Infectious Diseases of
The Lungs
Hu Suping
Pulmonary Department
1st clinical college, Wuhan University
Case
A 35 y.o. M presents with 2d cough,
productive of green-yellow sputum. He
complains of fever, chills, and dyspnea
PE: T 38.7℃, RR 26/min, BP 110/65 mmHg,
HR 125/min
Examination of the lungs reveals increased
fremitus and dullness at the right
posterior base. Crackles and bronchial
breath sounds are audible at the right base
Gram stain of the sputum reveals grampositive cocci and numerous neutrophils
目的和要求
• 掌握肺炎的临床表现和诊断程序
重点掌握肺炎球菌肺炎的病因、发病机制
和病理、临床表现、诊断、鉴别诊断和防
治。熟悉其它病原体所致肺炎的临床特点
和诊治
• 掌握肺脓肿的临床表现、诊断和鉴别诊断、
治疗原则
• 熟悉支气管扩张症的临床表现、诊断要点
• Overview of pneumonia
• Pneumococcal pneumonia
• Staphylococcal pneumonia
• Mycoplasma pneumonia
• Pulmonary mycosis
• Lung abscess
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Definition
Inflammation of the distal lung
terminal airways, alveolar spaces,
and interstitium
Causes: pathogen, physiochemical
factors, allergy, etc
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Pathophysiology of bacterial pneumonia
Sources of bacteria
Route of inoculation Response
Outcome
Colonization of
Naso/oropharynx
Air
Microaspiration
Inhalation
Lung
defenses
Non-pulmonary
infection
Bloodstream
Contiguous
infection
Sterile
lung
Direct extension
Pneumonia
Usual routes of inoculation
• Microaspiration：most bacterial pneumonia,
anaerobic pleuropulmonary infections
The concentration of aerobic bacteria in upper
respiratory tract secretions is about 108 organisms
per milliliter, and that of anaerobic bacteria is
about 10 times greater, aspiration of even small
quantities of oropharyngeal secretions introduces
an enormous bacterial challenge to the lungs
• Ambient air:
Mycobacterium tuberculosis
Viruses， including influenza
plague and anthrax bacilli
Organisms that are present in large numbers
in contaminated air in confined spaces, such
as Legionella organisms
• Bloodstream:
Staphylococcal
endocarditis, septic emboli
• Direct extension: Amebic liver abscess
(uncommon)
Pathogenesis
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Symptoms and signs
depending on the offending pathogen
and the state of the host
(1)Previously healthy person with
pneumococcal pneumonia (typical)
a brief prodromal upper respiratory illness
fever, chill
cough with purulent or “rusty” sputum
pleuritic chest pain
signs of consolidation
(2) Elderly confused patient
maybe only deterioration of mental
function
rhonchi without signs of consolidation
(3) Predisposing factors
old age, previous pulmonary diseases,
smoking history
A. a history of alcoholism, seizure disorder,
previous stroke, recent dental procedures
aspiration pneumonia or lung abscess caused by
oral anaerobes and mixed aerobic/anaerobic flora
B. a history of intravenous drug use
Staphylococcus aureus pneumonia with
tricuspid endocarditis (sepsis)
C. persons with depressed cell-mediated
immunity
increased incidence of bacterial, fungal, and
tuberculous pneumonia
Categories
Anatomy: lobar pneumonia; bronchopneumonia;
interstitial pneumonia
Causes: bacterial pneumonia; viral pneumonia;
mycoplasma, chlamydia pneumonia;
fungal pneumonia; radiopneumonitis;
etc
Contaminant source:
community-acquired pn（CAP）
hospital-acquired pn（HAP）
Lobar
pneumonia:
whole lobe(s)
involved
Fixed
specimen,
grey
hepatization
Lobar pneumonia
Bronchopneumonia,
patchy involvement
→
间质性肺炎
病理切片
间质性肺炎X片
间质性肺炎
CT片肺窗
CAP
an acute infection of the pulmonary
parenchyma in a patient who is not
hospitalized or residing in a long-term-care
facility for the 14 days before the onset of
illness
Common pathogens: S. pneumoniae, H.
