This document defines non-resolving pneumonia and discusses its causes and diagnostic evaluation. Non-resolving pneumonia is defined as persistence of clinical symptoms and radiographic abnormalities for longer than expected despite adequate antibiotic therapy. Common causes include inappropriate antibiotic therapy, complications of the initial infection, host factors, and presence of resistant or unusual pathogens. A thorough diagnostic evaluation includes assessing treatment response, looking for complications or superinfections, evaluating for unusual organisms, and examining host immune function. Radiological imaging, bronchoscopy with protected specimen brushing or biopsy, and CT-guided biopsies can help identify causative organisms or underlying conditions.

2. NON RESOLVING PNEUMONIA
Dr. Surabhi Sushma Reddy
Postgraduate
Department of pulmonology

3. DEFINITION
• PNEUMONIA is defined as inflammation of
lung parenchyma caused by an living/
infectious agent.
• PNEUMONITIS is inflammation of lung
parenchyma caused by non-living agent.
Eg., radiation pneumonitis, chemical
pneumonitis.

4. • The clinical syndrome include fever, sweats
,rigor/chills, and pulmonary symptoms like
cough, sputum, dyspnoea, pleurisy or
pulmonary lesions observed on radiographic
examination.
• The gold standard for diagnosing pneumonia
is Chest X Ray/ CT chest.
• Diagnosis and management of pneumonia
has been complicated by the discovery of
newer pathogens, expanded antimicrobial
resistance , increased populations of immuno-
compromised patients and by newer
diagnostic tools and antimicrobial agents

5. CLASSIFICATION OF PNEUMONIA
• Morbid anatomist’s classification:
lobar pneumonia
segmental pneumonia
sub segmental pneumonia
bronchopneumonia.
• Microbiologist’s classification based on the
etiological agent.

6. • Empiricist’s classification
community acquired pneumonia
hospital acquired pneumonia
aspiration pneumonia
immuno compromised host pneumonia
• Behaviourist’s classification
easy pneumonia
difficult pneumonia.
• 10% -CAP,60% of HAP have inadequate responses
to the empirical therapy.

7. Rate of resolution of physical and lab
abnormalities
Abnormalities Duration
fever 2 to 4 days
tachycardia and hypotension 2 days
cough 4 to 9 days
crackles 3 to 6 days
leukocytosis 3 to 4 days
CRP 1 to 3 days
CXR abnormalities 4-12 weeks
Patient is considered to have responded if:
1. Fever declines within 72 hrs
2. Temperature normalizes within 5 days
3. Respiratory signs (tachypnoea) return to normal.

8. • In 1975, Hendin defined slowly resolving as pulmonary
consolidation persisting more than 21 days.
• In 1991, Kirtland and Winterbauer defined slowly
resolving CAP in immunocompetent patients based
upon radiographic criteria.> 50% clearing by 2 weeks or
> complete clearing at 4 weeks.
• Non responding pneumonia-absence of clinical
response antibiotic treatment after 3-5 days.
• Progressive pneumonia- increase in radiographic
abnormalities and clinical deterioration during first 72
hours of treatment.

9. • Non resolving pneumonia is defined by the
presence of persistence of clinical symptoms
and signs(cough, sputum production, with or
without fever >100o F), failure of resolution of
the radiographic features by 50% in 2weeks or
completely in 4 weeks on serial chest X rays
inspite of antibiotic therapy for a minimum of
10days, and sputum for AFB smear negative
for 2 consecutive samples.
lung india 2012.

10. • Slowly resolving pneumonia are usually
defined as the persistence of radiographic
infiltrates in a clinically improved patient for
longer than 4 weeks. (<50% resolution in 1
month)
BMJ 2016

11. • In addition to clinical evaluation, reduction of
procalcitonin (PCT) levels after 3-4days of
treatment correlates with clinical responses.
• Therefore, initial high levels of PCT and CRP
represent a risk factor for inadequate response.
• A recent biomarker MR-proadrenomedullin is
associated with greater severity assessment
and levels greater than 1.8 were associated
with subsequent deterioration and ICU
admission.

