COMMUNITY ACQUIRED PNEUMONIA

Gagan BrarMBBS,MD, IDCCM,EDIC

DEFINITION

“An acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by an acute infiltrate on a chest radiograph (CXR), or auscultatory findings consistent with pneumonia (e.g. altered breath sounds, localised crackles) in a patient not hospitalised or residing in a long-term care facility for ≥14 days prior to the onset of symptoms.”

GUIDELINES FOR CAP American Thoracic Society (ATS)

Guidelines - Management of Adults with CAP (2001) Infectious Diseases Society of America (IDSA)

Update of Practice Guidelines Management of CAP in Immuno-competent adults (2003)

BTS guidelines 2009 ATS and IDSA joint effort IDSA/ATS Consensus Guidelines on the Management of CAP in Adults (March 2007)

INCIDENCE

Overall incidence is 3–40 per 1000 inhabitants

per year

40-60% require hospital admission 10% ICU amission

Mortality : 10%

Most common infectious cause of death3rd MC cause of death

CAP – Age wise Incidence

<5 5 to 17 18-24 25-44 45-64 >650

200

400

600

800

1000

1200

1400

# of cases

CAP – Age wise Mortality

<4 5 to 14 15-24 25-44 45-64 >650

10

20

30

40

50

60

70

80

0 0 0 25.7

74.9

# of deaths

COMMON CAUSES……….• Streptococcus pneumonia • Haemophilus influenza • Staphylococcus aureus• Legionella species • Mycoplasma pneumoniae• Influenza Virus, Other Respiratory Viruses( Parainfluenza Virus,

Respiratory Syncytial Virus, Adenovirus, Coronavirus, Human Metapneumovirus, And Rhinovirus).

LESS COMMON CAUSES………• Pseudomonas Aeruginosa Or Other Gram-negative

Rods• Pneumocystis Jirovecii• Moraxella Catarrhalis • Mixed Microaerophilic And Anaerobic Oral Flora

UNCOMMON CAUSES……• Mycobacterium tuberculosis• Nontuberculous mycobacteria • Nocardia species• Mycoplasma pneumoniae• Chlamydophila pneumoniae • Chlamydophila psittaci• Coxiella burnetii• Histoplasma capsulatum, coccidioides species, blastomyces

dermatitidis, cryptococcus and aspergillus species

NONINFECTIOUS

• Pulmonary edema• Lung cancer• Acute respiratory distress

syndrome• Pulmonary infarction• Cryptogenic organizing

pneumonia• Eosinophilic pneumonia

• Acute interstitial pneumonia • Sarcoidosis • Vasculitis (granulomatosis with

polyangiitis)• Pulmonary alveolar proteinosis • Drug toxicity• Radiation pneumonitis

CAP – Bacteriology in Hospitalized Pts

Viral and bacterial co-infection occurs in 4–17% of cases of CAP .

In 2009 H1N1 influenza pandemic, Staphylococcus aureus and Streptococcus pneumoniae were common co pathogens

Causes vary according to the

patient population, host immune status,

and geographic region.

No cause is determined in about half of patients with

CAP.

CAP – Pathogenesis

Inhalation

Aspiration

Hematogenous

ID Clinics 1998;12:723. Am J Med 1994;96:313

HISTORY

WHICH CATEGORY?

CAP

NHAP

HAP (VAP)

CAP

HAP/VAP

HCAP

CAN THE PATIENT BE IMMUNOCOMPROMISED?

HISTORY

HISTORY

ANY UNDERLYING LUNG DAMAGE?

HISTORY COMORBIDITY

“mimic” pneumoniaimpact on drug treatment

HISTORY WHAT IS HIS JOB?

Anything & everything

Q fever

Anthrax

Pulmonary TB

HISTORY7. CONTACT WITH….

Chlamydia pneumoniae

Francisella tularensis

Yersinia pestis

HISTORY Legionellosis

TRAVEL??

HISTORY ASPIRATION ?

stroke

vomiting

unconcious/fits

Ryle’s tube

HISTORY10. WHAT DRUGS ARE YOU TAKING?

Amiodarone

Nitrofurantoin

Bleomycin

Chlorambucil

Procarbazine

BulsulfanCyclophosphamide

Aziathioprine

Methotrexate

Sulphonamides

Lung infiltrates

Heroin

Methadone

Chlorthiaxide

Contrast media

Pulmonary oedema

Proton Pump Inhibitors

Age > 65Bacteremia (for S. pneumoniae)S. aureus, MRSA , Pseudomonas Extent of radiographic changesDegree of immuno-suppressionAmount of alcohol consumption

CAP – Risk Factors for Mortality

ID Clinics 1998;12:723. Am J Med 1994;96:313

CAP – Evaluation of a Patient

History, Physical exam, CXR

No Infiltrate

Alternate Dx.

