ventilator associated pneumonia treatment[1]

8/3/2019 Ventilator Associated Pneumonia Treatment[1]

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Ventilator Associated Pneumonia

Dr.Ashish Kumar Department of Anaesthesia, Critical Care

Medanta , The Medicity

Gurgaon



Definition-

Nosocomial Pneumonia that develops in someone who has beenintubated for mechanical ventilation;

Typically in studies, patients are only included if intubated greater than 48 hours

- Early onset= less than 4 days (<96Hrs)- Late onset= greater than 4 days(>96Hrs)

- Very early onset = with in 48 hrs

Endotracheal intubation increases risk of developingpneumonia by 6 to 21 fold

Accounts for 90% of infections in mechanically ventilated patientsAmerican Thoracic Society, Infectious Diseases Society of America.

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia



Why Do We Care?

VAP increases:• Medical costs• Ventilator days• ICU and hospital lengths of stay

Estimated direct cost of excess hospital stay due to VAP is $40,000 per patient.

Mortality ranges from 20 to 41%, depending on infecting organism,antimicrobial therapy, and underlying disease (Incidence of VAP 9.7%of patients receiving MV) 17% in medical units 9.1% in combined medical – surgical units

Risk of pneumonia 3-10 fold higher in intubated patients Crude mortality 24-50%, upto 76% if MDR pathogens 2-10 times higher mortality if pneumonia present, than if absent Attributable mortality > 25%, range 5-39%

CDC.gov. Guidelines for preventing health-care-associated pneumonia, 2003.

Safdar N et al. Clincial and economic consequences of ventilator-associated pneumonia: a systematic review2



When does VAP occur? intubation and risk.

Cook et al showed . . .• 40.1% developed before day 5

• 41.2% developed between days 6 and 10

• 11.3% developed between days 11-15

• 2.8% developed between days 16 and 20

• 4.5% developed after day 21

Risk of pneumonia at intubation days• 3.3% per day at day 5

• 2.3% per day at day 10

• 1.3% per day at day 15

Cook et al. Incidence of and risk factors for ventilator-associated pneumoniain critically ill patients. Cook, D.

J. et. al. Ann Intern Med 1998;129:433-440



Who gets VAP? (Risk factors)

Patient related; Male sex, Age, Malnutrition, Immunosupression,

Diagnosis; - Burns (risk ratio=5.09),

- Trauma (risk ratio=5.0) ,

- Respiratory disease (risk ratio=2.79) ,

-CNS disease(Comatose) (risk ratio=3.4)

- Cardiac disease (risk ratio=2.73)

Treatment related- Intubation,rentubation & mechanical ventilation -- Enteral feeding, Parenteral nutrition

- Antibiotics- Hyperglycemia

- Supine position

- Immobilization, sedation, muscle relaxants

- Surgery of head/neck/thorax/upper abdomen



Risk for MDR

Antimicrobials in 90 days

Hospital stay > 5 days

Hospitalised > 2 days in last 90 days Nursing home or chronic care facility

Chemotherapy or wound care within 30 days

Home infusions Chronic dialysis in 30 days

Home wound care

ATS Guidelines AJRCCM 2005;171:388-416



Pathogenesis;

OROPHARYNX COLONIZATION

BACTERIAL PATHOGENS

CUFF LEAK / BIOFILM

Bacterial pathogensNumber,Types &Virulence

Tracheal Colonization

VAP

Lung DefencesCilia, Humoral,Cellular



Etiology

David R Park MD presented a version of this article at the 35th RESPIRATORYCARE Journal Conference, Ventilator-Associated Pneumonia, held

February 25 –27, 2005, in Cancu´n, Mexico.



MDR Pathogens : Definitions

Multidrug-resistant (MDR) Acinetobacter baumannii , Pseudomonas

aeruginosa, or Klebsiella pneumoniae strains

Resistance to 5 out of the 7 anti-pseudomonal classes of antimicrobial agents

antipseudomonal penicillins, cephalosporins, carbapenems, monobactams,quinolones, aminoglycosides, and colistin.

CCOS-colistin-carbapenem-only-sensitive

sensitive only to colistin and carbapenems

Colistin-only-sensitive (COS) resistant to all anti-pseudomonal agents, except colistin,

PDR if it exhibited resistant to all 7 anti-pseudomonal antimicrobialagents, including colistin.



