138avap presentation ramayya

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Pneumonia can be a life threatening

condition

Is Something Serious ? Hospital-acquired

pneumonia (HAP)

and ventilator-

associated

pneumonia (VAP), is

an important cause

of morbidity andmortality in

hospitalized patients.

3doctortvrao@gmail.com

Ventilator associated pneumonia

Ventilator associated pneumonia (VAP) is

defined as nosocomial pneumonia occurring

in a patient after 48 hours of mechanical

ventilation via a tracheal or tracheostomy

tube. It is commonly classified as either early

onset (occurring within 96 hours of start of

mechanical ventilation) or late onset (>96hours after start of mechanical ventilation)

doctortvrao@gmail.com 4

Early concepts

As early as 1972, studies have shown that theairway of mechanically ventilated patientsquickly becomes colonized with gram-negative

organisms. In the past, it was thought thatpathogens came from the ventilatorequipment in use. However, as the problemwas studied and evidence accumulated, it

became evident that the origin of the VAP wasfrom a source other than the ventilatorequipment.

Centres for Disease and Control

The diagnosis of pneumonia inmechanically ventilatedpatients is difficult, and

still there is no "gold-standard" diagnosticmethod. It is usually basedon the combination of clinical,radiological, and

microbiological criteriadefined by Centres forDisease and Control(CDC)

Challenge and Controversy

The diagnosis andmanagement of VAPremains one of the

mostcontroversial and challenging

topics inmanagement of critically ill patients.

Who are prone -High Risk Patients

For Sepsis ± Post op / post procedure / post trauma

± Post splenectomy (encapsulated organisms)

± Cancer

± Transplant / immune supressed

± Alcoholic / Malnourished

For Dying ± Genetic predisposition (e.g. meningococcus)

± Delayed appropriate antibiotics

± Yeasts and Enterococcus

± Site

For Both ± Cultural or religious impediment to treatment

Nosocomial infection are

Multidrug Resistant Many patients with HAP,

VAP, and HCAP are atincreased risk for colonization and

infection with MDR pathogens

HAP and VAP are afrequent cause of nosocomial infection thatis associated with a higher crude mortality than other hospital-acquiredinfections

Aspiration Aspiration of colonized

pathogenicmicroorganisms on theoropharynx andgastrointestinal tract isthe main route for thedevelopment of VAP. Onthe other hand, the major

risk factor for VAP isintubation and theduration of mechanicalventilation

V ariation of Incidence Rate

In different studies, the incidence of VAP was

reported different, depending on the

definition, the type of hospital or ICU, the

population studied, and the type of rate

calculated and varies from 7% to 70% In a

large database, 1-day point prevalence study,

conducted in 1417 European ICUs, pneumoniaaccounted for 47% of nosocomial infections

Aero digestive ,upper airway + upper

digestive tract contribute pathogens

The primary route of

VAP pathogenesis is a

combination of two

processes: bacterialcolonization of the aero

digestive (upper airway

+ upper digestive) tract

and the subsequentaspiration into the

lower airway.

Time frame of intubation and risk

Risk of pneumonia at

intubation days

± 3.3% per day at day 5

± 2.3% per day at day

± 1.3% per day at day

PAHOGENESIS ± The pathogenesis of

ventilator-associated

pneumonia usually

requires that two

important processes

take place:

Bacterial colonization of

the aero digestive tract

The aspiration of contaminated secretions

into the lower airway.

Mechanical device also

contributes the events

Etiology

Bacteria causemost cases of HAP,VAP, and HCAP

and manyinfections are polymicrobial;rates are especiallyhigh in patientswith ARDS

Causative Organisms

Early onset: ± Haemophilus influenza ± Streptococcus pneumoniae ± Staphylococcus aureus (methicillin sensitive) ± Escherichia coli ± Klebseilla

Late onset: ± Pseudomonas aeruginosa ± Acinetobacter ± Staphylococcus aureus (methicillin

resistant)

Most strains responsible for early onset VAP are antibiotic sensitive. Those responsible forlate onset VAP are usually multiple antibioticresistant

Am J Resp Crit Care (1995)

Summary of pathogens responsible for VAP in a study of 420 patients.

