Pulmonary infectionPulmonary infection

Asma Navasakulpong, MD.

Respiratory and Respiratory Critical Care divisionRespiratory and Respiratory Critical Care divisionPrince of Songkla university

Respiratory tract defencesRespiratory tract defences

• Ventilatory flow• Cough• Mucociliary clearance mechanisms

• Mucosal immune system

OutlinesOutlines

• Pneumonia

CAP HAP VAP HCAPCAP, HAP, VAP, HCAP 

• Tuberculosis• Tuberculosis • Lung abscessLung abscess 

• Fungal infection

PneumoniaPneumonia

PneumoniaPneumoniaPneumoniaPneumonia

• Infection of pulmonary parenchyma

• Infection usually involves the distal airspaces y p

OrganismsPneumoniaOrganismsPneumoniaOrganism

• Viruses : Influenza, Parainfluenza, Measles,Viruses : Influenza, Parainfluenza, Measles, Varicella‐zoster, Respiratory syncytial virus (RSV) Cytomegalovirus (CMV)(RSV), Cytomegalovirus (CMV)

Common, often self limiting but can be complicated

• Bacteria• Bacteria

• Atypical bacteria: Chlamydia, Mycoplasma

• Fungi

PathologyPneumoniaPathologyPneumonia

Pathology

• Inflammatory cell infiltration exudate edema

• localized hemorrhage of bronchiolar submucosa,localized hemorrhage of bronchiolar submucosa, 

Interstitium, alveoli, Interalveolar septa and lymphatic 

lvessels

• Necrosis of bronchiolar and alveolar epitheliump

• Collapse  of the distal lung tissue

PathologyPneumoniaPathologyPneumonia

Pathology

• Interstitial involvement is relatively common in viral pneumonia or atypical pathogenviral pneumonia or atypical pathogen

• Bacterial pneumonia is characterized by the presence of damages of alveolipresence of damages of alveoli 

PathophysiologyPneumoniaPathophysiologyPneumonia

Pathophysiologyp y gy

• acute respiratory failureVentilation and /or perfusion disorder 

(V/Q mismatch)(V/Q mismatch)

Diffusion defects : interstitial edema

Intrapulmonary shunt : alveolar flooding

PneumoniaPneumoniaPneumoniaPneumonia

• Typical presentation : sudden or acute onsetTypical presentation : sudden or acute onset of fever, dyspnea, sputum production, chest pain tachycardia tachypneachest pain, tachycardia, tachypnea

AND

• Abnormal breath sound:fine crepitation bronchial breath soundfine crepitation , bronchial breath sound

Atypical PneumoniaAtypical pneumoniaAtypical PneumoniaAtypical pneumonia

• Legionella commonly complicated by GILegionella commonly complicated by GI symptoms including abdominal pain, vomiting and diarrheavomiting and diarrhea

• Chlamydia usually causes a mild sub‐acute illness with sore throat mild fever and dryillness with sore throat, mild fever, and dry cough

Atypical PneumoniaAtypical pneumoniaAtypical PneumoniaAtypical pneumonia

• Mycoplasma causes a subacute respiratory illness and occasionally causesillness and occasionally causes extrapulmonary symptoms including 

bullous myringitis

RashRash

neurologic symptoms

Arthritis

hematologic abnormalities: AIHAhematologic abnormalities: AIHA

PneumoniaPneumoniaPneumoniaPneumonia

Diagnostic Tests/Findingsg g• Chest radiograph

Vi l ll b i ith tt d ihil• Viral usually begins with scattered perihilarand peribronchial infiltrations

• Bacterial :patchy , lobar infiltrates• Acute aspiration usually develops in portion of lung that is dependent at time of aspiration

PneumoniaPneumoniaPneumoniaPneumonia

• CBC: White blood cell count may or may not elevate

• Viral cultures of nasopharyngeal secretionsViral cultures of nasopharyngeal secretions

• Blood cultures

• Sputum stain• Sputum  stain 

• Sputum cultures

Classification of PneumoniaCl ifi ti f P iClassification of PneumoniaClassification of Pneumonia

• By morphologyBy morphology

(lobar pneumonia, bronchopneumonia) 

• By clinical setting 

(e g community acquired pneumonia)(e.g. community acquired pneumonia)