influenzae, Mycoplasma pneumoniae, Chlamydia
pneumoniae, Moraxella catarrhalis
HAP or nosocomial pneumonia
Colonization of the upper respiratory tract with
potentially pathogenic organisms, including
gram-negative bacilli and S. aureus, commonly
occurs in hospitalized patients
The prevalence of colonization is proportional to
the duration of hospitalization and the severity of
underlying illness
Organisms most frequently involved in HAP
S. aureus, H. influenzae, K. pneumonia,
Pseudomonas species, Escherichia coli,
Enterobacter species, Acinetobacter, et al
• often resistant to multiple antimicrobials
• knowledge of the resistance patterns in a
given hospital is essential
Chest radiograph
Lobar consolidation with small pleural
effusion —pneumococcal pneumonia
Cavitation — S, aureus, gram-negative bacilli or
mixed anaerobic infection, or Mycobacterium
tuberculosis
Multilobar or segmental consolidation with large
pleural effusion — H. influenzae
Chest radiograph
Upper-lobe air space consolidation, abscess
formation, bulging interlobar fissure with
the accumulation of large amounts of
inflammatory exudate — K. pneumoniae
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Sputum
(1) before antimicrobial is instituted
(2) a deep cough
(3) be transported to the laboratory and
processed within 2 hours
(4) include Gram’s stain, cytologic
evaluation, and aerobic culture
Cytologic criteria for sputum culture
purulent, <10 squamous cells and >25 leukocytes/low
power field
Gram’s stain: predominated organism
encapsulated gram-positive cocci – Pneumococci
Quantitative culture
Cp ≥107 cfu/ml
definitive pathogen
104< Cp<107cfu/ml
Cp≤104cfu/ml
undetermined
exclusive
肺炎链球菌纯培养的
镜下形态 (革兰染色)
肺炎链球菌肺炎患者
痰标本直接涂片
(革兰染色)
肺炎链球菌在血琼脂
平板上的菌落特征
(18~24h)
肺炎链球菌荚膜形态
(Hiss荚膜染色)
金黄色葡萄球菌纯
培养的镜下形态
(革兰染色)
流感嗜血杆菌纯培养
镜下形态(革兰染色)
军团菌纯培养的镜下
形态(革兰染色)
军团菌在荧光显微镜 军团菌在BCYE琼脂
下的形态(荧光染色) 平板上培养的菌落
特征(3~5d)
Limitation
(1) difficulties in obtaining a proper specimen
pneumococci: extremely fastidious
(2) difficulties in interpreting the results
overgrowth with less fastidious oral flora
false positive diagnoses of GNB and S. aureus
prior antimicrobial treatment
false negative
Cultures of transtracheal aspirates,
transthoracic needle aspirates, and
bronchoalveolar lavage fluids or protected
brush catheter specimens
more sensitive and more specific
Blood cultures
(1) not necessary when the patient does not
require admission
(2) should be obtained from all hospitalized
patients before treatment is initiated
• Pleural fluid cultures
• Special tests
Antigen tests for viral pneumonia (influenza
virus, respiratory syncytial virus, adenovirus, and
parainfluenza viruese1,2, and 3)
Urine antigen assays for pneumococci and
legionella pneumoniae: very specific (>90%) but
low sensitivity(50%~60%)
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Diagnostic procedure
(1) Clinical diagnosis of pneumonia
a chest radiograph, WBC count and DC, sputum
examination, history and physical examination
Differential diagnosis: pulmonary tuberculosis
lung cancer
lung abscess
pulmonary thromboembolism
noninfectious diseases
Diagnostic procedure
(2) Identifying the etiologic pathogen
(3) Assessing the severity of infection and
need for hospitalization
In general, hospitalization is needed if
patients have multiple risk factors for a
complicated course
Risk factors
1. Age over 65 yr
2. Presence of coexisting illnesses such as COPD,
bronchiectasis, malignancy, diabetes mellitus, chronic
alcohol abuse, malnutrition, cerebrovascular disease, and
postsplenectomy
3. Certain physical findings: RR ≥ 30 /min; DBP≤ 60
mmHg or SBP < 90 mmHg; pulse ≥ 125/min; T< 35 ℃ or
≥ 40 ℃; confusion; and extrapulmonary infection
4. Laboratory findings also predict increased morbidity
or mortality:
a. WBC < 4×109/L or > 30 × 109/L, or N <1 × 109/L
b. PaO2< 60 mm Hg or PaCO2 of > 50 mm Hg (room air)
c. Serum Cr >1.2 mg/dl or BUN > 20 mg/dl (> 7 mM)
d. Chest radiograph findings: multilobar involvement,
presence of a cavity, rapid radiographic spreading and
the presence of a pleural effusion
e. HCT of <30% or Hb < 9 mg/dl
f. Sepsis or organ dysfunction as manifested by a
metabolic acidosis, or coagulopathy
g. Arterial pH < 7.35
Severe pneumonia
ICU
The major criteria included (1) a need for
mechanical ventilation, (2) septic shock
The minor criteria included (1) RR ≥ 30 /min; (2)
PaO2/FIO2 ≤ 250; (3) multilobar pneumonia; (4)
confusion; (5)BUN ≥ 20mg/dL;(6) WBC <
4×109/L;(7) BPC < 10×109/L;(8)T<36℃;(9)
systolic BP≤ 90mm Hg
Definition of severe CAP: the presence of one
major criteria or three minor criteria
• Definition of pneumonia
• Pathophysiology of pneumonia