12. Causes of non resolving pneumonia:
• Inappropriate antimicrobial therapy.
• Super-infection.
• Complications of initial pneumonia.
• Host factors.
• Delayed radiological recovery
• Presence of resistant organisms
• Presence of unusual organisms.
• Defects in defense.
• Diseases mimicking pneumonia

13. 1. Inappropriate anti microbial therapy
• Includes inadequate dosing
• Agents that fail to penetrate infected lung
tissue (often aminoglycosides)
• Use of agents to which organisms are or have
become resistant.
2. Super infection
• Super infection with resistant microorganisms
Including fungi, mycobacterium tuberculosis
• Viral co infection with community – acquired
respiratory viruses.

14. • 3)Complications from initial pneumonia:
• Sequestered foci of infection may prevent adequate
amount of antibiotic from reaching site of infection.
• Empyema/Para pneumonic effusion
• Abscess
• Metastatic focus of infection eg:
• Infective endocarditis
( Require drainage and appropriate antibiotic
therapy and addressal of the basic disease.)

15. 4)Host factors :
• Age esp. greater than 50
• Co morbid illnesses- Diabetes
• COPD
• Alcoholism
• Immunosuppressive/cytotoxic therapy
• Bacteremia .
• Multi-lobar pneumonia
• Intubated patients ( colonized with resistant
microorganisms)

16. 5)Delayed Radiological recovery :
• Non resolving pneumonia encompasses failure
of clinical or radiological recovery.
• Many will have clinical improvement but
radiological recovery lags.
• Important to know what time it takes for
radiological recovery.

17. causative agent time for clearance
1. Pneumococcus
bacteremic
non-bacteremic
3-5months
1-3months
2. Legionella 2-6months
3. Mycoplasma ½ - 2months
4. Chlamydia
5. Viruses
1-3months
variable

18. 6)Presence of Resistant pathogens :
• 1- Drug-Resistant Streptococcus pneumonia (
DRSP) suspected if :
• Treated with beta lactams within 6 months.
• Close exposure to young children.
• Pneumonia in last one year.
• Hospitalized in last 3 month.
• HAP in last 2 months.

19. 2- MRSA suspected if –
 Advanced age .
 Indwelling IV catheters.
 Prior antibiotic coverage.
 Contact with pts having MRSA.
 Dialysis.
 Burns.
 Surgical wounds.
 Tertiary care centers
• Around 50% of non responding VAP are due to MRSA,
P. aeruginosa, carbapenemase producing klebsiella
and acinobacter species.

21. 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, multilobar disease, infection with
drug resistant organisms
• Radiographic improvement is much slower
• Risk factors for delayed radiologic resolution:
persistent fever & leukocytosis > 6days, COPD,
advanced age alcoholism
• Radiologic clearance : 1-5 months.

22. • 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

23. • 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 abnormalities is unusual.

24. • 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.

25. • 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.

26. 7)Presence of Unusual organisms :
• Tuberculosis .
• Nocardia (Nocardia as an oral microflora)
• Atypical mycobacteria.
• Fungi: aspergillus , cryptococcus, mucor,
histoplasma,coccidiodomycosis.
• Exposure to animals-Francisella,yersinia
leptospira,chlamydia psittaci.
• Travel to Endemic areas- Hantavirus,
Paragonimiasis.

27. 8. Defects in defence:
• Nasal filtration-( ET tube , tracheostomy)
• Oral adherence- (aging ,smoking, severe
illnesses, viral illness.)
• Epiglottitis-( stroke,ET,sedatives.)
• Impaired cough-(sedatives, neuromuscular
illness, stroke.)
• mucociliary transport- (chronic bronchitis,
• ET, dehydration, alcohol, vit A def.)

