|Year : 2017 | Volume
| Issue : 2 | Page : 74-83
Implementation of ventilator associated pneumonia prevention bundle in the neonatal intinsive care unit at Alexandria University Children’s Hospital, Egypt
Reem M.A Tayel1, Abd El Haleem A Badr El Din1, Soad F Hafez2, Bahaa S Hammad1
1 Department of Pediatrics, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
2 Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
|Date of Submission||21-Aug-2017|
|Date of Acceptance||19-Sep-2017|
|Date of Web Publication||17-Jan-2018|
Reem M.A Tayel
Department of Pediatric, Neonatology Division, Faculty of Medicine, Alexandria University, Alexandria, 21523
Source of Support: None, Conflict of Interest: None
Introduction Ventilator-associated pneumonia (VAP) is a nosocomial lung infection that develops at or later than 48 h after mechanical ventilation (MV). It is the second most frequent hospital-acquired infection in neonatal intensive care units (NICUs). It results in high morbidity, mortality, prolonged NICU length of stay, and increased cost of hospitalization. Egypt and other developing countries report higher VAP rates compared with developed countries. Furthermore, studies monitoring VAP rates and success of intervention strategies in Egyptian NICUs are few.
Aim The aim of the present study was to estimate the incidence of VAP during the implementation of the prevention bundle and also to identify the causative agents and significant risk factors in the NICU at Alexandria University Children’s Hospital.
Patients and methods A nonrandomized clinical trial with historical control was conducted. All neonates admitted to the NICU in the period from July 2015 till March 2016, who spent more than 48 h on MV, were subjected to a VAP prevention bundle. Eligible neonates who spent more than 48 h on MV were monitored closely for VAP development. A thorough assessment of history, clinical examination, routine investigations, and chest radiography were carried out on all enrolled infants. Neonates who developed clinically suspected VAP were further subjected to nonbronchoscopic bronchoalveolar lavage for bacteriological confirmation of the clinical diagnosis. A review of records was performed to determine the incidence of VAP in the 9 months before intervention. Oral swabs were taken to study the pattern of oral colonization in ventilated neonates to trace its role in VAP development. Also, cultures of residual gastric volume and water traps inserted into the ventilator circuits were studied.
Results A total of 108 episodes of VAP were diagnosed, with a cumulative incidence of clinically diagnosed VAP equal to 37.6% (34.2 VAP cases/1000 ventilation days). The incidence of bacteriological-confirmed VAP in this study was 19.97/1000 ventilation days. The most important risk factors for the occurrence of VAP were prematurity, low birth weight, prolonged duration of ventilation, re-intubations, and enteral feeding. Gram-negative bacteria were the predominating cause of VAP in the NICU and Klebsiella was the most common pathogen isolated from nonbronchoscopic bronchoalveolar lavage cultures.
Conclusion VAP is a severe complication of MV as it significantly increases neonatal mortality. The VAP preventive bundle implemented in the present work was associated with a reduction in the VAP rate in the NICU.
Keywords: Center for Disease Control and Prevention, mechanical ventilation, neonatal intensive care unit, neonatal intensive care units length of stay, nonbronchoscopic bronchoalveolar lavage, ventilator-associated pneumonia, ventilator-associated pneumonia bundle
|How to cite this article:|
Tayel RM, Badr El Din AA, Hafez SF, Hammad BS. Implementation of ventilator associated pneumonia prevention bundle in the neonatal intinsive care unit at Alexandria University Children’s Hospital, Egypt. Alex J Pediatr 2017;30:74-83
|How to cite this URL:|
Tayel RM, Badr El Din AA, Hafez SF, Hammad BS. Implementation of ventilator associated pneumonia prevention bundle in the neonatal intinsive care unit at Alexandria University Children’s Hospital, Egypt. Alex J Pediatr [serial online] 2017 [cited 2018 Jun 24];30:74-83. Available from: http://www.ajp.eg.net/text.asp?2017/30/2/74/223454
| Introduction|| |
Advances in mechanical ventilation (MV) in the neonatal intensive care units (NICUs) have contributed markedly to the survival of newborn infants in the last decades; especially extremely preterm ones. However, it is not free of severe complications in this population. Remarkably, ventilator-associated pneumonia (VAP), a severe complication in ventilated neonates, has received limited attention in the neonatal literature . According to data published by the Center for Disease Control and Prevention (CDC), VAP is the second most frequent cause of hospital-acquired infections in pediatric intensive care units and NICUs ,,. The risk is even higher in newborn infants because of their immature immune system and their exposure to multiple invasive medical devices ,. Although a universally accepted definition of VAP is still lacking, an incidence of 15.7–52 episodes/1000 ventilation days has been reported in the neonatal population ,,. Discrepancy in the incidence rate of VAP may be explained by the different diagnostic criteria used in each study. It also follows a geographical distribution and varies according to the type of hospital (whether academic or nonacademic), the country’s income level, and the economic development. Higher VAP rates were reported in academic hospitals and in lower and middle income countries compared with upper income countries . Also, VAP reported an associated mortality rate up to 71% in neonates, hence described as a threat to ventilated infants .
