Ventilator - Associated Pneumonia (VAP)

BR Bansode

INTRODUCTION

VAP is subtype of hospital acquired pneumonia which occur in people who are on mechanical ventilator, through endotracheal tube (ET) or tracheotomy tube for at least 48 hrs. VAP is medical condition that result from infection which floods the alveoli - small, air-filled sacs in the lung responsible absorbing oxygen from atmosphere.

VAP is distinguished from other type of pneumonia (HAP, CAP) by different types of microorganism (MDR, non MDR) responsible, use of antibiotics, methods of diagnosis, ultimate prognosis & effective preventive measures.

EPIDEMIOLOGYVAP is common complication amongst patients who require mechanical ventilations. Prevalence is 6-52 cases per 100 pts on any given day in ICU an average of 10% of pts will have VAP. The frequency of diagnosis is not static but changes with duration of mechanical ventilation, but highest in first

5 days. But it is very high i.e. 70% in pts who ventilated for 30 days. Once pts is off the ventilator & transfer to ward/home the incidence of VAP drops significantly in the absence of other risk factors for pneumonia.

ETIOLOGY OF VAPMDR non MDR pathogens are potential agent causing VAP. Non MDR pathogens are identical to pathogen found in severe CAP. The VAP develop in first 5-7 days of mechanical ventilation.

In patients having other risk factors for HCAP, MDR pathogen may vary from hospital to hospital & different critical care unit in same institution. Many hospital have problem with P. aeruginosa & MRSA. Viral & fungal infection causing VAP is less common, but in immunocompramised pts VAP can cause by these organism. (Table I).

Table I. Microbiologic Causes of Ventilator- Associated Pneumonia

ESBL, extended -spectrum β lacttamase; MDR, mutidrug - resistant; MRSA, methicillin - resistant Staphylococcus aureus; MSSA, methicillin -sensitive S. Aureus.

Non - MDR PathogensStreptococcus pneumoniaeOther streptococcus SPP.Haemophilius influenzaeMSSAAntibiotic - sensitive EnterobacteriaceaeEscherichia ColiKlebsiella pneumoniaeProteus SPP.Enterobacter SPP.Serratia marcescens

MDR PathogensPseudomonas aeruginosaMRSAAcinetobacter SPP.Antibiotic- resistant EnterobacteriaceaeEnterobacter SPP.ESBL - positive strainsKlebsiella SPP.Legionella pneumophilaBurkholderia cepaciaAspergilius SPP

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PathologyThe three factors are critical in pathogenesis of VAP1. Colonization of the oropharynx with pathogenic

microorganism,2. Aspiration of these pathogen from oropharynx into lower

Pathogenic Mechanism Prevention strategy

Oropharyngeal colonization withpathogenic bacteriaElimination of normal flora Avoidance of prolonged antibiotic courses

Large-volume oropharyngeal Short course of prophylactic aspiration around time antibiotics for comatose patients of intubation

Gastroesophageal reflux Postpyloric enteral feeding, avoidance of high gastric residuals, prokinetic agents

Bacterial overgrowth of stomach Avoidance of gastrointestinal bleeding due to prophylactic agents that raise gastric PH, selective decontamination of digestive tract with nonabsorbable antibiotics

Cross-infection from other Hand washing, especially with alcohol-colonized patients based hand rub; intensive infection control education; isolation; proper cleaning of reusable equipment

Large -volume aspiration Endotracheal intubation; avoidance of sedation; decompression of small-bowel

obstructionMicroaspiration around endotracheal tube Endotracheal intubation Noninvasive ventilation Prolonged duration of Daily awakening from sedation ventilation weaning protocols

Abnormal swallowing function Early percutaneous tracheostomy

Secretions pooled above Head of bed elevated; continuous endotracheal tube aspiration of subglottic secretions with specialized endotracheal tube; avoidance of reintubation; minimization of sedation and patient transport

Altered lower respiratory host defenses Tight glycemic control; lowering of hemoglobin transfusion threshold; specialized enteral feeding formula

respiratory tract.3. Compromise of the normal host defense mechanism.

