NON RESOLVING PNEUMONIA

An overview of non resolving pneumonia

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

2. 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 .

3. 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

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

5. 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.

6. 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: Fever declines within 72 hrs Temperature normalizes within 5 days Respiratory signs ( tachypnoea ) return to normal.

7. 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.

8. Non resolving pneumonia is defined by the presence of persistence of clinical symptoms and signs(cough, sputum production, with or without fever >100 o 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 .

9. 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

10. 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.

11. 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

12. 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.

13. 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.)

14. 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)

15. 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.

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

17. 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.

18. 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.

19. 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.

20. 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

21. 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.

22. 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.

23. 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.

24. 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 .

25. 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.)

26. 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.)

27. 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 .

28. 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)

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

30. 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 .

31. 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

32. 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).

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

34. 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.

35. 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.

36. 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

37. THANK YOU