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?????????