The VAP microbes vary between and within hospitals according to the population of patients, length of stay (LOS), diagnostic methods, and antibiotic policies . Invasive sampling of the distal respiratory tract in NICUs, reported that Gram-negative infections; including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Enterobacter spp., and Acinetobacter spp. are responsible for nearly 60% of VAP cases ,.
The pathogenesis of VAP involves four routes: hematogenous spread, contiguous spread, inhalation of infectious aerosols, and aspiration. The majority of VAP episodes appear to result from aspiration of potential pathogens that have colonized the mucosal surfaces of the oropharyngeal airways . Recognized risk factors of VAP in children differ between studies; however, prematurity, low birth weight, duration of MV, re-intubations, enteral feeding, and use of sedation have been consistently reported in NICUs .
The diagnosis of a VAP episode requires a combination of radiological, clinical, and laboratory criteria defined by CDC for infants less than 12 months. Neonates who are mechanically ventilated for 48 h or more should have a new onset of abnormal chest radiographs and worsening of gas exchange (e.g. O2 desaturations, increased oxygen requirements, or increased ventilator demands) with at least three of the following criteria: temperature instability; new onset of purulent tracheal secretions, increased respiratory secretions with increased suctioning requirements, leukopenia [≤4000 white blood cells (WBC)/mm3] or leukocytosis (>15 000 WBC/mm3), apnea, tachypnea, retraction of chest wall, nasal flaring, grunting, wheezing, respiratory crackles, bradycardia (<100 beats/min), or tachycardia (>170 beats/min) .
Chest radiographs are considered the backbone of VAP diagnosis as the initial diagnosis is based on clinical suspicion and the presence of new radiographic changes 48 h after the initiation of ventilation . The CDC defined these changes as the presence of at least one of the following: a new or progressive and persistent (>24 h) infiltrate, consolidation, cavitation, or pneumatoceles in two or more serial chest radiographies .
Defining the infective organism causing VAP increases the accuracy of the clinical and radiological diagnosis. It also helps in modifying the initial antibiotics according to culture and sensitivity tests, thus preventing the emergence of resistant strains. The nonbronchoscopic bronchoalveolar lavage (NB-BAL) has been described in ventilated newborn infants as a very useful technique for collecting distal respiratory tract secretions, with a minor degree of contamination. It is safe, easy to perform, well tolerated, and clinically useful even in premature neonates receiving MV ,.
The CDC has published guidelines for the prevention of VAP, which is primarily achieved by the ‘bundle approach’. This involves simultaneous application of several evidence-based preventive strategies that, when implemented together, achieve better patient outcomes ,. As neonates have different anatomy, physiology, underlying diseases, and they undergo different invasive procedures compared with adults and older children, specific studies for evaluating different ‘VAP bundles’ efficacy in preventing VAP in NICUs are still needed . In Egypt and other developing countries, reports on the success of VAP intervention strategies, particularly among neonates, are few .
| Aim|| |
The aim of the present study was to:
- Estimate the incidence of VAP during the implementation of the prevention bundle.
- Identify the causative agents.
- Determine significant risk factors in the NICU at Alexandria University Children’s Hospital (AUCH), Egypt.
| Patients and methods|| |
A nonrandomized clinical trial was carried out during the period from July 2015 till March 2016 in the NICU at AUCH. It is a tertiary referral NICU with 70 incubators and 35 mechanical ventilators. All neonates admitted to the NICU at AUCH and who spent more than 48 h on MV were included in the study as the experimental group. Neonates who were diagnosed with neonatal pneumonia on admission or mechanically ventilated for less than 48 h were excluded from this study.
This prospective study was carried out in two phases: an education phase (2 months) to all NICU staff on how to apply the VAP bundle. This was accomplished by multiple presentations explaining how to diagnose and prevent VAP by correctly applying the bundle. The second phase was application of a VAP preventive bundle aiming at decreasing the VAP rate.
