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Year : 2011  |  Volume : 54  |  Issue : 2  |  Page : 339-343
Viral ventilator-associated pneumonia: Uncovering tip of the iceberg

1 Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College and KEM Hospital, Mumbai, India
2 Department of Pediatrics, Seth GS Medical College and KEM Hospital, Mumbai, India
3 Children's Hospital of Pittsburgh/UPMC, Pittsburgh, PA, USA

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Date of Web Publication27-May-2011


Context: Hospital-acquired infections are frequently encountered by the physicians for ailments demanding prolonged hospitalization, especially in intensive care units, where patients are often mechanically ventilated. The organisms most often implicated are bacteria; viral etiology is infrequent. Aims: The study aims at reviewing lung pathology at autopsy in mechanically ventilated children admitted in pediatric intensive care unit (PICU) to assess the incidence of viral ventilator-associated pneumonias (VAP). Setting and Design: Retrospective analysis. Materials and Methods: Among the 275 children who had been autopsied, 13 who had been admitted in the PICU satisfied the criteria for VAP. These cases were analyzed on the basis of clinical data and pulmonary pathology. Depending on the overall histology, the cases were classified as being viral or bacterial in etiology. Immunohistochemistry (IHC) for detection of viral antigens was also performed. Results: Of the 13 children, nine (five males and four females) had shown the histomorphologic features, suggesting viral inflammation. The mean age was 33 months. Falling oxygen saturation and increasing respiratory distress had necessitated ventilator support. Acute lymphocytic bronchiolitis, interstitial pneumonitis, diffuse alveolar damage, and necrotizing pneumonia were the histological features. The viruses identified in five patients were adenovirus, respiratory syncytial virus and cytomegalovirus. Conclusion: This communication, though not representing the true incidence, emphasizes that a proportion of nosocomial infections is due to viral infections. This should alert the treating intensivists to actively pursue investigations to confirm viral etiology.

Keywords: Adenovirus, cytomegalovirus, hospital-acquired infection, respiratory syncytial virus, ventilator-associated pneumonia, virus

How to cite this article:
Vaideeswar P, Bavdekar SB, Biswas P, Sarangarajan R, Bhosale A. Viral ventilator-associated pneumonia: Uncovering tip of the iceberg. Indian J Pathol Microbiol 2011;54:339-43

How to cite this URL:
Vaideeswar P, Bavdekar SB, Biswas P, Sarangarajan R, Bhosale A. Viral ventilator-associated pneumonia: Uncovering tip of the iceberg. Indian J Pathol Microbiol [serial online] 2011 [cited 2023 Mar 30];54:339-43. Available from:

   Introduction Top

Hospital-acquired or nosocomial infection (HAI or NCI) is a necessary evil that is frequently encountered by the physicians for ailments demanding prolonged hospitalization. Since such infections add to the health-care costs and are, more importantly, associated with enhanced morbidity and mortality, they have to be curbed promptly and effectively. [1] Intensive care units (ICUs) have an increased risk and incidence of NCI due to prevalence of several risk factors such as presence of severe illness, deranged immune status, and prolonged antibiotic therapy, invariably accompanied by use of invasive devices and procedures. This is also true for the neonatal and pediatric intensive care units (NICU/PICU), which manifest as blood stream infections or nosocomial pneumonias; the organisms most often implicated are bacteria. [2] We recently came across adenoviral nosocomial ventilator-associated pneumonia (VAP) in a child with prolonged PICU stay. [3] This prompted us to review the lung pathology in all autopsied PICU patients during 1-year period to assess the incidence of such viral-associated infections.

   Materials and Methods Top

Pediatric Intensive Care Unit Set-Up

At our institute, the PICU was established in 1988, and was expanded and upgraded in the year 2000. Currently, the unit admits about 250 patients a month and is a nine-bedded medical ICU. There are nine ventilators and is served by a pool of eight nurses in such a way that there are at least two nurses at a given time. Four resident doctors are on duty and a consultant supervises the work on a daily basis.

