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Swamy Journal Presentation

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  • 7/29/2019 Swamy Journal Presentation





  • 7/29/2019 Swamy Journal Presentation



    William Osler once described pneumonia as

    the old mans friend as death was often

    quick and painless

    CAP is the second most common cause of

    death from infectious diseases in India

    the leading cause of childhood mortality

    Studies reveal that the causative organism of

    CAP is identified in only 29% of cases.

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    Risk factors

    Case fatality with invasive pneumococcal

    pneumonias in India was reported to be about

    30% according to the IBIS study for a 10-year


    CAP incidence is the highest in winter

    more in males with ratio of 1.4 : 1

    increased with age (1564 years)

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    Streptococcus pneumonia is more frequentlyisolated from alcoholic patients than others

    There was no relationship between mortality

    and alcohol, but the severity was more inthese patients.

    tobacco smoking is a risk for CAP

    HIV-positive patients had a higher prevalenceof Mycoplasma pneumonia in a study fromCMC Vellore

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    Fang et al. conducted a prospective, multicenterstudy in 359 cases to evaluate the new andemerging causes of CAP

    S. pneumoniae (15.3%), H. infuenzae (10.9%),Legionella spp. (6.7%) and C. pneumoniae (6.1%).Mortality was the highest for S. aureus (50%) andthe lowest for C. pneumoniae (4.5%).

    The study concluded that empiric antibiotic

    prescriptions must be infuenced by therealization that C. pneumoniae and Legionellaspp. are common etiologies for CAP

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    The emerging etiologies for CAP were alsoexamined in a 12-month prospective study,which evaluated the microbiological yield with

    a new diagnostic polymerase chain reaction(PCR) platform along with conventionalmethods

    It was possible to establish microbial etiologyin about 67% (n=124) of patients

    . A microbiological agent was identifed in 89%

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    S. pneumoniae [70 patients (38%)] and

    respiratory virus [53 patients (29%)] were the

    most frequently detected pathogens.

    Forty-three (35%) patients out of 124, were

    detected with two or more pathogens.

    The most common causative pathogen in Europe,

    the United States, the United Kingdom, Iraq,Delhi, and Mumbai is S. pneumoniae

    whereas in Singapore, it is K. pneumoniae

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    Indian Data

    In the Indian scenario, studies on

    bacteriological etiology are a few and far

    between, and are mostly confned to limited

    geographical areas

    S. pneumoniae predominates as etiological

    agent of CAP in Shimla and Delhi

    whereas, P. aeruginosa in Ludhiana

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    bansal et al. conducted a study to identify the

    clinical and bacteriological profle in Shimla

    S. pneumoniae, S. aureus, K. pneumoniae, M.

    pneumoniae, E. coli and other Gram-negative

    bacteria were the most frequently isolated


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    A study by Shah5 et al. showed that factors thatcan predict mortality in a patient of CAP at thetime of admission are

    Patients above 65 years of age

    History of chronic obstructive pulmonary disorder


    Hypotension and altered sensorium Respiratory failure

    Staphylococcal pneumonia

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    Tests to Determine Etiology of CAP

    Blood cultures, sputum Gram-stain andculture are the most common tests used

    In addition to this, serological tests are also

    performed. an adequate sputum sample is defned as >25

    polymorphs and

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    Serologic Tests

    The Immunoglobulin M (IgM) antibodies againstmycoplasma rise 1 week after infection and remainpositive for 6 months to 1 year after infection.

    This accounts for poor sensitivity and specifcity

    The IgM antibodies to Chlamydia take 3 weeks tobecome detectable accounting for poor sensitivity.

    Antigen detection tests for viruses in respiratorysecretions have reasonably good sensitivity andspecifcity, but are not currently available

    Antibody tests for viruses have poor sensitivity/specifcity

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    Limitations of Common Investigations

    Gram-Stain and Culture: Microbe identifcation

    is possible in 50% of patients only and

    depends on quality of sputum sample.

    Blood cultures give poor results

    Serology requires rising titres; it is expensive

    and not easily available

    Viral cultures are not useful; viral antigens are


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    General and Radiological


    The most useful signs and symptoms for thediagnosis of CAP include:


    Dyspnea Tachypnea

    Positive signs on respiratory examination

    Studies show that traditional chest physicalexamination alone is not sufficiently accurate toconfirm or exclude the diagnosis of pneumonia

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    Especially in elderly

    the symptoms are less severe and at times are

    replaced with nonspecifc symptoms, such as

    functional failure, falls or confusion.