28. • Ig or complement def-specific disorders,
(aging malnutrition,B6,folate ,zinc def.)
• Bacterial adherence to airway epithelium and
decreased function of alveolar macrophages.
• Immune deficiency states-primary and
secondary, (B cell and T cell.)

29. 9. Disease mimicking pneumonia:
Non infectious causes :
• Neoplasia mimicking infiltrative process:
*Bronchoalveolar cell carcinoma.
*Lymphoma.
*Lymphangitic carcinoma.
• Lobar Atelectasis-Bronchogenic CA,
• carcinoid,metastatic disease.
• Pulmonary infarction
• Pulmonary hemorrhage
• Hypersenstivity pneumonitis.

30. Inflammatory disorders:
• Systemic vasculitis – CTD(connective tissue
diseases)
• Wegeners including DAH(Diffuse alveolar
hemorrhage)
• BOOP.(Bronchiolitis obliterans with organizing
pneumonia.)
• AEP,CEP(Acute &chronic eosinophilic pneumonia)
• PAP (Pulmonary alveolar proteinosis )
• Sarcoidosis
• AIP (Acute interstitial pneumonia)

31. Drugs induced lung disease :
• Nitrofurantoin.
• Amiodarone.
• Methotrexate.
• Bleomycin .
• Mitomycin.
• Paclitaxel,Docetaxel.
• cyclophosphamide.
• IL-2 (Aldesleukin)

32. • Drug-induced interstitial lung disease (DILD) is
not uncommon.
• Causing either benign infiltrates to life-
threatening acute respiratory distress syndrome.
• By 2 mechanisms :
i) Direct, dose-dependent toxicity.
ii) Immune-mediated. Cytotoxic lung injury may
result from direct injury to pneumocytes or the
alveolar capillary endothelium.
• DILD can be difficult to diagnose; diagnosis is
often possible by exclusion alone.

33. Diagnostic evaluation :
• Re evaluate host factors.
• Possibility of antimicrobial failure :
*patient noncompliance
*improper dosage.
*review antibiotic resistant pathogen.
*review sensitivities.
*unusual pathogen.
• Infectious complications :
*empyema Rpt CXR/chest CT
*endocarditis. Echo.
*super infection

34. • Gram stain and culture of sputum is neither
sensitive nor specific due to :
contamination by upper airway flora
failure to get secretions from lower airway
previous use of antibiotics
• Look for atypical organisms
• Hence the role of secretions is from endotracheal
aspirate and protected brush specimens.
• Blood cultures.
• Urine- antigen test for detection of legionella
• Pleural fluid analysis (if present).

35. Radiology :
• CXR repeated -infiltrates, pleural effusion,
lymphadenopathy, cavitation
• CT scans -detailed study of parenchyma,
interstitium,pleura & mediastinum.

36. Bronchoscopy :
PSB.(protected specimen brush).
BAL (bronchoalveolar lavage )
TBLB ( transbronchial lung biopsy)
• Sensitivity of PSB 40% -non responding
• Gram stain of cytocentrifuged BAL-identifies intracellular
organisms.
• Biopsies seldom useful in achieving bacterial diagnosis.
Invaluable in TB, fungal, neoplasms, BOOP,histocytosis.
• Also of important role in Immuno-suppressed.

37. Protected brush specimens:
• Reported sensitivities of 50-80%
• Specificity >80%
• Gram,ZN, Giemsa,IF and C/S of the specimen
• However it is of limited utility due to:
lack of standardization of the tests
paucity of studies demonstrating benefit in
morbidity or mortality.

38. CT/USG guided FNAC:
• Establishes the diagnosis in 93.7% of cases.
• Sensitivity and specificity for malignancy are 87%
and 100% respectively.
• Specially useful in peripheral lesions.
• Also helpful when FOB cannot establish any
diagnosis.
lung india 2015

42. THANK YOU