key: cord-0059528-czuztwr5
authors: Mittal, Saurabh; Madan, Karan
title: Ventilator Associated Pneumonia
date: 2020-08-01
journal: Infectious Diseases in the Intensive Care Unit
DOI: 10.1007/978-981-15-4039-4_5
sha: 9936a0cfbcb6bd1f44ce163ef1e04006fbf8e0c5
doc_id: 59528
cord_uid: czuztwr5

Infections in ICU is a common occurrence likely due to patients’ vulnerability due to their illness and prevalence of various virulent organisms. The common sites involved in ICU infections include lung, urinary tract, skin, paranasal sinuses and oral cavity though most common site remains lung. Ventilator associated pneumonia (VAP) is an important entity to be understood by all physicians dealing with critically ill patients as it has a major impact on patient outcomes.

Infections in ICU is a common occurrence likely due to patients' vulnerability due to their illness and prevalence of various virulent organisms. The common sites involved in ICU infections include lung, urinary tract, skin, paranasal sinuses and oral cavity though most common site remains lung. Ventilator associated

• Ventilator associated pneumonia is pneumonia occurring in an individual on mechanical ventilation for more than 48 h. • Endotracheal tube placement leads to loss of protective mechanisms predisposing the patient to development of pneumonia. • Though predominant organisms include gram negative bacilli such as Acinetobacter, Pseudomonas and Klebsiella, gram positive organism methicillin resistant Staphylococcus aureus is also an important diseasecausing pathogen. • Diagnosis is based upon clinical features and is supported by radiograph and respiratory secretions culture. • Empirical treatment depends upon various risk factors and usually include a combination of antibiotic regimen covering gram negative as well as gram positive organisms. • Prevention of VAP remains the most important strategy and hand hygiene plays a dominant role in prevention of this disease. pneumonia (VAP) is an important entity to be understood by all physicians dealing with critically ill patients as it has a major impact on patient outcomes. VAP is defined as pneumonia occurring in patients after 48 h of endotracheal intubation. It is an important subset of hospital acquired pneumonia (HAP) patients. Early onset VAP is defined as occurring within 4 days and is usually caused by sensitive organisms while late onset VAP (occurring on day 5 or after) is associated with multidrug-resistant (MDR) pathogens and is associated with a worse prognosis. Most often VAP is caused by bacteria but it may occur because of fungal pathogens as well as viruses during viral epidemics.

Despite major advances in ICU care, VAP continues to remain a nightmare for intensivists and it leads to increased treatment costs, increased hospital and ICU stay as well as increased mortality. To implement preventive strategies for the same should be the aim of all ICU services. The management of VAP centres around early diagnosis and effective treatment for appropriate duration.

The exact incidence of VAP depends on the definitions used and the population studied. The maximum risk of VAP is in early in the course of ICU stay. VAP affects around 9-27% of all intubated patients and its incidence increases with increasing duration of mechanical ventilation. The risk is about 3% per day during first 5 days, 2% per day during fifth to tenth day and 1% per day thereafter. As duration of mechanical ventilation is short for most patients, the maximum cases of VAP occur within 4 days of mechanical ventilation. About 35% to 70% of ARDS (acute respiratory distress syndrome) patients develop VAP. Independent predictors of VAP include a primary diagnosis of trauma/CNS/respiratory/cardiac illness, witnessed aspiration and use of paralytic agents. Other risk factors for VAP are diabetes, alcoholism, hypotension, azotemia, enteral feedings, surgery, supine position, malignancy and severe illness (APACHE >18). Older age of the patient and presence of co-morbidities increase incidence of VAP as well as lead to poor outcome. Presence of co-morbidities predisposes patients to specific organism as well such as H. influenzae and pneumococcus in COPD, Pseudomonas and S. aureus in bronchiectasis and MRSA in diabetics and alcoholics. Inappropriate antibiotic therapy, steroid use, sedatives and excessive use of antacids and proton pump inhibitors predispose patients to VAP. Routine change of ventilator circuits, use of nebulizers, bronchoscopes and endoscopes are also associated with increased risk of VAP. VAP is usually linked to aspiration of oropharnygeal and/or oesophageal contents, direct inoculation of lower airways during intubation, infected aerosol inhalation, infection through biofilms which form on endotracheal tube and haematogenous spread.