Diagnosis of VAP

Clinical approach : CPIS

Radiological approach

Bacteriological approach :-Blood and pleural fluid culture

-Semiquantitative airway sampling

-Quantitative Cultures



Modified CPIS

CPIS at baseline assessed on the basis of first 5 variables

CPIS at 72 hours assessed on all 7 variables

Takes progression of infiltrate and results of qualitative culture of tracheal aspirate into account

Score of > 6 indicates at baseline or at 72 hours indicatespneumonia

CPIS is not superior to classical clinical criteria to definesuspicion of VAP. However, it is useful to follow theevolution under therapy

Singh et al AJRCCM 2000;162:505-11Torres et al. ICM 2008; DOI 10.1007/s00134-008-1336-9



Modified Clinical Pulmonary Infection Score

0 1 2 Remarks

Temperature oC >36.5

<38.4

> 38.5

< 38.9

> 39.0

< 36.5

WCC /mm3 > 4000

< 11000

<4000

>11000

Band forms >50%, +1

Tracheal secretions Absent Non-purulent

purulent

PaO2/FiO2 >200 or ARDS

<200 andno ARDS

Infiltrate on CXR No infiltrate Diffuse or patchy

Localised

Progression of infiltrate None Yes

Trach asp Culture None-light Mod-heavy GMS seen,+1

Singh et al AJRCCM 2000;162:505-11



Radiological features

A new and persistent (>48-h) infiltrate on chestradiograph is the commonest finding in VAP.

The overall specificity of a pulmonary radiographic

opacity consistent with pneumonia is only 27% to 35%

Radiograph findings can be useful in establishing thediagnosis because of their high specificity.

-air space process abutting a fissure(specificity, 96%)

-air bronchogram, especially if single(specificity,96%)



Blood and pleural fluid cultures

Evaluation of suspected VAP Two sets of blood cultures &

Thoracentesis for nonloculated pleural

effusions of >10 mm in diameter on alateral decubitus chest radiograph.

Sensitivity of blood cultures for thediagnosis of VAP is less than 25%.



Bacteriologic Diagnosis of VAP

Quantitiative cultures of lower respiratory secretions

Non-bronchoscopic techniques Tracheal aspirates NDBAL Blind PSB

Bronchoscopic BAL, mini-BAL PSB

Growth above a threshold concentration (cfu / ml) to distinguish

colonisers from pathogens > 106 for tracheal aspirates > 105 for NDBAL > 104 for BAL > 103 for PSB



Use of Surveillance Cultures toGuide Empiric Therapy?

Generally not recommended

Recent study

good positive predictive values (67 –94%) and negative predictive

values (73 –100%) for VAP caused by Acinetobacter,Pseudomonas, or Klebsiella species

surveillance-guided initial antibiotic therapy was appropriate in91% of patients with VAP

Another study found rate of empiric appropriate therapywas 85%, which was significantly higher than what wouldhave been achieved by following the ATS guidelines

Papadomichelakis et al. ICM. doi:10.1007/s00134-008-1247-9

Jung et al. Intensive Care Med. Doi:10.1007/s00134-008-1248-8



Initial Empiric TherapyRecommendations

Choice of specific agents should be guided by localmicrobiology, cost, etc

Inappropriate therapy is a major risk factor for mortality andexcess LOS

Early, appropriate, broad spectrum antibiotic therapy mustbe given in appropriate doses

When patients have recently received an antibiotic, theempiric antibiotic for VAP should be from a different class




Recommendations

If high probability of pneumonia, or if sepsis is present,prompt antibiotic therapy is essential

Antibiotic therapy should not be delayed to perform diagnosticstudies in unstable patients

Either bronchoscopic sampling or non-bronchoscopictechniques can reliably obtain lower respiratory secretions

Semiquantitative or Quantitative culture data may be used

Semiquantitative cultures are not as reliable as quantitativecultures

Quantitative cultures increase specificity of diagnosis of VAP




Clinical VAPPatient Unstable, deteriorating

Bronchoscpic expertise

Microbiology facilities

PSB and BAL

Yes

BAL culture+ve

-ve

ET Aspirate

Broad-spectrum antibiotics

No

ETA Culture

STOPantibiotics

-ve

ModifyChangeContinueantibiotics

Clinical VAPPatient Stable

>50% neutrophils>5% intracellular organismsGram stain positive

Antibiotics No antibiotics

+ve -ve



Initial Empiric TherapyEarly VAP, no risk factors for MDR pathogens

Potential pathogen

Strep. Pneumoniae

H. influenzae

MSSA Sensitive EGNB

Klebsiella

E. Coli

Enterobacter

Proteus

Serratia

Recommended Antibiotic

Ceftriaxone

Or

Levofloxacin, CiprofloxacinOr

Ampicillin / sulbactam

Or Ertapenem




Initial Empiric TherapyLate VAP, Risk factors for MDR pathogens

Potential pathogen All Early VAP pathogens MDR Pathogens

Pseudomonas

Acinetobacter

Klebsiella (ESBL producers) Acinetobacter

MRSA

Legionella

Recommended Antibiotic Ceftazidime or cepfepime

Or Carbapenem (Imipenem, Meropenem)

