Introduction
Ventilator-associated pneumonia (VAP) is responsible for substantial morbidity and mortality. There is wide variation in reported VAP depending on the setting, geographical variations, and due to variations in surveillance definitions. The prevalence of VAP in pediatric intensive care unit (PICU) in the USA varies between 3% and 65%.[1] One study from Peru and few studies from North India reported the incidence of VAP to be between 17% and 40%.[2,3,4,5]
VAP is defined as nosocomial pneumonia that develops after more than 48 h in mechanically ventilated patients.[6] VAP is suspected when a patient develops a fever, leukocytosis, or leukopenia, new or progressive pulmonary infiltrate along with purulent trachea-bronchial secretions after 48 h of mechanical ventilation. Such patients may also have decreased PaO2/FiO2 ratio, increased respiratory rate, minute ventilation, and increased requirement of FiO2. VAP had mostly been reported to have bacterial etiology.[7,8,9] The pathogen responsible for VAP remains unknown in 30%–50% of cases, according to the standard bacteriological procedure.[10,11] Recent studies have reported viral etiologies for VAP. Some studies emphasize that a higher proportions of VAP were due to viral etiology.[12,13] The identification of causative organisms of VAP is crucial for the selection of appropriate antibiotic/antiviral, to improve the survival of the patients and to prevent the emergence of antibiotic resistance. Hence, it is important for a treating pediatrician to actively pursue investigations to find out the causative agents (both bacterial and viral). Studies regarding virus as a causative agent for VAP are very few, so the present study aimed to describe the clinical profile of pediatric VAP patients and determine the proportion of viral etiology in VAP and factors associated with it.
Materials and Methods
A descriptive observational study was conducted at PICU of a tertiary referral center of North India from June 2017 to May 2018 in 120 cases. The sample size was calculated at a 95% confidence level, 0.05% alpha error assuming 25% of detection of respiratory virus in the tracheobronchial aspirate among the patient on ventilator. At 8% absolute allowable error, the required sample size was 117 cases on ventilator. Etiological agents were calculated as the simple frequency of individual agents in VAP.
Patients aged 1–18 years with clinical suspicion of VAP and modified Clinical Pulmonary Infection Score ≥5 were included after taking informed consent.[14]
Patients with primary respiratory disease were excluded from the study. VAP was clinically suspected by the presence of a new or evolving infiltrate in the chest X-ray, purulent airway secretions, and the presence of systemic inflammatory response syndrome. Any increase in amount or changes to purulent nature of the secretions and worsening of X-ray findings accompanied by signs of inflammation in blood tests were considered suggestive of VAP [Table 1]. Ethical clearance was obtained from the institute's ethical committee before initiation of the study and written informed consent was obtained from all parents of all patients before data collection.
;)
Table 1: Modified clinical pulmonary infection score
Sociodemographic and clinical data were collected using a predesigned semi-structured pro forma. Endotracheal aspiration (ETA) sample was collected by the same researcher from all patients. ETA was done using sterile suction catheters of 53 cm length (GS 2006, Romsons) of sizes appropriate for the different sized endotracheal tubes. No tube was shortened at the lip level. The lengths of both the connector and the ETT were taken together for the estimated length of the suction catheter to be inserted for ETA. The catheter connected to the mucus trap unit (GS 51800, Romsons) was inserted through the ETT and advanced up to the tip of the tube. Suctioning was performed with wall-mounted suction, and the aspirate was collected in a sterile mucus trap.
The sample was shifted from the trap to (viral transport media) tube and immediately sent to the microbiology laboratory. Samples were tested for rhinovirus, herpes simplex virus (HSV), influenzavirus A and B, respiratory syncytial virus (RSV), enterovirus, parainfluenza virus, and adenovirus. Virus identification was made by reverse transcription-polymerase chain reaction (RT-PCR) using bio-rad real-time PCR system.
Observations
In the present study of 120 VAP cases, most of the patients were males (66.7%). The mean age of the patients in the study group was 6.7 ± 4.12 years ranging between 1.2 and 16 years. Virus was isolated in 14.2% of cases of VAP [Figure 1]. Human adenovirus (29%), RSV (29%), and HSV (24%) were the most common viruses identified [Table 2]. Fever (85.8%), seizures (49.2%) and unconsciousness (58.3%) were the most common clinical complaints [Table 3]. Viral VAP was most common in the 3–6 years of age group (P = 0.002). Males showed a higher proportion of Viral VAP (15%) as compared to females (12.5%). Among primary diseases, dengue (50%) and sepsis (40%) were significantly associated with viral VAP (P = 0.010). Lymphocyte count was significantly higher in viral VAP (P = 0.025). No significant difference was found in total leukocyte count, neutrophil count, and platelet count among patients with and without viral isolation [Table 4]. No significant change was seen in total leukocyte count before and after VAP. There was significant decrease (P < 0.001) in neutrophil count and significant increase (P < 0.001) in lymphocyte count after development of VAP [Table 5].