    They also have a lesser tendency to have fever

    compared to younger patients.

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    Symptoms specific to organism

    Streptococcus pneumoniae: Increasing age,

    comorbidity, acute onset, high fever and pleuritic

    chest pain.

    Bacteremic pneumonia: Female sex, excess alcohol,diabetes mellitus, chronic obstructive pulmonary


    Legionella pneumophila: Younger patients, smokers,

    absence of comorbidity, diarrhea, neurological

    symptoms, more severe infection and evidence of

    multisystem involvement (e.g. abnormal liver

    function tests, elevated serum creatine kinase).

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    Mycoplasma pneumoniae: Younger patients,

    prior antibiotics, less multisystem


    Chlamydophila pneumoniae: Longer durationof symptoms before hospital admission,


    Coxiella burnetii: Males, dry cough, high fever.

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    Absence of vital sign abnormalitiessubstantially reduced the probability of theinfection.

    The gold standard for the diagnosis ofpneumonia is chest radiography.

    Sensitivity and specifcity of chest radiograph

    are not well-known and also limited data isavailable on costs of false-positive and false-negative results.

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    Wipf et al.2 conducted a study to determinethe accuracy of various physical examinationmaneuvers in diagnosing pneumonia and to

    compare the inter-observer reliability ofmaneuvers among three examiners.

    Male patients with symptoms of lowerrespiratory tract infection (cough and changein sputum) were enrolled in this prospectivestudy (n=52).

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    A standard form was used to record the

    examination fndings by lung site and whether

    the examiner diagnosed pneumonia.

    Radiologists read the chest radiography flms.

    the three examiners clinical diagnosis of

    pneumonia had a sensitivity of 4769% and

    specifcity of 5875%

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    Vital Sign Abnormalities

    Nolt et al. conducted a study which examined thestrength of the association among vital signabnormalities, advanced age and the diagnosis ofCAP in the evaluation of adults with acute cough

    illness It was found that vital sign abnormality (including

    fever, hypoxemia, tachycardia or tachypnea) andage greater than 50 years were the only signifcant

    predictors of CAP strong association was found between hypoxemia

    and CAP

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    Mayaud et al. carried out an evaluation study

    on data related to age and clinical and

    radiological fndings.

    The data showed that absolute lack of vital

    signs has a good negative predictive value in


    The presence of unilateral crackles has a good

    positive predictive value

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    Role of Chest Radiograph

    Lieberman et al. conducted a prospective,

    clinical study with the aim to determine the

    reliability of physiciansjudgements in

    respiratory tract infections (RTIs) patients byclinical assessment alone compared with chest


    Ambulatory patients with febrile RTI wereenrolled (n=250).

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    compared to the results of chest radiography,physiciansjudgements of pneumonia had asensitivity of 74%, a specifcity of 84%, a negative

    predictive value of 97% and a positive predictivevalue of only 27%.

    Physicians had good ability to negateradiography-confrmed pneumonia by clinical

    assessment in febrile adult RTI patients. However, they had poor ability to successfully

    predict the condition

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    OBrien et al.9 carried out a study to develop aprediction rule for the use of chest radiographs inevaluating CAP based on presenting signs and

    symptoms. The study included 350 adult patients with acute

    respiratory symptoms and positive chestradiographic results

    The study included an equal number of age-matched controls with acute respiratorysymptoms but negative radiographic results

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    It was found that vital sign and physical

    examination fndings are useful screening

    parameters for CAP, demonstrating a sensitivity

    of 95%, and a specifcity of 56% in the presence ofvital sign or physical examination abnormalities.

    The study fndings were suggestive of non-

    requirement of chest radiographs in the absenceof vital signs abnormalities or physical fndings

    Chest X ray is Considered as Gold

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    Chest X-ray is Considered as Gold

    Standard for Diagnosis of Pneumonia:

    The Netherland Study Findings In a study conducted in three hopitals in theNetherland, it was found

    Pneumonia cannot be treated based on clinical fndingsalone. Manifestation of pneumonia on chest X-ray

    varies considerably depending upon the degree ofinfammation and stage of the disease process.