(Table II)The most obvious risk factor is ET, which by pass the normal mechanical factors preventing aspirations. But

Table II. Pathogenic mechanisms and corresponding prevention strategies for ventilator associated pneumonia

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microaspiration can reach lower respiratory tract. ET & suctioning can damage the tracheal mucosa, facilitating tracheal colonization. Pathogenic bacteria can form a glycocalyx biofilin on ET surface that protect them from antibiotic & host defenses. These pathogen can dislodged during suctioning & small fragement of glucolyx can embolise to lower respiratory tract carrying bacteria with them.

In critically ill pts normal oropharyngeal flora replaced by pathogenic microorganism, cross infection from other pts or paramedicals, contaminated equipment & malnutrition contribute to development of VAP. Severely ill pts with sepsis & trauma enter a state of immunoparalaysis several days after admission in ICU are greater risk of developing VAP. Hyperglycemia affect neutrophil function & many recent trial have shown that keeping blood sugar close to normal with exogenous insulin have beneficial effects like decrease risk of infection. The frequent blood transfusion (leukocyte depleted) also affect the immune response in individual pts.

The quantitative culture approach is to discriminate between colonization and true infection. The sampling from lower respiratory tract exclude the colonization & require lower threshold of growth necessary to diagnose pneumonia. For example samples endotracheal aspirate require diagnostic threshold is 106 cfu/ml the sample from lower respiratory

tract require 103 cfu/ml the sample from lower resp. tract should be collected properly by bronchoscopy or BAL to increase sensitivity. The IDSA & ATS guideline have suggested that all these methods are appropriate & choice depends on availability & local expertise. High diagnostic threshold can be obtained if sample taken before starting of antibiotic therapy or changed the antibiotic.

The clinical approach (CPIS) improve the diagnostic criteria. The clinical pulmonary infection score was developed considering various clinical criteria. The CPIS can help to decide the choice antibiotic requirement, MDR coverage to be given or not and outcome of VAP affected individuals. (Table III).

Transport of bacteria from sinus, stomach or blood stream is rare.

CLINICAL MANIFESTATIONThe clinical manifestation of VAP in pts who are on mechanical ventilation are often sedated & are unable to communicate. Many typical presentation of pneumonia will be either absent or unable to be obtained. The most important S/S are fever or low body temperature new purulent sputum, hypoxia, leukocytosis, appearance of new infiltrate on x-ray chest or consolidation, other signs like tachypnea, tachycardia, increase minute ventilation.

DIAGNOSISVAP should be suspected in any patients on mechanical ventilation exhibiting increasing leukocyte count, new shadows (infiltrate) on chest x-ray as is indicative of pneumonia. Blood culture may reveal the microorganism causing VAP. The strategic approach i.e. collect culture from trachea/ET & new or enlarging infiltrate on x-ray chest. The other is invasive i.e. bronchoscopy plus bronchoalveloar lavage for pts with evidence of VAP. When both these methods yield negative culture the diagnosis of VAP is unlikely.

The differential diagnosis of VAP is a typical pulmonary edema, pulmonary contusion/hemorrhage, hypersensitivity pneumonia, ARDS & pulmonary embolism. Clinical finding inventilated patient with fever & leukocytosis may have different diagnosis than VAP, like antibiotic associated diarrhea, sinusitis, UTI, pancreatitis, drug fever, which require antibiotic from different group than VAP, surgical drainage, or catheter removal for optimal management.

Table III. Clinical Pulmonary Infection Score (CPIS)

@ The progression of the infiltrate is not known and tracheal aspirate culture results are often unavailable at the time of

the original diagnosis; thus, the maximal score is initially 8-10 Note: ARDS, acute respiratory distress syndrome; CHF,

congestive heart failure

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MANAGEMENT OF VAPManagement of VAP should be matched to known causative bacteria. When first time VAP is suspected bacteria causing infection is typically not known then broad spectrum antibiotic (Empiric therapy) are given until particular bacterial culture and sensitivity determined. Empiric therapy should be started taking into both risk factors particular resistance bacteria as well as local prevalence of resistance microorganism. So management entirely depends on knowledge of local flora which vary from hospital to hospital. (Table IV).