Pharmacologic interventions in form of concurrent steroid therapy, sedatives, and use of gastroprotective agents lead to increased risk of VAP. Inappropriate use of antimicrobials leads to selection of MDR pathogens causing difficult-to-treat infections. Risk factors for MDR pathogens are shown in Table 5 .1.

Patients with VAP have two to tenfold higher risk of death, though attributable mortality to VAP is unclear as it is difficult to determine the role of VAP in patients dying with severe illnesses.

The various pathogens causing VAP are enlisted in Table 5 .2. The most common organisms remain gram negative bacilli including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter and E. coli. Gram positive organisms like MRSA have also emerged as a challenge. Polymicrobial infections are also common.

The respiratory tract has many protective mechanisms including anatomic barriers, cough reflex, mucociliary clearance mechanisms and innate and humoral immune factors. Due to placement of endotracheal tube, and poor sensorium and sedation, these mechanisms are lost. It often involves colonization of aerodigestive tract with pathogenic organisms, aspiration of contaminated secretions, colonization of lower airways and then leading to invasive infection. Endotracheal tube facilitates the entry of bacteria into lower airways by pooling and leakage of secretions from subglottic area through small channels formed around ET cuff. Biofilm formation on ET and patient's position also have an important influence on VAP occurrence. 

The early diagnosis of VAP requires a high clinical suspicion and timely evaluation. But all worsening in ICU patients should not be attributed to VAP. The gold standard for the diagnosis of VAP is still lacking. Usually clinical features including patient's symptoms in form of fever, new chest examination findings, radiographic changes and hematologic parameters are taken into consideration to start empirical antibiotics but reliance on only these parameters usually leads to over-treatment. Current American Thoracic Society (ATS) guidelines recommend microbiologic sampling of lower airways in form of semi-quantitative or quantitative cultures of non-bronchoscopic lavage (mini-BAL), broncho-alveolar lavage (BAL) or protected specimen brush (PSB).

There are few definitions which have been proposed as the diagnostic criteria for VAP. Among these the definitions suggested by ACCP (American College of Chest Physicians) and CDC (Centers for Disease Control and Prevention) are widely used. Their description is given below:

ACCP Definition A diagnosis of pneumonia is defined as the presence of new, persistent pulmonary infiltrates not otherwise explained, appearing on chest radiographs. Moreover, at least two of the following criteria are required:

1. Temperature of >38 °C. 2. Leukocytosis >10,000 cells/mm 3 .

A pneumonia is ventilator associated when it occurred after intubation and was judged not to have incubated before an artificial airway is put in place.

Two or more serial chest radiographs with at least one of the following:

1. New or progressive and persistent infiltration. 2. Consolidation.

For any patient, at least one of the following:

1. Fever (>38 °C or 100.4 °F) with no other recognized cause. 2. Leucopenia (<4000 WBC/mm3) or leukocytosis (>12,000 WBC/mm 3 ). 3. For adult ≥70 years old, altered mental status with no other recognized cause.

And at least two of the following:

1. New onset of purulent sputum, or change in character of sputum, or increased respiratory secretions. 2. New onset or worsening of cough, or dyspnoea or tachypnoea. 3. Rales or bronchial breath sounds. 4. Worsening gas exchange (e.g. oxygen desaturation (e.g. PaO 2 /FiO 2 ≤ 240), increased oxygen requirement, or increased ventilator demand).

Some clinicians emphasize a weighted approach for clinical diagnosis of VAP. The Clinical Pulmonary Infection Score (CPIS) is an example of this approach. It includes six parameters assessment and each is scored from 0 to 2. A score of 6 or more is considered predictive (not diagnostic) of VAP. It should be performed at initiation of antibiotic therapy and then serially after 2-3 days to assess its effectiveness and de-escalation of antibiotics. Table 5 .3 shows various parameters and scoring system in CPIS.