Hunter J D Postgrad Med J 2006;82:172-178

Drug resistance a concern in Ventilator

Associated Pneumonias

A. baumanni was themost common emergingisolated pathogen manyof them were multidrug-

resistant (MDR) or pandrug-resistant (PDR). Theother common isolatedpathogens were K.

pneumoniae, P.aeruginosa andmethicillin-resistantS. aureus (MRSA).

Other Isolates in Ventilator associated

Pneumonias

± Pseudomonas aeruginosa. the most common MDR gram-negative bacterial pathogen

causing HAP/VAP, has intrinsic resistance to many

antimicrobial agents ± Klebsiella, Enterobacter, and Serratia species.

Klebsiella species ± intrinsically resistant to ampicillin and other aminopenicillins and

can acquire resistance to cephalosporins and aztreonam by the

production of extended-spectrum ±lactamases (ESBLs)

± However ESBL-producing strains remain susceptible tocarbapenems ?

Ent erobact er species

C i t robact er and

Serrat ia species 22doctortvrao@gmail.com

Acinetobacter species

± Acinetobacter species

More than 85% of isolates aresusceptible to

carbapenems, butresistance isincreasing , Mostrecent concern.

Stenotrophomonas

maltophilia, andBurkholderia cepacia:

± resistant tocarbapenems ?

N ewer Carbapenemases

As of June 2010, therewere three reportedcases of Enterobacteriaceae

isolates bearing thisnewly describedresistance mechanism inthe US, the CDC statedthat "All three U.S.isolates were frompatients who receivedrecent medical care inIndia."

Staphylococcus aureus and

Streptococcus pneumoniae

± Methicillin-resistant Staphylococcus aureus

vancomycin-intermediate S. aureus

± sensitive to linezolid

±linezolid resistance has emerged in S. aureus, but is currentlyrare ?

± Streptococcus pneumoniae and Haemophilus

influenzae.

sensitive to vancomycin or linezolid, and most remainsensitive to broadspectrum quinolones

Influenza too can cause VAP

Nosocomial virus and fungal

infections are uncommon

causes of HAP and VAP in

immunocompetent patients.

Outbreaks of influenza haveoccurred sporadically and

risk of infection can be

substantially reduced with

widespread effective infection

control, vaccination, and use of anti influenza agents

F ungal pathogens can cause

VAP ±F ungal

pathogens.

Asper gillus

species

C and i d a

albicans

P athogenesis Entry of P athogens

Where do the bacteria come from?

± Tracheal colonization- via oropharyngeal

colonization or GI colonization

± Ventilator system

How do they get into the lung?

± Breakdown of normal host defenses

± Two main routes

Through the tube

Around the tube- microaspiration around ETT cuff

Oropharyngeal colonization can be

source of VAP

Scannapieco et al showed a transition in thecolonization of dental plaques in patients inthe ICU

Control=25 subjects presenting to preventivedentistry clinic

Study group=34 noncardiac patientsadmitted to medical ICU at VA hospital(sampled within 12 hours of admission andevery third day)

Viral Pathogens

Outbreaks of HAP, VAP, andHCAP due to viruses, suchas influenza, parainfluenza,adenovirus, measles, andrespiratory Syncytial virushave been reported andare usually seasonal.

Influenza, pararinfluenza,adenovirus, andrespiratory Syncytial virus

account for 70% of thenosocomial viral cases of HAP,VAP, and HCAP

Bio films Many species, including

P seud omonas aerugi nosa

and St aphy lococcus

aureus, produce bio films,which surround the

organisms when attached

to endotracheal tubes,

and make them relatively

resistant to the actions of

antibiotics and host

defences.