• By organism 

(mycoplasma, pneumococcal etc)

Pathological description of pneumoniaPathological description of pneumonia

By morphology

Lobar PneumoniaP i G h i i ( l b )Lobar PneumoniaPneumonia: Grey hepatization (upper lobes)

Lobar pneumonia• Confluent consolidation 

involving a complete lung lobe

M t ft d t• Most often due to Streptococcus pneumoniae(Pneumococcus)(Pneumococcus)

• Can be seen with other organisms g

(Klebsiella, H. influenza , Legionella) 

RadiologyRadiology lobar pneumonialobar pneumoniaRadiology Radiology –– lobar pneumonialobar pneumonia

• Homogeneous orHomogeneous or     Inhomogeneous

d idensity

• Alveolar/Intersitial/infiltration

• Lobar involvement• Lobar involvement

ComplicationsC li ti f P iComplicationsComplication of Pneumonia

• Organisation (fibrous scarring)Organisation (fibrous scarring)

• Abscess

• Bronchiectasis

• Empyema thoracis (pus in the pleural cavity)cavity)

BronchopneumoniaPneumoniaBronchopneumoniaPneumoniaBronchopneumonia• Infection starting inInfection starting in airways and spreading to adjacent alveolarto adjacent alveolar lung

• The consolidation is• The consolidation is patchy and not confined by lobarconfined by lobar architecture

RadiologyRadiology BronchopneumoniaBronchopneumoniaRadiology Radiology ‐‐ BronchopneumoniaBronchopneumonia

Focal / patchy /Multinodular/cavitory lesions

Staphylococcus pneumonia Mycoplasma pnemoniaStaphylococcus pneumonia Mycoplasma pnemonia

Pneumonia : by clinical settingClassification of Pneumonia

li i l i

y gClassification of Pneumonia

By clinical setting

C it i d i (CAP)• Community‐acquired pneumonia (CAP) : acute infection of the pulmonary parenchyma in a 

ti t h h i d th i f ti i thpatient who has acquired the infection in the community

• Hospital acq ired (nosocomial) pne monia (HAP)• Hospital‐acquired (nosocomial) pneumonia  (HAP) : onset in hospital 48 hr after admission

Classification of Pneumonia

li i l i

Classification of Pneumonia

By clinical setting

• Ventilator‐associated pneumonia (VAP) : onset 48 72 after on ventilatoronset 48-72 after on ventilator

• Healthcare associated pneumonia (HCAP) : h h l h f l hacquired in other healthcare facilities such as 

dialysis centers, transfusion and outpatient clinics 

CAP- criteria diagnosis

1 N l i fil i

CAP criteria diagnosis

1. New pulmonary infiltration2. Acute onset, < 2 weeks3. Symptoms and signs of lower respiratory tractinfection (at least 3 in 5)

• fever• cough + productive cough• dyspnea• pleuritic chest painp p• consolidation or crackle on physical examination

Thai Thoracic Society guideline for CAP 2001

CAP severity :CURB‐65CAP severity :CURB‐65

• C = Confusion  (1)• U = Urea > 7mmol/L ( (1)• U = Urea > 7mmol/L ( (1)• R = Respiratory rate >/= 30/min (1)• B = BP systolic < 90mmHg or diastolic 

≤ 60mmHg (1)≤ 60mmHg (1)• 65 = Age ≥ 65 years (1)

British Thoracic Society guidelines 2009y g

CAP severity :CURB‐65

30 d li

CAP severity :CURB‐65

• 30-day mortalityFactor Mortality0 0.7%, 1 2.1%,

2 9.2%, 3 14.5%,3 14.5%, 4 40%, 5 57%5 57%,

Lim WS et al. Thorax 2003 ; 58 :377–82

58:377–82CAP severity :CURB‐6558:377–82.l i k f d h h i

CAP severity :CURB‐65

• 0 or 1‐ low risk of death, treat as having non‐severe pneumonia, may be suitable for home treatment (1.5% mortality rate )

• 2  increased risk of death, consider short ,inpatient stay or hospital supervised outpatient treatment (9.2% mortality rate )p ( y )

• 3 or more – high risk of death and should be managed as having severe pneumoniamanaged as having severe pneumonia (22% mortality rate )

