 72
hours.
• In 1975 Hendin defined slow resolving pneumonia (SRP) as pulmonary consolidation persisting for
more than 21 days.
• In 1991 Kirtland & winterbauer defined SRP in immune competent patients based upon radiological
criteria ; Less than 50% clearings by 2 weeks or less than complete clearing 4 weeks.

3. Incidence
• 15% of pulmonary consultations needing hospitalization and 8% of bronchoscopies.
• 10% of community acquired pneumonia (CAP) and 60% of hospital acquired pneumonia (HAP) show
inadequate responses to empirical therapy initiated

4. NORMAL RESOLUTION OF PNEUMONIA
• Normal resolution of pneumonia is not easy to define. It depends upon the underline causes.
Subjective improvement starts 3-5 days after initiated treatment.
• Figure 1 showing rate of resolution of clinical, Laboratory and Radiological abnormalities.
• Pneumonia resolution depends upon many key factors.
• Rapid resolution of pneumonia occurs when-
1. Host is young, nonsmoker and non hospitalized.
2. CAP is of mild severity.
3. Causative microorganisms are mycoplasma pneumoniae or Chlamydia pneumoniae.

5. CAUSES OF NON RESOLVING PNEUMONIA

6. Infectious Causes:
40% of the causes are attributable to infections which may be:
• Primary infections. Demonstration of a pathogen not detected in initial investigations (“atypical” or unusual
pathogens or pathogens associated with the development of empyema).
• Definite persistent infections. Demonstration of the same pathogen in initial and repeated investigations.
• Probable persistent infections. Demonstration of a pathogen in initial but not in repeated investigations.
• Nosocomial infections. Demonstration of a pathogen not present in the initial evaluation (sputum or
tracheobronchial aspirate [TBAS]) usually associated with early- or late-onset ventilator-associated pneumonia.
• Noninfectious etiology. Definite alternative diagnosis.
• Nondiagnostic. Neither definite infectious nor noninfectious etiology.

7. • In patients hospitalized for CAP, specific infections are responsible for 40% of nonresponding cases.
The most frequent microorganisms found are S. pneumoniae, Legionella, P. aeruginosa, and S. aureus.
• Up to 50% of episodes of nonresponding VAP are caused by multiresistant microorganisms; the most
frequent causes are MRSA, P. aeruginosa, carbapenemaseproducing Klebsiella, and Acinetobacter
species.
• Causes of non response may be-
 Inappropriate empirical coverage. (risk factors for likely organisms not cosidered)
 Inappropriate dose
 inappropriate duration
 Inherent or acquired resistance of microbe.
• More unusual microorganisms in nonresponding CAP include Mycobacteria, Nocardia species,
anaerobes, fungi, Pneumocystis jirovecii, and other organisms requiring antibiotics other than those
recommended for CAP or HAP.

8. • Empyema is one of the most frequent complications in pneumonia and is thus a cause of
nonresponse that must be evaluated with thoracentesis when a pleural effusion is present.
• Other causes of treatment failure are abscess formation, necrotizing pneumonia, Metastatic
infections such as endocarditis, arthritis, pericarditis, meningitis, or peritonitis.

9. Non Infectious Causes(Pneumonia mimics):

11. Approach to diagnosis
History:
• comprehensive history taking, e.g.--
 A patient with history of heavy smoking, hemoptysis, cachexia or weight loss with non resolving
opacities points to malignant etiology.
 Hematuria may indicate DAH whereas joint pain or rashes indicate CTD.
 Asthma and persistent migratory opacities are suggestive of ABPA.
 Drugs history is important cause of pulmonary infiltrate.
 Similarly occupational history is also suggest occupational lung diseases.
• Past history of comorbid conditions like COPD, renal failure and alcoholism should also be sought as
they delay radiological clearance.
• Review of previous microbiological reports.
• evaluation for response should be undertaken after 72 hours of antibiotic treatment, as this
represents the median time required to achieve clinical improvement

12. Physical examination:
• Pedal edema, raised JVP and basal crackles are signs of heart failure.
• clubbing of fingers and toes may indicate idiopathic pulmonary fibrosis, bronchiectasis, asbestosis and
malignancy.
• Involvement of eyes, joints, skin, kidneys, heart and salivary glands may suggest sarcoidosis.