The designed VAP prevention protocol that has been applied in this study was composed of adherence to hand hygiene guidelines, daily assessments of readiness for weaning from MV, encourage the use of noninvasive ventilation, sedation vacation for sedated infants, elevation of the head of bed 15–30°, minimizing re-intubations, residual gastric volume monitoring, oral care with chlorhexidine gluconate (CHG) 0.12%, changing VCs only if visibly soiled or mechanically malfunctioning, and careful handling of collected condensate in the water traps placed in the expiratory limb of VCs.
Neonates were closely monitored, during the entire period of ventilation, for the appearance of any of the clinical or radiological criteria defined by CDC for VAP diagnosis in infants less than 1-year old. Ventilated infants who experienced a new onset of abnormal chest radiographs along with criteria for the clinical diagnosis were diagnosed with VAP. They were further subjected to the NB-BAL procedure for bacteriological confirmation of the clinical diagnosis. Record reviews (historical control) of all ventilated neonates admitted during the 9 months period preceding the study were used as a control arm. This was achieved by calculating the incidence of bacteriologically confirmed VAP per 1000 ventilation days among ventilated neonates diagnosed 48 h after being intubated.
Baseline characteristics of enrolled neonates were obtained from records including their demographic characteristics, gestational age (GA), birth weight, anthropometric measurements, and diagnosis on admission. Also, full physical examination, assessment of vital signs, clinical evidence of sepsis, and type of feeding whether enteral or total parenteral nutrition were recorded. Baseline chest radiography was ordered for all ventilated neonates, and then serial radiographies were repeated as required. Laboratory investigations including complete blood count, C-reactive protein (CRP), blood chemistry, renal functions, and arterial blood gases were performed.
Microbiological studies included blood cultures, oral swab cultures, residual gastric volume cultures, and cultures of the collected condensate in the water traps placed in the ventilator circuits (VCs). Oral swab cultures were taken once ventilation was initiated to determine baseline microbial status and before CHG 0.12% application. They were repeated every 72 h till the neonate was weaned from MV or died. Also, NB-BAL cultures obtained from clinically diagnosed VAP were collected in a sterile mucous trap and immediately sent to the microbiology laboratory for species identification.
Ethical approval was obtained from the Ethical Review Committee.
Plan for data analysis
Data were entered and analyzed using IBM SPSS software package version 20.0 (IBM Corp, Armonk, New York, USA). The Kolmogorov–Smirnov, Shapiro, and D’Agostino tests were used to verify the normality of distribution of variables. Comparisons between groups for categorical variables were performed using the χ2-test (Fisher’s or Monte Carlo). Student’s t-test was used to compare two groups for normally distributed quantitative. The Mann–Whitney test was used to compare between two groups for abnormally distributed quantitative variables. Odds ratio (OR) was used to calculate the ratio of the odds and 95% confidence interval (CI) of an event occurring in one risk group to the odds of it occurring in the nonrisk group. Receiver operating characteristic curve (ROC) was used to determine the diagnostic performance of the markers. Area more than 50% gives acceptable performance and area about 100% is the best performance for the test. The significance of the obtained results was judged at the 5% level. Agreement between markers was determined using sensitivity, specificity, positive predictive value, and negative predictive value.
| Results|| |
A total of 493 neonates, with variable admission diagnoses, were invasively ventilated in our NICU during the 9-month period of the study. Out of the 493 ventilated neonates, 94 were excluded as they were diagnosed with congenital pneumonia on admission. Furthermore, a total of 112 neonates were also excluded as 38 died and 74 were weaned from MV within 48 h of MV. This left 287 ventilated for more than 48 h eligible for the study. They were closely monitored for clinical, radiological, and laboratory changes that suggested VAP diagnosis according to the CDC criteria for infants up to 1-year old. VAP developed in 108 of 287 ventilated neonates; hence, the incidence of VAP on the basis of clinical and radiological diagnosis was 37.6% or 34.2 VAP cases/1000 ventilation days. Clinically diagnosed VAP neonates (n=108) were further subjected to NB-BAL sampling to confirm the clinical diagnosis. Out of the 108 NB-BAL samples carried out, 63 yielded cultures and 45 were sterile. Hence, the incidence of bacteriological-confirmed VAP in this study was 19.97/1000 ventilation days ([Figure 1]). Only the bacteriologically proven VAP rate was used in comparison with the previous VAP rate calculated retrospectively from the statistical data of the NICU. The incidence rate of bacteriological confirmed that VAP pre-prevention bundle implementation was 24.62/1000 ventilation days. Therefore, the VAP bundle implemented in the present work was associated with a reduction in VAP rates in the NICU ([Figure 2] and [Figure 3]). [Figure 3] shows a VAP outbreak that occurred in February 2016. This was because of the fact that the majority of admissions in that period were premature neonates of very low birth weight and extremely low birth weight.