• Clinical manifestation & Categories
• Microbiologic examination
• Diagnostic procedure
• Treatment and Prevention
Determine the most likely causative pathogen
• Interpret clinical and epidemiological clues
• Obtain appropriate microbiological sampling
Determine appropriate breadth of coverage
• Estimate the likelihood of antimicrobial resistance
• Consider the severity of the patient’s condition
Integrate Pharmacologic Considerations
• Pharmacokinetics and pharmacodynamics
• Interactions and toxicity
Narrow to directed therapy
• Interpret microbiological findings
• Assess clinical response
Determine the likely pathogen
• Clinical presentation
• Clinical course
• Acute vs. sub-acute vs. chronic (consider TB, fungus)
• Sputum characteristics
• Amount, color, bloody, odor
• Extrapulmonary features
• Body aches, gastrointestinal complaints (suggests
Legionella)
Determine the likely pathogen
• Epidemiologic Clues
• Geography
• Endemic mycoses (e.g. histoplasmosis), travel
• Contacts and exposures
• Comorbidity
• Alcoholism, diabetes, COPD
• Community epidemiology
• Seasonal illness, clusters
Determine breadth of coverage
• Physiologic Reserve
• Severely ill patients
• Consequences of inappropriate therapy may
be dire
• Usually provide more broad coverage
initially
• Mildly ill patients
• Will tolerate even a bad choice of therapy
• Coverage could be broadened if no
improvement
Determine breadth of coverage
• Likelihood of resistance
• Highly variable between community- versus
healthcare-associated pneumonia
• Clinicians require ready access to information
about national, regional, local and institutional
resistance trends
CTX ERY LEV PCN VAN
S. pneumoniae 100% 70%
96%
67% 100%
Duration of therapy
• For bacteria, usually treat for 10- 14 days
• Less therapy may be sufficient
• When hospitalized, usually begin IV
therapy
• Treat longer for abscess or cavitary disease
• For fungi and mycobacteria, treatment
duration is measured in months
Response to therapy
• Fever can last for 2–4 d, with defervescence
occurring most rapidly with S. pneumoniae
infection, and slower with other etiologies
• Leukocytosis usually resolves by Day 4
• Physical findings (crackles) persist beyond 7
d in 20 ~ 40% of patients
Three groups according to clinical response
to therapy
(1) patients with early clinical response
be
considered for rapid switch to oral therapy,
followed by prompt hospital discharge
(2) patients with lack of clinical response, which
should be defined at Day 3 of hospitalization
(3) patients with clinical deterioration, which can
occur as early as after 24 – 48 h of therapy
Patients in the second and third categories need
an evaluation of host and pathogen factors, along
with a reevaluation of the initial diagnosis and a
search for complications of pneumonia
Because of the natural course of treatment
response, antibiotic therapy should not be
changed within the first 72 h, unless there is
marked clinical deterioration or if bacteriologic
data necessitate a change
The common causes for clinical
deterioration
• Inadequate Antimicrobial Selection
• Unusual Pathogens
• Complications of Pneumonia
• Noninfectious Illness
Prevention
pneumococcal and influenza vaccine: safe
and effective
• Pneumococcal vaccine
The vaccine contains the purified capsular
polysaccharide from the 23 serotypes that cause
85–90% of the invasive pneumococcal infections
in adults and children
Effectiveness ranged 56 ~ 81%
The vaccine in its current form leads to an
antibody response that declines over 5–10 yr
Recommendations for use
• All patients aged 65 yr or greater
• Persons age ≤ 64 yr if they have chronic
illnesses or if they are living in special
environments or social settings
• Immunosuppressed patients: HIV, leukemia,
lymphoma, Hodgkin’s disease, multiple myeloma,
generalized malignancy, chronic renal failure, or
nephrotic syndrome, and immunosuppressive
therapy (including long-term steroids).
If immunosuppressive therapy is being contemplated,
vaccination should be given at least 2 wk before, if
possible
Influenza vaccine
the current vaccine contains three strains of
virus: an influenza A strain (H3N2), an
influenza A strain (H1N1), and an influenza B
strain
is modified annually to reflect the
anticipated strains in the upcoming season
Recommendations for use
• Those at increased risk for influenza
complications
• Those who can transmit influenza to high-risk
patients
• Those who wishes to reduce the chance of
becoming infected with influenza
Since the relevant viral strain changes annually,
revaccination is needed yearly, and should be
given from the beginning of September through
mid-November