CAP pathogens associatedCAP pathogens associated

25

30

%)

20

case

s (%

10

15

tion

of c

5

10

Prop

or

0G-neg

enterobacteriaH influenzae M pneumoniaeViral C pneumoniae S pneumoniae

enterobacteria

Aetiology of Community Acquired Pneumoniaein Nakhonphanom Hospital

Known aetiology 19 (24 %)

S pneumoniae 11 (58 %)S.pneumoniae 11 (58 %)

B.pseudomallei 3 (16 %)

S.aureus 2 (11 %)

Modifier Affecting BacteriologyModifier Affecting Bacteriology

• IDSA/ATS  guideline 2007

• BTS guidelines 2009BTS  guidelines 2009• NEJM 2014

HAP VAP HCAP :pathogenHCAP/HAP/VAP thHAP, VAP, HCAP :pathogenHCAP/HAP/VAP pathogens

• Usually caused by bacteriay y

• Currently the second most common

nosocomial infectionnosocomial infection

• HAP accounts for up to 25‐60 % of all ICU

infections

Nosocomial infectionNosocomial infection

UTI 31%

BSI Wound 12%

Other 11%

Pneumonia 27%

19%

ICU Pneumonia 47%BSI 19%

UTI 19%ICULRTI 19%

Nosocomial pneumonia is the leading cause ofp gmortality from nosocomial infection

Treatment of pneumoniaTreatment of pneumonia

• Antimicrobial treatment based on etiologyh dil d h h i h• Bronchodilators and chest physiotherapy 

may improve airway clearance• Other supportive therapy may include additional fluids and/or oxygen , ventilator/ yg ,

• Can progress rapidly and should be monitoredmonitored

Treatment of CAPO i

Treatment of CAP• OutpatientNew oral macrolideN l i i lNew oral respiratory quinoloneOral beta lactam plus macrolideI i• Inpatient IV beta lactam plus oral macrolideIV i i lIV new respiratory quinolone

• ICU patientIV beta lactam plus IV macrolideIV beta lactam plus IV new resp. quinolone(± Anti‐pseudomonal antibiotic)

Treatment of HCAP‐HAP‐VAPTreatment of HCAP‐HAP‐VAP

ATS/IDSA guidelines 2005

Treatment of HCAP‐HAP‐VAPTreatment of HCAP‐HAP‐VAP

Treatment of HCAP‐HAP‐VAPTreatment of HCAP‐HAP‐VAP

immunocompromised hostimmunocompromised host

• Virulent infection with common organism (e.g. Usual bateria, TB) ( g )

• Infection with opportunistic pathogeni ( t l i CMV)virus (cytomegalovirus ‐ CMV)

bacteria (Nocardia, Rhodococcus, Mycobacterium avium intracellulare)

fungi (Cryptococcus,  Histoplasmosis,  Penicillosis, Aspergillosis, Candida,  Pneumocystis) 

HIV positive patient CMV (cytomegalovirus)HIV‐positive patient CMV (cytomegalovirus)

Special stain also shows PneumocystisHIV positive patient PJPSpecial stain also shows PneumocystisHIV‐positive patient PJP

Pneumocystis jiroveciiPneumocystis jirovecii

• Bilateral perihilar/basal  interstitial infiltration

• Diffuse , symmetric to medium reticular or reticulonodular

• Pattern of ground‐glass opacificationp

Tuberculosis

TuberculosisTuberculosis 

• 22 million active cases in the world

• 1.7 million deaths each year 

I id h i d ith HIV d i• Incidence has increased with HIV pandemic

TuberculosisT b l iTuberculosis Tuberculosis 

• Mycobacterial infection

• Chronic infection described in many bodyChronic infection described in many body sites : lung, gut, kidneys, lymph nodes, skin….

P h l h i d b d l d ( IV)• Pathology characterised by delayed (type IV) hypersensitivity (granulomas with necrosis)

Transmission : influenced factorsTransmission : influenced factors 

Source caseSource case Environmental Contact

Bacillary loadBacillary load Volume of air ClosenessBacillary loadBacillary load

SymptomsSymptoms

ThTh

Volume of airRecirculationFiltration

ClosenessDurationPrevious infectionTherapyTherapy Filtration

UV light

Previous infectionImmune status

Tuberculosis: Transmission and natural historyube cu os s:Transmission and Natural HistoryTransmission and natural history

Self-Cure – 90%

30 % Infection Initial containment – 95%

Late Progression - 5%(reactivated TB)Early Progression 5% (reactivated TB)Early Progression - 5%

(primary TB)

Pathology of Tuberculosis (1)Pathology of Tuberculosis (1)

• Primary TB (1st exposure)inhaled organism  phagocytosed and carried to g p g yhilar lymph nodes. 