Bio films,

The surviving

organisms may

play a role inrelapses by

shedding infective

particles from theendotracheal tube

into the lower

respiratory trac35doctortvrao@gmail.com

Multidrug resistant organisms are

associated with

The prevalence of MDR pathogens varies by patient population, hospital, andtype of ICU, which

underscores the need for local surveillance data

MDR pathogens are morecommonly isolated from

patients with severe, chronic

underlying disease, thosewith risk factors for HCAP,and patients with late-onsetHAP or VAP

Diagnosis?

A pulmonogist with25+ yearsexperience guesses

he is only correct60% of the timewhen diagnosingpneumonia before

seeing the CXR. Ali tt le better than acoin-toss.

Diagnosis is imprecise and usually

based on a Combination of

±Clinical factors - fever or hypothermia;change in secretions; cough; apnea/bradycardia; tachypnea

±Microbiological fact ors - positivecultures of blood/sputum/tracheal

aspirate/pleural fluids

±CXR factors - new or changing infiltrates

Strategies in Diagnosis in VAP are

multifaceted Clinical

Strategy

Bacteriologic

Strategy

ComparingDiagnostic

Strategy39doctortvrao@gmail.com

Diagnostic practices

± Invasive versus non-invasive techniques

± BAL/PBB versus tracheal aspirate

± Quantitative versus non-quantitative methods

Infection definitions

± Clinician decision or standardised definitions

S pecimen collection for Optimal Results

Distal airway samples may be obtained by

using bronchoscopic or nonbronchoscopic

techniques. With nonbronchoscopic

techniques, a catheter is blindly advanced

through the endotracheal tube or

tracheostomy and wedged in the distal airway.

Various sampling methods include blindbronchial suction (BBS), blind BAL, and blind

PSB sampling.

Bacteriologic Strategy

Quantitative cultures can be performed onendotracheal aspirates or samples collected either

bronchoscopically or nonbronchoscopically,and each technique has itsown diagnostic thresholdand methodologiclimitations. The choice of method depends on localexpertise, experience,availability, and cost

tvrao 2

tvrao 2 doctortvrao, 7/18/2010

Nonquantitative or

semiquantitative airway sampling.

Gram staining and nonquantitative andsemiquantitative cultures of tracheal secretionshave the advantages of reproducibility and of

requiring little technical expertise and nospecialized equipment or technique. However,these studies add little to the sensitivity andspecificity of the clinical diagnosis of VAP, as the

upper respiratory tract is rapidly, within hours of intubation, colonized by potential pulmonarypathogens, even when pneumonia is not present

Specimen collection

Tracheobronchial secretions were collected by

the pulmonologist , following specimen

collection guidelines, after tracheal instillation

of 5 ml saline. The specimens were sent to the

laboratory and cultivated within 1 hour of

collection. A dilution of the tracheal aspirate

was prepared and inoculated with a calibratedloop on chocolate agar and MacConkey agar

Culture positivity true or false?

Qualitative cultures were considered positive

when the growth of any micro-organism

occurred and quantitative cultures were

considered positive when the growth of 105

colony-forming units (cfu)/ml or more was

observed. cultures from tracheal aspirates

were calculated according to standardformulae

Which is optimal sample ?

Despite numerous publications on the subject,

controversy still exists on the optimal method

of microbiological diagnosis of VAP,As the

trachea and tracheal tube rapidly become

colonised with bacteria in the critically ill

patient, cultures of sputum or tracheal

aspirates may simply yield colonising organism

Differentiates between pathogenic

from non pathogenic ?

Analysing samples using quantitative culture

techniques theoretically permits

differentiation between oropharyngeal

organisms present at low concentrations and

the higher concentrations of pathogenic

organisms.

WHY IS THERE NO GOLD STANDARD?

After more than 10 years of trying multiple

invasive and non-invasive diagnostic

techniques, the procedure which is specific,

sensitive, rapid and inexpensive is yet to be

developed. No studies have shown the

superiority of any specific diagnostic method

currently in use, thus, medical community still has no gold standard for the diagnosis of VAP

Good Microbiology practices reduces

Antibiotic usage

Invasive tests such as bronchoscope BAL or

protected specimen brush (PSB) may avoid the

extended use of antibiotics for clinically

insignificant organisms, but no direct

consensus or evidence suggests that one test

is superior to the other; all have their

advantages and disadvantages.

