VENTILATOR - ASSOCIATED PNEUMONIA

VAP IN ICU
HAP
VAT

1. VENTILATOR - ASSOCIATED PNEUMONIA

2. Definition HAP is defined as infection of the pulmonary parenchyma that occurs 48 hours or more after admission, which was not incubating at the time of admission. VAP refers to pneumonia that arises more than 48–72 hours after endotracheal intubation. VAT is characterized by signs of respiratory infection, without new radiologic infiltrates. HCAP includes any patient who was hospitalized in an acute care hospital for two or more days within 90 days of the infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic. HCAP need therapy for MDR pathogens .

3. Incidence Infections involving the lungs are the most common nosocomial infections in ICU patients, accounting for 65% of all nosocomial infections. It is often difficult to define the exact incidence of HAP and VAP, because there may be an overlap with other lower respiratory tract infections, such as tracheobronchitis , especially in mechanically ventilated patients. Over 90% of ICU-acquired pneumonias occur during mechanical ventilation, and 50% of these VAPs begin in the first 4 days after intubation. VAP develops in 10% to 20% of patients who undergo mechanical ventilation for longer than 24 hours and is associated with longer ICU stays, increased costs, and increased mortality.

4. Etiology Unlike community acquired pneumonias, where the predominant pathogens are pneumococci,atypical organisms, and viruses, three-quarters of the isolates in VAP are Gram-negative aerobic bacilli such as (Pseudomonas aeruginosa , K. pneumoniae , Acinetobacter species) and Staphylococcus aureus . VAP may be due to polymicrobial infections, but rarely due to anaerobes, viral and fungal pathogens especially in the immunocompetent hosts.

5. Patients with early-onset VAP who have received prior antibiotics or who have had prior hospitalization within the past 90 days are at greater risk for colonization and infection with MDR pathogens and should be treated similar to patients with late-onset VAP.

6. Risk Factors For VAP Major risk factor = Endotracheal intubation Factors that enhance colonization of the oropharynx &/or stomach : Administration of antibiotics Admission to ICU Underlying chronic lung disease Conditions favoring aspiration into the respiratory tract or reflux from GI tract : Supine position *GERD NGT placement *Coma/delirium Intubation and self- extubation Immobilization Surgery of head and neck, thorax & upper abdomen Host Factors: Extremes of age Malnutrition Immunocompromised Underlying condition/disease process

7. Pathogenesis Sources of infection for HAP include healthcare devices or the environment (air, water, equipment, and fomites ) and can occur with transfer of microorganisms between staff and patients. HAP requires the entry of microbial pathogens into the lower respiratory tract, followed by colonization , which can then overwhelm the host’s mechanical (ciliated epithelium and mucus), humoral (antibody and complement), and cellular ( polymorphonuclear leukocytes, macrophages, and lymphocytes and their respective cytokines) defenses to establish infection.

8. ASPIRATION – PRIMARY ROUTE OF BACTERIAL ENTRY INTO LRT MICROASPIRATION Mucociliary clearance Halved after 2hrs of intubation Mostly GNBs Mostly GNBs

9. BIOFILM FORMATION ANOTHER MAIN MECHANISM It is an aggregate of micro-organisms kept together within a complex matrix of polysaccharides, proteins and DNA. Develops within hours of intubation. Provides mechanical scaffold around bacteria. Protects against host defences and antibiotics.

10. Aspiration of oropharyngeal pathogens or leakage of bacteria around the endotracheal tube cuff is the primary route of bacterial entry into the trachea. Colonization of the endotracheal tube with bacteria encased in biofilm may result in embolization into the alveoli during suctioning or bronchoscopy . Inhalation of pathogens from contaminated aerosols, and direct inoculation, hematogenous spread from infected intravenous catheters, and bacterial translocation from the gastrointestinal tract lumen are uncommon pathogenic mechanisms.

11. Diagnosis The traditional clinical criteria for the diagnosis of VAP includes :- (a) fever or hypothermia, (b) leukocytosis or leukopenia , (c) an increase in volume of respiratory secretions or a change in character of the secretions, (d) a new or progressive infiltrate on the chest x-ray . When fever, leukocytosis , purulent sputum, and a positive culture of a sputum or tracheal aspirate are present without a new lung infiltrate , the diagnosis of nosocomial tracheobronchitis should be considered . Unfortunately, in patients who are suspected of having VAP based on these clinical criteria, the incidence of pneumonia on postmortem exam is only 30%.