Definitions [4],[5]

An NCI was defined as an infection not present or incubating at the time of PICU admission, with onset after 48 hours of ICU stay. For diagnosing VAP, the patient should have been on mechanical ventilation for at least 48 hours and developed new and persistent radiographic evidence of focal infiltrates 48 hours or more after initiation of mechanical ventilation. This should be accompanied by at least two of the following criteria: (a) Fever above 38°C; (b) leukocytosis of more than 12 × 10 9 /L; (c) purulent sputum or change in the character of sputum; (d) an organism isolated from a blood culture that was not related to another source of infection; (e) isolation of pathogens from a specimen obtained by transtracheal aspirate, bornchoalveolar lavage or protected specimen brush, or lung biopsy; or (f) histopathologic evidence of pneumonia on lung biopsy.

Data Collection

Since this was a preliminary retrospective autopsy analysis, we selected the autopsied cases of children, in whom the heart and lungs had been studied in detail in the Cardiovascular and Thoracic Section of our department. Among the 275 children who were autopsied, 13 who had been admitted in the PICU satisfied the criteria for NCI and VAP. These cases were further analyzed on the basis of clinical data and pulmonary pathology. As a protocol, the lungs were perfusion-fixed with buffered formalin and five to ten sections were taken for histology. All the gross and histological features were reviewed by one of the authors. Appearances of the tracheobronchial mucosa, the visceral pleura and cut surfaces of the lungs were noted. Particular attention was paid to the distribution and type of inflammatory cells, alteration in the epithelial lining, and presence of necroses. Depending on the overall histology, the cases were classified as being viral or bacterial in etiology; blocks in all 13 cases were also submitted for immunohistochemistry (IHC) for detection of viral antigens.

   Results Top

Of the 13 children, 9 had shown the histomorphologic features that suggested inflammatory changes secondary to a viral etiology. There were five males and four females, with ages ranging from 2 months to 10 years, with a mean age of 33 months. The patients' demographics, modes of presentation, duration of admission and mechanical ventilation and relevant investigations are summarized in [Table 1]. Falling oxygen saturation and increasing respiratory distress had necessitated ventilator support.
Table 1: Viral ventilator-associated pneumonia: Clinicopathological features

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The lungs on gross examination at autopsy were firm to rubbery in four [Figure 1]a (cases 1, 2, 3, 8), and were firm and nodular in five cases [Figure 1]b (cases 4, 5, 6, 7, 9). The cut surfaces in the former revealed multiple small and large foci of congestion and revealed features of acute lymphocytic bronchiolitis with luminal plugging, interstitial pneumonitis, with formation of hyaline membranes [Figure 2]. Inclusions with features suggestive of cytomegalovirus (CMV) were seen in Case 2 in only one of the seven sections taken [Figure 3]. In the lungs with consolidated parenchyma, the histology revealed the alveolar spaces filled with eosinophilic granular material and abundant nuclear debris with destruction of the septal walls. The surrounding alveoli also contained fibrinous material, foamy macrophages with the septa lined by hyaline membranes, and/or hyperplastic lining with associated acute bronchiolitis and interstitial pneumonitis. Inclusions characteristic of adenovirus were seen in two of the cases (cases 4 and 7) [Figure 4], which were confirmed on IHC. Two additional cases (cases 6 and 9) [Figure 5] on IHC were also positive for respiratory syncytial virus (RSV) antigens.
Figure 1: Cut surfaces of the right lungs showing the two gross morphologies: (a) Foci of congestion, seen here predominantly in the lower lobe; (b) multifocal foci of grayish white to pale yellow consolidation

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Figure 2: (a) Alveolar septa are widened due to infiltration of mononuclear cells, chiefly lymphocytes (H and E, ×100); (b) alveolar septa are lined by thick hyaline membranes as a reaction to alveolar damage (H and E, ×250)

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Figure 3: Case 2 showing interstitial pneumonitis with the classical inclusions of CMV (H and E, ×200). Inset shows details of the inclusion (H and E, ×400)

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Figure 4: Case 4: (a) Thickened alveolar septa lined by plump epithelial cells with enlarged and smudged nuclei (H and E, ×100); (b) these smudged nuclei were positive on immunohistochemistry (IHC) for adenovirus (×100). Inset shows positive IHC control