Or B-lactam /Blactamase inhibitor

Piperacillin - tazobactam PLUS

Ciprofloxacin or levofloxacinOr

AminoglycosidePLUS

Linezolid or Vancomycin




Use Appropriate Antibiotic Doses

Antipseudomonalcephalosporin

Cefepime 1 –2 g every 8 –12 h

Ceftazidime 2 g every 8 h

Carbepenems Imipenem 500 mg every 6 h or 1

g every 8 h

Meropenem 1 g every 8 h

β-Lactam/β-lactamase inhibitor Piperacillin –tazobactam 4.5 g

every 6 h

Aminoglycosides

Gentamicin 7 mg/kg per d

Tobramycin 7 mg/kg per d

Amikacin 20 mg/kg per d

Antipseudomonal quinolones

Levofloxacin 750 mg every d

Ciprofloxacin 400 mg every 8 h

Vancomycin 15mg/kg 12 h

Linezolid 600 mg every 12 h




Penetration into the lung

Aminoglycosides are not ideal drugs

lung tissue penetration reaches only 30 –40% of the serum-level.

b-lactams also exert a penetration of 50%.

In contrast, quinolones achieve a cellular and lung tissuepenetration 1,000% higher than the serum-level

Continuous IV infusion targeting a serum level 20 –30

mg/ml is superior to discontinuous IV Linezolid has better lung pentration than vancomycin

Torres et al. ICM 2008; DOI 10.1007/s00134-008-1336-9



Clinical cure rates for linezolid and vancomycin therapy inpatients with Gram-positive, nosocomial pneumonia




Antibiotic therapy

Linezolid is an alternative to vancomycin for MRSA VAP

De-escalation of antibiotics must be considered based onculture results and patient’s clinical response

A short duration of antibiotic (8 days instead of 14-21 days)is recommended for patients with

Uncomplicated VAP

Initial appropriate therapy No evidence of Pseudomonas, other Gram negative non-lactose

fermenters




Pulmonary infiltrates onAntibiotics

Patient on antibiotics > 3 days develops VAP Current anitbitoic Rx, high chance of organisms being resistant

PSB, BAL are sensitive

Patient on antibiotics <24 hours develops VAP

Recent Antibiotic Rx PSB, BAL less sensitive

In practice, when antimicrobials have been recently modified, anegative finding indicates patient has been successfully treated and the bacteria are eradicated (but de-

escalation is impossible) or that the lung infection was not present to begin with (leading to an active

research of other diseases and cessation or modification of antibiotics).



Combination Therapy vs. Monotherapy

Combination therapy

Combinations to provide broad spectrum cover with activityagainst MDR pathogens, esp. Pseudomonas

In immunocompromised patients Monotherapy

Cheaper, does not expose patient to too many antibiotics

Successful with early, mild VAP

For documented Gram positive pneumonia

Combination therapy may be converted to monotherapy if dictated by culture results




Combination Therapy or Monotherapy?

Combination treatment may still be advisable as initial

treatment (e.g. for the first 48 h) Decreases the probability of inadequate treatment

Switch to monotherapy once the susceptibility is

documented Therapy could be switched to monotherapy in most patients

after 3 –5 days, provided that

initial therapy was appropriate

clinical course appears favourable, and

microbiological data do not suggest a very difficult-to treatmicroorganism




Assessing Response to therapy

Clinical improvement takes 48-72 hours. Therapyshould not be changed unless there is deterioration

CPIS may be useful

Biomarkers - PCT

Responding patient should have de-escalation of

therapy based on culture data Non-responding patient should be evaluated further



Duration of Therapy

8-day regimen can probably be standard for patients with HAP vs 15-21 days.

