European Respiratory Society
Nosocomial and Ventilator-Associated Pneumonia

Nosocomial and ventilator-associated pneumonia continue to be a major challenge in the management of intensive care patients. In particular, recent developments in microbial resistance are a cause of great concern. Internationally renowned experts provide comprehensive reviews on all the major topics within the field and, in particular, the recent insights into epidemiology, diagnosis and treatment surrounding this field. This Monograph is an essential reference book for both clinicians and researchers alike on this challenging subject.

  • European Respiratory Society Monographs
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  4. Page 1
    Correspondence: H.D. Aya B, Intensive Care Dept, Vall d’Hebron University Hospital, Pg. de la Vall d’Hebron 119–129, 08035 Barcelona, Spain, Email

    Ventilator-associated pneumonia (VAP) is an infection frequently caused by Pseudomonas aeruginosa, Haemophilus spp. and Klebsiella spp. or by Staphylococcus aureus. Anaerobes are a rare cause of VAP. Virus or fungi are extremely infrequent in immunocompetent patients.

    The physical placement of the endotracheal tube is the most important risk factor for the colonisation of oropharyngeal secretions and establishment of VAP. Aspiration of oropharyngeal secretions or leakage of bacteria around the endotracheal cuff is the major route of access by bacteria to the lower respiratory tract. Infected biofilms on the endotracheal tube can work as a reservoir of pathogens that can eventually trigger an episode of VAP.

    Patients with late onset of VAP and prior exposure to antibiotics have a greater risk of being infected by a multidrug- resistant pathogen, such as P. aeruginosa, methicillin-resistant S. aureus or Acinetobacter baumanii.

    Although the reaction to the infection is not homogeneous, in critically ill patients the mechanical, humoral and cellular responses are suboptimum, which means another challenge in the research and treatment of this disease.

  5. Page 11
    Correspondence: E. Bouza, Dept of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Dr. Esquerdo 46, 28007 Madrid, Spain, E-mail

    The aetiologic diagnosis of ventilator-associated pneumonia (VAP) is a microbiological emergency because of its impact on the morbidity and mortality of the disease. Lower respiratory tract samples should be obtained before treatment is commenced or modified. Surveillance cultures are not recommended when there is no suspicion of VAP. Bronchoscopic techniques do not seem to offer clear benefits over noninvasive methods. It is essential that microbiological tests provide quantitative results such that bacterial colonisation is distinguished from infection.

    Bacterial identification and antibiotic susceptibility tests take 2–4 days, so there is a need for rapid diagnostic procedures. Rapid information is clearly more beneficial to the patient than more complete but delayed information. Gram staining, quantifying microorganisms in polymorphonuclear cells in bronchoalveolar lavage samples and antibiograms prepared directly from clinical samples may provide rapid information that reasonably correlates with subsequent culture results.

    Better communication between microbiologists and attending physicians will improve the VAP management. Microbiological information is also key to preparing guidelines for the empirical treatment of these patients in each hospital unit.

  6. Page 24
    Correspondence: S. Ewig, Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, Evangelisches Krankenhaus Herne und Augusta-Kranken-Anstalt Bochum, Bergstrasse 26, 44791 Bochum, Germany, Email

    Several biomarkers have been studied as diagnostic tools in patients with ventilator-associated pneumonia (VAP) to assess prognosis, antimicrobial treatment response and duration.

    Promising results for the diagnosis of VAP have been reported. However, these results need further validation by independent cohorts. Procalcitonin (PCT) appears to be of limited value, although most data have not been sufficiently controlled for potential confounders. Soluble triggering receptor, expressed on myeloid cells-1, could not be confirmed as a useful diagnostic tool. Overall, diagnostic data for biomarkers are impaired by the same limitations as all data on quantitative cultures of respiratory samples are, i.e. the lack of a gold standard for validation.

    All investigated biomarkers differentiated survivors and nonsurvivors; however, predictions were limited by restricted patient numbers and unvalidated results.

    Intervention studies using biomarker-based algorithms (particularly PCT) have been shown to safely and effectively reduce the duration of antimicrobial treatment. However, data are affected by obvious overtreatment practices in the control groups. Thus, the role of biomarkers, within simple and inexpensive clinical rules and algorithms, to shorten antimicrobial treatment needs defining.