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Figure 5: Case 9 : (a) Alveolar septa are lined by metaplastic cuboidal pneumocytes. There is increased number of macrophages in the spaces with fibrinous exudates (H and E, ×100); (b) a large focus of necrotizing inflammation complicates interstitial pneumonitis (H and E, ×100); positive IHC for respiratory syncytial virus seen in (c) the pneumocytes (×100) as well as (d) bronchiolar epithelium (×400). Inset shows positive IHC control

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   Discussion Top

This pathological study unveils the occurrence of viral-induced lung infection that developed secondary to mechanical ventilation in a PICU setting. The diagnosis was based on two criteria of duration of mechanical ventilation for more than or equal to 48 hours and histopathologic findings at autopsy (backed by immunohistochemical studies in four of the nine cases). Among the NCIs that occur in any ICU, the nosocomial pneumonias (with or without mechanical ventilation) form the second common manifestation, and in PICUs, the incidence ranges from 20% to nearly 50% of the infections encountered. [6] The risk factors are nearly identical to those of blood-stream infections, and added independent predictors included reintubation and movement out of the ICU. [6] In general, indications for mechanical ventilation in children are cardiac and/or respiratory failure or central nervous system diseases, [7] which were the reasons in all our cases. The common causative organisms were bacteria, which were Gram-positive cocci (especially, coagulase-negative Staphylococcus) and Gram-negative rods (especially, P. aeruginosa), isolated using routine microbiological methods in most instances. [8],[9]

On the other hand, diagnosis of viral pneumonias is beset with problems and hence its incidence is probably underestimated. The reasons for this are manifold. Most importantly, the clinical presentation of viral pneumonias is nonspecific or is often similar to bacterial consolidations. Though it has been said that viral infections are often associated with other organ manifestations, [10] this aspect was not noticeable in the reported cases and the only clue would have been a lack of response to antibiotic therapy. In resource-poor countries, the students are trained with the notion that bacterial infections are extremely common. This notion is so powerful that it leads to overuse of antibacterial drugs in routine practice and also gets translated when practitioners think of serious and nosocomial infections. Another lamentable factor, faced at many centers, is the technical difficulty encountered in identification of viral agents. Viruses require more sophisticated procedures such as serological tests, cell cultures or even polymerase chain reaction for identification or isolation. [10] It is also worth mentioning that though pulmonary histopathology is part of the VAP criteria, [4],[5] it is seldom resorted to. [11] In the present study, the main feature on histology that made us suspicious of viral etiology was the predominant mononuclear cell inflammatory response. There were two cases each of RSV and adenovirus pneumonias, showing characteristic necrotizing pneumonia, accompanied by interstitial pneumonitis and diffuse alveolar damage. They were confirmed on IHC. Both these viruses are the most common viral pathogens for VAP. [10],[12] Other viruses include influenza virus and parainfluenza virus, [13],[14] CMV [15] and even herpes simplex virus. [16] However, the latter is considered more of a reactivation rather than induced by ventilation. [17],[18] We had seen CMV inclusions in only one of the seven sections taken.

The occurrence of viral VAP (nine of 13 children, 69.2%) in this study may not represent the true incidence since all patients who expired following PICU admission were not autopsied. Besides, viral markers were not available for the patients admitted in that period. This communication, nevertheless, emphasizes that a proportion of nosocomial infections is due to viral infections. This should alert the treating intensivists to actively pursue investigations (specific viral markers or cultures) to confirm viral etiology and undertake measures (antiviral drugs, where applicable) to treat these patients. When a child does not seem to respond to antimicrobial therapy, it is tempting to go for higher antibiotics. Under such circumstances, it is imperative to also think about an alternative viral etiology and to take appropriate measures to ensure that intra-ICU spread of these infections does not occur.