Immune activation (few weeks) leads to aImmune activation (few weeks) leads to a granulomatous response in nodes (and also in lung) usually with killing of organismlung) usually with killing of organism.

in a few cases infection is overwhelming and spreadsspreads

Pathology of Tuberculosis (2)P h l f T b l i (2)Pathology of Tuberculosis (2)Pathology of Tuberculosis (2)

• Secondary TB• reactivation of disease in a person with some pimmunity

• disease tends initially to remain localized oftendisease tends initially to remain localized, often in apices of lung.

• can progress to spread by airways and/or• can progress to spread by airways and/or bloodstream

Tissue changes in TBTissue changes in TB

P i• PrimarySmall focus (Ghon focus) in periphery of mid zone of lung

Large hilar nodes g

(granulomatous inflammation)

S d• SecondaryFibrosing and cavitating apical lesion

Primary and secondary TBPrimary and secondary TB

• In secondary there are primed T cells which 

• In primary the site of infection shows non‐

stimulate a localised granulomatous response

specific inflammation with developing granulomas in 

dnodes

Primary TB vs secondary TBPrimary TB vs secondary TBNecrosis‐fibrosis‐cavitation

Gohn fociNecrosis fibrosis cavitation

T cell response: CD4 (helper) enhance killing. CD8 (cytotoxic) kill infected cells givingCD8 (cytotoxic) kill infected cells giving necrosis

Granulomatous inflammation with caseousnecrosis

ComplicationsComplications 

• Local spread (pleura, lung)

Bl d d• Blood spread 

• Miliary TB or “end‐organ” diseasedisease 

(kidney, adrenal etc.)

• Swallowed intestines• Swallowed ‐ intestines

Antituberculosis drugsAntituberculosis drugs

• กลุมยาหลัก (first line) มีประสทิธิภาพดีและเลือกใชเปนอันดบัแรกในการรักษาเปนอนดบแรกในการรกษา

• กลุมยาสํารอง (second line) มีประสทิธิภาพปานกลางหรือต่ํา ผลขางเคยีงสูง ราคาแพง เลือกใชกรณีเชื้อดื้อ

ใ ัยาในกลุมยาหลก

Antituberculosis drugs currently in useFirst line Antituberculosis drugsAntituberculosis drugs currently in useFirst line Antituberculosis drugs

WHO guideline 4th edition 2010

Second line Antituberculosis drugsSecond line Antituberculosis drugs

Drugs Dose

Levofloxacin 1000 mg orally or IV•g y

Moxifloxacin 400 mg orally or IV

CapreomycinΔ 15 mg/kg IM or IV (max 1 g)Capreomycin 15 mg/kg IM or IV (max 1 g)

KanamycinΔ◊ 15 mg/kg IM or IV (max 1 g)

AmikacinΔ◊ 15 mg/kg IM or IV (max 1 g)Amikacin 15 mg/kg IM or IV (max 1 g)

StreptomycinΔ 15 mg/kg IM or IV (max 1 g)

15 to 20 mg/kg orally as a single daily dose or twoEthionamide

15 to 20 mg/kg orally as a single daily dose or two divided doses (max 500 mg twice daily)

Cycloserine10 to 15 mg/kg orally in two divided doses (max 500 

Cycloserinemg twice daily)

Paraaminosalicylic acid 8 to 12 g orally in two or three divided doses

WHO categories of treatmentWHO categories of treatment 

• CAT I 2HRZE(S) / 4HRCAT I   2HRZE(S) / 4HR

• CAT II  2HRZES / 1HRZE / 5HRE• CAT IV Reserved drugs (second line)

Dose and side effectDose and side effect

Drugs Dose/day Side effectsDrugs Dose/day Side effectsIsoniazid (H) 300 mg Hepatitis , rash , N/V, neuritis