|Figure 1 Diagram of ventilator-associated pneumonia diagnosis. MV, mechanical ventilation; VAP, ventilator-associated pneumonia.|
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|Figure 2 Bacteriologically positive ventilator-associated pneumonia rate before the intervention of the ventilator-associated pneumonia prevention bundle. LCL, lower control limit; UCL, upper control limit; VAP, ventilator-associated pneumonia.|
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|Figure 3 Bacteriologically positive ventilator-associated pneumonia rate during the intervention of the ventilator-associated pneumonia prevention bundle. LCL, lower control limit; UCL, upper control limit; VAP, ventilator-associated pneumonia.|
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[Table 1] shows the demographic data and baseline variables of neonates with and without VAP. There were no significant differences in sex, admission diagnosis, maternal risk factors, mode of delivery, and antenatal steroids. However, the mean GA (31.73±3.04 weeks) and birth weight (1.58±0.82 weeks) among VAP-diagnosed infants were significantly lower than the non-VAP group. Possible risk factors among mechanically ventilated neonates for more than 48 h are summarized in [Table 2]. Only re-intubations, duration of MV, and enteral feeding were significantly associated with the development of VAP (P<0.05).
|Table 1 Comparison between neonates with or without ventilator-associated pneumonia according to different parameters|
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|Table 2 Comparison between neonates with or without ventilator-associated pneumonia according to possible risk factors|
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[Table 3] shows a multivariate logistic regression analysis model of the statistically significant risk factors that were associated with VAP. The duration of MV (OR: 1.578; 95% CI: 1.384–1.799; P<0.001) and GA (OR: 0.788; 95% CI: 0.622–0.999; P=0.049) were statistically significant as independent risk factors and predictors for the development of VAP in this study. Furthermore, a ROC curve analysis was carried out to estimate the association between duration of MV and VAP. The area under the curve (AUC) value has shown that the duration of MV is a good predictor for VAP in this study as a value of 0.921 is of high accuracy (AUC: 0.921, 95% CI: 0.889–0.945, P<0.001). The cut-off value of greater than 5 days spent on MV was associated with VAP at the highest sensitivity recorded (92.59%).
|Table 3 Multivariate analysis of significant risk factors associated with the development of ventilator-associated pneumonia|
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[Figure 4] shows the clinical findings in VAP-diagnosed neonates according to the criteria of the CDC for infant’s up to 1-year old. The appearance of mucopurulent secretions in endotracheal tube (ETT) was found to be the most predominant clinical sign of VAP in this study. The investigations carried out for ventilated infants have shown that an increased level of CRP, leukopenic episodes, and attacks of hypoxia and hypercapnia were statistically significant in VAP-diagnosed neonates. Also, the result of blood cultures in this study showed that Gram-negative infection was the dominant type of infection in the NICU, with Klebsiella comprising the majority in both studied groups.
|Figure 4 Distribution of clinical findings associated with ventilator-associated pneumonia.|
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[Table 4] shows the results of NB-BAL cultures carried out for bacteriological confirmation of the clinically diagnosed VAP (n=108). Out of the 108 NB-BAL samples, 41.6% (n=45) were sterile. Gram-negative infection comprised 54.6%, whereas Gram-positive infection was only 0.9%. Polymicrobial infection present in 2.8% of the total positive cultures was mainly because of the presence of three Gram-negative organisms in high counts, suggesting infection rather than colonization. Klebsiella was the most predominant cause of VAP in the current study, accounting for 35.2% of the positive NB-BAL cultures, followed by Acinetobacter spp., comprising 17.6% of the total results. Blood stream infection and VAP were caused by the same organism in only 10 out of the 108 VAP-diagnosed neonates. Eight yielded Klebsiella spp. from both cultures and two yielded Acinetobacter spp.