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    Correspondence: M. S. Niederman, Dept of Medicine, Winthrop University Hospital, 222 Station Plaza N, Suite 509, Mineola, NY 11501, USA, Email

    Guidelines for the therapy of nosocomial pneumonia, including ventilator-associated pneumonia (VAP) and healthcare-associated pneumonia, have been published by the American Thoracic Society and the Infectious Diseases Society of America, in 2005, and are in need of updating. The basic approach, which has not changed, is to ensure timely and appropriate therapy for all patients, focusing on identifying those at risk of infection by multidrug-resistant pathogens, including extended-spectrum β-lactamase producing Gram-negative bacteria, Acinetobacter spp., Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA).

    In the delivery of adequate antimicrobial therapy it is important to ensure that patients receive the correct dose of antibiotic and, in the case of multidrug-resistant pathogens, to administer regimens that optimise drug pharmacokinetics. New options for the treatment of multidrug-resistant Gram-negative bacteria have emerged with the availability of doripenem and tigecycline, the re-emergence of colistin and the use of aerosolised antibiotic therapy. The role of combination therapy in patients with VAP has been clarified and therapy for MRSA VAP has been evaluated with new data focusing on the use of telavancin and linezolid. To optimise antibiotic use for nosocomial pneumonia, it is essential to have a good knowledge of each intensive care unit’s dominant organisms and ensure proper antimicrobial stewardship, focusing on de-escalation and optimal duration of antibiotic therapy.

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    Correspondence: R.G. Wunderink, Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, 676 N. St Clair Street, Suite 14-044, Chicago, IL 60611, USA, Email

    Several new antibiotics with activity for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) have recently become clinically available. All are variations of existing compounds. Doripenem is probably equivalent to the already available meropenem and is slightly more active than imipenem. Its stability in solution allows use in prolonged infusions. Ceftaroline has been approved by the US Food and Drug Administration for the treatment of community-acquired pneumonia, and may be appropriate for HAP/VAP without multidrug-resistance risk factors. Unfortunately, although active against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, no patients in the ceftaroline clinical trial had MRSA pneumonia so this advantage remains theoretical. Televancin appears to be roughly equivalent to vancomycin, with potentially greater efficacy in MRSA isolates with high mean inhibitory concentrations, but with an equal to greater risk of nephrotoxicity. Tigecycline should not be used as front-line therapy for HAP/VAP but as salvage therapy only in patients infected with extremely drug-resistant pathogens. Colistin finds its greatest use in this same niche, although aerosolised colistin demonstrates trends toward improved outcomes. New antibiotics are clearly needed for nosocomial pneumonia.

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    Correspondence: C-E. Luyt, Groupe Hospitalier Pitie Salpetriere, Service de Réanimation Médicale, 47 boulevard de l’Hôpital, 75013, Paris, France, Email

    Antibiotic aerosolisation in patients with ventilator-associated pneumonia (VAP) has renewed potential with the recent development of a new generation of nebuliser, which uses a vibrating mesh. However, data in humans are limited, and with the exception of one randomised study, most of the reported incidents are of case reports, descriptive studies or literature reviews. The unique randomised study, so far only published as an abstract, showed that amikacin aerosolised with a vibrating-mesh nebuliser, a new generation device, was well distributed in the lung parenchyma and might lead to reduced intravenous antibiotics use. Recent pharmacokinetics studies on amikacin nebulisation with vibrating-mesh nebulisers showed promising results. Prospective cohort or retrospective studies showed that colistin nebulisation could be of interest in patients with VAP due to multiresistant strains.

    Despite recent promising findings, the widespread use of aerosolised antibiotics to treat VAP cannot be recommended. It should be restricted to the treatment of multidrug-resistant Gram-negative VAP. In these cases, using a vibrating-mesh nebuliser seems to be more efficient.

