MANAGEMENT & FOLLOW

UP
OF NON-RESOLVING
PNEUMONIA

------ Dr Himadri Shekhar Mondal.

2nd year pgt,
Dept of Internal Medicine,
RGKMCH
 PNEUMONIA- definition
Pneumonia is defined as inflammation of the
pulmonary parenchyma caused by an infectious agent.

Clinical symptoms-- fever, sweats ,rigor/chills, and

pulmonary symptoms like cough, sputum, dyspnea, pleurisy or

pulmonary lesions observed on radiographic examination.

( CXR / CT CHEST is gold standard)
 PNEUMONIA- definition
Pneumonia is defined as inflammation of the
pulmonary parenchyma caused by an infectious agent.

Clinical symptoms-- fever, sweats ,rigor/chills, and

pulmonary symptoms like cough, sputum, dyspnea, pleurisy or

pulmonary lesions observed on radiographic examination.

( CXR / CT CHEST is gold standard)
 DIAGNOSIS & MANAGEMENT OF
PNEUMONIA IS GETTING
COMPLICATED BECAUSE OF-----
● Newer pathogens
● Expanded resistance to antimicrobials
● Increased immunocompromised populations
● Newer diagnostic tools and antimicrobial
agents
 PNEUMONIA - CLASSIFICATION
● ANATOMICAL --- Lobar pneumonia.
Segmental pneumonia
Subsegmental pneumonia
Bronchopneumonia
● IN CLINICAL SETTINGS-
community acquired pneumonia
hospital acquired pneumonia
aspiration pneumonia

immuno compromised host pneumonia

.
# 10% -CAP,60% of HAP have inadequate

responses to the empirical therapy initiated.

# Rate of resolution of physical and
lab abnormalities --
Abnormalities Duration
Fever ------------- 2 to 4 days
Cough ------------- 4 to 9 days
Tachycardia ------------ 2 days
Hypotension ------------- 2 days
Tachypnoea -------------- 3 days
Crackles ------------- 3 to 6 days
Leukocytosis ----------- 3 to 4 days
C-reactive protein ------ 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 (tachypnea) return to normal

# The expected time course for resolution" is controversial,

#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
# The terms non-resolving and slowly resolving pneumonia have

been used interchangeably to refer to “persistence of radiographic

abnormalities beyond the expected time course.

#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

# 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
Non resolving pneumonia is defined by
-The presence of persistence of clinical
symptoms and signs(cough, sputum production,
with or without fever > 100oF),
- 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

# 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.
# 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.
Causes of non resolution :
•Inappropriate antimicrobial therapy.
•Superinfection.
• Complications of initial pneumonia.
• Host factors.
• Delayed radiological recovery
• Presence of resistant organisms
• Presence of unusual organisms.
• Defects in defense.
• Diseases mimicking pneumonia
1)Inappropriate antimicrobial 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.
 Penetration of Antibiotics into
Respiratory Secretions
Good Penetration: Lipid Soluble,
Concentration of the
Antibiotic is Not Inflammation-
Dependent
Fluoroquinolones
Macrolides (newer azalides: azithromycin,
clarithromycin)
Tetracyclines
Tigecycline
Clindamycin
Trimethoprim/sulfamethoxazole
Linezolid
Poor Penetration: Relatively Lipid
Insoluble, Concentration of the
Antibiotic is Inflammation-Dependent
Aminoglycosides
Vancomycin
2)Superinfection.
Superinfection with resistant microorganisms
Including fungi, mycobacterium tuberculosis

Viral co infection with community – acquired

respiratory viruses
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
4)Host factors :
# Age esp. > 50 YRS
# Co morbid illnesses- Diabetes
# COPD
# Alcoholism
# Immunosuppressive/cytotoxic therapy
# Bacteremia .
# Multi-lobar pneumonia
# Intubated patients ( colonized with resistant
microorganisms)
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.
6)Presence of Resistant pathogens :
1- Drug-Resistant Streptococcus pneumonia (
DRSP) suspected if :
Treated with betalactams within 6 month.
Close exposure to young children.
Pneumonia in last one year.
Hospitalized in last 3 month.
HAP in last 2 months
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.
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.
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
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 abnormalities 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.
7)Presence of Unusual organisms :
• Tuberculosis .
• Nocardia (Nocardia as an oral microflora)
• Atypical mycobacteria.
• Fungi: aspergillus , cryptococcus, mucor,
histoplasma,coccidiodo.
• Exposure to animals-Francisella,yersinia
leptospira,chlamydia psittaci.
• Travel to Endemic areas- Hantavirus,
Paragonimiasis
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.)