|Table 4 The organisms isolated from nonbronchoscopic bronchoalveolar lavage cultures among ventilator-associated pneumonia-diagnosed neonates|
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[Table 5] shows the distribution of the organisms colonizing the oral cavity of the VAP-diagnosed ventilated neonates. Swabs were taken before oral care and repeated every 72 h till the infant was weaned from ventilation or died. Streptococcus viridans was reported to be the most frequent Gram-positive organism colonizing the oral cavity, whereas Klebsiella spp. was the most common Gram-negative pathogen. Even though most of the species of bacteria examined were reduced after single oral care by CHG 0.12%, yet, some cultures yielded organisms even on applying this antiseptic solution. Results of cultures taken from the water traps inserted into the VCs showed that all samples were sterile, except for one, which was colonized with Staphylococcus aureus. Also, residual gastric volume checked before feeding was taken to study gastric colonization in VAP episodes. Klebsiella spp. (12.9%) was reported to be the most predominant colonizer, followed by Acinetobacter spp. (4.6%).
|Table 5 Organisms isolated from oral swab cultures of ventilator-associated pneumonia-diagnosed neonates|
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The results of the present study showed that mortality was significantly higher among VAP studied cases (91.7%) compared with the non-VAP group (43.5%). Also, the NICU LOS was significantly longer in the VAP group compared with those without VAP, i.e. 14.74±10.15 versus 12.30±14.78 days. It is noteworthy that the majority of VAP deaths were encountered in preterms of GA (27 to ≤34) weeks and birth weight less than or equal to 1 kg.
| Discussion|| |
VAP is a severe complication related to ventilation in the neonatal period. It is the second most frequent cause of hospital-acquired infection in pediatric intensive care units and NICUs ,. The diagnosis of a VAP episode requires a combination of radiological, clinical, and laboratory criteria defined by CDC for infants less than 12 months. Neonates who are mechanically ventilated for 48 h or more showing any of these criteria are diagnosed with VAP .
Published studies reported evidence that implementing a VAP prevention bundle can result in significant and sustained reductions in VAP rates ,. A 9-month prospective study at the NICU of AUCH was launched to implement the VAP bundle and to estimate its effect on decreasing VAP rate. All staff education was provided by multiple presentations to discuss how to diagnose and prevent VAP. Also, multiple sessions during clinical rounds were carried out to stress on VAP bundle items, particularly hand hygiene, securing the ETT, sterile handling of respiratory equipment, and proper timed mouth care. A signed statement from each staff member acknowledging their understanding to ensure the connection between policy and practice was obtained.
The incidence of VAP on the basis of clinical and radiological diagnosis during the bundle implementation was 37.6% or 34.2 VAP cases/1000 ventilation days. The incidence of bacteriological-confirmed VAP in this study was 19.97/1000 ventilation days, whereas the incidence of bacteriological-confirmed VAP pre-prevention bundle implementation was 24.62/1000 ventilation days.
The NICU at the AUCH is a tertiary referral academic hospital where the majority of admissions are high-risk pregnancies. This explains why most of the admissions in our NICU are premature babies. Hence, our VAP rates are probably more representative and comparable to NICUs of large academic tertiary hospitals in developing countries. Also, overcrowding and subsequently understaffing represent a huge problem that the infection control team faces in the NICU.
Azab et al.  reported that the VAP rate has declined from 36.4 VAP episodes/1000 ventilation days to 23/1000 after VAP prevention bundle implementation in their NICU at Zagazig University. Others reported VAP incidence in different NICUs in Egypt to be 57.1% and 25.9/1000 ventilation days ,. Incidence rates reported in the literature from NICUs in Thailand, Brazil, China, and India were 70.3, 52, 48.8, and 37.2/1000 ventilation days, respectively ,,,. The situation is markedly different in the developed world as incidence rates in the USA and Germany ranged from 1.9 to 2.2/1000 ventilation days ,.
The mean GA and birth weight of the infants diagnosed with VAP were significantly lower than the non-VAP group. Studies showed that premature infants are at a higher risk for developing VAP. This is because of the fact that their need for MV is often for a prolonged interval of time, resulting in a greater number of ventilator days with a steady increase in VAP episodes ,,. Respiratory distress syndrome was the most common indication for MV in our nursery (73.5%) as the majority of the admitted neonates were premature. However, there was no association between VAP and underlying illness. Also, maternal risk factors, mode of delivery, and antenatal steroid course showed no significant difference between both studied groups. This was found in agreement with the studies carried out by Cernada and colleagues ,,.