Infiltrate or Clinical evidence of CAP

Evaluate need for Admission Severity scoring

Out Patient

Medical Ward

ICU Adm.

Diagnosis of CAP

Clinical Radiologic MicrobiologicRequired forDiagnosis

• Onset: Acute (more common) or Subacute (suggestive of atypical pneumonia) General (Systemic) Manifestations: • fever, Approx 80% febrile ( be careful in elderly….)• myalgia • Tachycardia

Local (Pulmonary) Manifestations

• Productive cough, dyspnoea, pleuritic chest pain.• Bronchial breathing, Vocal resonance• RR>24 (45%-70%) ( most sensitive finding in older pts….) • Crackles on auscultation

• Extra- Pulmonary Manifestations in Atypical Pneumonia:• Erythema nodosum: in Psittacosis• Erythema Multiforme: in Mycoplasma pnemonia• Headache / mental confusion.• Abdminal pain / diarrhoea.• Relative bradycardiaNo clear constellation of signs and symptoms found to accurately predict

• Classic signs of consolidation occur in less than 25%• Multi-organ dysfunction or failure may occur depending on the type and severity of

pneumonia• Over 50% may also have non-respiratory symptoms and over a third may have no

systemic signs of infection

RADIOGRAPHS…

• Routine evaluation • To establish the diagnosis and to aid in differentiating CAP from

other causes of cough and fever, such as acute bronchitis.• Useful for suggesting the etiologic agent, prognosis,

alternative diagnoses, and associated conditions.

Rarely, the admission chest radiograph is clear, but thepatient’s toxic appearance suggests more than bronchitis.

Infiltrate Patterns and PathogensCXR Pattern Possible Pathogens

Lobar S.pneumo, Kleb, H. influ, Gram Neg

Patchy Atypicals, Viral, Legionella

Interstitial Viral, PCP, Legionella

Cavitatory Anerobes, Kleb, TB, S.aureus, Fungi

Large effusion Staph, Anaerobes, Klebsiella

• For patients who are hospitalized for suspected pneumonia but who have negative chest radiography findings,it may be reasonable to treat their condition presumptively with antibiotics and repeat the imaging in 24–48 h.

• In this cohort of patients with severe CAP, radiologic progression of pulmonary infiltrates in the first 48 h is a significant adverse prognostic feature. In contrast, bacteremia does not affect outcomes

Three hundred sixty-two patients with suspected CAP were enrolled in 14 Europeancenters.

DIAGNOSTIC TESTING FOR MICROBIAL ETIOLOGY• Treatment is best when it is pathogen directed….

• Little consensus on practicality of achieving this goal due to controversies in the value of diagnostic tests

CAP – Gram Stain of Sputum

Efficiency of test S. pneumoniae H. influenza

Sensitivity 57 % 82 %

Specificity 97 % 99 %

Positive Predictive Value 95 % 93 %

Negative Predictive Value 71 % 96 %

Good sputum samples is obtained only from 39%83% show only one predominant organism

• A sputum Gram stain specimen is considered satisfactory for interpretation when the neutrophil count is >25 and the epithelial cell count is <10 per low power field.

• Positive quantitative culture of bronchoalveolar lavage fluid (>104cfu/mL) or PSB (>103 cfu/L) or >5% of leukocytes containing phagocytosed bacteria.

• For Mini-BAL a threshold of more than 10,000 cfu/ml (104 ) is considered positive .

• For TA, a threshold of more than 1,000,000 cfu/ml (106 ) is accepted as positive .

• >10 leukocytes per high power field in Gram stain of tracheal aspirate

PATHOGENS RETRIEVED FROM BLOOD CULTURE

68%

16%

11%5%

S.pneumoniaeEnterobacteriaStaph.aureusOthers

Blood cultures have a relatively low yield, positive in 5–14% of patients,

• Additional tests include serology, urinary antigen testing for S.pneumoniae and L.pneumophila serogroup 1 and NAAT specifically for respiratory viruses and atypical bacteria

When multiple diagnostic tests were employed, the diagnostic yield increased in one study from 50 to 80%

Mortality of CAP – Based on Pathogen

P. aeruginosa - 61.0 %K. pneumoniae - 35.7 %S. aureus - 31.8 %Legionella - 14.7 %S. pneumoniae - 12.0 %C. pneumoniae - 9.8 %H. influenza - 7.4 %