12. In both studies, the clinical criteria for identifying VAP were just as likely to occur in the presence or absence of pneumonia. These studies demonstrate that the diagnosis of VAP is not possible using clinical criteria alone. The clinical approach is overly sensitive, and patients can be treated for pneumonia when another non-infectious process is responsible for the clinical findings .

13. N oninfectious Causes Of C hest Infiltrates Atelectasis : It is common in postoperative period following upper abdominal surgery due to hypoventilation. Left lower lobe atelectasis is very common following coronary artery bypass grafting. Aspiration: Right lower lobe is commonly involved. Infiltrates may take up to 12 hrs to appear in the chest x-ray after the event. Pulmonary embolism: It is generally acute onset in the background of risk factors for deep venous thrombosis and pulmonary embolism (PE).

14. Cardiogenic pulmonary edema . Acute respiratory distress syndrome (ARDS) : The most common non-infectious cause of pulmonary infiltrates in ICU patients. ARDS is an inflammatory disorder of the lungs that produces bilateral infiltrates on chest x-ray. Fluid overload. Drug reactions. Cryptogenic organizing pneumonia. Pulmonary hemorrhage .

15. C linical P ulmonary I nfection S core (CPIS) The CPIS ( developed by Pugin & co-workers ) combines clinical, radiographic, physiological (PaO2/FiO2), and microbiologic data into a single numerical result. Baseline is calculated from the first five variables. For positive culture, two points are added to the CPIS baseline score. A score of more than six at baseline or after incorporating the culture result is considered suggestive of pneumonia (sensitivity 77% and specificity 42%).

16. MODIFIED CPIS Given by Singh and colleagues. Include all criteria of CPIS except culture. Instead, use gram staining of BAL or PSB sample which is reported as + ve or – ve . Advantage - Can be used for screening. Used to direct initial empiric antibiotic therapy and may increase the diagnostic value of CPIS.

17. National Health Safety Network Algorithm,2013 Given to overcome the subjectivity & variability of VAP diagnosis. Based on objective and recordable data. Ventilator associated events , in form of algorithm. Include 3 tiers: VAC , IVAC , P VAP. Include all the conditions and complications occuring due to mechanical ventilation. Detects all ventilator associated complications, not only VAP. Omission of Chest Xray . VAE algorithm is for use in surveillance only. Not intended for use in clinical management.

18. VENTILATOR ASSOCIATED CONDITION (VAC) After 2 days of stability or improvement on the ventilator, the patient has at least one of the following indicators of worsening oxygenation: 1 ) Increase in daily minimum* FiO2 of ≥ 0.20 for ≥ 2 days . 2 ) Increase in daily minimum* PEEP values of ≥ 3 cmH2O for ≥ 2 days .

19. INFECTION RELATED VENTILATOR ASSOCIATED COMPLICATION (IVAC) After at least 3 days of mechanical ventilation and within 2 days of worsening oxygenation, the patient meets both of the following criteria: 1) Temperature > 38 °C or < 36°C, OR white blood cell count ≥ 12,000 cells/mm3 or ≤ 4,000 cells/mm3. AND 2 ) A new antimicrobial agent(s) is started, and is continued for ≥ 4 days . Patient meets criteria for VAC AND

20. POSSIBLE/PROBABLE VAP After at least 3 days of mechanical ventilation and within 2 days of worsening oxygenation, following criteria are met : - Purulent secretions and/or P ositive culture Meets criteria for VAC and IVAC AND

21. POSSIBLE VAP Gram stain evidence of purulent pulmonary secretions OR Positive pathogenic pulmonary culture PROBABLE VAP Gram stain evidence of purulent pulmonary secretions AND Positive pathogenic pulmonary culture

22. Microbiological Evaluation Respiratory Sampling :- Non- bronchoscopic methods:- - tracheal aspirates - mini-BAL Bronchoscopic methods:- - BAL - Protected specimen brush (PSB)

23. Tracheal Aspirate :- Specimens should be screened by microscopic examination and discarded if there is evidence of contamination with mouth secretions. The presence of more than 10 squamous epithelial cells per low-power field (× 100) indicates that the specimen is contaminated with mouth secretions. The presence of macrophages, regardless of the number, is evidence that the specimen is from the lower respiratory tract. More than 25 neutrophils per low-power field (x 100) can be used as evidence of infection. Qualitative culture (sensitivity>90% and specificity≤40%) Quantitative Culture (sensitivity 76% and specificity 75%) Quantitative cultures increase specificity of the diagnosis.