Risk factors can offer prognostic information about the probability of developing VAP and may lead to the development of effective preventive strategies . In this study, re-intubation was statistically significant among VAP-diagnosed infants. It plays a very important role in the pathogenesis of VAP as it helps in the translocation of the pathogenic bacteria colonizing the oral cavity directly into the lower airways. Cernada et al.  reported that re-intubations were performed in 81.2% of VAP patients, whereas Yuan et al.  reported that re-intubation per say increased the risk of VAP 5.3 folds in their NICU. Duration of MV is well known to be a major risk factor for the development of VAP ,,. In the current study, VAP-diagnosed infants tended to receive MV for a longer duration (10.18±3.93 days) than those without VAP (5.38±2.78 days). Prolonged duration on a ventilator in the VAP group can be attributed to the poor general condition on admission mainly because of extremes of prematurity. This generally increased the risk of infection because of the exposure to VCs, humidifiers, and nebulizers that are proven to be an important source and media for microorganisms . Several studies reported results in agreement with our findings ,,,,,,. This highlights the importance of implementing new strategies in our NICU that encourage the medical staff toward early weaning from MV and supplying ventilatory support by noninvasive ventilation.
The policy of our unit is to initiate enteral feeding as early as possible. In the present study, enteral feeding was found to be associated significantly with VAP as 76 out of the 108 VAP-diagnosed infants were enterally fed. This can be because of the increased risk of aspiration, gastroesophageal reflux, and gastric colonization with VAP potential pathogens because of elevated stomach pH. This was consistent with studies that considered enteral nutrition a risk factor for the development of VAP ,.
There was no relation between intubation in the delivery room during resuscitation and the development of VAP later on. Lung-protective strategies, such as early surfactant administration and high-frequency ventilation (HFV) mode, were applied in some of the ventilated neonates aiming to decrease ventilator-associated complications. However, there was no statistical significance between the initial mode of ventilation whether it was conventional (assist-control/synchronized intermittent mandatory ventilation/pressure support ventilation) or nonconventional (high-frequency ventilation) and surfactant administration on the outcome. Tripathi et al.  reported the same results in their study that was carried out in a NICU in India. The placement of central catheters was insignificant in both studied groups. This is because the majority of ventilated infants were catheterized in this study. Apisarnthanarak et al.  reported that the presence of these catheters might be a marker for the severity of illness.
Risk factors including GA, birth weight, re-intubations, enteral feeding, and duration of MV were the ones that reached statistical significance for VAP development. A binary logistic regression was performed to identify independent risk factors and predictors of VAP in this study. Only GA and days of MV were statistically significant as independent risk factors for developing VAP. In fact, the duration spent on MV has shown the highest significance among all studied risk factors (P<0.001). Multiple logistic regression studying risk factors of VAP in NICUs reported similar results as the present study ,,. The AUC value of the ROC curve showed that duration of ventilation is a significant predictor for the onset of VAP as a value of 0.921 shows a very high accuracy (P<0.001). The duration of MV more than 5 days was associated with VAP at the highest sensitivity recorded (92.59%). Yuan et al.  reported that the value of the AUC of 5 days of MV was 0.73 with sensitivity of 45.1%.
The most prevalent clinical signs associated with VAP were the appearance of mucopurulent secretions in the ETT (88.9%) and increased the ventilator settings (85.2%). Also, an increased CRP level, leukopenic episodes (WBCs≤4000), attacks of hypoxia (PO2<50), and hypercapnia (PCO2>55) were all significantly higher in the VAP group. This was in agreement with the results that reported nearly the same observations ,,,. Blood culture results of ventilated neonates in this study showed that Gram-negative infection was the dominating type of infection in the NICU, with Klebsiella spp. comprising the majority in both studied groups.
The lack of a gold standard for VAP diagnosis is still a problem that intensivists face ,,. In this study, samples were obtained from the distal airways by NB-BAL that was reported in some studies to be the most reliable sampling method applied in the neonatal patient ,,,. Gram-negative bacteria was isolated from the majority of ventilated infants (54.6%), with Klebsiella spp. predominating the positive NB-BAL cultures (35.2%), followed by Acinetobacter spp., comprising 17.6% of the total cultures. Gram-positive cultures included only one case that isolated methicillin-resistant Staphylococcus aureus pathogen. The bacteriological confirmation was contributive to decision making on antimicrobial therapy; hence, the initial therapy was modified on the basis of NB-BAL culture results. The results of the present study were similar to nearly all studies carried out in NICUs investigating VAP in the neonatal population ,,,,,,.