SCORING OF DISEASE SEVERITY

• PREDICTION OF ADVERSE OUTCOME AND ADMISSION TO ICU

• Predict adverse outcome and ICU admission including

• PNEUMONIA SEVERITY INDEX (PSI) • CURB-65, CRB-65• MODIFIED ATS MAJOR AND MINOR CRITERIA• SCAP PREDICTION RULE• SMART-COP, REA-ICU INDEX AND CAP-PIRO• A-DROP,CORB,SOAR

Classification of Severity - PORTPredictors Absent

Class I

70

Class II

71 – 90

Class III

91 - 130

Class IV

> 130

Class V

Severity indices

PSI versus CURB-65

• Meta-analysis by chalmers et al. Showed no difference in their ability to predict mortality

• PSI score was more sensitive than the CURB-65 score• PSI score better at identifying nonsevere CAP patients that may not need

hospital admission • helpful in situations where CAP mortality is high.

Chalmers JD, Mandal P, Singanayagam A et al. Severity assessment tools to guide ICU admission in community-acquired pneumonia: systematic review and meta-analysis. Intensive Care Med. 37(9), 14091420 (2011)

• Curb-65 more specific with a higher positive predictive value than the psi score• Correct identification of patients at higher risk, but a chance of mismanaging

high-risk patients as nonsevere CAP due to the low sensitivity• CURB-65 may help in situations where mortality is low and resources are

limited

Loke YK, Kwok CS, Niruban A, Myint PK. Value of severity scales in predicting mortality from community-acquired pneumonia: systematic review and meta-analysis. Thorax 65(10), 884890 (2010).

PARAMETER AGE <50 AGE >50 POINTS

S SBP < 90 mmhg <90 mmhg 2

M Multilobular CXR involvement + + 1

A Albumin <35gm/l <35gm/l 1

R Resp.rate >25 /min >25 /min 1

T Tachycardia >125/min >125/min 1

C Confusion(acute) + + 1

O Low OxygenPaO2 <70 or SpO2<93 or PaO2/FIO2 < 333

PaO2 <60 or SpO2<90 or PaO2/FIO2 < 250 2

P PH < 7.35 <7.35 2

CAP – Criteria for ICU Admission

• IDSA/ATS criteria had a higher sensitivity than the PSI and CURB-65/CRB-65 scores.

• Two major criteria are not always met by patients with severe disease on presentation.

• Patients without these major criteria are at high risk for clinical deterioration, needing icu care and death

• Presence of more than three minor criteria may be of value in predicting icu admission, prediction of 30-day mortality and need for mv/vasopressor support

• SCAP has been shown to be superior to the modified ATS criteria and CURB-65, and similar to PSI for the identification of severe CAP

• The study by Brown et al. found that patients with severe CAP had a longer hospital length of stay and similar 30-day mortality when compared with other definitions for severe CAP

Brown SM, Jones BE, Jephson AR, Dean NC; Infectious Disease Society of America/American Thoracic Society 2007. Validation of the Infectious Disease Society of America/American Thoracic Society 2007 guidelines for severe community-acquired pneumonia. Crit. Care Med. 37(12), 30103016 (2009).

The CAP-PIRO score overlaps multiple variables involving the lung and other systemic organ dysfunctions, which is a concept already proposed by several investigators of severe CAP [5,9] . However, this score only predicts ICU mortality in CAP, and future prospective studies should determine the ability of this score to predict ICU admission.

. Clinical judgment remains critical; do not

blindly follow scores!

CAP – Laboratory Tests

• CXR – PA & lateral• CBC with Differential• BUN and Creatinine• FBG, PPBG• Liver enzymes

• Serum electrolytes, ABG.

• Gram stain of sputum• Culture of sputum• Pre Rx. blood cultures• Oxygen saturation

• History

• Newly recognized lung infiltrate on chest imaging together withfever, cough, sputum production, shortness of breath, physical findings of consolidation, and leukocytosis.

• Some patients……..No cough , sputum production or elevated wcc , afebrile

Biologic Markers

• Pro-BNP has been shown to increase in CAP and correlate with mortality

• Pro-BNP had the highest sensitivity for predicting the need for mechanical ventilation as well as 28-day mortality (90% and 98%, respectively) but had low specificity (42% and 47%) compared with acute physiology and chronic health evaluation II scores,curb-65 and PSI

Nowak A, Breidthardt T, Christ-Crain M, et al. Direct comparison of three natriuretic peptides for prediction of short- and long-term mortality in patients with community-acquired pneumonia. Chest 2012; 141:974–982.Xiao K, Su LX, Han BC, et al. Analysis of the severity and prognosis assessment of aged patients with community-acquired pneumonia: a retrospective study. J Thorac Dis 2013; 5:626–633.