    Radiographic fndings may lag behind clinical fndingsand are poor indicators of etiological diagnosis.

    Pneumonia was frequently overdiagnosed clinically bygeneral practitioners.

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    British Thoracic Society Guidelines

    British Thoracic Society guidelines do notrecommend chest radiography in patients withsuspected CAP unless the diagnosis is not clearand chest radiograph would help in differential

    diagnosis and management of acute illness. ChestX-ray is considered when

    there is no satisfactory treatment progress at thetime of review or

    the patient is at risk of underlying lung pathology The guidelines also recommend routine chest

    radiograph 6 weeks after discharge.

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    American thoracic society

    The IDSA/ATS consensus guidelinesrecommend the use of chest radiograph orother technique with or without

    microbiological data for the diagnosis ofpneumonia.

    Identification of causative microorganismthrough microbiological studies may supportthe diagnosis of pneumonia.

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    Importance of Severity Assessment


    Community-acquired pneumonia (CAP)represents a signifcant therapeutic challengeto physicians, as they have to decide whether

    the patient is to be treated in a clinic or ahospital setting.

    Therefore, it is vital to assess the severity ofthe disease

    Several scoring systems are available to helpclinicians assess the severity of the illness

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    there are three scoring systems available for

    assessing the severity of CAP. These systems

    aim to assess the mortality risk associated

    with the illness and thus accurately determinethe severity. The three scoring systems are2

    Pneumonia Severity Index (PSI)

    CURB 65

    CRB 65

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    Pneumonia Severity Index

    It is a mortality prediction tool that was first

    introduced by Fine et al. in 1997.

    It classifies CAP patients into five categories of

    an increased risk for short-term mortality

    based on 20 variables routinely available at


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    The PSI score is assigned after answering thefollowing three questions:3

    Is the patient >50 years of age?

    Does the patient have any coexistingabnormalities

    Does the patient have altered mental status,

    pulse rate 125 beats/min; respiratory rate30 breaths/min; systolic blood pressure

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    While the PSI is a relatively reliable tool for

    mortality assessment in CAP, there remain

    some limitations that prevent its widespread


    One of the major limitations is that the tool

    relies heavily on the age of the patient, which

    may result in underestimation of the severityof the illness, especially in younger patients.

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    CURB 65

    CURB 65 is a modification of the British ThoracicSociety (BTS) rule in assessing pneumoniamortality risk.

    It uses five variables to arrive at overall death riskin CAP

    Lim et al. also examined the efficacy of thisscoring system after excluding BUN.

    CRB 65 that effectively categorizes patientsaccording to the need for home care, hospitalassessment or urgent (ICU) hospital admission

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    Bauer et al found that CURB and CRB 65 hadan equivalent predictive power for 14-daymortality.

    Thus, CURB, CURB 65 and CRB 65 allow forsimilar predictions of death from CAP ascompared to the PSI.

    Among these severity assessment scales, theCRB 65 is the only tool that can be applied tooutpatients as wel

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    PSI vs. CURB 65

    PSI is indicated for identifying low-risk patients

    CURB 65 is ideal for identifying high mortalityrisk patients with severe illness.

    In the Indian context, Shah et al. found thatboth PSI and CURB 65 had equal sensitivity inpredicting the risk of death from CAP.

    The PSI was more sensitive in predicting ICUadmission than CURB 65, although the latterhad better overall specificity.

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    Use CURB 65/CRB65 over PSI in India forjudging site of care and severity

    both PSI and the CURB 65 have several

    limitations These scoring systems are designed primarily

    to predict mortality.

    They are not very effective for predicting ICUadmission and are of limited use in the criticalcare environment.

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    Importance of Identifying Patients in

    Need of ICU Admission

    Identifying appropriate patients to optimize

    the use of limited ICU resources.

    An increase in mortality is observed in

    patients who are transferred to the ICU for

    delayed respiratory failure or delayed onset of

    septic shock.