If MDR pathogen not suspected the VAP should be treated with antibiotic used for severe CAP. However MDR pathogen isolated like drug resistance MRS & ESBL positive Enterobacteriaceae or intrinsically resistant pathogen P aeruginosa & acinetobacter, the β lactum drug specially cephalosporin should be given. P aeruginosa develop resistance to all routinely used antibiotics. Acinctobacter, stenotrophomanas maltophillia & Burkholderia cepacia are intrinsically resistance to many empiric antibiotic regimens or during therapy of VAP.

Most pts without risk factor for MDR infection should be treated with single agent. Legionella which can be nosocomial microorganism in VAP, where potable water deficiency in the hospital.

Once etiologic diagnosis is made the antibiotic therapy may be with single drug in 50% cases, while in 25% pts require two drug combination, like ? lactum & aminoglycosides. VAP causes by MRSA is associated with 40% clinical failure, Linezolid is more efficacious than standard dose of vancomycin in pts with renal insufficiency.

FAILURE TO IMPROVETreatment failure is more common in VAP caused by MDR pathogen. 40% failure when VAP (MRSA) treated with vancomycin & 50% failure in VAP caused by P.aeruginosa by any antibiotics.

Recurrent VAP caused by same pathogen is possible because of biofilim on ET allows reintroduction of microorganism. VAP due to new super infection and pressure of extra pulmonary infection & drug toxicity must be consider in the differential diagnosis of treatment failure.

COMPLICATIONSApart from death, the major complication of VAP is prolongation of mechanical ventilation & stay in ICU. Some time necrotizing pneumonia & pulmonary hemorrhage occur due to pseudomonas aeruginosa. Bronchiectasis & pulmonary scarring leading to recurrent pneumonias, catabolic state in pts who is malnourished. Elderly pts more crippled & need lifelong nursing care.

Patients without Risk factors for MDR Pathogens Cefriaxone (2g IV q24h) or Moxifloxacin (400mg IV q24h), Ciprofloxacin (400mg IV q8h), or Levofloxacon (750mg IV q24h) or Ampicillin/ sulbactam (3g IV q6h) or Ertapenem (1g IV q24h)

Patients with Risk Factors for MDR Pathogens 1. A β- lactam Ceftazidime (2g IV q8h) or Cefepime (2g IV q8 - 12h) or Piperacillin/tazobactam (4.5 g IV q6h), imipenem (500mg IV q6h or 1 g IV q8h), or meropnem (1g IV q8h) plus 2. A second agent active against gram - negative bacterial pathogens: Gentamycin or tobramycin (7 mg/kg IV q24h) or amikacin (20mg/kg IV q24h) or Ciprofloxacin (400mg IV q8h) or levofloxacin (750 mg IV q24h) plus 3. An agent active against gram - positive bacterial pathogens: Linezolid (600mg IV q12h) or Vancomycin (15mg/kg, up to 1 g IV, q12h)

Table IV. Empirical Antibiotic Treatment of Health Care - Associated Pneumonia

MDR, multidrug-resistant

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The clinical improvement if it occur is evident in first 48 to72 hrs of initiation of antibiotic therapy. Hypoxia disappear but clinical infiltrate initially worsen during the treatment, the clinical criteria are good indicator of response to therapy in VAP. Once pts is improved stable follow up with x-ray chest may not be necessary for few weeks.

PROGNOSISVAP is associated with 50-70% mortality. Pts who develop VAP are at least twice risk of death than who do not develop.

VAP in trauma pts mortality is less. VAP caused by MDR pathogen has significant mortality than non MDR pathogen. VAP caused by S.Maltophilia is a marker for pts who is immunocompramised that death is inevitable.

PREVENTION At early stages of illness use of noninvasive ventilation via

nasal or face mask can avoid ET associated risk factors. Early extubation, avoiding heavy sedation, proper aseptic

precaution for suction procedure, use of mouth wash can reduced incidence of VAP.

Reintubation, transport pts for different procedure have higher incidence of VAP. Recently use of silver coating ET may also reduce incidence of VAP.

Elevating head end 30-45° above horizontal significantly reduce VAP rate.

MRSA & the nonfermenters P.aeruginosa & Acinetobacter SPP are normally not part of bowel flora but resides primarily in the nose & on the skin respectively. So controlling overgrowth of bowel flora & proper cleaning of nose & skin can reduce VAP rate.

Consistant infection control practice in hospital/ICU can minimize VAP rate.

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