Seizure , SLE , vasculitis

Rifampicin (R) 10 mg/kg Hepatitis , rash ,N/V, secretion di l tidiscoloration,Hypersensitivity, Flulike

Ethambutol (E) 15‐25 mg/kg Optic neuritisEthambutol (E) 15 25 mg/kg Optic neuritis

Pyrazinamide (Z) 20‐30 mg/kg Hepatitis rash N/V arthralgiaPyrazinamide (Z) 20 30 mg/kg Hepatitis , rash , N/V, arthralgia, Uric , gout , Photosensitive dermatitis 

( ) /k i i h i iStreptomycin (S) 15 mg/kg Ototoxicity , nephrotoxicity

Side effects : Risk factorsSide effects : Risk factors

• Old age• Alcoholism• Malnutrition, Low BMIMalnutrition, Low BMI• HBV , HCV , HIV infectionLi di• Liver disease

• Liver toxic agents  • Pregnancy 

Lung AbscessLung Abscess

Lung AbscessLung Abscess

• Localised collection of pus

• Central tissue destruction

• Lined by granulation tissue/fibrosis t ssue/ b os s(attempted healing)

• Tumour‐likeTumour‐like

Lung abscessL AbLung abscess

S t

Lung Abscess• Symptoms

• Fever (sub‐acute or prolong)P d ti h• Productive cough 

• Haemoptysis (massive or non‐massive)i ht l• weight loss

• Chest pain i• signs• Fever Cl bbi f fi• Clubbing of fingers 

• Decrease BS • Crepitation• Crepitation

Lung abscessL AbLung abscess

O i

Lung Abscess• Organisms

Staphylococcus , StreptococcusA bAnaerobesGram negativesF lFungalTB

• Clinical contextsA i tiAspirationFollowing pneumonia

Lung abscessL AbLung abscessLung Abscess

• Managementg

Antimicrobial treatment based on etiologyAntimicrobial treatment based on etiologyChest physiotherapy may improve airway lclearanceOther supportive therapy may include pp py yadditional fluids and/or oxygen supplementpp

Fungal infection

Fungal infection

h

Fungal infection

Common in immunocompromise host

• Cryptococosis

• Histoplasmosis• PenicillosisPenicillosis

CryptococosisCryptococosis

• acquired by inhalation

• HIV and non HIVHIV and non HIV

• subacute onset, fever, headache, and irespiratory symptoms

• productive cough, dypsnea, and chest painp g , yp , p

• Nonspecific CXR: 

diffuse interstitial infiltrates, localized interstitial, alveolar,or nodular involvement

CryptococcosisCryptococcosisC t iCryptococcosisCryptococcosisCryptococosis

Mass like lesion Mass like lesion with multinodular lesions

CryptococosisC t iCryptococosisCryptococosis

• Serum cryptococcal Ag is highly sensitive andSerum cryptococcal Ag is highly sensitive and specific

IV A h i i B• IV Amphotericin B

• require maintenance therapy with q pyfluconazole to prevent disease relapse

HistoplasmosisHistoplasmosis

• Dimorphic fungus : mold (filamentous)/yeastbi d b d i• bird or bat droppings

• HIV and non HIV

• Subacute onset of fever accompanied cough ,  p g ,dypsnea

HistoplasmosisHistoplasmosis

Diffuse nodular infiltration Mediastinal lymphadenopathy

HistoplasmosisHi t l iHistoplasmosisHistoplasmosis

• CXR often shows diffuse nodular infiltrates, mediastinal lymphadenopathymediastinal lymphadenopathy

h i i f ll d b i h• Amphotericin B followed by treatment withitraconazole

PenicilliosisPenicilliosis

• Dimorphic fungusDimorphic fungus

• Mostly found in HIV

• Fever cough dyspnea and generalizedFever , cough , dyspnea and generalized papular skin lesions

PenicilliosisPenicilliosis

PenicilliosisP i illi iPenicilliosisPenicilliosis

• CXR showed diffuse reticulonodularCXR showed diffuse reticulonodularinfiltration or  localized pattern

Di i bl d b ki• Diagnosis : blood, bone marrow, or skin biopsy specimen

• Amphotericin B or itraconazole. 

QUESTIONS?????????