    Microbial etiologies for ICU patients aredifferent from that of CAP in general

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    Predictive Models for Severe CAP

    There are three scoring systems available for

    identifying severe CAP that necessitates ICU


    ATS/IDSA Criteria

    SMART-COP Rule

    SCAP Rule

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    ATS/IDSA Criteria

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    Variables like ventilation and vasopressors, asspecifed in the ATS criteria, might not beavailable at admission in the emergency

    department (ED). This might lead to errors in deciding the site-

    of-care; for example, patients might beadmitted to the ward instead of the ICU.

    This might lead to an increase in the risk ofmortality.

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    SMART COP score

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    SMART COP is the result of an extensive studyon CAP called the Australian CAP Study

    (ACAPS). The tool was designed to overcome the

    limited ability of PSI and CURB 65 to predictwhich patients will require intensiverespiratory or vasopressor support (IRVS).

    Th i i f SMART COP

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    The interpretation of SMART-COP


    0-2 points: Low risk of needing intensive

    respiratory or vasopressor support (IRVS)

    3-4 points: Moderate risk (1 in 8) of needing


    5-6 points: High risk (1 in 3) of needing IRVS

    7 or more points: Very high risk (2 in 3) of

    needing IRVS

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    SCAP rule

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    advantage of this model is its ability to identifyseriously ill patients with CAP who are at risk for anadverse outcome.

    The variables are easy to interpret and access in

    causality The sensitivity of SCAP to identify severe CAP is 92%

    it is more sensitive but not specific when compared toPSI or CURB 65

    In the study, SCAP was found to be effective inpredicting adverse outcomes such as ICU admission,mechanical ventilation, development of severe sepsisand therapeutic failure.

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    Keeping in view the limitations of the ATS and

    the SMART-COP scoring systems, SCAP may be

    more suited in the Indian scenario.

    More practical in predicting ICU admission



    Useful in taking quick decision for ICU


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    Role of Biomarkers

    Three prognostic markers, C-reactive protein(CRP), procalcitonin (PCT) and cortisol, have beeninvestigated to assess CAP severity and predictoutcome

    Biomarkers can help differentiate patients withpneumonia from heart failure and chronicobstructive pulmonary disease (COPD)

    exacerbation, with the latter not requiringantibiotics.

    can be used to assess the treatment response.

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    Significantly higher PCT levels have been observed inpatients with a higher PSI score or with complications ordeath than those with an uncomplicated clinical course.

    In the CAPNETZ study, Krger et al. Nonsurvivors hadsignificantly higher median PCT levels than survivors (1.2 vs.

    0.3 mmol/L; p=0.0001) Even in patients with high CRB 65, low PCT was able to

    accurately predict patients who are at very low risk ofdeath.

    Procalcitonin has a high negative predictive potential(98.9% with PCT level of

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    Identifying need for aggressive management

    Identifying patients to be treated on

    outpatient basis

    When PCT is used as a prognostic marker,

    patients can be counseled appropriately for

    adverse events.

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    Reporting time

    Serial assessment

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    C-reactive protein is an acute-phase proteinsynthesized in the liver.

    Chalmers et al. carried out a prospective study andfound that admission CRP

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    PCT vs. CRP

    Simon et al. compared the predictive value of PCT andCRP in assessing the severity of CAP and found thatPCT (88%) was more sensitive than CRP (75%) in thedistinction of bacterial and noninfective causes ofinfammation.

    Also, PCT (81%) was more specifc than CRP (67%) indifferentiating bacterial from noninfective causes ofinfammation.

    SCAP criteria with the use of biomarkers is one

    potential solution. Procalcitonin seems to offer the greatest potential

    among all biomarkers

    Management of Community Acquired

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    Management of Community-Acquired


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    Indian Setting

    An important concern in India is tuberculosis.

    Tuberculosis accounts for 7% cases of CAP.

    Newer fuoroquinolones have excellent

    activity against Mycobacterium tuberculosis.

    There is a delay in the initiation of appropriate

    antituberculosis treatment (21 days vs. 5

    days), thus increasing the risk of spread oftuberculosis in the community.

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    The widespread and indiscriminate use of these broad-spectrum quinolones (often in subtherapeutic doses) canenhance the quinolone resistance of organisms, includingmycobacteria.