13. Laboratory examination:
• Rheumatoid factor, ANA & ANCA
should also be ordered in CTD
and vasculitis.
• Serum angiotensin converting
enzyme (SACE) in sarcoidosis.

14. In addition to clinical evaluation, reduction of procalcitonin (PCT) levels after 3 to 4 days of treatment
correlates with clinical responses.
Initial higher levels of PCT or C-reactive protein represent a risk factor for inadequate response (odds
ratio, 2.6), whereas low levels are associated with responses to therapy.

15. Imaging:
• Serial Chest X-Ray is an important investigation which confirms the persistence of radiological opacity.
Chest CT is the most helpful in NRP, which can detect plural diseases, empyema or abscess &
mediastinal masses.
• CT is also very useful in non infectious causes of NRP.
• Active interstitial pneumonitis may be suggested by ground glass opacity on HRCT.
• CT Pulmonary angiography is also indicated if PTE is suspected.
• In a patient with applicable risk factors, the appearance of nodular images with the halo sign (i.e., a
nodule surrounded by a halo of ground-glass attenuation, especially near the pleura) on CT scan is
suggestive of pulmonary aspergillosis or mucormycosis.
• Groundglass opacities consistent with interstitial pneumonia suggest P. jirovecii pneumonia.
• Nodules or multiple masses with or without cavitation are compatible with Nocardia species, M.
tuberculosis, or Q fever

16. Hypersentivity pneumonitis
1. GGO
2. Mosaic pattern
3. centrilobular nodule

17. NSIP
1. GGO
2. reticular opacity
3.mosaic pattern.
4.septal thickening

18. BOOP
1. patchy subpleural/peribronchial consolidation
2. mass
3.bronchial wall thickening
4.GGO

19. AEP
1. GGO
2. Septal thckeing
3.pleural effusion.
4. centrilobular nodule

20. AIP
1. GGO
2. traction bronchiectasis
3. consolidation

21. ARDS

22. Lung cancer

23. Bronchoscopy:
• fiber-optic bronchoscopy (FOB) is diagnostic in more than half of the cases of persistent pulmonary
opacity.
• Bronchoscopy allows direct visualization of affected area and the direct obtaining of samples.
Protected brush specimen (PBS), broncho alveolar lavage (BAL) and trans bronchial biopsy (TBB)
can be used to take the sample tissues.
• Microbiological studies of BAL and PBS may include staining in culture of usual bacteria, specific
staining for AFB and culture, legionella, fungi, virus and direct immunofluorescence for
legionella.
• Significant colony count is defined as-
 PSB >103 CFU/ml
 BAL >104 CFU/ml
 ET secretion >105 CFU/ml
mini-BAL:
non-bronchoscopic technique of obtaining lower respiratory tract samples. Studies have shown it as
sensitive and specific as conventional BAL.

26. Treatment:
Correction of Host Abnormalities-
• discontinuation of drugs causing immuno-suppression.
• Granulocytopenia (absolute granulocyte count less than 500 cells/mm3) should be treated with G-
CSF/ GM-CSF.
Antimicrobial Adjustment-
• The optimal time to make these changes is not defined, although it has been suggested that one
should wait until 72 hours after the initiation of treatment except in the presence of severe clinical
deterioration.
• Before initiating a change in antibiotics, new samples should be obtained for microbiologic studies.
• In nonresponding CAP, strong consideration should be given to extending the antibacterial spectrum
to ensure coverage of resistant S. pneumoniae, P. aeruginosa, S. aureus, and anaerobes.
• all abscesses or empyemas must have been drained.
• In nonresponding nosocomial pneumonia, combinations of up to three antibiotics may be necessary
to cover P. aeruginosa, MRSA, and the endemic flora of each hospital, such as Acinetobacter species or
other microorganisms.