24. Bronchoalveolar Lavage :- BAL is performed by wedging the bronchoscope in a distal airway and performing a lavage with sterile isotonic saline . A minimum lavage volume of 120 mL is recommended for adequate sampling of the lavaged lung segment, and this is achieved by performing a series of 6 lavages using 20 mL for each lavage . The lavage fluid is sent to the microbiology lab for microscopic analysis and quantitative culture. When intracellular organisms are present in more than 3% of the cells in the lavage fluid, the likelihood of pneumonia is over 90%.

25. BAL Without Bronchoscopy ( Mini- BAL):- A sheathed catheter is inserted through a tracheal tube and advanced “blindly” until it wedges in a distal airway. An absorbable polyethylene plug at the tip of the catheter prevents contamination while the catheter is advanced. Once wedged, an inner cannula is advanced for the BAL, which is performed with 20 mL of sterile saline. Only 1 mL of BAL aspirate is required for culture and microscopic analysis. Because of the diffuse bilateral nature of VAP and predominance in dependent lung segments, t he yield from quantitative cultures with mini-BAL is equivalent to the yield with bronchoscopic BAL.

26. Protected Specimen Brush :- Aspiration of secretions through a bronchoscope produces false-positive cultures because of contamination as the bronchoscope is advanced through the tracheal tubes and upper respiratory tract. To eliminate this problem, a specialized brush called a protected specimen brush (PSB) is advanced from the inner cannula to collect samples from the distal airways. The multifocal nature of VAP suggests that BAL and endotracheal aspirates can provide more representative samples than the protected specimen brush (PSB), which samples only a single bronchial segment.

27. Most studies show that the mortality in VAP is not influenced by the microbiological method used to identify infection, and this observation is used to support the continued use of tracheal aspirates in the evaluation of VAP. Negative lower respiratory tract cultures has a strong negative predictive value (94%) for VAP and can be used to stop antibiotic therapy in a patient who has had cultures obtained in the absence of an antibiotic change in the past 72 hours. Extrapulmonary site of infection should be searched if there is sign of infection but negative respiratory cultures.

28. VENTILATOR BUNDLE THERAPY Set of procedures to be implemented together. Different studies and hospitals have used different bundle components- Head end elevation Oral care with Chlorhexidine Daily sedation hold & SBT Stress ulcer prophylaxis DVT prophylaxis Shown to reduce VAP rates.

29. HAND HYGIENE Infection control measures: staff education, Compliance with alcohol-based hand disinfection, and isolation to reduce cross-infection with MDR pathogens. should be used routinely ( Level I ).

30. HEAD END ELEVATION 30-45 degree Decreases risk of aspiration Reduces VAP incidence Level I evidence

31. SUBGLOTTIC SUCTIONING Specially designed ETT Continuous suction -20cm H2O Decreases VAP Level I evidence Risk- mucosal injury SUBGLOTTIC SECRETIONS

32. ORAL HYGIENE Povidone -iodine , chlorhexidine Oral Chlorhexidine : most studied. Decreases oropharyngeal colonization. Several meta analyses show: reduction of VAP rates, mainly in cardiac surgery patients. Used as a standard measure.

33. SILVER COATED ETT Silver : anti-microbial, anti-adhesive properties Prevents BIOFILM formation. Studies show reduced VAP rates. Limitation: it can only delay ETT colonization, biofilm will eventually form over time as secretions accumulate. NASCENT study : decreased VAP rate, but no decrease in mortality. Further studies needed to make a recommendation

34. POLYURETHANE CUFF ETT Ultra thin cuffs. As compared to PVC cuff, they theoretically reduce channel formation and micro aspiration of secretions. Data is limited. Further trials are needed to evaluate its efficacy.

35. PREVENTION OF VAP (CDC 2014 Update)

36. Management All patients should have a comprehensive medical history obtained and undergo physical examination to define the severity of HAP, to exclude other potential sources of infection. All patients should have a chest radiograph to define the severity of pneumonia ( multilobar or not) and the presence of complications , such as effusions or cavitation . Arterial oxygenation saturation should be measured in all patients to determine the need for supplemental oxygen OR to manage patients who require mechanical ventilation. Other laboratory studies (complete blood count, serum electrolytes, renal and liver function), can point to the presence of multiple organ dysfunction and thus help define the severity of illness.