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    Correspondence: A. Torres, UVIR, Servei de Pneumologia, Institut Hospital Clínic del Tórax, Hospital Clinic de Barcelona, Villarroel 170, 08036 Barcelona, Spain, Email

    Validation of guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to confirm the reliability of such guidelines in clinical practice and to ascertain their impact on patient-outcome parameters. In order to improve outcomes, guidelines need to be adapted to the local microbiology, accurately predict pathogens, and help physicians to administer the most appropriate empiric antimicrobial therapy. Overall, the implementation of guidelines is followed by an increase in the initially adequate antibiotic treatment. Rather than the onset with time, a proper identification of risk factors for specific pathogens is crucial in choosing an appropriate empiric treatment and needs to be addressed in future guidelines. However, only a few studies have demonstrated that the prediction of microorganisms by HAP and VAP guidelines is reliable. Guideline validation studies are not easy and have to take into account different variables, potentially related with the outcome of patients.

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    Correspondence: L.E. Morrow, Creighton University Medical Center, 601 North 30th Street, Suite #3820, Omaha, NE 68131, USA Email

    Ventilator-associated pneumonia (VAP) is common, costly and portends a poor prognosis. Given the limited supply of effective antibiotics to treat the antibiotic-resistant pathogens increasingly associated with VAP, increasing emphasis is being placed on VAP prevention. Such VAP-preventive strategies can be broadly classified as either pharmacologic or non-pharmacological. Pharmacologic interventions include attempts to reduce host colonisation, optimisation of comorbid conditions and avoidance of agents which promote infection. Non-pharmacologic efforts include education, prevention of cross-infections, minimising the duration of intubation, reducing colonisation of the endotracheal tube-associated biofilm, minimising aspiration, avoiding patient transport, and use of kinetic beds. In this review we assess the evidence supporting various VAP-preventive strategies within this framework.

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    Correspondence: A. Torres, Servei de Pneumologia i Al·lèrgia Respiratòria, Hospital Clínic, Calle Villarroel 170, Esc 6/8 Planta 2, 08036 Barcelona, Spain, Email

    Ventilator-associated pneumonia (VAP) is one of the most common infections in the intensive care unit (ICU) and is associated with high morbidity, mortality and costs. As a result, prevention of VAP is highly relevant in critical care settings. Pulmonary aspiration of colonised oropharyngeal secretions across the tracheal tube cuff is the main pathogenic mechanism for development of VAP. Recently, several strategies have been applied to improve the design of tracheal tubes and reduce the likelihood of aspiration of pathogen-laden secretions across the cuff. The use of endotracheal tubes that allow aspiration of subglottic secretions have demonstrated a decrease in the rate of VAP. In critically ill patients, following tracheal intubation oral flora frequently shifts into a predominance of aerobic Gram-negative pathogens. Extensive efforts have been devoted to reducing the risks of oropharyngeal colonisation with pathogens, including selective digestive decontamination (SDD). Although SDD is a controversial measure, it reduces the incidence of VAP and respiratory infections. The long-term effects of SDD on the emergence of bacterial resistance and risk of superinfections are still controversial.

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    Correspondence: C.M. Luna, Acevedo 1070, Banfield (1828), Buenos Aires, Argentina, Email

    Animal models of ventilator-associated pneumonia (VAP) represent a unique scenario for the study of the different aspects of human VAP. Several years of investigation have yielded important information regarding: the understanding of lung and systemic inflammatory responses to pneumonia and potential therapeutic modulation; the different diagnostic sampling methods with the advantage of having a gold standard for microbiology and histopathology of lung samples; clinical efficacy of intravenous and aerosolised antimicrobials and their pharmacokinetic parameters in lung disease infections; how pneumonia affects the different patterns and modes of mechanical ventilation; and the study of preventive measures in VAP. This chapter focuses on: the basic principles of animal model VAP preparation; how the above-mentioned aspects are studied; and how more realistic results are produced and how their translation into clinical practice can occur.