In ICU, all radiologic infiltrates do not support a diagnosis of VAP. Pneumonia accounts only for one-third of all pulmonary infiltrates in ICU. The noninfectious causes include pulmonary oedema, ARDS, atelectasis and effusion. The quality of portable X-rays in ICU is almost always suboptimal for complete assessment predominantly due to patient position, soft tissue oedema and presence of various wires and catheters obscuring the view.

The National Healthcare Safety Network has recently published a new algorithm for the diagnosis of VAP independent of radiological findings as shown in Fig. 5.1 .

It is yet to be validated but it has led to new insights into diagnosis of VAP.

Many clinicians believe that microbiologic diagnosis is necessary for VAP to optimize the antimicrobial therapy. Many studies have shown that obtaining respiratory specimen for cultures from lower respiratory tract using bronchoscopic or nonbronchoscopic methods can improve diagnostic yield and facilitate appropriate treatment. Using fibreoptic bronchoscope, we can visualize lower airways and obtain samples in form of BAL and protected specimen brush. The selection of appropriate site for sampling is usually based on radiological involvement but in case of diffuse infiltrates samples should be obtained from area with maximum endobronchial abnormality. These samples should be sent for quantitative cultures. Quantitative cultures of BAL and/or PSB specimens consistently yield fewer microorganisms above the diagnostic threshold than are present in qualitative cultures of tracheal aspirates. Thus, when therapeutic decisions are based on these data, fewer patients are treated with antibiotics and a potentially narrower spectrum of therapy is used than when using the clinical diagnostic approach, thereby limiting the emergence and dissemination of drug-resistant strains and minimizing antibiotic-related toxicity.

After 2 days of stability or improvement on the ventilation, Patient has at least one of following:

a. Increase in daily minimum FiO 2 20% for at least 2 days b. Increase in daily minimum PEEP 3 cm H 2 O for at least 2 days 2. Infection-related Ventilator associated complication (IVAC) After at least 3 days of mechanical ventilation and within 2 days of worsening oxygenation, the patient has: a. Body temperature 38°C or < 36°C OR b. WBC count <4000 or > 12000

After at least 3 days of mechanical ventilation and within 2 days of worsening oxygenation, the patient has one of the following:

A: Purulent secretions AND one of the following: a. Positive culture of endotracheal aspirate at 10 5 CFU/mL b. Positive culture of BAL at 10 4 CFU/mL c. Positive culture of lung tissue at 10 4 CFU/mL d. Positive culture of protected specimen brush at 10 4 CFU/mL B: One of the following: The non-bronchoscopic techniques include mini-BAL and blind protected specimen brush. The advantage of these techniques is that they can be performed by individuals not qualified to do bronchoscopy. Mini-BAL involves insertion of one thin catheter through a large catheter, so that outer catheter works as a sheath for the inner catheter and preventing contamination from proximal airways (Table 5 .4).

The treatment of VAP is challenging and involves knowledge of likely causative organisms and spectrum of various antibiotics. It involves the usage of an appropriate antibiotic in optimal doses for adequate period. Antibiotic therapy in VAP is a two-stage process. First one involves initiation of broad-spectrum antibiotics for early treatment and second, narrowing the antibiotic use after cultures to prevent overuse and resistance. Empirical choice depends upon knowledge of likely organisms and local antibiotic susceptibility patterns. The aim is to obtain culture and sensitivity reports and then shift to monotherapy by day 3 whenever possible and reduce the duration of therapy to 7-8 days. A stepwise strategy for the same is shown in Fig. 5 .2.