37. Samples of lower respiratory tract secretions e.g. endotracheal aspirate, bronchoalveolar lavage , or protected specimen brush sample should be obtained from all patients with suspected V AP, and should be collected before antibiotic changes. A sterile culture of respiratory secretions in the absence of a new antibiotic in the past 72 hours virtually rules out the presence of bacterial pneumonia, but viral or Legionella infection is still possible. All patients with suspected VAP should have blood cultures collected, recognizing that a positive result can indicate the presence of either pneumonia or extrapulmonary infection. The sensitivity of blood cultures is less than 25%. A diagnostic thoracentesis to rule out a complicating empyema or parapneumonic effusion should be performed if the patient has a large pleural effusion or if the patient with a pleural effusion appears toxic.

38. Clinical Strategy The presence of a new or progressive radiographic infiltrate plus at least two of three clinical features (fever>38C, leukocytosis or leukopenia , purulent secretions) represents the most accurate combination of criteria for starting empiric antibiotic therapy. A reliably performed Gram stain of tracheal aspirates is used to guide initial empiric antibiotic therapy. The etiologic cause of pneumonia is defined by semiquantitative cultures (light, moderate, or heavy) of endotracheal aspirates with initial microscopic examination. If a clinical strategy is used, reevaluation of the decision to use antibiotics based on the results of semiquantitative lower respiratory tract cultures and serial clinical evaluations, by Day 3 or sooner, is necessar.y . Diagnostic techniques that identify etiologic pathogens on the basis of qualitative cultures leads to therapy for more organisms than diagnostic techniques based on quantitative cultures.

39. Bacteriological Strategy The bacteriologic strategy uses quantitative cultures of lower respiratory secretions (collected with or without a bronchoscope) to define both the presence of pneumonia and the etiologic pathogen and can be used to guide antibiotic therapy decisions. Semiquantitative cultures of tracheal aspirates are not as reliable as quantitative cultures to define the presence or absence of pneumonia and the need for antibiotic therapy. Growth above a threshold concentration is required to diagnose VAP (separate colonizing from infecting pathogens), and to determine the causative microorganism(s). The use of a bronchoscopic bacteriologic strategy has been shown to reduce 14-day mortality, compared with a clinical strategy, in one study of suspected VAP. Patients started on therapy within 24 (and up to 72) hours may have negative cultures and false negative culture can lead to a failure to treat either a specific patient or a specific pathogen. Another issue with the bacteriologic strategy is that culture results are not available immediately.

40. Initial Empiric Antibiotic Therapy

41. Delay in the initiation of appropriate antibiotic therapy for patients with VAP is associated with increased mortality. Choice of specific agents should be dictated by local microbiology , cost, availability, and formulary restrictions (Level II). Initial empiric therapy should be adapted to local patterns of antibiotic resistance , with each ICU collecting this information and updating it on a regular basis (Level II). In selecting empiric therapy for patients who have recently received an antibiotic, an effort should be made to use an agent from a different antibiotic class , because recent therapy increases the probability of inappropriate therapy and can predispose to resistance to that same class of antibiotics (Level III).

42. Initial therapy should be administered to all patients intravenously , with a switch to oral/ enteral therapy in selected patients with a good clinical response and a functioning intestinal tract. Highly bioavailable agents, such as the quinolones and linezolid , may be easily switched to oral therapy in such patients (Level II). Fluoroquinolones and linezolid equal or exceed their serum concentration in bronchial secretions. Efforts should be made to shorten the duration of therapy from the traditional 14 to 21 days to periods as short as 7 days, provided that the etiologic pathogen is not P. aeruginosa , and that the patient has a good clinical response with resolution of clinical features of infection (Level I).

43. Provided Good clinical response to therapy is present, use short duration therapy in pts with VAP without - Immunodeficiency CF Empyema Lung abscess Cavitation Necrotizing pneumonia Prolonged therapy leads to colonization with antibiotic resistant bacteria, which may precede a recurrent episode of VAP.

44. Combination therapy vs Monotherapy Combination therapy should be used (agents from different antibiotic classes ) if patients are likely to be infected with MDR pathogens (Level II). No data have documented the superiority of this approach compared with monotherapy , except to enhance the likelihood of initially appropriate empiric therapy (Level I). Although quinolones can penetrate into the lung better than aminoglycosides and have less potential for nephrotoxicity , a trend toward improved survival has been seen with aminoglycoside -containing combinations. If patients receive combination therapy with an aminoglycoside -containing regimen, the aminoglycoside can be stopped after 5–7 days in responding patients (Level III).