• 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.)
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)
Drugs induced lung disease :
• Nitrofurantoin.
• Amiodarone.
• Methotrexate.
• Bleomycin .
• Mitomycin.
• Paclitaxel,Docetaxel.
• cyclophosphamide.
• IL-2
• Drug-induced interstitial lung disease (DILD) is
not uncommon.

• Causing either benign infiltrates to

lifethreatening
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
 DIAGNOSTIC EVALUATION
# Re evaluate host factors
# Possibility of antimicrobial failure--- may be due to--
*patient noncompliance
*improper dosage.
*review antibiotic resistant pathogen.
*review sensitivities.
*unusual pathogen.
# Infectious complications :
*empyema ---> Rpt CXR/chest CT
*endocarditis. -----> Echo.
*super infection
# Gram stain and culture of sputum ----

Neither sensitive nor specific . because-

contamination by upper airway flora
failure to get secretions from lower airway
previous use of antibiotics

# look for ATYPICAL organisms-- endotracheal

aspirate and protected brush specimens are to be
studied for this reasons
 #Sputum for AFB, CBNAAT, LPA and Culture and
Sensitivities if tuberculosis is suspected

# fungal stain of respiratory samples

# Blood cultures.
# Urine- antigen test for detection of legionella
#Pleural fluid analysis (if present) – stains &
culture – both aerobes & anaerobes
# D-dimer assay for PTE
#Serum ACE --- For sarcoidosis
#RF, ANA, ANCA –For vasculitis & CTD
 9)Diseases 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, pulm. Thromboembolism.
• Hypersenstivity pneumonitis
 RADIOLOGY
# Repeated CXR---
infiltrates, pleuraleffusion,
lymphadenopathy, cavitation
# CT SCANS ---
-detailed studyof
parenchyma,interstitium,pleura & mediastinum
- HRCT – GROUND GLASS OPACITY – in
active Interstitial pneumonitis.
- CT angio-- for PTE
BRONCHOSCOPY( FIBREOPTIC)
# PSB.(protected specimen brush) -
Sensitivity of PSB 40% -non responding.
# BAL (bronchoalveolar lavage) –
gram stain of centrifuged BAL fluid helps in
identifying the organisms
#TBLB ( transbronchial lung biopsy)--
– no bacteriological use
- very useful in
neoplasms,fungal,histiocytosis,BOOP,Tb,and for
immunesuppressed
 Routine Laboratory Evaluation of BAL
Specimens in
Immunocompromised Hosts
Pathology
Wright–Giemsa stain
Papanicolaou stain
Silver stain
Modified Jimenez stain (or other suitable for
detecting Legionella)
Fluorescent antibody stain for Pneumocystis
Microbiology
Stains: ---Gram’s: Wet mount KOH or calcofluor
white
Modified acid-fast , Fluorescent antibody
stain for Legionella
Antigen/Molecular:----
Cytomegalovirus ,Mycoplasma PCR ,Legionella
urinary antigen
Cryptococcal serum antigen
Culture:
Virology
Assays (molecular, ELISA, fluorescence,
culture) for:
Cytomegalovirus (consider resistance
testing)
Herpes simplex virus
Adenovirus
Respiratory syncytial virus
Influenza
Parainfluenza
Metapneumovirus
Endemic viruses (e.g., SARS, West Nile)
Possible Diseases Depending on Differential Cell
Count in Bronchoalveolar Lavage Fluid
PREDOMINANCE OF POLYMORPHONUCLEAR
LEUKOCYTES
Bacterial infection
Organizing pneumonia
PREDOMINANCE OF LYMPHOCYTES
Tuberculosis
Hypersensitivity pneumonitis
Sarcoidosis
Fibrosis
HEMOSIDERIN-LADEN MACROPHAGES
Alveolar hemorrhage
EOSINOPHILS
Pulmonary eosinophilia
Fungal infection
Pneumocystis jirovecii
Systemic diseases
Drug-induced disease
 Protected brush specimens
# sensitivities of 50-80%
# sensitivities of 50-80%
# 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
 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.
THANK YOU