• Procalcitonin is upregulated in sepsis and severe infections.• Procalcitonin levels are higher in bacterial versus viral or atypical cap• Procalcitonin levels less than 0.5 mg/l had negative predictive values

of 99% and 97%, respectively, for viral and atypical CAP compared with bacterial CAP

Menendez R, Sahuquillo-Arce JM, Reyes S, et al. Cytokine activation patterns and biomarkers are influenced by microorganisms in community-acquired pneumonia. Chest 2012; 141:1537–1545. Ugajin M, Yamaki K, Hirasawa N, Yagi T. Predictive values of semi-quantitative procalcitonin test and common biomarkers for the clinical outcomes of community-acquired pneumonia. Respir Care 2013.

When antibiotic therapy was guided by procalcitonin levels, there was no difference in mortality or treatment failure, but there was a reduction in total antibiotic exposure

NEW TREATMENT PARADIGM

Hit hard and early with appropriate antibiotic(s)

Short Rx. Duration; De-escalate where possible

Objective 2Objective 1

Avoid emergence ofmultidrug resistantmicroorganisms Immediate Rx.

of patients with serious sepsis

The Therapy Conundrum

Risk assessment approachEarly Antibiotic selectionChange treatment driven by local surveillanceHit hard and hit earlyAs short a duration as possibleDe-escalate when and where possible

CAP TREATMENT CONSENSUS

Empiric Treatment – Outpatient

• Substantive evidence for macrolides having an immunomodulating effect on the host immune response

• Most patients with community-acquired pneumonia and sepsis-related organ dysfunction have high systemic pneumococcal bacterial loads

• Suggests well-recognized anti-toxin effects of macrolides, even in macrolide-resistant organisms

• Neither fluroquinolones nor tetracyclines observed to have anti-pneumolysin effects in pneumococci

• odds ratios for death ranging from two to six times greater in non-macrolide-treated patients

Empiric Rx. – Suspected Pseudomonas1. Piperacillin-Tazobactam, Cefepime, Carbapenems

(Imipenem, or Meropenem) plus either Cipro or Levo

2. Above Beta-lactam + Aminoglycoside + Azithromycin

3. Above Beta-lactam + Aminoglycoside + an

antipseudomonal and antipneumococcal FQ

4. If Penicillin allergic - Aztreonam for the Beta-lactam

Empiric Rx. – CA MRSAFor Community Acquired Methicillin-Resistant Staphylococcus aureus (CA-

MRSA) Vancomycin or Linezolid

For Methicillin Sensitive S. aureus (MSSA) B-lactam and sometimes a respiratory Fluoroquinolone (until

susceptibility results). Specific therapy with a penicillinase-resistant semisynthetic penicillin or

Cephalosporin

RECOMMENDED ANTIMICROBIAL THERAPY FOR SPECIFIC PATHOGENS

DURATION OF THERAPY

• Minimum of 5 days• Afebrile for at least 48 to 72 h• No > 1 CAP-associated sign of clinical instability• Longer duration of therapy

If initial therapy was not active against the identified pathogen or

complicated by extra pulmonary infection

New data – The Speed of Delay ! (Class 4,5)

0

10

20

30

40

50

60

70

80

90

0.5 1 2 3 4 5 6

Delay in treatment (hours) from hypotension onset

Surv

ival

(%)

Each hour of delay carries 7.6% reduction in survival

Kumar, et al. Crit Care Med 2006;34:1589–1596

SWITCH TO ORAL THERAPYFour criteria

Improvement in cough, dyspnea & clinical signsAfebrile on two occasions 8 h apartWBC decreasing towards normal Functioning GI tract with adequate oral intake

If overall clinical picture is otherwise favorable, hemodynamically stable; can switch to oral therapy while still febrile.

TREATMENT FAILURE

What defines a treatment failure?

Clinical deterioration or a lack of response to empiric antimicrobial therapy within 3 days often indicates treatment failure, warranting thorough reassessment and additional investigations.

What defines a treatment failure?

• Majority of patients receiving appropriate therapy show a favorable clinical response within 72 hours.

• Initial antibiotic therapy should not be changed before 72 hours unless indicated by significant clinical worsening or microbiologic data.

• Advanced age, alcoholism, and chronic obstructive pulmonary disease, have been associated with delayed resolution despite appropriate treatment.

POTENTIAL REASONS WHY A PATIENT MAY NOT RESPOND FAVORABLY TO EMPIRIC THERAPY.