    Based on this, with the use of newer fuoroquinolones,

    there may be: Potential masking of active tuberculosis

    Probability of an emerging epidemic of extensively drug-resistant tuberculosis

    Therefore, in areas of tuberculosis endemicity, restricteduse of newer fuoroquinolones may be considered.Macrolides may have an extended role in these endemicareas.

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    Amoxicillin remains the preferred agent to initiateempiric antibiotic therapy in clinic/ outpatientsettings.

    Macrolides such as clarithromycin andazithromycin are recommended in those patientswho are hypersensitive to penicillins.

    Given the endemic nature of tuberculosis in India,

    macrolides such as clarithromycin andazithromycin may be preferred to quinolones/doxycycline as the initial empiric therapy.

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    Most of the bacteria causing community-

    acquired pneumonia are found to be resistant

    to doxycycline. Hence, doxycycline is not

    recommended. In the presence of comorbidities, a respiratory

    fuoroquinolone or a -lactam plus a macrolide

    or amoxicillinclavulanate is preferred.

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    Coverage of Atypical Pathogen

    Restrepo et al. compared clinical outcomes ofpatients with CAP treated with and withoutatypical coverage. In the study, the long-term (90days) and short-term (30 days) mortality was

    assessed with the use of macrolides in patientswith severe sepsis due to pneumonia.

    The use of macrolide was associated withreduced mortality at 30 as well as at 90 days.

    The study concluded that empiric therapy with aregimen that covers atypical pathogens might beconsidered for all hospitalized patients with CAP.

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    Monotherapy vs. Dual Therapy

    Waterer et al. confirmed that monotherapy may not beoptimal for CAP patients hospitalized.

    On the basis of culture results, empirical therapy in thisstudy was classified as single effective therapy (SET), dualeffective therapy (DET) or more than DET (MET).

    Multivariate analysis confirmed that SET was anindependent predictor of worse outcome. Among patientswho were given coverage for atypical pathogen, 9.9% diedas compared to 22.6% without atypical coverage (p=0.02).

    Subjects who did not receive coverage for atypicalorganisms had a significantly higher predicted mortalitythan those who received it (27.3% vs. 21.8%, respectively;p=0.047);

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    It was observed that subjects receiving SET were

    6.4 times more likely to die of their illness after

    adjusting for the severity of pneumonia.

    The same premise was also evaluated in a reviewby Weiss and Tillotson.

    This review also suggested that for hospitalized

    patients, dual therapy combining a -lactam andan advanced macrolide represents a good choice

    potental benefts of combinaton

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    ptherapy include

    Better atypical microorganisms coverage The combination regimen that acts at two different

    sites in the bacteria (cell wall for -lactams and theinhibition of protein synthesis for macrolides),

    Demonstrated effective antiinfammatory properties ofmacrolides via reduced production of interleukin-8 andtumor necrosis factor-.

    Beta-lactams and fuoroquinolones that might beresponsible for perpetrating the inflammation process

    because they are known to kill a large number ofbacteria in a short amount of time, thus releasingnumerous intracellular components.

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    Agents Used in Combination Therapy

    Anderson et al. compared the effects of subinhibitoryconcentrations of antibiotics

    on pneumolysin production by a macrolide-susceptiblestrain and two macrolide-resistant strains [erm(B) or

    mef(A)] of S. pneumoniae This study indicated that only macrolides and

    macrolide-like antibiotics were found to inhibit theproduction of pneumolysin by all three strains of thepneumococcus, with clarithromycin, erythromycin,

    telithromycin and clindamycin exhibiting comparableactivities, whereas azithromycin was generallysomewhat less active..

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    Furthermore, in comparison with the otherclasses of antibiotics tested, macrolides atsub-MICs effectively antagonize the

    production of pneumolysin by both macrolide-susceptible and macrolide-resistant strains ofthe pneumococcus

    compatible with a role for these agents as

    adjuncts to p-lactams in the treatment ofsevere pneumococcal disease

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    Combination therapy is the way forward in patientshospitalized with moderate severity CAP.

    Amoxicillin plus macrolides like clarithromycin orally is thepreferred regimen in these cases. In patients hypersensitiveto penicillins oral doxycycline, levofoxacin or moxifoxacin isrecommended.

    If oral administration is not possible IV amoxicillin orbenzylpenicillin plus macrolide like clarithromycin IV isrecommended.