Within 48 h of hospital admission, the composition of the oropharyngeal flora especially in ventilated ICU patients undergoes a dramatic shift to more virulent microbes that includes potential VAP pathogens, predominantly Gram-negative organisms ,. Colonization of the oropharynx is one of the most critical risk factors and is considered a key component in the development of VAP . Oral swabs cultures obtained from ventilated infants showed that Streptococcus viridans was the most common colonizer. Furthermore, Klebsiella spp. was the most common Gram-negative bacteria colonizing the oral cavity in ventilated neonates who later developed VAP. Even though most of the species of bacteria examined were reduced after a single oral care procedure by CHG 0.12%, yet, some cultures yielded organisms even on applying this antiseptic solution. The results of the collected condensate cultures showed that all water trap samples were sterile, except one, which yielded Staphylococcus aureus. The contaminated condensate in the VCs has been proven to play an important role in the pathogenesis of VAP. Simple procedures, such as turning the patient, may accidentally spill contaminated condensate directly into the patient’s tracheobronchial tree .
The stomach often becomes colonized with enteric Gram-negative bacteria during critical illness. These pathogens were the most frequent ones isolated from BAL cultures of patients with VAP. This was described in the literature as the ‘gastropulmonary hypothesis’ . Gastric colonization was monitored by taking cultures of the gastric volume residual checked before feeding in the ventilated neonate. Klebsiella spp. was reported to be the most predominant colonizer, followed by Acinetobacter spp. Unfortunately, to our knowledge, no clinical studies have been published showing the relation between gastric colonization and VAP in the neonatal population. However, Koksal et al.  reported in his study that Acinetobacter spp. was the most common organism colonizing the stomach.
In the present study, the mean LOS at the NICU was 14.74±10.15 days in the VAP-diagnosed infants. This was significantly longer in comparison with the non-VAP group (12.30±14.78). Also, mortality was significantly higher among VAP-diagnosed neonates (91.7%) compared with the non-VAP group (43.5%). The majority of VAP deaths were encountered in preterms of GA (27 to ≤34) weeks and birth weight less than or equal to 1 kg. It is noteworthy that NICU patients, especially preterm neonates, generally have a high mortality rate unrelated to nosocomial infections; hence, the attributable morbidity and mortality associated with VAP was difficult to determine in this study. A few studies carried out exclusively in neonatal populations reported similar results ,,,.
The paucity of literature on VAP in the neonatal population speaks to the need to carry out studies to examine various practices used to prevent VAP. To date, there are no published reports of the success of best practices for VAP prevention in the NICU. Hence, additional studies are necessary to develop evidence-based interventions to prevent neonatal VAP.
| Conclusion|| |
VAP is one of the severe complications of MV in the NICU that significantly increases the LOS and neonatal mortality. The risk factors associated with VAP encountered in this study were prematurity, low birth weight, re-intubations, prolonged duration of ventilation, and enteral feeding. A bundle of infection control practices can help reduce VAP during neonatal ventilation.
Medical staff should be encouraged toward early weaning from MV and supplying noninvasive ventilation as an initial management of respiratory distress, especially in premature infants. This might help in reduction of the rate of intubation and its associated complication. Also, we recommend strict and continuous staff training and supervision of the VAP bundle protocol. Avoidance of overcrowding and understaffing should be ensured as there should be a reasonable patient/nurse ratio to insure that infection control policies are strictly applied. Isolation of potential VAP pathogens found from oral cultures of ventilated infants before diagnosing VAP highlights the importance of adherence to an oral care protocol before intubation. Additional studies with larger sample sizes are still needed to show the protective effect of oral decontamination by chlorhexidine and its significance in reducing VAP rates.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Cernada M, Aguar M, Brugada M, Gutiérrez A, López JL, Castell M et al.
Ventilator-associated pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study. Pediatr Crit Care Med J 2013; 14:55–61.
Cernada M, Brugada M, Golombek S, Vento M. Ventilator-associated pneumonia in neonatal patients: an update. Neonatol J 2014; 105:98–107.
Foglia E, Meier M, Elward A. Ventilator associated pneumonia in neonatal and pediatric intensive care unit patients. Clin Microbiol J 2007; 20:409–425.
Apisarnthanarak A, Holzmann-Pazgal G, Hamvas A, Olsen MA, Fraser VJ. Ventilator associated pneumonia in extremely preterm neonates in a neonatal intensive care unit: characteristics, risk factors, and outcomes. Pediatr J 2003; 112:1283–1289.
Yuan TM, Chen LH, Yu HM. Risk factors and outcomes for ventilator-associated pneumonia in neonatal intensive care unit patients. Perinat Med J 2007; 35:334–338.
Aelami MH, Mojtaba L, Zingg W. Ventilator-associated pneumonia in neonates, infants and children. Antimicrob Resist Infect Control 2014; 3:1–10.
Chastre J, Fagon JY. Ventilator-associated pneumonia. Am Respir Crit Care Med J 2002; 165:867–903.