Precautions in collecting and

transporting

After proper hand washing and wearing sterile

gloves before suctioning, the endotracheal

secretions were collected by instilling 1-2 ml

of sterile normal saline into the endotracheal

tube and then collecting it back with the help

of sterile mucous trap. The specimen collected

was immediately transported to thelaboratory within one hour of collection.

Gram stain is highly sensitive

Sputum or tracheal suction gram stain

NO ORGANISMS

in non-neutropenic pts.

NO HAP/VAP 94%

Bacterial culture of trachealsecretion

Qualitative culture- non specific

Semi-quantitative

culture- low specificity

Quantitativeculture : TS, BAL,

PSB- increase

specificity

Collection of bronchial Secretions

techniques, a catheter is blindly advancedthrough the endotracheal tube or

PSB sampling.

The sensitivity of quantitative BAL is 42 to 93% with amean of 73%. Specificity is 45 to

100% with a mean of 82%. Specific affected area of thelung can be visualized and sampled

More accurate than sputum or tracheal aspirates

May enable physician to identify non-infectiouslesions

Detects intracellular organisms inB

culturesquickly and specifically

with highly positive predictive value

Bacterial culture of trachealsecretion

Qualitative culture

- non specific

Semi-quantitative culture

- low specificity

Quantitative culture : TS, BAL, PSB

- increase specificity

Protected Specimen Brush

ProBAL© PSB by Mill-Rose The protected specimen brush

technique for the diagnosis of pneumonia has been used for20 years. This bronchoscopictechnique use a sample

collection brush (protected bya sheath) inside the scopechannel until the suspectportion of the lower airwayhas been reached. The brush isthen extended into the desiredspecimen and withdrawn. Thistechnique was first describedin 1979 by Wimberly, et al.

Semiquantitative

1+ : rare <10 colonies/plate

2+: few 10-102 colonies/plate3+: moderate >102-3 colonies/plate

4+: numerous >103-4 colonies/plate

5+: numerous >104 colonies/plate

PSB sampling.

Q ualitative and quantitative

Qualitative endotracheal aspirates are easy to

obtain but have a high false-positive rate in

ICU patients because of airway colonization.

When quantitative endotracheal-aspiratecultures are used, a cutoff value of 106 is the

most accurate, with a sensitivity of 38-82%

and a specificity of 72-85%

Differing opinions in specimen collection

Recent studies have consistently shown thatoutcome in VAP may not be influenced bywhether cultures are obtained by

bronchoscope or from tracheal aspiratescollected at the bedside. Furthermore, a costeffectiveness analysis strongly supported theemployment of tracheal aspirates in the

management of VAP. Ruiz M, Torres A, Ewig S, Marcos MA, Alcón A, Lledó R, Asejo MA,Maldonado M: Non-

invasive versus invasive microbial investigation in ventilator associated pneumonia:

evaluation of outcome. Am J Respir Crit Care Med 2000, 162:119-125.

hi h h d f ll i i

Which methods of collection is

better

Two diagnostic strategies for ventilator-

associated pneumonia bronchoalveolar

lavage with quantitative culture of the

bronchoalveolar-lavage fluid and endotrachealaspiration with nonquantitative culture of the

aspirate are associated with similar clinical

outcomes and similar overall use of antibiotics A Randomized Trial of Diagnostic Techniques for Ventilator-Associated

Pneumonia N Engl J Med 2006; 355:2619-2630December 21, 2006

False negative False Positive Results

Investigators reported

that the clinical diagnosis

of VAP is associated 30

35% false-negative and

2025% false-positive

results . And also, ICU

patients do not always

have systemic signs of

infection due to theirunderlying disease

(chronic renal failure)