Figure 1: Virus identical in ventilator associated pneumonia
Table 2: Type of virus identified in viral ventilator-associated pneumonia
Table 3: Clinical complaints among study subjects*
Table 4: Factors associated with viral ventilator-associated pneumonia
Table 5: Laboratory parameters in before ventilator-associated pneumonia and after ventilator-associated pneumonia
Discussion
VAP is a cause of significant morbidity and mortality in pediatric ICU. In the present study, most of the VAP patients were males (66.7%), similar with the results of various other studies.[2,3,4]
In the present study, most (65.8%) cases of VAP had central nervous system pathology, followed by dengue (8.3%) fever, metabolic disorders (5.8%), and septicemia (4.1%). Eleven (9.1%) patients had renal/hepatic failure, 5 (4.1%) patients had malignancy acute lymphocytic leukemia. In a south Indian study from PICU, neuromuscular diseases were significantly associated with VAP.[15,16] Cook et al. and Ali et al. studies also showed neurological diseases in higher proportions in ICU's VAP.[17,18] Similarly, in a pediatric study, enrolled cases associated with dengue, hepatic and renal failures were 3.4%, 5.8%, and 2.3% respectively.[4]
In this study virus, RT-PCR was positive in 14.2% of cases of VAP. Esperatti et al. reported that the incidence of viral infections in VAP was 23%.[19] This slightly higher proportion might be because of the inclusion of samples from the upper and lower respiratory tract both, while in the present study, only endotracheal aspirates were taken. A study done by Daubin et al. observed that nosocomial viral VAP is likely to be rare in ICU, as assessed by the absence of respiratory virus-induced VAP identified in a prospective cohort study.[20] This difference in findings might be probably due to the longer duration of mechanical ventilation, immunocompromised patients and different (higher) age group patients as they are more prone to bacterial infections. Vaideeswar et al. in a pediatric study to review lung pathology at autopsy in mechanically ventilated children, concluded that out of the 13 children, nine had shown the histomorphologic features that suggested inflammatory changes secondary to a viral etiology.[12] This high percentage may be due to The fact that all patients who expired following PICU admissions were not autopsied in their study. In a study from Mexico, at least one virus was detected in 65% of episodes of hospital-acquired pneumonia.[20]
The viruses identified in the present study were human adenovirus (29%), RSV (29%), HSV (24%), human bocavirus (12%), and human rhinovirus (6%). In a study of 240 patients of suspected VAP by A Gadani H et al. HSV1 was isolated in 13%, influenza in 2%, cytomegalovirus (CMV) in 1.3% and RSV in 1% patients.[21] Emilio Bouza et al. reported HSV isolation in 13.4% of VAP.[22] In a study of 93 respiratory distress syndrome (ARDS) patients, Coisel et al. found 28% of patients to be positive for HSV and 24% for CMV.[23] Luyt et al. found HSV Broncho-pneumonitis in 21% of the 201 patients who deteriorated clinically.[24] Tuxen et al. found HSV in 30% of tracheobronchial secretions in patients with the ARDS.[25] In a PICU study, 80% of viral hospital-acquired pneumonias were due to influenza.[20] This clearly indicates that prevalent virus will vary geographically.
In the present study, neutrophil count decreased significantly after the development of viral VAP. White blood cell (WBC) counts showed increase in lymphocyte counts and decrease in granulocytes after viral VAP. Viral infections affecting the systemic circulation are often accompanied by an increase in lymphocytes. The WBC differential identifies lymphocytes as reactive or atypical, indicating the response of this cell type to the virus.[26]
Conclusion
Viral VAP was found in 14.2% of cases, emphasizes that a proportion of VAP was due to viral infections. This should alert the treating pediatrician to go for investigations (specific viral markers or cultures) to confirm viral pathogen and undertake measures (antiviral drugs, where applicable) to treat VAP patients not responding to antibiotics. 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 prevalent viruses may vary geographically; hence, hospitals should try to identify the common viruses causing VAP in their settings to guide an appropriate battery of tests and antiviral drugs.
Limitation
The number of the study subjects was less, so there is a need for more studies. We compared our results with pediatric as well as adult studies as there are only few pediatric studies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
We are grateful to the cooperation by the Department of Microbiology and all participants and their parents/guardians.
REFERENCES
1. Gauvin F, Dassa C, Chaïbou M, Proulx F, Farrell CA, Lacroix J. Ventilator-associated pneumonia in intubated children: Comparison of different diagnostic methods Pediatr Crit Care Med. 2003;4:437–43
2. Becerra MR, Tantaleán JA, Suárez VJ, Alvarado MC, Candela JL, Urcia FC. Epidemiologic surveillance of nosocomial infections in a Pediatric Intensive Care Unit of a developing country BMC Pediatr. 2010;10:66.