Köksal N, Hacimustafaoğlul M, Celebi S, Ozakin C. Non bronchoscopic bronchoal veolar lavage for diagnosing ventilator associated pneumonia in newborns. Turk J Pediatr 2006; 48:213–220.
Grossman RF, Fein A. Evidence based assessment of diagnostic tests for ventilator associated pneumonia. Chest J 2000; 117:177–181.
Obeid A, Kamel R, Naous A, Merhi BA, Rajab M. Preventing ventilator-associated pneumonia (VAP) in a pediatric intensive care unit using a modified ventilator-associated pneumonia bundle: pre-interventional and post-interventional trial. Int Med Res J 2014; 2:14–19.
Resar R, Pronovost P, Haraden C, Simmonds T, Rainey T, Nolan T. Using a bundle approach to improve ventilator care processes and reduce ventilator-associated pneumonia. Jt Comm J Qual Patient Saf 2005; 31:243–248.
Azab SA, Sherbiny HS, Saleh SH, Elsaeed WF, Elshafiey MM, Siam AG et al.
Reducing ventilator-associated pneumonia in neonatal intensive care unit using ‘VAP prevention Bundle’: a cohort study. Infect Dis J 2015; 15:314–321.
Badr MA, Ali YF, Albanna EA, Beshir MR, Amr GE. Ventilator associated pneumonia in critically-ill neonates admitted to neonatal intensive care unit, Zagazig University Hospitals. Iran Pediatr J 2011; 21:418–424.
El-Kholy A, Saied T, Gaber M, Younan MA, Haleim MM, El-Sayed H. Device-associated nosocomial infection rates in intensive care units at Cairo University hospitals: first step toward initiating surveillance programs in a resource-limited country. Am Infect Control J 2012; 40:216–220.
Petdachai W. Ventilator associated pneumonia in a newborn intensive care unit in Prachomklao Hospital Thailand. Southeast Asian Tropical Med Public health J 2004; 3:724–729.
Günlemez A, Atasay B, Güriz H, Aysev D, Arsan S. Multi-resistant viridans streptococcal pneumonia and sepsis in the ventilated newborn. Annals Trop Paediatr J 2004; 24:253–258.
Cai XD, Cao Y, Chen C, Yang Y, Wang CQ, Zhang L et al.
Investigation of nosocomial infection in the neonatal intensive care unit. Chin Contemp Pediatr J 2010; 12:81–84.
Tripathi S, Malik GK, Jain A, Kohli N. Study of ventilator associated pneumonia in neonatal intensive care unit: characteristics, risk factors and outcome. Internet Med Update J 2010; 5:12–19.
Hocevar SN, Edwards JR, Horan TC, Morrell GC, Iwamoto M, Lessa FC. Device-associated infections among neonatal intensive care unit patients: incidence and associated pathogens reported to the National Healthcare Safety Network, 2006–2008. Infect Control Hosp Epidemiol J 2012; 33:1200–1206.
Leistner R, Piening B, Gastmeier P, Geffers C, Schwab F. Nosocomial infections in very low birth weight infants in Germany: current data from the National Surveillance System NEO-KISS. Klin Padiatr J 2013; 225:75–80.
Deng C, Li X, Zou Y, Wang J, Wang J, Namba F et al.
Risk factors and pathogen profile of ventilator-associated pneumonia in a neonatal intensive care unit in China. Pediatr Int J 2011; 53:332–337.
Moradi M, Nili F, Nayeri F, Amini E, Esmaeilnia T. Study of characteristics, risk factors and outcome for ventilator associated pneumonia in neonatal intensive care unit patients. Tehran Univ Med J 2013; 71:373–381.
Afify M, AI-Zahrani S, Nouh M. Risk factors for the development of ventilator associated pneumonia in critically-ill neonates. Life Science J 2012; 9:302–307.
Khattab A, El-Lahony D, Soliman W. Ventilator-associated pneumonia in the neonatal intensive care unit. Menoufia Medical J 2014; 27:73–77.
Chlebicki M, Safdar N. Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. Crit Care Med J 2007; 35:595–602.
Grap MJ, Munro CL, Elswick RK, Sessler CN, Ward K. Duration of action of a single, early oral application of chlorhexidine on oral microbial flora in mechanically ventilated patients: a pilot study. Heart and Lung J 2004; 33:83–89.
Kallet R, Quinn T. The gastrointestinal tract and ventilator-associated pneumonia. Respir Care J 2005;50:910–923.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]