Other Supporting Bacterial Cultures

Bacteraemia and positive pleural effusioncultures are generally considered to be able toidentify the organisms causing the pneumonia,

if no other source of infection is found.Therefore, most experts recommend thatinvestigation of suspected VAP should includetaking two sets of blood samples for culture

and tapping pleural > 10 ml, even thoughspread to the blood or pleural space occursin < 10% of VAP

Multiresistant pathogens in Ventilator

associated pneumonias

The incidence of multiresistantpathogens is alsoclosely linked to localfactors and varieswidely from oneinstitution to another.Consequently, each ICU

must continuouslycollect meticulousepidemiologic data

Uncommon microbes are often

missed

Legionella species , anaerobes

fungi viruses, and even

P neumocy st is cari nii should be

mentionedas potential causative

agents but are not considered to

be common in the context of pneumonia acquired during MV.

However, severalof these

causative agents may be more

common and potentially

underreportedbecause of difficulties involved with the

diagnostic

I l i l th d i

Immunological methods in

Diagnosis

A recently described immunological method

for the diagnosis of VAP holds great promise

for the future. The triggering receptor

expressed on myeloid cells (TREM-1) is a

member of the immunoglobulin super family,

and is involved in the acute inflammatory

response. Neutrophils express high levels of TREM-1 on exposure to infected tissues.

N ewer Methods in Diagnosis

Gibot and colleagues prospectively studied 148mechanically ventilated patients with suspectedVAP. A rapid immunoblot technique was used to

measure soluble triggering receptor expressedon myeloid cells TREM-1 in bronchoalveolarlavage fluid. They showed that the presence of soluble TREM-1 in the bronchoalveolar lavage(BAL) fluid was a highly accurate method for thediagnosis of fungal or bacterial pneumonia with asensitivity of 98% and a specificity of 90%.

H h li i i d f

H ow much a clinician needs from

Microbiology

Culture results are currently used to guideadjustment or withdrawal of antibiotic therapyrather than to decide whether to treat or not.

The practice of changing therapy with cultureresults has resulted in reduced consumption of antibiotics.

Conversely, studies have shown that over-

treatment with antibiotics may select organismssuch as P seud omonas aerugi nosaand

Aci net obact er calcoacet icus

E id b d l d

Mortality Mortality

Appropriate Appropriate Mortality Mortality

InappropriateInappropriate Mortality Mortality

Early Early Mortality Mortality

Evidence-based early andappropriate therapy in VAP

Benchmarking prescribing practice

Triggers to starting antibiotics

± Regular sampling versus clinician guided

± Timing in relation to investigation

Choice of antibiotic regimen ± Early empiric broad-spectrum cover versus narrow

spectrum with escalation

De-escalation practice

Duration of prescription

l f b l

Continuous Removal of Subglottic

Secretions

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No uniformity in treatment schedules

However, despite theseadvances, the majorityof issues related to themanagement of VAP

remain unresolved andare subject tocontroversy. This isparticularly true for the

diagnostic evaluation of the patient withsuspected VAP.

Clinical diagnosis of ventilator-associated

pneumonia

What is not controversial? Clinical criteria for the diagnosis of VAP

have a limited diagnostic accuracy .

This is true for single criteria such as infiltrates

in chest radiograph, fever or hypothermia,leukocytosis or leucopoenia, and increase inthe amount and/or purulence of tracheobronchial secretions, as well as fordiagnostic rules incorporating some of thesecriteria.

HandwashingHandwashing

What role does handwashing play innosocomial pneumonias?

The greatest role

VAP PreventionVAP Prevention

Wash hands before

and after

suctioning,touching ventilator

equipment, and/or

coming into

contact with

respiratory

secretions.81doctortvrao@gmail.com

Epidemiological data differs from

situations The incidence of

multiresistantpathogens is alsoclosely linked to local

factors and varieswidely from oneinstitution to another.Consequently, each ICU

must continuouslycollect meticulousepidemiologic data

Can we deliver a successful

Treatment

Successful treatment of patients with VAP

remains a difficult and complex undertaking.