   References Top

1.Sheng WH, Wang JT, Lee DC, Chie WC, Chen YC, Chang SC. Comparative impact of hospital-acquired infections on medical costs, length of hospital stay and outcome between community hospitals and medical centres. J Hosp Infect 2005;59:205-14.  Back to cited text no. 1
2.Mireya UA, Marti PO, Xavier KV, Cristina LO, Miguel MM, Magda CM. Nosocomial infections in paediatric and neonatal intensive care units. J Infect 2007;54:212-20.  Back to cited text no. 2
3.Vaideeswar P, Bavdekar SB, Jadhav SM, Balan R, Pandit SP. Necrotizing adenoviral pneumonia: Manifestation of nosocomial infection in pediatric intensive care unit. Indian J Pediatr 2008;75:1171-4  Back to cited text no. 3
4.Elward AM, Warren DK, Fraser VJ. Ventilator-associated pneumonia in pediatric intensive care unit patients: Risk factors and outcomes. Pediatrics 2002;109:758-64.  Back to cited text no. 4
5.Almuneef M, Memish ZA, Balkhy HH, Alhem H, Abutaleb A. Ventilator-associated pneumonia in pediatric intensive care unit in Saudi Arabia: A 30-month prospective surveillance. Infect Control Hosp Epidemiol 2004;25:753-8.  Back to cited text no. 5
6.Edward AM, Warren DK, Fraser W. Ventilator-associated pneumonia in pediatric intensive care unit patients: Risk factors and outcomes. Pediatrics 2002;109:758-61.  Back to cited text no. 6
7.Kendirli T, Kavaz A, Yalaki Z, Oztürk Hismi B, Derelli E, Ince E. Mechanical ventilation in children. Turk J Pediatr 2006;48:323-7.   Back to cited text no. 7
8.Maldini B, Antolić S, Sakić-Zdravcević K, Karaman-Ilić M, Janković S. Evaluation of bacteremia in a pediatric intensive care unit: Epidemiology, microbiology, sources sites and risk factors. Coll Antropol 2007;31:1083-8.   Back to cited text no. 8
9.Patra PK, Jayashree M, Singhi S, Ray P, Saxena AK. Nosocomial pneumonia in a pediatric intensive care unit. Indian Pediatr 2007;44:511-8.  Back to cited text no. 9
10.Stralitto SM, Siqueira MM, Machado V, Maia TM. Respiratory viruses in the pediatric intensive care unit: Prevalence and clinical aspects. Mem Inst Oswaldo Cruz 2004;99:883-7.  Back to cited text no. 10
11.Lim SY, Suh GY, Choi JC, Koh WJ, Lim SI, Han J, et al. Usefulness of open lung biopsy in mechanically ventilated patiens with undiagnosed diffuse pulmonary infiltrates: Influence of comorbiditieis and organ dysfunction. Crit Care 2007;11:R93.  Back to cited text no. 11
12.Diniz EM, Vieira RA, Cecon ME, Ishida MA, Vaz FAC. Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation. Rev Inst Med Trop S Paulo 2005;47:37-44.  Back to cited text no. 12
13.Holladay RC, Campbell GD Jr. Nosocomial viral pneumonia in the intensive care unit. Clin Chest Med 1995;16:121-33.  Back to cited text no. 13
14.Valenti WM, Menegus MA, Hall CB, Pincus PH, Douglas RG Jr. Nosocomial viral infections: I. Epidemiology and significance. Infect Control 1980;1:33-7.  Back to cited text no. 14
15.Chiche L, Forel JM, Roch A, Guervilly C, Pauly V, Allardet-Servent J, et al. Active cytomegalovirus is common in mechanically ventilated medical ICU patients. Crit Care Med 2009;37:1850-7   Back to cited text no. 15
16.Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, et al. Herpes simplex virus lung infection in patients on prolonged mechanical ventilation. Am J Respir Crit Care Med 2007;175:935-42.  Back to cited text no. 16
17.Cohen JI. CMV in the ICU: Pathogen or passenger? Crit Care Med 2009;37:2095-6.  Back to cited text no. 17
18.Groeneveld ABJ, Vandenbrouchke-Grauls CM. One swallow does not make a summer: Can Herpes simplex virus-1 cause pneumonia and acute lung injury? Am J Respir Crit Care Med 2007;175:865-7.  Back to cited text no. 18

Correspondence Address:
Pradeep Vaideeswar
Department of Pathology (Cardiovascular and Thoracic Division), Seth GS Medical College and KEM Hospital, Parel, Mumbai 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.81633

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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