    For hospitalized patients, the necessary change inantibiotics can be done only after the sputum culture test,till then empiric therapy is continued.

    Empirical Antibiotic Choice for Adults

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    Empirical Antibiotic Choice for Adults

    Admitted in ICU with CAP

    Macrolides may contribute to better

    outcomes in patients with severe sepsis due to

    CAP, as they have

    A synergistic antibacterial mechanism

    Atypical pathogen coverage

    An immunomodulatory effect

    If the specific pathogen has been isolated,

    then the choice is relatively straightforward.

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    IDSA/ATS recommends a respiratory fuoroquinolone ora combination of b-lactam plus a macrolide for non-ICUinpatients (strong recommendation, Level 1 evidencefor both regimens).

    IDSA/ATS recommends a b-lactam plus eitherazithromycin (Level II) or a respiratory fuoroquinolone(Level I) for ICU-admitted inpatients.

    BTS recommends an I.V. combination of a broad-spectrum b-lactamase-stable antibiotic such as co-

    amoxiclav plus a macrolide like clarithromycin. Inpatients allergic to penicillin, cephalosporins can beused in combination with clarithromycin.

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    Dual or combination therapy should beconsidered for severe CAP.

    Macrolides were found to be compatible asadjuncts to broad-spectrum -lactamase stable

    antibiotic in severe CAP. An intravenous combination of a broad-spectrum

    b-lactamase stable antibiotic such as co-amoxiclav together with a macrolide such as

    clarithromycin may be preferred overfouroquinolones or their combinations in Indiaconsidering the tuberculosis endemicity.

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    Timing of antibiotic

    an important performance indicator in

    community-acquired pneumonia (CAP).

    The European guidelines recommend initiation

    of antibiotics within the first two hours ofhospitalization,

    whereas the current Infectious Disease Society of

    America/ American Thoracic Society consensusguidelines advise the initiation of the first

    antibiotic dose in the emergency department.

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    A prospective observational study conducted bySilber et al. reported that there was no reductionin the time to clinical stability with theadministration of antibiotics within 4 hours

    Bruns et al. conducted a study to evaluate theeffect of minimizing the TFAD on the early clinicaloutcome

    Time to first antibiotic dose was however, not

    associated with early clinical failure. Hence, it is not advisable to consider TFAD as a

    performance indicator

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    Metersky et al. determined the frequency of medicarepatients who are discharged with a diagnosis ofpneumonia with atypical presentation.

    This could lead to diagnostic uncertainty and a

    resultant appropriate delay in antibiotic administration. A fnding from a retrospective study of 548 patients by

    Welker et al. reported that there was a reduction in theaccuracy of the initial diagnosis of CAP when the

    required TFAD was changed from 8 hours to 4 hours.

    Concerns with the Administration of

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    Concerns with the Administration of

    Antibiotics within 4 Hours

    Overdiagnosis/misdiagnosis of CAP,

    inappropriate utilization of antibiotics,

    no association to mortality,

    length of hospital stay, time to clinical stability

    and pressure on clinicians to start the first

    dose of antibiotic despite diagnostic

    uncertainty, were the concerns with theadministration of antibiotics within 4 hours

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    Rhew et al. investigated the effectiveness ofearly switch and early discharge strategies in CAPpatients

    Ten prospective, interventional, CAP-specifcstudies that evaluated length of stay wereincluded in the study.

    Early switch and early discharge strategies may

    signifcantly and safely reduce the mean length ofstay (LOS) when the recommended LOS is shorterthan the actual length of stay

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    Athanassa et al. conducted a meta-analysis There was no difference in the treatment success,

    mortality and recurrence of CAP between thegroups

    Shorter duration of hospitalization was observedin the early switch group.

    It was concluded that early switch to oral

    antibiotics can be as effective as continuousintravenous treatment in patients with moderate-to-severe CAP

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    Ramirez and Bordon conducted a study to evaluate theclinical outcomes while switching from intravenous tooral therapy in hospitalized patients with CAP. He usedfour criteria

    Improvement of cough and shortness of breath

    Patient being afebrile for a minimum of 8 hours

    White blood cell count reaching normal levels

    Adequate oral intake and gastrointestinal tractabsorption

    It was concluded that it was safe to switch fromintravenous to oral therapy in hospitalized patientswith CAP after the patient was clinically stable

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    R d i

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    The timing of antibiotic therapy depends on theseverity of the CAP at the time of hospital admission.Severe cases of CAP require immediate institution oftherapy, which must be adjusted after confrmingmicrobiological etiology.