Despite broad clinical experience with this

disease, no consensus has been reachedconcerning issues as basic as the optimal

antimicrobial regimen or its duration. In fact,

to date, evaluation of various antimicrobialstrategies for the treatment of bacterial VAP

has been difficult for several reasons.

Supporting Evidences

Consequently, most

experts recommend that

two sets of blood cultures

and a thoracentesis for

nonloculated pleural

effusions of 10 mm in

diameter on a lateral

decubitus chest

radiograph should be partof the evaluation of

suspected VAP

Handwashing

Hand washing is the single mostimportant (and easiest!!!) method forreducing the transmission of pathogens.

Use of waterless antisepticpreparations is also acceptable and mayincrease compliance.

Oral Care Dental plaque contains multiple pathogens

(may include s. aureus and p. aeruginosa) After 48 hours, normal oral flora of critically

ill pts changes to more virulent gram (-)organisms Aspiration of oral secretions around the cuff

and ETT occurs in all vented patients

VAP rates are reduced when oral caremeasures are included in a comprehensiveprevention program

P robiotics in VAP

Probiotics prophylaxis of VAP using Lact obacillusr hamnosus GG appears safeand efficacious in a selectpopulation with a very high

risk of VAP, "Ultimately,probiotics may fulfil a role inantimicrobial stewardshipprograms given thereductions in antibioticconsumption.

American Jour nal of Respirat or y and C ri t ical C are Med ici ne.

Interdisciplinary rivalry increases

Mortality

VAP is an excellent

example of a problem

that can best be solved

by interdisciplinarycooperation rather than

interdisciplinary rivalry

and devaluing the

contributions of selected members of

the health care team.

Medical Profession is Changing from

Confidence to Confusion ?

References American Thoracic Society. HAP in adults: diagnosis, assessment of severity, initial antimicrobial therapy

and preventive strategies. Am J Resp Crit Care 1995;153: 1711-1725.

Chastre J. et al. Ventilator Assosciated Pneumonia. Am J Respir Crit Care Med 2002; 10:364-368.

Cutler C> et al. Improving oral care in patients receiving mechanical ventilation. Am J Crit Care 2005; 14(5):389-394.

Grap M. et al. Preventing VAP: evidence-based care 2004; 16: 349-458.

Keenan S. et al. VAP: prevention, diagnosis, and therapy. Crit Care Clin 2002; 18(1): 107-125.

Kollef M. Prevention of hospital associated and ventilator associated pneumonia. Crit Care Med 2002; 32:

1396-1405. Marik, P. et al. One good turn deserves another. Crit Care Med 2002; 30(9): 2146-2148.

Anesthesiology: Pneumatikos, Ioannis A. M.D., Ph.D., F.C.C.P.; Dragoumanis, Christos K. M.D., Ph.D.;

Bouros, Demosthenes E. M.D., Ph.D., F.C.C.P. March 2009 - Volume 110 - Issue 3 - pp 673-680

Centers for Disease Control and Prevention, 2003. Rumbak, M. J. (2000). St rat egies for prevent ion and

t reat ment . Journal of Respiratory Disease, 21 (5), p. 321;

Anesthesiology: Pneumatikos, Ioannis A. M.D., Ph.D., F.C.C.P.; Dragoumanis, Christos K. M.D., Ph.D.;

Bouros, Demosthenes E. M.D., Ph.D., F.C.C.P.vMarch 2009 - Volume 110 - Issue 3 - pp 673-680

Ventilator associated pneumoniaJ D Hunter Correspondence to: Dr J D Hunter Department of

Anaesthetics and Intensive Care, Macclesfield District General Hospital, Victoria Road, Macclesfield SK10

3BL, UK; john.hunter@echeshire-tr.nwest.nhs.uk

P resented as Guest Lecture at Indian

Association of Medical Microbiologists

(I AMM)- KC held at M.S. Ramaiah Medical

College, Bangalore India on 4th Sept 2010

doctortvrao@gmail.com

138avap presentation ramayya

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