Inappropriate antimicrobial therapy

• Is the dosing adequate?• Are all potential bacterial pathogens covered by the empiric regimen?• Are the organisms resistant or has a previously sensitive pathogen

developed resistance?• Is the pathogen bacterial? Consider other pathogens to include viruses,

endemic fungi, and mycobacteria.• Is the host immunocompromised and at risk for opportunistic infections?• Is the disease infectious? • Has the patient been misdiagnosed?

Complications

a. Has a lung abscess or empyema developed?b. Does the patient have acute respiratory distress syndrome ?c Have the bacteria seeded extrapulmonary sites (e.g. endocarditis, septic arthritis, meningitis)?d. Has the patient acquired a new nosocomial infection (e.g., urinary tract infection, central line infection, sinusitis)?

How Should A Patient With Non resolving Pneumonia Be Evaluated?

• Review initial culture results and sensitivities • Collect additional lower respiratory tract and blood cultures. • Broadening empiric therapy may be indicated while awaiting results of

additional testing. • Repeated chest radiograph/consider ct scan at this time.• Additional history may reveal HIV risk factors, tick exposure, travel history,

or other diagnostic clues

• A thoracentesis of a pleural effusion can exclude a complicated effusion or empyema.

NONINFECTIOUS CAUSES…..

• ARDS• Traumatic pulmonary contusion • Pneumonitis resulting from connective tissue disease (e.g

Systemic lupus erythematosus) • Acute hypersensitivity pneumonitis• Drug-induced pneumonitis • Diffuse alveolar hemorrhage (e.g., Goodpasture syndrome,

wegener granulomatosis, bronchiolitis obliterans) .

• Bronchoscopy has good diagnostic utility

• Send for quantitative bacterial cultures and sensitivities, as well as for stains and cultures of unusual organisms (mycobacteria, endemic fungi, and p. Jiroveci ).

• Trial of corticosteroids or a thoracoscopic or open lung biopsy

may be considered in the appropriate clinical setting.

MANAGEMENT OF POOR RESPONDERS

Consider non-infectious illnessesConsider less common pathogensConsider serologic testingBroaden antibiotic therapyConsider bronchoscopy

CAP – COMPLICATIONSHypotension and septic shock

3-5% Pleural effusion; Clear fluid + pus cells

1% Empyema thoracis pus in the pleural space

Lung abscess – destruction of lung

Single (aspiration) anaerobes, Pseudomonas

Multiple (metastatic) Staphylococcus aureus

Septicemia – Brain abscess, Liver Abscess

Multiple Pyemic Abscesses

• It remains uncertain why immunocompetent patients with bacterial community-acquired pneumonia (CAP) die, in spite of adequate antibiotics

• Patients with shock, acute renal failure and APACHE II score higher than 24 should be considered for inclusion in trials of adjunctive therapy in order to improve CAP survival.

STEROIDS……An excessive release of circulating inflammatory cytokines can beharmful and cause pulmonary dysfunction.

Systemic corticosteroids have anti-inflammatory effects, attenuating the systemic inflammatory process in the disorder

Adjunct treatment with corticosteroids has been discussed since the 1950s

Significant reduction of in-hospital mortality in patients with severe community-acquired pneumonia was noted testing a 7-day continuous infusion of hydrocortisone versus placebo.

Retrospective single-centre study6 ncluding 308 patients suggested that the use of corticosteroids was associated with decreased mortality

Did not find any benefit of adjunct prednisolone, but an increased recurrence rate

Patients received intravenous dexamethasone over 4 days reported a significant reduction in length of hospital stay by 1 day

IMPROVING OUTCOMES………•Use validated severity score in determining the site of care. Little to choose between pneumonia scores………

•Empiric therapy should be consistent with local guidelines. take into account local differences in cause….

•A macrolide should be part of the empiric regime in hospitalized patients

•Antibiotics should be given as fast as possible, ideally within 4 h of presentation

• Ensure that the patient • Has adequate fluid resuscitation, • Electrolyte disturbances are being addressed,• Hyperglycemia is being corrected• Thrombosis prophylaxis is considered and• Myocardial ischemia is considered and prophylaxis considered if appropriate.

• Hypoxic patients with any risk factor for co2 retention should have this assessed and managed if present

• Patients should be encouraged to ambulate as early as possible

•Failure to clinically improve within 48 h should prompt early review of potential complications such as empyema.

•Protocol should be in place to switch from intravenous to oraltherapy at the earliest appropriate time point

•Given the long-term poorer outcomes in CAP survivors , cardiovascular risk factors should be assessed during admission and after discharge

Thank you