Exceptions to this include pneumonia due to Psedumonas & S. aureus

immunosuppressed patients

those whose initial antimicrobial treatment was not appropriate patients whose infection was caused by very difficult-to-treat microorganisms

no improvement in clinical signs of infection

In these patients needing prolonged treatment, consider change of antimicrobialagents after 8 days if possible.

Serial PCT measurement may allow reduction of antibiotic treatment durationand exposure without apparent harm

Patients infected with P aeruginosa had a higher infection-recurrence rate whentreated for 8 days but did not have a difference in length of mechanicalventilation, ICU length of stay, or mortality

Clin Chest Med 32 (2011) 507 –515



Biomarkers status PCT provides no guiding light for clinicians to start antibiotics, as

confirmed by the PRORATA trial results. PNEUMA trial, the antibiotic duration for patients with MDR

VAP,based on biomarkers remains controversial A prospective, observational study examined the value of PCT

kinetics as a prognostic factor during VAP. CRP use for diagnostic purposes has yielded widely conflicting data sTREM-1 measurement in BAL fluid for VAP diagnosis remains

unclear: although it was apparently a reliable marker of pneumonia,especially VAP, more recent studies obtained contradictory findings,

thereby raising doubt as to its usefulness for VAP patients. Others- Endotoxin levels in BAL, bacterial permeability increasing

protein & Soluble E-selectin

Clin Chest Med 32 (2011) 431 –438 doi:10.1016/j.ccm.2011.05.004

R d i f i i bi l d hi h d ifi



Recommendations for antimicrobial stewardship have used specificPCT cutoffs. These specify 1 of 4 recommendations, ranging from

“strongly discourage” and “discourage” to“recommend” and “strongly

recommend,” respectively. Schuetz P, Albrich W, Christ-Crain M, et al. Procalcitoninfor guidance of antibiotic

therapy. Expert RevAnti Infect Ther 2010;8:575 –87.



Topical Antibiotics

Topical antibiotics – instillation or aerosolisation

Improved microbiological eradication but not mortalitywith tobramycin

May be useful for organisms with high MICs,unresponsive to systemic therapy




Inhaled antibiotics

Meta-analysis of 5 RCTs In 4 / 5 RCTs, patients received concurrent

systematic antibiotics

Higher treatment success with aerosolised / ETinstilled antibiotics No differences with regard to mortality, emergence

of resistance and drug-related adverse events

Aminoglycosides and Colistin

JAC 2007; 60:1216 –1226



Wrong OrganismResistant pathogen

Mycobacteria, virus, fungus

Inappropriate antimicrobial Rx

Wrong Diagnosis Atelectass, PE, ARDSPulmonary hemorrhage

Underlying diseaseNeoplasm

ComplicationEmpyema or lung abscess

Cl .difficile colitisOccult infection

Drug fever

Non - Responders




Preventions

Hand washing Non-invasive ventilation Avoid reintubation Use HMEs Regular circuit changes

Drain condensates from circuit Closed suction systems Continuous subglottic suction Semirecumbent position Postpyloric feeding

SDD GUP Tight glycemic control Restricted transfusion Sedation protocol

Yes Yes Yes ? No

Yes ? Yes Yes ?

? yes ? Yes Yes



Positional Strategies



Pharmacological strategies



Physical Strategies



Prospective, RCT, single-blind, 54 centers in North America

2003 patients expected to require MV > 24 hrs

Intubation with standard ETT or silver coated ETT

VAP in 4.8% (37/766 patients) with silver-coated tube vs. and 7.5%(56/743; P =.03)

Relative risk reduction of 35.9% (95% CI, 3.6%-69.0%; ) The silver-coated tube was associated with delayed occurrence of VAP

(P =.005)

No statistically significant differences in durations of intubation, ICU or

hospital stay, mortality and frequency and severity of adverse events

I h Sil T b h fi l



Is the Silver Tube the finalfrontier?

3 additional episodes of VAP in the group receiving the silver-coated tubewould have sufficed to render the trial statistically inconclusive

Absence of robustness of the results is worrisome investigators were not blinded, which could have introduced a bias in favor of the

new device.

quantitative culture results from BAL could be negatively influenced by theintroduction of new antibiotics

statistically significant imbalance in the proportion of patients with preexistingCOPD favoring the silver ETT group

Should not be viewed as the definitive answer for VAP prevention

Use should be restricted to high-risk patients treated in ICUs withbenchmark value –based infection rates that remain above institutional goalsdespite implementation of a comprehensive strategy

Chastre. JAMA. 2008;300(7):842-844

ventilator associated pneumonia treatment[1]

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