45. Monotherapy with selected agents can be used for patients with severe HAP and VAP in the absence of resistant pathogens (Level I ). Patients in this risk group should initially receive combination therapy until the results of lower respiratory tract cultures confirm that organism grown is not MDR (Level II ). Monotherapy is also the standard when gram-positive HAP, including MRSA , is documented .

46. Inhaled Antibiotics Increase the antibiotic concentration at the site of infection. Useful for organisms with high MIC to systemic antibiotics. Penetration is an issue (airflow limitation to diseased lung ). May be inactivated by sputum. May trigger cough, bronchospasm (induced by the antibiotic or the associated diluents). Colistin methanesulfonate (CMS): better tolerated. Dose: 1-2 mIU , 3 or 4 times a day. Aerosolized antibiotics have not been proven to have value in the therapy of VAP (Level I). However, an inhaled aminoglycoside or polymyxin may be considered as adjunctive therapy in patients with MDR gram-negatives who are not responding to systemic therapy (Level III).

47. Specific Antibiotic Regimens If P. aeruginosa pneumonia is documented, combination therapy is recommended. The principal justification is the high frequency of development of resistance on monotherapy . Although combination therapy will not necessarily prevent the development of resistance, combination therapy is more likely to avoid inappropriate and ineffective treatment of patients (Level II). If Acinetobacter species are documented to be present, the most active agents are the carbapenems , sulbactam , colistin , and polymyxin . There are no data documenting an improved outcome if these organisms are treated with a combination regimen (Level II).

48. If ESBL + Enterobacteriaceae are isolated, then monotherapy with a third-generation cephalosporin should be avoided. The most active agents are the carbapenems (Level II). If L. pneumophila is suspected, the combination antibiotic regimen should include a macrolide (e.g., azithromycin ) or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin ) rather than an aminoglycoside . Linezolid is an alternative to vancomycin for the treatment of MRSA VAP and may be preferred on the basis of a subset analysis of two prospective randomized trials (Level II). This agent may also be preferred if patients have renal insufficiency or are receiving other nephrotoxic agents.

49. Response To Therapy A serial assessment of clinical parameters should be used to define the response to initial empiric therapy (Level II). Modifications of empiric therapy should be made on the basis of this information, in conjunction with microbiologic data (Level III). Clinical improvement usually takes 48–72 hours, and thus therapy should not be changed during this time unless there is rapid clinical decline (Level III). Nonresponse to therapy is usually evident by Day 3, using an assessment of clinical parameters (Level II). Serial quantitative microbiologic studies of lower respiratory tract secretions can also define resolution end points.

50. In HAP/VAP, bedside clinical assessment vs serial biomarkers to predict adverse outcomes/clinical response at 72-96 hrs Routine measurement of biomarkers (CRP, Procal , Copeptin , MR pro ANP) in addition to bedside clinical assessment is  not recommended . {strong reco } Clinical assessment- Temp Tracheobronchial secretions Culture and purulence assessment of secretions TLC CXR resolution P/F ratio Scores- CPIS, SOFA

51. Chest radiographs are of limited value for defining clinical improvement in severe pneumonia, and initial radiographic deterioration is common, especially among patients who are bacteremic or who are infected with highly virulent organisms. In addition, radiographic improvement often lags behind clinical parameters. However, the finding of a rapidly deteriorating radiographic pattern, with a follow-up chest radiograph showing progression to multilobar involvement, a greater than 50% increase in the size of the infiltrate within 48 hours, development of cavitary disease, or significant pleural effusion, should raise concern.

52. Improvement in the CPIS occurring during the first 3 days of empiric treatment was associated with hospital survival whereas a lack of improvement in the CPIS predicted mortality. The responding patient should have de-escalation of antibiotics, narrowing therapy to the most focused regimen possible on the basis of culture data. Also, when the organism isolated is sensitive to a less broad-spectrum antibiotic than the antibiotic used in the initial regimen. (Level II).

53. The nonresponding patient should be evaluated for unsuspected or drug-resistant organisms, non-infectious mimics of pneumonia, extrapulmonary sites of infection, and complications of pneumonia and its therapy. Diagnostic testing should be directed to whichever of these causes is likely (Level III).