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    Correspondence: C-E. Luyt, Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié–Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47–83 boulevard de l’Hôpital, 75651 Paris Cedex 13, France, Email

    Viral ventilator-associated pneumonia (VAP) has recently been recognised as a true disease in non-immunosuppressed patients. Viral VAP is typically due to latent viruses that are reactivated in critically ill individuals. Herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) are the main viruses responsible for viral VAP. HSV-1 is frequently recovered from the upper and lower respiratory tract of intensive care unit (ICU) patients. In some patients, true VAP (HSV bronchopneumonitis) can occur. The clinical diagnosis is not specific, but patients frequently have herpes labialis or gingivostomatitis. If HSV bronchopneumonitis is suspected, bronchoalveolar lavage (BAL) can be performed to detect HSV and HSV-specific inclusions in cells recovered in BAL fluid. Whether or not a specific treatment is useful in this setting remains to be determined.

    CMV is less frequently recovered from the lower respiratory tract of ICU patients, but can be classed as true CMV pneumonia in some cases. Diagnosis is not easy and often requires lung biopsy. Whether or not noninvasive testing (CMV in BAL or blood) is useful in the diagnosis of CMV pneumonia, remains to be seen. To date, a specific treatment cannot be recommended.

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    Correspondence: S. Ewig, Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, Evangelisches Krankenhaus Herne und Augusta-Kranken-Anstalt Bochum, Bergstrasse 26, 44791 Bochum, Germany, Email

    Candida pneumonia is not usually a pathogen of ventilator-associated pneumonia (VAP). However, Candida pneumonia may occur. A diagnosis is difficult, if not impossible, to make in critically ill patients. Regular indications for treatment are restricted to histological proof or systemic infection. Because of the potential for Candida aspiration pneumonia and Candida colonisation, possibly favouring VAP and tracheobronchial colonisation with Pseudomonas aeruginosa, patients with oral and/or oesophageal candidiasis should receive specific treatment.

    Although uncommon, Aspergillus spp. pneumonia is a potential threat for critically ill patients. Patients with chronic obstructive pulmonary disease, advanced liver cirrhosis, solid organ cancer and, in particular, steroid use, should be recognised to be at a moderately increased risk for pulmonary aspergillosis. The diagnosis of pulmonary aspergillosis is based on histology or, if this is not available, a three-category approach including host factors and clinical and microbiological criteria. Patients with proven or probable pulmonary aspergillosis should be treated early and effectively. According to current guidelines, voriconazole is the treatment of choice. Alternatively, liposomal amphotericin B or echinocandins can be used.

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    Correspondence: M. Sabrià, Unitat de Malalties Infeccioses, Hospital Universitario Germans Trias i Pujol. Crta. De Canyet, s/n 08916, Badalona (Barcelona) Spain, Email

    Hospital-acquired pneumonia (HAP) is an important cause of nosocomial infection. Most studies have been carried out in intensive care units (ICUs) where patients requiring mechanical ventilation are at high risk of developing HAP. However, the epidemiological differences between intubated patients and those admitted to general hospitalisation wards suggest that the aetiology and therapeutic approach differ between these two groups. The present article reviews the epidemiology, diagnosis, treatment and prevention of HAP occurring outside ICUs.

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    Correspondence: S. Nseir, Intensive Care Unit, Calmette Hospital, University Hospital of Lille, Boulevard du Pr Leclercq, 59037 Lille Cedex, France, Email

    Incidence of ventilator-associated tracheobronchitis (VAT) varies from 1.4 to 16.5% of intubated critically ill patients. VAT represents an intermediate process between lower respiratory tract colonisation and ventilator-associated pneumonia (VAP). The definition of VAT is still controversial. However, the most specific definition includes: fever (>38°C) with no other recognisable cause, purulent sputum production, positive culture of respiratory specimen at significant threshold, and no radiographic signs of new pneumonia. VAT is characterised by lower respiratory tract inflammation and increased sputum production resulting in weaning difficulties and longer mechanical ventilation (MV) duration.

    Recent randomised trials have reported beneficial effects of antimicrobial therapy in VAT patients. In a randomised, blinded placebo-controlled trial, aerosolised antibiotics significantly reduced the incidence of subsequent VAP. Furthermore, aerosolised antibiotics increased weaning from MV, reduced systemic antibiotic usage and antibiotic resistance. The impact of systemic antibiotics on outcomes of VAT patients was evaluated in a randomised, unblinded controlled study. Antibiotic treatment increased MV free days and reduced the incidence of subsequent VAP and intensive care unit mortality.