3. Patra PK, Jayashree M, Singhi S, Ray P, Saxena AK. Nosocomial pneumonia in a pediatric intensive care unit Indian Pediatr. 2007;44:511–8
4. Vijay G, Mandal A, Sankar J, Kapil A, Lodha R, Kabra SK. Ventilator associated pneumonia in pediatric Intensive Care Unit: Incidence, risk factors and etiological agents Indian J Pediatr. 2018;85:861–6
5. Sharma H, Singh D, Pooni P, Mohan U. A study of profile of ventilator-associated pneumonia in children in Punjab J Trop Pediatr. 2009;55:393–5
6. Bulletin, Centers for Disease Control and Prevention. Device-associated Events/Ventilator Associated Pneumonia (VAP) Event. 2011;6:1–14.2
7. Awasthi S, Tahazzul M, Ambast A, Govil YC, Jain A. Longer duration of mechanical ventilation was found to be associated with ventilator-associated pneumonia in children aged 1 month to 12 years in India J Clin Epidemiol. 2013;66:62–6
8. Rit K, Chakraborty B, Saha R, Majumder U. Ventilator associated pneumonia in a tertiary care hospital in India: Incidence, etiology, risk factors, role of multidrug resistant pathogens Int J Med Public Health. 2014;4:51–6
9. Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culturepositive pneumonia Chest. 2005;128:3854–62
10. Fagon JY, Chastre J, Wolff M, Gervais C, Parer-Aubas S, Stéphan F, et al Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial Ann Intern Med. 2000;132:621–30
11. Ruiz M, Torres A, Ewig S, Marcos MA, Alcón A, Lledó R, et al Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: Evaluation of outcome Am J Respir Crit Care Med. 2000;162:119–25
12. Vaideeswar P, Bavdekar SB, Biswas P, Sarangarajan R, Bhosale A. Viral ventilatorassociated pneumonia: Uncovering tip of the iceberg Indian J Pathol Microbiol. 2011;54:339–43
13. Amanati A, Karimi A, Fahimzad A, Shamshiri AR, Fallah F, Mahdavi A, et al Incidence of ventilator-associated pneumonia in critically ill children undergoing mechanical ventilation in pediatric Intensive Care Unit Children (Basel). 2017;4:E56.
14. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription Am J Respir Crit Care Med. 2000;162:505–11
15. Torres-García M, Pérez Méndez BB, Sánchez Huerta JL. Healthcare-associated pneumonia: Don't forget about respiratory viruses! Front Pediatr. 2019;7:168.
16. Balasubramanian P, Tullu MS. Study of ventilator-associated pneumonia in a pediatric Intensive Care Unit Indian J Pediatr. 2014;81:1182–6
17. Cook DJ, Walter SD, Cook RJ, Griffith LE, Guyatt GH, Leasa D, et al Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients Ann Intern Med. 1998;129:433–40
18. Ali HS, Khan FY, George S, Shaikh N, Al-Ajmi J. Epidemiology and outcome of ventilator-associated pneumonia in a heterogeneous ICU population in qatar Biomed Res Int. 2016;2016:8231787.
19. Esperatti M, López-Giraldo A, Torres AVincent JL. Viral-associated ventilator-associated pneumonia Annual Update in Intensive Care and Emergency Medicine 2012. 2012Last accessed on 2022 Feb 15 Berlin, Heidelberg Springer Available form:
https://doi.org/10.1007/978-3-642-25716-2_28
20. Daubin C, Vincent S, Vabret A, du Cheyron D, Parienti JJ, Ramakers M, et al Nosocomial viral ventilator-associated pneumonia in the Intensive Care Unit: A prospective cohort study Intensive Care Med. 2005;31:1116–22
21. Gadani H, Vyas A, Kar AK. A study of ventilator-associated pneumonia: Incidence, outcome, risk factors and measures to be taken for prevention Indian J Anaesth. 2010;54:535–40
22. Bouza E, Giannella M, Torres MV, Catalán P, Sánchez-Carrillo C, Hernandez RI, et al Herpes simplex virus: A marker of severity in bacterial ventilator-associated pneumonia J Crit Care. 2011;26:6.e1–6
23. Coisel Y, Bousbia S, Forel JM, Hraiech S, Lascola B, Roch A, et al Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia PLoS One. 2012;7:e51340.
24. Luyt CE, Combes A, Deback C, Aubriot-Lorton MH, Nieszkowska A, Trouillet JL, et al Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation Am J Respir Crit Care Med. 2007;175:935–42
25. Tuxen DV, Cade JF, McDonald MI, Buchanan MR, Clark RJ, Pain MC. Herpes simplex virus from the lower respiratory tract in adult respiratory distress syndrome Am Rev Respir Dis. 1982;126:416–9
26. Korppi M, Kröger L, Laitinen M White Blood Cell and Differential Counts in Acute Respiratory Viral and Bacterial Infections in Children, Scandinavian Journal of Infectious Diseases. 1993;25:435–40