    Switch from intravenous antibiotics to oral treatment isrecommended in case of observed improvement insymptoms, improved respiratory rate and oxygensaturations, patient being afebrile for >24 hours,

    hemodynamic stability, reduction in white blood cellcount (if elevated earlier) and absence of nausea/vomiting.

    At i l i

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    Atypical organisms

    Streptococcus pneumoniae causes up to 70% ofcommunity-acquired pneumonia cases andatypical pathogens are responsible for 3040% ofcases

    Legionella, Mycoplasma pneumoniae andChlamydia pneumoniae are the atypical agents

    the other bacteria which cause community-

    acquired pneumonia besides Streptococcuspneumoniae are Haemophilus infuenzae,Staphylococcus aureus and Gram-negative bacilli.

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    Zaki and Godal reported that Chlamydiapneumoniae, Mycoplasma pneumoniae,Legionella pneumophila, Coxiella burnetii,adenovirus, and infuenza virus were the

    pathogens responsible for CAP. Streptococcus pneumoniae (22%)

    Haemophilus infuenzae (18%).

    Mycoplasma pneumoniae (5%) and

    Legionella pneumophila (5%) were the mostcommon isolated bacteria.

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    Appropriate oral medications should be usedwithout compromising on the spectrum of coverof the bacterial fora by the antibiotic.

    In the absence of a culture/sensitivity report

    identifying an organism and an appropriate oralantibiotic, following oral replacements aresuggested.

    Special care and intensive management is

    required in some special population of patientslike those with severe CAP, sepsis, hypotensionand respiratory failure.

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    In an Indian study conducted by Udwadia etal, the most common atypical organism

    causing CAP were Chlamydia pneumoniae and

    Mycoplasma pneumoniae

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    Therapy for pneumonia is empiric because specifcpathogens usually are not identifed at the time thetreatment is initiated.

    C. pneumonia and Legionella spp. are intracellularorganisms and M. pneumonia lacks a cell wall, p-lactams are not effective.

    In Legionell infection erythromycin is effective asdemonstrated in some trials and in case ofMycoplasma pneumonia, erythromycin and

    tetracycline are effective. They also reduce symptom duration in Chlamydia

    pneumonia infection.

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    Azithromycin and clarithromycin are very effectiveagainst Mycoplasma pneumoniae, Chlamydiapneumoniae and Legionella spp. and show bettertolerability profle as compared to erythromycin.

    Doxycycline is also effective and is associated withfewer gastrointestinal side-effects.

    Fluoroquinolones are highly effective againstMycoplasma pneumoniae, Chlamydia pneumoniae and

    Legionella spp. The advantage of fuoroquinolones is once-daily dosing

    and excellent bioavailability

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    The combination of rifampin plus a macrolideor a quinolone can be used for initial

    treatment in severely ill patients with

    Legionnaires disease

    Impact of Empirical Therapy of CAPon Treatment of M t berc losis

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    on Treatment of M. tuberculosis

    Infections Initiation of empirical therapy of CAP is known to

    have two important concerns:

    Delayed initiation of anti-TB treatment

    Resistance to fuoroquinolone

    Dooley et al. , Yoon et al. Conducted studies

    indicate that newer fuoroquinolones should be

    restricted in tuberculosis endemicity because ofits potential to mask active tuberculosis and

    emerging drug-resistant tuberculosis.


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    Atypical coverage is a must in moderate-to-severely ill patients withpneumonia requiring hospitalization and intensive care unit care.

    The only acute respiratory tract infection in which delayed antibiotic

    treatment has been associated with increased risk of death is CAP,

    hence prompt and accurate diagnosis of CAP is important.

    Tuberculosis should always be considered while treating CAP in India.

    Therefore fuoroquinolones (levofoxacin and moxifoxacin) though

    effective in the treatment of CAP should be used cautiously.

    Newer macrolides are the drug of choice for the treatment of CAP.

    Viral pneumonias, especially infuenza and H1N1 should be consideredin the clinical setting.

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