Failure to initiate prompt appropriate therapy has been linked with increased mortality in patients with VAP. Due to the emergence of multiresistant organisms such as P. aeruginosa, Klebsiella pneumoniae and Acinetobacter, and the increasing role of gram positive bacteria, such as MRSA, empirical treatment with broad-spectrum Step 1: Start therapy using broad-spectrum antibiotics

Step 2: Stop therapy if the diagnosis of infection becomes unlikely

Step 3: Use narrower spectrum antibiotics once the etiologic agent is identified

Step 4: Use pharmacokinetic-pharmacodynamic data to optimize treatment

Step 5: Switch to monotherapy on days 3 to 5

Step 6: Shorten the duration of therapy

Stepwise strategy for antimicrobial therapy for VAP antibiotics is justified in most patients with a clinical diagnosis of VAP. The choice of agents should take into account the antibiotics that the patients have received within the prior 2 weeks, striving not to use the same antimicrobial classes. The choice of empirical antibiotic therapy is shown in Table 5 .5. Risk factors of multidrug-resistant VAP are prior intravenous use within 90 days, septic shock at VAP onset, acute respiratory distress syndrome preceding VAP, five or more days of hospitalization prior to VAP onset, and acute renal replacement therapy prior to VAP onset.

De-escalation of antibiotic therapy based on culture reports should be done. Successful treatment of patients with VAP requires serial clinical and microbiologic assessment. In responding patient the antibiotics should be given for 7-8 days. Long duration (14-21 days) of therapy is required in the following conditions:

• Multilobar consolidation • Malnutrition • Cavitation • Gram −ve necrotizing pneumonia • Isolation of MDR Pseudomonas, and Acinetobacter species 

Establishing well-designed ICU practices can lead to significant reduction in incidence of VAP. Prevention of VAP should be a priority goal of every ICU as it is associated with poor patient outcome. The whole staff should be educated about infection control policy and the procedure for the same. It should be monitored that all staff members are following the policy. Adequate resources should be provided for prevention of VAP. Regular surveillance data should be collected and should be communicated to staff to motivate for further improvement.

Routine handwash with soap and water and regular use of alcohol based hand rubs remain the most important strategy to reduce the risk of infection transmission.

Hand wash should be used when hands are visibly soiled, before eating, after using the restroom and when exposed to C. difficile. Hand rub should be used before and after each contact with patient and patient's surroundings.

Supine positioning is associated with increased risk of reflux and aspiration. When it is feasible and patient can tolerate it, placing the patient in semirecumbent position (i.e. 30-45° elevation of head end) is a low cost measure for VAP prevention.

The use of orotracheal intubation is preferred over nasotracheal intubation. There are antibiotic coated and silver coated ET available. Silver coated tubes are associated with reduced risk of VAP but are not popular. The use of appropriate cuff pressure between 20 and 25 cm H 2 O is associated with reduced chances of aspiration and it should be regularly monitored. Higher cuff pressures are associated with increased risk of mucosal injury, bleeding and tracheal stenosis. Even with this pressure there is formation of microchannels around the cuff causing aspiration. So the role of endotracheal tubes with subglottic suction port becomes important. Continuous or intermittent aspiration of subglottic secretions is now a recommended strategy for VAP prevention.

Reducing ventilator circuit changes is cost-effective and it reduces the incidence of VAP. Ventilator tubings should not be changed regularly unless they are nonfunctional or if they are visibly soiled with secretions or blood. Use of certain humidifiers may be associated with increased bacterial transmission. Heat and moisture exchangers (HME) can filter bacteria and are more effective in reducing VAP than heated wire circuits and heated humidifiers. Use of in-line nebulizers is also associated with increased infection and they should be disinfected, rinsed with sterile water and air-dried.

Oropharyngeal decontamination with chlorhexidine has been shown to reduce the incidence of VAP. Selective digestive decontamination with oral antibiotics has not been recommended due to its ineffectiveness in prevention of VAP. It has been seen that skin decontamination with chlorhexidine, at ICU admission and regularly after that, leads to reduced VAP especially reduced incidence of MRSA VAP.

Most ICU patients receive stress ulcer prophylaxis in the form of gastroprotective agents like sucralfate or H 2 blockers or proton pump inhibitors. PPI increases gastric pH leading to increased gastric colonization, thus increasing chances of VAP but they have much higher benefit for stress ulcer prevention.

National guidelines for diagnosis and management of CAP and HAP

Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the

Antibiotic cycling